In this episode of Science with a Twist, host Terri Somers talks to experts in immunogenetics and histocompatibility about human leukocyte antigens, or HLAs, which are biomarkers on our cells that provide crucial information about our immune system. HLAs have been used for decades now to match the right donated organ or cells to a patient in need. As science has gained a deeper understanding of the immune system, the utility of HLAs has expanded significantly, helping to transform healthcare.

Guests-at-a-Glance

 Name: Marcelo Fernandez Vina
💡 What they do: Director, Histocompatibility & Immunogenetics Laboratory
💡 Company: Stanford Blood Center
💡 Noteworthy: International leader in HLA research with over 30 years of lab and academic experience
💡 Where to find him: LinkedIn

💡 Name: Dave Lowe
💡 What they do: Senior Director, R&D – Transplant Diagnostics
💡 Company: Thermo Fisher Scientific
💡 Noteworthy: Leads global development of HLA testing tools for transplant and immunogenetics
💡 Where to find him: LinkedIn

In this episode, Namritha Ravinder, director of cell biology at Thermo Fisher Scientific, explains the groundbreaking technologies that correct the genetic errors in our cells that lead to disease. These gene therapies may offer permanent solutions with single-dose treatments. Namritha also provides an expert’s view on what’s to come from more than 2,000 gene therapies in the pipeline, and the innovation needed to make these new treatments accessible to patients.

From energy-efficient cold storage to sustainable lab products, James and Alyssa discuss how the life science industry is evolving to meet ambitious climate goals.

• How health equity is a key component of Thermo Fisher’s core business.
• How Thermo Fisher leverages its capabilities and customer relationships to further its impact.
• Initiatives that improve health equity through accessibility to drug-resistant HIV testing, next-generation sequencing to diagnose lung and breast cancer in 30 underserved countries, increasing the accessibility to and diversity in clinical trials, and more.
• New programs in 2024.

• The challenges of recruiting women and minority groups for clinical trials, noting the logistical and societal barriers they face.
• Innovative solutions, such as telemedicine and flexible scheduling, to make trial participation more accessible. 
• Recent advances in clinical research, including a groundbreaking preeclampsia test and contributions to COVID-19 vaccine trials, highlighting Thermo Fisher's pivotal role in these developments.

Despite the challenges associated with plastic in the environment, Kat Knauer, Ph.D., emphasizes the indispensable role of plastics in healthcare, research, and daily life. She points out that while plastics have significantly improved quality of life and medical care, their improper disposal poses a significant threat to the environment. She advocates for a balanced approach to improving plastics use, suggesting that the answer lies not in eliminating plastics altogether but in innovating more sustainable management and recycling practices. This nuanced perspective encourages listeners to appreciate the benefits of plastics while acknowledging the urgency of addressing their environmental impact.

Innovations in Plastic Recycling and Sustainability

Kat introduces groundbreaking work on the development of sustainable technologies for recycling plastics and designing new materials that are recyclable by design. She highlights the BOTTLE Consortium's efforts in chemically upcycling existing plastic waste streams and creating plastics that are more compatible with the environment. This initiative reflects a significant shift towards reducing reliance on single-use plastics and fossil fuels, aiming for a circular economy where the life cycle of a plastic is extended through recycling and reuse. Kat's discussion on these innovations offers hope for a future where plastic pollution is significantly mitigated through scientific research and technological advancement.

Collaboration as a Key to Tackling Plastic Pollution

The conversation underscores the importance of collaboration across different sectors to address the plastic waste crisis. Kat mentions partnerships with companies like Amazon and Patagonia, which are working towards creating more sustainable packaging solutions and textile recycling methods. These collaborations illustrate how combining efforts from the scientific community, industry leaders, and consumers can lead to innovative solutions that promote a more sustainable future. Calling for increased collaboration and communication to bridge gaps in the recycling process, Kat also offers tips for more responsible consumption and disposal practices among consumers.

Dr. Peter Marks highlights the groundbreaking advancements in gene therapy, especially for rare diseases with high unmet medical needs. He discusses the FDA's role in fostering these innovations, underscoring the importance of understanding gene therapy's application and ensuring its safe delivery. Dr. Marks emphasizes the challenges in manufacturing gene therapies, noting that overcoming these hurdles is essential for treating large populations and common diseases. This insight reflects on the hope and complexity of gene therapy, aiming to provide one-time treatments that could drastically improve patient outcomes.

The Role of AI in Enhancing Gene Therapy Development

Dr. Marks points out the significant potential use cases for artificial intelligence (AI) in gene therapy, from product design to clinical development and manufacturing. AI’s ability to predict off-target effects and streamline the manufacturing process could be a game-changer in this space. By harnessing AI, researchers and developers can optimize safety signals and process large quantities of data for continuous improvement. This insight underscores the potential of AI to revolutionize gene therapy, making it more efficient and effective.

Emphasizing the Human Impact of Gene Therapies

Dr. Marks and Miller share personal stories of patients and families affected by rare diseases, illustrating the transformative power of gene therapy. They recount profound effects of recent gene therapy approvals on individuals and their communities, particularly highlighting Duchenne Muscular Dystrophy. Marks's narrative conveys the deep emotional and physical impact of gene therapy, not just as a scientific achievement but as a means to significantly enhance lives. This insight brings to light the importance of patient-centered approaches in the development and application of gene therapies.

Joshua J. Coon discusses the transformative role of mass spectrometry in biomedical research. This technology, as he explains, allows for the precise weighing of molecules, providing critical insights into their identity and quantity. Coon's lab utilizes mass spectrometry to analyze complex biological systems, such as cells and tissues, identifying over 10,000 molecules in a single sample. This capability has significant implications for understanding genetic and lifestyle influences on molecular behavior in organisms. Coon's work exemplifies how a fundamental scientific tool can lead to profound discoveries in disease mechanisms and potential treatments.

Linking Unknown Proteins to Disease: A New Frontier

Coon highlights a groundbreaking project where his team investigates proteins of unknown function, particularly those involved in metabolism and located in mitochondria. By creating cell lines with each lacking a different protein and then using mass spectrometry to analyze the resulting molecular changes, they can infer relationships between known and unknown proteins. This approach has led to identifying the functions of several proteins and linking them to specific human disorders. This research is not only pioneering in its method but also crucial in laying the groundwork for new therapies, as understanding protein functions can lead to targeted drug development.

Personal Journey: From Rural Roots to Research Leader

Joshua J. Coon shares his personal journey, beginning in rural Michigan, where his early interests in science and woodworking led him to the field of mass spectrometry. His path took him through the University of Florida for his PhD and the University of Virginia for postdoctoral studies, culminating in leading his research group at the University of Wisconsin-Madison. Joshua emphasizes the joy of training the next generation of scientists, with his lab producing over 50 PhD students and postdocs who are now contributing significantly to science globally. This insight not only sheds light on Coon's professional achievements but also highlights his role in mentoring and shaping future scientific leaders.

Brazil has been at the forefront of combating HIV, implementing proactive measures that have made a significant difference. The country began providing no-cost access to CD4 and viral load testing and antiretroviral drugs as early as 1996. This early intervention and consistent approach led to a remarkable outcome: the number of HIV cases in Brazil was significantly lower than initially predicted. An article from the New England Journal of Medicine stated that initial estimates predicted Brazil would have 1.2 million people infected with HIV by the year 2000, but with the strategies the country put in place, their actual numbers were about half of what was predicted. By offering free access to treatments and diagnostic tests, Brazil showcased the importance of early and sustained intervention in managing and reducing the spread of HIV.

The Rising Challenge of HIV Drug Resistance

One of the most pressing challenges in the fight against HIV is the development of drug resistance. Dr. Ricardo Diaz emphasizes that as the HIV virus replicates, it can produce strains resistant to treatment. This resistance threatens the efficacy of antiretroviral drugs, making it crucial to monitor and manage. The World Health Organization reports an increasing rate of HIV drug resistance, underscoring the need for continuous research, monitoring, and adaptation of treatment strategies.

Pre-exposure Prophylaxis (PrEP) Drugs Exist, but are not 100% Effective

PrEP, or pre-exposure prophylaxis, is also an antiretroviral drug given to uninfected individuals who are at risk of infection to reduce their chances of acquiring HIV. PrEP is highly effective at preventing HIV when taken as indicated, but much less effective when it isn't taken consistently. Additionally, it's possible to be exposed to HIV strains that are drug resistant while on PrEP, so monitoring resistance in people on PrEP is another important step in prevention.

The Gap in HIV Drug Resistance Testing

Despite the advancements in treatment, there's a noticeable disparity in HIV drug resistance testing, especially in Brazil. Dr. Diaz highlights that while a centralized lab in Brazil performs genotype testing, the number of tests conducted falls short of the actual need. With 10% of patients on treatment showing a viral load above the desired limit, the demand for resistance testing is evident. Bridging this gap and increasing surveillance efforts is essential to tailor treatments effectively and combat the spread of drug-resistant HIV strains.

⚡Some companies don't produce semiconductors in-house. The rationale behind such a decision lies in the need for a specific environment and certain conditions for making these chips. ''The fabs themselves are like huge low cities. All of this has to be clean room work. It needs to be done within one location generally. So because it's clean room work, you can't send that across until a critical step is completed in the manufacturing process. [...] If even a dust molecule were to land on any of these chips, the dust molecule's width is wide enough to block the passes of electrical current on the chip, thus making the chip ineffective," explains Geoff. 

⚡We use a wide range of gases to prevent impurities from harming the chips. The most commonly used are helium, nitrogen, argon, and hydrogen. However, the gases used must be in perfect condition. And that's Mark's job. ''My experience is mostly with mass spectrometry, which is one of the best ways to analyze compounds like this. Specifically, an API-MS — an atmospheric pressure ionization mass spectrometer — has a simplified analysis of big bulk gases. For example, in the past 20 or 30 years, you could not analyze oxygen, if you could not get down low detection limits, analyze oxygen in bulk nitrogen. That used to be a lot more difficult with traditional techniques. But Thermo Fisher Scientific has put out some new analyzers with such a low detection limit there that we can accurately say we will get 10 to 15 parts per trillion in our gases that are being put through all these processes.'' 

Eleanor emphasizes the importance of pursuing what you love in STEM. She advises students to focus on their interests rather than trying to impress judges or make a big impact. Eleanor encourages students to be scrappy and innovative and to believe in their ability to navigate through challenges. She underscores that STEM is not just for prodigies and professionals and that anyone can make a difference.

Community Can Help Advance STEM

Eleanor and Maya discuss the importance of community and mentorship in STEM. They highlight the need to break through the competitiveness of STEM and foster inclusivity. They also discuss the role of organizations like Thermo Fisher Scientific in promoting access and equity in STEM learning experiences.

Gratitude and Mentorship are Key

Eleanor and Maya highlight the importance of expressing gratitude to mentors and the value of paying it forward. They emphasize that mentors play a crucial role in guiding students in their STEM journey. Eleanor also encourages students to remember to thank their mentors, emphasizing that a little bit of gratitude can go a long way.

Jeff 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 Pharmacogenomics

Jeff 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 Healthcare

Jeff 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.

⚡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.''

⚡ 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."

⚡ 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." 

⚡ 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."

⚡ 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."

⚡ 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."

⚡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.''

⚡ 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."

⚡ 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. 

💡 Forensics can help answer questions regarding the history of humanity. Although the first association with forensics is solving crimes, Dr. Diepenbroek says forensic science can offer more. ''Yes, we solve crimes, but we can also solve missing persons cases — even if they are more than eight years old — because the power of forensic DNA analysis is that we can identify the victim despite how much time has passed.''

💡 The joint work of forensics and other sciences is critical. As mentioned above, forensics helps illuminate particular historical events. The Sobibor Project is an example that proves the significance of such collaborations. "We had scientists from many different fields involved — specialists in archeology, history, anthropology, and forensics — and what we achieved together showed how all of the sciences, even if a bit distant, completed and helped each other. So the remains would never have been found if it was not for the archeological work carried out in the camp, but the truth about their identity would not have been discovered without DNA analysis."

"What we need to capture in these surveillance efforts is how these viruses are changing and how quickly they are changing. So you've heard of mutations, and they are a result of these changes in the viruses. They change the nucleic acid or the DNA sequence of the virus itself and that changes the infectivity or the severity of the disease itself. So we monitor these viruses to see how the DNA sequences are changing and whether these changes pose any more threat to the population in terms of infectivity or the severity of the disease."

🎙 The uniqueness of COVID-19. Coronaviruses have been around for decades. But, COVID symptoms are considerably more severe than those of other coronavirus infections. Kamini shares her viewpoint on the uniqueness of COVID. "I think what is unique about COVID is just the level of population spread. It creates this reservoir for the virus to mutate much faster because initially, when COVID came out, we thought it mutated much slower than the influenza virus. But over time, we've seen it pick up speed and momentum, and it's changing more rapidly."

🎙 Viruses mutate constantly. Mutations are a regular part of every virus's life cycle, but we need to monitor them to identify variants of concern. Andy explains, "The virus is evolving, and all viruses constantly evolve, and they spin up new variants. Whether those variants rise to what Kamini described as a variant of concern depends on exactly what changes happen in the DNA sequence. But variants of interest and other variants that have no effect on what we are concerned about — which is the health outcome of being infected — happen all the time."

🎙️ Renvo makes the entire process more effective. As Miguel explains, when they first launched the solution, they had to take the sample to a lab and wait for up to 24 hours for the results. However, Renvo, a rapid PCR test, was developed to speed up the entire process. ''It allows us to bring it into the same space as the AerosolSense unit to be able to offer an answer as to whether or not coronavirus is present within about 30 minutes. Equally as important is that the sample transfer and preparation is very safe because it's intended to be used by virtually anyone who has the ability to follow our very brief video-based training program and to do so in a way where they are not put at significant risk of contracting the virus.''

🎙️ AerosolSense paired with other protective measures is the path to a safe school. Once they launched AerosolSense,  a pilot project began involving schools. Michelle Jensen of Deerfield Community School District saw this as a fantastic opportunity to improve two-year-old mitigation strategies. At first, they only got negative results, but AerosolSense detected coronavirus in their school after three or four weeks. ''When we have a positive in the same week that we have a negative, it does tell me that people are doing the strategies that we asked. Parents are remembering to keep students home and going and getting tested as soon as possible,'' says Michelle.