Science with a Twist

The Power of PharmacogenomicsJeff explains how pharmacogenomics, the study of how genes affect a person's response to medications, can revolutionize healthcare. By understanding a patient's genetic makeup, healthcare providers can prescribe the right medication and dosage, reducing trial and error, improving treatment effectiveness, and minimizing side effects. This approach acknowledges that each person is unique and recognizes the complex interplay of genetics and non-genetic factors to determine health outcomes. Real-World Impact of PharmacogenomicsJeff provides real-world examples of how pharmacogenomics can impact medication management. He discusses the role of the medication Clopidogrel, used with patients who are recieving a stent. He explains how genetic variations can affect the response to this medication, highlighting the importance of pharmacogenomics in ensuring effective treatment. The Future of HealthcareJeff discusses the future of healthcare, including the potential of wearable and implantable devices. He emphasizes the importance of giving healthcare professionals more tools to react in real-time and make informed decisions about patient care. He also discusses how companies like Coriell Life Sciences offer comprehensive medication management programs, highlighting the importance of scalability and accessibility in the adoption of pharmacogenomics.

⚡PFAS stands for Per- and Polyfluoroalkyl Substances. Simply put, PFAS are man-made compounds synthesized in a laboratory. ''They were first made in the 1940s. Teflon was one of the very first developments of PFAS. PFAS is a universe of chemicals useful for lots of different consumer and industrial applications over the last 60 to 70 years. These include things like firefighting foam, stain repellents on carpets and textiles, and also mist suppressants to protect workers in chromium plating activities.''⚡We all have the right to clean water, hence the necessity for testing it for PFAS. Although we can get exposed to PFAS in all sorts of ways, we are primarily interested in determining whether our drinking water supplies have been exposed to these chemicals. ''Water is one of the things that we all require. We can be exposed to PFAS through food and contact with materials that contain PFAS. But we all have to drink water, and because of the mobility and the persistence of PFAS, it's important for us to understand this base level exposure that we could potentially have from our water supplies.''⚡Over 96% of Americans have PFAS in their blood. The statistics may seem concerning, however, Dr. Ferguson shares advice on how we can minimize exposure to these chemicals. ''My kids and wife always tell me I cook like an 80-year-old grandmother. I use cast iron pots, stainless steel, and no Teflon in the kitchen. Also, choose a water filter that can help to remove PFAS. And then, in terms of the products you buy, things like clothing. Try to avoid things that have fluoridated stain repellents on them. That does a couple of things. First of all, it protects you because you've chosen a material that doesn't contain PFAS, but it also puts pressure on the manufacturer.''

⚡ Green chemistry aims to anticipate toxicity and global climate change. Green chemistry is an area of chemistry that focuses on reducing pollution and building a more sustainable world. John explains, "What you may be surprised to learn is that if you look at the curriculum, if you look at the classes that a chemist takes from the very beginning to getting a Ph.D., very few, if any, universities have within that curriculum, any skills, any ability to predict, ‘Will this molecule be toxic? Will this molecule hurt the environment?’ Of the massive curriculum that is chemistry, what has been missing is that. So if you put a box around that and say, ‘What are the skills necessary to anticipate toxicity, global climate change, energy use, all the things that we define as sustainability issues, the molecular mechanisms necessary to address them?’ That is the body of what is called green chemistry."⚡ Building a sustainable future needs to be collaborative. We're all in this together when it comes to building a sustainable future. John explains, "Over time, the two aspects of industry and industry have not become closer together but have actually become a little bit further apart. At the very time we need innovation, at the very time we need creativity to solve these sustainability problems, both aspects of the chemical enterprises are not coming together. So, in an ironic way, the closed-loop metaphor works against us. So this Mobius strip, interesting enough, if you look at it in a certain way, it looks like an infinity symbol, bringing and showing that we're all in this together, and this has to be a collaboration." ⚡ Green chemistry gives us the tools to put sustainability into motion. The desire for sustainability is not enough to make the necessary change. We also need to have the right tools. John says, "You can't achieve sustainability goals just by wanting them. There's a skillset that is required in the lab that will then bring about the technologies and the materials to achieve those goals, and so the relationship between green chemistry. You can have all the regulations in the world, you can have all the desires in the world, but if you don't have the ability to meet those desires, you just got a lot of sad people, and so we need to have green chemistry to move from talking about this stuff to actually doing it."

⚡ Cell therapy is a promising field. Cell therapies can potentially transform medicine and treat some of the most severe diseases, like cancer. Wendell says, "That's one of the innate challenges here — how do you make something that's very controlled and specific and yet also very potent enough to really overcome the disease. And that's where we really think that cell therapies can be very powerful because cells can read different signals and then process that information almost, like I said, a little computer and then make very intelligent decisions but ones that are also still very potent in terms of killing the tumors." ⚡ There are many challenges in the cell therapy field. Even though the cell therapy field is powerful, it has its limitations. Wendell says, "There are many challenges that cell therapies face. There are many challenges we face in trying to overcome, say, solid cancers. But all of these are multifaceted problems. There isn't one solution, but they have different aspects when we think about cell therapies and make them a viable platform; not only do they have to be more effective, but also issues of how to manufacture them, make them more accessible and make them cheaper are major bottlenecks right now."⚡ Cell therapies could potentially help treat many serious diseases. Cell therapies are not only promising for cancer treatment, but they could help fight other serious diseases. Wendell explains, "I think that engineering and developing cell therapies in cancer is really just the vanguard of a bigger movement. If we really understand how living cells work and can program them in specific new ways, this could have a huge impact on a lot of diseases that we are not very good at treating. These include things like autoimmune disease or fibrosis, cardiac or pulmonary fibrosis, as well as degenerative diseases." 

⚡ What are the ramifications from a clinical research perspective if diversity is not appropriately represented in a clinical study populations? Even as diversity becomes increasingly important across different sectors, minorities continue to be left out of clinical trials and medical research studies. So, why is diversity so critical in clinical trials? Nik explains, "I think in terms of the ramifications if diversity is not appropriately represented — I think we, unfortunately, saw this clearly playing out during the pandemic when we were seeing a lot of the data emerging that many underrepresented patients, particularly black and Hispanic patients, were having worse outcomes with COVID. Yet when we were looking at a lot of the trials for vaccines and therapeutics, those patients were not being included in the studies. And then as a result, from a scientific standpoint, when the results of the studies came out, people were understandably questioning, ‘Are these results that we're seeing generalizable to all the patients with the disease and especially the patients who're having the worst outcomes?’"⚡ Recruiting and enrolling more representative populations does not mean delaying the study. Despite what many people think, enrolling diverse populations in clinical trials won't slow down the process. Nik shares his experience with including underrepresented minorities in peri- and post-approval studies through decentralized clinical trial models. He says, "The great thing was that not only did we complete that study and we had the data and that really gave us a lot more confidence in our medicine but also that trial recruited in record time, which was one of the myths that people had been saying, 'Oh, we could have a more diverse trial population, but it's going to slow the study, and we don't want to do that.' So, this study, we had 84% from underrepresented populations and actually was one of the fastest studies that Genentech ever enrolled and was published in the New England Journal of Medicine."⚡ Clinical trials must strive to be more diverse. Enhancing diversity in clinical trials is a win-win for the entire public health system, not just for underrepresented populations. Nik explains, "We're thinking about this very carefully at Genentech, and we're trying to make sure that our efforts in terms of improving diversity in clinical trials is not just a one-off thing, that we really make this part of just the routine way that we do every clinical trial."He adds, "I think our vision, as I mentioned, is that we really need to make enrolling a diverse and representative population a routine part of how we conduct all of our trials, which will not only increase the robustness of our research, but it will also help ensure broad patient access, and as we've seen from a few studies, not only will it not slow down studies but if done right can even accelerate trials. If we can do all of that, that can really represent a true win-win for patients, for us as a company, and for society as a whole."

⚡ Decentralized clinical trials aim to reduce patient burden. Decentralized clinical trials can help make research more patient-centric. Tim explains the role of decentralization, "It's fair to say that that change management component is absolutely critical in terms of the decentralized adoption, and I think, when I look ahead in terms of decentralization, I see an amazing landscape for patients and the partnerships with EmVenio and also the kind of opportunities Thermo Fisher Scientific has in really driving forward unique and collaborative solutions for the better of the patient and really focusing on reducing that patient burden."⚡ We need to make clinical trials more patient-centric. Patient-centricity is key when it comes to improving participation in clinical trials and clinical research progress overall. Tim says, "As an industry, we talk about patient-centricity and I think we embrace significant patient-centricity by taking a research site with all the research professionals on board to the patient's home."⚡ Representation in clinical trials matters. Diversity is vital to preventing and treating diseases across race and gender. Thad says, "A couple of stats recently — there was one study we supported where of the 2,500 patients that EmVenio enrolled, 65% were from underrepresented populations, and so it really showed that value there. And what we're seeing more broadly is that across the studies we support, greater than 40% of the patients we're working with come from minority populations. And so, to contrast that against industry stats of around 10% to 20% as an average, we're offering more than double the ability to reach these populations that otherwise don't have access. So I think what we're seeing is that the results are really bearing on the value that we're bringing together."

⚡ There's a diversity mismatch in the oncology workforce. One of the biggest challenges in the oncology space is a lack of diversity in the workforce. The population of the United States is very diverse, while the oncology field is not. Dr. Upal Basu Roy says, "We know that the United States is very diverse. As we speak, the population is very diverse, and we have about 12% African Americans in the population — about 18% who identify as Hispanic/Latinx — and 3% of the population who identify as American Indians and Alaska natives. But is that diversity reflected in the oncology workforce? Absolutely not. So we have a problem. So if you look at the latest statistics from the ASCO workforce report in 2020, only 5% of oncologists identify as Hispanic/Latinx, 3% as Black or African American, and 0.1% as American Indian and Alaska native. So we have this mismatch."⚡ Patients have better health outcomes when treated by doctors who look like them.   Dr. Upal Basu Roy explains, "The population is very diverse, but the workforce is not diverse. So keeping that in mind, we created the Health Equity and Inclusiveness Research Awards specifically to foster minority scientists. Now you can ask me, ‘Why is that important?’ It is fundamentally important to have clinicians who look like patients because there's very good research that's shown that patients have better outcomes when they're treated by doctors who look like them. And patients are way more inclined to participate in clinical trials when those trials are being offered to them by clinicians who look like them."⚡ ‘No One Missed’ is an inclusive lung cancer campaign. ‘No One Missed’ is a community-led campaign driven by the LUNGevity Foundation. Dr. Upal Basu Roy talks about the campaign's main goals. He says, "As a scientist, I focus on science and innovation. But as a patient advocate, I focus on access. Because I think we need to keep in mind that science is a public good. Innovation is a public good. And we, as a patient advocacy group, need to make sure that the science we fund today reaches patients tomorrow. And biomarker testing targeted therapies are a huge piece of the treatment arsenal of lung cancer, and we, as a foundation, are committed to making sure that these innovative approaches treat patients no matter where they're diagnosed, no matter their gender, sexual orientation, their race and ethnicity, where they live, or their socioeconomic status."

⚡The most critical part is to shorten the time between doing the test and getting the results. From there, doctors will be better positioned to provide the best care to the patient. ''There's always pressure from the patient, the family, and the physician to start therapy as soon as possible. [...] So getting that test earlier allows us to do the right thing for the patients, improve their outcomes, and frankly, reduce costs.⚡Staying up to date with changes is the most noticeable obstacle to providing targeted therapy. We expect medicine and science to advance, resulting in better solutions in healthcare. But sometimes, patients don't feel comfortable exposing themselves to new approaches, such as targeted treatments. However, Dr. Scott thinks differently. ''I don't think that patients would be the barrier because patients want the best therapy with the least toxicity. The barrier is rapid advance. I've been in oncology for a long time, and I think that relying upon what we learned in medical school, what we did in residency and fellowship, and during our training when things are changing so quickly, it becomes more difficult to stay ahead and to stay up to date. Most oncologists in the community are generalists, and those are the typical oncologists I work with. So we've brought tools and programs to help them so that whether it's AI tomorrow in their EMR — their medical record tool — or programs today, we wanna drive awareness and appropriate utilization.''⚡The good news is that we already have tools that ensure efficiency. They result from science and tech companies' continuous and joint efforts. ''Historically, I would have a patient with lung cancer, and I would have to call up the pathology lab at my hospital — because I don't make that diagnosis in my office — and I'd have to ask them to send tissue or blocks via FedEx or UPS to a third party. So there's travel time. Then it would take two or three weeks for that third-party lab to do the analysis. And then, I would get back a report, and typically it'd be 26 to 29 days from that asking to have the test submitted. Now we have companies doing what's called a liquid biopsy or using liquid specimen blood where they can do a very similar analysis. [...] It can be as soon as eight days. So that's one event. The other advance, which is even more exciting, is the ability of clinics or hospitals to put the type of equipment we call next-gen sequencing testing tools into their practice. And if you do that, you eliminate the shipping time there and back, and theoretically, you could get results in three to five days.''

⚡ We can't limit ourselves to only humans and animals to fight diseases and cure illnesses. To cure diseases and illnesses, we need to understand how the environment, humans, and animals intersect. Professor Akebe explains, "We get that whole cycle that starts again. It [waste] leaves from our homes. It leaves from our hospitals. It gets into the treatment plants, gets into the river. It is used to irrigate our crops, goes back to the animals, and you see the whole vicious cycle continue. So that is where we now say that to solve that issue, we can't just limit ourselves to humans. We can't limit ourselves to animals. We can't limit ourselves to the environment. We need to have those three compartments coming together."⚡ The challenges of working as a microbiologist in a rural community. Having traveled to many of Africa's remote places, Professor Akebe believes that the continent's environment can expect a positive change in the future. He talks about what it's like working as a microbiologist in these rural communities: "The major challenge of working in a rural community is it limits, first of all, the quality; it doesn't compromise, but it limits based on the objective. It limits the quality of work you can do because you want to go cheaper. You have everything that you want, you know that you can get it, but it becomes a little expensive now because you can surround the facility, and so, you have to outsource."⚡ Giving back to the community by educating them. According to Professor Akebe, we need to help our communities understand our research. He says, "One of the things I'm doing now is that I'm working with one of my mentors in the US…and we are trying to see how to translate this whole concept of One Health and antimicrobial research and antimicrobial resistance into cartoons. We will translate them into cartoons so that even our kids who are watching TV can learn from that. So any form in which such messages can go out to the community, for me, is the best because I feel like it's unfair for the communities where we do research to not understand what we are doing."

⚡ The MoonArk is both conceptual art and a time capsule. Almost 15 years ago, the idea was to create a time capsule carrying fragments of the world as we know it today and  send it to the moon to be discovered in the distant future. Today, the project has 60 members from 18 institutions and over 250 contributing designers, scientists, poets, musicians etc. Mark Baskinger, one of the first to get involved with the project, shares what it was like at the beginning. ''The MoonArk was a conceptual idea concocted by a few pioneering faculty members here, namely, Red Whitaker in the Robotics Institute and Lowry Burgess, former Dean of the College of Fine Arts. And their thought was that if Carnegie Mellon were to go to the moon, it can't just be the sciences and the technologies and that side of campus represented and that the arts would surely have something to contribute.''  ⚡ Working on MoonArk was creative and exciting but challenging. As our guests say, creating an object like the MoonArk goes beyond making it look nice. It has to be safe and resilient to different conditions. ''We wanted it to be beautiful and aesthetic. So we went about making it with no real knowledge of what it was going to take to get it there. So, when it was time to put the rubber on the road, we were like, 'Oh, my goodness. It has to go through all this different, rigorous testing,''' says Dylan.⚡ Many components are handmade. What makes the MoonArk astonishing is the amount of work, especially manual work, that’s been put into its creation. ''[...], a sculptor metal worker made quite a contribution to this project. It was amazing to visit and watch him do this under the monitor, zoomed in significantly — getting to see the intricacy of the work that was a part of it. But the biggest issue was whether those micro welds would be strong and consistent enough to be able to sustain the rigorous trip that the MoonArk was going to go through,'' explains Matt.