Finding Genius Podcast

How can cancer be treated differently than how many others have accepted as standard? Gene therapy may be the solution to change the course of cancer treatment. Listen in to learn:

• The chances of getting cancer in your lifetime
• How CAR-T therapy operates
• How genetic therapies are limited

CEO of Poseida Therapeutics, Eric Ostertag, discusses his work to develop safe, single-treatment cures for cancer and other diseases.

Since cancer has a genetic basis for operation, gene therapy can be even more effective than the previously used viruses or other therapeutic techniques. Immuno-oncology is the bleeding edge of cancer treatment and has shown the most promising results in solid tumors.

Due to the genetic limitations of viral technology, it does not have the capacity for efficacy found in non-viral therapeutics. The next generation of CAR-T will have higher chances of not being thwarted by mutations and solid tumors.

Visit poseida.com for more information. Episode also available on Apple Podcasts: apple.co/30PvU9C

For the past decade, the Collins Lab at MIT has been focused on using bioengineering principles to better understand antibiotics with the primary goal of discovering novel molecules that work effectively against bacterial pathogens.

On this episode, you’ll learn the following:

• What four primary mechanisms of antibiotic resistance are used by pathogens
• How AI can be used to identify certain features of molecules out of massive numbers of molecules and amounts of data
• Where Collins hopes to see his research and applications applied in the coming years

James J. Collins, Ph.D., is a professor of medical engineering and science at the Broad Institute of MIT and Harvard, and head of the Collins Lab at MIT. About one year ago, he teamed up with colleague Regina Barzilay, one of the world’s leading experts on applying artificial intelligence (AI) to healthcare.

The goal was to determine whether the power of AI could be used to address the challenge of antibiotic resistance and bacterial pathogens through the discovery of new antibiotics.

They began by putting together a training collection of over 2,500 molecules, including 1,700 FDA-approved drugs. This library was tested against E. coli in the lab to see which molecules might lead to inhibitory activity against the bug. Next, a deep neural network was trained using the data gathered and information about the structure of each molecule in the library.

The trained deep neural network was then applied to a drug repurposing library containing several thousand molecules that have already been developed or are in the process of being developed as drugs. The neural network was challenged to identify molecules that are predicted to be antibiotics but don’t look like any existing antibiotics: one molecule fit the criteria, and was named halocin. Halocin proved itself to be a potent novel antibiotic that worked against 35 out of 36 samples of multidrug-resistant, extensively drug resistant and pandrug-resistant pathogens from the CDC.

In addition to the details of this exciting discovery that could change health and medicine for the better, Collins discusses the most common mechanisms of bacterial resistance to antibiotics, why gram negative bacteria poses an extra challenge to the search for effective antibiotics, how AI could be used to identify features of molecules that make them amenable to gram negative bacterial uptake, the most useful strengths at the core of the AI technology being used in these capacities, the soon-to-be-launched Antibiotics AI Project, and so much more.

Tune in for the full conversation and learn more at collinslab.mit.edu.

Professor John Hogenesch studies circadian rhythms and the genome. He talks about

• The influence of cues on our circadian rhythm and how lighting and even medication timing can affect us,
• Studies on hospital-specific lighting and how two new hospital wings in Cincinnati are designed accordingly, and
• Some unusual sleep patterns, such as Delayed Sleep Phase Syndrome, and how it can affect people.

Dr. John Hogenesch is Professor of Pediatrics at Cincinnati Children's Hospital Medical Center in Human Genetics and Immunobiology at the University of Cincinnati Department of Pediatrics. He specializes in genome biology with a focus on the molecular mechanisms of circadian rhythms in mammals. He explains to listeners the basics of circadian rhythm as a daily rhythm of behavior and physiology that persists in the absence of external cues. He discusses how healthcare and specifically hospital design and schedules are often at odds with most patients’ rhythms. In fact, he mentions one study in which NICU patients under a cycled light schedule went home two weeks earlier than babies under constant dimmed light conditions. He discusses his hospital’s design of two new areas for NICU and PICU patients under the advisement of his lab that will integrate beds with circadian natural-light systems. He adds ways in which medication delivery and procedure timing could also be better paired with circadian rhythms and efforts to do so.

Dr. Hogenesch also talks about Delayed Sleep Phase Syndrome (DSPS). Richard has such a sleep pattern and the two discuss how it manifests itself, as well as other sleep patterns, and how they affect those who experience them. He also addresses how cortisol’s peak has an effect as well as how external cues interfere or work with our sleep patterns. For example, he mentions our eating timing, light exposure, and light temperature and type. He discusses how the pandemic is pushing many of us to later sleep schedules and possible hypothesizes for why. Along the way he offers some suggestions for eliminating excessive blue and green light and other similar measures.

For more, see his lab page at cincinnatichildrens.org/research/divisions/h/genetics/labs/hogenesch and the Society for Research in Biological Rhythms, which publishes helpful blog posts and articles. Available on Apple Podcasts: apple.co/2Os0myK

Wynand De Beer, independent researcher and philosopher, specializing in Hellenic philosophy and Patristic theology, discusses philosophy; socio-political discourse; and metaphysics, the specific branch of philosophy that pertains to the nature of existence, being, and the world.

De Beer is a member of the Russian Orthodox Church and he has written numerous articles for Orthodox publications and various websites, penned under his Orthodox name, Vladimir de Beer. He is the author of From Logos to Bios: Evolutionary Theory in Light of Plato, Aristotle, and Neoplatonism.

De Beer discusses his thoughts on philosophical, socio-political, theological, and metaphysical issues. He explains that much of the mindset regarding issues of this nature has been lost due to rationalism, secular humanism, and materialism. He talks about the important works of others who have come before him, such as Albert Camus, the French Algerian philosopher, author, and journalist.

De Beer talks in detail about some of the areas of his latest book, analyzing big issues from various chapters, from well being and love, to good vs evil, to consciousness, and the three manifestations of consciousness. Digging deeper, De Beer provides an analysis of gender, as it relates to our current and historical interpretations.

He states that the traditional understanding of man and woman, male and female, must function as polar opposites in order to constitute the reality that we live in. He provides an interesting account of the views on feminism, and the militant forms of feminism, and male chauvinism... all of which must be rejected as wrong, as they present an imbalanced view. There is no subordination or domination he states.

De Beer explains that the views and function of gender and sexuality, etc. are often taken to the extreme, perhaps as a form of rebellion, but ultimately too extreme. De Beer continues, discussing the details of other areas of his book, including a salient discussion on modern liberalism. He discusses his views on the immortality of the soul, referencing early Greek mythology from significant voices such as Plato.

The influential author and philosopher provides further details on his thoughts on politics and conflict. He discusses his next book, currently titled, Origins, and expounds upon some of the topics he will touch upon in the upcoming work.

In this podcast:

• An overview of metaphysics
• What would Plato do: various thoughts on the great philosopher
• Man vs Woman: the gender divide

How can we view evolution through comparative genomics? By understanding how viruses and various organisms have evolved, new views of world issues can be gained. Listen up to learn:

• How long have specific viruses been known to us
• Why complex roads are hard to find and valuable to use
• How specific mutations arise from zoological resources

Denis Jacob Machado, a Postdoctoral Researcher at the University of North Carolina at Charlotte, shares his work with viruses and attempting to model and annotate genomics to understand them better.

Even though humans may have been affected by viruses similar to what we face today, our ability to detect them has grown exponentially. Through research and phylogenetic analysis, we can begin to see clues as to how all of these subjects relate.

Through this better understanding, we may be able to more quickly and effectively respond to future threats. With continued research into how mutations can pose a threat in the future, there is even hope to prevent situations like the one in which we find ourselves today.

For more information, visit about.me/machadodj. Episode also available on Apple Podcasts: apple.co/30PvU9C