From Organ Donation to Drug Safety: The Power of HLA

How is a decades-old scientific tool that revolutionized organ transplantation now being used in cancer immunotherapy and autoimmune disease?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

Imagine a future where diseases like leukemia, sickle cell anemia and multiple sclerosis are no longer life sentences, but treatable and even curable. That is the promise of gene therapy.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.

Laboratories use up to ten times the energy of typical office spaces, making sustainability in science a pressing issue. In this episode of Science with a Twist, host Terri Somers speaks with James Connelly, CEO of My Green Lab, and Alyssa Caddle, Senior Director of Global Sustainability at Thermo Fisher Scientific, about steps laboratories can take to reduce their environmental impact. 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. 

Listen to the conversation as they discuss: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.

Dr. Blackburne shares insights into: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.

The Critical Role of Plastics in Modern SocietyDespite 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 SustainabilityKat 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 PollutionThe 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.

Gene Therapy's Potential to Transform Rare Disease TreatmentDr. 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 DevelopmentDr. 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 TherapiesDr. 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.

Revolutionizing Biomedical Research with Mass SpectrometryJoshua 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 FrontierCoon 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 LeaderJoshua 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's Proactive Measures Against HIVBrazil 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 ResistanceOne 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% EffectivePrEP, 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 TestingDespite 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.

⚡Semiconductor chips go through a long manufacturing process. It all depends on the type of chip, but the standard timeframe is between 120 days and nine months. It is a three-phase process that includes design and frontend and backend manufacturing, all dependent on various factors. ''These are global supply chains supporting the completed product. Semiconductor chips could be manufactured by a large fab, maybe most of it within the house, but there are diversified approaches too, where the chip is moving across the country to complete certain stages of manufacturing.''⚡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.''