Deep Future

Deep Future
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Jan 23, 2022 • 1h 18min

Top Sleep Doctor's Brain Dump - Michael Breus, Ph.D

Sleep is the most natural process that you can do other than breathing. Like breathing, we don’t need technology to help us sleep. The reason many people don’t sleep is because of what’s between their ears – their mental stability, anguish, or stress. Do you fall asleep easily or does the slightest noise wake you up? Dr. Michael Breus, gives me a full brain dump as I try to learn everything I can about sleep in one session. He takes on taboo ideas like polyphasic sleep and the role of nutrition and the microbiome in having a good night’s rest, how melatonin, CBD, and some pharmaceutical interventions such as Zolpidem affect the sleep process, how much sleep we should have, and more. Pablos: The thing I’m trying to go after is that at least my way of seeing the world is through all these problems that we have. This is a pile of problems that are possibly growing. We also have this other pile, which is tools and technologies, and it’s also growing because of what I mentioned. The job for us is to figure out how we sit in the middle and connect to those things. If we have some optimism that it’s possible and we can demystify the problems so people understand what the real problems are, we can demystify the technology so they’re not terrifying and complicated. People then can build that sense of optimism about how we could make the future better. That’s how I think about things a lot. Not only the idea here is to give people some insight into how we think about things and our experiences. One of the things I’m curious about is that years ago, there was no such thing as a sleep doctor. Maybe there were some researchers or whatever, but it wasn’t a legitimate career track. How did you end up being a sleep doctor? What does that mean? Michael: What’s interesting about the field of sleep medicine in general is it’s an incredibly small new field. The very first sleep lab in 1945, Walla Walla, Washington, built demand on narcolepsy. It wasn’t even about sleep apnea. When you look at medicine and you think about Hippocrates. Thousands of years of innovations in medicine, we’re literally at the sperm and egg stage of sleep medicine. That’s where it was. I fell into it by accident. I was doing my residency. I was getting my PhD in Clinical Psychology at the University of Georgia and I was interested in Sports Psychology. I had no interest in sleep at all. I wanted to tell athletes how to get the mental game of sports and run faster into all this cool shit with psychology. I went to the University of Georgia, the top twenty programs. The best internship residency program, believe it or not, is the University of Mississippi Medical Center in Jackson, Mississippi. They had an eating disorders and athletes program that I was fascinated with. This was going to be an interesting area for me to get into and understand more about, but I couldn’t get into the program. Harvard, Yale, Princeton, they all got in the program. I went to Georgia’s top twenty programs, but to be fair, it wasn’t Harvard. It wasn’t even top seventeen. I’m sitting there, I’m looking through the application and they have like a specialty track for sleep medicine and a specialty track for neuropsychological testing. I didn’t know anything about sleep medicine in Jackson. You figured out, “I can’t get on a program I want, but I can at least go to Jackson.” I had an ulterior motive because when I saw this thing, I had worked my way through graduate school in the Electrophysiology department. I’m the kid who used to take the old rotary phones apart, put them back together, there would be 4 or 5 pieces on the side, and this thing would work like a gem. I took the phone apart for different reasons and did not get it back together.   I like to tinker with stuff. I like to measure stuff. I have that kind of a brain. When I saw that there was a sleep track that used those machines, I said, “I’m going to sell myself as a sleep guy. I’m going to transfer as soon as I get there. Just because you didn’t let me in the fucking place, that doesn’t mean I’m not going to get in.” I get in on the sleep side. I get there and they say, “You have to start on the sleep side. If you want to transfer, you can do it later.” By the third day, I fell in love. You haven’t gotten around to transferring back. You gave up on that and sticking with sleep. This was many years ago. Tell me what research was going on there.   Back in those days, the field of sleep medicine is an interesting one because it was taken over. There are two sides, research and clinical. What’s difficult about the clinical is it pretty much only treats sleep apnea. In the world of sleep medicine, we’ve figured out how to treat sleep apnea. That’s primarily what is going on. When you say clinical, that means we’ve got actual patients, we’re trying to help them. On the research side, we’ve got people with problems and we’re trying to understand them. We may or may not be able to help them. That might be a way of describing the difference.   When you look at clinical sleep medicine, we’ve identified 88 different sleep disorders. You can fuck up your sleep, which is amazing when you think about it. We were starting to design protocols for each one of the diagnostics to be able to start to lower the symptomatology. That’s the basics of medicine. Meaning, you are down with each of those 88 things you have.   Sleep is recovery. You have to have something to recover from.Tweet The assessment narrows it down. What I’m talking about is the treatment side of things. You are good at figuring out which of the 88 things you have.   We’re good at that, but the problem is that I believe that there are sleep disorders and what I call disordered sleep. Sleep disorders are diagnosable apnea, narcolepsy and insomnia. Disordered sleep is I went to that room in the back of my house. I was there for 6, maybe 7 hours. My eyes were closed. I come out, I don’t feel great. Why? How do I fix that? That’s been my area of specialty for the last six years where I’m only focusing on how do I improve the quality of sleep. There are probably about 6,000 guys and gals out there who are board-certified sleep specialists. They treat apnea and narcolepsy. In some cases, insomnia. We’ve got pros who can do that, but the things that don’t fit into that rubric. Are you talking about the 89th thing? To be fair, I don’t think it’s a diagnosis. It has to do with lifestyle. It has to do with intensity. I don’t have an actual physical problem that maps to my diet, but it could be better. You could have more energy or better results if you improve your diet, but I don’t necessarily have a clinical problem.   That’s how I look at sleep in certain ways. I’m a high-performance sleep coach. I used to be a sleep doctor, apnea, narcolepsy, insomnia. Now, people come to me and they’re like, “I know that I need eight hours to get good sleep, but I only have six. Can you do that?” The answer is, “Yes, you can.” What science has shown us is that there are certain scheduling swim lanes for your sleep schedule. This is based on something called your chronotype. Chronotype might not be a term that people are familiar with being called an early bird or a night owl. Those are chronotypes. It turns out those are genetic. There’s a variation on the PER3 gene. There’s a particular snip that is altered and that can make your entire body schedule go early or make your entire body schedule go late. If I have 23andme, I can look it up and explain why I’m a night person. That’s the cool part of science, but what the fuck do you do with it? That’s where I come in. I love that science and I was tinkering around with it. I was doing it all myself. I said, “What happens if I only sleep during my chronotypical sleeping hours?” I’m a night owl. That meant I had to go to bed at midnight. I decided not to have an alarm because I was going to check if my body wakes up naturally and see what happens. The first month I started this experiment, I went to bed at midnight and woke up at 7:30. Within 40 days or so, all of a sudden, I was waking up at 7:15 on my own. I am still going to bed at midnight. All of a sudden, it was 7:00, and then it was 6:45. I get up at 6:13 every single morning now with no alarm. I could close my eyes at midnight. That midnight I wake up at 6:13 AM. The punchline is it won’t go lower. At age 52, in my shape, my body only needs 6 hours and 13 minutes of high-quality sleep because I’m sleeping in that swim lane. Here’s what happens, when I stay up until 1:00 in the morning, I still get up at 6:30. That’s what I experienced. I’m tuned for the wake-up time.   That’s what you’re supposed to be because that’s the circadian anchor. When the sun hits the melanopsin cells in your eyeballs and turns off the melatonin faucet in your brain, there’s a whole circadian side of things that has to agree with that. When it doesn’t, you got involved. I should tune my wake-up time to maybe the sun, although that moves around all year. Maybe I could do it to a grow light or whatever so I have a consistent wake-up time. I don’t seem to be able to change that one as much. That one stays the same. I can go to bed whenever I want. For fifteen years, I was dancing salsa, probably at least every other night. The better you get at salsa, the later you go. On a Tuesday night, I would show up at midnight until 2:00 in the morning. It didn’t matter. If I danced, I’d go to bed at 2:00, I would get up at 8:00. If I didn’t dance, I go to bed at 11:00 or 12:00 and get up at 8:00. I felt like what was happening was, “If I dance, I need less sleep,” but you wouldn’t diagnose it that way. Here’s what I would tell you is if you dance, you’d get higher quality sleep. One of the biggest things we now know is movement. Sleep is recovery. You have to have something to recover from. On the nights when you were salsa-ing, what I would do is I’d love to put a tracker on you on the nights when you’re dancing and the nights when you’re not. I would like to look at the different stages of sleep because we probably see a much bigger increase in stage 3 or 4 sleep, which is your physical restoration because of the salsa dancing. We then might see less mental restoration on the REM sleep side of things, but we can change those at will. If I could do anything I wanted having no sleep problem, pretend I have no constraints on when I sleep pretty much, whatever, what do you think would be the optimal thing for a guy to do? I’m not trying to solve any problems. I’ve got no issues, but I am going to get older at some point. Should I do something like you described? No alarm, see what happens, go to bed at a consistent time every day, and see where I land over the course of six months? It was less than six months. It slowly happened at first and all of a sudden, it was quick. What ended up happening was it took a grand total of 90 days. All of a sudden, my entire sleep schedule had shrunk and it was improved in quality. One thing to tell every reader is about the consistency of your wake up time. At first, you might have to set an alarm to wake up at a particular time, but then when you start waking up before the alarm, and then it starts to scoot further behind, we’re in the money here. That’s where we want to be. It all has to do with this chronotypical swim lane of a schedule that you follow. As we get older, the swim lane changes. Our circadian rhythms dial back because our body’s ability to produce melatonin begins to decline. We have two options at this point. We can rotate our schedule backwards or we can use supplemental melatonin to help us on the front end and try to keep that schedule. There are two schools of thought about how you want to do that. To be fair, if I want to wake somebody up in the mornings, I can use a blue light. They’re commercially available out there. It is easy to get your hands on to basically turn off my melatonin faucet in the morning. You can lower blue light by wearing things like blue light blocking glasses and have the red light and things like that. There’s a lot of biohackingness that can be done within the sleep universe. I like those Wi-Fi smart lights and stuff that they’ll do blue. I could have that to be my alarm instead of be obnoxious.   What a lot of people have found is those sunrise alarm clocks are cool. What you can do is put on a timer with a dimmer in it. What about this? My girlfriend needs to wake up earlier than me. Is there a product that seems like I need a vibrating watch on each person or something? There are pillow vibrating alarms. There are these little disks and you slide them in your pillow. It’s got an alarm on it and it will just vibrate. It doesn’t wake up your neighbor. Also, there’s a new product by Bose. They’re called Sleepbuds. They’re earbuds that you wear all night long. They have a private sound library. I’m helping them with it, and then there’s an alarm that only you hear in your ear. Is that available now? It’s commercially available now. You’ll love them. I have got a couple of lines of inquiry here. Go back to the phone when you were a kid. I remember disassembling rotary phones for a variety of reasons. One, I wanted to be able to make that bell go and harass people. I wanted to make it sound like I had a phone ringing in my car, which at that time didn’t exist. I mounted a rotary phone to the dash in my car in 1985, something like that. There were bag phones or car phones at that point, but they were $7,000. They were huge, but I just had a rotary phone with a windy cord on it. The thing is we had learned to trick the phone network a little bit. There were things you could accomplish by taking the phone apart and getting control of the switch hook and something like that. What I think about now is my daughter is raised in a world where you take the screws out of something and there’s nothing observable. It’s a pile of computer chips. For you and I, taking the rotary phone apart, you could see how it worked.   You can see the coils wrapped around the magnet. You could see the bells. I remember it distinctly. You could see the rotors and when they finally came out with push buttons. All these wires were coming out and you’re like, “That connects to that, and that goes to this.” It was 40 hours to assemble a touch-tone phone. I think of that as being a gift because all these devices were observable. I could take them apart, play with them, fuck with them, and then put them back together. I learned a lot from that and I feel like in the world our kids are growing up in, why would you bother to take an iPad apart? You are going to find more computer chips. It’s the same, everything is computers. Even computers, when I was a kid, the code was all observable. You learn by looking at the ones and zeros literally. That’s also obfuscated behind a pretty cartoon interface and stuff. If that’s what you described, you learned about this taking phones apart and stuff, and then that attracted you to the machines being used, can you talk about what were those machines?   The machines were things that took vital signs. I was particularly curious about how a signal could come from your body and be then translated into this idea. When I started, it was all paper. It wasn’t digital. There were pens on the paper. You had these inkwells. You would have to pump the inkwells to get the pressure to go through and then they would be squiggling along. I remember the first night I worked in the sleep lab on my residency. I went in and my dad or my mom had bought me this beautiful new white doctor’s coat. I was excited. I was on my internship. People are going to call me doctor and I go up to the thing. I’m working in and then what happened was the patient turned and the pens went fucking crazy and ink went flying. I had ink all down my thing and everybody was laughing because they knew the joke. It was fun. Back at that time, when I was learning about sleep, we would have a paper record. It would be a thousand pages long of one night, 30 seconds per page. There was an art to it. It was called throwing paper. You knew how to grab one sheet and you created the scroll yourself manually. I’m throwing paper and I’m watching EEG go by and I’m like, “Apnea.” You learned to flip a thousand pages in a couple of minutes and spot the apnea. Those machines were machines that were telling me something that wasn’t a machine and that was interesting to me. You were monitoring an analog device for humans. This is something super fascinating and snuck upon us. You’re talking about essentially a primitive monitoring device compared to now standards. In the last couple of years, I see an extraordinary explosion in sensor development. A lot of it came from MEMS because that’s where we got our IMUs with the accelerometers and the gyros delivered chips before a MEMS-based accelerometer. That was a $15,000 thing that weighed 80 pounds and was on a bench or in a cruise missile. Now, we have them in phones almost speculatively. When the first accelerometers were on the iPhone, we didn’t have an application for it. It was just there because it was cheap to do it, and might as well try it.   Many people don’t sleep because of what’s between their ears – their mental stability, their anguish, and their stress.Tweet Now, they’re in everything which is cool. Beyond that, for almost every day, we get new sensors and there’s almost nothing we can’t measure with extreme precision. We have networks to bring that data back to giant supercomputers to analyze it. I feel like maybe one of the things that makes this particular point in time, the inflection point for a sleep study, is that now we have the tools to do it better. We have those sensors. We have those data science, which is a thing now too. In a way, that’s different than what it was before, many years ago. My prediction is that sleep laboratories will go away to a certain degree. Is it because we’ll learn so much? No. It is because technology is advancing quickly. When you go into a sleep laboratory, we put 27 electrodes. At first, we had to glue them onto your body with something called collodion. When we had to pull them up, it rips up hair, skin, and all that. It was terrible many years ago. Now, there’s a home study. You send it if they have a nasal cannula, they have something on their finger and they have a box on their chest, and we’re almost done. The technology advancing in the assessment is great. Unfortunately, technology in the treatment has not gone well. That’s the order of operations. When we look at technology and we look at the influx of technology into the idea of sleep, here’s part of the problem. Technology is great for sleep disorders but not great for disordered sleep. Why is that? Sleep is the most natural process that you can do other than breathing. We don’t need technology to help us breathe. The reason many people don’t sleep is because of what’s between their ears. It’s their mental stability. It’s their anguish. It’s their stress. Seventy-five percent of insomnia is either depression or anxiety. My goal is to try to help people figure out how to not just lower their anxiety in the acute state, but to help them figure out how to lower their anxiety in a chronic state, and that’s hard. That gets you back to that psychology and the same interventions people are using for anxiety in general. They need to improve their sleep with all the stuff around meditation and breathing and those things that people are taking on.   They have to be tweaked because when you do traditional meditation and traditional breathing, it doesn’t make you sleepy. It brings you to the present. It makes you relaxed. Being present, being relaxed, and being unconscious are three separate states. Does being present, relaxed, and unconscious show up differently on your monitoring devices? It does. If I have that device on when I’m meditating and it makes me feel present, that’s not getting me ready to sleep.   I would argue that there are certain meditations that you would do prior to bed and there might be ones that you do in the morning. I would say that there are breathing techniques that make more sense in the evening versus the morning. Sleep works in the sympathetic nervous system and parasympathetic nervous system. There are two systems, sympathetic and parasympathetic. Sympathetic, I always think of as energy, and parasympathetic is relaxed. I always think of it as Sympathy for the Devil, that song from the Rolling Stones. That makes me think of going in dancing. When we’re looking at parasympathetic, that’s the relaxed situation, and relaxing is different than sleep. Relaxation primes the pump for the sleep process. It all comes down to some physiology, believe it or not. If you can get your heart rate below 60 for a period of time, the sleep process will institute. It’s literally that simple sometimes. When you’ve got people who’ve got high blood pressure, stressed, and got anxiety. What’s the thing that is up? Their heart rate. Heart rate variability becomes an interesting issue. When you start to look at heart rate, you want it to go down and get to 60 because when it’s at 60, you slip the car into third gear and the brain clicks on. That’s when things like growth hormone are emitted during a phase 3 sleep or 4 sleep, which is all that physical restoration. During REM sleep, that’s when you start to move information from your short-term memory to your long-term memory. That’s where it gets interesting. People come to me sometimes and they’re like, “I’m not as concerned about the physical. Do I have Alzheimer’s, Michael? What’s going on? My memory is shot. I’m 40 years old.” I’m like, “How much do you sleep?” They say, “I sleep 5.5 to 6 hours.” I’m like, “There’s your problem. Can we extend your sleep a little bit? Give it three months and let’s see how your memory does.” What people don’t realize is REM happens in the last half of the night. If you only started the first half and you wake up after six hours, you’re missing that last two hours of REM sleep. That’s where the problem comes in. I have a couple of questions here. I have low blood pressure. I have a low heart rate. You should be sleeping all time. I sleep all the time. I lay down flat and I’m asleep. It is easy. I don’t feel like I need as much sleep as I get, but I’d take it because I can. It seems like it’s not hurting anything. There’s not a lot to do now. It might be easier for me because my heart rate and blood pressure are low in general. I don’t have a lot of anxiety or problems and things that keep me freaking out. It’s going smoothly. Michael, I want to up my quality. What would I do? We would get you again in your chronotypical swim lane. We’d start to look at what’s going on in your body. I’d look at your vitamin D, magnesium, iron, and melatonin levels. Let’s make sure that you’re not deficient. I think it’s something 80% of the US is deficient in magnesium and vitamin D. We’ve got to get you back up to par levels and see if your unit is functioning right. If you’ve got low energy, vitamin D would be a good thing for you to have every morning. I’ve been doing it, but I didn’t necessarily know to do it in the morning.   I prefer mine in the morning. It’s a fat-soluble vitamin so you have to have a little bit of food with it. If you’re an intermittent faster, that may or may not work for you. I don’t eat anything for sixteen hours. I only eat lunch and dinner. I’m the same way and my body is used to it. I would try it out with you and see. Most people take 5,000 international units every single morning. I could do that maybe with lunch.   I take it in the morning without food. You’re supposed to take it with food for absorption, but you can get higher absorbing stuff. What about magnesium? I started taking magnesium because I figured it will be good for my muscles. It will be good for your muscles, but you’re deficient in it because most people are. Unfortunately, our soil has been over tilled. Magnesium doesn’t appear to be coming up through the roots and getting into the stocks for our fruits, vegetables, and things like that. I do supplemental magnesium. I had a cardiac event years ago. We think that the reason that I had it was because of low magnesium in my cardiac muscle. When you have marathoners who dropped dead in the middle of a marathon and you autopsy them, it turns out that they have low magnesium in their cardiac. We wanted to avoid that. I take 250 milligrams of magnesium with vitamin B12. That helps catalyze it in. It helps absorption, but it also helps with the rapidity of metabolism. It speeds up overall metabolism, which is interesting. I take them together in the mornings and it’s been highly effective for me. Once I’ve checked you out and decided what’s going on with you, and you’re at par level, then you say to me, “Michael, now I want to up my game,” I’m going to look at your alcohol and caffeine and try to understand where do those play a role in your 24-hour cycle. I never had a drink. What about caffeine? Melatonin is the key that starts the engine for sleep.Tweet I have caffeine every afternoon. What time? Between 1:00 and 2:00, after lunch.   Do you feel like you need caffeine in the mornings? No. I feel like if I don’t take it by 2:00 or 3:00, I’m going to have a headache. I’m feeling like I need a nap. Do you get a headache from not having caffeine? How much do you take at night or in the afternoon? Probably 250. You are at 2.5 cups of coffee. I never had a cup of coffee, but I drink either Red Bull or an energy shot or something.   There are two things I would do with that. It’s not a bad practice if that’s what helps you get there, but I’d rather find more natural sources of caffeine for you than a Red Bull because you get a ton of sugar. No, I take the sugar out. I’m on a sugar-free energy shot.   That’s better, but there are some better like green coffee, green tea extracts if that’s what your goal was, I’d rather see you taking that long-term. When we look at caffeine, here’s the thing to remember. Depending upon how quick of a metabolizer you are, caffeine has a half-life between 6 and 8 hours for half of it to be out of your system. When we’re talking about refining our sleep, caffeine is a stimulant. It doesn’t matter how you slice it. I’ve got lots of people who say to me, “Fuck, Michael. I can have a cup of coffee at 8:00 at night and still fall right to sleep. Caffeine doesn’t affect me.” Let’s be clear, caffeine is a stimulant and affects everybody. People have different sensitivities and amounts and metabolism is which changes the variability of the effect. Somebody who’s lean like you and takes 250 milligrams of caffeine, you’re at the upper dose of what a human should have in a day. I would look at the timing of that. If I could, I might start to dial it back a little bit. Maybe you don’t need 250. Maybe we’d start with 200 and see how you feel. Maybe we go to 150. The goal then is to start to look at how much what’s called alpha intrusion that we see into your EEG. What caffeine does is it makes your brain waves go a little fast. When we’re sleeping, we want our brainwaves to go slow. What happens is it’s hard to get that. Sometimes the fast brainwaves lay over the slow brain waves, or they push out the slow brainwaves and all we have is fast brainwaves. When all we have is fast brainwaves, we don’t get stage 3 or 4 sleep, which means we don’t get that physical restoration. We then wake up in the morning and feel like shit, and we want to drink more caffeine. Caffeine is a way to speed up the brainwaves. Is melatonin a way to slow them down? Can you think of them as the opposite of caffeine in some sense? Is that what you use to slow down your brain waves? With melatonin, it’s a circadian pacemaker. Melatonin has an effect on certain neurotransmitters that cause a cascade of reactions to start the sleep process. Melatonin is the key that starts the engine for sleep. You still have to have oil and all these other things when you have an electric car, maybe not. It does seem mild, but remember it’s a hormone. It’s not supposed to act like a sleeping pill. It’s not a drug. It’s supposed to act like a hormone. It is supposed to be subtle and be able to have an overarching and reaching effect across the body. The biggest thing about melatonin is understanding when you take it. The moment of ingestion, it begins to be absorbed, it’s going to be sending signals to different parts of your brain to say, “We’re going to change that internal schedule.” Caffeine is the opposite. What I would say the opposing from caffeine is something called adenosine. As you go throughout your day, your brain accumulates adenosine. When a cell eats a piece of glucose, something comes out of the backend. One of those things is adenosine. It works its way through the system. It goes to a specific area in your brain. As it accumulates, you get sleepier. If I was looking for the opposite of caffeine, it would be that. Why don’t people take that? When you look at the molecular structure of adenosine and caffeine, it dropped by one molecule. Caffeine fits right into the adenosine receptor sites. That’s why caffeine blocks sleep. That’s biology, which is interesting. I haven’t ever seen anybody make. You’ve explained to me before with melatonin, people are doing it wrong. They’re taking a bunch when they’re tired or when they want to go to sleep. You’ve said that they should start earlier in the night to take it. It’s like 90 minutes beforehand. It takes about 90 minutes for the plasma concentration levels. If you’re taking it in a pill form, you’re looking at 90 minutes for you to reach plasma concentration. If you’re taking it in a tincture or liquid form that you put under your tongue or sublingual, it would be 30 to 40 minutes for better absorption. I’ve never done melatonin, but you’ve said that 1.5 hours before taking one pill and an hour before taking another and a half hour before you want to be asleep. Is that right? No, take it one time an hour and a half before. I misunderstood. What are the other things that are meaningfully effective for people if they want to take a pill to affect their sleep and what’s up with Ambien? There are a lot of different ways we can walk down that path. There’s a pharmaceutical intervention. When we look at something like Ambien or what’s called zolpidem, it’s a particular compound that was built to affect the benzodiazepine, alpha 1 and alpha 2 receptor sites. The compound has a molecule that can fit into that receptor site and turn it on. By turning that benzodiazepine receptor site on, it lowers anxiety. In this specific 1 and 2, it increases the possibility of sleep. When you look at benzodiazepine receptors as a whole, it’s an anti-anxiety thing. The first sleeping pills were anti-anxiety drugs. What happens if people get so chill that they fall asleep and then people are like, “Maybe there’s a second use for that. Let’s do sleeping pills.” That was what was all the benzodiazepine universe. Now we get an Ambien called a non-benzodiazepine hypnotic. The difference between the old benzos and the new non-benzos is the addictive potential. It’s better technology. It is cleaner. It’s the right receptors that move through. The next question becomes, when are we going to get to the drugs that improve sleep, not just put us to sleep? I call those the Frankenstein drugs. Why? I’m not convinced that our brain isn’t the best regulator of how much sleep we should have. Do you think your brain could do the job? It just needs a little training sometimes. My concern is, what if you’re not supposed to have more stage 3 or 4 sleep than your body has? You’re not supposed to have REM sleep than your body has. Mother Nature is good at shit. When I look at those types of structures, I want to go forward but with mild, healthy trepidation and concern. One of the things that happen is when you start to improve on a natural process, you end up with a supernatural result. Sometimes supernatural results are positive and sometimes they are not. That’s when we have real problems. When you say you’re less optimistic about technology helping with the sleep issues that you’re attacking, which are less clinical problems and more life habits and patterns that people have established, resolving anxiety and things like that. Maybe it’s true that you would not look to pharmaceutical innovations necessarily.   There are holistic technologies that are coming up that are interesting to look at. I started working with this company and it was all of it. I’ve learned a lot. Let’s say you get into a car accident, your head cracks open, you go into the ER. One of the first things they do is they wrap your head nice. The reason they wrap your head nice is to slow down all of the blood flow and all of the fluid that’s going on because they’ve got to figure out what’s the problem. They’ve got to fix it up. That’s how that works. It’s called the neuroprotective effect of cold. It’s important. The question becomes, when are we going to get the drugs that improve sleep, not just put us to sleep?Tweet There’s a sleep researcher, Dr. Eric Nofsinger, who has been doing this for many years. His main interest was what we call ruminative thought. “I can’t turn off my brain before I go to bed.” It’s the number one complaint I ever hear in my office. We call that ruminative thought. It was like, “My brain is going. I can’t slow it down. I can’t get to sleep.” We know what that’s doing is it’s causing a lot of autonomic arousals. That sympathetic nervous system is kicking into gear because you’re in bed. Nobody is talking to you. Nobody is asking you to do anything. Thoughts come flooding out like, “What am I going to do with this problem?” It’s anxious. We want that blood. He did MRIs on these people while they’re trying to fall asleep. He discovered massive blood flow in the frontal cortex. He said, “I used to work in the ER and they had this thing called the neuroprotective effect of cold. What happens if I cool their head?” He did and it worked. They fall asleep with their head freezing. Ten years’ worth of research, they’ve had 12 or 15 publications in real journals, real science. Here’s what they discovered. It was almost like a headband that goes around your head. There was a string that came down and it came down here and there’s a unit here. It would throw liquid in this thing that goes around your head and it would make your head cooler throughout the night. It’s a little bulky, cumbersome, whatnot. They discovered that people who could turn off the brain, turned off the brain and went to sleep. What they’ve done is they’ve miniaturized it and they’ve got it into a traveler pack. This is a product now. I don’t just need an ice pack on my forehead. That wouldn’t even work. Why? It is because you have to have a particular temperature and it changes throughout the night based on your circadian rhythm. There’s real science. What’s that product called? It’s called Ebb therapeutics. They came to me and they’re like, “Michael, we want you to test our device.” I said, “I don’t have ruminative thought.” They said, “We just want you to wear it and tell us what your experience is.” I put this thing on and to be fair, it looks damn goofy. It’s like 2 inches off my forehead, a big black thing. It’s got a cord, it’s battery operated and I have to click the button, but it’s not as bad as the first one was. I’m like, “This is going to be ridiculous. How am I going to sleep with this thing on my head all night long? My wife is looking at me like I’m crazy,” because I test out all this shit all the time. I put it on, I turned it on, and I closed my eyes. When I opened my eyes, it was 6:13. It’s a luck. People are going to love that thing.   I said, “I’m not going to wear it the next night.” The next night didn’t work the same. I woke up multiple times, and that stuff. I tried it again. You put it on people with bigger problems than you? Yep. It takes about three weeks. We discovered that over the course of time, it helps keep people’s foreheads cool. Does it train them to do a better job on their own or do they need to keep with it as a habit?   What’s great about this product is there’s counseling that comes along with it. You use the product and use the counseling, and then eventually you come off the product. It sounds harmless to do. It’s super harmless. It has no side effects. Most people seem to have their brains have frozen already. They found out it’s working well for migraines and they started using it for menopausal women. They’re reducing hot flashes in the middle of the night. This is incredible.   It was cold, but that’s it. I love the technology aspect that I think is interesting for sleep. We’re going to come up with better drugs. By the way, I think we should, because most people think insomnia has just one flavor. There are like 30 flavors of insomnia. If we can dial in, if there’s insomnia associated with pain, if we had a special pharmaceutical that could break that cycle, then we can teach people how to deal with their pain and get them off that drug. That would be a fucking miracle. Why can’t we have more sleep drugs that are more personalized to people’s problems? That’s great in the pharmaceutical universe, but that’s fifteen years and $15 billion to get down that path. I’m also interested in some of these more holistic things like cold, breathwork, meditation, circadian timing, things like that. What are the quack things that you see people are trying? CBD. One of the biggest things that drive me crazy is I had a company come to me and they said, “Michael, we want you to endorse this product. It’s a CBD pillow.” I said, “What? I don’t get it.” They said, “What we’ve done is we’ve soaked the pillow in CBD. When you turn it on your head, this break open, and then you breathe in the CBD.” I said, “That is the biggest crap of shit I’ve ever heard. Tell me, how much CBD did you put in the whole pillow?” They said, “You’re going to love it, 300 milligrams in the whole pillow.” I said, “That’s a dose for one night.” They’re like, “What?” I’m like, “Did you read the literature? I haven’t seen CBD effects in sleep in anything less than 200 to 250 milligrams of CBD. That’s like a whole bottle.” Have you seen it have an effect on people if there’s no THC content? I have. I’ll tell you where I’ve seen it the best is in pain patients because it helps lower inflammation. A lot of people in pain got three problems when it comes to sleep. Number one, they’re anxious that they’re not going to be able to get comfortable. Number two, they’re anxious that they’re going to have a painful event in the middle of the night, which is going to wake them up and there’s a lot of anxiety associated with that. The third aspect that’s for sleep with them, usually has to do with what a pain medication that they’re taking that can have a side effect or an effect on their abilities. We’re always trying to look for things, and CBD might not be a bad idea but have the right dose, and they don’t need a pillow to get it. What other ridiculous stuff? Maybe another way of thinking about it is, what old wives’ tales or urban myths do people have internalized about sleep that are counterproductive or not working?   One of my favorites is when people tell me that they need to eat a turkey sandwich or drink more milk before bed. Those are based on the idea that there’s a trip to bed in each one of these. I calculated it out. You’d have to eat a 42-pound turkey to get enough trip to bed in your system. What about milk? One gallon and a half of milk to drink to get enough trip to bed. It’s freeing because I grew up in Alaska, where we were the highest per capita consumers of ice cream. We drink a lot of milk. It was normal. I would drink milk as a beverage. One day someone told me, “The lactose in milk makes you tired.” From that day on, whenever I drink milk or eat ice cream, I feel tired. It fucking programmed me and I stopped. I have this impressionable psychosomatic response or something from people telling me that milk makes me tired. I stopped drinking it, which is probably fine, but it also keeps me from eating ice cream when I want to because I don’t want to get tired. Don’t go to bed hungry because if you have an empty stomach, you’re going to be thinking about your stomach going to sleep.Tweet To be fair, you can eat as much ice cream. My brain will accept that and believe you and I’ll be fine now.   When we look at foods before bed, it’s interesting. I worked with this company called Nightfood and we create snacks prior to bed, which is sleep-friendly. We don’t want people to go to bed hungry because if you had an empty stomach, you’re going to be thinking about your stomach going to sleep. There are also some data to suggest that we want to keep the microbiome happy as we’re going to bed as well. I worked with this company, we had bars, but your favorite thing is about to happen. We have an ice cream. What’s different about your ice cream? It’s not like melatonin flavored ice cream. It’s got an ingredient profile that’s very pro sleep. I mean that it’s about 75% carbohydrate and 25% protein. You keep the calorie profile down to about 150 calories for the pint use. Most people seem to like the pint, but what’s interesting is carbohydrates make you sleepy. The reason that they do is that they promote serotonin. What’s interesting is when you’re sleep-deprived, what do you crave? I don’t know. I’m high calorie, like donut, muffin, that kind of stuff. Deep-fried stuff. What your brain is doing is sleep deprive. For whatever reason, you’re sleep-deprived, which has caused your cortisol levels to jack up. The cortisol levels stay high and your brain doesn’t like how a lot of cortisol is all in it for long periods of time. That’s when you get things like adrenal fatigue and real long-term stress, acute stress disorders and things like that. It wants to calm it down. Your brain tells you to eat a Snickers bar because when you eat that Snickers bar, it causes serotonin to be produced, which quells cortisol. The reason that when you’re tired, that you want to reach for a Snickers is because of cortisol. You’re not going to get energy from that. You’re going to get sleepier from that. You get a small sugar boost and then you crash. It’s terrible. If you get sleepy in the middle of the day, you’re better off walking outside, getting fresh air and sunshine because between 1:00 and 2:00 in the afternoon, your core body temperature has a bi-modal distribution. At 10:30 at night, your core body temperature drops. That’s a signal for the brain to release melatonin. There’s a secondary drop between 1:00 and 3:00 in the afternoon, but it’s smaller. That’s why everybody gets tired because it is 1:00 or 3:00 in the afternoon. Don’t go and eat a bucket of muffin. Go outside and get some sunlight, reduce that melatonin production and you’re good to go. I bet you could try that and reduce your caffeine. What about modafinil?   It’s an interesting compound. When you look at modafinil, which is also called Provigil, this was a medication it’s called. It was an orphan drug when it was first brought over. The idea was to bring it over to treat people with narcolepsy. I believe it’s an orexin agonist. I’m pretty sure what it does is it goes for these particular receptor sites that are your sleep center and it turns those off. We did this for narcoleptics because initially, we thought the narcolepsy was where the brain was switching on to sleep in the middle of the day. People were having nap attacks and sleep fits and all these different things. We’re like, “Let’s stimulate the hell out of them and see what happens.” Later on, modafinil comes on board and says, “We don’t have to stimulate the whole body. We can focus more on the brain and the sleep centers. Let’s go there first.” That’s what Provigil does. We call it a non-stimulating stimulant. Here’s the thing. Narcolepsy only makes about 50% of the population. It’s tiny. There are more Provigil prescriptions out there. There are north of 5% of the population, ten times in the US. The question is, why? People use it as a performance-enhancing drug or nootropic. What’s interesting about it from an nootropic standpoint is all it’s designed to do is focus on the sleep centers and be able to calm them down, make it so that you’re not sleeping. It turns out over the course of time, we realized that narcolepsy isn’t that problem. Narcolepsy turns out to be a nighttime problem, not a daytime. Narcoleptics get shitty sleep at night. We now give narcoleptics sleeping pills, which seems completely counterintuitive. We give them sleeping aids to make them sleep deeper, and then they’re not as tired during the day. We use the Provigil to maybe stave off a little residual daytime sleepiness. What’s nice about Provigil is it’s not a full-on stimulant. If you took Adderall, caffeine or cocaine, it’s going to jack and there are side effects and problems. Provigil has less of that, generally speaking. My understanding is there’s not a lot of negative side effects.   I’ve taken it personally before to try it out. It’s a clarity that seems to come with it and the level of alertness, but it’s not like you’re jittery. I learned about it from fighter pilots who were using it when they got up flying for sixteen hours.   The military has these things called the go pills and no go pills. Go pills are Provigil, no-go pills are Ambien. That’s how it works. I’ve seen people using it in the early introduction to Provigil. It was like, “At midnight, when you normally go to sleep, take one of these and you’ll get another four hours.” That worked. After that, you could have another one and get another four hours. We could do it all week long and not sleep. That’s a bad idea, why? We can’t replace the natural process of sleep. There are consequences. For example, if you continue to take Provigil, what occurs over the course of time is that it isn’t changing that adenosine buildup that’s still going on inside your brain. The body will eventually crash. The good news here is nobody has ever died of sleep deprivation. The longest person that’s ever been awake is a guy named Rudy Gardner, 11 days and 25 minutes. He used tons of caffeine and he was playing pinball. It was in the ‘70s. He played pinball for a week or some crazy shit like that. He had some significant side effects and consequences for it. By day 5 or 6, he was hallucinating badly. When you look at deprivation, it’s going to take a toll. I tell people all the time, “You can’t fool Mother Nature. She’s a bitch.” If you take sleep out of the equation, she’s going to put it back and it’s going to hurt. You’re not going to like this one either. Years ago, I read this firsthand account by these girls who were in college and decided to try this alternative sleep schedule. The polyphasic sleep schedule. They were doing what’s called Uberman schedule. Uberman contacted me. Is there an organization? There’s actually a person, I think. Uberman schedule is a twenty-minute nap every four hours of being awake, and you do that six times a day. There is no core sleep in Uberman. In Uberman, you do twenty-minutes, every four hours. You sleep six times a day. Your total sleep investment is two hours a day. That was the state of the art many years ago. Then a couple of years ago, people started to play with what they call Everyman’s schedule, where you have a core sleep of usually three hours at night and then you take three twenty-minute naps during the day. I know a lot about this part. With Uberman, the problem people were having was the naps had to be precise. You had to take it every four hours. Skipping one of those naps was like skipping a full night for you and I. The schedule is wildly inflexible and these people were up 22 hours a day. I read a hundred firsthand accounts by people who did them at that time. The patterns I saw were transitioning to it was painful. Sleep deprivation is horrible for a couple of weeks. Once they got transitioned to it, if they could stick to the schedule, they loved it. These girls, they finished their degree. They worked three jobs. They partied more than anyone. They had a great time. What happened to almost everybody is the successful people who get into it and stick with it for a year or more rarely lasts longer than that. Almost always, the reason is their partner makes them quit because you can’t make that schedule work with a real-life or any normal societal thing. You are awake 22 hours a day. I found YouTube videos of these people online because they’re up in the middle of the night with nothing to do. They’re talking to YouTube and they would tell you like, “It’s 4:00 in the morning. Nobody is up. There’s nothing to do. I wanted to share my ideas for ways to kill time.” They burned through their to-do list. The first two weeks, they’ve got nothing to do. They’re up in the middle of the night trying to trade ideas for ways to kill time until the world wakes up. It was fascinating.   Not much has changed. We have the core of the three-hour night in Everyman. We’ve got these twenty-minute ones that are particular times you can cycle down to about 3 hours to 3.5 hours. Here’s what happens in my experience. I’ve had multiple CEOs come to me and want to do the Everyman. Almost nobody wants to do the Uberman. It’s too difficult to try to accomplish. There are three problems there. Number one, you’re 100% correct. You didn’t say the actual word that I was looking for you to say, but I’ll tell you what I want. People get lonely and loneliness leads to a lot of major problems. When people start experimenting with things like drugs or alcohol, you have to be almost completely no drugs, no marijuana, none of that. That’s one problem is people get lonely. Number two, what I’ve discovered and I’ve only had one person do it successfully is that by the third week, if you have any proclivity for depression, it pops and you end up with a major depressive episode. Some people are suicidal. For any single person that asks me about this, my first thing is, “Do you have any depression in your personal thoughts or do you have any in your family history? If you do, this is probably not a good idea.” You are right, there are certain fragilities out there that don’t withstand this system. The final thing is there’s loneliness, depression, and it’s the sheer boredom of it. How many times can you watch Netflix? We can’t replace the natural process of sleep. There are consequences to that over the course of time.Tweet The other thing to screen is, do you have something to do? Some people do. If you want to write a book, then that might be good for you. I haven’t looked into this for years now, but I remember at the time, sleep scientists didn’t want to touch it. You’re talking pure heresy. You’ve got to remember something, I’m a heretic. People don’t like the stuff that I do because I look into the science and I want to push and innovate the science, but 99.9% of sleep specialists would never consider in a million years. They’re not recommending your books. Maybe it was certainly true then, apparently still true now, but one of the theories of why Uberman worked is because there were people who got on it and did it for years and were fucking prolific. I remember reading, the theory at the time was that you’ve got these different sleep cycles. You’ve got your deep sleep, light sleep, REM sleep, and is there a fourth one? There are two phases of six, 1 and 2, 3 and 4, and then there’s REM. The theory was, once you train yourself to take the twenty-minute nap, people under Uberman lay down and sleep for exactly eighteen minutes. They then wake up. I got the Zeo Headband. I was on their scientific advisory. The first sleep tracker company in history. I got the sleep tracker. I put it on my head and went to sleep and I watch in the morning. In the morning, you get a graph that shows you all your sleep cycles. I would get spread over 3 or 4 sessions in the night, about 1.5 hours of REM. What I think I saw if I remember correctly with the people on Uberman who used EEG or whatever to see their sleep cycles was they would lay down, get eighteen minutes of REM and wake up. They’re still getting about 1.5 hours of REM in a day. They’ve trained themselves to do it specifically in those naps. The lay theory at the time was maybe the REM is an important part of sleep and this deep sleep is some evolutionary artifact that we can forgo, which I thought was an interesting way of interpreting that as like, “That’s why the people on Uberman are fine.” They’re getting all the REM. They’re getting as much as me. I’m wasting a bunch of time in between my REM cycles in the middle of the night to get that 1.5 doing deep sleep. You are almost there. I would say yes for REM sleep, but you’ve left out arguably the most important component, which is stage 3 and 4. Why is that important? It’s all physical restoration. The body isn’t going to work without stage 3 and 4 sleep. If all you got was 1.5 hours of REM, your brain might be swimming, but you are not going to be able to move. It describes a lot of people. There’s the opposite. Maybe a lot of other people are getting a lot at stage 3 or 4 with no REM. That’s why their brains are useless.   We can say about the Uberman system is it takes out a lot of the noise. That’s the goal. What I do with my high-performance people is I do the same thing, but I don’t have to use Uberman. I don’t have to use Everyman because if I put you in your chronotypical bedtime swim lane, it automatically shrinks. If I shrink you to six hours a night of super high-quality sleep versus four hours, and you have to do this crazy rotation desk schedule, what would you rather do? I’m doing the same idea but in a healthier and more genetic way. I’m looking at your genetics. I’m matching your schedule to your genetics as opposed to somebody saying, “I’m going to do this Uberman schedule, and I’m going to arbitrarily pick this time to sleep.” I would argue that what I’m doing is a little bit safer. That helps a lot. I’ve seen you work on and other people work on a variety of different kinds of dietary supplements, things that look to me like deluxe placebos. I’m curious about, what supplements might be meaningful to take and then, how do we substantiate that? What I see with this is not just sleep-related necessarily, but with a lot of these supplements is a shit ton of total bullshit like the CBD pillow. It looks like that to me. I can’t seem to map their claims. We have two problems with the supplement. One is almost no clinical testing. That’s what you’re starting to talk about. We have a secondary problem that’s bigger than the nonclinical testing. The secondary problem is whatever testing that’s been done on a single ingredient, then people would use that to substantiate what I call kitchen sink products. They’ll take twelve ingredients, mix it up. They’ll take twelve different studies to say that this thing was effective. This one study and one ingredient profile, as opposed to what are the interaction effects and what was your population? There’s no real research. What happens is people go out there and they say, “I’ve got a supplement. That’s going to be good for sleep. It’s got valerian in it, which has got a research study behind it.” They can say it’s scientifically proven, but it’s not. It’s a big farce for everybody out there. My goal in the supplement world is to number one, not give anybody anything that they don’t need. Step number one is what vitamins, minerals, nutrients are in your body, in a lower state, in a deficient state that we need to bring up to par levels. That’s when we were having a discussion about PER3, magnesium, iron and melatonin. For all those, we need to do blood work. Although you can do saliva for melatonin, but remember for melatonin, you want to look at what time of day you take it. It’s going to be different levels at different times of the day because it’s circadian. Once we get past that, then there are two questions, “Do I want to give you an herb that helps you fall asleep or do I want to give you an herb that accentuates a particular aspect of your sleep?” Those are two different animals. I’ve been playing around with some mushrooms, not like psilocybin mushrooms, but general mushrooms, and starting to learn more. Lion’s mane, it turns out, appears to help with REM sleep. I have heard that before. Do you know Paul Stamets? This guy has been doing mushroom research, like renegade shit for a long time. You’ve got to beat this guy. I don’t know him. I’ve listened to some interviews with him and he was also a computer nerd way back. I knew that, but there are some good interviews online with him. I’ll find him. That guy knows a shit ton about what’s possible with mushrooms aspects of it. For me, I’m not trying to create something that’s not in nature. All I want to do is I want to get you back to a functioning level. By the way, your generalized nutrition has a lot to do with it as well. There’s a lot of data servicing about something called your microbiome. We now know that your microbiome is the nerve center and send signals all over your body to tell your body to do different things. A lot of people know what the microbiome is by now, but it’s fascinating because it was not part of anyone’s conversation many years ago. We’re at the beginning of understanding it and the way I always describe it, you’ve got all these bacteria that live in your gut and what you eat, it feeds them. What they spit out feeds you. That layer of indirection is in everyone, but it’s different for both of us and everyone else. Since we don’t have a way to measure it, this is why a lot of these diet concepts that work for one person don’t work for someone else.   We’re starting to see more personalization in the diet side of things because what we can do is you can measure your microbiome and you can get stool samples and things like that. It’s a little bit more sophisticated and you can get a nutrient profile of like, “What do you need? What do you not have?” What I’d be interested to learn is what your view is on how understanding the microbiome is going to play out? We now know that microbiome has an influence on our circadian rhythms and the microbiome itself has a circadian rhythm. If we tune up our microbiome, by understanding our nutrition, getting rid of things like high fructose corn syrup, lowering our processed sugar, things like that are generalized good recommendations in any way, what we will find is our microbiome, the biology of it will get better, which will allow our entire human unit to work better, which makes us sleep better. A recommendation like that is more true for some people than other people because of the makeup of the gut. It has a lot to do with your dietary lifestyle. I started to learn not that long ago, I love McDonald’s French fries. They do not work well for me and that’s something that I have to accept. There are food consequences. My doctor prescribed French fries because my blood pressure is low.   I would say salt it up, brother. You need more fried food, I don’t, but that brings to your point, the personalization of it all. My prediction is that we’re going to see more personalized medicine, diet and sleep, moving into the future. I’m excited about the technology that’s starting to come out in pharma, in holistic, and what’s coming out in lifestyle. I’m learning about things that I never would have thought about before like breathwork like, “I know how to breathe. Why would I need breathwork to help me sleep?” It helps you sleep. We need to be more exploratory in the sleep unit. These ideas, let’s fucking go and try them out. Let’s test them. Let’s put it through a scientific methodology so we can see if it works and let’s advance the field. That’s what I want to do. Unfortunately, a lot of my colleagues are stuck in the clinical side of it. They just treat apnea. It’s true outside of sleep science and a lot of areas in science. We have this problem where people are getting narrowly focused. A lot of the incentives are screwy to keep people from wanting to do these new things. What’s the thing that you wish you had that could advance sleep science? Do you want the truth of it? I am working on it, cannabis. I think cannabis is where the revolution is going to start. Historically, unfortunately, something like insomnia has been what we call door handle diagnosis. When I am in the room with the patient and I am about to leave, I will have my hand on the door and they will say, “By the way, doc, I am not sleeping well.” Here is what the doctors generally do. They reach in their pocket, they pull out the prescription pad, write the prescription for Ambien and say, “Try this for 30 days and you should be fine.” Nothing can prove that true. When the person got hooked on this drug, they have to ask for this gamekeeper. If you are a drug addict for trying to go to sleep, it is not like I am saying, “I’m smacking heroin here.” Ambien doesn’t even have a street value but we have to beg doctors to give us something to help us have a natural process. It’s like there is something wrong with that. If we tune up our microbiome, it will allow our entire human unit to work better, making us sleep better.Tweet I believe that cannabis has the ability to lower pre-sleep anxiety. In our conversation, we were talking about how 75% of insomnia is related to depression. If we can find the right constituents within cannabis, I am not talking about getting people stoned. I am talking about helping people to sleep. A lower level of THC can lower anxiety. Here is the most fascinating part and many people haven’t seen this research, the pathways of melatonin and THC are almost identical. They use similar neuro pathways. There is a mixing that’s going on there somewhere. It gets interesting. My goal is I want to be the tip of that sphere. I want to be the guy that’s right on their front and doing the research and saying, “Let’s fucking figure this out.” It is one of the oldest plants there is. People have been using this for thousands of years. We are now in the state at least here in the US. It’s where we could finally start to learn how it works and what works. Thirty-five states have proven it for medicinal use, it is 15% to 18% for recreational. The horses left the barn and let’s wrap some fucking science now. I see extraordinary results for people but not, unfortunately, the science we need to understand what is happening. Do you have any other cool things you are working on? Don’t you have at least a couple of books? Are they any good? I do. I like my books. I am working on my fourth book. It is going to be all about energy and humans. My first book is called Good Night. That is a do it yourself 30 days make yourself better. Is it obsolete now or is it still useful? It is useful all the time. My second book is The Sleep Doctor’s Diet Plan, lose weight for better sleep. There is all about the relationship between the metabolic process and sleeping, how those two influence each other. I give an interesting recommendation of how to sleep better to help your body be prime to losing weight. My third book is called The Power of When. It is all about the chronotype and the circadian rhythmicity. I was looking at that aspect and starting to learn how my bodily hormones are on a particular schedule. If I can predict it, I can choose what time of day to do something when my hormone levels are going to help me. That was my third book which I thought is fucking awesome. My fourth book is moving into taking all of that and saying, “Why do we sleep? We sleep to live. We sleep to spend time with our family, for our career, to innovate, and all of these things. I want energy from sleep.” I am combining with an expert on movement. We have created a way to identify your chronotype and body type. We have a series of sleep aspects and movement aspects to give you energy throughout the day without having to use caffeine and stimulants. That’s going to be the next one. How long before that’s out? It will be out in December 2021. You were working on a couple of other products. I work in the supplement arena, non-cannabis supplement because a lot of people are interested in that. I am also learning a lot more about counseling and scaled counseling people. When you look at the mental health aspect, we are finally getting technology like texting, it is a form of therapy. Michael Phelps is working with the company where they’ve got a whole platform and people can text therapy sessions. We are starting to see that this is moving. I want to see it happen for sleep counseling because there are many people that need a little attention. They need to learn from a trusted source that they can get their hands on and they need to scale. That does not exist yet but you want to work on that. I do. Do you need help? What kind of help do you need? I need to better understand the landscape to see if I can build it or buy it. The Power of When: Discover Your Chronotype–and the Best Time to Eat Lunch, Ask for a Raise, Have Sex, Write a Novel, Take Your Meds, and More The state of the artists, we have chatbots that you can train by having them watch or read a zillion conversations. It could be audio or text these days, but it learns from reading a zillion other conversations. When someone is conversing with it, it knows what to ask next. It can train the chatbot to lead them to a logical progression. You can make a decision tree and a flowchart. You can program that ahead of time. That’s how these things work. There are a number of off the shelf framework for doing that. A lot of reuse for customer support. There are better ones that can be used for healthcare. You can specifically train them despite what you have read in the thousands of conversations that don’t even recommend CBD pillows so they can be used as a way of scaling and counseling. Some of those tools are accessible. You can spend your weekend playing with it and bake your own chatbot. People can do that. You can bake a rudimentary one. What would be cool is for somebody that spends a little time with you, make your first draft one so you have your head around that process. Using machine learning, if you’ve got data that shows what you want, for the progression you want a patient to go through, these days are trivial for the computer to learn from all that data how to take a new person through that in the conversation. Most of my stuff is protocolized. If that’s true then, computers fucking love that. What machine learning gets you is pass that part is like, “What do we do in the situation where we don’t have the decision tree?” The easy way to think is for our lives, computers have been able to do anything that you can define in a series of logical steps. What machine learning brings us is the ability to have computers do things when we don’t understand what the logical steps are. That’s the difference. That is why it powerful, fascinating, scary, and difficult to get your head around because it can do things that we don’t understand. That might be something for you to play with, but you could start the old school decision tree style chatbot systems because they are powerful. They need to be applied to a problem. If you know what direction to take somebody in, like the chatbot can take care of doing that, 24/7 on text whenever somebody wants. I don’t think it is going to be that hard for you to make something like that. Show me the flowchart and maybe they can reach out to you. I thought of one for a couple sleeping. I created this quiz that would be a chatbot thing that would have compatibility. Wouldn’t it be great if Match.com has it before you hit? It’s like, “You are a morning person, she’s not. No chance.” There is a lot. By the time you are sleeping with somebody, it’s too late. I would like to create something that would be fun. That’s part of the screening process. Can you imagine how well that will be? I did have some experience in dating women that were not compatible in bed for sleeping. It is like, “You run too hot, if I can’t cuddle you, forget it. It is not going to work.” Somebody might want to cuddle, but there is this temperature. By the way, a chatbot or an app like that has a lot of utility, not just from a fun and interesting standpoint but it is going to catch people’s interest. They start to think about those things, and then I can teach them about body temperature, circadian rhythmicity, melatonin. Let’s figure this out in a scientific way. That’s the goal. You can use the chatbot for intakes screening like, “Chat with this bot for a while. If we have a good recommendation for you, we will let you know.” That’s a way to scale it. Are there any other products that people can get that you worked on? I made my own line of blue light blocking glasses, which I like quite a bit. Do you wear those at night? Wear that 90 minutes before going to bed to help lower the amount of blue light exposure if you have a problem sleeping. If you don’t have a problem sleeping, you don’t need one. Those are interesting products. Also, I worked with different companies to help them learn more about the science of their products. Part of what I am working on now, which is interesting, is the Mattress Universe. I believe that sleep is a performance activity. I am a runner. If I go running, I can run in my flip-flops, cut-offs, my torn t-shirt, and my Boombox. I think you should do it though. There is a relationship between the metabolic process and sleeping; the two influence each other.Tweet If I’ve got my Asics on, my Dri-FIT wear, and my iTunes going, I can run. It is a performance. Sleep is the same way. If you’ve got the right equipment, you will sleep better. I will argue that between 20% to 25% of sleep is environment influence for someone. Especially for the people who have got insomnia, believe it or not, there is now a way to look at people’s sleep genetics even it has 23andMe. I’ve got a company that I work, I can run your genetic in 74 different sleep markers. I can look if you have genetics for poor sleep quality or for lower amount of sleep total time. Is that something you do or something that people can sign up for? There is a group online that helps you with it but they just give you the data. They don’t interpret it. What I do for my client is I get data and I will do a full-on interpretation. I’ll say, “These four snips are variations for obstructive sleep apnea. Let’s take a look at each one of these studies and see what identifies for you and let’s take a look at the data.” It is a little painstaking at first. I have to get it down a bit more refined. It is possible. That becomes a roadmap in walking that path. Are you available for people who need a sleep coach? One of the things I’m trying to do is scale because there is only one Michael. I have a small practice. I see 68 patients and I do see people like Paris Hilton. At the end of the day, I want the best in the world so I can focus on interesting problems and then take that information and spread it. For everybody else, they can read your books. Do you have a podcast? I have a podcast called Sleep Success with Dr. Michael Breus. In my website, I’ve got over 800 blogs on these topics. People can dig in there. Any question you have about sleep, I have written 1,000 to 15,000 words exposé, all reference and full documented on anything that you want to know. Do you have any questions for me? I don’t but I want you to know that I enjoy our friendship, our talks, and our time of innovation. You are the most innovative and interesting person I know. I enjoyed our time. Hopefully, we can come up with more good ideas. I think we will. Important Links: Michael Breus Sleepbuds Ebb Nightfood Paul Stamets Good Night The Sleep Doctor’s Diet Plan The Power of When Match.com Sleep Success About Michael J. Breus, Ph.D. Michael J. Breus, Ph.D. is a Clinical Psychologist and both a Diplomat of the American Board of Sleep Medicine and a Fellow of The American Academy of Sleep Medicine. He is one of only 168 psychologists in the world to have passed the Sleep Medical Speciality board without going to Medical School. Dr. Breus was recently named the Top Sleep Specialist in California by Reader’s Digest, and one of the 10 most influential people in sleep. Dr. Breus is the author of The Power of When, (September 2016) a #1 at Amazon for Time Management and Happiness, #28 overall) a bio-hacking guide book proving that there is a perfect time to do everything, based on your genetic biological chronotype. Dr. Breus gives the reader the exact perfect time to have sex, run, a mile, eat a cheeseburger, ask your boss for a raise and much more. His second book The Sleep Doctor’s Diet Plan: Lose Weight Through Better Sleep,  discusses the science and relationship between quality sleep and metabolism.  His first book, GOOD NIGHT: The Sleep Doctor’s 4-Week Program to Better Sleep and Better Health (Dutton/Penguin), an Amazon Top 100 Best Seller, is a do-it-yourself guide to better sleep. Dr. Breus has supplied his expertise with both consulting and as a sleep educator (spokesperson) to brands such as Hastens Beds, Ebb Therapeutics (FDA approved insomnia treatment),  Princess Cruise lines, Six Senses Hotel and Spa, Lighting Science Group,  Advil PM, Breathe Rite, Crowne Plaza Hotels, Dong Energy (Denmark), Merck (Belsomra), iHome, and many more. Dr. Breus lectures all over the world for organizations such as YPO (Young Presidents Organization) 20+ times in 2018-19,  AT&T (10 times), on stage for Tony Robbins (Unleash the Power), hospitals, and medical centers, financial organizations, product companies and many more. For over 14 years Dr. Breus served as the Sleep Expert for WebMD. Dr. Breus also writes The Insomnia Blog and can be found regularly on Psychology Today, and Sharecare. Dr. Breus has been interviewed on CNN, Oprah, The View, Anderson Cooper, Rachel Ray, Fox and Friends, The Doctors, Joy Behar, The CBS Early Show, The Today Show, and Kelly and Michael. He is an expert resource for most major publications doing more than 250 interviews per year (WSJ, NYT, Washington Post, and more). Recorded on November 12, 2020The post Top Sleep Doctor’s Brain Dump – Michael Breus, Ph.D appeared first on .
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Jan 16, 2022 • 53min

Urban Transportation & the Truth about Garbage — Assaf Biderman

About two billion people that are going to move into cities by 2050 and with that growth, the demand for efficient transportation is going to increase dramatically. In an era where we’re already seeing inefficiencies in urban mobility having a massive impact on the economy, public health and environmental health, it’s hard to imagine a future of transportation that doesn’t border utter chaos. Cognizant of these projected problems, Assaf Biderman, is working on solutions that harness the power of artificial intelligence, robotics and other technologies that are already within our reach. Assaf is founder and CEO of Superpedestrian, founder of the Senseable City Lab at MIT and an awesome guy to learn from. I’ll admit, I have been dubious about the rentable scooter business, but Assaf has me convinced there’s an important place for these things in our cities. If you have any interest in urban mobility, this conversation is important. You’re still at MIT, but you don’t have to go anymore because no one goes to work anymore. The whole lab has been removed since March. I’m still on the board of the lab. I spend most of my time at Superpedestrian. Is the Senseable City Lab still going? Yes. What are you guys trying to do? Senseable started in 2003, 2004, where the goal was to say, computers are becoming part of everything. They can emit data. They can act on data. You can embed them in your environment. That allows us to completely change the way we study design and impact cities. Some people call this field of smart cities and I don’t like that. It is because there’s no such thing People are smart enough, but there is a lot that you can do. You can discover new things about how people organize themselves and about how it flows through the city, energy flows, waste, the things we consume, people, and communication. A lot of that can impact how you design them and how you manage them in real-time. It’s got a lot of value. It’s one of the largest lab fields. I’ve been doing work since 2004 in partnership with cities all over the world. Those are big city partners and a lot smaller. It was funded by corporate for the most part and more will survive by long-term brands, but most of the money came from corporate where cities volunteered themselves as a subject matter and tell us about what problems they care about. Probably they want to look at together with us. We use the bigger money from corporate, all thrown together into one pot. We basically manage the deployment of dollars into research areas that we care about and the cities care about and the consortium that the management cares about. Most of the time, technology surrounds machine learning, robotics, various types of analytics. For example, when you think of the seventeen-year history or something, what are the things that stand out to you as examples of what that lab is doing so that I could understand? The impact areas that we care about are the stuff that makes cities function better or worse. We look at a lot of transportation, and probably half of those are transportation, whether it is dispatch algorithms to global taxis that we’ve been working on for many years. There’s quite a bit of knowledge there that’s generated this whole micro vehicle angle, which is what Superpedestrian is spun into. How do you define micro vehicles? These are tiny vehicles that take vertical space. The key thing is you got to take much less space on the road than a car does, but the longer answer it depends on the occupants. We want to make sure that we are able to get a lot more people on the road. There are about 2 billion people that are going to move into cities by 2050. There is no way that these people are moving. Cities are already overbooked so 1.16 people in a car, which is what we do today, like Sedan don’t cut it. Think of something else where the utilization is a lot higher, either a tiny vehicle for “1.16 people” or some way to decline transit with these other modes. It’s classically called multimodality. Cities have done this for over a century with subways. You walked into the subway. Now we want to extend the reach of these systems or any new modes on either end. Two billion people are going to move into cities by 2050. There is no way those people are moving if we don’t revolutionize transportation.Tweet I have a zillion questions about this. That’s one thing about transportation. We’ve got a lot of work on housing. I work on energy, waste production, and communication. How do communities lay themselves out in space, which touches on the essence of why we come together probably in cities, in the first place? It is to get access the diversity to human capital. There’s increasingly work on the intersection between biology and cities because you can learn so much about how we are impacted by a built environment or how it should be better designed by studying, for example, the collective microbiome of communities. It’s public health that provides that like the spread of pandemics. It is quite a bit of work on that in the last several years with robots that eat your shit and tell you something about the collective gut. It’s been spun off. They started doing well when COVID came around. I’ve heard multiple pitches for companies that want to sample sewer systems to figure out where in the city there’s COVID or whatever pandemic. There is this company called Biobot, which we spun of Senseable from the project we called Underworlds. I’m looking at it for a while at Eric Alm’s lab. Well trying to amply signals in the sewer that relate to that. You said you’re on the board, but are you actively doing anything at the lab or you’re pretty much busy with the startup? I am, but much less than intensive. A startup is something you want to put yourself into completely. Coming at it from a different perspective, at Intellectual Ventures Lab where I was working., we created a group called Institute for Disease Modeling. Essentially, what the team was doing was computational modeling on the spread of disease. Mostly third world stuff, but what happened was we created computational models on things primarily like malaria and big infectious diseases there. When the first Ebola outbreak happened, 12,000 lives were lost. When the second Ebola outbreak happened, twelve lives were lost. In between what happened among other things was we were able to do computational models to optimize the ring vaccination campaigns so that we could quickly contain those outbreaks. That’s a two order of magnitude improvement on lives lost. With infectious disease, it could be a pandemic candidate. A lot of the gains came because we were able to use computers to help us make better decisions. I use that in my mind as an example of how computers with these modern tools, computational models, big data, machine learning, network models, being able to help humans make better decisions about what to do with large complicated problems. Things that our intuition would fail us. That’s the rough thesis I have in my head about what’s possible. What I imagine is that you have a lot more experience than me with the Senseable Lab going and figuring out for cities. Exactly that because in my mind, in the future, even the near future, we should be able to use these types of tools to help us make better decisions about city planning, transportation, infrastructure like sewer systems, water, power and all those things. We should be able to make use models to create thousands of possible futures and let us choose which one is the best from that. It seems like that’s the work you’ve been doing for a long time, in some sense. What I want to do is figure out if you have examples from that work to help me substantiate this view, help people see the potential and how we make decisions for situations, where asking an expert isn’t going to get you the best answer because we’ve tapped our tapped out on our potential with that type of decision-making process. There’s plenty of examples. When we started this work, it was a few groups around the world looking at this and there was very little data to go by. We had to do a lot of data, to partner with companies that have data running through them for other purposes, cell phone companies. We worked with a lot of vehicle services and also the computational capabilities, the analysis, the science behind the analysis, the mathematics was it a difference. Some of this is being put to practice. It’s in a very different state. I still think we’re fairly early on. I’m not sure that the biggest value to be had from this cyber-physical city is in the ability to somehow centrally make decisions that are smarter. When it comes to pandemic, you definitely want that. That’s the great rule, catch to spread, know how to cut the chain of contagion, what we’ve all learned to think of a split flattening the curve. All this stuff is perfect for centralized decision-making systems where theaters can be effective. However, if you think about a lot of the things that are happening in the city. People, the citizens, the actors themselves are the ultimate decision-makers, how something ends up behaving, how you navigate yourself through the city by what you throw away, where you work, and where you live. Almost all the decisions about the way a place functions played by the people who use the place, not the people who mattered. I think there is an important distinction that I want to put out there first. It becomes interesting when part of these computer models or computer analysis becomes open and information brings a citizen as an ultimate decision-maker, so that citizenship could become smarter. It’s a good, amazing dream. There’s little stuff that we’re already doing, but there’s a lot more that we can do. When you say that, what I imagined is like, Mumbai versus Seattle or where in Mumbai, citizens are making all the decisions. There’s nothing central going on. That’s affecting the city. As far as I can tell, Seattle, the city is making decisions, largely poor ones about everything. The citizens aren’t making a lot of the decisions I don’t feel. Am I wrong about that? Do you see a spectrum there? Think of the things that you do from the moment you get up in the morning until you go to sleep, how much of that is being dictated by somebody else? There are very few. It’s in your immediate environment that predicts how you move, where you eat, what’d you buy, how you consume, pollute, contribute what you work on, and all that stuff. Transportation, housing, and education are big pillars of cities. They are navigated by cities. At the end of the day, people are driving these pillars. Let’s leave it at this abstract level for a second and try to focus on it. Let’s talk specifically about transportation. Now, we make choices about transportation that are driven by where we were, where we live, and where we’ll spend our time. We might choose where to live based on the availability of transportation, how bad is traffic. Is there a rail going to where I’m going to move to? At the end of the day, there is the impact of the decisions made by the Central Transportation Authority. It can be a mess. It is something we’re planning for an alternative can be a mess. Let’s think what’s positive. We have a pretty good understanding of how demand has been shaping for transportation. It has been growing and growing. It hasn’t had a flat year since 1984. Except for this one. Cities have been completely overbooked on the streets, but demand keeps piling on, so what are we going to do? Many cities have been focusing on mass transit. For the past 100 years, we’ve seen subway systems pure around the world. They’re expensive, but they’re very effective. Many cities do not have the ability to put a subway system yeah together. Those who have them, can’t expand them as effectively. We’re seeing examples all throughout the world, but almost every developed city very slow expands the subways. Not only this, when you expand it, the city develops around the subway system in a way that it immediately creates new demand for transportation further in the peripheral. The subway system reaches a certain neighborhood then that neighborhood will be more integrated with the city. Farther into the periphery, you’ll have new developments where people will buy cars and end up driving into the city from there. Historically, how do you plan that? You ask a bunch of households where they go to and from and create what’s called origin-destination makers. Now, we can derive those matrices with much higher procedures, whether it is through cell phone data. There are quite a few other ways. Think of the data that flows through an Uber-like service, a lift-like service, a transit authority, a taxi service, a micro-mobility company, and a cell phone company. When you put those together, you get a pretty good understanding of what’s going on in the city from the demand perspective. The insurance companies are increasing. You’re looking at that so you get a pretty good understanding of demand, but at the end of the day, you can’t change the supplier of transportation real-time. The cities are made of concrete. It takes a long time to change those big things like infrastructure. There is planning that happens as a result and the planning is quite long-term of the transit system. You do these demand surveys and the city ends up making decisions, 10 sometimes 20 years into the future in terms of massive investments or even management. Now, the question is we did an explosion in urbanization and the complete over-consumption of transportation, especially in the urban part, but also in four-doors in the Bay Area. It’s congested throughout almost all week days. The same is true for our latest industry in London, Beijing, Jakarta and Bangkok. What do we do now? If historically, we learn how to plan transportations that have walked to the subway and then you’d walk again, we’ve learned how to do this. They are all planners who specialize in this. They work in City Halls and they can be using the latest and greatest data tools or the sources, but still, you walk to the subway. There were some ways systems evolved very slowly. We added the Bus Rapid Transit system. If you want to expand the regional systems, there need to be new modes of transit that can let you go farther than what you get than by walking. Think of the KickScooter that we’re seeing a lot more around, shared e-scooters, shared e-bikes, and mopeds. One person covered vehicles like a tiny car electric. All these are going to become a part of a multimodal, very flexible transit system. That’s most likely going to be part of mobility or urban mobility systems into the future. Do you think these scooters that we see for rent on the street are here to stay in cities? Are they improving things? In some ways, yes, but let’s take a step backward. First of all, I think from a form factor perspective, what matters is that people like them. They find them useful. They have improved. They will improve a lot. That is what Superpedestrian is about, that technologies that make them safer and more manageable, but you’ll see multiple forms. This one form factor addresses a certain type of user, which is those short 1 to 3-kilometer trips. They’re not great for groceries or whatever. You can’t hold stuff on them very easily. You don’t want to go too far, but they’re great if you’re wearing a skirt, if you’re wearing a suit, or if you want something non-committal and they’re fun. Most importantly, people seem to like it. In 2019, there are 250 million trips made on those and it is growing. That means that there’s something that people are willing to do instead of using other modes. The question is, what does it come at the expense of? Is it replacing walking? Is it replacing subway trips or other transit trips? Is it replacing a ride-hailing trips or private carts? There are more and more research that shows that at least a third of the hour on average is already thinking mode shift away from private car use or ride hailing what cities crave. Elected officials are being elected into office to do something about traffic problems, which wasn’t the case, get cars off the street. If you have one mode, the scooters, which takes care of the short end of the trips, we’ll see something else which takes care of the medium-range trips, electric bikes, for example, or even longer the moped. Perhaps a slightly different type of trip would be something where you have covered vehicles and you can carry your shopping or your child, all of this under the mandate of being small. It takes little space on the road and it is electric so that it doesn’t pollute. The question is, can these things combined so that you now have an option for coming from the periphery of a city into a transit hub or the city center? By combining walking with a scooter with a car or whatever, any kind of combination thereof, that’s multimodality. We know how to plan this. Now, we have the data system that can allow us to merge these new vehicles. From the academic perspective, the planning is pretty well figured out. The vehicles themselves have been lagging behind the engineering that the technology of businesspeople making them a possibility has been lagging behind planning of this. I’m glad to hear you say that because first of all, you said a quarter billion trips, but that’s not much. Don’t quote me on the number, but compared to something on the order of 20 to 25 trillion passenger kilometers, driven by individuals in cities every year. We have a ways to go. That’s a way of measuring ran from a mobility passenger, a trillion passenger-kilometers per cab. If I am not wrong, there are over 22 trillion passenger-kilometers around the world and the way you want to measure it is by passenger-kilometers per cab by a trillion passengers. You divide 22 trillion by global population. We’re expecting 60 trillion to 70 trillion passengers-kilometers by the middle of the century. It’s mind-blowing. The question is, how do you provide that in giant vehicle space? There’s not going to be room to support that. If you don’t supply this, it is not just about our life is going to be terrible or understanding traffic. It’s other things. Eighty percent of the world’s GDP is provided by the cities. If you don’t keep supplying it with transportation, if you don’t keep up with its growth, you get stuck to the GDP. Environmentally, there is an impact. In terms of anything from productivity to public health, the impact is major. Did you say 60 to 70 trillion on what timeline? By the middle of the century, by 2050. These are predictions by Arthur D. Little and the Bureau of Transportation Statistics. There is another similar magnitude. The vehicle’s been lagging behind It’s an engineering problem and it’s a business model. The business model problem is clear. My experience with multimodal is that the transitions are expensive, especially waiting for a bus, waiting for a subway, getting off the subway, looking around for a Lime scooter, or whatever. The transitions are expensive and it makes me not want to rely on it. If I can afford something else, I’ll choose it and I can usually so I pick a car. Dependability is key. You need to be able to make a choice of transportation mode or modes. If you don’t know that it’s going to be there for you in the morning, you got to be late for work. Once or twice, and you’re done. That’s key. That’s a lot of what we ended up focusing on Superpedestrian tend to do with the reliability of service and dependability. At the moment, it is still in juvenile stages, if you look at scooter services out there because the vehicles are wrong vehicles. The technology within them is not the right one. What’s an example and how it could be better? They failed to offer. They come there and it’s broken. It’s driving me nuts. I get so mad trying to fire up a Bird scooter in Santa Monica and it’s just pathetic. The battery’s dead. I didn’t park it in the right place. I got to drag it to some place where it’s geo-fenced properly. The fact that the technologies behind them are not fit for the purposes, making it so that it’s expensive for the operators to offer a service that they can’t offer enough, in any way, that’s economical. If we want to see success in cities, we need to see sometimes two orders of magnitude, more of these vehicles, which means they need to be a property. They can’t be just thrown everywhere. Technology is required there. How do you do a much better location? How can the vehicles autonomous needs enforce their own geofences in a much more precise way, which is something we have investing on? Manage the vehicles, but then economically, if your vehicles fail all the time and your cost of offering a service is driven by the amount of people you have to throw at the problem or keeping them up and running, replacing parts in them all the time, which is what scooter company does. That means that you’re going to offer a very small fleet. Even if it’s 3,000, 4,000 or 5,000, it’s still small. A portion of them is never going to be worth it. If the unit economics don’t work, it doesn’t work. That means that you can’t depend on the service. That’s at the heart of the problem we’re focusing on. I need to understand why this is worth pursuing in a city like Boston where it’s going to get some snow. Nobody’s going to ride a scooter for some part of the year. It is the same for a lot of cities. In Seattle, we have scooters, it’s not raining, but it’s wet. I heard there’s something about that, but I don’t know anything. Back up and tell me about Superpedestrian and what the real point of this. Having done quite a bit of work at MIT on this issue of transportation, what can we do to meet this future transportation demand, which is not slowing down but blowing up? We saw two main avenues. Number one is increased utilization of the car. Instead of having 1.1 people in the car on weekdays, can we get to 4 or 5? We did a lot of work on vehicle dispatch algorithms. Number two changes the vehicles so that it’s smaller. At every point along your trip, you’re using the right scale of the vehicle. If you’re sharing an origin destination with many other people, be on a large view, train view, bus view, or something, but those ones which are small, they don’t exist. They cost a fortune to maintain. Companies cannot make sense of their business models. They’re not safe enough. Cities can’t manage them. It’s a mess. In these micro vehicles, there is a world where if you addressed technological models, if you create vehicles that can ask themselves if they’re safe to ride before arrive. Vehicles that can predict when something’s about to break before it goes bad to prevent damage from occurring in the first place. Vehicles that can open their own repair tickets and say, “Here’s what I need if they couldn’t protect themselves.” That certainly does not exist, but if you could do that, you’re changing completely the game for a small scale. It makes sense for fleets, but it doesn’t make sense for auto manufacturers. There is no reason why it shouldn’t work for auto manufacturers, other than the model of building a car now is very different they have a lot of Tier 1, 2, and 3 suppliers which bringing various black box or technology that you can’t control. It’s a business model. I found it Superpedestrian in 2013, we focused on asking what are these technological bottlenecks that we can unlock, these fundamental technological problems we can solve in order to scale micro vehicles into the large scales that cities meet. We spent the first 4.5 years in R&D. One of the reasons why it’s great to be in New England is you have people that come from the robotic industry specializing in the diagnosis and automated response systems. It is an embedded system control. We hired a whole bunch of smart and interesting people, top engineers from segway before they went bankrupt in the first incarnation who became Amazon Robotics moving the packages in the warehouse. The VP of engineering for my robot work is cool. A whole bunch of smart people came together to ask, “What is that platform that we can build that will be embedded in the vehicle that can make an affordable, super safe, electric vehicle that could provide the backbone for it.” We call that platform Vehicle Intelligence. We commercialize it in various ways. We have a product called the Copenhagen Wheel, which has a lot of it inside. Can you describe that real quick? The key thing we did was we developed a Powertrain. We designed our own motors, choose their own chemistry for battery lithium chemistry, and we build our own battery management system. That’s basics, but that’s not done in micro-mobility at all. For some reason, these are always procured efficient, much safer ways of providing power. We have encryption on the vehicle and User Access Management. We can track the performance of every smart component on the vehicle and also worry about it’s after a sales service in field service on the vehicle itself. If you know how well is my motor controller doing over, communicate that with, “I need to fix it.” I started to appreciate that. I’ve been obsessed with electric toys so I have been buying a ridiculous number of things I can with wheels and electronics. I never have a clear picture of what’s going on in the controller. A lot of times, there’s some weird incantation you’ve got to do to change a mode. I have an electric dirt bike that you pull the left brake and then the right brake three times then twist the throttle and then turn it off and on again. That’s how to turn off the regen braking. There is all this stuff and I have no idea what’s going on inside that thing. I don’t know if my battery is wearing out over time or what the status of that. There is a lot I don’t know. I’m expecting it to die at some moment. I don’t have any diagnostics. Sometimes the throttle dies while I’m riding it. I got to restart the thing while moving. I have no way of knowing. I put on three different throttles and it still has this problem. I don’t know what to do. I can see how even for a lot of these products, for them to evolve, that’s maybe not buy another one for my girlfriend or my daughter because it’s a little scary. I don’t mind. I’m fine with things half working, but to be reliable in the way that you’re describing, they don’t even realize that the state-of-the-art isn’t good enough for general use. The last piece we have on our vehicle platform is decision-making. You can observe it. What components on the vehicle they’re doing and then say, “Can I attribute their performance to failures upstream?” What we realized early on is that the key to be able to do that is to completely swap out all the software of that vehicle. If you want to have full control of the software, not a third party IOT device, third party battery, a third-party motor controller, then you can start to have decision-making systems on your vehicle because you have access. Do we have information that can detect the thing that is about to fail? What fails in the scooter industry? Mostly electronics, otherwise the rest of it is the 1970s, technology mechanical engineering. It is pretty simple. The L-shape vehicle people abuse its fenders on them yet. The vehicle is very simple. It’s all in the electronics. If you can have full control over the software, onboard the vehicle, now you’re getting somewhere. Now you can respond in nanoseconds, milliseconds, and prevent fires from happening and from going out of equilibrium that if you move away from a thermal issue. If you don’t manage your system thermally well enough for long enough, you’re creating permanent damage to the vehicle. You can put the eventually the rider at risk. Can I break that down a second? One of the toys I got obsessed with is these electric unicycles, like a solo wheel. I started with the Onewheel, which looks like there’s no way to look cool on a Segway. My daughter looks cool on a Segway, but I can’t look cool on a Segway. I look like the mall cop. I got us one wheel, which is the one you stand on sideways, like a snowboard, and you can look cool and feel pretty cool. It is cool, except that is probably the most dangerous product I’ve ever gotten. I own the fucking lawn darts. That thing is actively trying to kill me. With the Onewheel, you can over torque the motor at full speed because you have so much torque with that deck that there’s no warning. By the time that happens, there’s no recourse. You’re flat on your face at 26 miles an hour. It’s a very powerful and amazing, but the wheel’s not big enough. The diameter doesn’t allow to have enough torque for my body weight. That is probably the most dangerous product I’ve ever gotten. I own the fucking lawn darts. Tweet Everybody who has one of these has titanium pins in their elbows now. I’m not kidding. Everybody, if you look on the Facebook group for Onewheel, it’s all photos of guys in a surgery going, “I can’t wait to get back out on my Onewheel,” and their arms are pinned. It’s insane. Fortunately, my Onewheel got stolen. I figured out that those electric unicycles where you have the big wheel between your feet, those things have bigger diameters so they can have higher torque on the motor. You don’t have as much leverage on it. I started looking into it and they’re dramatically safer. I don’t think they have a higher torque on motor. You have lower torque as a rider. Small wheels have more torque. The thing is that because the wheel is bigger, you’re impacted a lot less by the surface of the road. It wasn’t the road surface. Maybe you’re right. It felt safer because it’s much bigger. It’s clearly are safer. That being said, the electric unicycle community seems hell bent on making them less safe by making them faster. Now, you can buy these things that go 45 miles an hour. It’s insane. Mine goes 31 and it’s the first one that has full suspension. I feel safe on it. I specifically want it because Seattle’s roads are shitty and there are a zillion potholes. I could go 30 miles an hour on it. I wear full gear. I have full motorcycle gear. I ride at 30 and it’s got a full suspension. I can hit a speed bump at 20 to 25 and I won’t fall. I wasn’t trying, but I’ve tested that accidentally and I didn’t die. I have not fallen off it yet, whereas when I had the smaller one that I learned on, I wear a full helmet, full motorcycle gear, boots, everything because I know I’m going to bite it at some point. The point I’m making is those things, the email list or the Facebook group or whatever. For those things is a lot of people saying, they’re posting a video of the thing that went up in flames or they’re posted a video about, “How do I get the settings right to do this or that?” There are weird Chinese devices and nobody has to make their own third party. They’re making apps to try and mod the firmware. Nobody knows what’s going on. Nobody even knows how to change the tire on one of these things. They’re all swapping notes on how to maintain them. I wish we were at the office because you would see how we do development on each. We have our embedded software team and each person on their desk have three printed circuit boards, five armed processors. That’s the development. There’s no black box. We write code on. We have multiple modularized state machines that work constantly with one another. Your region is an app. Your geofence parking is an app. Your sidewalk detection is an app. Your safe stock, how do you save stock? How do you stop that vehicle if you need to, in a way safe as possible, better, and do its best? The electric unicycle companies need to come to you guys and get their next-gen firmware. We don’t sell the platform. You need to make an electric unicycle, “It’s totally safe and goes 45 miles an hour.” It sounds like you’re ready to do it. The key to this is the testing that you do. What level of purification you’re looking for before you put the things on the road? We’ve been engineering our control system for the scooters for years. It’s very mature. There are some things we just don’t touch and don’t fix it. There are some things that we need twelve months of regression testing and we’re good. The reason is that we know what our system can do. We also know what it can’t do. We feed some data regarding, for example, we can detect and in real-time, completely resolve more than 50% of issues that would break other scooters into one. That’s helpful to understand. What’s an example? A temperature and balance on battery. When I go to a Bird scooter, and it says the battery is dead, it’s because something like that went wrong. It was not recharged, there is an issue internally that made its battery damaged, or there is an issue electrically that’s not bringing energy from the batteries. There could be a whole bunch of issues. I can show you the way out. We can log onto a scooter. You can see the log in the back end. There are tons of stuff. There are over 1,300 data points. A scooter you’d think with two wheels, you couldn’t have that many data points. We continuously monitor them. First of all, we tried to detect events. We call them events. We have five hierarchies of things that could happen. If you start from info, then we say, “Where is it happening? Is it important? Could it become a safety list? Should we keep an eye on it? There then was a decision-making tree that can upgrade until code red. These are rare cases where we stop arrived. In between, the least and the most urgent is when most of the stuff is going on, where the assistant rebalances itself, thermo management or the system is able to attenuate, energy where we continuously monitor, for example, the integrity of commands and make sure we’re not asking for something reasonable. We have maps on the vehicle. It knows where it is. Also, it knows what the city rules are by itself. The good thing about it, one of the biggest problems that have been is that pedestrians end up being penalized. If you want to see tens of thousands of vehicles like this, they can’t be preventing the disabled person from crossing the road or somebody from getting out of their house. Managing them is important. What city has the most uptake on these things as far as for scooters? Is there a model city? Model, not really but Paris is doing a lot these days. What about bicycles? I know some European cities are big on bicycles. Is that part of what inspires you to think that we could have this many of these scooters like Copenhagen or Amsterdam? Anne Hidalgo, Paris mayor is taking a major action upgrading the infrastructure of the city to be micro vehicle-friendly. They’re investing a lot and they’re taking away car lanes and they’re putting in two wheels small vehicles lane. Seattle did that. We have them. During the pandemic, you should see the number of people on bikes and scooters because you didn’t want to drag yourself into the subway. In Paris, traffic is always messy, even worse, and people don’t want to get into a cab or Uber. They’re using those lanes now. That’s interesting. During the entire country of the UK, speeding up scooter permitting processes this year. In 2021, just because of the pandemic, there have been places that have been the makers of cycling for a while, like Copenhagen and Amsterdam. Several other cities in Germany and the Northern Islands. In Copenhagen and Amsterdam, what’s the uptake on like rentable scooters or whatever like? Amsterdam, it’s not legal. There are no dockless scooters for rent. In Copenhagen, it is growing. It’s pretty good. It’s good, but forget about that, look at what’s happening there with bikes, 50% of the trips, all the trips in the city center. They ride in the winter too. Will you describe it because it’ll be interesting? What you described is it goes back to your early thesis of saying, “Computers are going everywhere. You guys have been leading the charge on computers that are going to go into scooters.” This is what’s possible. They can be so much better than people even realize. We could be in the future where there’s always a Bird scooter or whatever brand available. Don’t you guys have a brand that you’re working with? Our brand is LINK. We acquired the company in May an operator of Douglas. We operate in Salt Lake City, Utah, Columbus, Ohio, Knoxville, Tennessee, Fort Pierce, Florida, Rome, Italy, Arlington Virginia, and Provo, Utah. We won to Seattle RFP. You’ll soon have LINK Scooters in Seattle? We’re launching LINK in Seattle. When LINK exists in Seattle, if I go up to a LINK scooter and it’s going to work, instead of going up to a Lime scooter that doesn’t. When we look at the data we’ve had scooters thrown into the river. I don’t know why people do this, but we’ve had this in Provo and Columbus. We didn’t even design for this. It turns out that this thing can detect that this is happening. We test for watering, but not for submarines. It turns out that these things had an 83% survival rate from deeping into the water. Not only are they recovered. What it does is it allows us to offer the service with the right number of students that cutting the place. Number two is you throw a lot fewer scooters into the environment. I think about it almost a million scooters were thrown into the trash talking about the apparel. Imagine maybe scooters and landfill. It is terrible. Lithium and Aluminum is polluting. We extend the life of these vehicles. We have equal to 2,500 rides and counting batteries that can go on 5 to 6 years. Vehicles since January 2 or 3 times a day are still at 15 cycle counts out of 500 because we have such an efficient powertrain in such a big battery, we can go 50 to 60 miles in a single charge. Your first product was the Copenhagen Wheel, is that right? Tell me about that. You might be sick of this, but I remember when you guys made the Copenhagen Wheel, I saw it on Weeds. You showed me the Copenhagen Wheel and then it showed up on TV. It is such a good show that was many years ago. For people who don’t know, describe that one because it was pretty cool and pioneering at the time. We started that in 2008. The question was if you think biking is such a great solution for cities, but sometimes distances that you need to cover is longer, or you don’t want to get to look sweaty. The use case for electric bikes. We started studying electric bikes and we realized that they’re booming in Europe, but they’re very expensive. The median price was around €3,000. They’re expensive. If you’re looking at anywhere mid-end and up, you can easily pay $35000 and they’re okay. For that money we’re like, “You’d expect a lot more. You can even buy a small car for that money,” especially if you want to see this scale into the millions, it can’t be at that price point. We were asking a naive question, which is, “How can you increase their quality so that people can’t resist writing them and make them more affordable.” At the same time, if you take the whole power, control mechanism and not sell it into the supply chain, if you look at the industry companies, the bike manufacturers buy a motor with a battery and a controller from a supplier, and then they build a bike for it. They sell it to a distributor, to shop, or to you. By the time you get it, you’re paying 3 to 5X on the electronic parts. That’s what drives the high price of electric bikes. We want it to smarter, what if we allowed people to buy direct tiny components? They have only one layer of margin on it. We cannot get a Ferrari for the price of a Toyota. We’ve built this thing. It is a Ferrari, it’s an incredible machine. There’s a culture around it. Many people say the best eBike ever built. It is learning how you move and respond faster than your body can sense under 10 milliseconds. Is it still the drop-in wheel replacement? How does that work? The only way to do it so that you can sell direct to power foreign factor was by making it a drop-in wheel. It’s designed in order to be a way to convert your bike necessarily. We’re happy when people do that. You could go to a store and buy any bike you want and make it electric. Is that happening now? What’s the status of this? Being this is my first attempted business of tens of millions of dollars, we’ve developed something that’s still an incredible ride. There is a whole cult around it and we make any of the United States. It turns out that if you don’t have a distributor, shops or margin, you don’t have all these layers, you have very little help from the distribution. It means all the customer acquisitions and marketing is on you. With what we put up as fifteen-point margin, more or less, that’s philanthropy. I learned a lot from that. It is an amazing vehicle. It’s the basis of our technology and they are super reliable, more than 55% of the technical issues are addressed without human intervention. On the Copenhagen Wheel, the electrical issues, we know what’s going on. We can detect issues and prevent them from causing further damage. We try to parallel. If you look at most of our work on what I call automated maintenance and self-protection, it’s been done in 2014 and 2015. There is a lot of pens and sharing and did a lot of developing this platform. We tried to sell it initially to other operators and tried to sell it with the few large ride-hailing companies in 2016 and 2017, to the large bike-sharing operators in 2016 and 2015. There was very little desire to go electric. Basically, what I learned are two things. Number one is you don’t want to take everything on you. Reinvent the marketing channel, the sales channel, and do all the technology and all the manufacturing and all the supply chain and all the purchasing. Everything is new. It almost no off-shelf part idea. On the other hand, what we did learn is that technology that we’ve made works and real. It’s fundamental. This issue of detecting problems in real-time like water, temperature, balances, thermal management, and that has many applications. We’re monetizing this now in the scooter world because I’m passionate about its mobility. Scooters, the first mode will be the other mode. We will be enabled in many ways by reliability, safety and scale. That’s a way to completely drop the cost of offering a service is different using this technology. It’s about 75% cheaper who offers scooter trip with this platform. It changes the game. That’s an example of how you can start to embed. The intelligence could also be local in the thing. The users don’t even know about it, to seize your scooter, you unlock it, ask yourself if it’s safe before every ride it tells you this is safe, but otherwise, it should be a street bench on wheels. Be there when you need it. That’s different from the high-level analysis or the centralized Oracle view that you were talking about back to the beginning of our conversation saying, “How to disrupt the contagion chain in the pandemic,” which is a different way to think about what computers aid us with. Think of it locally. It’s an example where you’ve trained the device to know what it’s optimal operating circumstances and what to do in response to different failure modes. Your knowledge keeps improving. Does the device itself keep improving? Is it connected? It’s online so it can talk back to you. You can see the whole fleet. We started from an embedded system, but it’s all online, the cloud. That is in conversation with embedded soft. I love that because my scooter’s learning from all the other scooters. I think the public discourse around these devices is missing this key attribute with robots. These devices, they all learn from each other. When one of them gets thrown in the river and figures out and you figure out what to do about it, they all learn what to do next time. When a Tesla, most somebody down, walking in a dark alley where they’re not supposed to be crossing the street, all the other Tesla’s learn never to do that again. That’s a terrible situation, but that’s not true for human drivers when a human driver most somebody down, then no other human learns from that. You seem more bullish on human intelligence and decision-making than I am. Didn’t you teach me that analog visual hacking is easier than computer-based stuff? It’s true. There’s an opportunity here to see these technologies as being able to help us do a better job. You’re proving it in a sense because a scooter is like another place where a computer hadn’t gone, now it’s gone there and we can use it to make it a lot better. By extension, I’m sure you got the fundamentals of what you guys are building could be used for any electric vehicle, if not other electric stuff. Our platform now, the system is directly applicable to any vehicle under 12 kilowatt per hour, so the battery to motors. Is that anything DC? We were in a 52-volt DC system, but it’s just a circumstance of the power rating of the different components, but if somebody wanted, they could put this in winter for detection or prediction of issues. That is a big deal. That’s exciting. What do you guys need for Superpedestrian? What would be helpful for you? Do you guys need more scooter deployment partners? Do you need windmill companies or like what would be helpful to make you guys turbo boost the company? I didn’t come with an ask but I will tell you where we are. We acquired a company in May and since COVID lockdown to remove, we expanded fast. We entered Europe and hired some great people. We have this special engineering team that’s been built over seven years. That’s great. We then acquired a company that’s ten years old from Baxter. We acquired their fleet management business. We closed the gap and then some on operations on the ground. We have our own W-2. We have our own employees, but then we needed to close the gap on because of the government relations side of things. How do we directly the city? We hired some of the best people from across the industry and senior executives from other scooter operators. We are happy about that. We also fundraise some more. We’re good on that front as well. What kind of help? Most interestingly, for us, is to get as many opportunities as possible to show cities our ways of offering safe, manageable micro mobilities. Cities are tenuous because they’ve had some mediocre operation come in, make a mess, end up with a lot of SKUs in a river. A lot of promises were made by essence operations company but with engineering capability. There are a lot of problems, but many of them were not catched. The cities got burned. You want to be able to show them like, “We can do better. We can be 75% more efficient. We can come in and make these things safe and reliable.” We look forward to a less affluent community. It could be a lot more dependable because it’s there. You need to manage it so that it doesn’t ride in a park or next to a school. Our vehicle stopped within 0.83 seconds. We’re at 99.91% success because the maps are on board, vehicles autonomously enforce the rules. It’s very different. It’s like half a minute without a vehicle. If there’s no connectivity, sometimes it’s never enforced. There are 250 cities around the world that didn’t have scooter licenses. The number is growing to over 600 in 2021. There are more cities to deploy scooters. There is supply even throughout the world, irrespective of a lie. However, it’s important to tell the story that technology and capabilities matter. Cities need to know that they don’t want to go make the same mistake and end up getting burned in the same way. Otherwise, it is just a commodity. I remember seeing piles and piles of rental eBikes or something. In Beijing, companies tried to deploy right. Bikes for rent and that ended up failing somehow. There are stacks of them. That’s an industry where the unit economics works. It baffles me how these things go. I want to let you get out of the wind here, but let me ask about one thing because this is interesting to me. One of the projects I remember you doing years ago which I guess must have been in the Senseable Lab was throwing away GPS trackers and the trash maybe all over America and then seeing where the trash goes around the world. This is an epic project that everyone should see even now. It a decade or more ago, but that was an amazing enlightening project where I could see for the first time what was invisible to me. It was so much more dramatic than what you would have guessed or what I would have expected. If you ask me at that time like, “What happens when you throw a can of Coke or a pair of sneakers in the trash,” I would have thought, “It gets picked up by the truck that goes to the transfer station where they send the recycling one direction and they send the trash another direction. The sneakers go to a landfill that’s 30 miles away and the can goes to a recycling center somewhere in the state. It gets becomes aluminum that’s melted down and turns into cans again.” That’s what I would have guessed. That is not at all what you showed. Better than me trying to do a shitty job of summarizing, why don’t you describe what that was about? The genesis was in 2008. We started seeing anecdotes about how waste moves. We wanted to try to verify this with a quantitative study. How do you do that? If you’re a waste management operator, all you have is a statistical data. You don’t get to know the pieces of trash flow through your system. We built these sensors that are IOT devices. They detect their own location and they communicate. We partnered with Qualcomm. They need to survive in the trash. That’s quite an IOT device. I was talking 2008, 2009. Was it easy then? It wasn’t too difficult, but we’re not as good. We wanted to get six months of life of those. That required a lot of smarts and how you designed to power. The key thing there was we went to Seattle on purpose because it was their recycling time squad in the United States. Most investments, a lot of compliance on behalf of citizens. We wanted to see how it functions. We partnered with waste management, one of the biggest waste removal company, maybe the biggest back then, Qualcomm, Architectural League of New York and the City Hall in Seattle. We then invited 500 households. We gave them a list of average household goods that we want to track. We went to their home to help them tag their trash and told them, “Throw it away as if we were never there in the first place.” There are various other programs and that’s when people brought it over to the library. Long story short, the first deployment was a few thousand pieces of trash that people put away. We started getting in real time because what we saw is that the things that we learned to recycle in the previous century, and been doing for a long time, metal, glass, and paper, have been getting to their end destination quite effectively. In three days, they get processed. We saw some anomalies, like some cheating, some recycling going into it, getting buried so you can catch some fraud. The interesting thing that we saw is that the newer thing to recycle, like electronic waste, nobody had a full bird’s eye picture of it. Let’s call it the removal version. We saw things going from Seattle to the East Coast and then back to the West Coast for processing. There’s a tipping point where the emissions due to transportation, the advantages of recycling cell phones with the Florida printer cards went through Southern California. There are a whole bunch of things that we started observing. There was then a big flow to the Nikon Delta, which we did not yet understand. That led to a follow on project with an undercover operation that ended up exposing the flow of CRT (cathode-ray tubes) monitors to the Mekong Delta instead of being recycled in California. Governments would pay US companies to recycle CRTs because they are toxic. Because they contain cobalt? We need to dispose of them through particularly good control process and expenses. Instead of paying for that process, some of these companies took the money and ended up shipping them to be reinstalled in products or another life of these DVDs combined with a monitor repackaged into new cases. We put cameras as well as backers and these CRT monitors documented their road trip. Like GoPros in them or something like that and they’re just recording. It is based on Android. There were multiple incarnations of the same product, which as you said, allowed us to take something that was fairly invisible before sprinkle a little bit of digital stuff on it, to bring it to light and learn several things I assume that I can find that stuff online still. The original product was called Trash | Track. I don’t know if you’ve followed this, but in the last few years, we’ve been able to reflect on recycling. Some important studies have been showing that we probably shouldn’t have done it. We’ve been doing recycling in the US for 40, 50 years. There are almost no cases where it’s working at all even now, which is sad. Especially, living in Seattle where there’s a lot of compliance. Everybody follows the rules, “We all separate our trash. We all do our part.” We all feel like we’re solving a problem and we’re not. I feel strongly that we’re running out of time to do these feel-good things. We need to be focused on metrics and figuring out what’s working and what’s the potential to work. With recycling it’s, I think fundamentally, it’s an energy issue. If you have cheap carbon-free energy, then you can recycle stuff. If you don’t, then you’re going to burn more coal to recycle stuff than not. I don’t know if you saw this. I have to look this up to show you, but there’s a pretty damning analysis of recycling for plastic, less than 10% of the recycled plastics we get are significantly reused. They’re trying to frame it as a case where the plastics industry tried to promote recycling as a way of making people feel like it was okay to use plastic. The whole premise of plastic to begin with is to do something indestructible. It’s great for that. At least to last as long as I do and that’s good enough. George Carlin used to say, “There is a reason why God made us the first place.” I never saw that. I got to find it. I haven’t gotten to spend a lot of time on it yet, but what I think is probably the right thing to do now is go evaluate what cases we’re recycling works has near-term potential, focus on those, probably get rid of and shut down the rest of them, and then focus on improving energy. If we can make abundant carbon-free energy, then we can get back to recycling. It’s a very good point you’re making. There is another world which is the material world. When you blend materials together, sometimes, there is no amount of energy that will get them back apart, which could be crucial for recycling. Most part, with clean much cheaper energy, we’ll be doing a lot better. Your point is very important. We saw a similar thing with electronic waste. People would come with a laptop and pay $20 in 2008. In Seattle, they would pay $40 to get it recycled. They didn’t know that this thing would travel 6,000 miles. There is exactly. In Seattle, everybody’s going to follow the rules and do it. It’s insanity. They wouldn’t know either. They had nine links on the way from the person who drops off their trash until the final facility. Sometimes nine service providers, each handing a part off to one or another, None of them realizing the origin or the destination. “I shipped it to Florida. I shipped it to California. I just shipped it to Chicago. It’s the battery and it’s the plastics now. It turns out this whole thing travels all around the country. That’s an awesome work. I’m excited about that project. It made an impression on me. Hopefully, other people got that. Hopefully, there’s still some life in it and we can spread the word about it some too. We can wrap up and get out of the wind. We have some pretty interesting audience of people who are excited about technology. I think of them as a pretty high-value audience, so if there’s anything you want to share, we can do that too. I shared so much. I’m excited now. There’s a moment where robotics can take so many shapes. I focus on the robotics inside these rentable vehicles allows us to make them safer, more affordable, more ubiquitous. There have been like 30, 40 years of work since the late 60s about robotics. It’s come to such a point where we can start to deploy that incredible technology in ways that make people live a better life, better with the environment, and make us be more healthy, productive, or having more fun. Transportation is my area, but I think it’s an exciting moment because we’ve been talking about what to do about transportation problems since the 70s. It is the first time where we see something fundamentally new that people love and cities love as well. That works technologically that can be scaled. We’re at the beginning of something. It’s not the end of all the hype. We’re scratching the surface. I had this experience a couple of years ago. I was in Brooklyn with a buddy of mine and I was going to hang out with him. He was at the City Advisory Council meeting, where I went to meet up with him. I sat in on a little of this meeting and the meeting was about what to do for the future of transportation in Brooklyn. I want to say years ago, I wasn’t invited. I’m just sitting there. These guys gave a presentation about their vision for the future of transportation in Brooklyn. Their idea was to deploy streetcars in Brooklyn. Now, Brooklyn doesn’t have streetcars, but it did a hundred years ago. They tore them out. You still see the tracks. In a hundred years, the idea has progressed from streetcars to streetcars. It drove me insane to hear them talk about this. They were talking about the economics of it. Apparently, it’s like $5 million to build a streetcar. I literally grabbed a napkin, started writing down, “If a Tesla costs say $50,000, how many of them can I get for $5 million?” They’re going to tear out road lanes and put in dedicated lanes for streetcars. I’m like, “How about if we make those dedicated Tesla lanes and we buy a zillion Teslas and we programmed them to drive around and pick people up and drop them off? They can do that now in Brooklyn. If they had their own lane, they could certainly do it. Doing it is a lot cheaper. You could do it cheaper. You don’t even need a Tesla. You can create an electric bus. It’s insanity to me that after a hundred years, the best idea Brooklyn can come up with is streetcars. I got kicked out of that meeting. I haven’t been back to Brooklyn since. That’s the thing is we’re not doing a good job of asking ourselves, “If we were starting from scratch, what’s the best that we could do?” Use that as our metric for the goal and say, “With no new breakthroughs, what’s the best we could do if we were starting from scratch?” I know we got to knock that down a little bit because of tradition and regulatory issues and maybe some safety things we hadn’t thought of and whatever people are used to. You’re not shut down a little bit from optimal, but we could do so much better. People are not thinking that way and they set their sights to low. The thing is that there’s so much understanding on what can be done before you have been introduced technological innovation to improve on urban mobility. Urban mobility starts from how you plan a city. If you live above an office, that’s above a restaurant, you’re going to drive a lot less. That’s been well figured out since Jane Jacobs years ago. There’s the world of planning, but cities changed slowly. It is not always under the ultimate control of the city because there are many pressures that the city has to deal with. Now, as an example, cities had to spend money on the virus. Some of the programs have to go out the window to find new ways of doing a thing. If you were going to describe urban mobility in 2030, how do you imagine a city? You could pick any city in the world and say, “Here’s how good it could be knowing what we know now.” I think we can fantasize about it to get it. First of all, we know is that most likely cities are going to look pretty similar. There’s a good reason. The lowest energy is required for us to move on the surface. Elevating us makes no sense. This whole idea of all that stuff to me is baloney. It can be done, but your question is, why would you ever want to do it if you’re going to spend an order of magnitude more? It’s so much energy, it’s noisy and bulky. What’s the point? Maybe for wealthy people to go from SFO to Palo Alto, that’s great, but that’s not the killer app. The killer app is to raise venture money though. I respect that because maybe one day we’ll become ubiquitous enough to replace aviation with something electric. It doesn’t solve over urban mobility. Urban mobility is going to be a combination of mass transit from subways to buses to electric buses to call corralled electric vehicles. Whether on a predetermined route or on an agile flexible route mass media. You and I shared the same origin and the same destination along with many other people in combination with a multitude of other things. Other modes of walking, scooters, tiny little electric cars, like coats, and the combination of those, I think the common denominator is going to be slower and more individualized. I call them packetized. If you look back at internet architecture, we used to have this like hub and spoke thing where it’s like the telephone of the 70s. Every wire from every house went to a central switchboard and you had to have a wire from there all the way out to every house. That got replaced with TCP IP, which is packet switch, where you got to get near something that’s online. The packets, can be routed to their destination. That’s what I see is wrong with a lot of urban transport is that it’s not packetized. You get on the bus where you at the bus stop, you get off at another bus stop, and instead of taking me like Uber does from where I’m at to where I’m going. It takes me all the way to where I’m going. That’s got to be part of what makes it more successful because you reduce transitions and you make it. You increase convenience, reliability, safety, and all those things. Let me give you an example. We’ve looked at 45 cities around the world. The demand for transportation in them, this is through various publications at Senseable City Lab to do that at MIT over the better part of twelve years. Most of that data we got from cell phone service aggregated or anonymized, or a combination of those tell mode independent mobility, like walking included as well as cars must, as well as the subway. How do people move at large scale? You take that data and then you superimpose it on the city’s transit system. You see exactly what’s missing because you say, “I want to get from my origin to my destination.” You wouldn’t care jumping on and off various things if they seamlessly connected with it. That’s going to be fine, especially if it’s affordable and reliable. If you save an hour in the process, we overlaid that. We see, “First of all, which types of vehicles are missing?” You can see that there are some trips that are 1 to 2 miles, and then you got the 2 to 4 miles, and then the 3 to 7 miles. In the vehicle categories, you can see how many people shared routes, given time along same parts and/or you can decide if is it a 1, 2, 3-person vehicle that I need? Google Maps could tell you all these things now in real-time. Google maps, if you chunk it into trips, that’s relatively simple logic. We had to deal with the same problem. We’ve done a lot of thinking about vehicle form factors. How big do they need to be? How many people did they need to take to be able to help you address as mobility demand as possible? We’re starting with this tiny and basic thing. If those things existed, like the Uber app could ask you how many passengers and send you the right car or vehicle for the job. You can easily imagine it. There’ve been in this future that you get from your home. Let’s imagine you live in a suburb. You get from your home in a one-person car or on a moped or something like that. You dropped at a transit hub. An Uber could come by and drop a scooter off in front of your house if that’s what you needed at the moment. The drone could deliver a scooter. Those things are becoming so affordable. You can also overcompensate for them with greater numbers so you wouldn’t need to drop them off in somebody. It’s a matter of lowering utilization. Thanks a ton for taking the time to do this with me. Important Links: Superpedestrian MIT Underworld Institute for Disease Modeling LINK Copenhagen Wheel Qualcomm Architectural League of New York Trash | Track About Assaf Biderman Assaf Biderman is an entrepreneur, author, and technology inventor. He is the founder and CEO of Superpedestrian, a robotics company that develops platforms of small electric vehicles for shared use. Together with the team at Superpedestrian, Assaf has developed fleets of scooters, e-bikes and other micro-vehicles with autonomous-maintenance capabilities and active-safety systems that enable much safer, cost-effective shared mobility services. Assaf is also the Associate Director and founding member of the MIT Senseable City Lab, a research group which develops technologies in big data, machine learning and robotics aimed at improving livability in cities. He has supervised research in areas of urban sensing, data fusion, and urban transportation, and also leads lab partnership initiatives with cities and the private sector. Assaf has a background in physics and design. He holds over 150 patents and publications, and has been honored with multiple international awards including the Red Dot Luminary, Time Magazine, Thomas Edison, and James Dyson awards. Recorded on October 12, 2020The post Urban Transportation & the Truth about Garbage — Assaf Biderman appeared first on .
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Jan 2, 2022 • 1h 34min

Reimagining Entertainment, Work & Education — Brent Bushnell

Brent Bushnell, an inspiring entrepreneur and CEO of Two Bit Circus, dives into the future of entertainment and education. He discusses the impact of technology on creativity, emphasizing play as a catalyst for innovation. Brent addresses the ethics of 'frankenbiting' in media and the rise of virtual actors, while exploring the challenges of remote communication. His passion for reimagining experiences shines through as he advocates for personalized education and the importance of social connections in fostering mental wellness.
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Dec 21, 2021 • 51min

Kids Building Dyson Swarms — Levi Hurt

Meet Levi Hurt, a 12-year-old space aficionado with a passion for building Dyson swarms, structures designed to harness energy from stars. His youthful curiosity shines as he discusses revolutionary learning methods that inspire creativity and independence. Levi simplifies advanced concepts like solar energy capture and future propulsion techniques for space exploration. He even dives into innovative ideas for space colonization and the fascinating dynamics of matter and gravity, all while embodying infectious enthusiasm for cosmic possibilities.
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Sep 12, 2021 • 1h 19min

Exosomes, Stem Cells, Ketamine & VR — Dr. Melissa Selinger

My friend, Dr. Melissa Selinger is a Doctor of Neuropsychopharmacology who has done actual research on using psychedelics and virtual reality for treating things like depression, anxiety, and PTSD. A huge frontier where there are all kinds of potential, and very little actual scientific research has been done here so far. It’s an exciting frontier to be able to help a lot of people who we don’t have any real idea how to help otherwise. I’m super thrilled about that and the potential for it. It’s great to get to talk to somebody who knows what state of the art there is. Melissa knows a lot about all kinds of things that I don’t know anything about. As you guys know, part of what I love to be able to do is sit down with somebody who has a lot of knowledge and experience in something that I don’t know about, pick their brain, try and break it down, see if I can understand it and take you guys along for the ride so that we can all learn. Carcinogens, teratogens, exosomes, stem cells, cytokines, CRISPR, gene editing, all these are things that we talk about in this conversation. A lot of it is me trying to get her to explain in layman’s terms what this stuff is and how it works. There is incredible potential here. If you were ever interested in what’s possible in stem cell therapy, you’re going to want to learn about exosomes and her experience with that. A couple of biotech startups had some ups and downs in that and learned a lot. I’m thrilled to be sharing our conversation with you. Enjoy this episode. Pablos: I’m going to explain what I know, which is not very much, and you could tell me if I’m full of shit. Sound good? Melissa: Yeah. Human bodies are made up of a bunch of cells, most of which are not actually human. They’re like parasites and shit, and microbiome crap and other bacteria are living on your body everywhere. To the extent that there are human cells, the cells are super complex little cities inside. I’ve seen these microscope photos of all the shit inside of a cell, and it’s a lot. It’s complex. Most people like me have a vague notion that there’s a cell wall, which makes it like a balloon or a bowl or something, and then on the inside is all these goodies, including DNA, RNA, and other stuff. That’s the extent of anybody’s general education on this stuff. There are different kinds of cells. There’re bone cells, blood cells, meat cells, and shit. There’s a variety of different cells that do different things. All of them started out as stem cells which were basically blank cells. The thing got written into being whatever they’re going to become. You have some of those in an embryo. Over time, as your body is growing, these cells get programmed to be different things. Muscle tissue or brain cells, and then what happens is gamma rays come from space, bombard them, and you get these cell mutations. You end up with all kinds of variations and mutations, and then everybody ends up eventually getting cancer and dying. Is that pretty much the circle of life? It’s fairly accurate. There’s a lot of causes of cell mutations. There’re other causes like nicotine. A lot of just manufacturing in our environments in general are heavily laden with carcinogenic compounds that was a byproduct of the industrial area. Look at California, for example. Everything is a possible carcinogen. Stem Cells: Donating birth tissue for scientific research doesn’t go to academia for research but to for-profit mega-corporations. What does carcinogen mean? It’s a compound that’s able to alter the cell’s DNA structure in a manner that causes aberrant growth, like a malignant tumor. Essentially, the way that cells operate is they have a terminal point of senescence where they die. With cancer cells, they lose that, and they are able to live continuously. They don’t die like they’re supposed to. They just hang around and replicate. I know some people like that. Carcinogen means that it’s some chemical that you could ingest or come in contact with that can alter the DNA in a cell. Also, teratogens, which are birth defect causing chemicals in unborn babies as well. Those are chemicals that the mother could be exposed to, or that the babies get exposed to, or what? The mothers got exposed to, and then they cross the placental barrier in vivo. Not every carcinogen does that, but some subset of them are teratogens? Some subset of them and then there are various prescription drugs that were used during pregnancy that over time were pulled from the market when they realized that some of them cause pretty severe birth defects. Some people are attempting to live these carcinogen-free lifestyles. I don’t know if that’s possible in America because there’s such a heavy amount of it. Food in America is heavily chemical-laden and you have everything from the interior of cars and mass-produced furniture are full of anti-flammable chemicals. If I sit on a couch, that shit’s rubbing off? It depends on the manufacturer. If you grab a Walmart couch, for example, they have questionable materials and then anything that’s synthetic usually has something. If you have a synthetic vinyl couch or anything plastic, you have plasticizers that leach out over time. Water bottles, for example, the plasticizers that enable the plastic to have a bendiness or softness to them, that leaches out into the water, especially with heat or microwave food and plastic containers. The BPA alternatives are not necessarily safer than BPA. Even with Fiji Water? I would say pretty much anything bottled in plastic and then shipped in plastic is. I thought these plastics were FDA approved for holding food? FDA approval is still wishy-washy and you have FDA-approved artificial colorings, which may or may not be linked to possible disorders. We’ve had so much ingestion of artificial coloring, you would think we would know by now. They say it’s something like 99% of Americans test positive for BPA in their blood at any given time. I think aluminum cans are lined with plastic anyway. There’s some lining and the cans. You’re seeing a lot of times, the “BPA-free lining,” but it’s still the way that they’re manufactured. There’s still the joint where it’s sealed as a circular cylindrical piece and there are some metals that leach out. It’s in almost everything. It’s a losing game and the idea is to try to die before you get sick from ingesting all this crap. The statistics are something like 1 in 6 Americans will be diagnosed with cancer at some point in their life. It’s a pretty prevalent thing at this point. It’s like a when, not an if, kind of thing. You have a clear understanding of cell biology. Can you explain what a stem cell is? With stem cells, if you want to start as far back as the fertilized ova, it gets fertilized with sperm, you get the zygote, which becomes this rapidly dividing mass of cells. That’s what a zygote is? Yeah. It’s just, “Let’s make a bunch of cells.” At this point, these cells are pluripotent, meaning they can transdifferentiate into all the types of cells in the body. It depends on how far along they’re within. In the beginning, they could be anything. That’s the appeal of using fetal cells for stem cells, but obviously, there are ethical concerns with that. It’s not really used anymore. We used to harvest fetal stem cells. There was a period where they were using aborted fetal tissue. Some people are very opposed to that. They passed a law that legalized the use of fetal tissue with the exception of a couple of established lines. There’re few countries where everything is fine. Possibly, you can get away with a lot of stuff in China. Do you think that there’s some important stuff that we’re missing in the US by not allowing that? For sure, but we’ve turned to other types of tissue. With mass manufacturing, as the regenerative medicine industry is starting to, they’ve found a way to start to scale up to levels that are able to produce pharmaceutical quantities. In some of the tissues that they’re looking at now, they can isolate stem cells from bone marrow, from adipose, which is fat tissue, and then placenta, which is the mesenchymal stem cells that I’ve had the most knowledge about. One in six Americans will be diagnosed with cancer at some point in their life.Tweet You’re not getting them as fresh as they are in an embryo, but pretty close. Are you able to get stem cells from the fat in the knee? The issue is you’re getting stem cells from an adult that’s already of adult age. There’s still some floating around in there. Ideally, in theory, we’d like to have cells from a young individual with placental tissue. Mine are old and decrepit and they’re obviously dropout stem cells because they didn’t bother to turn into something else by now. With something like the placental stem cells, you’re generally getting them from a C-section. It’s tissue that would be generally discarded as medical waste to begin with, but you have a younger mother. Usually, ages 18 to late 20s is the optimum age. They essentially isolate the cells and they’re able to culture them in vitro and expand them out into larger cell lines that are capable of creating very large quantities of product that is, from a characterization standpoint, almost identical. There’s a variation from one woman’s placental cells to another. That’s the nature of biologics in general because it’s human-derived tissue. Even if you have the same process, you might end up with a slightly different composition of matter on the final product. Do you think that there are supply constraints on this or is there plenty of placental stem cells? There’s definitely some highly competitive market with human tissues in general. A lot of companies are getting exclusive contracts with the tissue procurers. There’re companies that their sole purpose is just to acquire birth tissue or organs, the whole organ market trade. There might be some screwy incentives there. Do you think it’s possible this explains why there has been a massive uptick in the number of C-sections performed? It’s not necessarily related to the organ market. The C-section issue is more of a convenience thing for the factory perspective where they’d like to get women in and out as fast as possible. There’s a huge amount of unnecessary C-sections. There’re some interesting books on the topic where they’ll push women into C-sections that are not medically necessary just because it’s faster. That’s what I heard but maybe not because they’re trying to get more placenta. There’re some laws in place regarding the sale of human organs. It’s done in a strange way where the mother of the child will give consent. Informed consent is one of the laws regarding human tissue acquisition. She has to sign. The way that they word it is, “I hereby donate my birth tissue for scientific research,” which is interesting because the way that’s worded you think it’s going to academia and you think it’s going to be, but a lot of this is going to for-profit mega-corporations. They don’t realize that their one placenta is probably going to make hundreds of thousands to over $1 million with a product. It’s a little bit misleading and it’s a little unfair, in my opinion, that they can’t legally compensate them. There’s a lot of steps required, with, for example, the American Association of Tissue Banks. When you receive the tissue, there’s an entire process of handling. It has to be kept at a specific storage. Sometimes there’s a sealing rinse or sometimes they’ll use an antibiotic rinse because sometimes there’s a little bit of exposure to different types of microorganisms from the skin when they do the C-section. Essentially, you want it as sterile as possible. You don’t want to introduce any sort of organisms into your cultures that you’re going to be using. With the exosomes, you’re culturing the stem cells for the explicit purpose of harvesting the exosomes and creating a cellular product. The final product is completely stem cell free, which is interesting. There’s been a lot of stem cell research. There are interesting therapeutic applications, but it’s with the gray market in the United States because there’s been a lot of adverse effects associated with the stem cells. That’s why you see a lot of people flying to Mexico or flying to another country for stem cells themselves. The issue is they’re allogeneic, meaning they’re coming from another human being, in which they could have an immune response in you because they have MHC Class II cell surface markers that the body may recognize as antigen. “This is a foreign tissue. It does not belong to me. It’s an invader.” The same situation with organ transplants. Sometimes the stem cells have transdifferentiated into the wrong type of tissue. For example, there was a scenario where a woman had some injected into her face. It migrated to her eye and transdifferentiated into osteocytes, which is bone. She ended up growing a chunk of bone in her eye. There was another, they were trying to cure paralysis in somebody with a spinal cord defect or spinal cord injury, a quadriplegic. The stem cell injection that they got overseas was from a bad line that turned into a large tumor mass that is extremely difficult to remove once it’s in the spinal cord. That’s a very serious area for surgery. In that case, if the reason it became a tumor was because of the stem cells that were used, and that you used a different stem cell from a different donor, maybe you would have had a different outcome? It’s possible it’s that the donor may have had a genetic defect. Sometimes when they mass culture these cells, they’ll do what’s called expansion, where the cells will divide and you’ll continuously divide them to additional passes. It’s called passaging. You’ll passage more and more, but after the cells have gone through this division stage through around 68 passages and beyond, that’s the point where you might get some genetic aberration. As with humans, after 6 or 8 generations, your grandkids are total assholes. In that case, from what you’ve said, if I understand, if it had been stem cells derived from a fetus, there’d be less risk of this kind of genetic passing of a tumor through a stem cell to a new person. It’s possible. I don’t have a whole lot of experience with fetal stem cells directly. The other thing is if you inject me with stem cells in my cheek and it crawls up to my eye and creates a bone and that’s not what I intended, how are you supposed to be telling these stem cells what they’re supposed to transmogrify into? That’s the interesting thing now is we aren’t quite at a place yet where we have full control. We inject into a site and we hope that it differentiates into what the neighboring cells are. The neighboring cells are releasing signaling molecules that will communicate and they know what they’re supposed to do. What they’re finding in research is that when people are getting these stem cell injections, initially, the mode of thinking was that, “When you get these injections, these live stem cells are ingrafting into the human and transdifferentiating into whatever tissue and exerting whatever the effects are that you’re aiming for.” There have been some studies showing that large portions of live cells that are injected actually die off very quickly. They don’t survive in the host. The exosomes being released from the injected stem cells are actually inferring most of the effects that we’re seeing. With exosomes, we’re able to cut out this middleman or this other product that has all these issues. Another issue with stem cells is their lives. You have to transport them at cryogenic temperatures. You have to have a whole Coltrane shipping and storage versus exosomes which are off the shelf, stable, and can be kept at slightly warmer temperatures for shorter periods of time. Let’s rewind here and explain what an exosome is. I don’t have a strong association with what an exosome is. Can you try and school me on that? Exosomes are starting to gain a lot more attention in research because initially, the thought was that they were just waste molecules. What they are is a lipid vesicle membrane, which is a package that is produced within the cell that is released by the cell. It’s used for paracrine communication, which is cell-to-cell communicational travel to a different part of the body and exerts an effect there being, they’ll have uptake into that cell. It’s like little bits of code and they contain different types of protein like micro mRNA, various anti-inflammatory and immunomodulatory cytokines, lipids, etc. There are growth factors and healing factors. The exosome itself is about 70 to 100 nanometers. They’re nanoparticles. It’s very interesting because they’re very small-sized and able to travel through the bloodstream, but interestingly they’re able to cross the blood-brain barrier. You’re able to use them for a lot of conditions of the brain that have, for example, neural inflammation. We’re seeing in even something like depression, anxiety, PTSD, you have some level of neural inflammation. You can have inflammatory processes within the brain that creates this chicken and egg scenario where if you’re somebody with PTSD, severe panic attacks, or anxiety, and you have depression, you have these circuits wired for these types of thoughts. Those different unit hyperinflammatory state causes more symptoms, and the symptoms then cause more depression and anxiety, and it creates a feedback loop of continuing this cycle. Inflammatory stages mean more blood is being sent to those tissues? More blood and more active inflammatory cytokines. What are cytokines? Cytokines are signaling molecules. Are they like exosomes? Exosomes contain them and they also have various mRNA that codes for them. An exosome contains cytokines, which contain mRNA. We’re still elucidating exactly what the full characterization of it is because when you do a protein panel assay, you might see that there are hundreds of thousands of different compounds within an exosome. It depends because we’re focusing mainly on stem cell exosomes because that’s the therapeutic applications that we’re interested in. Most eukaryotic cells produce exosomes in some manner. What does eukaryotic mean? It’s cells that are from average animal or average plant, a lower life form. An exosome is like a FedEx delivery driver. Cytokine is a package, and then mRNA is like a floppy disk inside. Yes, the executing code that once it’s taken up by the cell becomes the blueprint to manufacture more proteins based on what that is in particular. What I’m trying to understand is, do all cells have these exosomes that they spit out? Most cells do, but they’re not all necessarily things that are therapeutics. One of the interesting things that they’re researching exosomes for is biomarkers for specific disease states. If you have a specific type of cancer and we find that a specific type of exosome is released by that cancer, they could be developing a diagnostic test. It’s very hard to diagnose certain types of cancer, especially if it’s an organ that’s very hard to get to. If we’re able to find that in the bloodstream and create diagnostic tests, it’s early preventative, finding diseases earlier, and being able to treat them earlier. The other interesting application besides therapeutic use is drug delivery systems. We’re able to take these nanoparticles and there are different techniques that you can load them with a pharmaceutical drug. Since they have this targeting effect in vivo, you can use the exosomes to target a specific disease state. For example, you want to get a drug across the blood-brain barrier that normally cannot cross the blood-brain barrier. It can cross within the exosomes and now you can deliver a certain substance to the brain that you could not previously. Stem Cells: Some recent studies show that a large portion of live cells injected die off very quickly. It’s the exosomes being released from the injected stem cells that infer the effects that you experience. How does the targeting work? Targeting is when you have a specific site of inflammation. If you have a highly inflammatory disorder, autoimmune disorders, osteoarthritis, various muscular-skeletal disorders, these sites are actively releasing inflammatory molecules. There’s a homing effect for exosomes where they’re able to target and find, within the body, where they’re supposed to be going. It’s pretty interesting. Can you somehow program it to go where you want? The interesting area now is synthetically engineered exosomes. Creating an exosome that has a specific purpose or specific indication, for example, there’s some outside of Israel. There’s a new one that they’re developing for COVID that is very specific to acute respiratory distress syndrome from COVID. It specifically targets the lungs and inflammation in the lungs. It’s had some very interesting results. In terms of having a differentiated product that uses synthetic biology to create a very specific exosome that’s targeting a very specific indication, that’s very valuable. Anybody can open up a laboratory and start mass manufacturing exosomes that have a broad general use. Essentially, the way the market is structured right now is that it’s a very gray market, a lot of the Wild West frontier where doctors have the legal right to use products off label in a manner that they see fit for their practice. It’s not illegal for them to purchase the product and, for example, inject that into the spine of somebody paralyzed but the companies that manufacture it absolutely cannot advertise it for that purpose. You can only advertise it for whatever the purpose is that they have FDA clearance for. If it’s for cosmetic use only, they can advertise it for cosmetic use only but that’s becoming a loophole now where they’re marketing it for cosmetic with a wink-wink nudge, and a lot of physicians are purchasing it and injecting it into the articular spaces for arthritis. Is there any legitimate cosmetic use of injecting these stuff in people? Cosmetic and legitimate are subjective. Maybe like a bunch of exosomes in my lips for filler. Possibly not your lips but like your skin, I haven’t seen highly conclusive data on this yet but some who have received this claim that the rejuvenation of the skin cells is causing the new skin to grow back with the texture of the baby skin. Very soft with very small pores and reduction in pore size. I personally have seen a patient that was injected that had very severe rosacea around his nasolabial folds. Very red and blotchy. Within about 48 hours, he had complete remission of the rosacea. It’s completely clear. It did return after a few months. It’s not a permanent fix because the underlying causative factor that’s causing that condition is ongoing. It’s not a permanent cure. It was exosomes injected into that skin and it’s generic exosomes harvested from a placenta like you described before? Yeah. We’re at the beginning of figuring out all the places this could be used. This is the thing that’s the most fascinating is, when you go into pharmaceutical or biopharmaceutical development, whether you’re a startup or whether you’re a multibillion-dollar corporate entity, they dump massive amounts of money. To the thousands of drug candidates, you might get a handful of drugs that end up making it through. Some of them will make it through phase one clinical trials and then they won’t pass to phase two. A lot of us don’t pass it. Most of them never make it to market. It’s a very high-risk ratio of the cost of R&D and trying to get through the clinical trials to get it to the point where it’s perfect for humans, but then you have something like exosomes where you don’t have your one indication. There’s this massive variety of so many indications that we’re seeing efficacy for. There’s a lot of rat studies that are fascinating and now we’re starting to see some human studies and case reports for human clinical trials. For example, post-stroke, if it’s administered immediately after stroke, there’s a very high chance of not having permanent brain damage from stroke if it’s a particular type of stroke or from a CTE from a brain injury. This is only, so far, tested on strokes that rats have had? I’ve seen some case studies in some hospitals where it’s being used with humans. I’m low risk for stroke but I’m terrified of it. Can I get a bottle of exosomes and stick it in my backpack and whenever I have a stroke, just chug it? How close to that could we get where instead of an EpiPen? Right now, the big issue is needing to be stored because the mRNA may be denatured at high temperatures. In general, you want to store it at around negative 80 Celsius. I heard somewhere that the mRNA vaccines, I don’t know if it was both of them or one of them, are working out to be pretty effective stored at normal. They have a shorter lifespan but they’re also working on what I’ve seen as layoff-alized versions, where it’s essentially a freeze-dried version that’s reconstituted. I haven’t seen a lot of shelf-life data on that yet, so I don’t know. It’s too soon to know. How does mRNA work? An mRNA or messenger RNA provides the translation of the RNA into the target cell where it will aid in the manufacture of the new proteins. Can I think of mRNA like a system update like injecting some new code into a cell? Yeah. It’s like a little floppy disk that’s hopping over there and has a little executable program. If you extrapolate 100 years from now, imagine that we learn a lot about mRNA and we learn to write code. That’s the holy grail of gene editing in general. There are so many incurable diseases right now. They are tinkering with congenital blindness and they’ve actually had some success where they were able to rewrite code that was for certain types of blindness. The type that someone’s born with. It’s genetic and we’re rewriting the genetic part that made them. The holy grail is, “Can we cure people that have congenital diseases by altering their DNA long-term?” There’s also CRISPR which is this great invention, but there is a concern about off-target effects. If you’re editing a certain gene sequence, there may be an unintended downstream edit somewhere else that comes with other unintended effects. We don’t fully know the long-term implications of stuff like that. That’s why you haven’t seen, “Here’s the blockbuster drug that was made with CRISPR.” It hasn’t happened yet. This seems like a big data problem and over time, we’ll know more and more about what’s in that genome, what the different bits of code do, and we’ll be able to write it. We already know how to write it, so in some sense, if all that went well, which might take more or less than 100 years, maybe 1,000 years, who knows. At some point, though, we’ll probably be able to figure out what all the code is and we’ll be able to write any and all of it. We’ll be able to repair the code that’s damaged or causing things like congenital diseases to be passed on, and then we’ll be able to design radically new variants of humans. This is where people start to get into ethical dilemmas because it’s like, “What is fair?” I know that ethical dilemmas are not part of this discussion, though. We want to touch about what’s causing them. I have a mad scientist approach to things. I’m very much a fan of tinkering. This is a little off topic but when I think about space exploration, there’s a lot of talk about, “Do we need to do gene editing in the future in Mars?” It happens, for example, where there are species of animals that are in sunlight all day long like elephants and dolphins, who don’t have high rates of cancer. It’s something about the compounds within their gray skin that they don’t have this crazy high rate of cancer that we humans have. If we’re talking about putting people in space or sending them for long time, they’re getting bombarded by all the different types of cosmic radiation. What if there is some gene sequence in their skin that would allow humans to have some? This is just me guessing. There are a lot of interesting applications for space travel. With the radiation, you also have a lot of immune system suppression. That’s a big issue in space. Your immune system goes to shit. mRNA is like a little floppy disc that contains an executable program for your body.Tweet That’s what we’ve seen with the astronaut with the twin brother. Ethical questions require a completely different conversation. I try to stay out of that just because. I do too but it’s not because they aren’t important. It’s important but I also have a thing for the idea of experimenting a little bit on the edge because that’s how you make progress. You get a little bit outside of the boundary. You have some people push things a little too far. There’s no argument like with the Chinese CRISPR editing of the babies. Did they really need to be edited? Can you describe that? The Chinese scientists did some CRISPR editing of these babies to give them immunity against HIV. Arguably, is that really a concern? Number one, nobody’s doing CRISPR experiments on human babies. We don’t know the long-term effects or the downstream effects of this. What are the odds of these babies encountering HIV in their lifetime? Where do you draw the line? Do we start to edit for every single disease? To my knowledge, they weren’t coming from parents that were HIV infected. If they could make all future humans HIV resistant, we could eradicate that disease. Yeah, but I don’t think he started in monkeys or rats. He wanted to get a name for himself. My understanding is, it was ego-driven and he wanted to be a famous person. It’s interesting because I don’t have this fascination with the slightly not okay experiments of Russia and China. They do push the boundaries in a way that’s not acceptable here but it’s fascinating data. I’m not endorsing any particular thing. I’m not either. I just have curiosity. We only want to know what’s possible. If you just imagine, we get to a point where we comprehensively understand all the code and the DNA. We understand how to program mRNA and do whatever we want, we eradicate all the diseases and we bolster immune systems. We get rid of all the things that can kill you. Do you think that would be a problem for evolution? You’re cutting out the natural selection, which is another ethical dilemma. Everybody gets to live. We cut out the survival of the fittest while keeping natural selection. You get to choose a mate. Is that going to increase long term some defects? If you’re in a poor country, you need to have access to those gene editing technologies. If you’re in a third world country, are you going to have access that the other people in the first world countries have? I don’t think we’ll have third world countries much longer. You don’t think so? I don’t know. When I visit these, I still see how far behind they are. Automation will come and we’re hoping that these menial labor tasks such as the cruel labors ideally will be replaced by robots and hopefully get these people into better and maybe universal. A lesser form of humans that we can create with our genetic superpowers to do our bidding. Biological robots. No conscience, clean my clothes, bad idea. I am just kidding. I have a fascination with the idea of growing brain organelles which you can grow these mini-brains from neural tissue. The question right now is, do they have consciousness? Are they suffering? We don’t know. Do we grow them and put them in geckos? I would love to have a gecko that could braid hair. They’ve done something interesting. I saw a pig and a human brain chimera. There were some monkeys that they had mixed with some human genes. That does have a bit of a creepy feeling. If we give a monkey some aspects of human consciousness, are they suffering? We don’t really know, but what if we’re able to grow this organelle, place it into a computer system. If we can use the computational power of a brain versus a computer, obviously, it’s two very different styles. If you look at the way that memory in the brain works, the millions of various neural connections between so many disparate areas of the brain and different memories and recall the way that we process things. When you’re heading in the direction of artificial general intelligence, I don’t think they’re ever going to replicate that purely in silico. The hybridization of human neural tissue like tissue on a chip or brain-computer interface with an actual neural brain, that’s the area I’m interested in. If that works, maybe we can make a big one. The human brain is pretty big but what if we could make a 40-pound brain? That’d be cool. We could modify humans to have thinner skulls, more brain, that seems like it would have an effect. Maybe there’s some point of diminishing returns where the circumference of the brain is too high but we could hybridize the architecture and take these multi-core chip architectures and have multiple brains with high-speed interconnects. We have them get into the whole BCI Neuralink area. Can we master the understanding of electrical and data transfer? We’ve had a little bit of progress. If you see, for example, people that were born blind, they were able to bypass the optic nerves and able to put cameras on these people’s heads that send rudimentary images into the visual cortex of the brain and they’re able to see. They don’t see 20/20 like us but they can see light, dark areas, navigate within their homes, find their way, and see the outline of contrasty things. You see that now with hearing. You’re seeing the hearing implants that they’re bypassing the defective cochlear structures and able to implant it directly into the auditory portions of the brain and they’re able to hear. I see all these senses that are now being able to be augmented or completely replaced in people that are born without them. It’s like, “How far can this go? Can this go to the point where we can plug in computers and then start to use it with the neural language?” Neuralink is not the first or the end all be all. The people in the neurotech community have been working on BCIs for decades before Neuralink. If you go into the NeuroTechX Communities, they’ve been working on this forever and it seems the spotlight was stolen from them because they have been working on this for years. There’s probably a story just like in electric cars and spaceships too. When we think about computers, the computers have a bus. They have an interface. You don’t try to tap into every transistor in a chip. You have a bus where the chip does this processing and then there’s like an I/O bus where you can move data in and out. You might think of it like the eyeballs or the spine is I/O for the brain. I’m making shit up here but I’m guessing there’s a lot more to be gained in the short run by trying to understand those interfaces and use them than to try and go tap into and monitor every neuron in the brain. Even Neuralink has no concept of how to get there. It’s very much in the stages of infancy. It’s very early days. I like where it’s going and that the initial use cases are going to be for people with quadriplegia or people who have locked-in syndrome that cannot communicate outside, they have no method of communication whatsoever with the outside world. With BCI, they’re going to be able to have some life skills where they can communicate on a computer. They might be able to drive their wheelchairs around their house even though they’re completely paralyzed. They can have some basic living functions, which are really special. In some sense, it’s a way to circumvent the ethical questions about the work because we look at them and say, “These people got less than the average human. There doesn’t seem to be any ethical concern about trying to close that gap for them.” That’s also a little bit presumptuous to say. I don’t know. Maybe somebody knows but if you have Down syndrome, who’s to say? They seem pretty happy a lot of the time. Maybe they don’t want to be like us. I don’t know. I’m just making that up. We do seem to circumvent the ethical discussion out, whereas if you’re talking about making humans that are advanced on some access beyond what we’ve seen, then it gets sketchy. I imagine a near future where the NBA is entirely populated with super tall, blond Chinese people because they’re smarter than us and are way better at math. I see that coming because they have a different ethical sensibility in that region. We have been very conservative about gene editing. We’re going to see a lot of the innovative stuff in the countries that have slightly more lax regulatory controls on what they’re able to do and not able to do. I see the double-edged sword on this because if you went back to look at some of the unethical experiments a few decades ago, they did some pretty wild stuff. In other countries, too, they did some pretty wild experiments. There was one where they were attempting to cross hybridize women with sperm from a specific chimpanzee or some type of monkey and it was very unsuccessful. I don’t think any of them fertilized or any of the embryos made it but you can never get away with that now. It’s so wild but at the same time to me, that’s fascinating because what if it works? What is ketamine? It’s a dissociative anesthetic. I know there are different classes of drugs, and that’s one of them. What are examples of classes of drugs? What does dissociated mean? What does anesthetic mean? With anesthetics, you have more typical inhaling gas. When you do surgery, they’ll often intubate somebody. They’ll have an anesthesiologist that will control the levels of the gas and sometimes there’ll be a paralytic agent where their body is paralyzed. They’re not experiencing pain and they’re not conscious. Ketamine is a fascinating dissociative anesthetic for many reasons. It’s on the World Health Organization’s top ten most essential drugs because it does not require an anesthesiologist to be present to monitor it. It completely spares the respiratory system. You don’t have a risk of suffocation. This is something that’s still used in American hospitals, mainly for pediatrics, and now off-label for pain and depression, on battlefields or third world countries where they don’t have the resources to have a full-time anesthesiologist. They’re doing field surgery, and a lot of third world countries are just doing quick surgeries that are subpar, it’s a very critical drug for that. It’s regained a lot of interest over the years because it has a very fascinating efficacy rate for depression, especially suicidal ideation. It is far more statistically effective than typical SSRI antidepressants, especially for people that have suicidal ideation. People that are suicidal, within 45 minutes of infusion, are no longer suicidal. The main reason it was removed from main use in hospitals is it does have a psychedelic, disorienting, or dissociative effect when people start to awaken from the anesthesia. It can be very psychedelic and scary for them. It’s used mainly in pediatrics and in people with asthma or with other respiratory system issues. With depression, there’s so much overwhelming evidence. Ketamine has been off-label for patent for many years. It’s generic and a very cheap drug. It’s something like $10 for a vial of it. They’re reselling that for thousands. Cash pay for these ketamine clinics, one of the major companies, SPRAVATO, which is the S enantiomer of ketamine versus the racemic which is the normal RNS. What’s the difference and what does that mean? With the manufacture of drugs, you have something that’s called stereoisomers, which is basically you have the same bonding configuration of the molecules, and you have what’s a left-handed and right-handed version. It’s still the exact same young compound but in 3D space, they might be bent in one direction. You have receptor sites in your brain, for example, NMDA receptors for ketamine, and the left glove might not necessarily bind as tightly to the specific receptor site. It might confer slightly different effects. With ketamine, you have the R-isomer, which supposedly has more of the drunken kind of stupor high feelings, and then you have the S-isomer, which is used medically in Europe that can be a little bit more psychedelic and it seems to be lacking in the physical drunkenness components. Regardless, the SPRAVATO, which is being used very for PTSD in veteran’s hospitals. When you get that administered, they make you wait three hours before you’re allowed to leave. You’re not allowed to drive. Stem Cells: The brain has millions of various neuro connections. It is extremely difficult to replicate such a complex system in artificial intelligence. They want to make sure you don’t have some weird psychedelic side effects. It’s a fairly low dosage nasal spray compared to the IV bolus or the IV infusion. It’s interesting to see it’s not just depression, but it’s also pain. They’re finding a lot of pain relief, neuropathic pain, especially, with ketamine. We used to think that it was just NMDA receptor antagonism, but now we’re finding that there’s a multitude of other possible mechanisms of action. There’s quite a variety of possible reasons why it is so effective for depression. The main downside is it has the potential to be highly addictive. It is something that does have addiction potential. The relief of depression is so intense that people who have severe depression start to chase that relief of depression to the point where they can become addicted. If you’re not receiving psychotherapy, in addition, if you’re just getting straight-up infusions with no psychotherapy in conjunction, you’re not making any long-lasting changes. It’s not covered by insurance, so it’s a cash payment. In a major city like Manhattan, you might be paying $600, $800, $1,000 per infusion. It’s not cheap. It’s not covered by insurance yet. It should be cheap because the actual product itself is something around $10 for a generic vial. It’s not expensive. There’s massive markup, and there’s a gold rush of these ketamine clinics just because they’re very easy to open. What are they doing, mostly? Suicide prevention? That and pain for chronic pain patients and then chronic depression patients, it’s done in a very sterile doctor’s office that’s not conducive to something that has a slight psychedelic element. You’re in a brightly, fluorescent lit room. What would be better? In my opinion, is the use of virtual reality as an adjunct, which is what I’ve been studying. I completed an eighteen-patient pilot study clinical trial. With that, you have an additional layer of immersion. It’s interesting, especially with pain patients where the objective is you would like to get these people off of opiates. We do not want people to do opiates. It’s a dangerous route to go down because then you can’t get off of them. With something like VR, you have what’s called immersive distraction, where you have a finite amount of processing power in your brain for all your senses. If you’re experiencing greater high levels of pain but then I expose you to high levels of visuals and I expose you to sound, there might be a physical component. Some people are adding in a sub-pack which is like a subwoofer vibrating vest. There are all different things. The more sensory stimuli that you’re putting in, especially if they’re watching something with some emotional component, your brain cannot process the pain, the visual, and the auditory. They’ve been doing studies on this and finding that VR alone is reducing the perception of pain. This is something that’s very important for people with severe burn injuries who have burned and lost 50% of their skin. It is excruciatingly painful to do the wound changes. They don’t have skin. It’s completely burned off. They’re finding that with the use of VR, they’re able to tolerate a lower level of opiate painkillers. They have less fear and anxiety built up about the wound dressing changes because they know that they’re going to be distracted. They’re not seeing what’s going on, and you’re not paying as much attention and they’re occupied mentally. There’re also some other use cases for VR. They did a study with twelve paralyzed patients that they were able to show in VR, there’s this very interesting phenomenon where if you show the paralyzed limbs moving and the physical therapists move the limbs, you start to regenerate neural growth where they were able to regain motor function in parts of the body that were previously paralyzed. It’s a fascinating study if you google it. It goes to show that the effect of VR has on the brain alone is very powerful because it’s so immersive that it can be nearly indistinguishable for the brain from a real experience. You see people on the edge of a cliff in VR and consciously, you’re safe, you’re in your house. There’s no hole in your floor. People, as soon as they approach that hole, they lose their balance and fall. In the Oculus with the plank simulator, everyone should try it. It’s insane because you can have that exact feeling. People fall. It’s hilarious. They do. I put my dad in it. He would not step off the plank-like, “Nope. Not doing it.” It preys on people’s fear of heights and be falling. It’s like your carpeted house is part of the brain that it does not accept. The one that fascinates me the most, I don’t know anything about it, but I heard about a project where Navy SEALS or something, were using VR to treat PTSD. 100% of Navy SEALS have PTSD. It’s part of the job. I don’t know anything about this stuff. I’m making this part up, but in what I learned about trauma before, it seems to me that a lot of cases of PTSD where you get yanked out of a situation before your brain got to finish a story. Your brain gets stuck in this cycle of trying to find an ending for the story that never got finished. You’re stuck in that spin cycle. With VR, what they’re doing is they’ll put you back on the battlefield where your buddy got shot or whatever. You’re there and you get a chance to finish the story. I’m making that part up. I honestly don’t know what they do. I made all that up but maybe it’s something like that. From what I’ve seen, one of the issues with mass adoption and mass scaling of that is PTSD is personalized visually, which means some 3D designer has to rebuild like, “Was there an exact incident in Afghanistan where this is what happened?” The next person might have had a completely different experience. They have to rebuild. It makes it a little bit more expensive and harder but it seems to be effective because through this therapy, they can relive the situation, and they realize that they’re safe now and they’re not in the war zone. With the right kind of therapist, they’re able to revisit these emotions. There seems to be a pretty good high rate of treatment for this and PTSD. The circuitry in the brain is rewiring to create hypervigilance, which is you’re in a state of constant anxiety, you’re sensitive to sounds, and sensitive emotional triggers. It’s sad because it’s such a massive issue in the United States, PTSD with veterans. They’re not doing a whole lot to treat them. It’s an area that they deserve to have a lot more options for therapy. Fully understanding how mRNA works is the Holy Grail of curing people with congenital diseases by long-term altering their DNA.Tweet I have a friend who’s a pediatric doctor and he wants to use or has used, I don’t know what the status of it is, virtual reality and ketamine with kids who have a variety of different problems to help them adjust. It seems like a frontier. I’m working with virtuality with ketamine. I would like to see data on the long-term safety of any type of psychedelic on a child. Some of the early research that I did when I was a teenager was on psychedelics on the developing brain. Your brain is still developing up until you’re about your early twenties. You’re not fully formed. The question is, “Are we causing any long-term damage to a developing brain by exposing them to psychoactive substances at a young age?” Some of the data that I produced seems to suggest that there might be long-term effects. I focused on cognitive development in adolescent rats with a substance called the five immunity IPT, which is a tryptamine psychedelic drug. We did find some minor deficits in spatial navigation and flexibility in learning related to the serotonergic pathways in the brain that are associated with memory and flexibility learning and it wasn’t massively drastic. These rats probably weren’t going to have a good time without MapQuest or GPS. Now there are some data coming out saying that teenagers that smoke marijuana may have some brain issues later in life from smoking early. I have mixed feelings on the whole idea of psychoactive for children. Although I’ve seen some interesting case studies that some of them were not published for fear of legal reasons. There were some children that were semi-autistic, born mute, and could not speak English. There was a story that I had heard from somebody reputable where the family was associated with some major hippie touring bands of the 1960s and the child accidentally got a piece of candy that had lysergic acid diethylamide, LSD. The parents freaked out. They’re like, “We don’t want to go to jail.” Shortly after the incident, the child began to become verbal. It’s interesting now because, in the past few years, the major breakthrough is we now have FMRI studies of brains on LSD. We’re seeing the hyper-connectivity between parts of the brain that were not connected. We’re seeing different parts of the default network that are cut off. It’s was a totally different operation of the brain. Now they’re even suggesting psychedelic psilocybin mushrooms for patients that are in a vegetative state. They think that because it does regenerate neural tissue, can we wake them up out of the vegetative state? That’s interesting. Would it be amazing if we figured out that anyone can be brought out of a coma? It’s possible with people with brain damage. We see with neuroplasticity that some people that have had a traumatic brain injury, even though that part of the brain has become as ischemic and died, they’re now seeing with DMT, LSD, psilocybin that they’re able to regrow new neural connections. The brain has fascinating neuroplasticity because it’s able to remap. Once you’ve lost some important part from brain damage, you can often remap to a different location. You get some interesting results. It goes against the old school of all the neurons that you’re ever born with and they die over time because you drink alcohol and you do this and that. Now they’re starting to say that maybe that’s not true. It seems like we are still regenerating. There are stem cells in the brain. From what I read, alcohol is not particularly kind to your neuro stem cells that you do have present. Personally, alcohol is a toxin that should be moderated upon. It’s been around for millennia. Its effects are at least well accepted. I don’t drink at all. We’ve seen people live to 120 years old who drink a glass of whiskey a day. I learned that in junior high. Alcohol kills brain cells. I figured I might as well keep as many as I can. I never started. It’s an interesting social lubricant. You’ve seen it in Greek times and ancient times. It’s ubiquitous through all stages of human culture, some sort of fermented alcohol. It’s not a drug per se. It’s a toxin. You’re poisoning yourself. The effects that you’re feeling are the effects of being poisoned. It’s interesting to see how much of the brain is generative and neuroplastic. Looping back to exosomes, now that we can get them through the blood-brain barrier, some of the damage is being caused by stroke or by exposure to chemicals or by various brain injuries or drug use. There’s a high probability that there might be between psychoactive substances like psilocybin mushrooms for example and between stuff like exosomes that are showing efficacy for treatment of post-stroke and all these other neurodegenerative conditions. There’s some possibility on the horizon of being able to repair some level of brain damage. Who knows? Maybe stave off dementia or have some treatment for dementia. I’m interested to see how far this goes. What do you think the near-term priorities for exosome research should be? There are many different areas. Whatever it is, there can’t be enough. It’s connecting back to what I was mentioning earlier with the big pharma companies that have their one-hit-wonder drug that does the one thing and they poured their billions of dollars of research. If they fail the clinical trial, it’s garbage unless they can repurpose that. Can exosomes cure erectile dysfunction? They then could get all the funding they need. There are people who claim that it does. I haven’t seen solid research on it. There are clinics advertising this. There’s this little gray market going on. The FDA, their stance on it is what they call selective enforcement where they’ve agreed to look the other way as long as the companies are not manufacturing it and marketing it explicitly for injection. That’s not legal. A drug is injected. They’re marketing it for topical use. The doctors legally have the right to use it off-label for whatever they would like. Is there any topical use of exosomes that does anything? With the cosmetic clinics, there are all these interesting Vampire Facial procedures, post-laser resurfacing microdermabrasion mixing it with PRP. They use it for hair-loss. What’s PRP? Platelet-rich plasma. You’re essentially extracting from your own blood and then it’s being returned to you. It’s being ultracentrifuged and returned to you and injected back into you. You’re back to the scenario of your old cells and you’re giving your old cells back to you. From what I understand, the PRP makes scaffolding. In Korea, they already have a multibillion-dollar exosome company. Korea’s skincare industries are massive. Most women have plastic surgery at a young age. I was talking to some of my female Korean friends. It’s normal for your parents to pay for a nose job and eyelid surgery. You’re expected to have flawless skin. It’s a massive beauty industry there. In the United States, we have a big regenerative anti-aging market where a lot of people would like to live forever, lifespan extensions. It’s getting into is it pseudoscience or not? If people have the money to play around with that kind of stuff, I don’t see the issue. It’s one of the only substances that I’ve seen working in pharmaceutics that does not seem to have a detrimental side effect that I’ve seen. If you look at something like Tylenol, which has a massive amount of overdoses, a massive amount of liver damage, all kinds of side effects. You have something like the exosomes, there are not many reports with the exception of a few unscrupulous labs that are selling contaminated products out of the warehouse, basement, or whatever. That’s why the FDA does need to step in and regulate a little bit better because those are the people that mess it up for everybody. Stem Cells: VR alone is reducing the perception of pain, which is useful for people with severe burning dreams. It’s relatively safe to try different things with this stuff, it sounds like. We have not seen off-target or downstream effects thus far. I’m not saying that there isn’t. People should be allowed to try it. We have enough extra humans anyway. Some of them can be devoted to exosome research of their own volition. I was one of the first guinea pigs. I had myotonic synovitis and my wrist was 99% cured. For that, I had five CCs of an exosome and saline preparation that was injected into the carpal tunnel. I had severe inflammation of my tendon from repetitive stress injury from poor risk posture when typing for my entire life. In the past 5, 7 years or so of grad school, it became excruciating. The nerve pain that was shooting up my elbow made it unbearable for me to use a cell phone, to type, or to use a computer mouse. I ended up having the product injected into my wrist and I started feeling improvement that was not placebo within a few days. Eventually, it’s been several years now and the pain is 99.9% gone. It’s what converted me over like, “This is a real product.” It removed the inflammation. Hand surgeons were saying, “There’s nothing we can do about it. We can inject corticosteroids into it.” It’s not a long-term solution of steroids injected into anything, atrophy muscle and the atrophy tissue. It depresses the immune system. Steroids are not a good thing. I was at my wit’s end because I had gone to multiple top hand surgeons in Miami and they’re all telling you, “It’s not carpal tunnel syndrome. There’s nothing we can do about it. We can’t do the carpal tunnel release surgery because you don’t have a carpal tunnel.” What do I do now? I’m learning how to type with my left hand. I’m flipping over my brain. Finally, I was like, “I’ll try it. Why not?” It was life-changing for me. I haven’t had an IV yet. It’s something possibly on the horizon. If I do get COVID, I want to get an exosome treatment because we’re seeing now there’s some IND, Investigational New Drug Applications, with the FDA. We’re seeing a lot of the detrimental symptoms of COVID is not so much from the virus itself but it’s from the immune system going hyperdrive. Your body is starting to attack its tissues in response to the viral infection. Oftentimes, the viral infection clears out but your organs are still being attacked and attacked. This cytokine storm of inflammatory molecules thinks that it’s being helpful by continuing to attack the tissue where the virus was initially. That’s where you end up with multi-organ system damage. We’re seeing brain inflammation where people are starting to see hallucinations. It’s almost schizophrenia. These are people with zero mental histories of anything. You’re seeing young people with kidney damage, lung damage, and repetitious pneumonia. You’re thinking that it might be possible to inject somebody with exosomes who had COVID and it might reduce the possibility of this cytokine storm? Yes. It seems like for the subset of people who are experiencing the cytokine storm, there are some case studies and there are a few hospitals that are already incorporating it. There are a few controlled trials that are underway. There are certainly some companies submitting INDs. Not necessarily exosomes but there are a few stem cell companies submitting that are already in early clinical trials. With a lot of the use cases for stem cells, it’s fair to say that stem cell exosomes are possibly efficacious for some of the same indications. With a safety profile and better ease of use, you can transport it much easier. You can throw it in the freezer. You don’t have to worry about frosting live cells. They’re not alive. I’m excited about what I learned about all this from you. That’s cool. I learned a lot. There’s so much more. This goes on and on. It’s fascinating because it’s one of the only biopharmaceutical drugs that almost has an infinite possibility of indication and formats. You can have nasal sprays. You can have injections. You can have a transdermal patch that contains a skin permeability compound like DSMO that allows it to be absorbed through the skin into a joint without having to have needles. There are many interesting applications. I can’t wait to have a problem so I can get some. You can hop into one of those life expansion clinics on the West Coast. Get some exosomes. That’s the hot tricky thing right now for some of the people that are into lifespan extension and biohacking. There’s doesn’t seem to be a negative side effect profile thus far that we know of. There’s a small chance that if you have some hidden cancer tumor that you’re unaware of, it’s possible it could increase the growth in some manner through additional angiogenesis. Also, additional acceleration of biomass, it’s something that we don’t know for sure. There are people that are on the opposite side of it. They say, “No. It’s efficacious against tumors.” We need to see more data on that. It’s a frontier. Do you have any questions for me? Probably a lot. I’ve been picking your brain. There’s a lot in your brain to pick. Now is the chance. You can ask the most incriminating questions you can think of. Sometimes, you have to go beyond your boundaries to make actual progress.Tweet Don’t challenge me to that. Is that within the topic of healthcare? Anything. I don’t care. It doesn’t matter. Are you becoming more involved in the healthcare space? No. You’re mostly in the application of technology to solving more global problems. Exactly. I want to try to close that gap. What it comes down to is you have to understand the problems. A lot of times, the people who understand the problems are so deep in it that they don’t also have the capacity to learn about the whole world of possible technologies that could affect the problem. It’s almost always true. On the other side, you have people who know a lot about technology. They’re specialists in something, but they don’t understand the problems that they might be able to affect. They’re often far removed. As an inventor, I was always trying to escalate my knowledge on both sides, know more about what technologies exist and are coming, and know more about what problems exist in the world. Even if I can’t become an expert in them, I want to know the people who are. That way, sometimes you can match them up. All the time now, I’m trying to fill my head with what problems can I learn about and different industries, regions, people, and get a sense of them. Even if I can’t fully understand them, I can learn more about them. On the other side, for me, it was computers. I wanted to learn everything I could about what’s not just everything about computers but what’s possible with them and try to understand where they could go and try to take them to new places. I’ve been making that my whole career. In some sense, we’re still at the beginning. Computers have been super powerful. Outside of computers, where I know a lot less. There are also these amazing frontiers like gene editing, exosomes that I have no idea about, and material science. There are all different areas where you get this progression from scientific discovery. It gives you a sense of how things work. From there, you can advance on, “What’s technically possible?” That’s where you’re taking the output of scientific discovery and trying to figure it out. It’s almost independent of whether it’s a good idea or not. What’s technically possible? I like to be in that space. What could we do with the knowledge we’ve attained? Every day, you get new scientific discoveries. There’s a new sensor, a new algorithm, a new paper on how something works. To me, that’s input and I want to know so that I can match them up. There’s probably a real sharp limit on how many things I’m going to affect but that’s part of why I like sharing these conversations on the podcasts because then other people can learn those things, too. I’m learning them but maybe somebody who’s going to be useful at advancing exosomes will listen to this and get excited about it. Probably, I won’t be that one but somebody else could be. A lot of people don’t get the chance to come and hang out with you and pick your brain. For me, what’s exciting is it’s a much longer path than a traditional path of being a specialist in one field. I like trying to learn a lot in disparate industries and fields and trying to see what the crossover is between these disparate industries. You have science and technology. You have something like art or architecture. How can you combine these different areas? You have AI and then you have molecular drug design. You have something else. I like seeing the crossover of it. It’s things that if you don’t have a background in multiple fields, you’re never going to come up with these ideas of cross-pollination. There’s a real value in having depth in something. I meet a lot of generalists who haven’t done that. That erodes their ability to create a sense of perspective with all the new things. If you explore different areas and you’re trying to learn about different things, you need to be able to connect it to something. If the thing you’re connecting it to is deep, then you could have an effect. When you look at the invention work that I was involved in, all of our inventions are at the borders of different areas in science and technology. Have you read Consilience, E.O. Wilson’s book on this? No. You probably heard E.O. Wilson. He was a badass in science. He wrote this amazing book. I don’t know if he’s still alive. He was pretty old at the time. The book was trying to show scientists that these artificial constructs of chemistry, biology, physics and mathematics. It’s all science. They all interconnect. Those silos are keeping us from advancing. Nobody’s contributed more science than E.O. Wilson, so no one can argue with him. It’s pretty amazing. That’s a good one. For me, my hope for the future is I want to learn quite a bit in one field and then move to the next field and move to the next field. Life extension is going to become necessary for you. I see that there are connections that people are missing. You need specialists. You must have expert specialists. You also must have people that are more generalist because they can see where all the different areas connect. You have your specialists who have the expertise in those fields. If you can see the bigger picture, you can see connections that other people can’t make. That’s where the new innovations are going to be coming from. It’s this cross-pollination of all of these. These fields are advancing fast right now. It’s exponential. Compared to when I started my Doctorate versus what I see now, I can’t even keep up. No one can. I’m trying to keep up with multiple fields of science. The papers that come out every day are mind-blowing. Some of this stuff is amazing. It’s exciting. I love it. The tools are better than ever. The tech is getting amazing. Even in biotech, we’re getting further and further down into nanoparticles, nanoparticle medicines. Regenerative medicines are getting more and more of synthetic biology and gene editing. It’s going in all these directions that when I started this journey as a child. It’s sci-fi coming real. It’s amazing. My entire life has been characterized by the fact that I got a computer early on at a young age, and I stayed ahead of people because I stuck with it. You got into the next frontier, which is all that’s possible with genetics and with the future of biology. Now, we’re advancing that because we have computers, essentially. It’s too late for me to get into that. You got in on the beginning of it. I don’t think you’re too late, though. The world doesn’t need me for that. Even with me in the beginning, I still feel like I need to catch up with people. My little insecurity being a generalist is I know I’m never going to have the depth that a specialist has, and I’m happy with that. I want to have generalists. I go as deep as I can. I don’t go to shallow level. It means that for someone that finishes their PhD and their one specialty, whereas I already finished my Doctorate and I’m still going deep on my own personal time. The next thing is like, “No. It’s going to take me an extra 10 or 20 years to reach the level where I can start to see how are all these different things going to connect and how I can innovate and create something that all the specialists we’re not going to be able to meet?” It’s a little frustrating. This is a longer-term timeframe. Some people have to be looking out of the box bigger. I’m not necessarily saying that I will innovate or create something, but it’s a possibility if they continue. A lot of people should try to learn multiple areas if they’re able to and motivated. That’s where the best innovations are going to come from, especially now that we can apply all this new technology to other healthcare principles to biotech principles. It’s such an exciting time. The equipment that is coming out is so advanced, and it’s fascinating. Stem Cells: Oftentimes, the viral infection clears out, but your organs are still just being attacked and damaged. If I have a stem cell in a microscope and I put it next to an eyeball cell or some other cell, can I watch it transform into that on time-lapse? Is that something that someone can observe? I suppose you could set up a time-lapse camera and see it. How long does it take for a stem cell to turn into a skin cell or some other kind of program? Something that’s often done with most stem cells is they’ll do a differentiation test where they will add a certain compound to ensure that it will turn into chondrocytes or adipocytes, which is the bone, the cartilage, and the fat. Osteoblasts chondrocytes, that’s a characterization confirmation to see if it indeed is undifferentiated. Also, take one and test it to make sure it’s good. Yes. In theory, you could set up a time-lapse camera and watch it. I’ve never tried it. I’m going to look on YouTube. There’s got to be one. I’ve played with microscopy of stem cells. They’re fun to look at. When you have a beautiful cell culture, they grow in a swirl form. It almost looks like art. If you print it and put it on your wall, they look so beautiful. That should be your art project. Thanks for doing this. Thanks for having me. It’s an honor. People are going to love it. I hope so. This is an amazing conversation to share. The best ones are when you do more of the talking than me. We got a lot out of you. Thanks. Thank you. Important Links: Dr. Melissa Selinger Neuralink NeuroTechX Communities SPRAVATO Consilience About Dr. Melissa Selinger Dr. Melissa C. Selinger, Pharm.D Scientist, #MeToo survivor, former biotech exec/founding team, tech artist ssd.jpl.nasa.gov/sbdb.cgi?sstr=21744+Meliselinger NASA minor planet 21744 Meliselinger (1999 RF168) Published neuropsychopharmacology research https://www.researchgate.net/scientific-contributions/Melissa-C-Selinger-31520206 Upcoming research KVR Idea conception for and first author for KVR: A novel pilot virtual reality adjunct therapy for intravenous ketamine infusion for pain and depression in 18 patients, collab with Hamilton Morris Journal publication TBA Early KVR media coverage https://www.practicalpainmanagement.com/patient/virtual-reality-for-pain-depression https://www.freethink.com/articles/virtual-reality-ketamine-therapy Recorded on March 7, 2021The post Exosomes, Stem Cells, Ketamine & VR — Dr. Melissa Selinger appeared first on .
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Jul 6, 2021 • 1h 2min

Sex on Demand for Women — Saundra Pelletier

There’s this kind of pattern you can see sometimes, when you dig behind very successful projects, a lot of times there is some woman who is dead set on making it happen. And for a lot of them, she’s working behind the scenes and you don’t find out until you get real close, what’s really going on. But occasionally you meet these women who are badass leaders that are so dogged that they’re going to make something happen by force of will. And I’m always honored to get to meet them. Today we get to spend some time with Saundra Pelletier, the CEO of Evofem Biosciences. This is a super fascinating company that is dedicated to creating medical and healthcare products for women. You don’t find a lot of companies focused on that, which is sad because women are the ones who drive a lot of the healthcare decisions for their entire families. So I don’t understand why the market hasn’t picked up on that one. I think you’re going to love Saundra. She’s created a product at her company called Phexxi. It is the first and only FDA approved, non-hormonal contraceptive gel for women. They can use it anytime on demand whenever they want. This is the kind of product that is really important to change the balance of power and determining who ends up procreating and when. We want that control to be in the hands of everyone, but in the past, a lot of the responsibility has landed on women and, they’ve been given, in some sense, relatively crude tools to do it. Most women in America at least are using a hormonal contraceptive, which has a lot of additional health side effects. As Saundra will tell you, she developed late stage breast cancer. She survived through a double mastectomy but the doctors told her the only real reason that she probably had cancer, in the first this place was being on a hormonal birth control for 20 years. Lots of stories like that, that you probably know and have heard with your own friends and family. So I think this is a very important project. This type of advancement in a technology that changes what humans can do,  when they can do it, who has the decision-making power is important. We have a lot of options here where I’m at, but when you look globally at what’s happening with contraception in other countries especially in the developing world, there’s a lot of social stigmas that affect what women can get away with when they’re trying to find contraceptive choices. Giving them some options is paramount, not just because I would like to see population managed in a more thoughtful fashion. And hopefully create a few less humans that we don’t have a plan for, but also to give them the ability to choose when the time is right, who the right partner is, what they want to do,  and not have to subject themselves to the entire weight of society’s idea about what they should do with their lives. That’s important, I believe for humanity as a whole. And so I’m really excited about Phexxi getting some support.  Evofem Biosciences is publicly listed. So I certainly  don’t want to give anybody investment advice, but these are some folks who could really use some help. And if they can get enough support for this company, they’ll be able to take Phexxi around the world and that’s gonna make a big difference for a lot of people. I hope that you guys love this very soulful conversation I got to have with Saundra, and I’m thrilled to be sharing her with you. Pablos: What I’m really excited about here is that I think the things that matter in the world for humans to do is how we’re gonna evolve as a species. How we are going to keep going? How are we going to make it possible for more lives to exist? And but also for those lives to thrive in some sense, right? And when you look at what has worked so far in all of human history, it’s humans inventing a new technology, bringing it into the world, solving a problem at a bigger scale, and being able to advance the species. That’s really how we got where we are and we’re not done…we might be done. But we might also be able to effect our fate go forward. And so it is  super exciting to me because, one of the biggest problems in the world in some sense is that we went from millions of people on this planet just a couple hundred years ago to billions of people in the last 200 years. 7 billion in 200 years. And we’re making a lot of extra people. It’s not totally clear that we need them all, but I’m not going to tell you which people are extra. I just think that it might be smart for the species as a whole to figure out if we want to course correct on that a little bit and maybe in the future make a few less. And maybe less but better people would be a goal. But anyway so I know Evofem is…I don’t know if you are fixated on contraception. Is that the only thing guys trying to do or want to do, or is that just the main thing where you started? Saundra: That’s the main thing where we started. I will say this to your comment. I just want to tell you this, that not only do I find your opening statement provocative but I actually believe that one of the biggest levers to poverty elimination, as we evolve is for women being able to choose when and if, and how often they have children. Access to contraception that they’ll use is a huge poverty eliminator. So yes, contraception is our beginning. But we also are in late stage phase three development for the prevention of chlamydia and the prevention of gonorrhea with the same product. Which by the way, the CDC has said they are on the rise for the sixth year in a row. And gonorrhea, it’s an epidemic because it’s antibiotic resistant. So we’re really leaning into innovation. And that’s why it’s so cool. We’ll pick this all apart, but just to get the audience up to speed, why don’t you describe the product you have Okay. So the company Evofem Biosciences, the whole platform is innovation for women. And that might sound like great words, but we are  delivering. So there has not been innovation in the contraceptive category in two decades. So our product is called Phexxi, not just because it rhymes with sexy which is a nice attribute. So here’s it works: it is a gel that comes in a pre-filled applicator. And I know your audience is hearing us, but I’m going to show you. A prescription is a box of 12 pre-filled applicators, and you put it in right before sex or up to an hour before sex. Now women have used tampons. It’s scary to guys. It might be scary to guys, although I will tell you… But the guys will get to use it. Not only that but guys really love the fact that this is very lubricating. So if any woman has vaginal dryness or pain with intercourse. But here’s how you see. So 5 mLs in each applicator. Is that the whole dose? That’s the whole dose. Okay. So what I’m seeing is like a size of three or four jelly beans worth of gel. Yep. And you can feel it. And it just feels like Vaseline or something. Yeah. And the gel is just so you know, it’s lactic acid, it’s citric acid and potassium bitartrate. And here’s how it works. So a normal vaginal pH is 3.5 to 4.5. When semen enters the pH goes to seven or eight, and a woman gets pregnant. When chlamydia enters and when gonorrhea enters, the pH goes up to seven or eight and a woman gets a sexually transmitted infection. So what Phexxi does is it is acid buffering. So it helps the vagina just maintain normal vaginal pH inhospitable to semen and inhospitable to STIs. It keeps it low. Correct, so there you have Phexxi. So just like men who have had condoms forever. So for example, you could go out with a condom in your pocket and can have safe sex, but women have had to use a hormone every day, every week, every month, year after year. And the side effects… Doesn’t it seem like a  lottery winner for the few women who take the pill and don’t have a problem? Yeah. Without question. Want to hear something crazier? I say the worst trick played on women is that most hormones lower your libido. So they’re taking a drug every day that makes them not want to have sex. And they’re having side effects of headache and weight gain  and bleeding. And the one crazy part is that I talked to a lot of young women and they say to me, they were put on an antidepressant or  put on an anti-anxiety product. And then when someone really looked at their levels, they realized it was their hormonal birth control. And once they got off of this hormonal birth control, they felt normal again. Yeah,  I’ve experienced that multiple times as a close observer. And by the way, women don’t have sex every day, which you may, or may not have experienced. But like seriously for example, would you take something everyday if you were having side effects that you didn’t even need to save your life. Well, men don’t have to do that, but I get your point. Okay cool. If I’m using this, can I also use lube? Yes. You can use lube. You don’t have to use a condom. Like any contraceptive it says it can’t protect you against HIV. But the  wonderful thing about this product, are you ready for this? So in the United States, half of all pregnancies are unplanned. So I want you to imagine that the pill was introduced, even now. There’s 18 categories of contraception. They pill came out in 1960 and still all pregnancies are unplanned because 23 million women identify as saying, we are not going to use a hormone. We’ve tried pills, patches, IUDs . We are beyond hormones and they say stuff like, look, I don’t have hormones in my milk. I don’t have it in my meat. And I joke and say if chickens can be hormone free…come on! Why do women have to put up with hormones? So these women are saying like, I do yoga and Pilates and eat healthy and I care about my longevity. Why am I going to take a synthetic hormone? It doesn’t  make sense. But 23 million women is our target audience and those women are without question very engaged. They are ready to go. Yeah. A of times these technologies, we take them for granted because  it’s what we’re used to now, but that’s just the best technology we had at the time. Fucking with your hormone cycle was the best technology we had at the time. Now we can do better. This is an example of being able to do better. And it seems remarkably straightforward. I’m looking the box it has the ingredients listed. And by the way, I joke that like I could make this in my garage. I don’t, but it was originally developed by Rush University in Chicago. And when they developed it as a vehicle looking to do HIV prevention studies. So at the time in the early 2000s, there were a whole bunch of academic institutions who said, we need to find something for HIV prevention. But those studies are very challenging, like in South Africa with vulnerable populations. And so the majority of those failed. So what Rush University knew this product is considered to be something called an MPT, multipurpose prevention technology, which means has the capability  to continue to look at areas. So contraception, sexually transmitted infection, bacterial vaginosis. So they knew getting to market as a contraceptive would be the quickest way to get it approved by the FDA. Okay. So we’re going to play all the legal disclaimers for this, but we’ve got this thing approved already as a contraceptive and it’s on the market. If you want to buy it, you can get it at a pharmacy or where? Yes, you can go to https://phexxi.com/. We have a concierge, or you can go to your doctor, and they can give you a prescription, but if you go to our website, you can it mailed to you within 24 hours. Okay, cool. And then the way it works is you install it using a tampon. Yeah. And throw away the applicator. Load it up and  throw it away. Yep. You’re good to go to have sex and get started within an hour. Correct. Yes, as long as you put it in right before or within an hour. What if you’re an all night operational? Well, you got to use it again. Good for you by the way! Okay. And then you’re currently working going back and doing trials for some other benefits that it already provides, but aren’t already approved and aren’t already proven and phase three trials, whatever. So that’s the work now? That’s correct. And then what hope to show with those is? The prevention of chlamydia and the prevention of gonorrhea. And just to give you an indicator of how pervasive those are: in the U S there’s 1.8 million cases of chlamydia annually, and 600,000 of gonorrhea. And for the sixth year in a row, the CDC has said both of those are on the rise, is antibiotic resistant and literally there are no products approved for the prevention of either of these. And look, I want to tell you why some people say to me, why the hell, hasn’t a bigger company with a lot more money done this? And I say, look, number one, it’s easier for them to just come out with a lower dose of hormones. So they’ve got something and they come out with new ways of giving you hormones. And by the way all it is that women aren’t stupid. Come on. They understand that it’s still a hormone. Just because it’s in a patch, doesn’t mean it’s not a hormone. Just because it’s in an IUD, doesn’t mean it’s not a hormone. So they come up with lower doses because it’s cheaper and quicker. But we have really taken the heart painful work of developing this new innovation. But the good thing is that the year, the FDA has given us a fast track review for chlamydia and gonorrhea. So we’ll have a six month review instead of a month review. So we’re excited about that. I have to be honest right now we are getting so much positive response from women on this product and that is phenomenal. So let me ask a couple questions. If you get through all those trials, then the same product will be approved and could even be prescribed in some sense. Yes. If maybe if you don’t care about like I got fixed, but I am excited because I still get to use this product Yes. And women who cannot get pregnant, they can still use it to prevent chlamydia gonorrhea. Yeah. Or will be able to. And I think one of the things you mentioned that I think is important to point out is a barometer for whether something is worth developing, whether it’s a good idea or whether it’s gonna work or whether it’s any of those things is not whether or not existing medical technology companies who got around to working on it. That is not a good metric because, I think one of the things you alluded to earlier is the market, that they go after 23 million women in their minds probably isn’t enough. And maybe partly because it’s only 23 million and partly because it’s women. And so we’ve got to find a way to change those dynamics and show that this is a viable market. We’ve gotta be able to show that we can make products that are profitable in that market. And that seems like the more pioneering thing that you’re doing as a company. I have to tell you, I love you for saying that. Because you gotta think about it this way, right? When you really evaluate, women are really the healthcare consumers for themselves, or their husbands, for their children, for their parents. When they get older. If you can get the right positive lever in a woman’s mind as a company, right? A woman trusts you and thinks you really care about innovation: 1) They are the consumers and 2) to your point, they’re half of the population, but 3) so little innovation is introduced to women. I have gotten a lot of investors will say to me, if it’s not immuno-oncology, diabetes is man and women, heart disease is man and women. This is just and women and we don’t know if we’re interested. And I say, listen, I want to remind you’re here because of a woman. And at the end of the day, when a woman’s quality of life is better because she feels better. She doesn’t feel a little crazy because she has a synthetic hormone in her body and when she doesn’t feel that she’s suffering every day. You know that whole adage, when mama’s happy, everybody’s happy? This product is so important because women now are more empowered than ever. And they’re saying to themselves: I need to care about my longevity. This isn’t just about having sex with my partner. I need to be around for my kids. Women really getting savvy on what are the silence sins that happen when I take something that I don’t even need everyday. Some girls start the pill when they’re 17 and they stop taking it when they’re 35. Oh yeah. It’s it seems insane to me. So we haven’t really done better than—we’ve done slightly better than the pill—but basically haven’t done better than hormones. If you took hormone based contraceptives for women out of it, what’s the second most popular contraception like in America? After hormones, I would say that condoms. Withdrawal is actually considered a method. I think it really is considered a method Don’t try that at home, kids! Yeah. But I would tell you this, there is one other non-hormonal product, but it’s a copper IUD. It has to be put in by a provider and taken out by provider. And it has pretty intense side effects of abdominal pain and bleeding. I’m always shocked by that one too, because basically the idea with the copper IUD is that you’re living with a wire inside of you that’s supposed to scrape the wall of the uterine lining. And it’s just seems so primitive. And you have to think about that, right? You know what I said the other day, I was talking to a friend of mine and she is into yoga, into meditation, and  she rides her Peloton every day. And then I said to her, and then you go and you pop your synthetic hormone. I said why don’t you swig whiskey and and smoke a pack of cigarettes tonight?  I’m like what the hell are you doing? You need to look at your total healthcare! Whiskey and cigarettes! You want to know what else is awesome? This doesn’t have systemic side effects. It doesn’t matter what your weight is. It doesn’t matter what are concomitant medications you are on. So I talked to ER doctors and they said when somebody comes in and something happens, if there’s an event they have to give a woman contraception, they know if they give her this they don’t have to worry because there’s no hormone. Okay. This seems like dream product to sell. How hard could it be to talk people into buying and using this product? I feel like I could have girl scouts sell them in front of Safeway. I’ll tell you this. You know wha? It’s a double-edged sword. So when we did our direct to consumer campaign called Get Phexxi on Valentine’s day when we launched the commercial, everything changed. Our units doubled. So the FDA requires to educate doctors first, before you can go out and talk to women. So women get this so intuitively, it’s amazing. I obviously love women, but I love women everything from the brain, backbone, and soul. It has been a challenge in two ways. When talking to some male doctors, some of them will say things like, these women don’t want to have something on demand or something they control, rather they should have an IUD. And I say, look half of all women won’t use something that they can’t control. And if you take a moment to think about and counsel your patients and let them know that this is available you would be surprised. For example, even the simplest thing like  breastfeeding women, they don’t want hormones in their breast milk. And women are spacing their pregnancies. They don’t want to put up a hormone in their body, that they then have to  cleanse out of their body before they can get pregnant again. And I said there’s, by the way, there’s lots of young women between the ages of 18 to 25 that say, are you kidding? I don’t want my mother’s contraception. I don’t want something draconian. Why wouldn’t we just put this in our pocket and put this in our purse? But so the challenge has been to convince some providers who have old mindsets Because they have to prescribe it? Correct. How much of the market do you expect to be provider’s suggesting it versus women going and asking for it? I think it’s going to be 75% women asking for it and 25% of people prescribing it. No question. So women are driving the demand. But even considering these old fogy doctors, it seems like you’ve got a compelling enough product and story should be able them in the dust and say okay thanks, anyway and move on to the next one. How hard could it be to find gynecologists or doctors who want to get behind it? And now we just started to expand to say how about all the women? There’s 23 million women that won’t use hormones, but there’s also a lot of women that can’t cause they’re contra-indicated. So there’s a huge amount of women that they’ve had a cancer, many of them can never use a hormone again. So we’re starting to now talk to oncologists. I just did a keynote oncology conference for a group called Ncoda. And was remarkable to see that one of the really cool oncologist said to me, I got to tell you something. When I see male patients who have prostate cancer privately, the first thing they say to me is can I get an erection again? She said, I want you to imagine that if a woman came in and said can I have an orgasm again. So do you know what we would think? We’d say, what is wrong with her? You just saved her life. Why is she worried about it? But women are so worried about the disruption of their partnership. They want to go back to the life they had before. They want their intimacy. They don’t want to be left because they’re a cancer patient. They don’t want to deal with that stigma forever. You want to get better and beyond, move on, and have your life again. And so that’s what I found fascinating is that because this is lubricating, that after you have cancer often times you are on anti-estrogen products, which produced vaginal dryness pain with intercourse. And this lubricating product with no hormones, it’s perfection for these women. Yeah. Okay. Good. All right, so can we go talk about where this can go? How long you’ve been on the market? Just since May of last year. Less than a year in and the job is to go sign up doctors. So do I need to tell my doctor about it or how does that work? Yes. So a few things. We are educating doctors and we’re educating women. So we’re doing direct to consumer advertising with social media influencers. We have an incredible 20 social media influencers that cover all demographics. So they’re influencing—incredible and extraordinary. So social media influencers. We have ads on Hulu and Bravo and all the channels of our target audiences. We’re also doing the same journals and CME programs and sending it out to doctors. Women are either going on phexxi.com. We have a concierge program, which means that you click in and a provider interacts with you. They ask you all the right clinical questions and as long as you answer all the right questions, boom, you get it sent to your house. They can can do a prescription. Or they go into the doctor’s office and say that I want this non-hormonal option backseat and boom. And by  the way, they can go in and say you know what  I’m having sex more than 12 times a month. So their monthly prescription could be 24. It could be two bucks, depending. Yeah. Oh, okay. Otherwise get on a drip and it comes in the mail every month. Exactly. Is there a shelf life to this stuff? Three years. Okay. Can I use it with toys? Yes, definitely. Definitely. Definitely. And I would you our chief commercial officer—once we have world domination—he has big plans. He’s like we should do flavor. Is there anything sitting between you and world domination, other than time? It sounds like this is a slam dunk, but what’s the hard part now? Money. You need more money to do more advertising? You can’t grow fast? Yes, because what happens is direct to consumer advertising is super expensive. Oh my goodness. It’s super expensive. And so here’s our issue: I am convinced we have the right product. I am convinced that we have the right team and I’m convinced we have the right strategy. However—not that I’m on an island—but when you have an innovation that has no benchmark that has never been done before. When you’re doing uncharted territory. Sometimes people are like I’ll wait and see and once you’re successful, I’ll give you the money you need. Then how are we going to get successful f you don’t give us any money we need? The classic chicken and egg. Now we have had some amazing investors who know the category very well. They not only are believers, but they recognize that there’s a huge need for innovation within women’s health. It is almost like it’s like a joke. It is like me telling you I’m going to grow a third eye right now in the next five minutes. People don’t innovate in women’s health because to your point, it doesn’t impact both the male and the female population. So we have some great investors, but raising money is hard. It’s very hard. Admittedly, I don’t want to be a cry baby because I signed up for this and look, I was raised raised in the northernmost city in the US, in a place called Caribou, Maine. It is the Northern most city you can fly to from here. I grew up in Anchorage, Alaska. So I don’t think you quite convinced me of that, but I’ll take the word for it. There were probably should have been a military general. She was like, you can be sad for one day. You got 24 hours to feel sorry for yourself and that’s it. You know what I mean? Yeah. So she would be like suck it up buttercup, you know what I mean? Like she’s hardcore women, but my point in telling you that is that what has been a little bit hard is that there is a group of not long-term healthcare who understand pharmaceutical launches in the category and how it’s done. And look, it takes time to build demand. You gotta educate doctors. Then you gotta educate women. Then you’ve got to drive them in. Then they’ve got to get prescriptions. Then they got to get refills. And it’s not like we’re not going to get there. We’re already on our way, but it just takes a little bit of time. And there’s some impatience that exists with some of the retail investors. Who invested in iPhone apps. Yes! That were dreamt up last week and were supposed to be worth a billion dollars this week. When they get angry, they go on social media and the stuff that they say, it’s staggering to me. A t first, I was reprimanded by our counsel and our advisors said I should not engage. Because I said, who raised you? Like  why would you say this to another human being, for God’s sake? Like these things are violent and vile. And that, I will admit and it might make me sound naive but that that gobsmacked me and shocked me. And then I had to grow a pair. And I have strong backbone, but I needed to strengthen it a little more to just be like, you know what? I just gotta my head down because you know what the best revenge is? Results and success. So I’ve had to really shake that off. But it’s not always easy for me to shake it off. Look I get it. It’s hard. This is a world where there’s just an epidemic of bad behavior on the internet and there’s no way to hide from it. And I think if you look, there are very few successful examples of engaging. I couldn’t agree more. You got to take the high road. It’s really sad that you have to have that experience and that you have to even have the same problem. I have the same problem if I read the comments, I’m like oh my God. But I think the right answer is you gotta stay focused on what you’re doing and what you’re good at and just ignore them. They’re not your audience. Ans hopefully your audiences and listening to them, anyway, A great person from our audience and one of our biggest investors sent me this quote that said: don’t let success go to your head, but don’t let criticism go to your heart. Don’t let it go to your heart. Just shake it off. You’re doing the right thing. Keep your head down and keep showing progress. Especially with investors, you have a real problem where because of the way that access to the public, because you have as a publicly traded company access to public markets. And we saw this with RobinHood and GameStop and all these kinds of things. You have a lot people in the market now who are trading. A lot of them are doing derivatives trading options. They don’t any comprehension whatsoever of you, your company, your product, anything at all. They’re just looking at technical data on the stock performance and trading on that. There’s a kind of abstract argument to be made that this is valuable for making sure that market stays efficient. But it’s not really something that is going to help your  company at all. And the flack from those people, it needs to be ignored and not just by you, but by everyone. And I agree, and I think your point is right. It’s so important because when you look at the long-term opportunity to really deliver  shareholder return. I’ll  give you one example that, when you talked about being able to build a market, the interesting thing about this category is that if we were to just get two and a half percent, two and a half percent, that’s a billion dollar market opportunity. So for shareholders, it’s extraordinary, but they have to be patient. If you’re patient and wait. Like right now, we’re so undervalued that it’s a joke. But the point is that if you look at what our growth is now, and you look at that being compounded month after month, quarter after quarter, it’s amazing the impact that we can make for shareholders. But the tough thing is that you want people to listen to all that negative rhetoric because they get nervous. I don’t know if this’ll help, but there’s no exceptions, right? It’s not just you. It’s everybody. Yeah. Every single company gets flack. Tesla gets more flack than  positive support from the same people. And there’s a noise there. It’s not signal. You gotta learn to ignore that. I like that. I appreciate that sentiment. If customers are saying this sucks for some reason or you heard investors were saying this sucks some for reason, that is signal, but it’s not signal, it is noise. And especially that those particular type of investors—they’re not really investors—they’re opportunistic folks who are trying to milk the market. Yes. You’re right. It’s like a pump and dump kind of strategy. Women, I will tell you and our long-term health care investors know, not only do they know and recognize the opportunity for non-hormonal contraception, they also recognize the forthcoming to your point. We’re in this phase three study, we have top line data readout in the second quarter of next year. And we’re very excited about that. You know what I loved and I want to go back to is your comment that sometimes people make an investment. I’ve found that sometimes I meet , incredibly smart people, scientifically minded people, who have this great idea, but what they haven’t done is the market research. Just because it’s a good idea doesn’t mean payers are going to cover it. It doesn’t mean you’re going to get investment for it. I meet some people and they have a great concept and they’ve gotten through phase one but they have no money. They don’t have way to differentiate themselves in the market. They don’t have any marketing opportunity to show investors. And here they are having spent all their money they had to get to this one point and they can’t get any further. And it’s heartbreaking. And one of the things we say is look just because there’s an unmet need, it doesn’t mean that the market’s going to bear it. It doesn’t mean that payers are going to cover it. And unfortunately, if you’re bringing a pharmaceutical product to market, you have to make sure that the insurers and payers are going cover it. Because if they’re not, you can’t get access. And healthcare is so complex.  So complex. Yes. In my mind, any entrepreneur willing to work in healthcare or medical technology or about tech is a Saint just because you’re willing to try and innovate in a heavily regulated, very complex, big, old institutional environment. I couldn’t do it. I cheat and I go where there’s no regulation make a big mess and then set it on fire and bail out. You are smart. Smarter than I. I have to tell you the truth, it is sometimes like a torture chamber. I’ll give you an example. And this isn’t Don’t Cry for Me Argentina. There’s a reason to do it, which is that we’re trying to take your scar tissue and help the next generation of entrepreneurs and people who are trying to make a difference. Look, there’s very few people who can learn from their own mistakes. And then it’s like a subset of them who can learn from other people’s mistakes, but they’re the ones who are going get furthest and that’s who we’re trying to help out here. So, let’s get to the story. It’s not to cry for you.  No. But what I meant was is when sometimes when I talk about our story, sometimes depending on the audience and in the right moment, one the reasons I’m so passionate is I spent my whole career on women’s health, literally. And my whole career when I say that, looking at the mindset, doing quantitative and qualitative market research, puberty through menopause. So when women do want to get pregnant, when they don’t want to get pregnant, when they want to space their pregnancies. And so really what are the levers? What do women really care about? But then a few years ago, I shockingly was diagnosed with late stage cancer. And when I was diagnosed, I had no family history. I had no genetic predisposition and I had a clean mammogram the year before. So for me, what was so shocking was that howI have all those positive factors and end up having aggressive late stage breast cancer and have to have a double mastectomy three weeks after my diagnosis start chemo. I had to my uterus removed and my ovaries removed. Wait, they’re not in your breasts. How does that work? Because they wanted me to get rid of everything that was going to increase estrogen. Everything because my cancer was estrogen positive breast cancer. So they said we need to kill a fly with a sledgehammer because your form of cancer is so aggressive. And then they said the only thing that we can really point to frankly, is that you have used hormonal birth control for 20 years. Wow. But here is where we talk about the regulation of this, right? I was on a podcast months and months ago. It was a very provocative broadcast. and they were talking about sexuality and intimacy and couples and it was a man and wife and I joked that chose to not have reconstruction so I look like Edward Scissorhands. So then I talked my own journey, just mine, but one of our competitors turned in the interview and said that I was suggesting that any woman who took any hormone was going to get cancer. And I was trying to scare women, it was outside of regulations, and I was doing off-label promotion and we got in trouble. And all I said was, this is my reality. This is my truth. It happened. It’s real. I didn’t have any of those factors and I ended up with cancer. Okay, that scares the hell out of you. And I said, look, if I had a daughter, which I don’t I have a son, but if I did, I would never let her use her mobile contraception. Not because we have a long family history because we didn’t, and I still ended up with cancer. That’s no joke. And so why this regulation is that any little thing you say in any little nuance and why they make us of those little disclaimers at the beginning is because the FDA wants to just make sure that it’s regulated but the one thing that I think is a bit of a bummer is my story. Yeah, of course. Right? It is. That’s not FDA jurisdiction. Right. Exactly. I get it. You’re not the one who said that it was possibly hormonal birth control it caused the cancer. Correct. You had a medical professional who’s suggesting that possibility or at least the highest probability thing they know of. And yeah we don’t know for sure or when you were going to know for sure, but regardless it can’t be hard for any woman come up with a reason to not want to externally modify their hormonal balance all the time. There might be times you want to do it on purpose for a reason. But anyway, so look, you’re on the right track with the product. That’s awesome. How did you end up at Evofem? What were you doing? Oh, wow. I be too verbose. At least I say sometimes what you choose chooses you. So I honestly mean this. I don’t know what Anchorage what was like, but where I grew up women really didn’t think they had a lot of choices and they really thought their choices was who they married or how many kids they had. My mother and all her friends, all felt like they were martyrs, that they have an opportunity to really be empowered. It wasn’t a thing yet. So I had all this in my subconscious. So when I left, my mother said to me, when you leave here you should not come back. And if you want me to visit you, you should send me a plane ticket. And we’d never been on a plane. We didn’t have enough money to go on a plane. I’m sitting at her like what? Honestly when I was growing up, she taught me no domestic skills. She said, you don’t need that. Cooking and cleaning is never going to get you out of here. Who cares about that? And I left and I thought wow. So my point is that my job out of college was in pharmaceuticals for a women’s healthcare company. And I started out as rep calling on  doctors. So the one great thing about being the CEO is not only do I know the drill. The reps that for us are pretty extraordinary humans. And they like me and I like them. And one of the reasons they like me is that I know what the hell I’m talking about. I’m not somebody who is just a scientist who’s never been in the field. I lived and died by going out and talking about a product and how it worked. And I sold a variety of different products. Anyway, I did every job. I was a rep. I was a manager. I took over a region that was last in the country and turned it around. I was in marketing in the US and marketing internationally. And so long story short, I spent most of my time running a global franchise. And that’s when I got my bug for what are we going to do for this vulnerable? Women that are outside of the United States. It forever changes you. So, I ran this franchise where we launched brands outside of the US where we went in to say what are the right products to launch in these markets because of socioeconomics and religious belief systems. And what changed me when I went, there was my ignorance. I had all of crazy ideas about what people wanted and thought there. And it was so insane. I literally was so foolish. I thought like they had pharmacies they could go to to get pads and tampons. I’m only smart and Silicon valley everywhere else in the world. I’m completely idiotic. That’s what’s amazing about traveling and learning. So I was so humbled and ashamed. I was humbled and ashamed and I thought, God I’m like silver spoon fed. I was still like oh my God I’m just so privileged. And it was extraordinary. What part of the world had you gone to? So most these experiences were in Kenya. And South Africa, okay. And I went to urban rural villages. I talked to the ministry of heath. I talked to distributors. But I also spent a lot of time in one of the largest slums called Kibera. There’s 600,000 people in the size of central park. And it was extraordinary to see that women are so desperate to not have children that they can’t feed and clothes and educate. They will do anything. They will walk two days to get access to contraception. And sometimes they’re not even real. It sugar pills, because there’s so much corruption that’s happening. But the one thing that I thought was amazing is that even these women, would literally, want the same thing as women in Beverly Hills, or Kentucky or New York City. They want a better life for their kids. And they don’t want five or six kids they can’t take care of. So the global footprint matters to me because once we are able to obtain the prevention of chlamydia and gonorrhea, this product I think is going to be very significant for us. Because maybe like aid money could be used? Yes. When these women have side effects from hormonal contraception, some of them think that they shouldn’t be using it anyway and these side effects are a way of punishment, right? If they don’t have information or education on how their body works. American women don’t know! I’m not kidding. A lot of American don’t know. Sex education  isn’t even really taught anymore in the school system. We don’t know our bodies and how they work. There’s so many myths and misconceptions. As an aside and not to go down a rabbit hole, but our Chief Medical Officer, who’s an OBGYN, Kelly Caldwell. She is doing this series called #UnpHiltered. So pH filtered for Phexxi. And it’s really educating women about their bodies and how they work. And it’s super cool and funny. And she’s very approachable. Good. What is it on? online? So right now it’s on Instagram, but we’re going to be putting it on Youtube next month. UnpHiltered with a pH. On Instagram. Get on it people! But anyway, the global foot print matters. And I have to tell you that innovation, when we talk about innovation, why I cared so much about talking to you today, is that innovation in women’s healthcare is not only necessary, but it will positively impact. Think about how they care about global warming? Think about how they care about clean water. How they care about education. More bodies the planet by choice, not chance. Choice, not chance. Less bodies on the planet that are unwanted, unplanned, and unwanted pregnancies come on! I have to be candid, I am a huge proponent of contraception that women will use, right? Why not? This isn’t about population control. This is about choice, not chance. Sometimes, I’m unpopular at dinner party. And I’m never really invited. Not that I ever been to any dinner parties. But I say things like look at some of these countries where rape is a weapon of war. It’s not a matter of if it’s when and how often. Okay. That’s no joke. It’s worse than that. This is what gets me kicked out at dinner parties. If you just look back in history like most of the sex for women was nonconsensual 100%. It’s a fairly modern notion that women should have any say at all. And we definitely have some work to do to get the rest of the way where women have as much say as they really should have. There’s a lot of, a lot to overcome. And in the west, we’ve had a chance to make some progress on that. That’s not necessarily true everywhere in the world. And so there’s a lot of work. I love that you said that because I will tell you this too. One of the underpinnings of this launch, and this brand, and this company is empowerment. And not just by the way for women. The one thing that I really honestly care a lot about. So I’m a single parent of a 13 year old boy. I say, hopefully I’m raising a feminist and a gentleman. I also joke that he’s either going to run the mob or be president. Hopefully the former. So much more legit and fine upstanding citizens. Why I say that is that even with the predisposed ideas to little boys like man up and be a man and grow up. All these ideas that take out their kindness, and their emotional capacity. There’s so many good men out there that want to support women, that loved their mothers and loved their daughters and loved their spouses. And I think that sometimes what people mistake about me as a woman and a human and about us, is that oh feminism is about man-hating and wanting to castrate men. Not only is it not about that, I think they are extraordinary dads that say, I want to know the conversation with my daughter, because I my daughter to have access to the right healthcare. And I want her to be empowered and I don’t want her to put hormones in her body. And I want her to know how her body works. But what I love is that there’s more people being willing to have that as dinner conversations. Why does it have to be so taboo? Why is it dirty? Why is it a dirty little secret? Why can’t we talk about your menses and your periods and why is that off topic? Because everybody has it. Everybody does. We do it just like after dinner? Yes. We can do it after dinner. Look, I think it’s great that you’re claiming this for women, but I feel a little slighted this doesn’t feel women’s biotech. It feels like something I want too. I was like why is this for women? This is all the things I want are in this product. Men should want this. Yes, men should want it because they could have this and if their partner doesn’t have one, they can say, look I’ve got a Phexxi. If you’re a guy, and you someday get a girlfriend, she’s probably going to get on the pill if she’s not already. And she’s probably gonna have a whole bunch of problems you don’t want to deal with she’s on the pill. So just short circuit that. Help her so she doesn’t have get on the pill, get yourself fixed and also get her on Phexxi. That’s like A. Plan B is get a boyfriend and condoms. It’s true! Honestly, we have investor who honest to goodness, his significant other reached out to me and she said, I have not felt like myself in a year. And she said when he said to me, you should go off of this because not only do I think you’re not yourself, but you don’t think you’re yourself. Come on. And she said that she would all of a sudden cry for no reason. And also pointed out that nobody gets on a pill and it gets, becomes a better version of themselves because of it. That’s not one of the options. So I really I’m thrilled about that. I look at this product, the ingredients list, just so you guys know. Lactic acid, which is in like milk. Citric acid, which is in like red bull and lemonade, and potassium tartrate. All of these ingredients are food grade. It’s a food grade ingredients. Why does this why can’t this be over the counter? How could it go wrong?What orifice could I shove this in to cause a real problem? Let me tell you why it’s prescription. So we in combination with the FDA, that where to chose prescription is a few reasons. 1) Under the Affordable Care Act, one product in each category of contraception is covered so women don’t have out of pocket pay. So it’s cheaper for women to get access under the affordable care act then to make it over the counter. 2) also in market research the majority of women said, even though, yes, there’s over the counter products. But said if a product is FDA approved and they’re doing something as serious as from getting pregnant. So that was why we knew that we wanted to further the chlamydia and gonorrhea. And so getting it approved first as hormonal contraceptive was a very smart and quick way to do that. So that’s why. Down the road though and in the future, yes. Okay. All right. So then the plan for getting this to the rest of the world? So the plan is this. So we actually got an investment from a group called Adjuvant Capital. So that investment was to lower the cost of goods. And that investment was to look at going into emerging markets. So we’re looking at three-five countries a year over a five-year period. So we’re literally working on that right now. We have a joint steering committee to say two things. Where are places where we access quickly? So can show success. And where are the places where it’s most needed? Which sometimes isn’t quickest. So not just quick wins, but a few quick wins so that we can get feedback to provide that feedback to some of the places to convince them you should help us get this approved. How hard is it to get approved? Especially once you get FDA clearance? Some countries will accept the application, but other countries make it much more challenging. And but we are looking at all of those factors, but the intention is to 100% ticket globally, but there’s also some countries that want license it. There’s a lot of partners in Asia that want to give us an upfront payment to license it, which would be great because it’d be non-dilutive capital coming into the company with milestones and royalties. So we’re actively talking partners literally right now. So that’s a good of investor for you. Very much. Might be a licensee? Correct. Might be a regional licensee? Yep. Asia? The Middle East?  Latin America. Because Latina women they are one  of the mindsets that some of the donors said to us about women in Africa is that they thought that women in Africa didn’t want to touch themselves vaginally. Putting an applicator and touching their vagina was considered taboo. When we went (meaning me and my chief medical officer,) to do a proof of concept. And we only went to Kenya and South Africa, but we actually found that to be contrary to the truth. These women said to us very directly  that they are being told by their male partner, to your point of not having consent, that they must use a lubricant for the pleasure of the man. And they’re already using lubricant for the pleasure of the man. And I will tell you these women, it didn’t take them very long to figure out that they could say oh this is just a lubricant. They didn’t have to put in the part that, oh maybe I won’t have your fifth child or eighth child because you think that you have a virility is measured by procreation. In your experience, is there a lot of pressure to keep having kids?  Oh my goodness. Yes. So yeah. One of the things that I think people often don’t realize is the way progression has gone. You look at what we Western societies largely like Northern society, right? It’s north of the equator, it’s Europe and United States and some extent Russia and those things. This is all the countries that got rich early basically. And we’re all past our midlife crisis now. And we’re in the  past the prime of our lives in some sense. And the future is all south of the equator. It’s South America, it’s India, it’s Africa, it’s places in Southeast Asia and other parts of Asia. With the possible exception of Australia, it’s all south of the equator and what’s happening if you look in those regions is they are late to the urbanization game, but they’re urbanizing at extraordinary rates. And what happens is when you move to a more urban environment, kids flip from being an asset, working on the farm to a liability, go to private school, right? So now these are costing you. They’re not paying for their keep. And so you start having less kids, you get better educational opportunity to get better economic opportunity, which a lot of times why he got there in the first place. And so this is why the population for humans doesn’t just continue to grow exponentially because urbanization basically curves it. And so urbanization is the most efficient way the farm humans basically. So it’s important and these are good trends in some sense, but there’s a lot of growing pains and some things that we have to get through. And I think that especially you see, like in South America even with your urbanization, they’ve been a little bit slow to recognize the economic change means you can have fewer kids now and it’s okay, but cause they still have that in their minds. And I think it’s hurting a lot of women like you said. It’s hurting a lot of women. It really is. And I will tell you that women, if they’re given access to the right choices, they will make them. They will. And that whole point and that women really are the center of these family units. Making, doing everything. And bringing in income as well, oftentimes.And so that’s, what’s so critical is that, so we’re really trying to really be the company. So our blind to science with a soul, and that’s not bullshit science where the soul, meaning that we really care It’s such a meaningful way that women recognize that we’re the kind of company that knows not only are they worth it, they deserve to be empowered with it on demand. So back your choice, I want to say this is that when you, just said, I loved about your statement is that we’re really just now coming into the age of real consent. So the idea that women should have pleasurable stuff. right? Oh my goodness. What a concept? My gosh. I’ve been advocating for that person. I bet you have. There’s only so much I can do. I’m telling you this. I have been so passionate about that I said, because you know, the whole adage, right? A guy who has sex with a lot of partners. Oh, he’s a Romeo at gigolo and a woman’s a slot, and not about that. about women being able to have control and empowerment have effects in their pocket or the breast. They know they can go out, they can have on demand, they can protect themselves. And they’ve got this, got this women are more empowered and more in tune with their bodies now than they’ve ever been. In my opinion. And particularly young women. Oh my I’ve had so many groups of young college girls and they have said to me, I’m not kidding. They’re like we are going to do a case study and a project on this brand. We are going to start talking about what that has made me. You don’t even know like an orgasm, frankly. These young women in there, and they’re smart, they’re capable and they’re driven. And they’re like, look, we are in control and empowered over our bodies. And we’re not in patriarchal mindset that we just do what we’re told no, that we don’t want to do this and put a synthetic hormone in our body. they. the idea of sex on demand. fact that it’s lubricating. So I said to a group of them, I said, it’s also discreet. You can go into the bathroom and you can put it in very and throw away the you know what they said? They said, are you kidding? We use this as part of intimacy, we have our partner play for us. And I was like, wow, good for you. And they joked and they said with the lights on and I’m like, even better. You need like doctors to go on like tours of sororities and Yes, this whole archaic mindset. Like come on! These girls can depend on themselves. Like they are in charge. That’s what I love. It’s awesome. And even, I think, probably it’s important to say that it’s not that necessarily that they should make that same choice, but that they should be able to make that same choice. Without question. And I think especially when you look in other cultures where it’s going to be a little bit more of a cultural change for them. Yes. The story might have to be framed in a way that accommodates their belief system, which isn’t necessarily where we’re at. No, I’ll tell you a provocative thing. And this is way down a rabbit hole.  But so we are very passionate about getting our own category at the Office on Women’s Health. And when I say that, why that matters is that with our own category, we’re the only product like this. So once they give us our own category, payers have to cover this so women will have access. However, one of the things that I talked about strategically is we’re even the kind of product that we could get perhaps religious organizations and even people who are on the other side of the aisle  because this does not impact a woman’s natural body. There’s no systemic effects. This is the way of a woman’s body, God given. So for some people they think that might be a bridge too far. They’re having to revisit these notions anyway. It’s very difficult for religions to keep up the no contraception stance. The stance that’s against contraception has been pretty difficult to maintain even in very conservative societies and I could see that Being a benefit,  if needed. The one wonderful thing is that having something like this that doesn’t have synthetic hormones. There’s an opportunity to do a paradigm shift. and change the conversation with people who otherwise were complete resistors to it. And so that’s what we’re really trying to do in hopes that frankly, we start softening some of these, very narrow-minded views about giving women the choice. Just having the choice is what it’s really about. And innovation is about choices. Innovation and evolution is about coming out with new and better ways for us to evolve as humans. For us to procreate. For us to feel better. For our connected relationships to feel better. And so that’s the other thing too is that it’s sexual pleasure, connectivity, lack of side effects, all of those things, that create connection. So that’s why this innovation I think, is so important because it’s not just about the prevention  of pregnancy. Like fear-based, you don’t want to get pregnant. you don’t want to get pregnant. You don’t want to get raped. You don’t remember it. This is about pleasurable sex and feeling good about it. And people that a really tough thing for a lot of people, not just women. But people in general, to be able get comfortable with sex, with a partner, exploring, getting over their hangups, anxieties, all the things that get in the way there’s so many things. And not even counting the possible STDs or pregnancy or any of these other things. And so it’s just really exciting to see a product like this could take that venn diagram of things that make it hard to line up with your partner. And just laugh off a whole bunch of things at once that to get in the way. How far along was this company when you came here? The company had received a complete response letter by the FDA. The previous management and previous board had moved forward a study that had a lot of flaws and not a lot of agreement with the FDA. And the FDA said they weren’t going to approve the product. That was when I arrived. And I was told by the way, every  box was checked, this practice was so safe, nothing was going to happen. And it was a moment where you think to yourself oh my goodness, what have I done? What did I do? What did I do to deserve this? But I will tell you this, I  knew that this product was worth it. And I met with the investors and we then picked a different clinical research organization to do the confirmatory study. I brought in a whole new team of people. I separated from the parent company. I reconstituted this company in 2015 as standalone Evofem Biosciences. And we then we did this confirmatory study in agreement with the FDA. But yes, when I got here, the company was on fumes and just about ready to be shut down. And the thought that maybe they should just try to sell the asset for whatever they could get. And luckily, I think my women’s health care background convinced me that this was a diamond in the rough. There’s like we see a lot and especially an innovation trying to do new things. And one of them is that the early team is maybe good at figuring out that the thing was possible in the first place, but their strengths aren’t in the perspective on what it would take to make it into a real product, the business, the regulatory environment, what it would take to sell the product, those kinds of things. And so they suffer a lot because they’re the people who are most invested in it. And I think this is one of the things that we’ve really done a poor job of coming from Silicon Valley is that we have kind of a mythical entrepreneur who is also an inventor and super technical and can do everything. That’s what we think these people are. And they’re really not like I know all of them. Those people are very rare. And it doesn’t scale. And what I think is really what we have to start getting some ideas in our heads about the progression that are different. Your inventors are not your entrepreneurs necessarily. And you need to be able to transition,  something like this, a technology through those different life cycles, different stages of development. That’s why your first grade isn’t your college professor. You need different people at different stages. And so I think one of the things that actually makes me super optimistic and excited about this is seeing you here with your sales background and your knowledge of what it takes to get a product out that’s worth a  ton. I see the opposite so much, which there’s a big swinging dick scientist who left his professor role at the university, to be the CEO of company who has no clue about what it takes to actually make it a successful product and actually sell. And we said it’s all the time but the startups that fail, it’s almost never because they failed to make a product it’s because they failed to sell it. Wow. Thank you. I find that true. It’s worth so much and the so cool thing is that it’s only been the last 11 and a half months this product has been at the stage where it can take advantage of your strengths. I spent seven years doing the part you’re okay at to get to the part you’re good at. And so now you’re there. So it’s pretty exciting. And so you need some licensees, that’s one of you need.  I guess you need who are excited about this invest publicly. You’re listed as EVFM on the NASDAQ stock exchange. So you go buy the stock. I can say that you can’t probably can’t. I appreciate it. But don’t sell it, just buy it. And then, I guess it might also be cool if some other strategic investors who maybe wanted to help you bring it to other markets or maybe expanded more quickly in the US market. And then assuming all that goes few years, then you could go build the next thing. Exactly. Do you know what you want to do? Yeah, I don’t. The right answer though is shopping. Easier shopping instinct. Because you don’t need to invent a new thing. There’s thousands of things sitting with biotech entrepreneurs or founders don’t know what the hell they’re doing. And man it’s hard for them. To tell you the real truth, if I had access to strategic investors really what I would do is I would go shopping and find all of these companies and do a roll up. These smart great  products that need sales and marketing expertise, which is what this company has. And we would do a roll up of five or six or seven products like literally 10, 15, 20, and start building and be the company that once they get through the concept phase that they take it to us and we can manifest it. It would be incredible to be the hub. It would be really extraordinary. I think you should go for it. Yeah. That’s the hack. Because I can feed you an unlimited number of three person startups that have a killer tech. There’s so many, and it’s amazing. But I look at them and I said, okay guys you’re going to need an entrepreneur and a lot of stamina to get through FDA and all that stuff. No, it’s true. It is a lot to get through that, but in the end it’s worth it. You know how that is. Phase one, phase two phase three, but yes now that we’re here at this point in journey, it’s what we’ve been waiting for so it’s really exciting. Wow. Okay. I hope we can get you off, get you a turbo boost.  I appreciate your interest. I do. And I love talking about innovation and I think it’s great. And I actually like the format to just talk about it all. No, that’s the way to do it. People need to have real conversations. And I think some people never got to and some people forget what it’s like. So I’m just like, let’s have real conversations! It’s freaky, some people cannot operate outside of a script. You know what I mean? They have the canned questions and by the way, no matter what you ask them, they’ll only give you canned answer. The truth is even those people, I think they just don’t know. Like I can still, probably, maybe because my whole career has been hanging out with somewhat poorly socialized nerds. That’s normal to me. And I think they’ve been conditioned to believe they need a script and they believe that. And they’re nervous or whatever. But I think a lot of times you can get past that. At least I’m trying to do that. And I want to have real conversations with anybody and it shouldn’t matter whether what they’re into. Most people know about something. And if you talk to them about what they know about. And then, sometimes I don’t have to do it with you, but with some people I can try to translate it and make it more accessible. If it’s a super technical thing and get to the point where people can follow along and start to get their heads around it, because the natural instinct is to be terrified of things you don’t understand. And it turns out you can understand pretty much anything if you just hang in there for a bit. I love that attitude and mindset. That’s great, but it’s true. You’re right. You can understand anything. You just have to have it positioned in a way. But yeah, that’s great. Anything else you think people should know about? I think we’ve covered it, honestly. Awesome. Do you have any questions for me? A million. Yeah, we can do that. I’d love that. There are some interviews of me, but yeah. All right. We can do that next time. It’ll be our dinner party. Okay, sounds good. I like that since we’re going to be thrown out of all the other different parties. Awesome. Thanks so much. It’s really important. And I’m really excited about seeing what happens with you guys and hopefully it goes well from here. Brilliant. Yeah, my pleasure. All right. Thanks. To learn more about Phexxi, speak to your healthcare provider and see full product information at Phexxi.com.  Do not use if you have a history of repeated urinary tract problems. Side effects include vaginal burning, itching, discharge, genital discomfort, yeast infection, urinary tract infection or bacterial vaginosis. Phexxi does not protect against STIs. Important Links: Evofem Biosciences Phexxi Office on Women’s Health #UnpHiltered The Pill Helped Start the Sexual Revolution Rush University About Saundra Pelletier Saundra Pelletier is the Chief Executive Officer, President, and Executive Director of Evofem Biosciences. She leads an impressive team of passionate and highly skilled professionals committed to developing and commercializing innovative products to address unmet needs in women’s sexual and reproductive health. Recorded on May 5, 2021The post Sex on Demand for Women — Saundra Pelletier appeared first on .
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Mar 24, 2021 • 2h 21min

Diving Deep into the World of Computer Hacking & Becoming a Hacker — Riley Eller

One of the things I get asked the most about is questions about how to be a hacker and how to learn hacking skills. And I think there’s a few people I know who really epitomized what that’s all about, and we’ve had pretty deep journeys and in their lives and their careers about about computer hacking. We talk a lot about the mindset of hackers, which is one of the things I’m super interested in and attracted to. I find to be very helpful way of thinking about things. But you know, when we’re talking about the technicalities of computer hacking, what that means, it really appeals to a certain kind of person and I think a lot of people just don’t know where to start. And so I wanted to share one of the folks that I find inspiring and who I’ve known for a long time. I think his life and his career sort of epitomizes what a lot of folks are thinking about when they’re asking about computer hacking. And so his name’s Riley Eller and Riley’s sort of a famous in the hacker community because he used to run the most popular party for hackers called Caesar’s challenge. And we’d have this party once a year at DEF CON and only the league got in. Riley has done a great job over the years of figuring out how to get hackers partying, and get us all connecting to each other and making friends with each other. I think that’s a really important and valuable thing for a community of folks who maybe having focused on social skills so much previously. And so Riley’s also known for being a member of the ghetto hackers, which was the first team of hackers to win the DEF CON Capture the Flag contest three years in a row. Then they took it over and ran that contest for a few years and really up the game. This was the notorious, you know hacking contest, cause it was the first big hacking contest. It was the place where that got started. And now of course you have hacking contests all over the world, but capture the flag at Def CON is where it started. The ghetto hackers were one of the first real teams to take that on and they advanced the game and really turned it into a spectator sport at DEF CON. And it’s, it’s gone on and evolved since then. We talk about that a bit in this conversation. We go deep into a little bit deep into talking about a wifi mesh networking at a company called CoCo Communications where Riley worked another one of our upcoming guests on the podcast, Jeremy Bruestle who was the founder of that company. You can listen to that to learn a little more about CoCo, but a lot of those inventions and those technologies are just coming of age now. And so I think it’s actually pretty relevant and interesting because mesh networking is one of these things that keeps coming up again and again, and the problems are hard and interesting. So that’s a cool conversation. And then later on, we talk about Caesar’s experience as a hacker growing up, how he got into it, what he’s learned, what he values about it as well as his ideas for how you can become a hacker. I am really excited to share Riley with you guys. He’s made a big impression on me and my life, so I hope you enjoy it. Pablos: This has been one of the conversations I’ve had in my mind as being important for the podcast and what I want to do. I’ve known you for more than twenty years. We have similar progression or timelines in our lives of getting interested in computers, hacking, and ending up in the social dynamic of the hacker community in those days. There’s a lot to learn from that. What I want to do with you is talk about some of those experiences early on and how we got into it. First, let’s talk a little bit about what you’ve been working on professionally because you spent a lot of time on the last company you were at. It was a company started by Jeremy, who was one of the founders, so it was started by hackers. I remember talking to him before he started the company about the ideas for trying to create mesh networks that were ad hoc mesh networks. That was, in those days, one of the hard problems with networking to solve. I’d seen lots of trial and error and lots of difficult problems in that. Jeremy was amazing because he was able to get further than anybody, as far as I could tell, technically. I was always interested in that company, and you and a bunch of other friends end up working there, so can you tell me a little bit about what the progression of that was like? Riley: Originally, we were doing a Business 2.0 article. Jeremy was explaining on the whiteboard in the Ghetto Hacker workspace how that all worked and I was trying to repeat it back to him to see if I understood his ideas, because it was difficult to grasp with what I knew at the time. There’s a photo of him and I talking over that particular moment right before the company was taking off. It was a pivotal moment in my life. Maybe the first thing to do is describe what the point of that was at that moment because this must have been about 2005, 2006 or something. No. The company was started in 2002 and I joined in 2003. They had about a year to go around, raise funding, talk about it and get their hands around what the problem was that they were trying to solve. What happened was a whole bunch of families who are proud of the country in Seattle, people with some money to invest, saw the communication failure on 911 as a critical infrastructure defense problem that could be solved commercially. It should be available so people who are busy doing things, running toward emergencies and disasters, will know that they’re not going to get cut off from the lifeline and the lifeline for those people is always information. Having that access to information or failing to have that access to information was responsible for about 10% of the deaths that day. It’s not solving all of the world’s problems they thought, but it was something that they could focus on, it was narrow. This was about a year after the dot-com crash, so they’d all been gotten used to investing in technology. They saw this problem and they decided to try to get somebody smart and they knew Mark Tucker, who was the CEO. Mark and Jeremy had worked together on a project before, so they brought Jeremy in and he took some initial ideas out of IEEE and what was available at the time and said, “We’re going to build the stack of these existing technologies.” He went around and talked to people who were in the upper echelons of communications, telecommunications, first responder communications, and military comms. He found that there was huge resistance on cost because centralized networks are much cheaper to operate than networks where all the smarts have to be in every device. The more decentralized a network, the more expensive it is, period, because like a smartphone, the phone part of it is low power, tiny little chip. Most of what we call phone now is a lot of other stuff. Adding anything, even communication technology that is constantly running, trying to help other people on demand, all those things that the first responder would need if the central communications went down, each of them is a real challenge. Jeremy kept pushing on invention after the invention and built a four-tier stack of pieces that would be needed. At the bottom layer, you need to be able to defend against denial of service attacks because that’s an easy way to knock down a network like this. It’s to send crappy messages, so we had to have link security and link identity but we needed to provide application communication concerns like police and firefighters have common missions. You may have police and firefighters on the same scene at the same time but they have distinct missions. You can’t get the communications crossed up. A firefighter can’t misunderstand that shoot comes from a police officer or firefighter. They need to know what their lingo is and their jargon is. They need to use their words their way and not have to double-check who’s talking. We needed to have a separation of communications as well, even though we had to have a common trust model, being able to join a lot of groups of people who have different interests in missions. Journalists, possibly even those who may need to talk to each other or send pictures back and forth to their cameras and so forth. All of these problems turned out to be tractable but complicated. It’s building up to pieces one at a time and working out how we can make a network that doesn’t have a central registrar. In the end, we found that we couldn’t create trust without some centrality. We had to have some trusted arbitrators of identity, but once you had an identity service, then the rest of it could be done purely decentralized. We saw in the 802.11p or 802.11r, whichever one is the automotive spec they ended up rebuilding almost the same technology stack. They came around and they’re like, “These vehicles are going too fast. We need them to be able to talk to each other. They don’t know each other. A Ford doesn’t know to trust a Toyota.” All these same problems came back out so the model proved to be correct and effective. The way we implemented it, and our desire to make the network scale to essentially infinite size, make it scale-free. That ended up being too costly for the amount of network resources available at the time, especially if you think about high-speed devices like airplanes or cars relative to bicycles and humans. Having that slow stability is great, but having those high-speed movers can shuffle the topology of the network quickly if you do any automated algorithms or if you consider those to be all part of the same network. There are good reasons that the military divides the universe up into upper air tier, middle air tier, lower air tier, ground tier, sea tier, undersea tier and cyber tier. These are all different dimensions and each one of them has a completely distinct communication technology. That was an opportunity for improvement and we didn’t see that. A lot of our designs were homogeneous. It’s a little over-engineered. That took us a long time to recover from. In those days, if we’re talking about 2002, 2003, 2004 or 2005, basically, we’re at a point in the world where the internet has completely taken over. TCP/IP 1, people, especially at that time, thought of it as this is a decentralized protocol, in a sense compared to centralized networks that came before us. The telephone network is a hub and spoke design where you have a switchboard in the middle and anytime you want to talk to anybody else, you go through the switchboard in the middle. TCP/IP, all you’ve got to do is find anybody else on the network and you can connect through them. We think of it as decentralized but in fact, for it to work the way you described, there’s a bunch of quasi centralized services like name service, issuing IP addresses and that stuff that has to be managed too. You have to have an identity database. You have to log into all these services. We have a whole bunch of different identity services but those are all essentially centralizing services. Even the IP address assignment is a central function. I remember we were first playing with Wi-Fi probably by ‘98, or something. It was for extreme nerds and nothing had Wi-Fi in it, so you had to plug a Wi-Fi card the size of an iPhone into your laptop to get on Wi-Fi. By 2001 and 2002, it’s getting normal. The first laptops with Wi-Fi were probably the iBook, Apple’s Titanium PowerBook, or something. It was one of those that had Wi-Fi build in. We were using PalmPilot or Pocket PCs, which were a phone board and PC board jam together with a serial port and stacked with it with a screen. The HP iPAQ and the Compaq iPAQ were the things because it had Wi-Fi and that Wi-Fi in the old days had to have ad hoc mode. Lately, that’s not supported on most radios. A lot of the companies wanted to put this communication technology into an employee problem rather than a job problem.Tweet They don’t even support ad hoc mode anymore. Ad hoc mode, I thought, were some descendant of it. It is basically what’s used when you do personal hotspot on your iPhone. It’s a descendant and it has a parent and a child relationship even then. The point being is all these networks that we use have that hierarchical relationship where, in Bluetooth, you pair to your other devices. There were occasional cases like airdrop as an example of an ad hoc thing where you could find devices on a network that you didn’t even know about before and talk to them for a little bit. I remember those days. As computer nerds, we were all fantasizing about how to build the next generation of the wireless network to be an ad hoc wireless, we call it a mesh network, meaning there was no centralized authority in the network. What we imagined was you would be able to go anywhere, devices and all find the other devices around them. As long as one of those things was on the internet, everybody could route through them. It ended up being intractable because largely, the overhead of managing routing tables and those things. What I saw with the company that was called CoCo at the time, what Jeremy had come up with was a more practical way to solve that routing problem. Did it not end up being a big deal? It did but what it ended up doing at the scales we wanted to achieve was creating a lot of ongoing or zombie connections. It wasn’t even the routing that was complicated. It was keeping all the devices leashed together. The big problem for multi-party or multi-security domain mesh networks is that we give them to the police and the firemen. We want to keep the comms separate. The big problem is to track a firefighter who has moved through and past the end of the police area. We have to hop that firefighter’s connections through those policemen and back to where the other firefighters are. That is such a core conceptual model that your workgroup stays together as long as you exist and you’re connected to the mesh. You have this constant application layer concept of group communication or a group connection. When you have that, then it’s cool because you can have an IP subnet in your mind or your machine. You can represent a group of any nature that you’re a part of in the whole world with an IP range and use all your standard TCP/IP applications. The problem was to keep that real, then there needs to be a path for people in, for instance, that big group of firefighters that have one of their own orphaned out and at the end of the police network. They need to have a live connection in tracking where other firefighters are moving, so when messages come for them, there’s a path selected. It is a routing problem but it’s an online routing problem and it turns out that, even though nobody cares, except for your people and that was our goal. It was to make it lightweight for everyone else. Everyone still has to pass along updates about destination locations as you move. It’s got this whole mobility problem and nowhere to send the mobility information so it can be permanently routed in a central place. Mobile IP doesn’t have this problem, because mobile IP does not allow two mobile devices to talk to each other ad hoc. It’s not mobile. It’s both of them. Each of them has a static IP somewhere and they proxy through that. Only that one device needs to know about their location updates and everyone else can forget it. In a truly purely ad hoc mesh, you can’t do that. There’s a connection overhead, a connection load. Where did you guys land? I know that you build various iterations of this product to try and help emergency services and in those situations, what did you end up with? We ended up with the first high res audio USB audio digitizer that was pluggable for firefighters or emergency response radios. We went down to Katrina as soon as Hurricane Katrina happened in the aftermath. We went down and we hooked up a lot of the radios to each other and created multi-discipline talk groups to help them out. That was one of our successful products, our tactical radio gateway. Instead of all the police and firefighters having analog radios on channel thirteen, talking to each other, you could have them all on channel thirteen, but you’re using digital sampling of their audio when they’re talking, sending it digitally and separating out on the network. This goes to the police group and this goes to the firefighters’ group. We could do that but we also have the power to then cross those groups up. Maybe by regions EMP 25 and these other guys are using a more legacy Motorola StarTAC or something network. They’re unrelated radio networks and we get them to give us one radio each plug it into the gateway and now those two top groups are merged. It was either a distributor like you’re saying or a mock server. We did that and we were able to at least to some degree, effectively negotiate the push-to-talk problems. Push-to-talk networks that have an incredibly low timing sensitivity. You have to be as fast as possible. Because if I push my button and you push your button, we both talk and nobody hears. Everyone else hears both of us, but we don’t hear each other. We don’t know that there’s a problem. The farther apart those networks are, the harder it is to mediate an effective push-to-talk regimen, so we came up with some patents in that area as well. We branched out all over the space of communication in hastily assembled or dynamic environments. We built a chat network so it was your Jabber chat client but it would connect to a localhost. There’s a local service that you were running that pretended to be a chat server and would transact all your messages out to multicast well and track which ones of them arrived and didn’t retransmit correctly. You could on a multicast plane have a bunch of people using this chat service, transacting files at extraordinary speeds. That makes sense. Because everyone’s getting a copy of the packet at once so you didn’t have to send ten copies to ten people. You had one copy to the network and if anyone needs a particular frame retransmitted, somebody else can do it while you’re still spewing. It was efficient and it worked effectively up to 70% packet loss and you get delays of one second in your chat. That’s tolerable in chat. Is this stuff being used widely in emergency services scenarios now? No. Emergency services are utterly owned by Motorola Public Safety. They own the regulators, schools and engineers. They own everything. It sounds like a great business. Three years after we got going and they heard of us, they bought Mesh Networks Inc., which made a much simpler product that wasn’t meant to solve the world’s hunger. Many Motorola devices have mesh network devices in them, which is interesting because the radio at least at one time, beaconed all the time, and beaconed a clear crystal simple sound on the unique frequency. You could easily build a, “Where’s the police officer near me,” direction pointing to yourself. It’s a convenient GPS overlay of, “Where’s the nearest police officer?” We pivoted into the military space and we did that. We took those same radio gateways and mesh network repeaters. There was a company that was making Pocket PCs in a scanner form factor with four bar codes. It was rugged. We took some of these rugged Pocket PCs and mesh network repeaters that look like little bricks and tactical radio gateway, which looks a little pelican case. We took those out for the Coast Guard and helped them to build a hastily assembled boarding team interdiction network. What does that mean? I didn’t get up close to a freight ship before but they’re the size of a skyscraper lying sideways in the water. They’re utterly huge. You think about a 40 or 50 story building covering that in communication seems a hard problem. When you think about a ship, it’s not clear necessarily. It wasn’t to me anyway what the problem would be. It turns out the ship is made out of a Faraday cage. It does not permit radio to pass any part anywhere at all ever. Coming up with a way for people with bulletproof floating vests, rifles, comm systems, flashlights, these Coast Guard are there to see if there’s smuggling. They’ve got their border mission. Coming up with a way that guys can operate a mesh network became a real challenge. On the bricks, we had to come up with a light signal system. We had an ON button but no OFF button so you couldn’t turn them off later to screw up the network. They’re rugged. They break it in and it stops working and the crypto falls off. On the front, there were four lights: red, yellow, green and purple. It was that blue LED that was popular at the time. Blue meant that the device was connected back to the radio gateway. You’re on the network. As long as blue was lit, you’re live and you’re okay. Red, yellow, and green was the link quality of the first hop back to the radio gateway. We would tell people to leave them off in the provisioning center, on the cutter, they would be off, pack them in their jackets, and take them across. They turn on the radio gateway, talk back to the cutter, turn on the first mesh node, and it’s likely to go green and blue. The green and the blue. They’d walk away and it would drop to yellow. We’d have them step back up until it got to green, set it down there and that’s as far as this device can go. They leave breadcrumbs all the way. BreadCrumb is a registered trademark of the Rajant Corporation, which makes a similar communication device so I’m not going to say that word. The Hansel and Gretel story is the way that went. The cool thing was, by making it real-time, live and visible, this utterly impossible concept of link quality that no Boatswain’s mate is going to ever be able to jump to lecture on. That usability in real-time changed the future of our product in an interesting way. It turns out that there are these spots where a guy would be taking one round to see. As an experiment, we did it on an icebreaker, the Polar Star. We went around playing with them and playing with them, Grant Wallace moved a live one that was in a red state. The blues off. You’re not on the network. You can’t see what’s going on. You’re too far away. He’s like, “These don’t cover enough ground. We’re going to have to take 40 of them over.” They weigh a couple of pounds and that’s unrealistic. He moved it in front of an air vent and it turns out that the ventilation system is a perfect effing waveguide. He mounts it outside and it goes green and blue. We ended up filling the Polar Star with six Wi-Fi radios. It’s like a 30-story skyscraper lying on its side on the water and we’ve got six 2005 era Wi-Fi radios. You could go down into the hold and live talk back and forth with Groton, Connecticut, over a SATCOM back on the cutter. They could take a picture, have it go round trip, be in Groton within a minute or so with several seconds anyway. They were slow radios back then and have an analyst tell you whether it was a problem or not. You wouldn’t have to do what they did before, which was go over, go down and below decks in pairs, take photos of everything that could be found and come back up every fifteen minutes to make sure nobody got shot. Anyone being shot is not an acceptable experience. It’s a US problem. That was my feeling. We’ve got to change this. We’ve got to do something different so giving them live round trips back to Connecticut made a huge difference. To be clear, the reason they would have to do it that way before is because the analog radio, a Faraday cage means all the radio communications are going to get blocked if you’re below the deck or whatever. Your cell phones don’t work on the inside of the big ship. Cable TV and satellite phones, none of that shit works when you’re inside of a big ship. You guys develop that type of technology and other things around it and end up selling the company at some point. We worked on rebranding as well. We pivoted out of the Federal space and went into construction first. We thought that construction was a natural thing. It turns out if you can rig a communication system for a skyscraper on its side in the water, you could also do that for one that’s being built. It was an easy pivot to stand that skyscraper back up and go into the construction industry. Did it end up being a successful market for guys? Not as much as we wanted. Construction is hard to sell into because it’s conservative. We got written into some IT plans like this as part of the IT budget for a bidding process. We made it all the way through the selection and integration process. I don’t mean to say that it was unsuccessful but there’s a weird intersection for those guys. There are some things that they buy every time they do a job. There are some things that they buy every time they hire an employee and they expect the employee to track that device like a cell phone. A lot of the companies wanted to put this communication technology into an employee problem rather than a job problem. There were weird technical issues that made that go way slower than we wanted and potentially not have a lot of resales because the company would reuse the same system building after building. They buy enough for how many jobs they do at once, rather than enough for every job. Finally, we went to residential and started building residential Wi-Fi mesh networks, so home routers and extenders. Nokia was moving into the Nokia Wi-Fi space. Nokia makes most of the phone equipment that’s not Huawei or outside China. They’re the leader. They build the head and equipment and lay the fiber or somebody lays the fiber. They even built the CPE. What’s that? Your router, your fiber modem or terminal. They wanted to provide the carriers the capacity to deliver that gigabit fiber service all the way through even an extender to the far edge of the home. They acquired our company, Unium was the rename of CoCo. Unium like E Pluribus Unum. Unium, the element of connection. That’s where we wanted to take the brand eventually. We rebranded it and turned it around. Mike Chen from Linksys that we had met before had gone over to head up the digital home business unit there. He knew about us and came. He found our people and talked through them. Over about a six-month period, we worked our way to a partnership and that’s been going for a few years now. I want to change gears a little bit. When we first met was probably at DEF CON sometime in the late ‘90s. In those days, DEF CON, which is now the world’s largest hacker convention, probably always was, but there were maybe 1,000 people there, maybe 2,000. Maybe up to 1,500. I was still at Alexis Park which is the size of a Motel 6 or something. It’s a small hotel off the strip in Vegas that gets invaded by 1,000 hackers or so every summer, every August maybe. It’s 106 degrees, you’ve got 1,000 pasty white computer nerds in black t-shirts with witty slogans about internet protocols, Linux or something, laptops the size of VCRs, some of them with dual VCR decks in them. Can you explain VCR to me? I don’t think anyone reading this is going to know what you’re saying. We’re definitely losing people. My daughter has no idea what a VCR is. Hacking is like this bottomless pit of puzzles. It’s that bottomless pit of intrigue about the computer.Tweet Laptops that are the size of stoves. They were huge. People who have probably heard stories or anyone interested in hacking have probably heard stories or read about DEF CON in those days. I remember at that point, we were at Alexis Park because we’d been kicked out of every hotel on the strip for being poorly behaved, essentially cutting the power to a wing of the hotel and arson. Breaking the security system and throwing bottles off buildings. There you go. The ATM is going haywire. Who knows why? All payphones being destroyed. It’s all those things. People dying the fountains. Hackers in those days were fringe. It hadn’t gone mainstream. These days, a hacker is anybody who plays video games. There’s nothing to it. That’s not that big of a pride point. I still call myself a hacker because I’m still proud of it but there’s something definitely diluted about it. That’s the progression. Hacker in those days was not something that you advertised. It was essentially considered a criminal. For most people, it was isolated, at least for me. I grew up in the ‘80s, in Alaska, and I lived in a small town where there was nobody around who was interested in computer hacking, except for me. I would get these floppy disks mailed to me with The Anarchist Cookbook, information about hacking phone systems, how to crack video games and Apple II. It’s that kind of stuff. I get the floppy disk mailed to me once every few months. By whom? There were others but the one I remember was called the Bootlegger. It was a magazine for hackers on a floppy disk. You could subscribe to it and get mailed out. That was probably in ‘81 or ‘82. It was bad. By ‘82, I got a modem. I was in Alaska in those days and long-distance calls were expensive. Freaking was the law. The physics of the environment. If you don’t freak, you don’t play it. You couldn’t afford to call. Do you remember the first time you ever turned on a TCP/IP connection and you were like, “Russia, oh my God, it was free?” TCP/IP, I didn’t get it. It was like legal freaking but the internet was like a crime that you could buy. You could go out and buy this thing that could commit crimes for you by sending packets for free around the world. That’s the best feeling in the entire universe. That’s well put. I got on mainframes in the early ‘80s. How did you learn all this so young? It’s because I had nothing else to do. It was cold outside. You were going to die if you left the house and I had a 300 baud modem. The thing was, the university had mainframes, which in those days, were VAX mainframes. VAX, to be clear, has the computational power of a Tamagotchi but it was a multi-user computer, and it could have 100 people connected at once and a lot more in the computer lab at the university. The most boring LAN party possible. It was the most boring LAN party but we were all so excited. The cool thing was because I was a kid with nothing else to do, I managed to finagle my way onto the system even though I’m a 13 or 11-year-old kid, whatever it was, and everybody else was a computer science professor. They didn’t know I was a kid, but they all had jobs and in school and stuff to do and I didn’t have anything. I could spend sixteen hours a day learning about the mainframe, but it was painful. I learned the hard way as I’ve told other people. I learned to code by reverse engineering 6502 assembly language. There was no one to teach me. There was no YouTube video. There was no how-to for dummies guide. You didn’t get the Commodore 64: Programmer’s Reference Guide? I had Apple II and I had the manuals that came with it, but that was not how to code. There’s an assembly reference in that, isn’t there? There isn’t a Commodore. There is a reference that’s generous. It shows you, “Here’s what jumps statements are in hexadecimal.” What does a jump statement do? I don’t know. Let’s delete them all and see what happens. It was bad. I had pin-free Dot Matrix printer so I could print out all the assembly for a program. Was it like fanfold? Yeah. You printed all that, it would be hundreds of pages and you would go through and look like how you would crack video games in those days. Find all the jump statements one bite at a time. I didn’t learn a lot too fast but I had made up for it by time and enthusiasm. That’s what they called talent, time plus enthusiasm. These days, that’s about as good as it gets. Once I got on the mainframe, I could finally talk to people who knew more than me and there was an email system on there where you could email the other people on the mainframe. There are a couple of hundreds of people you could talk to, so I would ask them dumb questions, “How does this work? What does that do?” Because the mainframe was limited, you could only get so much processing time, so much storage and memory, and I always wanted more. I would write these programs, which we call Mail Bombs, and you would write a little program in DCL, which was the scripting language for the mainframe for VAX and you name it like Star Trek Game. You would email it to somebody and get them to run the Star Trek game. It would give them an innocuous error because they didn’t have a game. It would give them errors and I’d say, “I’ll go try and fix it,” but in the background, it would be locking them out of their account if they’ve given me all the resources and access to all their stuff. It’s a computer virus, but we didn’t have that nomenclature yet. We independently invented Mail Bombs. I believe that’s called a Logic Bomb, not a virus because it doesn’t make more viruses If you’re nitpicking, that’s true. I didn’t get to the automatically replicating part of it. The point being, that’s what, in a nutshell, my childhood was like. It was trying to learn as much as I could about computers and having nobody and almost no resources to lean on, and now it’s so much different. Kids can go on YouTube and watch how-to videos with animated cartoons explaining everything. The point being, by the time the internet came along because there’s a window of time where you got past mainframes into BBSs and things like OBS. I’m one tech generation later, like four years later. BBSs were more accessible communities of fringe wackos essentially who wanted to get into nerd stuff. For me, you go over to the Disk Copy Party that happened once a month and steal everybody’s software with each other and copy everybody’s stuff. Somebody came into a place that I’ve had my first job and they had a duffel bag full of pirate floppy disks. No envelopes, nothing protecting them, it was jammed in there. Floppies were oddly resilient. It’s so true. It’s surprising compared to even a CD or a DVD. You get a little scratch in the plastic and it’s all ruined. Out of the backdrops CCGMS, the modem program for Commodore 64. I had no idea. I didn’t have a modem so I’m asking this guy what does he do and all this stuff. We end up becoming short-term friends. He was on the run and making his way toward Vancouver and had some stuff. He was from Portland and they had some stuff going on. He was on the run with a duffel bag of floppies. We stayed in Arlington for a little while and we were friends for a minute. I went to his house once and there were five discs left on the floor and he’s gone. Everything is gone. In that meantime, he taught me how to get Sprint to issue a calling card that didn’t bill. I thought, “This is acceptable. This is my solution.” This guy tells me one thing and for eighteen months, I don’t have to work to dial internationally. I’m not a freaker. I script kiddie the solution from a guy and that solved my problem. I got a 300 baud modem, 1,200 baud modem, and 2,400 baud modem as fast as I could upgrade. I got two and ran a little BBS of my own. It’s like being part of a global underground. Our German teacher was the head of Brain Damage Studio, which was a distribution group in the Pacific Northwest, pulling out of Frankfurt. He would be on the phone on one of his phone lines 24 hours a day pulling down from Frankfurt. I was like, “I’ll help.” He’s like, “Great. Here’s another Fairlight BBS. You go here and get this stuff and bring it in.” That was my introduction to it. I fell into it. I had a sense that that existed out there but I was far removed that I couldn’t get to that thing. There was no place to do floppy copy parties. I remember one time, I met a guy on a mainframe, who also had Apple II. My parents drove me across town to a sketchy mobile home park, a trailer park. They dropped me off to hang out with some weird guy. Mine did too. I did the same thing too. I went to his house because he had dual floppies and I only have one, so it’s a lot better to copy. That was weird stuff. That seems amazing because you probably got far fast doing that. I got to learn about password security and logging. Joe Grand was the one who remembered this guy’s name. There used to be a guy on the East Coast and it’s because I could call anywhere on this scheme at the time. There used to be a guy on the East Coast who would set up voicemail boxes because all the voicemail systems were brand new at the time, they all had stupid hardcoded backdoors. You could call into one, dial a few different codes to see which brand it was, get yourself administrator privilege, and set up a voicemail box on (77245) extension, which no one is ever going to dial in history because it’s a two-digit extension box. (77) is not allowed, so you’d make these absurd voicemail boxes, no one ever knows they’re happening. This guy would call in and he’s like, “Here we go. I’ve got numbers for six bulletin boards,” and read them fast. It was like the Micro Machine’s commercial guy. He read them so fast. He’s like, “Here are thirteen Mastercards all fresh in the last 24 hours. American Express, Visa.” The Hacker ethos has always been anti-aesthetic. It’s not as good to look good as it is not to be cool.Tweet He’s reading the stuff up in the voicemail boxes. He’s not even putting it on a digital packetized thing and leaving a modem tone or something. He reads it off. The capacity to do stuff was far away from the practice of how to do it. If a guy is reading you into a phone and you’re calling, in the end, the next voicemail box would be a phone number and a voicemail by extension. That one would never get used again and get deleted a couple of days later. Once you get on the train, you’ve got to stay on the train. It’s like a podcast that was hard to get. When did you first end up going to DEF CON? Shortly after all of these shenanigans, my age of majority was starting to approach and I was working a lot. I bought my first car when I was fourteen. I wanted to get going in life. With Operation Sun Devil and some of the other police anti-hacker moves in the late ‘80s and at the transition to the ‘90s, with that stuff going on, I decided to put away all of those childish things and go out in the world and do my thing. I got my first programming job before my eighteenth birthday and went fully professional. I helped the guy who built the Sonic Arris Assembly Line and all these little projects and cool little things I fell into working with Datalight, Roy Sherrill in particular. They lifted my career up. I went in for a programming interview and they said, “The Program is Tic Tac Toe in C.” I was like, “Cool. Do you have a book on C? I’ve never seen that language before.” I sat there and for eight hours, I learned C and got a partly working Tic Tac Toe and they were like, “If that’s your first day in C, you are in.” That was mostly because I’d had Mr. McKay and Ainsworth in the Marysville high school system. They put a lot of effort into exposing kids early and effectively to programming. I learned logo when I was eleven. I would assume it would be now the normal programming course. I’m meeting more kids that haven’t taken a programming class and I’m a little surprised. It’s finally been legitimized. When I was a kid, I remember everybody’s parents wanted them to grow up to be a doctor or a lawyer because those were legitimate career choices. Computer programmer sounded psychedelic. Now, it’s like, “You should be a computer programmer or doctor, definitely not a lawyer.” That’s the progression. It’s the revenge of the nerds. We ended up succeeding at making careers, businesses and a lot of money. The explicit goals of the Ghetto Hackers were to improve our skills, our revenue and our careers. Hacking was a thing when you’re a kid and you ended up getting jobs. I remember when I got out of high school, I got a zillion computer consulting jobs. Whenever somebody wanted to do something with a computer, somebody goes, “Call this guy because he knows computers.” I never knew what I was doing. It’s like the C thing, I’m like, “I’ll figure it out.” I figured it out because I wanted to prove that I could do it or I wouldn’t get another job. That’s was my whole early career, but I might still be doing that. I am. I don’t know if that’s a personality thing or the window in time. I didn’t go to college because I was busy. I could get these jobs to play with cool, new computers. Why would I pay somebody else to play with their old computer? That’s how it went and that worked out for me. I lived for two years because a friend said, “You have to go to college and I’ll drive you.” I was like, “Did someone gave you a ride to college?” In two years, I almost finished it. I quit because it was too boring. For similar reasons, I did get signed up for college as a way to get the student loan so I could buy a car. I skipped all my classes to go snowboarding and that wasn’t considered copacetic. I was going to drop out but I wanted another student loan. I signed up again and I decided to only take classes that sounded fun or interesting. I was looking through the course catalog and I found the dance classes. I had never taken any dance classes but I signed up for dance classes. I took tap dance, ballet dance, jazz dance, African-Haitian dance and every kind of dance class they had. It was fun. It paid off. I’m still there. That was a good life decision. It worked out great and then I dropped out. You got the good stuff. First is dessert then screw the meal, let’s go dancing. You got legit. Somewhere along the way, professionally, you ended up falling in with hackers again or somehow ended up with them. I was working on a newsreader to convert Usenet to FidoNet. I mostly spent my time on FidoNet at the time and using it for binaries, for downloads of a certain kind. I was working on a QuickReader format translator to package back and forth and connect up the old FidoNet to the Usenet. It turns out it didn’t matter. One of the things that choked my reader was this message posted to Usenet and it was an invitation to DEF CON 4 and it was two months after DEF CON 4. I opened it and I looked at it and it was like, “Underground Hacker Convention.” I was like, “You are sending this out in public.” I got this weird ASMR thing. My hair stood up on my skin. I got all weird feeling, I was like, “Hackers are outside now. You can meet people in real life.” I was always taught like, “Don’t use it from home. Don’t admit it. Pretend to be an amateur spy.” When I saw that, it stuck in my head. For month after month, I kept reopening this file and looking at it. I can’t even explain what it was like. It was something magical. I ended going to the website. I found the DEF CON 5 invitation. I made my plans. I went to the opening discussion and Mudge is on stage and I’m fanboying, squealing. Mudge points at me and he says, “That guy right there is one of the best hackers you’ll ever know.” I’m like, “Something is wrong.” The Hobbit is right next to me. Hobbit stands up and he’s like, “Thank you. I wrote Netcat.” I lost my mind. I went from fanboy to fangirl or fan kid. I was sitting in this room and there were 500 or 1,000 hackers together. You could see it in everyone’s eyes, every person there had something to tell you about. I started little conversations here and there. Do you know when they say, “I found my people?” Yep. I walked into the room and I found my people. I was adopted as a kid. I’ve always felt a little on the fringe. How old were you when you were adopted? Two months. Did it felt different? It felt different. My family all look alike and I look different. I go in there and I’m like, “Everyone here is pasty white. I’m the man or at least a boy.” It was like a clone army. It felt like being a Stormtrooper and we’re on the Death Star. I’m like, “I’m home.” These days, it’s something that the hacker community gets much credit for being a place to feel included. For a certain class of person, that was the case. It was a life-changing moment when I sat there and met these people. The Anarchist Cookbook Being a computer nerd in the ‘80s, for those who weren’t around for that, wasn’t cool. It was maybe like what drug problems are. You’re alone at home, in the basement. No one is looking. No one will talk about it. No one wants to hear about it. If you’re into drugs and you at least have a leather jacket, it might be cool. If you’re a computer nerd in the ‘80s, there’s nothing about being cool. It can be isolating. You’re the first one to get kicked off the raft. It’s like, “The raft doesn’t have room for you.” “I’m skinny.” “There’s no room for you.” “Code a raft for yourself.” That’s a great story. It’s probably equivalent to the story for every other single individual in that room at the time. It was a community made of nothing. That Saturday night, there wasn’t a huge amount of well-known or well-publicized parties. It wasn’t like now where you go around and you get sixteen invites to go to a party on a Saturday night at DEF CON. DEF CON now is 25,000 people. It’s massive. Corporations throw parties at DEF CON now. Microsoft and Facebook do. All the little security firms do it. For me, when I was there, I didn’t know what to do on a Saturday night but I wanted to do something with the hackers. To be honest, I’ve told that story several times that way. My wife at the time went to the liquor store and got a couple of bottles, brought them back to the hotel room, and I stood at the hotel room door like a lady of the night. I’m standing there and pulling my jeans up a little shorter and seeing if I could attract hackers to come in and get free drinks. I’m standing in the doorway and pulling people into the room. Everybody was happy to come in and say hi and meet each other and stuff. The social tools they had available to them lasted about 2 or 5 minutes. They’re standing on the wall waiting for somebody to have a party. It was about to be a magical thing. I’m looking at all these people and I’m thinking, “You all love each other. You all have all this stuff in common. You love the same stuff. Why aren’t you either making out if you’re inclined or talking and making out with your brains? Why aren’t you doing stuff together? I’ve put you in the room. Why aren’t you doing the thing?” It was this breakthrough moment, I said, “I need $10,000. Let’s steal it from Western Union. Let’s get Western Union to give us fraud money.” They were like, “We can’t do that.” I was like, “Let’s decide whether we can do that once we make our plan.” All of a sudden, it turns into Ocean’s Twelve up in there. All of a sudden, everybody is a criminal. They’re like, “Let’s analyze this. Is there a backdoor? Do we have pictures of the place? Where’s the wire? What protocol do they use? Is there encryption? What about the terminals? Can we dig?” Immediately, everyone jumped in and started throwing their passion at it. Of course, we were never going to do it and no one ever did. There’s no conspiracy to be active further. It’s a fun conversation. People in the hallway who were walking by and looking like they were ready for bed would hear the noise and turn and come back and join. The party went from 8 or 10 people by about midnight to 30 people crammed into a single, small hotel room. All was jamming and talking and yelling, “That doesn’t work.” All this crazy energy and I looked at it and I thought, “Something about what happened is the most important thing in my life and I need to figure it out. I need to be able to reproduce this. I need to bottle this crap.” I came back the next year and I decided to brand the party as the challenge. I hadn’t worked out to put the puzzle on the invitations yet. It was an invitation to a party. I took them around and I set them in innocuous places. They were on a clear laminate with a fragile ink. If you rubbed your thumb over it, you’ll destroy the entire invitation. I set out 200 of them on tables and places where they were hard to see. I’m not sure which year this was. It was the second year I did the party. This is about ‘95. No, more like ‘98. I went back. Once the party got going, I said, “Let’s try this other challenge. Let’s try this other thing.” Wallflowers turned into extroverts. As soon as the state of their brain could lock on to something that was a challenge, something they couldn’t get their whole mind around quickly. For the kinds of friends we have, for the hacker mind, putting something in their brain that they’re okay with and that they want to think about that’s fun, that is complex enough that it gets their creativity chewing, it occupies their critical voice. This is my hypothesis from watching this party happen. As soon as they get this thing in their brain to work on, all of the self-criticism and internal doubt finds no exit. They can’t start talking in their brain because this problem is talking to them. They lose that sense of self-consciousness that can be toxic. It’s interesting because if you think about what’s attractive to computer hackers, hacking is like this bottomless pit of puzzles. It’s that bottomless pit of intrigue where everything about the computer, it’s like, “That’s funny. It wasn’t supposed to do that. What happened?” You dig. That’s what debugging code is like. It’s puzzles. Security problems, in particular, like puzzles, it’s like, “You’re not supposed to be able to do that but I got it to do something it’s not supposed to do.” That’s mentally stimulating and interesting and a lot of it’s done in isolation. It’s done alone. That conversation isn’t happening with another person in the room. What’s interesting about those challenge parties is it bridged the gap to doing the thing that they like to do but doing it with other people. Something that is still important to me is learning more about that, doing it better and finding ways to engage more in different people. Years ago, there was a battle of the sexes. Some horrifying men in the computer security community are taking some angst out on the women in the industry. If you had to stereotype DEF CON attendees over the years, there’s a lot of poorly socialized males. Like anything else, you get better at it with practice. If you grew up by yourself in your bedroom with a computer, you’re missing out on some of the work it takes to get good at cooperating with other people and treating them well and those things. It doesn’t surprise me. It’s a community that welcomes people. There’s no screening process. You just show up. All the behaviors that people would have that would signal to any normal person that’s like, “Stay away from that person. They’re creepy.” We don’t have a defense mechanism for those. You could be creepy and show up and we’re like, “You’re creepy.” I don’t know if you’re in a sorority or something. You wouldn’t get within 100 miles of a sorority before some football players were hired to get rid of you. There are those things. As inclusive as the community is for those reasons, it accepts people who are not specifically well balanced in other ways. I’m not saying everyone is that way. I would further that though. I would say that some of the people, myself included, who are part of the community have done a poor job of accepting and criticizing the artwork. It seems a little tangential but a lot of the artwork in our community in the early years, in the ‘90s at least, came from metal bands and industrial music or anime. In the anime, especially, there’s maybe an overly stereotypical presentation of females and that was the aesthetic. That was what was happening. Everybody wore those t-shirts. That’s what it looked like to be around us at the time. Capture the Flag has done more to escalate the defenders than anything else.Tweet Not enough people had absorbed that the artwork that they choose, the decorations that they choose are messages that reinforce or subvert stereotypes. By having a social norm of reinforcing certain stereotypes, especially the love of Japan, whatever that was going around in the late ‘80s and early ‘90s, Snow Crash and all those cultural iconic moments and the movie Akira. Letting that become the visual language we use to represent ourselves has the consequence of giving us a reduced conversation around, for instance, gender issues. One of the things that have been tickling me in the back of the brain is how could we bring a discussion around personal aesthetic into the hacker community in a way that gives people a much more diverse self-presentation? A much more diverse self-presentation, one that they can talk to and one that other people can criticize effectively to say, “That thing that you’re wearing is like a pro-holocausts t-shirt. I don’t like that. There’s something wrong with that,” and opening that conversation. Now, people at DEF CON can wear some offensive stuff. People don’t think that’s part of the conversation. They don’t think that’s part of their environment. They don’t think that’s part of their responsibility. You think that other person is doing something wrong, maybe, or they don’t. The people who don’t know that they’re doing something wrong are having their stereotypes reinforced. There’s a ton of stuff in there to pick apart. You were talking about that on the other episode. I’m always a little cautious to throw people under the bus from history or to cast judgment on the past. People are doing the best they could with the situation. We know more now. We can go piece together how we got here. We can see the things that were happening in this community that led to the problems that happened and you certainly want to learn from that. It’s interesting because you’ve identified a set of issues that have become a big deal. One of the things I loved about my social group, my friends being hackers, is the comparative irreverence that they have. These are people who don’t take the status quo for granted. They’re willing to argue about anything. They want to find a way to reason their way to their beliefs. They have no compunction about telling you when you’re full of crap. I remember times when you did that for me. That’s why we’re friends. I value that. I need that. I want to be able to take an idea, shoot a bunch of holes in it and see if there’s something left standing at the end of the day. That has influenced my process as an inventor. That’s what we do. I don’t find that in other communities the same way. People are worried about social hierarchy. They’re worried about their status. They’re worried about offending others. They’re worried about all these things and it keeps them from having these honest conversations. Not to defend it but one of the things I saw in the hacker community in those days, the late ‘90s, is that it was accepting of whatever you brought. You could show up. You could wear a t-shirt with something offensive on it and everybody would be like, “Cool. Whatever.” It was accepting of marginally criminal behavior. It was accepting lots of anti-social behavior. It was accepting people who were gay. I saw that there are more than in other places I had been. You could be gay and that was no problem. Trans people, for sure, were more accepted there in general than in other places. This might be less true now. At DEF CON, maybe there’s a lot of that. It was accepting a wide variety. Drugs are more accepted, psychedelics and things like that, that wouldn’t be in other communities. I’m not somebody who had any of those things that I needed acceptance of. I learned to be accepting of those things or at least slow to judge. I appreciate that. I remember that having a positive influence on me. I’m not trying to defend it. I certainly know, especially for women, this was a hostile environment in a lot of cases. This is not an accepting environment that was comfortable for women. I have a lot of female friends who were hackers that would come and they had put up with a lot to be there. They were brave. Some of them had to compromise themselves in ways to be there. In my early experience with women, they were tough as nails and sharp. Even the term in and of itself is derogatory in a sense. It’s like saying, “They have no other value other than to look pretty and be there with some guy.” It isn’t cool but that’s the context. That’s what it seemed like at the time anyway. I only mean to say that looking forward. One of the things that would be a healthy endeavor would be to engage in some aesthetic discussion, which is new. The Hacker ethos has always been anti-aesthetic. It’s not as good to look good as it is not to be cool. That was how we tried to make the Capture the Flag game. It’s cool but we didn’t necessarily try to make it look good. We tried to give it a lot of experience, a lot of stuff. It was still gritty. That’s the origin of the challenge party. How did you end up playing Capture the Flag? Maybe describe that. Originally, Capture the Flag was a game run by Miles Connolly as far as I know, from the beginning. Miles would organize to have some people bring in servers and then everybody else could come in and they could play Capture the Flag. They could try to capture those servers by hacking them. Each server had to have a file on it and that was the flag. You’d hack into it and get the file. You’d write the file. You’d put your name in the file called flag.txt. The first year I went, I didn’t know about it or played it or anything. It was just talk. The second year, I went and saw that there was this Capture the Flag game. There were big banquet tables and different people at different tables had gone up and purchased some static IP addresses to participate in the network. There was a table that had a couple of spaces open in it and I sat down at that table and I opened up my laptop and introduced myself. I made the fateful decision to buy a round of drinks. After it, we’re blood brothers forever. I bought a round of drinks. We got our drinks. We drank them. We set all the empty cups in the middle of the table. The next guy bought the round and it went around the table. This went on for two days. We barely left the table that year. We sat there and we were all working separately. We didn’t know what we were doing. We didn’t know each other. It turned out that two other people at the table lived here in Seattle. When I got on the plane back, one of them was on the airplane with me and I was like, “You’re my blood brother. We bought drinks for each other. We’re bound together forever. Where do you live?” He lived four blocks from me and that was Michael Eddington from Deja vu Security. It’s is probably one of the few companies populated with actual hackers on this planet. The whole team, they are brilliant people and many of whom I’ve worked with before. He set up a mail server and that was the thing and I started inviting everybody on the mailing list, which was mostly those three of us but then we started going to 2,600 every month in Seattle. That was already going and you guys showed up. We showed up and we started bringing whatever we had hacked last, whatever was on Packet Storm. Bring in an exploit, go in and talk about it, see who could carry on a reasonable conversation, and invite them over to the house. We grabbed the entire hacking community in Seattle and made them into Ghetto Hackers, one after the next and up to the next. I don’t remember how we got in touch with MD5. Maybe he was the third guy. I got them all together. It started on Tuesday nights at my house, building up our idea of how to be ready for a hacking contest was. The truth of it is Michael Eddington did all the work. He was like, “I’ve downloaded Packet Storm and made it into a searchable database and you can have access to it.” We were all like, “Sweet.” On the back of his research and his collecting Packet Storm, his mirror, we won the contest the second year playing. You guys went and tried to do Capture the Flag as a team. We had this idea that it would be a cool thing to do. We went and we won. We came home. We’re super jacked and super excited. We went and rented a workspace and started to try and make a real thing out of it. At that time, this was probably the only hacking contest on Earth. I’ve never been in touch with CCC so I don’t know what their history timeline is. I know that’s even bigger and older. We went back the third year to win the second time and it was a little harder because people were getting a little more serious. The excitement was starting to ramp up about the contest. We had to resort to fairly shady means to win that. We won that year again. The third year, we went and we coerced the team that was going to win into joining the Ghetto Hackers and merging our points. We won the third year in a row. It was shady. That irritated one of the other teams, rightfully so. That was some out of the box thinking. This was a contest all about out of the box thinking. I don’t know which year it was, maybe before you went, there was a server room that had to be highly guarded because those are the machines you’re trying to hack into. They didn’t want to let anybody mess with them. I remember one year somebody brought a VAX mainframe to put in there. People bring all different kinds of computers. It had been gutted and there was a guy inside. In the middle of the night, he climbed out of the mainframe and locally routed all the machines because they were all there. It was easy and that’s how they won. There’s lots of shady stuff. It’s a hacking contest. Our view was if you have a hacking contest, do whatever it takes to win. That was the zenith of the idea that we would do anything to win. Hearing the other team’s frustration triggered a guilt reaction. I was like, “This is probably crossing the line into unfun.” We got up. We got our awards at the end of the conference and our Black Badges. I asked Jeff if I could use his mic and talk for a minute and I announced that we were taking over Capture the Flag. I remembered this. Did Jeff not know this? Jeff didn’t know. Miles didn’t know. Nobody knew. I was in the audience. I thought this is amazing. I didn’t realize that you hadn’t even got DT on board. Nobody was on board. Nobody agreed. Nobody ever approved. To this to this day, we never got approval to do it. Did you make this up on the fly? I made it up on the fly at that moment. What happened? We went home and we got serious. We cranked and we cranked. I’m going to say this in different two different ways. Michael Eddington built the core router that was the actual network. He’s such a talented hacker. MD5 built the client operating system. A few people put in all this amazing work. I wrote the scoreboard software. My main contribution was arguing over threat models the whole time for the whole year. How are people going to cheat? In the second year, we double NAT everyone so that you couldn’t tell either what IP address you were coming from or to through the central router so that it would look like everything was homogeneous. The central router also reached out to your machine and tested whether it was working. You had to get defensive points and offensive points. At this point, the Ghetto Hackers are running the contest. You guys changed the architecture of the competition. Instead of being either an attacker or a defender, we made everyone be both. Everybody has to be red team and blue team. We got the idea of there being service uptime points. We got the idea of there being transient points that were capturable, they’re like tokens that you had to capture in flight. You’re running services and you got to keep them going. The funniest one was one of the teams realized that when the packets went to hops from the enemy team to the central router to theirs, the TTL was 254. When it came from the scoreboard, the TTL is 255. They blacklisted all TTL 254 traffic. They got a perfect service uptime for the entire contest. Nobody could even see them or scan them. No one could figure out how they did it. That was one of those like, “We screwed up TTL.” I was doing this thing called Capture Capture the Flag. Me and the Shmoo Group had made this logging system that would try to log every packet from the entire competition. We thought, “This will be interesting, historical artifacts, to see the TCP dump from the entire Capture the Flag competition.” Now that it’s been decades, it probably would be interesting to go with those dumps. We still have them of like, “What kind of hacking were people doing because it should have been state of the art hacking on the network for that timeframe?” You have to remember that at that time, the way that we won the first year, the second year, and the third year was deploying known exploits. A hacker, at that time, might be building their own exploits. It was a good network search person with some script kiddie capabilities. That was the thing that we also added to the contest. We did use live services that were state of the art at the time. You could use state of the art exploits in attacks. We also started building custom services so that these were new pieces of software so that people would have to adapt and improvise. Our view was that it was a little too much of tactical exploit deployment in the original contest and a little too little of creative problems. We tried to get creative problem solving, real-time scoring, a lot of these pieces that are pretty much standard in every hacker conference in the world. In those days, the game went from Capture the Flag, which is all the thought that goes into it is in a tweet to a sophisticated game. You guys did a lot to turn it into a spectator sport. We wanted to bring the audience in and give them a reason. Before that, all you could see was a bunch of drunk guys on laptops. With what you guys did, it turned into something people could see in real-time play out, at least the leaderboards and things. You guys ran it for three years. If you take the frustration as a thing to stop at, as a negative signal, then you’re going to fail.Tweet We tried one with one and we ran three and then we handed it over to Kenshoto. That was a different gang of hackers who decided to run with it for a few years. They took it in a direction much more seriously, new exploit authorship, simpler, smaller systems so you could do a better job as a player, simpler scoring. One of my concerns and a well-founded one is that it tends to be the case that one of the teams is going to run away with the contest. If somebody figures out either how to never get hacked like a TTL 254 team or how to hack everyone at every time tick and get all the tokens at such a pace. You’re attacking seven other teams. Hypothetically, you can get a whole weekend’s worth of scoring in about five hours. My argument and one that has been unsuccessful but I would still stand up for is that we wanted to have the contest. We wanted it to remain relevant over the course of a three-day contest. The leaderboards that we came up with were a little hard to read and a little confusing. They were like deltas in a recent time. That didn’t give people a sense of who was winning or losing but it gave them a sense of who was pulling ahead and so forth. I wanted it to be a little more like NASCAR in the individual race sense as opposed to Formula One where the champion is well-known for weeks at a time. There’s a hacking contest every weekend somewhere all over the world going on. Do you think it has relevance in computer security? Yeah. Capture the Flag has done more to escalate the defenders than anything else. Maybe that’s a bold statement but I feel that when we started, the attacks were static because the defense was static. As the defense became more naked and simple, like with the Kenshoto version of the game where they shrunk it all down and made it a much less code, much less stuff to worry about, it’s was streamlined. The attacks, you could reasonably, in a day or so, build a custom exploit and send something in. You build zero days live. At first, it escalated a lot of hackers from script kiddies to exploit authors. At the same time, we saw the rise of a net exploit. We see all of these advances in counter defensive technologies and all these crazy exploit techniques. When I was winning Capture the Flag with the Ghetto Hackers, when we were there, no person I had met had that flexibility and capacity. Now, every DEF CON speaker has it. It burst the exploit author bubble and blew them up fast but that created intense pressure on all the other teams that maybe they did or they didn’t have a great exploit author. It created much more pressure on the defenders. That’s why we see Naval Warfare College. Chris Eagle’s team, the Naval Postgraduate School. We see these teams from military, from other countries. There’s a Chinese hacker team that comes to DEF CON. We see these guys coming and they bring new talent and they bring great exploitation capability but it’s not that much different than it has been in the past. However, the defensive capabilities, the power of these guys, these guys set up live DevOps shop at the table and they start deploying router configs. If something goes wrong, they got an alarm setup. These guys, in an hour, are setting up what used to take ten years of general dynamics. I thought it was there to measure and to separate hackers from moderate coders. I thought it was there to rank and organize people. That was my original concept of what it was doing as a mechanic, but it wasn’t. If done well, it gave the attackers a field to practice in. Once they seeded the field, it gave defenders a place to grow up. I don’t know if you remember Trustworthy Computing at Microsoft, the TwC initiative. Yeah. That was sensible, hardcore, smart people building security on chips and getting ready for a world of digital media. They were doing a great thing. They had nothing in that system that compares to what a DEF CON Capture the Flag team has now. The idea that one of the most vaunted security programs in the world, ten years later, is replaceable by sixteen-year-olds. In my mind, that’s the difference between trying to be smart and architect for a hypothetical future versus having your feet on the ground and testing and steering your way into what works. They say, “Steel sharpens steel.” It’s a much different game. Big companies make that mistake all the time. It’s why they suck at innovation. They’re trying to guess what the market is going to want years in advance. You can’t guess. Nobody can guess. That’s what’s amazing about not only hacking but the software in general. It gives us a way to test everything and that’s working well. You have to have it in-hand all day, every day and have an obsession to perfect it. You have to have both those pieces. That’s the progression of Capture the Flag and, to some extent, DEF CON. I get a lot of questions from people about, “How do I become a hacker?” I probably have 7,000 variants of that question in my email from people who’ve asked me over the years and I don’t have time to reply to them. One of the things I’m hoping we can do with the podcast is give folks a sense of at least what our experience has been and what our observations have been and maybe help people feel like they know what track to get on. A lot of that intrigue comes from kids who are interested in computers. It comes from kids or people in different stages of their life, maybe who are interested in computer security for different reasons. A lot of it is folks who are attracted to hacking with some of the same sentiments that we had where they’re slightly marginalized or loners or had more of a positive experience with their computer than they did with Boy Scouts. I don’t know what to tell people exactly. It would be good for us to try and figure out if there’s advice or where to start. A lot of times, the questions show that they don’t know where to start. It’s like, “What programming language should I start with? Where can I learn to hack?” Will you teach me?” “No, I won’t teach you. That’s not what you would want anyway.” I understand the question that you’re asking. I found that there are a couple of pieces that are important. I’ve tried to answer this a lot over the years. I’ve searched for the right answer. There’s one way that I started and this is a sarcastic joke but it comes in the form of a Japanese Koan, a Zen Koan. The pupil says to the master, “How do I become a hacker?” The master says, “You don’t.” The pupil says to the master, “Fuck you.” In a way, the way that you become a hacker is by refusing to let someone stop you. There’s a clinging to the decision to do it that is utterly required. The thing about anything that is purely noetic, purely idea space concept or an idea space mechanic is that you will feel frustrated until you don’t. If you take frustration as a thing to stop at, as a negative signal, then you’re going to fail. You’re going to fail once and never again. As I’ve seen many times, people who say they want to become hackers, get to the moment when they are angry, “It’s not working. It doesn’t work the way that it said it would. Screw this. This is too hard. I can’t do this.” Some word goes through their head and then they take the frustration as a reason to back away, reconsider themselves, and distance themselves from the identification with the hacker. It’s almost like oil and water. You have to be able to feel frustrated to know what frustration feels like to be able to call it frustration. Stand up and walk in a circle and sit back down and do it again. You have to be able to swim in frustration. Hackers are fish and frustration is water. It’s the only thing you get. I certainly never was able to articulate it that way but when you described that, it is entirely my childhood and my early career. Looking back, there’s nothing about my experience with computers. It was different than that. I was constantly frustrated and I’ll stare at something, “Why isn’t it working? It doesn’t make any sense.” There was no easy way out. That accurately describes my experience. Having it described is like a fundamental architecture for success in that mindset. You’re right. These days, there’s a popular notion of grit. Grit is like the people who are like, “Stick it out. If you give up early, you’re robbing yourself of that.” It’s an interesting point. How do you foster that? First, you have to identify as a person who’s not going to let things stop you. This is a case on the computer where there’s no injustice. In the machine itself, there is no injustice. There is never an unfair game. There is never an unfair set of rules. There’s never a software that doesn’t want to work for you because you don’t look, talk, sound, or smell right. You are the only thing that can screw up between you and your computer. That means that everything between you and your computer is perfectible because you can change, grow, and learn and the computer can’t. It can’t participate in this. It can’t let you down and it can’t lift you up. It is just there. It is going to work and do the same thing every time. You have to first decide that you’re not going to let other people stop you from doing it and then you have to decide you’re not going to let yourself stop you from doing it. Except that the computer is never smart enough to be a jerk and then decide that. When the frustration comes, that frustration is the heat that is melting your bad ideas and turning them into good ideas and they suck and it hurts to melt your brain and put it back together into pieces. It’s going to be painful. The thing to do is to build it up from the bottom. I know this is uncool in the way that people are taught now, but I highly recommend there’s a lot of programming games where you run little robots around and you set tiles down or something on the floor. The robot moves through the room and tries to do automated assembly instructions if you’re making a factory or something. These programming games contain all of the critical concepts in computing. They have recursion, iteration, enumeration and all of the things that you need to be able to do to assemble a concept in your brain that’s going to turn into a useful program. I recommend people start with games that don’t have an explicit programming language that are teaching you sequential reasoning. Commodore 64: Programmer’s Reference Guide If you don’t have access to one of those, then what you can do and I did because I didn’t have access at the time. Carl Cluster was a great geometry teacher. He told me, “If you write down everything you know, then you can do anything that you’ve ever been shown or ever been taught. You can do it because you won’t forget it. The only thing that can go wrong is forgetting how to do stuff once you’ve been taught. If you write it down, and you write it down in carefully detailed instructions how to do a proof or how to do algebra. If you write down the actual ideas in a row, then your brain will remember the pieces, but it will assemble the pieces into a larger concept.” I highly recommend for a person who wants to be a programmer that they begin to take excruciatingly detailed notes in math class. That has a strong mapping to the process of computational reasoning and sequential logic. Doing things like this that get your brain around those core ideas is so much more important than learning a programming language. First of all, the way I think about it is framed by this notion of computational thinking, which is what they call it in my daughter’s school. It’s not necessarily about learning to be a programmer, but it’s learning the way you and I did to understand the way that a computer does so that you can communicate with the computer. You have to communicate with it in a logical progression and that turns out to be a useful skill well beyond computers, programming and everything. They have a class for computational thinking every year from 6th grade to 12th grade, which I’m super excited about. She doesn’t know that it’s cool. She’s like, “I don’t know why I got to this computational thinking class.” The school is trying to figure out the best way to do that and you have some ideas there that will be helpful. I learned how chips work from Rocky’s Boots, which was a game on Apple II in probably ‘81 or ‘82 where you are going around configuring logic gates. You have AND gates and OR gates. To win the game, you have to put them in order. I didn’t know I was learning. I thought I was playing a game. It turns out, now I know how computer chips work from that thing. There might be other games like that. I know a popular one that a buddy of mine made. Dan Shapiro made this game called Robot Turtles, which is a board game that you can play with a five-year-old. I have a Kickstarter on that. He launched on Kickstarter and it’s wildly successful. Get Robot Turtles because you can play it with 5 or 6-year-old kids and they learn how to think logically about making a plan and embodying it in a set of logical steps. I don’t know what’s after that. I know with my daughter, she played Swift Playgrounds, which is a game on iPad that Apple made for kids. Half of the screen looks like a video game. You have a character on a map that you’re giving directions to, but you tell it what to do by writing Swift, which is a programming language Apple has now. It’s a scripting language. Each level is introducing a new programming concept. You learn what a four loop is at different levels. She was probably 8 or 9 or 10 when I started it out with her. I wouldn’t say she loved it, but she loved doing it as an activity with me. It tries to explain things so you don’t need somebody to do that. Having me go through it with her helped a bunch. She doesn’t even know it, but she does have some of those ideas in her head already because we did that stuff when she was a kid. I was going to say one extra thing about the ideas I have about how to become a hacker. One of them is finding someone on the internet, in a college, in your church or wherever you go that’s trustworthy. Kids, talk to your parents first. Not that we did, but yeah. We didn’t but they dropped us off across town at a trailer park. Find someone trustworthy who is a professional programmer while you’re learning. Go to them not as soon as you feel frustrated. You have to learn to accept and to perform with frustration. When your frustration turns to anger or fear or sadness or something when the frustration wells up and creates secondary emotions, then pull back, take a shower, go for a run, go outside, or do something different. Talk to the person when you can. It doesn’t have to be live, “Help me. I’m doing this right now.” Set aside time and send them an email, so they answer you the next day or something and be clear, “Here’s what I’m trying to figure out. Here’s the program as it sits now. Here’s the output. I’m supposed to make it look like this. What am I doing wrong? What’s the problem here?” There’s something about knowing that there’s someone who’s going to help you when you get stuck. That makes it a lot easier in my experience for younger people to accept frustration. Also, get yourself somebody somewhere. You’ve got to find some. That’s Stack Overflow if nothing else. Have a place you can go and ask the question. Don’t be quick about writing your question. Take a minute to introduce yourself and introduce what you’re doing. “I’m a sixth-grade student. I’m just learning Logo. My turtle doesn’t go left when I do this left instruction.” The person is like, “That’s because you spelled left wrong.” It may be simple stuff. Give people a sense of the story of what you’re going through and that will make one, you, accept your frustration better. Two, they want to help more. Three, it will focus their help and help generate some social relationships. That’s another one where you’ve articulated well, but that is what happened with me. Lots of times, it didn’t have that person, but I did find that person. That’s what those folks on the mainframe work. That’s what folks in Usenet groups work. I miss email lists. In the ‘90s, you had an email list for every programming language, every topic and everything. There were a bunch of nerds who were there and you could ask them questions when you got stuck. You didn’t want to waste their time by asking dumb questions, so you would try to work through it until you were too frustrated and then do it. That is equivalent. You and I probably have no experience with this, but I keep thinking the way you’re describing things sounds analogous to what people experience with in sports. The way you describe the computer as being completely objective and just. Sports are like that. You’re running on track against a clock. Everything about it is fair. It’s up to you to run as fast as you can. It’s not judging you because you showed up with a screwy haircut or wearing the wrong sneakers or something. That’s your problem. Maybe that’s another area where people get to shape themselves because they’re working against objective metrics, and then they get that frustration. They’re like, “If I could do it a little faster,” and that kind of thing. They have that coach. Once it gets too extreme, they can fall back on the coach and get that insight and that helping hand. Even if they’re saying, “I don’t think I can do this anymore.” They express the resignation they feel and the coach can be like, “That’s okay. You have to feel that way. You will make it. I promise. I’m going to help you a little more. We’ll push a little differently. Let’s fix this and make it better.” Sometimes, you need to know from the outside that, one, there’s a tribe for you, and two, that the tribe loves you and is going to stick with you. Your frustration does not make you a bad part of the tribe. It’s interesting because it puts a fine point on folks with other interests who might not ever get that kind of experience. They might not get that experience of working through frustration of being able to develop themselves in an objective situation where they’re not being judged and isn’t just. That might be true if you were into performing arts or something like that or something more social if you’re interested in politics. I think of different things, but we were lucky to have that. I’m starting a new company, so I have a lot of entrepreneurial things to do. I had to find a lawyer and get a lawyer. I don’t know how to tell which lawyer is better than any other lawyer, so I’m asking other entrepreneurs like, “Who have you used? Who was good and why?” I talk to lawyers and see if I like them and figure this out. I don’t know what I’m doing but I’ve got to get through that. I’m frustrated with it because I don’t even want a lawyer, but I got one. You’ve got to go through that frustrating process, but I’m doing the same kinds of things that I did when I was trying to debug a program. I’m still using that computational thinking. I’m making a list of features that I need. I’m figuring out the logical progressions like, “I can’t interview lawyers until I get introductions and I can’t get an introduction, so I’ve got to figure out who’s had them before and people I know that I can email or talk to.” All of that is a progression that I take for granted because I worked that way. Learning and developing that skill is the fundamental thing that kids should probably be doing or trying to do in any context and you could do it in any context. You’ve done a great job identifying the things to look for. There’s another one though, which I often associate with hackers. It’s a different mindset. What you’ve described so far could be applied to becoming a programmer, which is different than becoming a hacker. There’s a certain amount of time you have to spend becoming a programmer. Hacking, to pick an exact definition for me, is causing systems to produce unintended effects. To do that, you have to be able to understand the systems and to understand the systems, you have to be a programmer. I consider the path toward being a hacker as being initially all about becoming a programmer who can write in a low-level language like C Counts, ASM, VHDL and anything like that. Eventually, what you develop is a sense of the conceptual physics inside the computer like, “You can’t add numbers faster than X. You can’t multiply numbers faster than Y. You can’t divide numbers at all because it takes too long.” Don’t ever do that. If you can avoid it, just screw division. It’s not worth it. It’s better to multiply it until you find the answer. Getting an idea of how the memory works, prefetch queue, CPU instructions and those kinds of things, maybe you don’t need to be perfect at them and maybe you don’t need to be an ultra-guru at every one of these pieces. You at least have to be able to say, “That looks like bedrock. I don’t think I can solve this problem. I need to look elsewhere.” There’s this problem that sometimes people get to, which is they don’t know what part of the problem is solvable and they don’t know which problems to work on, so they end up either trying to solve an unsolvable part and trying to work around reality. That’s where a lot of bad software comes from because people decide that if they do something more complicated, that will make reality easier. That comes from not being close enough to the machine in your sense of aesthetic and your sense of what’s fair, just and reasonable. The computer can’t do that fast. In the machine itself, there is no injustice. There is never an unfair game. There is never an unfair set of rules.Tweet There’s a big path toward programming. The last piece of becoming a programmer in my mind and this is where it ties into the step up to hacker, is the scientific method. You have to be able to say, “I want to compare what this non-working software does in state A versus in state B. I want to make a random change and then change it back, compare the results and do it again.” You have to be able to do this guess and test thing. It’s almost like a guessing test effectively with the scientific method behind you is gaining eyes. You can start to see through the parts of the problem that are changeable versus seeing the part of the problem that will not budge. When you start to see that, then you can start to say, “I don’t want to try to go through that bedrock because I’ve learned enough times that every time I try to go through or around the bedrock, I start making huge mistakes. It goes off in the weeds and it doesn’t ever accomplish anything.” Your brain turns and it’s like, “What if I attack this other part of the problem?” That ability to think you’ve got a way in and a directed course to solve the problem you want to solve and realizing that you’re hitting up against a wall that’s not going to budge. Turning your attention to something different like, “What if I attack the password found or the user database?” That is where the famous lateral thinking part of hacking comes in. It’s not just throwing yourself at a wall every day dying on it. It’s throwing yourself against a wall once and going, “That wasn’t padded at all. That hurt a lot. Let’s not do that anymore,” and walking away from an idea. You have to have that ability to, one, recognize the ideas to be able to use them, test them and see what they work. That’s the programming part. Using the scientific method to decide what’s real and what’s not to convince yourself that you’re seeing what you think you’re seeing, and then having enough experience to know when you’re going down a fruitless avenue. When you have all those pieces together, you naturally begin to develop a sense of a quick pivot. That’s where the hacker’s mind turns the magic on. That’s a great description of a framework that I haven’t seen articulated well. Even I haven’t been systematic about trying to break down those pieces. Having done that, you could imagine, at least for the first one, which is computational thinking we talked about like, “What kinds of steps somebody might take to get there?” Computational meta-thinking. Also, the practical steps, like you described in your math class of learning to write down, what do I know? What do I understand? It then becomes part of your brain’s vocabulary. It might be possible to come up with ideas like that for these other aspects too, like lateral thinking. I certainly like the analogies of, find the bedrock, understand when you’re banging up against an immovable object and learning to steer faster. The only difference between me and most other people that think of me as being creative or whatever is that I’ll turn on a dime. If I get new data that affects my worldview, I can internalize that and have an entirely new worldview within 30 seconds. From then on, I’ll be using the new model. For other people, it could take months or years and that’s the difference. It is core to all great hackers because of this transformation and they develop this capacity to evaluate when they’re running in the wrong direction. The willingness to say, “I’ve got to skill up in skilling up. I can’t make the skill up process take so long. I need to cut out all this crap of arguing with people and disagreeing. I need to become humble. I need to say, “Yes. If you say so, let’s go for it. Let me make that the new truth.” When you get that limberness and flexibility of approach, then you can back away. You can even identify other tangential mistakes you’ve made in life because of a misunderstanding that you had. You change your worldview, you get working and then you’re like, “I remember this one time. I would now have succeeded at that moment with this new idea in place.” Your framework is super interesting because most people, and even myself included, have fixated and come at it from the other direction. “Hackers are irreverent. They don’t mind challenging the status quo. They almost do that by default.” Those might more be symptoms than causes, the way you describe it. This is interesting because it might get us closer to understanding how you make hackers. I often chicken out of that question and say, “Probably you know some and you don’t want to hang out with them because they don’t want to watch the Super Bowl with you.” That’s interesting. I’m going to have to pick that apart. I bet there are things we could do to back out from that. The other question I get is like, “What do I do with my kid? He doesn’t make any friends. He just loves making mods in Minecraft.” I’m like, “Have him drop out of school and play Minecraft because that’s where he’s more productive than other kids his age.” Minecraft is the starter drug for coders. I meet eight-year-old kids out there who can probably go circles around me. They learn to code in Minecraft because they wanted to blow up their friends or whatever and that was a way to do it. It’s absurd to me. I tried to get my daughter to load Minecraft and play it and I couldn’t even figure out how to load it. It’s complex. I’m like, “I don’t have time for this. I’ve got to load different versions of the JVM, and then I’ve got to get these mods.” I’m watching YouTube videos by kids in junior high telling me how to do it. You realize that’s their FreeBSD install. For us, years ago, trying to install an operating system was like pulling teeth. You learn so much about how a computer works just by trying to install your OS. I’m a fairly technical Minecraft player. I’ve got a ten-player server. I’ve got a whole world. I don’t play games so much, but I appreciate that. That was one of the amazing things to see in Minecraft. Maybe a good thing for you and I to do in some days is to figure out like, “For each of those things that need to be developed in that rubric you described, what are tools to do it for kids or college students, or professionals?” Maybe build a Coursera program. “What do you tell your kids? What do you tell the teachers at your kid’s school?” That could be a kingpin. It’s something that has been near and dear for a long time. It stems up out of the parties where I’m trying to get younger new people who are wallflowers to enact with people who are a little older, a little more mature and far-right on the road. I’ve always been fascinated with the degree of skill deployed by some of our friends. I mentioned Mike Harrington a couple of times. He’s a great example of what happens when someone decides they’re going to be great and sticks to it. It’s difficult to sit next to him and feel smart. Not because his personality makes him smart. He’s a nice guy. I like to hang out with him so other people think I’m probably smart too. If you’re standing next to the person with a mohawk, you are suddenly cool. You don’t have to get a mohawk. I’d be inclined to circle back and go deeper on all these topics but we probably should go forever. Do you have any ideas of questions for me? I heard a rumor that you once sold a patent to Carl Zeiss. Is that true? Not that I’m aware of. Maybe. I have a lot of patents, but I don’t track them. That would be cool. I don’t know. That’s funny. I never heard of that rumor. That was an explanation. Now you know that the rumor mill is bigger than your opinion. People spread that rumor far and wide because that sounds cool, but I’m not aware of it. I have probably 80 patents. Like 80 filings with numbers or 80 different issues. Yeah. Are those families and descendants and all the crap, or do you mean the actual top-level idea? Some of them are related and you might consider them to be in a family. They’re not near and dear to my heart the same way that some other inventors have that relationship. I had a lot of help on those. Almost all of them are things that I worked on with other inventors, with other people. It’s a community effort, but a few of them are things that I feel proud of that are close to me. It’s not clear to me that any of them have been sold to Carl Zeiss. What did you try to invent that you failed at? The first one that comes to mind is that we had tried to cure cancer at the Intellectual Ventures Lab. This came out of an invention session, which is our team sports invention concept. I might have described this before with another podcast. People misunderstand cancer in the first place. Cancer is a thing that your body does all the time. It should be a verb, not a noun. You’re cancering. Most of the time, your body kills that off and flashes it out and you’re fine. Occasionally, it gets out of hand and a whole bunch of cells grows fast, and you’ve got this cancer, which could be contextualized as a tumor. A lot of times, that doesn’t kill you. It’s fine. You get away with it for a long time. In a lot of kinds of cancer, what will happen is some of those cells break off and circulate in your bloodstream. Those are called circulating tumor cells and they’ll float around your bloodstream and then they’ll latch on somewhere else and metastasize. A bunch of cancer will grow in a completely different place and that’s what will kill you. What we had heard was that on average, these circulating tumor cells circulate your bloodstream one million times before they latch on. We thought, “If you get a million shots on goal, why not just look for them?” We came up with a bunch of inventions for ways to use fiber optics to jam lenses into your bloodstream and then we were going to use computers to take a photo of every cell in your bloodstream, which is trillions of cells. When I was working on this, it sounded preposterous because that’s a petabyte of photos or something, but we figured, “Why not try digital pictures? It’s cheaper and getting cheaper every year.” One of the ways that we cheated invention is to invent ten years out on Moore’s Law and say, “It would cost you $1 billion to take all those pictures now, but in ten years, probably an iPhone could do it.” We got some blood and we set up a bunch of experiments to circulate the blood. We try to take pictures of blood cells. We got all that working and then the idea was like, “If we could spot those tumor cells, then we zap them with a laser like we always do.” We’re always wanting to use the laser when we’re inventing stuff because lasers are cool. Down that road, we probably spent about a year on it, and then we found out that circulating tumor cells often only go around one time. We’re like, “If it’s one time, we’ve got no chance.” What I love about that story is that we didn’t keep banging our heads on cancer. We found the bedrock like, “That’s not going to work.” I worked on self-sterilizing elevator buttons after that because we had an idea for that that made sense. I was able to steer to wherever the next best idea was. I don’t know anything about cancer in the first place. I’m not a cancer expert. I’m not an elevator button expert for that matter, but in that context, it was using that same mindset. It’s moved from the thing that failed to the thing that had potential and that one does. That’s the one that comes to mind. I use that example sometimes because that story makes sense. There are things I wanted to invent that I didn’t get to work on and some, you could say, are failures. Some of them failed to get the time, money, resources, people and that kind of thing. There are other inventions that didn’t work. People think I’m a crazy futuristic inventor, but I’m quite pragmatic. Most of my inventions are things to do with computers anyway. If I can figure out how to make a computer do something, usually, there’s not going to be a big question about whether it’s going to work or not. A lot of my work is applying computers to things that you normally wouldn’t like. That’s how we ended up at cancer because that’s not a chemistry solution to cancer the way we’ve been doing it. It’s a computational solution to cancer. That’s how I think about those things. I don’t even track them as failures in my mind because you go until you can’t go or it doesn’t make sense. You find the bedrock and then turn and go somewhere else. They’re intersections. It’s not the destination. I think of almost everything like a Google Map now. I got started and I put in my destination. There’s a big map, but there’s a blue line showing you how to get there. There are some gray lines showing you alternative routes to get there. You get stuck in traffic, that thing recalculates. You make a wrong turn, it recalculates. You’ve still got your destination in mind. Halfway along the way, you might get hungry and decide, “Screw it. I’m going to go there instead.” I’m going to register for a career on Maps.Google.com. That’s how a career should be. That’s how it should look like. I spent 1.5 years thinking about healthcare in that context. The day I get a diagnosis, “You’ve got cancer.” “Show me the blue line.” “You’re going to do this. You’re going to do that. You’re going to get chemo. You’re going to do rehab. You’re going to spend this much time here and end up at the destination.” “I should get to see that blue line.” No one gives you that. If you break your arm, there should be a blue line. “You’re going to go here. You’re going to get a cast. You’re going to do physical therapy. There’s the blue line.” “Why can’t I see that?” How we should be doing everything in the world is like a Google Map. Daniel Suarez hit that well with Freedom (TM). It is great near-term sci-fi. You’ll want to read Daemon. That first is great about how powerful scripts and batch files can be. The second one is about encrypted mesh networks with HUD overlay blue lines. It’s my thing and your thing jammed together. Daniel Suarez is amazing. I don’t read a lot of science fiction. The truth is I did read those books. That was a while ago and they have not stuck with me, so I couldn’t recount them the way you did. It’s helpful to have those mental visual models of how to think about complex things. I love everything should be a blue line. Why couldn’t you just say, “I want to be a computer security consultant, a programmer at Google, a database administrator, or nurse and see that blue line?” It’s like, “Here’s the main way to get there. Here’s the fastest way to get there. Here’s the cheapest way to get there. Here are some other alternatives that might be more fun. Here’s the way to get there that lets you live in Santa Cruz for a couple of years.” Let people choose from any given moment, “Here’s where you are and here’s where you’re going. Here’s the map of potential choices.” Khan Academy and Coursera are helping people get there. They have a lot of those things. Khan Academy, in particular, is like, “If you’re going to know that, you’re going to know these things first. This is the secret.” You’re right. You’ve got your thumb on the pulse there. What does Coursera do that’s like that? They now have degrees and programs. It lets you pull your pieces together from different schools or different parts as you would do with a college registration. It lets you put together a degree. It’s like, “I’m trying to decide whether to get an MBA. I don’t know whether I need one. I didn’t want to go to college, to begin with. I definitely didn’t need it for my career.” Everything between you and your computer is perfectible because you can change, grow, and learn, and the computer can’t.Tweet If you think you want to do that, I probably know some folks you should talk to about it. I’ll take you up on that. I often feel like I’m faking it and I need an MBA. I don’t know what an MBA is. Everybody else can stop thinking I’m cheating. There’s this notion, “Whatever business I have, you know you need some around,” and they don’t self-identify as MBAs though. They do. They are Oxfords. That is certainly true, but they don’t like to be called MBAs. I keep calling them MBAs. “These are our MBAs.” They’re like, “That’s not exactly. We’re the people. We’re Oxfords.” As far as I can tell, in every company I’ve been in, you do need them. You need one from Harvard and you need one from Stanford. The main reason is they each have an email list with all the other MBAs that they’re on. That’s what you need it for. You and I are on the email list, but we need a proxy in their basic career. They need to have us with the email lists we’re on. You and I are on the email list they’ll never touch. MBA might be a way to buy your way into those email lists and then you just do deals. I would never start a company without an MBA from Harvard and Stanford because that’s where the deals come from. All the things that you would learn as an MBA is a way you described the Tic Tac Toe in C job interview. It’s like, “I know all the stuff that an MBA knows and probably a lot more and I learned it in the context of doing projects, businesses, and everything. I just don’t know that I know it and I don’t know the jargon that they would use and those kinds of things.” You have to get right with the jargon if you want to hack your way into a community. I don’t know if that’d be a good waste of your time or not. I probably haven’t done any of the prerequisites necessary to get into an MBA. I don’t know if this changed for you. I always felt like, even today, there’s no job in the world that I’m qualified for. I don’t even have a resume, but if I did, it certainly wouldn’t map to any job opening. For the first maybe decade after high school or something, or maybe even more, it felt like a dirty little secret. It’s like, “If people find out I don’t have a degree, I’m probably out of the run,” or that kind of thing. A computer consultant or something like that is what I would get referred to. I wouldn’t ever apply for a job I would get from word of mouth, introduced, referred, or something. For me, in early 2001 to 2003, or somewhere around there, in those days, I would go to DEF CON and the Shmoo Group would show off cool hacking tricks we came up with other hackers. It is the worst possible audience you can get that could hire you. They all think they’re smarter than you. They know everything. They’ve seen it all before. The only reason they came to your talk is to tell you why you’re full of shit. One thing I learned from you about this was you described speaking at hacker conventions. You had come up with this clever trick, which was to figure out who everybody in the room thought was the smartest guy in the room, and then get him in the front row, and then make fun of him from the stage. That would establish enough credibility that everybody paid attention to you. I have co-opted that. That’s what I do. I’ve taken that so far. My audiences are the presidents of companies and the presidents of countries, and I don’t give a crap because I know I can take a roomful of hackers and put them in their place. After that, it’s easy. My wildly successful public speaking career is a side project. I don’t know why I started doing it because I thought it was funny. I realized hackers were preaching to the choir. It’s a lost cause. I started taking all the fun things that hackers could do and going to other audiences that had never seen it. I ended up with this weird hacker magic show, stealing people’s passwords live on stage that blows everyone away, except for hackers. I’m like, “That’s a trick from the ‘90s.” I would be taking it to other audiences. That may be popular as a speaker, but it was always easy. For one thing, I’m a magician because I have superpowers no one else in the room has so that made it easy. The bigger one was that after speaking to audiences of hackers, a CEO wasn’t about to get funny. Probably for my own amusement, it progressed over years. Now I’m on stage making fun of CEOs who are in the audience because they’re going to suck at innovation. Whatever it is they know about, they don’t know what I know about. It got easy. From 2001 to 2003, I was the first guy to show up publicly and say, “I’m a hacker.” Other than Kevin Mitnick, who is a notorious hacker/criminal/script kiddie gone wild. In those days, it was unusual. Even everybody from DEF CON would say, “I’m a computer security expert.” They were trying to legitimize themselves in that way, but I didn’t have anything to lose because I wasn’t a criminal and I wasn’t trying to get a job in any conventional way. Being the hacker got me a lot. That’s how I got known, and then after that, within the next decade, it progressed gradually to being a mainstream thing. Now, no one gives a crap if you’re a hacker. That doesn’t get any attention. “I’ve seen that before.” Probably there’s some progression like that for you. You feel less imposter syndrome because you’ve had success. I did get past that many years ago because there was a flip where if I sat and went to college, they’ll be like, “You’re smart like Bill Gates and Steve Jobs. You need to go to college.” It’s like, “I like that.” I don’t have any of the imposter syndromes like that anymore. The truth is it’s not because I’m less of an imposter. I still don’t know what I’m doing most of the time, but I’m comfortable with it. I wouldn’t want to be doing something where I knew what I was doing. “Just take me out and put my head off the floor and kill me. I don’t ever want to do something where frustration goes away.” That’s what I was getting at earlier. The frustration is the water. Hackers are fish. If you’re out of the water, you die. You have to find your way back to the hard stuff. If you go into management, you need to learn how to be frustrated with people and be nice to them. You need to learn how to be frustrated with people and get them to perform. Not to just yell at them and inspire anger, fear, and those kinds of simple solutions, but to praise the person you’re frustrated with for how far they got without you, to see the pain that they went through and how difficult it was for them to embrace that. You have to be able to take that same idea of frustration with the machine and do it to a person. That’s the transition that a lot of fully well-formed hackers could make. If they wanted to deal with unjust and unfairness, that’s where the meta where the wheels fall off the trail. I’ve inadvertently stumbled into those situations at times and found myself largely unprepared for them. “This is unjust. Why are you being irrational? I pulled all the memory locations.” Applied Cryptography “I said the right magic words. You’re supposed to do what I want.” That’s not how people work. That’s another episode. Let’s wind this down. I’d be remiss not to ask you because I’m sure you have ideas and we probably have folks reading who would love that insight. What are the things people could do to learn more about the hacker mindset and getting comfortable with the technical side of computers, whether programming or otherwise? Are there books that you read that you learned? I learned a ton in the old days from reading things about what Alan Kay had said. I learned from different thinkers about computers and technology in those days. I’m wondering, what influences are on you? We don’t need the best sellers that are on the bookshelf at the airport. The most important thing that I ever read was called the Rebel Asm Tutorial. It was for people who knew how to program BASIC and it would teach them how to program Assembly. BASIC was easy to get your head around and Assembly was foreign and alien. Having something there that could pass your knowledge for the 1st step to the 2nd step and do it piece-by-piece, it took me two nights to translate my BASIC knowledge to Asm knowledge. All of a sudden, I’m able to read all these programmers’ work. That could have taken years back in the day. I’d figure out a little from the reference manual. This tutorial was like, “Make sure you have your reference manual because I’m not typing this stuff.” It was a 100,000 binary with a GUI and stuff. It was this fantastic little tutorial. I have to give credit to the author of the Rebel Asm Tutorial because that has escalated the speed of my knowledge gain quickly. If it were someone who wanted to follow in the track, I would say get your programming down to Assembly language. Even if you don’t stick there long, just having that comfort and that knowledge of what it takes to take a number and a different number and add them together, put it somewhere, and do these mechanistic computer actions. That’s critical for developing the sense of where the bedrock is. Applied Cryptography, Bruce Schneier’s book taught me a lot about how to think about security. I’ve heard people say that it’s not perfect, but it taught me so much about how to think about security, protocols, and information exchanges. One of my favorite books ever was a book by Danny Hillis called The Pattern On The Stone. Danny is a famous inventor who made a company called Thinking Machines, which was the first massively parallel processing computers in the late ‘80s. This machine has 64,000 processors and a lot of that is what’s in supercomputers now, but also even just chips now. The Pattern On The Stone is a tiny book. It’s out of print and might be hard to get. I loved it. I’ve given away all my copies. I bought dozens of copies of this book. Your mom could read it, understand everything from how chips work and what logic gates are, and how they’re constructed and put together into logical groupings to do different things. All the way up to massively parallel processing and everything in between. You can read it in a couple of hours. He’s a bright guy. I should figure out if I can get an eBook of that or something to get people. It’s incredible. On Intelligence by the creator of the PalmPilot. I don’t know that one. I don’t remember his name. It’s great because it’s pamphlet-length. It’s probably 5,000 words, maybe 10,000. It’s like, “Here’s how intelligence happens.” It’s a little bit about artificial neural networks and how those work ground up. It’s a nice little primmer, a place to start. For people who aren’t necessarily going into the pure math, pure neural networks, pure hacking side but want to have that creative outlet and are going to do it in a digital universe, I love the book Reminiscences of a Stock Operator. It’s a thin book in a big format. It’s old, maybe 100 or more years old. It’s the story of the development of a guy who made a lot of money on Wall Street. His story of development from six years old running numbers for the bookies in the neighborhood and developing his understanding of money all the way through being a major stock operator. In it are the lessons that for instance, the Bitcoin kids are all learning one by one as they get ripped off by people who learn these tricks. It’s all the first round tricks that stock players knew 100 years ago or so. It’s thin, easy to read and super personal. You think of him as, “That guy lied to me.” Instead of thinking about it as an arbitrage opportunity. There’s not a lot of technical wording. It’s like, “This person lied. I made a bad bet, so I need to learn that I have to vet my sources.” There’s a weird amount of solid reality wisdom in the book, Reminiscences of a Stock Operator. Anything else we didn’t cover that comes to mind? Not at all. Let’s wrap this up. Thanks. I appreciate it. Important Links: Riley Eller DEF CON IEEE The Anarchist Cookbook Commodore 64: Programmer’s Reference Guide Robot Turtles Stack Overflow Maps.Google.com Freedom (TM) Daemon Khan Academy Coursera Kevin Mitnick Applied Cryptography The Pattern On The Stone On Intelligence Reminiscences of a Stock Operator About Riley Eller Riley heads up all aspects of our software and hardware development and manages our IT infrastructure. Riley’s team builds the technology that is the core of the React Mobile offering ensuring that our products deliver exceptional customer value. Recorded on May 14, 2019The post Diving Deep into the World of Computer Hacking & Becoming a Hacker — Riley Eller appeared first on .
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Mar 17, 2021 • 2h 7min

Into the World of Genomics & Entrepreneurship — Adina Mangubat 

Today we get to hang out with Adina Mangubat, a friend of mine that I know from a salsa dancing, and also hanging out with computer hackers. She’s probably the youngest founder that I know. And she’s been running her company for almost a decade since starting it in college at age 22 called Spiral Genetics. It could be considered probably the most advanced bioinformatics technology for population genomics. And what that means is DNA sequencing, massive populations, hundreds of thousands of people, if you can, and then correlating that data to see what can be learned about it. And it’s a huge frontier there’s so much that can be learned from doing this kind of work. And Adina is really at the forefront of that. And so it’s a really fascinating conversation where she breaks down all that stuff: What it means, what DNA sequencing is about, the potential for bioinformatics, the potential for population genomics etc. So, this is the perfect episode for you. If you don’t know anything about it, because I’m asking Adina, a lots of dumb questions, you’re going to love it. She’s also a super entrepreneurial and hustler which is very inspiring. Adina has built this company. She actually sold it to a large biotech company and then spun it back out on. And so she’s been through a lot as an entrepreneur and we’d talk about that a bunch. And the other thing about Adina that’s super interesting to me is that she’s really committed to figuring out how you can create these transparent, high integrity, mission driven cultures in startups and small companies, and that’s pioneering work. It is really important and difficult work. It’s unproven. We don’t know if it’s even going to work, but it’s so necessary to figure out how we make better companies. Some people have to be the ones to try that. And so we talk about that and I think there’s a lot to learn at the end of this episode. Adina and I talk a little bit about adoption and parenting and I am kind of deep into that, having adopted a child and raised her to age 14, so far seemingly successfully. Adina is kind of early in that cycle. And so if you’re interested in that sort of thing at the end, there’s a conversation about that. I hope you guys liked this episode and get a lot out of it. Pablos: You seem to be possibly the youngest Founder/CEO that I know. I know other people who are young. You might not be the youngest now, but when you started, you were the youngest. Adina: 22? I know some people that are younger. It’s not common. I know people who started younger but they did not succeed at keeping it going for very long. You started at 22 and you’re still at it, which means you’re tenacious. Maybe also stupid or crazy or all three. I’m curious about that. First, I want to know how that happened for you. I don’t know if the track you’re on now is what you had planned. When you were a child, were your parents trying to convince you to be an entrepreneur? No, definitely not. My family had planned on helping me out with grad school if I wanted to do that. I was like, “I don’t want to do that. I want to start this company instead.” My dad wrote me a tiny check and he slid it across the table. He’s like, “This is going to be the hardest and most educational year of your life.” I was like, “Really?” He was like, “Yes.” My mom was supportive but worried. She would call me every couple of weeks and be like, “How’s it going? Are you thinking about applying for a normal job?” After a while, she figured out this was clearly not a phase and that I was going to be okay. I gathered later that the reason why she kept on asking is because she had started a company when she was young. She ran up a CPR business, a training business, and trained a bunch of the Secret Service. Back then, she had connections and you could roll up to the White House at midnight and be like, “Can I get a tour?” They would be like, “Yes.” She’d had to go through the entire process of starting a company back then. She knew that it was going to be hard. Were they right? Yes, it’s hard. Do you think that you believe them or you didn’t believe them? I didn’t. The blessing and the curse of being a newbie is that you’re so naive that you don’t know what you don’t know. If I knew everything that I know now if I were given the option of starting this particular company, I don’t know. I wonder about if I move on to another company someday… If you’d have the guts to take it on? It’s a big one. I’m clear that I have a reasonable business acumen. There are a lot of other companies that I could start that would be easy by comparison like stuff that is not this complicated. I have fantasies about easy companies. The reality is that I get bored after running a festival earrings company or something like that. That’s an idea that has been sitting around for a long time. One of the things that’s missing in our vernacular is a way of describing the difference between entrepreneurship and tech entrepreneurship because you could start a Taco Wagon or a festival earrings company or something that will be entrepreneurship but it’s something that’s been done before. There might even be more fine-grain definitions because I think that we have something to describe that there are “lifestyle businesses,” which is the Taco Wagon or the festival earrings company or whatever where the intention is to build a company that is going to feed your lifestyle and be fun generally. There’s then tech entrepreneurship, and it’s tech entrepreneurship of stuff that is hard but not bonkers hard. If you want to make enterprise software or a Fitbit device but for your animals or your pets, things like that. Things where you’re basically you’re taking off the shelf technology and you’re retooling it to a particular vertical or something. You’re doing some innovation but it’s not hard and never ever been seen before innovation. I call the hard stuff deep tech now. All that other stuff, I call it shallow tech. If it’s iPhone apps or enterprise software or modified Fitbit’s, shallow tech. I don’t know if that’s going to stick but that’s how I’m thinking about it. It’s unlikely because a lot of people feel like, “My tech isn’t shallow.” It’s revolutionary and it’s sprinkled with blockchain. You went to college and you finished college. It’s nothing related to this. I got my degree in Psychology with a focus on Bio Psych. Do you feel like you know about the brains of people? I do. At the time people were like, “What on earth are you going to do with that?” It turns out that a lot of things in life have a lot to do with humans that have brains. Understanding how humans work and how they tick and all of that stuff is ridiculously useful. That’s why I like computers. I just reboot them if things go wrong. They mystify me. You finished college for your parents. Was that here? Yes, at UDub. The plan was like, “I’ve got to find something to do and I don’t want a job.” How did you end up deciding to start a company? I’d been involved in two companies while I was in college as an intern. One was a smart grid company that was looking at like, “How can you optimize the usage of energy that come from green sources like wind energy.” Essentially, it was how can we use big buildings as batteries? If you know that the wind energy is spiking at a particular moment, you can overheat or over-cool your building a little bit. If it’s a large enough building so you can use that. Did it seem it would work? It seemed it would work. They had a good run but didn’t end up making it in the end. It turns out that the tech for building control is ancient and terrible. When you’re trying to integrate with that, that’s more complicated and there were a variety of reasons. I was involved in that company. I did a bunch of marketing related stuff for them, initial business strategy sales. How big was the company at the time? Seven people, maybe. The curse of being a newbie is that you're so naive that you don't know what you don't know.Share on X That’s cool though, as an internship, especially because you get to see pretty much every part of the company. If you go be an intern at Microsoft, you get to see one dime and you don’t get to see the whole operation. You learn about management, what works, what doesn’t work and all of those pieces. I was involved in that company and before that, my first job was an internship with a company that did home automation. Turning your lights on and off with a control panel. This is before cell phones. They were in direct competition with Control4. They did pretty well up until the housing crash. Nobody was looking to outfit their homes with cool smart techs. I had a lot of friends because lots of my friends are nerds, especially when one of them leaves the company or sells their company or ends up with some free time, they dive into home automation and they try and install everything and they tell you all about it. It’s all amazing. They’re spending full-time integrating their home automation stuff. A year later, I’ll ask them about it. They’ll be like, “I had to tear all that shit out.” You’re going to be a sysadmin for yourself for your home light switches. At some point you’re like, “I’m going to open the blinds by myself like an adult and it will be fine.” Another very interesting experience, they were larger, probably 30-something people. I learned a lot about what worked and what didn’t work. Back then, I was doing video creation for them, teaching people how to use the product and stuff like that. I took it to see the whole operation and have direct contact with all of the “upper-level management.” I was involved in those. After that, it seemed like, “It’s easy to start a company. I’ll do that.” No. It was cockier than that. It was like, “These guys are doing it wrong.” I had a whole thing about how people were managed. Especially as a psych person, I was like, “Maslow’s hierarchy of needs. Some of these people aren’t fulfilled.” I feel I could do that better. It turns out that that’s hard and complicated and they were doing it for the best that they could. There are definitely best practices but that stuff’s hard. That was part of it. I took an entrepreneurship course at the UDub Bothell because UDub Seattle wouldn’t let me into the normal course because you need prerequisites like accounting and stuff like that. I wasn’t going to do accounting for taking one class. Do you wish you had now? No. Accounting’s not that complicated. If you need deep accounting, you can call somebody that loves that, which I don’t. Somebody else can do that. That’s cool. I need to know how much money do I need in order to get to X and make sure I don’t run out of it before then. I commuted 40 minutes each way 2 to 3 times a week to take this class. Bothell is a very interesting campus because it’s got a lot more diversity in terms of its student population. One of the people that was up there, her name is Becky Drees and she was a non-matriculated student, Molecular Biologist, PhD at Berkeley. She had been the industry for years and ran one of the labs at UDub. On the first day, the way the entrepreneurship course works is you get up there and you either picked your skillset, which is what I did, or you pitch your idea because I didn’t have an idea. She pitched this genetic analysis company that was very similar to a 23andMe style company these days. Her ultimate pitch was if we are going to be able to impact disease, we have to understand the code of who we are. For me, that was compelling both from an intellectual perspective but also from a personal perspective. I’d had people in my life that had been significantly impacted by things that are entirely genetic in basis. Cancer is quite literally the disease of the genome. I’d had my grandfather pass when I was thirteen from lung cancer. I remember at the time when that was happening. Mine too. I was eleven. Where was he located? Was he in Seattle or no? No. I grew up in Alaska but he was mostly in California. That doesn’t seem that much in the way, but it was still my grandfather and it was hard. It was the first person I lost. What was striking for me at the time was like my dad is a doctor. He’s a surgeon but when you’re thirteen, you don’t differentiate between surgeon and oncologist. You’re like, “Doctors should be cool,” and it wasn’t. As I got older, I learned that in large part it was because they didn’t know what to do. Even now, to a certain extent, if you get diagnosed with cancer, there’s a super over simplification. They’re like, “You have this, we have X number of drugs that could be used to treat that. We’re going to try this first one. If that doesn’t work then we’re going to try the second one and we’re going to try and hope that we get the right one before it’s too late.” Becky’s basic pitch to me was if you could see what’s going on in there, then you could pick the right one the first time. That for me was far more interesting than any of the other companies that were being pitched. I didn’t want to do Fitbit for your dog or any of that stuff or a concierge service. It sounds like I should go pitch my crazy ideas to the entrepreneurial class and I can pick up people like you to run with them. People have a very interesting relationship or opinion about young students because I was 21, 22 at the time. I went back. I’ve maintained a good relationship with the professor that teaches it, Alan Leong. He now teaches at the UDub proper, the Seattle campus, but I’ve gone back and helped to judge classes and etc. Frankly, the younger they are, the better. I’ve even been in classes where there have been MBA students and freshmen and then they’re competing in a competition, a business plan competition together. I’ve got to tell you, the freshmen kick the MBA’s butts every time. The vast majority of the reason why, in my opinion, is that the older we get, the more we fall susceptible to thinking, “This is that way. This is possible. That’s not possible,” whereas the freshmen, they don’t know. They’re like, “Let’s try this thing.” There are probably two escape hatches, either personality or naiveté. Have you ever hired anybody from one of these? We’ve had bunches of them as interns. We’ve definitely hired some pretty young people sometimes. I want to dive into the problem with genetics. What happened to the woman who had the idea that you heard pitch it? Did you end up working on it with her? We were cofounders. She and I won a business plan competition and that’s how this whole thing got started. It’s 2009. If you recall back then, the economy was not so hot. Here I am graduating with a Psych degree. My options are stupid, boring, shitty job or go to grad school but I’d come to the conclusion that I didn’t want to get a PhD because it turns out that I’m impatient enough that research doesn’t appeal to me or it was like start this thing. It seems like a very similar risk profile at the time. Find a job, make a job. I was like, “How hard could it be? That was my naiveté speaking. We went for it and we found our third cofounder Jeremy through a Japanese tea ceremony, which is how you usually find cofounders. I worked for Jeremy for a long time. Maybe you should start with what you guys thought you were doing. At the time we thought that we were doing essentially what is 23andMe now. 23andMe then came out and pro tip, don’t go head-to-head with essentially what is a Google-backed company. This was in 2009. Was that when 23andMe came out? They were even maybe right before 2009. I’ll have to look but they weren’t so big at that time. There were large enough announcements where it was like, “Somebody already doing this. Maybe we should pivot.” At the time, the plan was to do exactly what 23andMe is doing in terms of snip chips. There are lots of ways to look at a genome. One way is to look at the whole three billion base pairs. Another way is to only look at certain markers that you’re interested in. That’s what they were doing at the time. They’re still doing that for the vast majority of things. It’s cheap to do that, etc. I met them in January of 2009. I’m one of the first 100 people on 23andMe. Now there’s all this cool stuff they can do, but my sample was done so long ago that they don’t have as much data about me. There’s a bunch of things they can’t do for me. I have to redo it again. The chips that they were using probably at that point didn’t have as many individual markers but even now, at least the last time I looked, they’re only doing about 500,000 markers, which sounds a lot but out of three billion, it’s tiny. They’re single base pair. They’re also usually the most commonly varying ones. While that’s interesting from, “Are you a fast metabolizer of coffee and caffeine? What color your eyes?” It is relevant for some medical things BRCA1, BRCA2, the breast cancer genes that research is on lockdown. It’s very good. Whereas your risk for diabetes or other things, the reality is that you might have a single-base pair that has been changed that increases your risk right next to something that you didn’t look at that decreases your risk and you would have no idea. It’s not high risk yet. If I go to a service that can do my whole genome because some of those exist, it could cost $2,000, maybe. It’s $1,000 for chemistry, plus the analysis on the computational side. That’s vastly less expensive than it was. Back in 2009, it was $100,000. If I did that, would I discover vastly more? Probably not. It’s because the analysis hasn’t been done on all those other things. The first 500,000 that the zillion people have done, we have a lot of data on. The game that we’re focused on now is how do you figure out what the rest of it means. That’s what our business is focused on now. As a juxtaposition, we started out with like, “Let’s do a 23andMe-like thing.” What we do now is we make the software to compare large groups of whole human genomes. We’re going after the folks that are doing country genome sequencing projects, where they’re sequencing hundreds of thousands or millions of people and trying to sort out what’s going on in there. Are they trying to do the whole genome for millions of people? The United States is doing that. Can you tell me a little bit about what that project looks like? There are over 50 countries now that are doing this thing. A fun fact that most people don’t know about that. If countries are doing it, what’s the example of a country’s project like? The one that’s furthest along is England, the UK. They have this project called Genomics England. It started out as 100,000 people and they did all of that. They did it for people generally that had gone through most of the medical system, hadn’t received a diagnosis and they were trying to still assess out what’s going on. At that point, they were given an option of, “We don’t know what it is. You can either be at a dead-end or we can sequence your genome. It’s totally up to you. If we sequence you, you’re consenting to research.” They had 100,000 people say yes to that and they were able to solve 23% of the cases. It’s pretty good. They were able to diagnose people who were unable to be diagnosed 23% of 100,000 people from genomic data. Diagnosed, maybe we shouldn’t use that word. It’s like a candidate is what they call it, a candidate-able gene. They made a very large dent. The essential problem then is even if you have the money and the people and you can do all these tests, it yields a ridiculous amount of data. How much data is sequencing three billion base pair are going to yield? It’s 120 gigs per person. If you multiply that by 100,000 people, that’s a good chunk. All the memory on my top of line iPhone would be full with my genome. The raw data of your genome. That’s just the raw data and it’s going to be more once I started trying to analyze it. The older we get, the more we fall susceptible to thinking one way is the way.Share on X In terms of getting into the tech side, this is where there’s a lot of debate about how should you do the analysis because the vast majority of the industry right now tries to take that 120 gigs and determine what’s important as part of it. They go through this whole process where they align your genome against a reference genome, which is a Franken genome of Craig Venter and a bunch of other people. They do a big diff and then they output the diff into what is essentially a glorified Excel spreadsheet. What they try and do is compare these Excel spreadsheets against one another. There’s a bunch of technical issues with doing that. One, you’re not going to see everything that’s in there. Two, if you’re trying to align against essentially what is mostly a European white male reference genome, you don’t see a bunch of stuff. There’s a lot of interesting challenges in the space of diversity within genomics and how do you get representative information about what’s going on in an individual? Are you making that up or is there any evidence that this is the case where people have gone back and said using the white male European reference turned out to make us miss out on this stuff though there are actual projects? There have been multiple efforts to make custom reference genomes for specific ethnic groups. There was a whole Han Chinese genome effort. The Japanese did a genome that was specifically for theirs. There’s an error of reference genome that’s in the middle of construction. They did their first version. They’re trying to do a second run. It seems that would be the thing that you would make by taking all the Japanese folk’s data, go find the stuff that’s the same in all of them and drop that out. It’s basic compression algorithm and then go looking into the rest. What am I missing here? Why is there work? How do you figure out what is present in there? We’re going to have to get a little technical in order to get there. Let’s start with what does the data look when it comes off the sequencer? A lot of people have the misconception that when you sequence a genome, it comes off like a book. You read it from the beginning to the end. It doesn’t go that way. In a super squishy way, it’s like how they did the human genome project, which is why we know what the order of a human being looks like, but it costs a lot of money to do it that way. It was slow, etc. They did this innovation where it’s called shotgun sequencing. What they do is they take your genome and they duplicate it 30, 40 times. They chop it up into 150 base pair long chunks. I’m glazing over a lot of technical details. For any of your technical readers out there, it’s not exactly that way but for the average reader, it’s 150 base pair long chunks. What the sequence reads is all of those 150 base pair long chunks. What comes off of the sequencer quite literally is a huge pile of text files. If you open up one of these text files, it’ll be 150 bases with a guess of the quality score for how likely it called that particular base correctly or not. That’s it. You don’t have any information about where that thing came from in the original. It’s the worst jigsaw puzzle of your entire life. It’s 150 base pair and base four is the notation. It’s got something 256 bits of data or something like that. Plus, the quality scores of how likely was the sequencer to call it correctly? Was it 90% sure? Where does that number come from? The sequencer generates it when it looks at it. It’s like, I’m 90% sure it was an A. I probably could have 36 or 34 or whatever copies of the same 150 base pair in my data. That’s how they fixed errors. That’s my check sum that they are correcting there because if I find ones where that’s a few bits off, then it’s easy to fix. If I’ve got essentially a 256-bit key, ostensibly looking at a unique chunk of the genome or are there duplicates? There are lots of duplicates. I’m trying to figure out how to put them all together in the correct order if half the battle. The reason why they use the reference genome thing is they take every 150 base pair long chunk and they look for the nearest match. That works great for small changes. In my 150 bases, if two of them don’t match the reference genome, that’s great. I know where that goes, but what happens when 50 of them out of the 150 don’t match? You then get to a place where there’s no longer a unique match. Where does it go? Does it go in this place in the genome or that place in the genome or this other place? What happens if the person has genetic code that didn’t show up at all in the reference genome, which totally happens? You can have a full 5,000 base pair of novel institution, which I know I do because I sequence my genome. You’re going to have this huge insertion. How do you figure out where that goes? Do I have to go do it the old-fashioned way? No, not exactly. What everybody else does is they try and do this process where they fish the things out of the garbage bin because when they don’t align, then they try and take all of the things that didn’t align. After the fact, they try and put things back together and figure out where it might’ve come from because there’s overlap with every little chunk. You could try and stitch it together and figure out where it goes. By then, you have already placed these little chunks potentially in the wrong spot. You’ve already biased everything against the reference. We try not to do that. I have an idea. I got my 150 base pair but if I have it overlap by 50 on each side and it’s only 50 in the middle, it’d be really good, but now I’ve reduced the efficiency of my shotgun approach by two-thirds but then I should get the order of stuff for free at the end. Why can’t we do that? They do a version of this. As I said, skipping over some stuff, it’s not 150 straight up. What they do is it’s about 500 or 600 bases. They read in from both sides of the chunk. There’s a gap in the middle of that they don’t hit. It’s about 300 bases. This is what is called a paired read. You have 150 bases, a gap of 300 where you don’t know what it is and then 150 bases. You can also get, to a certain extent, further with that because if one section aligns in this particular area and then this other one doesn’t align very well, then you can try and trace over that. It only works up into a certain extent for a 5,000 base pair insertion. It’s longer than the length of the overall chunk. The likelihood they’re going to have some error or dropout is relatively high such that you can’t assemble over it. Now that we understand the problem, tell me why you don’t have that problem. It turns out that there is another way of doing it. These little chunks are called reads. If you were to compare every read against every other read, you were essentially to create a probabilistic structure of how they could all go together without worrying about figuring out exactly how they go together. You could imagine that you could account for all of the possible paths and you’ll have a lot of information about what is more likely versus the other and you weight them. You could imagine that you could do that for one person. You could also imagine that you could do that for many other people and you could even overlay a lot of this information over one another. That’s part of the reason why population genomics is important. That sounds the big data approach to guessing more or less what the likely structure this is. Is there metrics now on how well that works? We’ve done testing a bunch of what are called truth sets, like golden datasets because one of the big challenges of knowing whether or not your stuff is good or not is how do you know what’s in there? There’s this one sample that has been sequenced a bazillion times with every single different sequencing technology out there. It’s run by this particular consortium out of NIST called the Genome in a Bottle Consortium. It’s very cutely named. They’ve done it with regular short-read sequencing, which is what we all described but they also have long read sequencing tech, which is much longer chunks like 10,000, 20,000 base for long chunks but it’s expensive, so nobody uses that at scale. Usually, it’s used for plant genomics, things like that. There are other various chemical sequencing technologies that you can use to try and get at these golden datasets. We’ve done a bunch of testing regarding the golden data set approach. Other technologies can see about 33% of the genetic variations that a represent. If you look at on a base for base basis, we can see about 72% if you’re using any amount of population style data. If you think about it, it’s intuitive. The burden of proof for finding a variation the first time is pretty high, but if you’re looking for evidence of whether or not you’ve seen that thing that you’ve already seen before, then it’s much lower so you can pick out things. If I do it the old school Craig Venter way, I get a complete and accurate genome. Is that right? You’ll get about as good as you’re going to get. That’s as close to 100% as we’re going to get. The best off-the-shelf technology we know of gets us to 33%. If you’re going to identify variations, yes. Your way, it’s 72%. That’s amazing. You can characterize it like that. Essentially the job of the company is to make the software tools to help us manage and analyze all this data at a large scale. What scale are we talking about here? How much data are you guys working with here? It’s 100,000 people or 350,000 people. It depends on the country. You guys have multiple countries you’re working with at this point. Is it a real business? Yeah. I don’t think that people would keep giving me money if it wasn’t. Is the customer is giving you money or investors? Both. If I understand all this correctly, we think that for a lot of the problems that people have, various diseases, different types of cancer and things, by analyzing their genome, we can probably at least gauge what risk they have of having this problem. In some cases, we might know. For sure you’re going to have this problem. I have the cilantro gene that makes me think cilantro tastes like soap. It’s pretty bad in Seattle because cilantro is everywhere. That’s not the worst one you could possibly have. It turns out there no other problems with me other than that. I got lucky. I suppose if we’d had a good analysis of my genome, I could have been more before the first time I had discovered that the hard way. What I’m wondering is if this is an important part of what we would want for this type of work. It’s tools that can handle the scale of the data that the testing is putting out and allowing us to analyze it in ever smarter ways. We would also want better testing or better ability to test a genome that’s more cost-effective. What else is missing? More research on what each of these markers would mean. That’s perpetual research project. I would say that’s the research project now. To give you a perspective, at this point as a globe, we have characterized about 1% of all human variation and associated with anything. When I say anything, I mean high breast cancer risk, everything. That means that there’s still a lot of stuff that we don’t understand even a little bit. If you think about it, to a certain extent, it makes sense why because your search base is large. It’s three billion bases. If you do a study of 1,000 people, that’s not enough information to be able to sort out much of anything, unless you happen to be looking at something that is so strongly correlated that it’s going to be obvious. We’ve gotten some of those great, low-hanging fruit things like the breast cancer genes, BRCA1, BRCA2. Those have massive impact. You can discover that in a sample of twenty people, which is how it was originally discovered. Is 100,000 people enough that we’re starting to feel confident or do you need 100 million? It depends on the disease or the particular phenotype. For some of them, 100,000 is going to be sufficient. For some of them, it’s not and we don’t know yet. That’s a mystery that we’ll find out. In some sense, to answer the question of to pick that mystery apart, you want to scale this up. In your life, what I suppose you’re hoping for is over the next 1, 2, 3 decades, we want to get from counting hundreds of thousands to millions or tens or hundreds of millions of people who we’ve got in the database so that we can start going after these things that have smaller that show up less frequently. Sometimes you’re going to get those one hits. If you have this single base pair change in this particular location, you have this significantly increased risk. For a lot of it, it’s going to be something more like if you have this and this, then you have an increased risk. You’ve got to have all four. You have to find all four to correlate them and that’ll take a lot of work. Do you think that the cases where we figure it out, what does that research look like? Is it lots of data and software finding it? There are a lot of analysis techniques that people had to use when the datasets are smaller. Now we’re entering a time where there’s enough data that you can do things like machine learning or even deep learning. You could use that technology to be able to assess it out. Deep learning is a little bit more complicated because search base is large and the number of examples you have are lower. You have to be smarter about how you do the feature detection, but you can make some of that stuff work. All of a sudden, you don’t have human beings that are trying to do basic statistical analyses anymore. You have things that can look for much more interesting, subtle patterns that frankly our little human brains can’t. In some sense, given enough data and desktop computers, we’re going to be able to set these things free and let them go find everything for us. To some extent. I don’t know if it’s that simple, but yes. Why wouldn’t it be? Can you think of a reason? What what’s missing from that? Machine learning is complicated. It can over fit easily. There are a lot of nuances, I would say. Plus, biology is a lot messier than people anticipate. I got interested one time. I saw this video of Danny Hillis talking about proteomics. He made a company called Applied Proteomics but his thesis was that cancer is a normal thing that your body does all the time. You got these cells mutating. Most of the time, nothing bad happens. They get flushed. Everybody is doing that. He is like, “Cancer shouldn’t be a noun. It’s more a verb. You’re cancering all the time.” You’re pairing and occasionally you screw it up. You don’t repair fast enough and things get out of hand and you end up with a tumor and then that breaks off and floats around your bloodstream and latches on to where it metastasizes and kills you. That’s the process. The way he described it was when we started the human genome project, we thought we were going to get the recipe for how to make the human. What we got after going through all that work and sequencing, the whole genome is more like list of ingredients but we still don’t have the recipe. The recipe is proteins and that’s interacting with your DNA. What he believed the next frontier was we need to go be able to sequence the proteins and figure out what they’re doing. I would say that to think that you’re going to get the whole enchilada in just genomics is naive. Frankly, to think that you’re going to get it with just proteomics is also naive. You got to have the whole thing. It’s going to be a combination of all of the omics’, if you will. Genomics, transcriptomics, proteomics, metabolomics, you name that. As I said, biology is complicated. Back to your question of like, “Can we have sort out everything? Can the computers work it all out?” Maybe if we gave it everything that it needed. Eventually, it gets all the data but right now we don’t even get all the data. It changes too. The genome, for the most part, it seems it’s stable-ish. It doesn’t change that much over the course of your lifetime. Certain cells might write the ones that become cancerous, but your proteomics and metabolomics, it changes by the moment. When I was a kid, we didn’t know any of this stuff. Not only did I not know it, the scientific community didn’t. In the last few years that we seem to have gotten our heads around things like the microbiome. To a certain extent, we know that it’s important. Do we know what any of it does? No. It hadn’t even been discovered. We thought your tummy is full of acid and then it eats up the food and then you poop it out. That was the entire understanding as far as I could tell. At this point, as a globe, we have characterized about 1% of all human variation and associated with anything.Share on X A lot of people still think of it that way. It’s way more complicated than that. I don’t know that much about it but you start to learn, you’re like, “I eat food that feeds a bunch of microbes in my gut and then they spit out what feeds me.” There’s a layer of indirection in there that there’s no measurement for. My microbiome is different than yours. It changes over time and none of us knows what we’re randomly shoving in our mouths. It’s crazy. It’s not that crazy. We have been doing it for thousands of years. That’s why we’ve got thousands of different microbes in case we eat that weird thing. This is also simplistic but coming from working on computers, my whole career, I lived through these multiple progressions where we started out with. I got the first digital camera with a CCD in it in 1990 or ‘91 or around that. I’m the world’s earliest adopter. I would go take pictures on the thing. It had a little Post-it note sized screen. I could show people immediately the picture that I took of them, which blew everyone’s mind because they’d never seen anything like that before. Times have changed. Before that, it was Polaroid. That was the only other option. Even Polaroids were slow. You had to stand up and wave them. Which apparently makes no difference, by the way. It’s detrimental. You do not shake a Polaroid picture anymore. The thing that happened is that camera sucked and the photos were 16k or something. Every year, it got a little better but you had this global scale argument going between photographers saying, “That digital crap will never be as good as real photography.” That progressed all through the ‘90s and into the 2000s. This asymptomatic progression where as the digital cameras got better, cheaper, higher resolution and better color management, all that stuff. All those guys started keeping their mouth shut because what they don’t realize is the chemistry was the best technology we had at the time to make photographs. Now we have a better technology and at the beginning, it’s low resolution. As the sensors get better and the data collection gets better and we can collect more data and we can collect data at a higher resolution than essentially the thing we’re sampling, that’s exactly the same progression went with audio too. Computer audio sucks, CD-ROMs aren’t as good as vinyl and all that. People still have that argument. They don’t understand how it works. It sounds warmer because there are imperfections in the vinyl. We go through those progressions but at some point with a lot of things, you get to a point where the resolution is high enough that you’re now dealing with high-quality, meaningful data. We’re there with things like audio, video and these things but we’re not there with all the biological stuff in a human sample. We’re close. It’s amazing, the progression. In the last few years, it’s been insane to watch because back then it was $100,000 to do one person. It would take 30 days of chemical churning to output the text files for one person. You had 30 days of computing to do the basic analysis to try and out, put the differences against the Craig Venter reference type style thing. At that time, the best sequencer in the world could do twelve genomes a year. Now the best sequencers in the world can do a whole genome for $1,000 and it can do 18,000 in a year. It’s been insane. It’s a different world. It’s been cool to watch it grow up. People have asked me like, “How could you even get into this field when you had no background in it?” It’s like, “No one had any background in it.” You think it’s one of those rare instances where if you get in early enough, nobody has a significant advantage over anybody else. That’s why I was able to do it. I hadn’t thought about it but that’s what happened with me and computers. It’s that I got there so early. There was no one else to call but me. Do you think that you can see any other frontiers that now? What’s the equivalent of that if you were 22 now and you knew that key fact to latch onto? Probably the AR and VR stuff. Maybe3 to 4 years back. Whatever’s happening now, I don’t know. It’s not like anybody has a ton of deep experience in how to make an AR or VR game. There’s some but there’s nobody that’s the premier expert that is taking out everybody else. If I was a young kid, getting into developing AR and VR games, that wouldn’t be a bad idea. I could see that. I don’t know what the super new hot thing is that’s coming up. I don’t spend time with the young cool kids anymore to know that. You hang out with the nerdy genomics people instead. How’s that going? I like it. Is it a class of humans, nerdy, genomics people? They’re great. They party a lot harder than you would think too. Especially the people that study plants and animals. If you want a raging party, go to the plant and animal genome conference in San Diego. It’s held at one of the lamest hotels in the world but it doesn’t matter. The lights are still on for the conference center, blaring and bright lights. It doesn’t matter. The second the music goes on, the dance floor is packed. I go to a lot of conventions for nerds, mostly computer nerds. One time I was at a conference called TiE, which is The Indian Entrepreneurs network. They’re like, “We’re the biggest entrepreneur club in the world,” because they’re from India and they have unlimited people. They have tens of thousands of members. I was speaking at the TiE conference. As soon as the conference is over, music comes on, everybody dances because they’re all from India and that’s normal thing for them. Did they lead a dance? That happened at the plant and animal genome conference. Somebody got up and led a Bollywood style dance. Everybody participated. It didn’t matter. I was like, “This is amazing.” They do if you’re at the plant and animal genome conference. If you go to the UDub to an entrepreneur’s class and talk to these folks, what do you tell them? Like, “I did it and I got lucky and you should get a job,” or, “Being an entrepreneur is hard but amazing. It’s like parenting. It will be the best and the worst thing you’ve ever done.” It’s close to the second one. I speak to the UDub a lot. I speak there once a quarter, maybe three times a year or something like that. A bunch of people came and spoke at my classes and it’s one of those pay it forward things. It makes a huge difference. For me, I remember that there were certain people that came and spoke at my class where I was like, “That’s cool. If she can do it, I can do it.” She was the CEO of Modumetal. It’s cool. They do the super-thin layering of metals in a specific meshing way. It could make armored cars but for way cheap and it’s way more effective. I remember watching her and I was like, “That’s cool,” or other people that were young that were coming back through. They were the graduates from 2 to 3 years ago, etc. I’m old now. I’m a ten-year veteran, which is bizarre. I go and talk to them all the time and the things that I say to them are it is going to be hard, so you had better pick something that’s flipping worth it. If you don’t and you’ve picked something because you’re only interested in it for the money or whatever, statistically you are way better off getting a job at Google or something. From a money perspective, in terms of expected value, if you’re in it for the money, don’t do this. If you’re interested in solving a particular problem, you’re passionate about having that particular problem be solved on this planet and you are willing to go through the pain suffering that will be required to do that, then you should do a company. Don’t pick something that you don’t love because otherwise you won’t stick with it when it gets hard and it will get hard. Do you think that advice is at odds with finding people who are motivated to sell, which is a big part of making it less hard? Motivated to sell what? Like the company? Something to make the company make money. It does seem that’s one thing that a lot of entrepreneurs have in them that makes them successful and take investors in particular to see it go because a lot of startups, most of them don’t fail to ship a product. Most of them fail to sell it. That is coupled with the advice of make sure you talk to your freaking customers. To be fair, when I started out, we had the exact same mistake of doing some amount of customer interviewing and then thinking that what you need to build and then building it without checking in with people. Being like, “It’s brilliant. It’s going to work. They’ll fall in love with their idea.” That has more to do with the inability to sell the product. The likelihood of burnout outweighs the likelihood of not being able to ship a product. I would say pick something that’s worth your life first and make sure you talk to your customers second, in that order. When we think about what is hard, what are the experiences that come to mind? Firing the first person that you ever have to fire. That’s a tough one. Maybe it’s not tough for some people but I care so much about people. In that moment where you’re letting them go, it’s easy to feel like a complete asshole. To think that you’ve screwed up or failed them somehow and to indulge in the conversation of how you’ve let them down, which you learn over time is not what’s happening and it’s not a healthy conversation to be having. The first time you do it and when you’re new to it, it’s an easy trap that pretty much everybody falls into. That one sucks. Running out of money for the first time, that one sucks. I don’t think people talk about that one very often, but I don’t know any entrepreneur that has gone for something relatively risky that hasn’t gotten within days of running out of money or if it has run out of money. It’s not like it happens only once. It’ll happen multiple times and people never tell you that. I tell the poor little entrepreneurs and it scares some of them. Some of them think, “That will never happen to me,” and that’s fine. It’s one of the naiveté things and that’s cool but that sucks because then you had to lay off everybody because you as a founder, you’re financially on the hook for anybody’s salaries, if you keep them past, etc. That stuff is rough. That stuff’s the hardest for me personally because it’s all about the impact on the people. Other people might have a different answer to that. I feel like I’m talking to my friends to go in with this crazy plan and when it doesn’t work out, I do feel I’ve let them down. One of the ways that I often let them down is by not firing people that I should because I’m very optimistic about people and I see the potential in them and those things. Especially as somebody who does care about people first, how do you end up getting through that and making decisions? One of the biggest alterations that I made in my overall leadership, I say moderately early on, was finally being transparent about where we were from a financial perspective at any given moment. In the first few years, I thought that I had to have it all together and I needed to put up this strong front of like, “Everything’s fine and it’s great.” What I realized is that it led to situations where people were caught off guard and surprised when shit was not fine and we were three weeks from running out of money. At this point, pretty much everybody in my company can ask me at any time how much money do we have left and how many months of runway and all of that stuff. A lot of people don’t do that. I can understand why they don’t do that. Maybe that does not work at scales of companies but for the scale that I’m at and for the risk that people are taking on now, I feel it’s the right thing to do because of exactly what you said. I’ve asked people to go with me on a crazy journey, crazy mission. It is highly likely to fail and everybody’s got a different risk tolerance. By not providing them that information, then they have no ability to choose for themselves about what’s going to work for their particular risk profile. For me, that’s where it gets irresponsible. If I provide them the information and they stick it out anyway, then they chose but they were choosing with full knowledge and then that’s okay. If we run out of money, it’s not a surprise even. In some cases when that has happened, people have been willing to stick it out for long periods of time until we get it worked out. I’ve been shocked to a certain extent in the cases where that has happened by the ultra-low churn. You might lose one person or something like that. For the vast majority of the times, pretty much everybody has stuck it out and come back, which is crazy. It has to do with the fact that they also feel like they’re trusted enough with the information and that they’re a partner in it, not just a standard cut the check employee, which is what they would get at a normal place. It probably varies depending on the scale of the operation because at my last startup, I tried to let the team not worry about money. I had to worry about it a lot, but I didn’t show them that because I wanted them to be able to focus on doing their job. It was probably the wrong way to go. I can see it both ways because I also tried that approach too. I also think it depends a lot on the type of people you hire. After going about this for a couple of years, we started to place a very large emphasis on risk tolerance as a factor for when we were hiring. We include a question in every interview, which is, “What is the riskiest thing you’ve ever done?” If you don’t have a good answer for it, this was probably not the company for you. I had this one woman, she was super well-qualified for what we were trying to hire. Her answer to that question was driving in the rain was the riskiest thing. I was like, “This is not the place for you because we were going to skim the treetops multiple times and we might even crash land and I need to have people that can handle that and not freak out when it’s happening. I’m going to have other things that I’m dealing with when we’re dealing with the crash-landing situation.” I’m making this up here. I don’t know if this will work but I imagined that I could tell people more upfront and say, “Here’s the situation. We’re trying this crazy mission. It’s probably not going to work. We’re probably going to crash land and all going to end up unemployed but we’re going to learn a lot along the way. We’re going to do the best we can. We’ve got some shot at getting through and if we do, it’ll be amazing.” I feel like if I could provide all those disclaimers upfront, then it wouldn’t be so bad on the day when I got to either fire them or lay them off or shut down the company or those things. We do that for people that are coming in that are new because we’re interviewing right now. Before we extend you an offer letter, it’s like, “Just so you know, this is how much money we have left. This is what you should expect.” I tell people upfront, “I cannot guarantee you employment past X date and you have to be okay with that. Clearly, we have been around for a long time and yes, there have been some bumps and it’s unlikely that you will be completely out of a job and you are joining a startup. It is a risk. Make sure you’ve had a conversation with your significant other if you need to do that before you accept this job.” Do you manage to scare anybody off that way? Yes. As I said, at the moment we’re dealing with an emergency landing situation. They need to be able to put on their own oxygen masks first. I can’t do it for them. You talked about this earlier but if you could do anything else, what would you do? Real companies or fantasy companies? Anything. Not even accompany to go on and walk about? I’ve considered that. I would walk about for about three months and then start another company. I tried to go on vacation for three days and I was stir-crazy. On the vacation front, it’s good for me. It’s very important. Long periods of time not creating something, not building something, not having a team, team is important for me. If I didn’t have a great team. I don’t know if I would put up with all of the crap that I’ve dealt with. I totally have fantasies about like, “Someday when I have achieved my mission, I’ll sell and then I’ll go and become a yoga teacher in Bali.” There’s nothing wrong with Bali, but I would get stir-crazy quickly. I don’t know what it is that I’m here to do. This is more life philosophy stuff but each one of us are here to contribute something, whatever that is. One of the things that I’m here to contribute is to create leadership and lead and inspire others to create great change in the world. That’s what I think I’m here to do. Genomics is a huge arena that I want to play in. At some point, neural augmentation would be cool. I’ve thought a lot about that. We’re still way too early, so I’m waiting for the market to mature on that one. A Matrix-like thing, I don’t think it’s completely insane. The other area that I’m passionate about is entrepreneurship and having people be supportive throughout the journey of it because entrepreneurship, this stuff can get lonely sometimes. Even if you have a great team, if you are the leader of the organization, there still is sometimes stuff that only you get to worry about. I have been good myself about building myself strong networks of people where I can go on talk to other human beings that get the thing I’m dealing with. Some human beings will never have the experience of payroll and some will. I participate in things EO, Entrepreneur’s Organization. That one’s great. I went to an EO event and I couldn’t believe how fun these people were. They’re a great group. The events are awesome but the thing that’s most valuable to me is that I meet with a group of people. It’s up to ten people in a forum, that’s what they’re called, and you share the highest stuff and the lowest stuff. It’s a mandatory attendance. You can only miss one a year. To get CEOs to work it out such that you don’t, you have to be committed. It creates a space where you can share anything personally or professionally, whatever it is that you’re dealing with. The vast majority of entrepreneurs don’t have something like that. While EO provides that for people that are at a level because you have to have raised an amount or have a certain amount of revenue in order to be part of that. There’s an absolute necessity for that for the people that are starting out. The people that are coming out of the entrepreneurship class that have won the business plan competition or whatever. They don’t have the network. They don’t have anybody else that understands what they’re dealing with. I remember what it was when I was first starting. Not that many of my friends were going down that route. I had some but not a lot. I had a number of my friends that were like, “You seem stressed out. I know this recruiter friend at Amazon, we could get you a regular job. You wouldn’t have to stress out.” They’re trying to be helpful but it’s in that moment it was the opposite of what I was looking for because you’re already doubting yourself enough at that stage, not that ever goes away. You’re still doubting yourself and your capabilities enough at that stage that’s the exact opposite of what is helpful. There’s a real need to have some network or space where people can be around other people that are dealing with the same thing. That’s important not from a sanity perspective because entrepreneurs also deal with a lot of mental health issues and there’s lots of statistics to back that sucker up. People would be more successful if they had other people they were around. That’s part of the reason why you see things the YC effect because I went through Y Combinator. How was that? It was awesome. You did that ten years in your company. We were acquired and then we unacquired ourselves. This is a reboot to focus entirely on the population genomics side and YC is what we took it through. It’s a restart. You applied to Y Combinator. You got in. What was the program like? You meet on specific days of the week. They’re large enough now that it used to be always Tuesdays but it’s now you’re either in the Tuesday or the Thursday batch. Is it just in the Bay Area? I went down every week. They usually ask you to move there. I did the math and the flying there every week versus living in the Bay Area, it’s cheaper to fly. Entrepreneurship can get really lonely sometimes, even if you have a really great team.Share on X How long is the program? Three months or ten weeks. I joined late. I originally wasn’t going to apply at all because I was like, “I’m a ten-year-old company. They’re not going to touch that.” A friend of mine said, “Ginkgo Biosciences joined YC when they were seven years in and it worked out well for them, so you should apply.” I did three weeks after the program had already started and I had an interview and then they flew me down and then they told me yes. The next day I went to my first thing. I don’t know what the beginning is like, so I can’t provide any information about that because I wasn’t there. What it is going forward is you have a group that you meet with every week. You have office hours with your YC partners. You’re assigned 1, 2 or 3 partners. You work with them and you’re looking to achieve specific metrics and improve those over time. They prepare you for fundraising. I would say that is the arena where I got the most out of it. I’ve done a bunch of fundraising successfully before. I’ve raised $5 million before without doing YC. What I can tell you is that they have that down to an art form. I was making a bunch of mistakes that I didn’t even realize. The primary one being that when you’re so down deep in the weeds, you think that everything’s important. I would have conversations with investors and try and tell them everything about how the sausage is made and they don’t need to know that. I thought I’d already scaled it back. The reality was that no, I was still telling them way too much information. That, for the most part, would scare people off because they were like, “It must be so complicated. I can’t possibly understand. Therefore, I can’t invest because I’m investing in an area that I don’t understand. I’m going to make a stupid mistake.” How do you tell your story in a way that still gives them all the information about what’s going on but doesn’t freak them out? I had that problem too. I want to explain everything. I’ll tell you for seven hours if you’ll listen what my plan is. Did you go raise some money after YC? Is there any way to characterize where you end up? What’s the size of the pitch for investors now? Is it like I do the whole thing in twelve minutes? They get you down to two minutes. How long would it have been left to your own devices when you started? Was it two hours? The shortest that I would ever do were maybe eight minutes or something like that. There are further diligence talks, etc., but I would try and give them all of the information upfront. The art is no, you provide them with all of the information that they would need to be able to say, “Yes, I’m interested,” and create a compelling case. You can feed them the pieces of information that they want as they request it, but don’t give it to them unless they ask for it. Otherwise, you’re just confusing them. The art of the two-minute pitch is incredible. I don’t know if you’ve ever watched YC demo day pitches. They’re amazing. What you put together so compelling. I listen to my pitch and I’m like, “Damn, that’s good. They’re great.” That’s one of the biggest things that I got out of it and they have a huge network of other entrepreneurs. It’s one of those things where you’re part of it for life. You are now in a place where you have access to a network of 4,000 founders. You can post on their internal forums for virtually anything and get responses back in hours. I asked for crazy stuff. I was like, “I’m looking for the introductions to the Ministries of Health for the following countries.” I got four introductions in four days. I was shocked. I was like, “That is more business development action than I’ve seen in the last six months.” It was crazy. That network and that collective experience is needed not just in the work part of the entrepreneur’s lives but also in the living part because also people go home. I don’t have this problem with my particular significant other but I can tell you having been at EO, for the vast majority of people, their significant others think that these people they’ve married are crazy. How do you have an environment that has those people be supported too? There’s a whole missing ecosystem. Back to your original question of what else would Ito work on, I think I would like to work on that and I have a lot of ideas about how we could solve that but one thing at a time. I was thinking as you were talking, being on a team is important to me as well. I don’t think I’ve been as good about crafting that over my career as I would have liked. I’ve been fortunate to have been put on some good teams. What do you think is necessary to craft one? I’m trying to figure that out. Looking around, the way society works, we have a lot of hero-worship. Even people who are sports fans, you’re a fan of a team but that’s not even a team. That’s whoever they hired this season, you’re more of a fan of the logo and maybe a fan of a player. You follow that player or rock stars or Instagram people or whatever. It’s not a team that you are observing. It’s not team worship. There are probably exceptions. You might be a fan of a company that makes a product you or something, but you don’t get to see teams. Even in reality TV, you see a lot of stuff where people are against each other but not teams. Things like a TV show or a movie or a company or everything, it’s all stuff created by teams. There’s some disconnect there. I always was wanting to be on a team, but figuring out, how do you make that and how do you make it good. That’s all stuff that nobody knows. You have to figure it out through trial and error. It’s clear that I have capabilities in that area because they seem to be able to do it. I’m trying to figure out how I would articulate like, “What is it that I’m trying to do exactly? What makes it work?” Safety, it’s one of the biggest ones and you can see research on this too. Psychological safety in workplaces, etc. There’s a whole Harvard Business Review thing about this. Psychological safety is also what breeds innovation, as it turns out, because if you feel you’re in a safe enough environment where you can throw out that crazy wacky idea and not get shot down for it, that obviously encourages you to do that. I would say safety is one of the biggest ones and safety shows up in a lot of different arenas though. It’s not safety to be able to say whatever it is that you’re thinking but it’s also knowing that you’re going to be the person that’s leading is going to make sure that you’re taken care of. I’ve asked people about this because honestly, sometimes I’ve gotten confused in the past where I’m like, “Why are you guys still following me? We have gone through some serious crap at this point. Why are you still here?” For them, a lot of the answers have been like, “I know that you’re going to have my back and I know that you are doing everything that you possibly can to make sure that we’re taken care of. I trust you to do that.” That’s the biggest thing that I would say if I had to point to anything around. I sometimes wonder if people who aren’t performing well, does that same things still apply? I’m making you feel safe. You’re not performing well but you’re getting paid. There’s no job security risk here. If I tell them that you need to step up and perform better or there’s no job security anymore, how do you reconcile that? It’s one of the things that I should to figure out. My opinion is that when people aren’t performing in jobs, something else is off. They’re either feeling confronted and they’re not willing to ask for the help that they need or they have something going on personally. Creating enough safety such that they can be like, “My grandfather is in the middle of passing away,” or, “My mother was diagnosed with cancer. I’m going to need some time.” Let me think about the times when people have been underperforming. It usually has to do with they’re dealing with something personally with their health or somebody significant in their life is dealing with something health-wise or they’re afraid of looking dumb so they don’t ask. Those are the places that I’ve seen the most non-performance. It rarely is that they don’t understand. I am working with people that are very smart. For me, it hasn’t been a lack of understanding or lack of capability. It almost always is people dealing with their own internal conversation about how their work is good enough or not good enough and the fear of being able to put it out there or not. That’s what I have found. Have you got any questions for me? I have tons of questions. How did you get to be the way you are? You’re a very unusual human being. What do you think is unusual? Don’t hold back. You’re obviously smart. You have gotten to a place in your life where there’s a certain, “I don’t give a fuck” attitude. You are very confident in whatever it is that you say and you don’t seem to care if people are like, “That dude’s overconfident,” because I’m sure that people say that to you and you clearly don’t care. You have this huge, bizarre diversity of interests, including dance, which I can get because we both dance. I know a lot of smart people from the computer science side or etc. and they don’t usually come in your form factor, if you will. One of the things you’ve said, like why don’t I give a fuck? Is it that you don’t or is it that everybody thinks you don’t? No, I do. I care about a lot of things. I don’t care about a lot of other things and I’m adamant about not caring about some of those things. You could say part of it is I’m older than a lot of those other folks that you know that are computer nerds. I grew up in Alaska and there was nobody for 1,000 miles who knew any more about computers than me and I couldn’t learn from anyone else. I was learning in isolation. I literally learned how to program by reverse engineering 6502 assembly language. This is the machine language for the Apple II. It’s not how you learn to program. I’m a shitty coder because everything I learned was before software engineering was a thing. I was so excited about computers and I would try to get other people interested in them. Did that work? At first, no. I would try to convince everybody that, “This computer is going to be amazing someday,” and nobody believed me. I was in a small town in Alaska. It was lost because but I had a bottomless enthusiasm for it. That is part of what got me to trying to be able to explain things. I was trying to explain these complicated technical things to people who not only didn’t understand but didn’t care. I had to be able to simplify very complex concepts. In some sense, I’m still doing that. You do a fair amount of speaking gigs and that’s what you do all day. Also feeling like an outsider, a loner as a kid because I wasn’t into sports or electric guitar and the normal stuff. I had to be okay with not being cool. Do you still think that you’re not cool? I think you’re cool. Revenge of the Nerds. I don’t feel that so much anymore but that’s part of one of the things that’s amazing to me about dancing. Being a salsa dancer, you show up and I’m on the same level as the Mexican dishwasher. It doesn’t matter how much money you make, how smart you are or what you’ve done in the past. No one gives a shit. You’re there and you’re not cool. I’m very specifically not cool when I show up dancing. You get a little bit cooler over the years and as you get better and as you get shirts with buttons on them and shoes that are not dirty, stuff like that, you can get slightly cooler in the dance community. Do you think that’s the key, the shirts with buttons and the cool shoes? Definitely. The salsa black belt is every year you advance levels by getting one less button. The guy who’s got a deep V with one button at the bottom, that’s the best dancer in the room. You can see it. I have to test this theory. Does it only apply in salsa? Do you think it applies in another dance? It probably carries through at least bachata but these are Latin dances and I don’t know. Those things I’m describing pretty much hold worldwide. As you know with Zouk and the very niche dances, you end up with these very strange communities with their own idea of what’s cool. There is always something. I get a lot out of that. It’s a different type of society. It’s a different angle on the world. It’s a level playing field so you meet people from all walks of life. I don’t bring anything into that room that makes me cool. I have to be a good dancer and I have to be cool to the people I’m dancing with and those things that’s how you got to do it. That’s good for you. It’s hard. It sucks. Especially as a lead, you have way harder of a job. I have tried leading. It is so much decision-making. That’s why I liked being a follower because I make all the decisions in my job. This is the one place where I’m like, “I’m not make any decisions. It’s a different role. It’s a different art form. They’re both cool but being a lead, even now, I’ve been dancing years and I’m not the best dancer but I’m competent. I show up in a new town or nobody knows me and I do this all the time, traveling for salsa, “Who’s the weird guy with the glasses on?” “I don’t know. I’ve never seen him before.” “Do you want to dance?” “No, thanks.” You’re at the bottom again, every time. Those things are good for me but one thing I was thinking of is just because of the way events played out, I didn’t go to college. I didn’t get a degree. I’m not qualified for any job on earth. There’s no job I can apply for and get. I don’t think I’ve ever done that in my life. If you’ve got, I don’t know that you would like it. Maybe not. I don’t think we’re ever going to find out. At this point and up until few years ago, I almost felt ashamed of it. I didn’t do that work. I didn’t get that degree to get that certification to get trained properly as I was talking about software engineering. It was a little too early. Universities couldn’t teach me much about computers yet and so I didn’t do that. Companies would pay me to buy a computer for them and so I did that but I always felt some of that imposter syndrome. What would I know if I’d done that? It’s because I don’t know, those things. For a long time, I felt that was a liability. What happened is society changed. Nerds won. We built the most successful companies in the world and everybody wants to be Mark Zuckerberg now and parents want their kids to grow up and be computer programmers, not lawyers. All that’s amazing. There are all these fables in people’s minds because, “Steve Jobs didn’t go to college and Bill Gates dropped out of Harvard.” Now when I tell people that I didn’t go to college, they think, “You’re too smart. You didn’t need to go to college.” I’m a computer hacker, which is like being a fake scientist. It’s like a scientist but without all the formal training and accountability. You can do whatever. No one’s expecting a computer hacker to be particularly diligent about anything. That has bought me a lot of self-assurance and freedom. I can sit down and ask you all the dumbest questions about genomics and I’ve got no professional reputation to protect because I’m a computer hacker. I’m already suspect. That worked to my advantage. That’s why those things you described that you see in me, it comes from having to make my own way. I’m not counting on anybody to give me anything. I’m not counting on that degree or certification or job title or anything. I know that I’m going to have to earn everything I got myself and build it. Second, the other thing you described, the don’t give a fuck thing comes, it’s important to me to be beholden to no one. I want to be only beholden to what’s technically true. What is the truth as best as we know it, not what is politically correct or not what’s in vogue or not what other people’s opinions are? That’s important to me. If I can’t do that because of the company I’m working for, the job I have, or the society on part over whatever, then I can’t be a part of those things. I maintained a lot of independence because of that. Where do you think that came from? A part of it could be Alaska was a weird place to grow up. Everybody there was an immigrant. It’s like Israel. Israel’s a fake country that all of a sudden, many years ago it was a startup and people moved there from everywhere and it’s this melting pot. Alaska is like that. Right before I was born, people moved there for the oil industry. There wasn’t a lot of people there before that, or at least not a lot of any kind of people. There were certainly Alaskan natives and stuff. They’re all Americans but they’re American immigrants. It’s a state full of people who came to Alaska to get away from somebody or something. It was hard living. The conditions are hard. People had to work to get by day-to-day. You have to shovel a lot of snow and it was dangerous. That attracted people who were very independent and felt they could make it all work and didn’t, so they had that attitude. I suppose, I grew up appreciating that aspect of those folks. Alaska is tamed now. There’s drive-through everything and everybody there have a suburban and drive-throughs. The Starbucks has a drive-through, the dry cleaners have a drive-through, the restaurants and everything you can drive because it’s snowing and cold. They didn’t have pizza delivery when I was a kid. You go get the pizza or you stay home and make one. That rubbed off on me some and then also I’ve been at it long enough that I can see how other people’s life choices have played out. I can see the way people chose to play it safe. They chose that college. They chose that degree. They got that job. I became a dentist. The first day of your career as a dentist, there’s a spreadsheet that will tell you exactly how much you’re going to make over your entire career and how much to put into 401(k) and how much to put in a mutual fund, what to do. That plan is safe. That appeals to people. People are over-optimizing for safety. You get those predictable results and it’s not all that safe anyway. I don’t want to make those choices. For me, I always tried to make good life choices, but I didn’t optimize for safety and security. I ran out of money a lot of times. Almost no company I ever worked for still exists. IV exists. That’s one. There are two. There’s Blue Origin. It’s a company has got thousands of people building rocket ships but it’s not a real business yet. It’s a weird one. Other than that, no company I’ve ever worked for still exists. They all went out of business because I was too early or the idea was too crazy or whatever. The amazing thing is I’m fine. The Silicon Valley mentality. I come from the Silicon Valley of the ‘80s. That was very much about using a startup as a vehicle to invent a new technology, bring it into the world, create a market, make something people didn’t even know they wanted. All that is what I grew up with and what I believe in and what I want to be a part of and what I want to do. That’s been diluted and eroded by a lot of what’s happening in the tech industry now but that’s still what I’m for and what I want to do, and so I did. I worked for startups, so a lot of them either I started them or my friends started them and I worked for them and even so they’re often too early but every single one of them, all those technologies exist now. They all exist in the market. We were right about every one of them. We’re ten years too early. Do you think you’ve gotten better at being able to predict when it’s too early or do you think you’re still just as bad? Now I know the difference. I’m not better at predicting but I know when I’m too early and I don’t make the same kinds of bets on things. I wouldn’t start a company that’s ten years too early again. What do you think is ten years too early right now? All kinds of things. Fusion reactors, quantum computing, probably a startup based on CRISPR, all things that are ten years too early or they still need research. They still need economies of scale and cost reduction. They need a market demand. There are so many things. You can’t create all of those things all at once as a small little tiny startup. You have to pick one. It’s like, we got to get lucky about one thing, not a Rube Goldberg machine of seven things that all have to line up. The companies I start are quite pragmatic. They look a little deranged from now outside because of how I described them. I’ll use technologies that I’m comfortable with but the rest of the world isn’t. I’m obsessed with rearchitecting entire industries using machine learning because this is a superpower that we have that we can use to change almost everything that humans do. It’s scary to everyone except for the handful of people who understand the technology. It’s hard to get your head around that but I don’t have those same problems. For me, if I can look it up a business or an industry and understand how it’s structured to understand its problems, then I can use those tools to radically reinvent how it’s done. That to me is exciting. What for you is the next thing? It sounds like you’re interested in that particular aspect. Is there a particular field that you’re thinking about yet? I’ve got obsessed a long time ago with these ideas around automating apparel manufacturing because this is a very manual industry. It’s a massive industry. The numbers, I say these almost every day, “Somebody but $2.4 trillion a year apparel, that’s almost as big as the oil industry or cars maybe.” This is a big industry. Every human on Earth is a customer. In 2019, we made 100 billion garments not for the 7 billion people on Earth but the 1 billion people who buy them. Twenty-five percent of those are in the landfill already. Of those, 30% of them still have the tags on. This is one of the most wasteful industries on earth. It’s sad because it’s responsible for a massive amount of freshwater depletion. This is a major natural resource for humans that we’re depleting. We’re running out of fresh water and it’s not easy to make more. It’s an industry that is polluting rivers and killing off all the life in them. The cities where your jeans come from in China, everyone has some kind of cancer. They have lesions on their skin. Everybody is suffering from this industry and we keep making it bigger and keep making it worse. What do you think the solution is? A big part of what I do is I try to understand problems and this is an industry that’s full of problems. They collected every problem and then they didn’t adopt any technology. They haven’t installed Windows 95 yet. This is an industry that they’re sticking their heads in the sand about the technologies we have that could change it. To me, that looks like a ripe opportunity and a chance to rearchitect the industry without all those problems. What do you think the biggest thing is? Part of it, to me, based on the statistics you said, it sounds like there’s a supply-demand issue and that they are not very good at predicting what’s going to be interesting in fashion. The way I think about it, they have got to have the lowest cost labor, which means you’ve got to do it in Asia, which means you have long product cycles. Six, seven, eight, nine months is normal for the fashion industry. That means you’re doing speculative manufacturing. When people have been underperforming, it usually has to do with what they're dealing with personally.Share on X It’s definitely not just in time. Just in time is a ‘90s term that means all of the components from the supply chain land at the factory in time to make the batch. Not like it’s produced at the time that you need it. On demand means I produce it after it’s sold. At the moment when I have a buyer, then I produce it. I’m trying to rearchitect the apparel industry beyond demand. That’s what Bombsheller does. That’s the company I built to prove that concept. Now that the concept is proven, I want to go do that at a larger scale. Anyway, that speculative manufacturing drives all the problems in my mind because they’re producing stuff and then discovering later whether they guessed right or not about what would sell. In 2019, H&M burned $4.3 billion worth of clothes. H&M is the bottom of the market already. There’s nowhere you can take it, “It didn’t sell at H&M. Send it to TJ Maxx and sell it for 50% off.” No, they’re already the bottom. There’s a liquidation after H&M. It’s obscene and it’s bad for humans. It’s bad for the world. It’s our responsibility to clean these things up. Historically maybe we didn’t have that opportunity, but we certainly have it now. In my mind, you’re responsible not to go use these technologies to solve these problems and we can do it. That one looks easy to me. That’s not hubris. We’ve already proven a lot of this with Bombsheller but it is still work. We have to build a company and build a brand to build factories and ship a lot of products and then get the rest of the industry to copy us. What you’re looking to do is you’re looking to be the demonstration such that they have to deal with and compete with you and then they copy. You’re like, “My work here is done.” By then, I can be the apparel equivalent of Tesla or Uber. The way that they’re structured is different. They aren’t in a position to make the change. I can take over the industry. We’ll see. I am curious about you being a dad, the choice to do that and what the whole process has been like. I have people in my life now that have tiny humans that are getting less tiny and I’m curious your perspective on that whole thing. My daughter was adopted from Ethiopia. Her mom and I were married at the time and we’re not anymore but when we decided to adopt, you look at these different kinds of adoption programs and the most popular ones here in the US are Eastern Europe. The reason is because you get white kids. It’s not politically correct but there’s higher demand for them. It’s unfortunate because a lot of the adoption programs in Eastern Europe come with a lot of problems. There’s a lot of fraud, lots of fetal alcohol. These kids are in fetal alcohol syndrome. There’s lots of abuse in the orphanages and things. These kids have it rough. You get over there to pick up a kid and find out they have siblings or find out they have Down Syndrome. Everybody has a horror story. It’s a sad situation but you still want to do the best you can for those kids. That’s one class. American adoption programs within the country are popular but most of those are set up so that you meet a pregnant mom and work out a deal with her. You can take the baby home when she has it from the hospital. She gets two days to decide if she wants it back. Those are the two craziest days of her life with grandmothers and aunties breathing down her neck. That didn’t sound like the stress I wanted. I made a spreadsheet of all the different countries you could adopt from. It’s not every country, it’s like fifteen countries. That has a paved route for adoption to the US. We did a comparative analysis and figured out, “Ethiopia sounds amazing,” and it was. Ethiopia, they don’t even drink. The country is dry by choice. In fact, the emperor back in the ‘70s tried to get them to start drinking and have bars as a way of improving tourism. It’s almost no alcoholism. There’s no drug abuse. The orphanages are happy places. Ethiopians are super genteel people. It was amazing. That worked out. It paved the charts for all the things we wanted. Those other things like, “Can you choose the gender or the age of the kids you get.” We went through all that, and you do nine months of paperwork and then you get a kid. That’s the start of it. It’s also very fraught with anxiety and there’s a moment along the way where you get what’s called a referral and that’s where they match you to a kid. At that moment, it becomes so real. I got a little photo of the size of a postage stamp of my kid who I’d never met halfway around the world, sitting in a third world country, waiting on paperwork from the government. That starts to get hard because I’m like, “Let’s go get the kid.” We had to wait another four months. That gets hard. I go into commando mode. I’m like, “We’re going to parachute in and extract the kid.” How old was she? She was eight months old when we got her. She was, undernourished, had scabies and Giardia and couldn’t sit up. We went to pick her up in Ethiopia. We spent a week or so there and every day we’d go to the orphanage. She’d spend the day with us a part of the day with us getting used to us. She goes spend the night there and they had nannies and all this stuff she’s used to there. She wouldn’t take a bottle from us and it started to get a little nerve-wracking because we know we’ve got to get on a plane for 33 hours to get her home and she’s not taking a bottle for us. I would go to the orphanage. I would get the nanny, the baby and a translator. I would say, “She’s not taking a bottle for us. Can you show us how you do it?” The nanny is an Ethiopian woman who would grab the baby, stick the bottle in, everything would work fine. It was amazing to see. Even at that age, even at eight months old, she knew that you don’t take a bottle from white people in black clothes. It’s black people in white clothes. She had that and it was amazing. After a week, she started to finally take the bottle from us and all worked out fine. It was things like that are amazing. We got her home and even flying home from Ethiopia, up until that moment the year before, you wonder about everything. You wonder like, “What’s it going to be like being a parent but also what’s going to be raising a black kid in a white neighborhood? What if I don’t like her?” I got other things going on. How are the hormones that are going with? How’s that going to work? By the time we landed the plane in Seattle, that kid was 100% my daughter for life. I was completely in love with her. I will never leave her, everything about it. It’s incredible. No question. That was years ago and not a moment of hesitation since. Another weird thing and this is an interesting thing about Seattle. You would think it would be a little bit weird sometimes. You got this mixed-race family, your daughter’s got an Afro. Am I doing a good job of keeping the braids in it? There might be some moments where it’s awkward. Never once. Nobody’s ever said anything disparaging about our family or even mildly awkward. That’s one of the amazing things about Seattle. That’s not true in a lot of places in the world. It’s not true where I grew up. It’s not true in a lot of places I’ve traveled to. We’d be weird. Here, it’s no problem. Everybody’s supportive. Everybody accepts the whole thing the way they should. It’s cool. Anyway, so that’s the origin. How old is she now? She’s in middle school. She’s super precocious. I wouldn’t have it any other way. Dating’s coming up soon. For her. Maybe, I don’t know. It’s extreme. Every stage of it is extreme. Every stage of it is overwhelming and you can’t believe how much work it is. What’s something that you didn’t know where you’re like, “No way?” They evolve to command all your attention. She’s a survival of the fittest rock star already from the day I got her. She was abandoned in Ethiopia. She’s not going to let me leave her for dead. She commands all your attention and it’s how she’s evolved. It’s hard as a parent because it’s relentless. You don’t get a break. Anything else you can be like, “Fuck off. I’ll call you back tomorrow,” but not being a parent. She’s on your mind, 24/7. Especially as a baby, you don’t get a break all day. When they’re a year old, you’re like, “We fed her. She’s had her nap. She peed. We changed her diaper. Everything’s fine. She’s playing with a thing. I can call the electric company and pay my bill.” That’s about as much attention as you can get and then you’re anticipating it. How do you run a business in the middle of all of that? It’s your wife who watches the kid and you get away. That’s the way to do it. Don’t be a mom, be a dad because that’s the winning strategy. Moms, I could never do that job. It totally consumes you because my daughter’s mom, her brain is fixated on the kid’s needs at all times. She knows when Sion has to pee about a month before Sion knows she has to pee. She’s focused on it. It’s an amazing and wonderful gift that she’s given up her entire life to be a mom. It’s intensive. I got a break for a few hours a day where I could go to work and get away. It’s insanity on a parent. How do you think that people do that? Here’s the thing. One parent stays home isn’t an option for the vast majority of people, at least in the United States, because of the need for double income. How do you think about that? When you’re on a farm, kids are an asset that can work for you. In a city, kids are liabilities that are going to cost you almost every dollar you’ve ever made. You should not have kids. That’s the right answer. If you can’t get away with not having kids, at least adopt a kid and try to keep it to one so that your because your life ends and the little kids’ life takes over. That’s not an economical thing for most people. We’re lucky to be able to afford to raise our kid in the city and do okay. The right way to do it. I had a friend from Zambia. She grew up in Africa in a village where it’s a whole bunch of kids. Some of the moms have died of AIDS. You have a kid and pop it into the village and the village raises all the kids in a giant swarm. It takes a village. She told me, “She can’t imagine raising kids in America.” If she has kids, she’s going back to Zambia because she needs a village and you can’t get one here. This is an interesting question. I’ve been thinking about the whole village concept when it comes to entrepreneurs and families. I’m very interested in co-housing and all of that stuff. How do we reinstitute the villages? Do you think that there’s anything that’s fundamental with our society that is preventative of villages? Do you think that it’s fell out of vogue and now we’re realizing how much we’re paying the price for it and now it’s going to come back into vogue? We’re definitely at the point where we’re realizing we’re paying the price for it. I feel that way. Even where I grew up, my family was small. I had a brother and my parents. We didn’t have any direct relatives in the state. My ancestors were in other states. My ex-wife’s family was big. They also had immigrated but they have big family concept. There were five kids. Most of the kids had kids and there’s a whole tribe going there. They all hang out at grandma’s house on weekends and it’s a village thing. They get a lot of support from each other. Grandma helped raise the kids, all of them. She’s amazing, I don’t know how they do that. There’s that thing that’s possible. Family, you can never get away from. Even though you abused your family members by making them babysit your kids and stuff like that, they abuse you by making you babysit their kids and stuff. It all keeps going. With friends, in my life, I optimize for friends more than family because I liked being able to choose. My family is good and all but I like to be able to choose people who have shared interests and things. It’s very difficult to build a relationship as deep and significant as a family member with friends because they’re here in the city for a while until you get a job offer in the Bay Area or vice versa. People are coming and going and you can’t abuse them the same way. My friends didn’t babysit my daughter too much. Is that a willingness issue or is that a willingness to ask issue? It’s a willingness to ask issue. That’s part of it. I don’t want to babysit anyone’s kids, so don’t ask me. That sense of community has eroded so much in modern life because we don’t need each other to survive. Up until 50 to 100 years ago, a person couldn’t survive on their own. You had to get married, you had to have a family, and you had to have somebody helping you out. Now, anybody can survive on their own. You can get a job, even if it’s a lame one. You can pay rent and you can buy food. You can get by. I’m not to disparage anyone who’s got a tougher situation but the point is your neighbors, I don’t know my neighbors. I know the one guy over here a little bit. The folks in the building, there are three neighbors. I don’t hang out with them. I don’t know anybody else who lives in this immediate neighborhood. Upper Queen Anne over there, I know people because my daughter goes to school there. What do you think that is? As I said, I’ve been thinking about the co-housing thing a lot and I live in the Pike Place Market. There’s a very interesting community aspect that happens there, more so than other places. I’ve been there for years now. You do know some neighbors but you’re the type of person who would know. I am the type of person that would try to know their neighbors. We got team-building and leadership stuff all starts to kick in. What’s happening is we’ve homogenized on a few life patterns, let’s say. That’s what people are growing up looking forward to and expecting. Humans are only good at doing what they’ve seen done before. We’ve only seen a few things. We’ve seen them become an old maid cat lady. We’ve seen get married and have a kid and then get divorced and then fight. There’s that pattern. They’ll get married, grow old together, and have nothing in common and don’t get divorced because it would look bad to the kids. There are a few patterns. I’m being disingenuous but basically, we have a few patterns. You notice there are not happy ones in your list. They’re off for a little while but I’m not being totally disingenuous. The truth is a lot of them are happy for a while. I was married for twenty years and a lot of them were good years and I’m not sorry about that. It was successful for a long time but it wasn’t something that would work for our entire lives. We’re already out living the median lifespan of a human. Those first 30 years, if a long time ago, let’s say, I got married at twelve and had babies by 13, 14, 15, died by 30, you’re doing pretty good. You don’t have time to get cancer. Cancer isn’t going to catch you if you died at 30. Now that we’re living to 70, we got a lot of problems and some of them, it’s hard to maintain those relationship structures for so long. Do you think that that’s fundamental or do you think that we just sucked at figuring out how to do that well? It’s fundamental but we suck at figuring out what to do because we’re trying to do what we’ve seen done, whether it works or not for us. The answer is you got to run a lot of experiments. This is one of the amazing things about Seattle, San Francisco, being on the West Coast. We are running lots of experiments. Co-housing doesn’t sound like a crazy thing. If you show up in Indiana or Tulsa, Oklahoma and talk about co-housing, I don’t think people know that work. No offense. You’re going to be like, “That’s some weird hippie stuff.” It’s especially going to fail and a lot of it does fail because it’s not a fair experiment. If you start an experiment, you don’t get equal support for this experiment that people doing the traditional thing would get, then it’s a doomed experiment. You have to have societies that are willing to allow people to try things like having multiple partners or having co-parenting situations or cohabitation situations or different kinds of things to figure out what works. Sometimes those things do work and I’ve seen a lot of them because I used to live in San Francisco and there’s some weird shit going on and everybody plays along and we’ll try to be supportive like, “What happens?” “There are three people in this couple and we’re trying to send them a wedding invitation but do we put Mr. and Ms. and Mrs.?” We don’t even have conventions for these things. Every time you don’t have a convention, it’s one more thing that makes it hard on the people and experiment even if they had something good going. These are very difficult things to solve in short order. They take a long time but overall, what I try to do is give people the benefit of the doubt, let them try the craziest thing that they can bring themselves to try and see if they discover something that can work. Don’t judge them based on whether they lived happily ever after. If it worked for a while, that’s pretty good. If you can take care of somebody and be good to them for a while, a good place to start would be better breakups. That’s totally possible. I’ve seen some amazing ones. I’ve heard some great breakups. Great divorces even. Those are things people should strive for. That should be part of your model and say, “We’re going to do this until death do us part or until we have a good breakup. Let’s try and get ahead of that.” That’s not usually what’s in people’s vows but if you can’t do that, you’re going to do more damage to each other, to kids, to people around you. We already know marriage is long in the tooth as an institution. It’s great for people who want to try it. It’s good for some people for some time but lots of them are failing. You have to accept the statistical probability that it’s not going to last forever. Don’t make your only way out raising everything and burning it to the ground. It’s sad to see that happen. It’s damaging to a lot of people. I don’t know what the answers are but the way to find those are through lots of experiments. I can keep asking questions all day long. We did good. It’s not so bad. We’ll let you go. Thanks for doing this. Important Links: Danny Hillis – TEDx video Y Combinator About Adina Mangubat Adina is the CEO and co-founder of Spiral Genetics, a leader in bioinformatics for population genomics. At Spiral Genetics, she leads complex sales to highly technical audiences, drives business development and product vision, and has built a diverse team of highly talented technical and scientific individuals to develop the world’s most advanced bioinformatics technology. In addition, she is the primary catalyst for creating a transparent, high integrity, and mission-driven culture. Early in her career, Adina worked with two other high-technology companies wherein her role included team development, brand development, marketing, channel development and sales for complex technologies. A graduate of the University of Washington, Adina holds a B.S. in Psychology with a focus on Entrepreneurship and was recognized by the Washington Biotechnology and Biomedical Association as one of the 2013 Women to Watch in Life Science. Additionally, she was featured in Forbes 2013 “30 under 30″ for Science and Healthcare. In 2017, Forbes named her as one of the All Star Alumni for the 30 under 30 in Science and Healthcare. Adina’s passion for world-changing technology, coupled with her adept entrepreneurial focus and clear team development skills have enabled her to bring Spiral’s technology to the forefront of bioinformatics innovation. Recorded on May 1, 2019The post Into the World of Genomics & Entrepreneurship — Adina Mangubat  appeared first on .
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Video Games: Optimized Learning Environments — David Edery

David Edery, co-founder and CEO of Spry Fox, shares his insights into the power of video games as learning tools. He discusses the unique dynamics of gaming, where engagement is key, and how this can translate into educational benefits. Edery emphasizes the capacity of games to promote empathy and personal growth, particularly in challenging contexts like mental health. He also explores the future of indie game development and the importance of practical learning in the educational system, advocating for a shift towards integrating games into curricula.
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