Twindemic: How the Seasonal Flu Collides with the COVID-19 Pandemic

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.'' 

The Power of Passion in STEM 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 STEMEleanor 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 KeyEleanor 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.

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."