The Future of Everything

Biomechanical engineer Scott Delp discusses advancements in diagnosing and treating motor dysfunction. He shares his personal journey recovering from a skiing accident and how his team uses sophisticated computer models for surgical, robotic, and neurostimulation interventions. Delp emphasizes the importance of seeing movement as vital for health and making physical rehab enjoyable.

Russ Altman: Today on The Future of Everything, the future of detecting DNA in your blood.Now DNA is the building block of life. It is a relatively simple long molecule or polymer made out of four components or DNA bases which have one letter abbreviations, the famous ATCG, which stand for their chemical names. It’s like a string of beans, beads, beads, but it is long. A human genome is made of about three billion DNA bases, divided into 23 chromosomes. So if you add up the beads in each chromosome, you get about three billion. You get a genome from mom and you get one from dad. So you have two copies of the genome, mostly the same but obviously not identical, or six billion total.Now DNA contains the blueprints for how your cells live, how they grow, how they interact with other cells, and like a computer program, it allows the cell to perform simple computations to make decisions about when and where things happen.If this goes wrong, you can get cancer. Mutations in the DNA cause the computations and decisions to go wrong.Other things can happen too. In the last ten years, researchers have learned that they can detect DNA in the blood. Now we knew that the cells in the blood had DNA, so that was not surprising, but what was surprising is that there is sometimes DNA from other cells in the body, often cells that have died and just released their DNA into the bloodstream. This is sometimes called cell-free DNA because it is floating in the blood and it’s not really part of a cell. Although this may seem like it’s junk, it offers evidence of lots of other processes going on in the body, processes diverse as cancer, pregnancy, stress on organs, or even death and many others.Dr. Stephen Quake is a professor of Bioengineering, Applied Physics and Physics and Stanford University. Steve pioneered the detection of DNA in the blood and some its first applications.Steve, what drove your interest in detecting DNA, and what was the first demonstration that this would actually be useful?Stephen Quake: Well, my interest came actually when I became a father. My wife and I were in to see the doctor, and the doctor says you guys should think about getting amniocentesis. And it was seemed like a theoretical question and something we have time to think about. We said yeah, okay, that sounds like the right thing if recommending it.Russ Altman: And this is a super risky procedure in many ways. A needle goes into the uterus near the baby to extract fluids.Stephen Quake: Big needle right in the mom’s belly, right next to the fetus to try to grab a few cells, and so to do genetic testing. And we said yeah, it sounds like a good idea, thinking we schedule another appointment for it. Next thing we knew, the guy was turning around with a giant needle, plunges it right into my wife’s belly,Russ Altman: Whoa.Stephen Quake: Yeah, whoa, exactly. That was our response. And it’s the response of many people who undergo that certain invasive testing. And not surprisingly, there’s risk associated with doing that testing. Sometimes, you lose the baby and other health problems that might happen.Russ Altman: How far into the pregnancy were you?Stephen Quake: That’s typically done, I don’t know, around 14 weeks, something like that, 15 weeks, somewhere around there. And so that sensitized me to holy cow, there’s a problem here that you’re asking a diagnostic question, and there’s a lot of risk associated with it. And so I began to think are there ways to ask these genetic questions and do diagnostics without adding risk? And I eventually stumbled upon this old scientific literature about this cell-free DNA that you were mentioning, which, as it turns out, was first discovered as a phenomenon in 1948.Russ Altman: That’s before Watson and Crick even articulated the importance of DNA for genetics.Stephen Quake: It’s before the structure, and it’s before people knew. It’s roughly contemporary people first realized that DNA was the molecule of inheritance.Russ Altman: Right.Stephen Quake: Oswald Avery just that same year was working that out. So it was blood chemistry to those guys who did it. But the field stayed alive, and it was mostly people doing cancer research. And eventually, it was figured out that when you’re pregnant, some of the DNA in your blood comes from the fetus, and that was worked out in the late 1970s. And –Russ Altman: And so this is not a large amount, I’m guessing.Stephen Quake: It’s not much, just a few percent of what’s there, so it’s a very challenging measurement problem and the decade-long search to try to figure out how to really use that to build a diagnostic that would allow you to understand the genetics of the baby without having to risk the baby’s life. And we saw that at Stanford, and it was through the work of a really terrific graduate student in my lab when the bioengineering department was young, Christina Fan. And that has now been the first real clinical application of cell-free DNA in diagnostics, and that’s how I got into it, to answer your question.Russ Altman: So in that initial demonstration or in your first industrial translation, what are the things that we can actually detect from the DNA of a fetus in the mom’s blood?Stephen Quake: Well, when we published the paper on this, started getting press inquiries. When is this gonna be available in the clinic? I said, I don’t know, decades, something like that.Russ Altman: That’s usually the answer.Stephen Quake: It takes a long time, right. It turns out people jumped on like you wouldn’t believe. Clinical trials were launched immediately. Within three years, the first real commercial diagnostic products had been launched, and now it’s four million women a year, something like that, get the test, and the use of amniocentesis has plummeted.Russ Altman: And so now you do this as a screening before you make the decision about the amnio. Is that the general use of it?Stephen Quake: That was the initial indication, and it’s very quickly moving to replacing amnio completely.Russ Altman: Completely, yeah. And what kind of things can we diagnose in the fetus these days?Stephen Quake: So the major genetic disorders you have for live births are things like Down syndrome; that’s number one. And it’s an aneuploidy is what it’s called technically, means the extra copy of a chromosome. And there’s a few other disorders, which are extra copies of chromosomes that are also detected with this approach.Russ Altman: Awesome. So that has had big-time market impact, and it’s changing people’s lives. I think it’s on the street now. People know you can get this blood test instead of the amnio, so it didn’t stop there. Now you had this hammer, and it worked. You hit one nail. What was the next nail you guys turned your attention to?Stephen Quake: Well, after we published that, word got around Stanford that I was interested in non-invasive diagnostics. And I got a call one day from Hannah Valantine, who’s a cardiologist –Russ Altman: Great cardiologist.Stephen Quake: Yep, and she says, well Steve, we got a similar problem in heart transplants. We give people a new heart, and after the operation, we then go biopsy that new heart and rip out pieces of the tissue to make sure it’s not being rejected by the body. And we’re doing that every couple of months. And so is there a blood test that could replace that? Same sort of problem, patients were having this painful, risky procedure, and there was a question of whether it could be replaced by a simple blood test. And so we thought about that a bit, and –Russ Altman: The key opportunity here is that the DNA and the heart that belongs to the donor is not gonna match the DNA of the person who received the heart, and, like the baby and the mom, because those are different DNAs, you have a chance of picking it up.Stephen Quake: Yeah, the key there is that the DNA is different. A little different with the baby and the mom because we don’t use differences in their DNA. But in the case of the transplant, absolutely. The whole principle is based on there being different genomes of every cell in the heart compared to other cells in the recipient’s body. And we monitor those so-called polymorphisms, those changes.Russ Altman: And so you went after this, and you were indeed able to show that people who were in rejection were spilling, so to speak, the heart DNA into the blood, and maybe we can avoid some of those biopsies.Stephen Quake: Absolutely. So we did a proof of principle study with some bank samples she had, and then we wrote a grant together and were able to do a very large study on both heart and lung transplants where pretty much every transplant patient at Stanford for those two organs was enrolled in our study over a period of three years, and were able to validate it. It was amazing. One of my kids was in elementary school at the time, and there was a new family who was in the class that year. And at the end of the year, we got a note around saying that, well, there’s a family that’s in town because they were at the Ronald McDonald House. One of their kids was in the hospital and very ill, and would anyone wanna put them up for the last couple of months because their time had run out there. And so we invited them –Russ Altman: Took them in.Stephen Quake: to our house, yeah, and very interesting family. They were immigrants from Africa. The father had been a nurse there, had some medical training and knew that when his son was infant and very ill that needed serious help and eventually got him to Stanford where the son had had a heart transplant.Russ Altman: Whoa.Stephen Quake: And we were talking around the dinner table one night, and the dad says well, and we’re just so proud to be part of this study where people are trying to figure out if they can replace the biopsies. And we enrolled our son in it and drew the blood. I said that’s my study. It was amazing and felt very good about it.Russ Altman: Of course, of course.Stephen Quake: And now that’s available. So there’s now tens of thousands of people every year who are getting that test, and it’s saving a lot of pain and suffering for those patients.Russ Altman: This is The Future of Everything. I’m Russ Altman. I’m speaking with Dr. Steve Quake about detecting DNA, and at this moment, detecting DNA in transplant, hoping to detect rejection. So does the test detect rejection potentially earlier than the old-fashioned biopsy approach would?Stephen Quake: It does, and we’ve proved that, absolutely. You see rejection weeks, if not a month, earlier than the biopsy.Russ Altman: And then presumably, that gives the docs more option for changing the immunosuppression.Stephen Quake: Oh, absolutely because yeah, as you mention, all these patients are immunosuppressed to try to prevent rejection, and too much of that, and they’ll get an infectious disease. Too little of that, you have rejection. So they can dial up the immunosuppressants a little bit and try to avoid the rejection event, and that’s much better for the patients. Once they hit rejection, all sorts of bad things happen, and so the whole thing is trying to keep them properly suppressed.Russ Altman: And just to flesh it out a little bit, how frequently are they getting these blood draws? Is this every six months or every three months or –Stephen Quake: The standard of care for the invasive biopsies was every two months, and that’s where they initially matched it. But this is the sort of thing that can and should be done more frequently, and I think it’s gonna change the way people treat the patients over time.Russ Altman: I know that there are more applications, and I’m interested to know which ones you wanna talk about, but let’s talk about one that fascinates me, which is the detection of infectious agents in the blood. Can you tell me how this technology has been used in that regard and what’s the future look like?Stephen Quake: Yeah, so when we were doing the large transplant study, my post doc at the time, Ian De Vlaming, was looking at all the sequencing data very carefully and realized that not all of the sequence reads off the sequence that were mapping to the human genome. And he said maybe 98% of it’s mapping; there’s one or 2% that aren’t. And I said that’s great. It means we’re not having a lot of contamination and it’s all good, and he didn’t let it go with that, thank goodness. And he started looking at those things that weren’t mapping, and he realized it wasn’t contamination, and they actually were not human, and it was part of the microbiome of these individuals. So the bacteria and the viruses and funguses that live in our body also release cell-free DNA, and we were measuring that as well. And he realized that we could use that to monitor things like what happens to your microbiome when your immune system gets turned offRuss Altman: Right, because a lot of folks —Stephen Quake: Because a lot of patients are immunosuppressed, exactly.Russ Altman: Right.Stephen Quake: And then we realized ‘cause some of them are getting infectious disease, we could also see infectious disease. And so that has evolved into a new kind of infectious disease diagnostic, which is hypothesis free. You don’t have to test for a particular thing. You’re essentially testing for a thousand infections all at once, and it’s just now reached commercial development. We’re seeing the first peer-reviewed studies showing how to use it, and it’s a very exciting innovation for infectious disease.Russ Altman: People might find this surprising so let’s just unpack this a little bit. We know that there are some bacteria that live in our gut, and we’ve always expected to see them there. Many of us have assumed that my blood should be pretty much infection free. That’s not where the bacteria and the viruses live. I guess the first question is how much of a surprise, what do you see in normal people who are not immunosuppressed, and how do we interpret this? Do we know that these are diseases? Are these pathogens causing problems, or might they be part of some ecosystem of health?Stephen Quake: Yeah, all good questions. So a fun way to think about it is to do an order of magnitude calculation. Could we talk about calculations here?Russ Altman: Yes, this is something that physicists do, folks.Stephen Quake: So there’s a statistic going around by the microbiome people. You’ve got 10 times more bacterial cells in your body than you do human cells. If you take that at face value and you say well, the human genome is 1,000 times longer. You said three billion base pairs, then the typical bacterial genome, which about three million base pairs. You do the math on that, and you say by mass, all the DNA in our body is 99% human, 1% bacterial. And so if you were to mush this all up in a blender, purify the DNA out, that’s what would come out.Russ Altman: And that matches what your post doc found.Stephen Quake: Yes, exactly.Russ Altman: So are these normal signs? Are these normal organisms, or are these things that we have to run to the doctor and get treated for?Stephen Quake: The vast majority of it, the vast majority of is our normal microbiome, bugs that live with us commensally and happy, equilibrium, with us as humans.Russ Altman: I’m guessing you saw viruses or bacteria that were either entirely novel or not appreciated as living in humans?Stephen Quake: Absolutely, we have discovered traces of novel organisms that is an area of ongoing research in the group to try to understand what they are and where they fit into the tree of life.Russ Altman: This is The Future of Everything. I’m Russ Altman. I’m speaking with Dr. Steve Quake, and now we’re talking about infectious disease detection.As a doctor, I know that we have patients come into the emergency room or into the clinic with what we call FUO, fever of unknown origin. They look sick, they have a fever, it’s not normal to have a fever, and they look infected, but we can’t find an infection. And so I’m guessing that one of the key applications of this technology would be, well, what DNA are we seeing in the bloodstream, ‘cause that might point us to the infectious agent. Is that how the infectious disease community —Stephen Quake: Absolutely, yep.Russ Altman: — is taking this up?Stephen Quake: Absolutely. That’s a major application. There’s a bunch of others that are really interesting. And to come back to the earlier point you raised about blood infections being a different thing, the point is that the blood is like the septic system of the body, and it’s exploring all the tissues and organs. And when cells are dying and they’re releasing their DNA, it picks it up and carries it. So even if the infection is not in the blood, you see the remnants of the infection in the blood from that cell-free DNA.Russ Altman: Yes, and so the final area that I wanted to get into, of course, is cancer. And, in fact, you mentioned cancer in your initial comments. Where are we with the detection of cancer from cell-free DNA?Stephen Quake: Yeah, that’s been an area of intense interest for decades. That’s the one that was primarily driving the field before the prenatal work and because tumors have different genomes than the normal body does. And so people would monitor those differences in the blood and try to understand how the disease was progressing and to try to do detection. And that’s been a little later into the clinic than the prenatal stuff, but it’s happening now. And it’s an area of intense interest. There’s a bunch of companies out there that have launched tests or about to launch tests, and it’s gonna be very important for helping monitor course of treatment, and that’s the first clinical application that’s out there.Russ Altman: That’s what I was gonna ask. Is this about detection or about monitoring? And it sounds like the monitoring.Stephen Quake: That’s the first one. It’s the easiest one ‘cause you’re in such a high risk group and it makes it an easier technical task.Russ Altman: And you know the cancer, so you’ve been able to characterize what you’re expecting to find if the cancer comes back.Stephen Quake: Correct. But the big thing to go after is early detection, and that would help a lot of people and save a lot of lives. And that’s something that is gonna be coming. Maybe it’s five years, maybe it’s sooner, but there’ll be some very valuable tools for that coming down the pike; I’m pretty confident about that.Russ Altman: Yeah, so let’s just think about that for a moment because one of the things that I know is an issue is when these new technologies arise, they often move up the time of detection. You could get the cancer detection earlier, you get the rejection. In general, that’s a good thing. But in cancer, it’s a little tricky because there is some, if I understand the literature, there’s some indication that some cancers arise, and it’s the body’s own immune system suppresses the cancer effectively before it can grow. Have people worked out what actions you should actually take if you see a very early indication of cancer? Is it definite that we’re gonna hit the patient very hard with chemotherapy and radiation and whatnot, or might we still have to figure out what to do about that?Stephen Quake: Yeah, that’s a really good question and important issue, and I think we’re so early on that that’s being worked out in the clinical community. But the initial thought is not that you would go right to treatment with chemotherapy but that you would reflex to other testing methods that are more expensive and more sophisticated and are not the sort of thing you use to screen people broadly but if you got a hint that something’s wrong, you’d use them, things like imaging techniques and such forth.Russ Altman: Makes sense. This is The Future of Everything. I’m Russ Altman. More with Dr. Stephen Quake about DNA, the future of health and biology and bioengineering, next on Sirius XM Insight 121.Welcome back to The Future of Everything. I’m Russ Altman. I’m speaking with Dr. Stephen Quake about the fabulous uses of DNA that’s floating around in our cells. Now Steve, we just went through a bunch of really killer apps, but I know that there’s yet another one, which is looking at pre-term birth. And that’s a funny one to me because it’s not immediately obvious how detecting DNA would have anything to do with a pre-term birth. So tell us that story.Stephen Quake: Yeah, so pre-term birth ends up being number one cause of neonatal mortality and complications later in life. It’s a huge problem, and there’s been, despite decades of effort, no real progress on creating a meaningful diagnostic that tells people who’s at risk. And there’s been a lot of effort put into –Russ Altman: So the goal would be very early, say this looks like a pregnancy that might have some pre-term problems.Stephen Quake: Exactly. And more generally, when is the baby gonna be due? Even if it’s not early, can you predict the due date? And there’s been a lot of effort put into understanding the genetics of that, the DNA base part, that has not really had a lot of predictive power or success. And so we turned to looking at RNA, which is carries the message from the genome and tells you about not the inheritance but the state of the cell and body at any given point. And it turns out same guys who discovered cell-free DNA in 1948 also discovered cell-free RNA.Russ Altman: They have a good year.Stephen Quake: They did.Russ Altman: Same year?Stephen Quake: Same paper!Russ Altman: Same paper!Stephen Quake: And so we began looking at cell-free RNA as a way to measure what’s going on in the mom’s body and with the baby and the placenta at any given point in time and how are things changing and can that signal to us when the baby’s gonna be born and if the baby’s gonna be born early. And we were able, after a long effort, it took seven or eight years of work by a very large group of people, a number of collaborators here at Stanford, including David Stevenson and Gary Shaw and Yair Blumenfeld, bunch of the MFM docs.Russ Altman: MFM is maternal fetal medicine.Stephen Quake: Fetal medicine, thank you.Russ Altman: It’s okay, it’s my job.Stephen Quake: But we managed to, we managed to figure it out. And we published a paper last year showing that there’s a handful of transcripts which indicate when the mom is gonna give pre-term birth, about two months in advance of that.Russ Altman: Wow, so these are like canaries in the coal mine.Stephen Quake: Exactly. And we found another set of transcripts which were predict gestational age, so you can tell how old the baby is and predict when it’s gonna be born. And that turns out to be a really interesting problem as well.Russ Altman: I was gonna say, I thought that good old-fashioned subtract nine months from the date of birth gets you a pretty, and in fact, I must say, I’m born on November 5th, and that’s important because if you go back nine months, that gets you to February 14th, Valentine’s Day. So that’s a side story.Stephen Quake: Okay, I got a couple of stories there for you.Russ Altman: But tell me about this.Stephen Quake: All let me give you a couple of stories.Russ Altman: Tell me about this.Stephen Quake: So when we were having our first kid, the one with the amnio, right, I asked the doctor what’s the due date, tells us the due date. I said what’s the error of your measurement, your estimate? And he got very offended ‘cause he thought I was questioning his ability as a doctor.Russ Altman: Of course, of course.Stephen Quake: We had a very tense discussion. Finally, I manage to communicate I was asking about the uncertainty in the estimate ‘cause I wanted to know when to adjust the travel schedule to make sure I didn’t miss it. And he couldn’t tell me the uncertainty, but he told me a number that I could use to derive the uncertainty, and so I did that. Worked out to two sigma three sigma. I had three sigma baby. So the baby was premature by three and a half weeks, and it was fortunate –Russ Altman: Oh, it was at the border of the plus minus.Stephen Quake: Yeah, I was fortunately in town, and fortunately, she turned out fine. But this got me aware of the importance of not only pre-term birth but also understanding, trying to understand when the baby’s gonna be born and prediction of due date.Russ Altman: Okay, so you sold me. This is actually an impactful question.Stephen Quake: Yes, exactly.Russ Altman: So what can you guys do?Stephen Quake: Well, it’s early still. Our first paper was a small number of women, few dozen women, and yet it seems very promising, and we’ve now been able to reproduce it in a different cohort that we can predict pre-term birth and gestational age and, from gestational age, hopefully predict when the normal baby’s gonna be born. But it’s all now going into much larger clinical trials to validate it. It’s very much the beginning of the story, but it’s an exciting one.Russ Altman: So, great. This is a new molecule for our discussion, this RNA molecule, also from the baby or the placenta or both and a combination of maternal and fetal factors gives you the data you need and a big data mining approach, not to overuse that, to actually draw inferences that might be very impactful both for the actual due date but, more importantly, for uh oh, we have a woman who might be having a pre-term birth, let’s do what we can, and again, the ability of doctors to intervene is probably much better if they have two-month warning.Stephen Quake: Correct, correct.Russ Altman: Well, so this has been an amazing ride, and I wanna turn our attention a little bit now to a separate thing but very excited that you’re involved with. A few years ago, I think three years ago, the Chan and Zuckerberg Foundation announced the creation of a big biomedical research institute with you and a colleague from UCSF, Joe DeRisi, as co-presidents, and it had a very bold mission. The mission was to, I believe, cure or manage all disease by the end of the century, something like that; you can correct me if I’m wrong.Stephen Quake: Cure, treat, or prevent all human disease by the end of the century.Russ Altman: Bingo. So you agreed to that charge. You’ve now been doing it for three years. Can you tell us a little bit about how it was set up and why it was set up, and is it really even possible to imagine that level of progress in the next century?Stephen Quake: Yeah. So since we’ve been talking about becoming parents, and Mark and Priscilla began to turn their attention to philanthropy in a pretty large way when they became parents. And they wrote an open letter before their first daughter was born that launched the Chan Zuckerberg Initiative and ultimately the Biohub with this idea of trying to create a better world.Russ Altman: It’s called the Chan Zuckerberg –Stephen Quake: Chan Zuckerberg Biohub.Russ Altman: Biohub, mm-hmm.Stephen Quake: And so in their children’s lifetime, so broadly in this hundred-year span, they wanted to see if they could fund scientific research that would help make the world a healthier place for their kids and everyone else, which is a lovely mission. And it sounds crazy, right?Russ Altman: Sounds crazy.Stephen Quake: It sounds absolutely absurd, and for awhile, I couldn’t say it even to them with a straight face.Russ Altman: And yet a few moments ago, you said it forcefully and convincingly, so wait to go.Stephen Quake: In, well –Russ Altman: What turned you?Stephen Quake: Well, you think about it for awhile, and it helps to think backwards in time and think about how far medicine has advanced in the last 100 years. And in this country, mortality has been cut in half. And the things that kill us now are very different than the things that killed us 100 years ago. Primarily, it was infectious disease then. Now it’s things like heart disease and such forth. And so we’ve eliminated entire classes of diseases, effectively, and cut mortality in half. So you can project forward another 100 years and say if we don’t do anything, we should get another factor of two. And with some really serious effort, maybe we can do better than that. It’s just very hard for people to think on century-long timescales. We’re thinking when’s our next grand proposal or something like that or when’s our next student gonna graduate, and it’s not often that we have the opportunity to think on that sort of timescale.Russ Altman: This is The Future of Everything. I’m Russ Altman. I’m speaking with Steve Quake, now about curing, managing, treating, and what was the other verb?Stephen Quake: Prevent.Russ Altman: Preventing all disease. Do you take a portfolio approach? It sounds like you were talking about the causes of death 100 years ago, so you have to look at the causes of death now. And I guess you have to pick the low-hanging fruit to say how do we make progress. So how have you decided to deploy the assets of the Biohub for the next five to 10 years?Stephen Quake: Yeah, well, a two-fold approach. One approach is to pick a couple of areas that capture a large part of the global burden of disease, and we’ve chosen two that we focus on in our internal research. One is cell biology, and a lot of diseases are a consequence of disorders of cell biology, cancer, heart disease, pulmonary disease, a number of neurological diseases. And so better understanding how cells work will lead to new therapies and treatments.Russ Altman: Could be a platform of discoveries that will have multiple applications.Stephen Quake: Right, exactly, and that covers a large part of the global burden, as you work out the numbers of that. The other big part is infectious disease.Russ Altman: So it’s still a problem.Stephen Quake: Still a problem worldwide, absolutely. There’s a bunch of open areas, malaria, HIV. There’s a bunch of other ones, TB, number of viral infections. So that’s our other big internal effort. And at the Biohub, our researchers have been hired to focus on those two areas. Now the other, all the rest, what we’ve done is we’ve partnered with the Bay Area University, to Stanford, UCSF, and Berkeley, and we fund research of nearly 100 faculty at those universities across everything else. We have an open competition. We’ve committed roughly $100 million to those faculty over the next five years, and we’ll do it again for the second five years. And we’re encouraging them to work on the riskiest, most exciting ideas, whether they’re basic science, technological, or more disease focused, to cover the span of where we think a lot of the great innovations are gonna come over the next decades.Russ Altman: So that does sound compelling. So basically, a two-fold strategy with some top-down projects that you know are gonna be impactful, and then you spread your bets by giving money to a bunch of smart people and say just do what you think is right. And the hope is that that will lead to the next set of challenges that you guys can perhaps adopt as top-down challenges.Stephen Quake: That’s right.Russ Altman: So how is it going?Stephen Quake: Well, as you mentioned, we just celebrated our third birthday three weeks ago. Joe and I have been working really hard, but it feels great. I feel like we’re at full steam, and great science is happening, and the people we’re funding are doing great work, and the future is bright.Russ Altman: And I guess are the donors satisfied? Are the people who put up the funds, are they starting to see their fruits of their vision?Stephen Quake: Well, you’ll have to ask them that. It’s not my place to say. But they haven’t fired us yet, and so we take that as a good sign.Russ Altman: Thank you for listening to The Future of Everything. I’m Russ Altman. 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They make a remarkable array of chemicals to survive the world around them. One engineer is using that knowledge to help people live better. When things aren’t going well for humans and other ambulatory creatures, they simply move on to a new location, a new life. For plants, it’s different, says chemical engineer Elizabeth Sattely, who studies the evolutionary adaptations plants make to survive. Unable to migrate, plants must make do with the hand that’s dealt them. And sometimes that hand is not very good. The soils where they are rooted can lack nutrients or play host to pathogens. The air can be polluted or too arid. This fact of life, however, has given rise to a remarkable breadth of evolutionary adaptations plants use to make the best of their surroundings. They produce powerful small molecules that help them get more nutrients from the soil or air. And, they partner with microbes that help them live. Sattely hopes to better understand and, possibly, employ these adaptations for human benefit by making crops more robust to environmental challenges and by learning how the small molecules plants create impact human health. She says we might even turn plants into biofactories that produce medicines and other valuable chemicals. Join host Russ Altman and Sattely for a deeper look at the remarkable world of plant biochemistry. You can listen to The Future of Everything on Sirius XM Insight Channel 121, iTunes, Google Play, SoundCloud, Spotify, Stitcher or via Stanford Engineering Magazine. Connect With Us: Episode Transcripts >>> The Future of Everything Website Connect with Russ >>> Threads / Bluesky / Mastodon Connect with School of Engineering >>>Twitter/X / Instagram / LinkedIn / Facebook Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

In breast cancer pathology, a 2 percent chance of malignancy is the accepted threshold at which a radiologist refers the patient for further study. In reality, that threshold varies among doctors; some are more conservative, others less so. The result is either more false positives, in which a healthy patient worries unnecessarily they have cancer, or more-worrisome false negatives, in which a patient is told they are fine when they are not.One researcher working to reduce that gap is Stanford’s Ross Shachter. He is a professor of management science and engineering and an expert in using probability to improve decision making. Though Shachter is an engineer, he applies his approaches not to operational efficiency or business management, but to the high-stakes field of mammography, where decisions often have life or death consequences.He says that probability and decision making theory could be integrated into artificial intelligence applications that could help doctors better evaluate patient options, outcomes and preferences to improve care.Join host Russ Altman and Ross Shachter for a look at how engineering and AI are changing the world of breast cancer diagnosis. You can listen to The Future of Everything on Sirius XM Insight Channel 121, iTunes, Google Play, SoundCloud, Spotify, Stitcher or via Stanford Engineering Magazine. Connect With Us:Episode Transcripts >>> The Future of Everything WebsiteConnect with Russ >>> Threads / Bluesky / MastodonConnect with School of Engineering >>>Twitter/X / Instagram / LinkedIn / Facebook Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

In cancer detection, could a blood test replace a biopsy? Once, when a cancer was suspected, the next move often involved a biopsy – literally cutting out human tissue to ascertain malignancy. But that highly invasive model is now being overshadowed by the promise of “liquid biopsies.” In these non-invasive approaches, blood, spinal fluid and other bodily liquids are drawn and tested for the presence of cancer cells, bits of DNA or other molecules that are the unmistakable markers of serious disease. Often, such non-invasive biopsies can be done before clinical symptoms appear. Ash Alizadeh is an authority on the rapidly evolving technologies and techniques of oncology. He says that information is reshaping not only how we detect cancer but also how we treat it. The data we gather about any given cancer is being combined with knowledge about the patients themselves, leading to highly personalized approaches that did not exist just a few years ago. No two cancers, nor two patients, are exactly the same, Alizadeh says. Cancer cells grow differently in each patient and cancer treatments should be personalized accordingly. Join host Russ Altman and Ash Alizadeh as they explore the exciting new age of cancer diagnosis and treatment on this episode of The Future of Everything. You can listen to The Future of Everything on Sirius XM Insight Channel 121, iTunes, Google Play, SoundCloud, Spotify, Stitcher or via Stanford Engineering Magazine. Connect With Us: Episode Transcripts >>> The Future of Everything Website Connect with Russ >>> Threads / Bluesky / Mastodon Connect with School of Engineering >>>Twitter/X / Instagram / LinkedIn / Facebook Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

Women face many roadblocks to careers in data science and other STEM disciplines. One Stanford professor is out to change perceptions and realities for women in these fields. It was in 2015 when Margot Gerritsen was asked to speak at a data conference with not a single other woman on the program that she knew that something had to be done to get women into the field. As then-director of the Institute for Computational and Mathematical Engineering (ICME), Gerritsen knew more than a thing or two about data science and became determined to change the male-dominated culture. This determination led to the creation of the wildly popular “Women in Data Science Conference.” In putting the first agenda together, she was insistent that the conference be not about the problematic state of women in the field, but on the exceptional science of the attendees. Now into its fifth iteration, with more than 100,000 participants worldwide, online and at satellite events spreading into six continents, Gerritsen and her co-directors of the conference have inspired women across the planet to enter the sciences and provided a platform for them to highlight their work. In addition to the conference, WiDS now includes a datathon, a podcast that Gerritsen hosts, and ongoing education programs. The results have been, quite literally, life changing for many. You can listen to The Future of Everything on Sirius XM Insight Channel 121, iTunes, Google Play, SoundCloud, Spotify, Stitcher or via Stanford Engineering Magazine. Connect With Us: Episode Transcripts >>> The Future of Everything Website Connect with Russ >>> Threads / Bluesky / Mastodon Connect with School of Engineering >>>Twitter/X / Instagram / LinkedIn / Facebook Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

How do new technologies and techniques for altering DNA get used? And who gets to use them? In recent years, the development of inexpensive genetic sequencing and easy gene editing technologies has given rise to a community of non-academic, amateur researchers who like to refer to themselves, only half-jokingly, as “biohackers.” But, says Mildred Cho, a research professor who has published frequently about bioethics, such communities are not bound by traditional “first-do-no-harm” ethical norms that professional biologists and physicians adhere to. There is, for instance, a group of such do-it-yourself researchers pursuing a low-cost insulin substitute that is free of patent protection; they hope to bring that life-saving medicine to millions who cannot afford it. On the flip side, Cho says, there are also bio-hobbyists who like to do things “just for fun” that could present considerable danger to society. “Would you want your neighbor recreating polio in his garage?” she asks, rhetorically, adding that these deep and challenging concerns are better addressed sooner rather than later. Join bioethicists Mildred Cho and The Future of Everything host Russ Altman for a provocative discussion about the shifting landscape in the ethics of biological research. You can listen to The Future of Everything on Sirius XM Insight Channel 121, iTunes, Google Play, SoundCloud, Spotify, Stitcher or via Stanford Engineering Magazine. Connect With Us: Episode Transcripts >>> The Future of Everything Website Connect with Russ >>> Threads / Bluesky / Mastodon Connect with School of Engineering >>>Twitter/X / Instagram / LinkedIn / Facebook Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

An expert on air quality talks about the hidden dangers inside our homes and offers some helpful tips on what you can do to reduce your exposure. We all know about the decades-long battle to improve air quality outdoors, but Stanford environmental engineer Lynn Hildemann says that while much progress has been made in that regard, it may have caused us to look past the pollutants in our own homes. Hildemann, who studies air pollution and its effects inside and outside the home, says that chemicals and microparticles from cooking, furniture, carpets, cleaning products and good-old household dust represent the latest air quality battleground. She says it’s such a big concern because most Americans spend some 90 percent of their lives indoors. Hildemann offers a few small steps we can all take to improve air quality at home. Using the ventilation hood when cooking is a great first step. Opening the windows whenever possible is another. And, opting for easily cleanable hardwood floors over carpet can help, too. You can listen to The Future of Everything on Sirius XM Insight Channel 121, iTunes, Google Play, SoundCloud, Spotify, Stitcher or via Stanford Engineering Magazine. Connect With Us: Episode Transcripts >>> The Future of Everything Website Connect with Russ >>> Threads / Bluesky / Mastodon Connect with School of Engineering >>>Twitter/X / Instagram / LinkedIn / Facebook Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

A mechanical engineer explains how more and better data is helping to create new prosthetics unlike any before. For years prosthetic limbs were merely functional devices, but recent advances in robotics and neuroscience are transforming the very meaning of the word "prosthetic." Steve Collins is a mechanical engineer who is helping to lead that transformation to the benefit of people who've had an amputation, stroke or battlefield injury. The field has come a long way since the days of strap-on wooden legs. Collins says that, rather than trying to merely mimic what the body does, he's working on new ways of discovering prosthetic limb designs that outperform unimpaired bodies. His team uses advanced robotic systems that record and analyze the wearer's response, continually tuning their mechanical assistance to optimize performance and make them better than ever before. Join host Russ Altman and Steve Collins for a glimpse into the changing world of prosthetics on the latest episode The Future of Everything radio show. You can listen to The Future of Everything on Sirius XM Insight Channel 121, iTunes, Google Play, SoundCloud, Spotify, Stitcher or via Stanford Engineering Magazine. Connect With Us: Episode Transcripts >>> The Future of Everything Website Connect with Russ >>> Threads / Bluesky / Mastodon Connect with School of Engineering >>>Twitter/X / Instagram / LinkedIn / Facebook Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

Russ Altman: Today, on The Future of Everything, the future of the microbiome. Now, the microbiome has gotten a lot of attention in the last few years. Now, what is a microbiome? I guess we will learn more, but for the purposes of this discussion, it’s the full set of microbial organisms, chiefly bacteria, but maybe others, that live in different niches within our body. Our mouth, nasal cavity, skin folds, everywhere that has contact with the outside world. The gut microbiome is one of those microbiomes and it’s the community of bacteria living in our digestive system, not necessarily related to disease, but as a normal part of our physiology. We have long known that there is a lot of bacteria in our digestive tract and we know, for example, that they help us digest our food. That’s what we were taught in medical school many decades ago when I was in medical school. We also know that when we treat infections with antibiotics, it can alter these species because these species are sitting in your gut and they also can be very susceptible to antibiotics. So when I treat a patient for urinary tract infection or for pneumonia, not only am I killing the bacteria, hopefully, that’s causing the infection, but I’m probably altering the microbiome of that patient in ways that might lead to some symptoms. They might have some digestive issues that are associated with that antibiotic. Now, it’s become clear that the bacteria living in our gut have much more complicated relationship with our health and with our disease. They seem to be involved in our immune system. They seem to be changing sometimes in both acute and chronic disease. The idea has even emerged that there’s a healthy microbiome, the set of bacteria that you would love to have and host in your bowel and that there might be treatments for some diseases that involve changing the microbiome to get it to be more healthy, so to speak. This has gotten probably the most publicity in the idea of fecal transplants. Yes, if you’re not familiar with that, you heard correctly. This is the idea where poop, forgive the terminology, the technical terminology, poop from healthy people is introduced into the digestive tract of people with disease in order to help them normalize their microbiome to hopefully get it back into a healthy state. So this is getting serious. Ami Bhatt is a Professor of Medicine and Genetics at Stanford University. She has a medical specialty of hematology and studies the human microbiome, mostly in the gut, and has developed new ways to measure the presence of bacteria in the human body and ways to interpret these for health and disease. Ami, you specialize in hematology, the study of blood and blood diseases. How does a hematologist get interested in bacteria that live in the gut? Ami Bhatt: So, thanks a lot for having me, Russ. It’s a pleasure to be here. I actually first became interested in the bacteria viruses and fungi that live in and on us, as I think many young people did which was by watching a TV show. I remember being about, I don’t know, nine or ten years old, and I was left at home for the first time, for like ten minutes by myself or something like that, and so I turned on the TV. My younger brother and I were watching a television show about germs and, they showed these horrifying microscopic images of all of the bacteria that are squirming around everywhere. And I thought, “Wow, this is fantastic and also very gross, and we should really learn more about this.” If you fast forward many years later, part of the reason I became interested as a hematologist and oncologist in viruses and bacteria was because I learned that viruses can cause cancers in some cases. And as you well know, there are viruses that cause well-known cancers like liver cancer. Liver cancer is caused, in some cases, by a hepatitis virus. We know that the human papilloma virus causes cervical cancer and other cancers. And I thought, “Wow, there are all of these relatively simple organisms. They don’t have many genes.” You know, a virus can’t even live by itself. It requires a human cell in these cases in order to replicate. It’s amazing that such simple organisms can alter the biology of such complex organisms like us. That was how I ended up getting interested in bacteria viruses and fungi that live in and on us. Of course, first I learned about them as kind of bad guys but there are trillions of microorganisms that live in and on us and most of them are probably not bad guys. Many of them are probably actually quite helpful and so I’ve taken a more holistic view of what bugs mean to us. Russ Altman: So tell me, what are we finding when we look at the microbiome? How many of these are old friends that we’ve known for years and how many surprises are there where we’re saying, “Wow, we had no idea that this bacteria species was living in us.” And then how do we figure out what they’re doing, good or bad? Ami Bhatt: Yeah, this is an incredibly complex question in part because we don’t even know most of the microbes that live within us. Despite the fact that now, there have been tens of thousands of papers published on the gut microbiome of humans, for example, we know relatively little about who these organisms are. The classical ways of studying microorganisms was by taking them, culturing them, looking at them under the microscope. Russ Altman: Right, give them a little sugar and they’ll grow. Ami Bhatt: Exactly. Describing them based on what they grow on, so what they like to eat, what color they stain, what shape they are. But now what we’re understanding is organisms that look really similar under the microscope, and have very similar growth characteristics, for example, can have totally different genomes which means that they can probably do totally different things. So one of the things that we’re learning in the field is that we know relatively little about the organisms even within our own guts. And so a lot of effort has been put into trying to better enumerate who’s there and what they’re doing. Russ Altman: I also know that these bacteria often, you can’t just grow them on sugar and salt, they actually need each other to live so it’s like a very highly interlinked environment. Is this idea of a healthy microbiome, is that an oversimplification or is it in fact true that you could look at a sample of somebody’s poop and say, “That looks pretty good,” versus, “Oh, we have a problem here.” Ami Bhatt: You know, I think in general we’re coming to a consensus that for the gut microbiome, at least based on the individuals who’ve been studied to date, having a more diverse community is better. And so having a larger variety of different types of organisms is probably better than the alternative, which is having a handful of organisms that are present at a high abundance. But in general, what we think we know now is that there isn’t just one healthy microbiome. There isn’t that golden poop out there that we should fecal transplant into everyone and then we’ll all look like a Kardashian and live for 250 years. Russ Altman: I know a young man in Boston whose name will not be mentioned who’s actually made several thousand dollars donating his poop to research and to microbiome stuff for the last couple of years so he’s in the money. Ami Bhatt: Yeah, oh yeah. It’s a great way to, you know, turn poop into cold, hard cash. Russ Altman: Poop into cash. Okay, that was a very distracting idea. So there are many healthy microbiomes. And how can a patient or a person who’s listening, how can they figure out what the state of their microbiome is? You know, it’s interesting. I think if I talk to most laypeople or my patients or family members who aren’t in medicine and I ask them, “How’s your gut health?” Most people can actually tell you. Most people have a very good sense of how their gut is functioning based on their daily bowel movement or bowel movements, how they feel, do they feel bloated, etc. And so I would say most people who don’t have gastrointestinal symptoms, I’m talking about diarrhea, constipation, nausea, vomiting, bloating, those are people who probably have fairly healthy gut microbiomes. Russ Altman: So that’s good news ’cause that means you can use your normal life experience to kind of self-diagnose if there’s a problem and if things are going well both literally and figuratively, then we’re okay and then there’s no need to worry. So what are the impacts… Well, this is The Future of Everything. I’m Russ Altman, I’m speaking with Ami Bhatt about microbiomes and healthy and diseased ones. What about when you take antibiotics? This is a huge insult to the system. Do we know what happens to the gut microbiome and does it bounce back or does it then change forever? Where are we in that knowledge? Ami Bhatt: Absolutely. So, you know, I liken antibiotic exposure to a forest fire. You’re basically getting rid of the vast majority of life that exists in the gut microbiome. And you don’t get rid of everything because even the most broad-spectrum antibiotics that we use don’t kill off every single microorganism in our gut. Russ Altman: And that’s also true of the forest fires where those few species come back right away. Ami Bhatt: Absolutely, absolutely. So it’s very, very similar of a situation. Some of the best work that we have in the field focusing on how antibiotics affect the microbiome have actually come here from Stanford from a colleague named David Roman. He and his colleagues did some really transformative early work in the early 2010s on the exposures of antibiotics to the gut microbiome in healthy individuals. They took a handful of individuals, gave them antibiotics, and studied what happened to their microbiomes. What they found was that, there was definitely a simplification of the microbiomes when people were exposed to antibiotics. Russ Altman: That loss of the diversity you were talking about. Ami Bhatt: Exactly, that’s loss of diversity and then basically after the people stop the antibiotics assuming they were living a healthy lifestyle, which they were, they regained their diversity, mostly. Russ Altman: So that’s good news. Ami Bhatt: Good news. On repeated exposures to antibiotics, what people have observed is that there may be a point at which you can’t quite get back to your normal and every time you’re exposed to antibiotics, you may be readjusting to a new normal. Russ Altman: Does the microbiome run in families? Can I assume that my wife and I, our kids are outta the house. That’s a whole different story, and I know nothing about their microbiomes. But do my wife and I have the same microbiome probably because we’re spending a lot of time together or could they be very different even in that home situation? Ami Bhatt: Yeah, so we call the scientific jargon for this is cohabitating adults. Russ Altman: That’s what I do with my wife. Ami Bhatt: Yes, so you and your cohabitating adult, your lovely wife, you probably do have some shared species and strains. So research has suggested that cohabitating adults do share some strains. There has been some limited work to show exciting results that people who own pets, for example dogs, may actually even share a few strains with their pets. Now this is really exciting because as you know, there’s this hygiene hypothesis out there and the idea that we’ve become too clean as a society that’s why we have, like, asthma and allergies and eczema that are increasing. Russ Altman: We need more exposures as youths. Ami Bhatt: Exactly, and we know that people who have animals when they’re young or who live on farms when they’re young actually have a decreased incidence of these diseases. So one question that has arisen is, is it because we’re actually getting microbes from these animals around us? Russ Altman: That raises an issue that I really, I did wanna get to so I’m glad that you’ve raised this, which is, the role of the gut microbiome with the immune system. In fact, you would think they might be at battle with one another but I think it’s much more complicated and I know you’ve looked into this. So, how should I think about the relationship of my gut bacteria with the health of my immune system? Ami Bhatt: Yeah, so we know that animals that can be reared without microbes, we call these germ-free animals. Russ Altman: So like the bubble boy but they’re the bubble cow or the bubble. Ami Bhatt: Yeah, bubble mouse. All kinds of bubble animals. Russ Altman: That’s probably easier than the bubble cow. Ami Bhatt: Yes, but you know, even bubble fish have been generated. You can generate these animals without really any measurable microbes and what we know about them, surprisingly, is that their immune systems are really messed up. That observation actually suggests that the immune system is really dependent on microbial exposures in order to mature properly. We also know, interestingly, and this is more of a correlational relationship, that the immune system develops over the first three years of life. You know, that’s why a lot of kids and babies get their immunizations or vaccinations in that early period of time. That’s actually also when the microbiome develops. So we know that the vast majority of microbiome and immune system development happens in those first three years of life. That suggests that just like having, you know, a sparring partner, someone who urges you. Russ Altman: Keeps you sharp. Ami Bhatt: Yeah, absolutely. I think the microbes keep the immune system sharp and I think the immune system keeps the microbes sharp. Russ Altman: Okay, so we should be rooting for a certain amount of healthy competition between the bacteria and the immune system and it’s part of developing this robust immune system. Taking that idea and combining with your earlier comments about there’s many healthy microbiomes, you’ve made a study of the cultural and geographic diversity of the microbiome including even in places like Africa where I imagine that the lifestyle, the diet, many things are different from the West Coast of the United States. Why are you doing that work and what are we finding? Ami Bhatt: The reason we’re doing this work which is really trying to broaden our understanding of all of the different types of healthy and diseased microbiomes that exist around the world, is that we know, unlike human genetics, like your human genome doesn’t really change over the course of your life, we know that the microbiome can change over life and that the microbiome is pretty much controlled by your lifestyle and your environment. For example, if you, Russ, were to move to Greenland and take up a diet that was entirely of fish and seals, your microbiome would change dramatically. And that suggests that the variety of lifestyle choices and environmental exposures that people have can really affect their microbiomes and they affect their microbiomes way more than their personal genetics do. Russ Altman: So it’s the environment that is playing a huge role. Even though I’m the same Russ, after six weeks in Greenland, I’m a different microbiome Russ. Ami Bhatt: Absolutely, absolutely. So one of the challenges in research has been that we tend to, in my opinion, overstudy kind of the same people over and over, in part ’cause they’re convenient. Honestly, if I was to do a study of a thousand people’s microbiomes, it’d be a lot easier for me to do the study here at Stanford and just to recruit, you know, the incoming freshman class. Russ Altman: It would be very diverse. It would be both Facebook employees as well as Google employees. Ami Bhatt: There you go, yeah. And then throw in like a little bit of Apple just for the fun. Russ Altman: There’s your diversity. Ami Bhatt: We know that many of these people are gonna have very, very consistent lifestyles. And so we thought that it was really important to broaden our understanding of all of the different types of microbiomes that can exist in the world, both for the purpose of better enumerating what is normal, normal can be a variety of things, but also because, not only should genetic research be done all over the world, we wanna make sure that genetic researchers are being encouraged all over the world. We started this collaboration with a really impressive consortium called the H3 Africa Genomics Consortium. They do a lot of human genetic work and as you know, life originated in Africa, there’s a huge amount of human genetic diversity there and we, being kind of a one-trick pony said, “Hey, we should collect poop and we’ll sequence it and we’ll learn about the microbiomes of these individuals.” Thankfully we have collaborators who are game for that and we’ve been studying the microbiomes of individuals in urban township settings and rural areas and trying to understand how they’re similar and different to each other and similar and different to us. Russ Altman: This is The Future of Everything. I’m Russ Altman, I’m speaking with Dr. Ami Bhatt about the microbiomes in Africa and fascinating because of the diversity and the history of Africa, it is possible that there will be more diversity of the microbiomes in Africa than there is in the rest of the world or certainly it will be more diverse than what we’re seeing in local areas as you described. And I also totally buy your argument that if there are gonna be in the future treatments of the microbiome, we really need to understand the range of normal so that we don’t start treating people in Africa with microbiomes that are irrelevant or even damaging. So let me ask that, we hear a lot about when people migrate from one place to another, after a certain amount of time they start getting the diseases of the local milieu. So, you know, we hear about people from China who come to the U.S. They have a certain diet and lifestyle in China, and after a couple of generations, they start getting the same heart disease that has been plaguing all of the U.S. Could there be a microbiome connection to this? Is it that changing your geography is not just the lifestyle and the McDonald’s and dietary considerations, but that you’re also now being exposed to microbiomes that might change your disease risk? Ami Bhatt: I absolutely believe so. One of the things that we don’t know is whether or not a healthy adult can actually acquire new microbes easily from the environment, but certainly the idea that changing someone’s lifestyle can change their microbiome is well established. There have been migration studies where immigrants have been studied over the course of time. I absolutely think this is related to disease. One of the things I’m really fascinated about is this observation that my parents, for example. My parents came over from India to the United States for school. They were born and raised in India. They could eat all of the delicious street food that is there. But when we used to go back to visit when I was a kid, my parents would say, “Absolutely no street food for you,” and absolutely no street food for them, because we would get terrible diarrhea, to be honest. Why is that so? My parents have been exposed to that. Russ Altman: They’ve grown up on it. Ami Bhatt: Yeah, they’ve grown up on it. Presumably their immune systems have gotten used to it, so why could they suddenly not eat these foods anymore? And I really do think part of it might be that their microbiomes had shifted over time. Russ Altman: Fantastic. This is The Future of Everything, I’m Russ Altman. More with guest Dr. Ami Bhatt about the microbiome and its significance for both health and disease, next on Sirius XM Insight 121. Welcome back to The Future of Everything, I’m Russ Altman. I’m speaking with Ami Bhatt about the microbiome. And in the last segment we had a great discussion about health and disease and immune system. People like to manipulate their microbiome and there’s been a lot of popular press about yogurts and probiotics. Is that all real? How should people think about the opportunities for manipulating or improving their bowel health by ingesting foods that modify it? Ami Bhatt: I think it’s natural for us to wanna improve our bowel health. I think almost every one of us has done this. By the time we’re an adult, we know that there are certain foods we don’t tolerate, certain foods that actually work out better for us. I think many people learn, for example, in their 20s and their 30s that they don’t tolerate lactose anymore, for example. Russ Altman: Right, so milk is out. Ami Bhatt: Milk is out. And probiotics are an interesting opportunity for us to try and change that microbiome. Russ Altman: Can you tell me what is the definition of a probiotic? Because I think there’s even confusion about that. It sounds great. Pro, biotic, I mean what could be wrong with it? Ami Bhatt: Yeah, it’s a fantastic thing, but, it is actually a moving target, also. So, the idea of a probiotic is it’s live microbial therapy. Right? It’s a compound, not a compound, but organisms that you can ingest or put on you if they’re skin probiotics. Russ Altman: Oh, so there are skin probiotics? Ami Bhatt: There are skin probiotics now, too. So you can ingest or put these things on you and that they will somehow improve your health. They can come in a variety of “flavors.” On one extreme, while fecal microbiota transplantation is not technically considered a probiotic, it is one of the most complex live microbial therapies we can administer. Russ Altman: Yeah, it’s a definitely cousin idea because you’re introducing bacteria on purpose to help. Ami Bhatt: Exactly. Most probiotics come in either pill form, so you can go to, often like the natural foods store and you’ll find an area where they have a bunch of bottles that are labeled with different complicated Latin and Greek names. Those are probiotics. Alternatively you can have things like foods that actually contain live bacteria or sometimes fungi. Russ Altman: On purpose. Ami Bhatt: On purpose. Turns out, this has actually been an important part of cooking for millennia. Bread, for example, is obviously fermented by yeast. In the classical way, it was not just fermented by yeast but also by bacteria that are present in the air and on the grains of wheat. Russ Altman: I believe that’s part of the sourdough magic is that it’s not just the yeast but a complex. My son teaches me about the complex bacteria required for high-quality sourdough. Ami Bhatt: Absolutely, so we consume bacteria in these ways. Of course, when we bake bread, the bacteria die but there are things like yogurt. Yogurt is made by actually culturing milk with bacteria, and we can buy live active culture food. Russ Altman: Now, will yogurt automatically come with bacteria or is it a special type of yogurt that would have bacteria? ’Cause I know that people often think, “I love my yogurt, it’s giving me good probiotics.” I don’t know if that’s true. Ami Bhatt: The majority of commercial yogurts that are available, the bacteria have been killed. So if you want to go to the store and buy a live active culture yogurt, meaning a yogurt that still has living organisms in it, you’ve gotta look for that. They usually say, “live active culture,” and if you turn the container around to the back, you can actually see the names of the organisms that are included. Russ Altman: The list of Latin names. Lactobacillus and things like that. Ami Bhatt: Exactly, exactly. Also if you make it at home, of course, you would also be live active culture. So there are other types of foods that are live active culture. Sauerkraut, kimchi, in fact, almost every culture has some sort of fermented food that’s an important part of their culture and their cuisine. Russ Altman: Yes, we’re overloading the word culture. Every culture has their favorite bacterial culture. Here’s the big question. Is there evidence for health benefit? Ami Bhatt: This is really where it gets kind of tricky. It gets tricky because there have been some big studies done on pills, like probiotic pills, used in the medical setting to do things, specific things, like, prevent antibiotic associated diarrhea. For example, many of our listeners have probably gone to the doctor, gotten an antibiotic for a bacterial infection, and have been told by either their doctor or friend, "Hey, eat some yogurt while you’re having this." In that concept there is, we know that antibiotic is killing a lot of the bacteria in your gut, maybe some of these bacteria from the yogurt will fill in the gaps, and prevent you from having the diarrhea that’s associated with having low diversity microbiomes. Russ Altman: And does that indeed happen? Ami Bhatt: You know, so, there are studies that say it does, there are studies that say it doesn’t. And I think really, the jury is out. It’s a really complicated topic. As a physician, I would say, there is really limited evidence for the utility of probiotics in the health setting, and in disease management. Russ Altman: So as a physician, it kind of falls into the, well, I don’t think it’s doing any harm, so I’m not gonna tell you not to do it, but I wouldn’t bet the farm that it’s gonna solve the problem. Ami Bhatt: Absolutely. And I would say in some extreme circumstances of health, like, you know, for example, there have been studies showing that, immunotherapy, which is a type of treatment that’s used to treat cancer patients, immunotherapy may depend on what the microbiome contains. We know that there may actually be risks associated with taking probiotics when you’re on an immunotherapy agent. Russ Altman: So that’s a big deal, because now we’re talking about risks. Can you tell me a little bit more about that? Ami Bhatt: Yeah. Russ Altman: Sounds like it’s new. Ami Bhatt: It’s really new. I think none of these data are published yet. But at conferences, at scientific conferences, people have been talking about observations that cancer patients on immunotherapy who are taking probiotics, may actually respond worse than those who are not. Which really begs the question of, you know, could we potentially be doing harm by giving people probiotics. Russ Altman: So that’s something we’ll have to keep a close eye on. And I’m sure that oncologists will pay close attention, because they don’t wanna undermine their treatments by saying, “Oh, it can hurt,” when in fact, maybe it can hurt. So that’s an important one. Ami Bhatt: Absolutely. Russ Altman: This is The Future of Everything. I’m Russ Altman, I’m speaking with Dr. Ami Bhatt, about the microbiome. And I wanted to move to the issue of the microbiome over time and in aging, folks, which we all are. I think you made a reference to this, that it doesn’t stay the same. What do we know about the process of aging? And is there things that elderly people should be thinking about in terms of their microbiome? I was struck when you were talking about the immune system, you were very convincing that people have a good sense of how their bowel is doing when you ask them. I’m not sure people have a good sense of their immune system when you ask them in the same way, maybe they do. So it’s all confounded together in my mind as the aging process, the immune system, what do we know about that? And what should people be thinking about as they age? Ami Bhatt: Yeah, so it’s interesting, there’s been a lot of focus on the microbiome and the immune system in early life, lots of studies on those first three years. And what we think is that, for the adult period, people to tend to be pretty stable in both of those things until later on in life, and our group and others are actually starting to study, the microbiome of aging individuals. From animal studies, it’s actually been demonstrated in the African killifish fish model. Russ Altman: Killifish? Ami Bhatt: Killifish. Yeah. These are really cool, short lived fish. They’re actually the, I believe the shortest live vertebrate animals. Russ Altman: So what are we talking? Ami Bhatt: Months. Russ Altman: Months of life. Ami Bhatt: Months of life. Russ Altman: So they really have to go for it. Ami Bhatt: Yeah, they gotta go big, go big and then they have to go home. So, an interesting study was done, where they took poop from young fish, and then transplanted it into old fish. And they actually find that the old fish can swim faster when they have young poop in them. Russ Altman: Am so glad you’ve mentioned this, ’cause I’ve heard about these kind of studies, and also like old mice giving their poop to young mice, and vice versa. So yeah, so what’s going on there? Ami Bhatt: You know, it suggests that there is something within the gut microbiome of these young individuals that can actually alter the biology of these animals, older animals, either through their immune system. Russ Altman: They are swimming faster. Swimming faster. The older fish. So now we just have to figure out what would that mean for a human, and when do I ask for my young colleague’s, well, I don’t even wanna say it. How do we approach this issue? And do we think that there’s a real hope now for therapies? I mean, are people now thinking about a future, where in addition to the pills that you’re getting from your doctor, they’ll be interventions to try to spruce up your microbiome? Ami Bhatt: Yeah, I think that there is a great opportunity here. In part because we know that there is this association between the alteration of the microbiome and diminishment of the immune system. I think in the future, although there are no data to support this yet, that older individuals will get things like, microbial therapies or fiber cocktails that will help keep their microbiome healthy, and maybe prevent them from getting things like shingles, you know, a reactivation of a viral infection, maybe that’s related to our gut microbiome, who knows? Russ Altman: And you’ve made a really important point here, it’s not just introduction of the bacteria, but you need them to be happy, so to speak, and to live. And so you mentioned fiber, because that might be one of the substrates upon which these bacteria live, in order to stay in your bowel after they’ve been introduced. Ami Bhatt: Absolutely. We can’t just put them there, we’ve got to feed them as well. And so, since fiber is what a lot of these healthy microbes eat, then we’ve got to feed them. Russ Altman: So when we think about high fiber diets, part of the reason we’re recommending this to patients is not just for the bulk and to help them the musculature of their bowel, it’s also to have a good relationship with the underlying microbiome. Ami Bhatt: Absolutely. Russ Altman: Thank you for listening to The Future of Everything. I’m Russ Solomon. If you missed any of this episode, listen anytime on demand with the Sirius XM app. Connect With Us:Episode Transcripts >>> The Future of Everything WebsiteConnect with Russ >>> Threads / Bluesky / MastodonConnect with School of Engineering >>>Twitter/X / Instagram / LinkedIn / Facebook Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.