Finding Genius Podcast

Phillip D. Zamore Bio: Phillip D. Zamore, Ph.D. has been an Investigator of the Howard Hughes Medical Institute since 2008. In 2016, he became the Chair of the RNA Therapeutics Institute, which was established at the University of Massachusetts Medical School in 2009. Dr. Zamore also is Professor of Biochemistry and Molecular Pharmacology, the department he joined in 1999, and he became the Gretchen Stone Cook Professor of Biomedical Sciences in 2005. Dr. Zamore received his A.B. (1986) and Ph.D. (1992) degrees in Biochemistry and Molecular Biology from Harvard University. He then pursued postdoctoral studies on the role of the RNA binding proteins in Drosophila development at The Whitehead Institute for Biomedical Research, in Cambridge, Massachusetts. Dr. Zamore's laboratory studies small RNA silencing pathways in eukaryotes and prokaryotes, including RNA interference (RNAi), microRNA, and PIWI-interacting RNA pathways. Dr. Zamore and his collaborators seek to use these insights to design therapies for human diseases, including Huntington's disease. Under Dr. Zamore's mentorship, the Zamore Lab has produced dozens of researchers working at top institutions both in the United States and abroad. In 2015, Dr. Zamore was awarded the Chancellor's Medal for Excellence in Scholarship at the University of Massachusetts Medical School. To date, Dr. Zamore has more than 150 publications and has been among the most highly cited researchers for more than a decade. He serves on the editorial boards of numerous journals and is in demand as a presenter at conferences and institutions worldwide. Dr. Zamore holds more than 20 patents, with other applications pending; he was elected a Fellow of the National Academy of Inventors in 2014. In 2002, Dr. Zamore co-founded Alnylam Pharmaceuticals (Cambridge, MA), a publicly traded biotech company which now has more than 1000 employees and multiple drugs in clinical trials. Alnylam's first drug, ONPATTRO, a first-of-its-kind RNAi therapeutic, for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults, was approved by the FDA in 2018. In 2014, he co-founded Voyager Therapeutics in Cambridge, MA. Chair and Professor at University of Massachusetts Medical School, Phillip Zamore, joins the show to discuss a new method of gene silencing called RNA interference (RNAi). Tune in to learn the following: How the RNAi system is analogous to the basis of vaccination How specifically the method of RNAi prevents a protein from being made and what happens to the mRNA after it has been cut Why RNAi will never replace the knock-out method, and the benefit of combining both methods Zamore states that the world's diseases can be divided into two broad categories: those with mutations in the genome that can be addressed by turning off the gene forever, and those with mutations in the genome that can be addressed by lowering the amount of a gene product, as opposed to turning off the gene completely. The gene knock-out method is used for the first kind of disease, and the effects of the knock-out are irreversible. This makes the method a good tool for studying model organisms in the lab, but rather risky as a therapeutic intervention for humans. This is where a new method called RNA interference comes into play and holds promise for the future of medicine and the treatment of diseases. RNA interference is a way of destroying messenger RNA (mRNA) in order to prevent the creation of a protein. Unlike other methods, RNA interference uses a natural cellular pathway, which makes it more effective than other mechanisms in turning off disease genes. And just like taking a drug, stopping this process means stopping any unwanted side effects, which means it's a lot safer and less risky than the knock-out method. There are currently two RNAi drugs on the market, both of which direct small RNA (sRNA) to the liver where the protein in question is made. By way of preventing the creation of that protein, the disease gene is turned down (almost off). Zamore explains why the liver is particularly amenable to these drugs, and the ongoing research and development taking place for drugs that target proteins made in other areas of the body. He also discusses the near-term goal of bringing to market an sRNA drug that blocks the production of a protein in the cholesterol biosynthesis pathway. This drug would function as a replacement for statins, and comes with fewer side effects and would only need to be taken by a patient twice per year. Zamore brings an impressive amount of insight and information to the show, discussing a number of topics in depth but with enough clarity to follow along with ease. Learn more by visting his Google Scholar page at https://scholar.google.com/citations?user=xYLmV7YAAAAJ&hl=en.

UC Davis's One Health Institute (OHI) focuses on problem-solving for emerging infectious diseases and conservation challenges to address global health issues. Executive Director Jonna Mazet shares their Predict project's current findings, including How they have discovered numerous viruses and more than a hundred different coronaviruses, the family to which COVID-19 (SARS CoV-2) belongs; How they identify high-risk transmission zones where people are working with animals in a especially stressful way that would cause virus spillover; and What risk factors they've developed to gauge the viruses themselves through the help of 70 different international researchers. In addition to her work as Executive Director, Joanna Mazet is a Professor of Epidemiology and Disease Ecology at the UC Davis school of Veterinary Medicine. OHI has been working since 2009 to understand viruses that spill over from animals. For the COVID-19 version specifically, they've been using their Predict platform to help global communities predict, understand, and identify its spread. OHI and their Predict project is especially looking ahead to prevention for future global health issues. She discusses the various approaches, from bringing together ministries of health, agriculture, and environment in countries with less resources to communicate and identify high transmission zones. She describes the factors they use to identify high risk zones and means for mitigation. Dr. Mazet also describes the essential efforts to prevent future global health issues such as pandemics, including the need to understand as much about viruses as we do about bacteria. She explains that predicting a virus's harm potential is more about its ability to jump to multiple host species rather than its relatedness to other harmful viruses. In addition, they are testing species that weren't the target host to understand SARS CoV-2 (COVID-19) better and figure out clues to help scientist fight other viruses. To find out more, see the list of published literature on predict.global, where maps of their surveillance work with test results and affected species are also posted.

Sonja Schrepfer Bio: Sonja Schrepfer, M.D., Ph.D., Professor of Surgery, founded the Transplant and Stem Cell Immunobiology (TSI) Lab in 2009 in Germany. In 2015, she joined the faculty of the Department of Surgery at the University of California San Francisco and was Director of the TSI Lab at UCSF. Sonja is scientific co-founder of Sana Biotechnology Inc. which she joined as SVP in 2019. Dr. Schrepfer's research career has been dedicated to making fundamental discovers in transplant and stem cell immunobiology. Pluripotent stem cell (PSC)-based approaches are effective in immunosuppressed/deficient animal models; but in humans, systemic immunosuppression cannot be justified, due to severe side effects and significant risk of infections and malignancies. So far, only a few immunological strategies have been proposed to overcome these hurdles. Work by Dr. Schrepfer is at the forefront of PSC immunobiology and paves the way for treatment of a wide range of diseases – from supporting functional recovery of failing myocardium to the derivation of other cell types to treat diabetes, blindness, cancer, lung, neurodegenerative, and related diseases. She spent many years examining in detail the fetomaternal interface for application to the envisioned cell therapy. Her work with one of the most antigenic phenotypes, antigen-presenting endothelial cells, demonstrates that hypo-immunogenic cells reliably evade immune rejection in allogeneic recipients that are entirely mismatched in their major histocompatibility complex profile, and further, these cells show long-term survival without immunosuppression in mice and humanized mice (published in Nature Biotechnology in 2019). Sonja is currently Adjunct Professor at UCSF investigating the immunobiology in "tissue chips in space"; that is sending tissue chips to the international space station (ISS). She participated in three flight missions as collaborator and was the PI on the SpaceX16 mission (December 2019). This research will provide insight into what physiological effects time in outer space might have on astronauts, with potentially important implications for future longer-term missions, and has the possibility to open the door to fascinating new discoveries that could be used in earth-bound immunology research. Tobias Deuse Bio: Tobias Deuse, M.D. is a cardiac and heart and lung transplant surgeon internationally renowned for his pioneering work in the development of minimally-invasive techniques for mitral valve repair. Dr. Deuse graduated the University of Stuttgart (Germany) in 1994 with a BS in Physics, and in 2000 earned an M.D. from University of Wuerzburg. Dr. Deuse thereafter received advanced training in cardiothoracic surgery at the University Hospital Munich-Grosshadern and University Heart Center Hamburg-Eppendorf. After obtaining his board certification in Germany in 2007 as a heart surgeon, Dr. Deuse completed a surgical fellowship in Lung and Heart-Lung Transplantation at Stanford and joined the UCSF faculty in 2015. Dr. Deuse's laboratory at UCSF is working on the immunobiology of pluripotent stem cells. To circumvent rejection, techniques such as somatic cell nucleus transfer (SCNT) into an enucleated oocyte (formation of a SCNT stem cell), fusion of a somatic cell with an embryonic stem cell (ESC; formation of a hybrid cell), and reprograming of somatic cells using certain transcription factors (induced PSCs, iPSCs) have been used. However, his work has shown that SCNT stem cells and iPSCs may have immune incompatibilities with the nucleus or cell donor, respectively, despite having identical nuclear DNA (published in Cell Stem Cell 2014). Further, he has demonstrated that mitochondrial (mt) DNA-encoded proteins as well as mtDNA mutations and genetic instability associated with reprograming and iPSC expansion can create minor antigens, producing rejection. His work also demonstrated that even autologous iPSC derivatives are not inherently immunologically inert for autologous transplantation (published in Nature Biotechnology in 2019). This has provided an important, promising avenue for selection of optimal stem cell therapeutics for future clinical applications ¾ via identifying the most compatible starter cell line and monitoring "near match" autologous iPSC products for mtDNA mutations and single nucleotide polymorphism (SNP) enrichments during the manufacturing process. Director Sonja Schrepfer, M.D., Ph.D., and co-director Tobias Deuse, M.D., explain the lab's research towards understanding and overcoming transplant rejection. They touch on Why finding ways to reduce rejection and successfully find transplantation avenues that don't require immunosuppression drugs is so important, How their research starts with pluripotent stems cells that must be differentiated and then transplanted, Why using a patients' specific stem cells still face rejection due to mitochondrial proteins that eventually form despite gene editing, and How the lab is working toward an "off the shelf" solution by altering proteins that trigger rejection and other means. Drs. Schrepfer and Deuse run the Transplant and Stem Cell Immunobiology Lab (TSI) at the University of California in San Francisco and specialize in heart and lung transplant issues through CRISPR, gene editing,and stem cell therapy. They begin by explaining the many complications a person taking immunosuppressant drugs faces and why their research seeks to address these issues and make for a safer system for patients. Further, they explain that patient-tailored stem cell therapy approaches are not suitable for large populations for several reasons, including the frequent need to treat a patient almost immediately for heart damage or other similar issues. They explain that while they can generate cardiac cells that don't get rejected at first, these cells can develop mutant proteins that causes rejection later. They are following a couple of approaches to address the rejections including learning how fetuses survive the mother's immune system. A big leap forward for the lab was learning how to knock out the molecule that signaled to the immune system its foreignness through CRISPR: in other words, they are learning how to make these introduced cells silent to the immune system. Finally, they describe their "off the shelf" goal of producing non-immunogenic cells ready for injection for a majority of patients and alternatively generating a hypo-immunogenic environment in the patient to prevent long-term rejection. For more, see the lab's web page at https://tsilab.ucsf.edu/

Gary Bolles discusses work concerns and opportunities, especially with the work-from-home dynamic that's grown from virus precautions. He addresses Ways the pace of change is accelerating in terms of tech, the digital economy, and what we are asking people to do, Some of the most important elements in effective company constructs, including an emphasis on alignment (communicating goals), and Some key specific strategies to follow in the face of the economic downturn to maintain the best in ourselves and our work life. Gary Bolles is the Chair of the Future of Work at Singularity University. He begins the podcast by specifying that the discussions about the future of work starts with addressing present concerns. He reminds listeners that change is accelerating, but also the spread of change is expanding—the skill set demands ask for much bigger switches than in the past—for example, consider the difference in going from a coal mine to computer science. He provides some modern examples of organizational innovations such as the manager-less company and distributed teams. He provides company examples for each and discusses ways these innovations may succeed and fail, but emphasizes what potential each innovation offers. As he acknowledges ways the virus has changed our work life, he advises that as we return to more interactions, it shouldn't be an either/or picture: in fact, a digital economy and technology allows us to build connections faster. Yet it's in-person when we really cement these relationships and can talk with less structure, and that holds creative value. He offers three strategies to follow: be a curious, life-long learner; maintain effective teams; and practice alignment, which means make sure people know what the company goals and priorities are. For more, find Gary Bolles' lectures on LinkedIn Learning and read his article in Techonomy called "Welcome to the Great Reset".

Beverly and Dereck Joubert are National Geographic explorers-at-large. They are featured in National Geographic's Earth Day commemorative special, Born Wild: the Next Generation. They share with listeners Some stories of the special animals featured in the Earth Day show, Their own concerns about wildlife conservation in the face of coronavirus stresses, and Elemental changes and policy shifts that must happen to take care of our planet. In addition to their National Geographic work, Derek and Beverly Joubert are conservationists and wildlife filmmakers. Derek is also an author and founder and director of Great Plains Conservation, which manages several wildlife reserves in Botswana, Kenya, and Zimbabwe. They've been involved in conversation for close to four decades. They discuss how in Born Wild, their adventure with a lioness and her new cubs is featured and share some of the extraordinary wildlife moments. They also talk about what it is like to be an explorer with National Geographic, how a typical day may start at 4:00 a.m. and end 14 hours later. They remark that National Geographic has encouraged the best in them for both storytelling and integrity. They end with ruminations about Earth Day, wildlife conservation, and climate change against the backdrop of the coronavirus lockdowns and crisis. They express that there's a tremendous opportunity to reassess and change our approach and demand policy shifts from governments toward conservation. They assert that we should be celebrating every day as earth day and give back to our planet host. For more about the special, see https://www.nationalgeographic.com/tv/shows/born-wild-the-next-generation.

Gregory D. Gorgas, President and CEO, explains what pharmaceuticals his company is developing to work with the body's endocannabinoid system. He touches on How our endocannabinoid system was discovered and how it works, The ways Artelo Biosciences approaches the development of pharmaceuticals, and What three products they are currently working toward releasing. Mr. Gorgas begins with how Dr. Raphael Mechoulam discovered our endocannabinoid system in Israel as he researched the effects of cannabis, trying to pinpoint what receptors it targeted. This allowed him to identify several receptors in our body, discovering this powerful system. Mr. Gorgas explains that the body makes chemicals that target these receptors and the cannabis plant mimics what the body already makes. He then discusses why his company is working on pharmaceuticals to address this system. He says that it's a powerful communication system throughout the body and handles responses to inflammation, stress, and any stimulus which the body would want to address. When the body is overwhelmed, introducing a chemical from outside the body may help this system. He then explains the three ways Artelo Biosciences is trying to target this system through pharmaceuticals: First, a naturally-occurring cannabinoid that's been altered to increase appetite yet avoid the euphoria or high state as a treatment for cancer patients; second, a cannabinoid called EBD with anti-anxiety and anti-inflammatory properties; and third, a fatty-acid binding protein-5 inhibitor originally researched as a cancer treatment. For more, see their web site at http://artelobio.com/.

After several friends were diagnosed with cancer, Marcus Freudenmann went on an intense research journey to try and help them fight the diagnoses. He shares his journey with listeners by describing His global travels and discussions with doctors that lead to an understanding of cancer treatment as process, How one particular doctor taught him to stop looking at treatments and start looking at what needs to be treated, and How he took these conversations and research and created his trulyheal.com program. When Marcus Freudenmann's best friend was diagnosed with cancer, he put his German mentality of "we can fix it" to work. After piles of research and ideas about new cancer treatments at hand, from paleo diets to ozone therapy, he had the humbling and demoralizing experience of seeing cancer progress further in his friends despite these remedies. He describes further discussions with one particular doctor who described three patients with the same cancer but very different backgrounds. He learned that an approach to any new cancer treatments, from special diets to ozone therapy, really needs to change its focus. For example, one patient had an intense bacterial presence in combination with living in a high EMF environment while another had a past history of Lyme disease. The doctor designed different treatments for all three patients despite having the same cancer, noting that one should stop looking only at treatments and start looking at what needs to be treated. That's how he was introduced to functional medicine doctors—he saw facing cancer as more of a process of putting a puzzle together. He made a mind map at the time that allowed for a fuller picture and understanding of a patient's situation as part of the treatment plan. This was the beginning of his training program, which he describes as a course-finding evaluation company. They offer a six-part training program that goes into key elements, matching new cancer treatments to an understanding of mental issues, lifestyle factors, physical imbalances, and inherited problems. For more and to access the free part of the training, see trulyheal.com/genius.

Author Dr. Tom O'Bryan shares his thoughts on how to boost immune systems as the coronavirus spreads. He touches on the following issues: Why testing for the Covid-19 antibodies is a beneficial tool, What we should have in our medicine cabinets and on our plates to boost immune systems, and What are some daily habits to reduce stress and improve our mental health. Author and National Book Award winner Dr. Tom O-Bryan is a strong and consistent voice in the medical world. He specializes in functional medicine and works to communicate with and educate the public on all sorts of medical issues. In this podcast he addresses ways listeners can boost their immune system amid the worries about the latest strain of the coronavirus. He reminds listeners of the basic timeline of how the virus hits and discusses the delay from the initial onset of symptoms to the drop to a much worse condition. He explains that this is because the virus can successfully hide in our cells from part of our immune system for a time. He comments that zinc is an effective way to protect our cells in this situation and in general. He also designates vitamin D and quercetin as helpful products to have on hand in addition to zinc and explains why. He then comments on why testing for antibodies is helpful in knowing the best actions to take and in knowing to what degree one needs to worry when the virus flares again sometime in the fall. He also discusses some mental health exercises, why it is important to not embrace junk food but rather eat every color in the rainbow especially now, and he offers several other methods for self-care. For more, listeners can tune in to "Coffee with Dr. Tom" at 9 am pacific on Facebook, Instagram, and his YouTube channel. The talks are being archived and past talks are available. For more and for links to his talks, see https://thedr.com/coffee/.

Professor James Shapiro shares his thoughts with listeners on all things viral. In this exploration of molecular biology, he touches on Some of the intricacies and differences in how retroviruses versus other types of viruses behave and affect their hosts; How viruses are sources of new information for cells that may be useful to evolving organisms at critical junctures; and Why he's studying the evolution of cancers in comparison to organismal evolution. James A. Shapiro has been with the Department of Biochemistry and Molecular Biology at the University of Chicago since 1973. He has written several books, including Evolution: a View from the 21st century. He begins by explaining some of the genome editing virus interactions bring about, including in the virus and bacteria-as-host relationship. He describes the protection phages (viruses that inhabit bacteria) offer bacteria from protozoans, for example. He adds examples of mammal and retrovirus interactions and genome editing, citing placental development as a result. These, he comments, are examples of how viruses introduce new elements into evolving organisms, leading to his virus-as-R & D analogy. Dr. Shapiro also describes this as a one-way transfer system and notes that viruses are part of what we call the biosphere. They are vehicles for cells communicating with each other. On their own, they can't do much, yet they can enact change on their hosts. He expands on some of this molecular biology phenomena and explains that viruses are sources of new information that may be useful to evolving organisms at critical junctions in evolution. He also offers an exploration of cancer behavior and evolution. Cancer is so destructive, he says, because cellular behaviors are enacted that wouldn't normally be, yet cancer uses normal evolutionary processes to change. He's working on understanding cancer by comparing its evolution with organismal evolution and noting the parallels. Finally, he discusses his theory of cellular cognition, and that in the near future, we will think about cells in a more systemic, cognitive way—ultimately learning about living organisms is really learning about how systems behave. For more, see his lab website at http://shapiro.bsd.uchicago.edu/, which links to his research, books, and past blogs and articles.

Erica Hartmann's Bio: Dr. Erica Marie Hartmann is an environmental microbiologist interested in the interaction between human-made chemicals and microbes. Her career began at the Johns Hopkins Bloomberg School of Public Health, where she worked on mass spectrometry-based methods for detecting microbial enzymes necessary for bioremediation. She then moved to Arizona State University where she was the first graduate of the interdisciplinary Biological Design PhD program. She when to France on a Fulbright, studying microbes that degrade carcinogenic pollutants at the Commission for Atomic Energy. She began leading studies antimicrobial chemicals and microbes found in indoor dust at the Biology and the Built Environment Center at the University of Oregon and is currently continuing that work as an assistant professor at Northwestern University. Assistant professor of civil and environmental engineering at Northwestern University, Erica Maria Hartmann, joins the show to discuss the interesting reactions that occur between antimicrobial chemicals and antimicrobial resistance. Tune in to discover the following: Why the molecular biological tools being used can lead to the inaccurate detection of microbes that are actually alive, and why this is a problem How common household paints containing antimicrobial agents might affect microbial communities in the environment How exposure to various microbes early on in life might provide a benefit, including lower chances of developing asthma and allergies Antibiotic resistance is one of the biggest global health threats right now, and according to Hartmann, the cleaning products we use, the way we clean, and the assumptions we make about microbes are not helping. Much of her work revolves around trying to understand how the use of specific chemicals impacts the microbes in indoor environments. She explains that while most people operate under the assumption that all microbes are bad, the vast majority of microbes are neutral if not good; ironically, it is the chemicals we use and the way in which we use them that can sometimes be more detrimental to our health, and actually foster the development of antimicrobial resistance. The main goal of Hartmann's work is to identify the specific impacts of specific cleaning products on different microbial communities, and thereby be able to determine whether the appropriate cleaning agent is being used in the correct way. For example, depending on the specific microbe that's being targeted by a cleaning agent, soap and water might be all that's necessary, as opposed to a harsh chemical such as bleach. Hartmann is a wealth of knowledge on environmental microbiology and these other incredibly relevant topics, so press play to hear all the details. Visit https://sites.northwestern.edu/hartmann/ to learn more.