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#077 Rewriting genomes to eradicate disease and aging | Dr. George Church

Aug 24, 2022 2h 8m 38 insights
<p>George Church, Ph.D. is a professor of genetics at Harvard Medical School and of health sciences and technology at both Harvard and the Massachusetts Institute of Technology. Dr. Church played an instrumental role in the Human Genome Project and is widely recognized as one of the premier scientists in the fields of gene editing technology and synthetic biology. </p> <p><strong>In this episode, we discuss:</strong></p> <ul> <li><strong>(00:00)</strong> Introduction to Dr. George Church</li> <li><strong>(07:13)</strong> History of the Human Genome Project</li> <li><strong>(15:20)</strong> Manufacturing cell phones (with biology)</li> <li><strong>(17:34)</strong> Genome Project-Write</li> <li><strong>(20:03)</strong> Writing a human Y chromosome (from scratch)</li> <li><strong>(20:48)</strong> What if you could eliminate viral disease?</li> <li><strong>(22:51)</strong> De-extinction and reinstating lost traits and genes</li> <li><strong>(27:06)</strong> The Vertebrate Genomes Project</li> <li><strong>(29:47)</strong> AlphaFold and other AI tools</li> <li><strong>(41:27)</strong> CRISPR vs. Base Editing (emerging tools of genetic engineering)</li> <li><strong>(49:40)</strong> Why multiplex editing will change the world</li> <li><strong>(52:18)</strong> Molecular flight recorder</li> <li><strong>(53:31)</strong> Preventing viral spillover and enhancing livestock</li> <li><strong>(57:40)</strong> PCSK9 gene therapy for cholesterol</li> <li><strong>(1:00:30)</strong> Is aging an evolved program?</li> <li><strong>(1:05:21)</strong> Treating aging with a combination gene treatment</li> <li><strong>(1:09:04)</strong> Does animal research help us understand human aging?</li> <li><strong>(1:11:40)</strong> Human organoids as a model and therapeutic</li> <li><strong>(1:13:34)</strong> Could engineered transplant organs become better than the originals?</li> <li><strong>(1:16:17)</strong> Embryo editing controversy</li> <li><strong>(1:28:41)</strong> Gene editing for space travel</li> <li><strong>(1:30:40)</strong> Can synthetic biology alleviate poverty?</li> <li><strong>(1:34:07)</strong> Is i<em>n vitro fertilization</em> and embryo selection practically similar to editing?</li> <li><strong>(1:39:12)</strong> The occasional cost of brilliance</li> <li><strong>(1:45:45)</strong> Eradicating disease with Gene Drive</li> <li><strong>(1:48:55)</strong> Technologies to solve Lyme disease</li> <li><strong>(1:51:57)</strong> Dr. Church's experience with narcolepsy as a bridge to creative insights</li> <li><strong>(2:00:42)</strong> Why George encoded his book in DNA</li> </ul> <p><a href="https://youtu.be/o4MZ-JaIvFI">Watch this episode on YouTube</a></p> <p><a href="https://www.foundmyfitness.com/episodes/george-church">Show notes are available by clicking here</a></p> <p>Join over 300,000 people and get the latest distilled information straight to your inbox weekly: <a href="https://www.foundmyfitness.com/newsletter">https://www.foundmyfitness.com/newsletter</a></p> <p>Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: <a href="https://www.foundmyfitness.com/crowdsponsor">https://www.foundmyfitness.com/premium</a></p> <p>Learn more about the premium podcast <em>The Aliquot</em>:<br /> <a href="https://www.foundmyfitness.com/aliquot">https://www.foundmyfitness.com/aliquot</a></p>
Actionable Insights

1. Stay Informed on Scientific Advances

Actively seek knowledge about radical transformative technologies like gene editing and gene drive to be better prepared for productive public conversations and to intuitively grasp their potential impact.

2. Prioritize Technology Development for Cost Reduction

Advocate for and invest in technology development upfront in large scientific projects, as this approach can significantly reduce costs and expand the scope and accessibility of the research outcomes.

3. Focus on Societally Beneficial Projects

Prioritize scientific projects that are consciously aimed at generating positive societal consequences, as these are more inspiring, garner broader support, and drive creativity and technological advancement.

4. Ensure Equitable Tech Distribution and Education

Work towards equitable distribution of new technologies and provide education and dialogue opportunities so that everyone on the planet can understand, access, and evaluate these advancements for their own benefit.

5. Radically Reduce Synthetic Biology Costs

Aim to drastically reduce the cost of synthetic biology technologies, such as reading and writing DNA, by millions of fold to ensure universal accessibility and impact, similar to the eradication of smallpox.

6. Diversify Funding for Grand Scientific Challenges

Pursue funding for large-scale scientific projects, such as the Genome Project Write, through multiple channels including philanthropy, industry, and various government agencies (e.g., NIH, DOE, NSF, ARPA, DARPA, IARPA) to ensure robust support and diverse perspectives.

7. Protect Biodiversity & Reduce Agricultural Footprint

Document, freeze, and protect existing organisms and genetic diversity, while simultaneously working to shrink agricultural land and water use by 10 to 100 fold to preserve natural environments.

8. Support Regulatory Agencies Intellectually and Financially

Provide strong intellectual and financial support to government regulatory agencies like the FDA, EPA, and USDA, as they are essential for overseeing the safe and ethical development of new technologies.

9. Integrate Genome Reading into Gene Editing

Prioritize and utilize genome reading at all stages of gene editing, from discovering tools and defining goals to monitoring editing success and assessing physiological outcomes, as it is fundamental to the entire process.

10. Employ Diverse Gene Editing Tools

Broaden the approach to gene editing by utilizing a diverse set of tools beyond CRISPR, such as homologous recombination and SSAPs/Lambda Red, which offer advantages in precision and scope for various applications.

11. Embrace Full Spectrum of Genome Engineering

Understand and utilize the full range of genome engineering methods, including reading, precise editing, and de novo synthesis, to achieve more nuanced and visionary applications beyond the public’s focus on single technologies like CRISPR.

12. Optimize Gene Therapy Delivery Mechanisms

Focus on optimizing delivery mechanisms for gene therapies to ensure the genetic material reaches the correct target cells at the right dose and time, with minimal off-target effects, which is critical for safety and efficacy.

13. Develop Enhanced, Resilient Cell and Organ Therapies

Aim to develop cell and organ therapies that are not merely replacements but are enhanced with superior qualities, such as immunological superiority, resistance to pathogens, cancer, senescence, and suitability for cryopreservation.

14. Utilize Soluble Factors for Systemic Gene Therapy

Consider gene therapies that deliver genes for soluble factors (e.g., alpha-Klotho, FGF-21, soluble TGF-beta receptor) to a subset of cells, allowing these proteins to circulate and achieve whole-body effects, especially when direct delivery to all cells is challenging.

15. Engineer Cell Therapies for Virus Resistance

When developing cell therapies, consider engineering the blood cells to be resistant to all viruses, which could offer enhanced safety and efficacy for patients, pending regulatory approval.

16. Leverage Dogs as Translational Research Models

Utilize dogs as a valuable model for developing human therapeutics, as their similar physiology, environment, and owner observation allow for better translation of results and earlier detection of subtle effects compared to rodents.

17. Screen Longevity Interventions in Rodents

Employ rodent models for initial screening of longevity and age-related disease interventions due to their short lifespan, which allows for rapid observation of significant effects before progressing to larger animal or human studies.

18. Utilize Human Organoids for Research

Integrate human organoids into research as an alternative to traditional animal models, as they offer increasingly accurate and human-specific insights into organ function and disease, potentially streamlining therapeutic development.

19. Apply Nuanced Protein Engineering

When modifying proteins, aim for nuanced engineering that selectively removes undesirable functions, such as viral binding, while preserving essential beneficial functions, like immunological activity, to achieve multi-faceted resistance or enhancement.

20. Extensively Test Gene Drive Ecological Impacts

Before deploying gene drive technologies, conduct extensive studies of ecosystem interactions and rigorous testing in large, enclosed ecosystems to ensure they do not inadvertently cause species extinction or other undesirable ecological impacts.

21. Prioritize Gene Drive Targets with Minimal Ecological Risk

When considering gene drive technologies, prioritize targeting species whose extinction would have minimal ecological impact, such as specific disease-carrying mosquitoes that are not keystone species, after thorough study of ecosystem dependencies.

22. Engage Public, Offer Gene Drive Alternatives

Foster open public dialogue about new biotechnologies and offer non-gene drive alternatives for pest and disease control, even if they are more expensive or less certain, to build trust and address community concerns.

23. Embrace Preconception Genetic Counseling

Opt for preconception genetic counseling to understand carrier status for genetic diseases, enabling informed family planning choices that can prevent severe conditions in children, offering a low-cost preventative alternative to expensive reactive gene therapies.

24. Support and Utilize Effective Vaccines

Actively support and utilize effective vaccines, ensuring public understanding is based on accurate scientific data to prevent the spread of misinformation and leverage these powerful tools for public health, as seen with the Lyme disease vaccine’s history.

25. Adopt Cautious, Phased Approach to New Tech

When developing new medical technologies, acknowledge that zero risk is unattainable and inaction is also risky; instead, proceed cautiously with small animal or organoid studies, followed by small human clinical trials, gradually expanding as safety and efficacy are confirmed.

26. Evaluate Trade-offs and Context, Not Perfection

When considering new biotechnologies or enhancements, focus on evaluating trade-offs and specific contextual benefits rather than striving for an ill-defined “perfect” outcome, as all solutions have situational advantages and disadvantages.

27. Distinguish Anecdotes from Clinical Recommendations

Always differentiate between personal anecdotes, even from experts, and recommendations derived from rigorous clinical trials, as only the latter provides generalizable and evidence-based guidance for health and lifestyle choices.

28. Communicate Personal Health Conditions

Openly communicate personal health conditions, such as narcolepsy or diabetes, to those around you, as hiding them can be more dangerous than communicating them, especially in emergencies.

29. Adapt Lifestyle to Manage Sleepiness

If prone to sleepiness after meals or during passive activities, consider adapting eating patterns (e.g., eating before bed if it helps, though not generally recommended) and incorporating light physical activity like standing or pacing to maintain alertness.

30. Choose Career and Activities Compatible with Health

Select a career path and daily activities that are compatible with personal health limitations, such as avoiding driving if prone to falling asleep, to ensure safety and find a suitable and fulfilling professional fit.

31. Empower Choice Over Neuroatypical Traits

Explore and develop technologies that provide individuals with neuroatypical traits the choice and control to modulate these characteristics, allowing them to leverage potential advantages for specific tasks while also adapting to social or functional demands.

32. Leverage Sleep for Problem-Solving (If Applicable)

For individuals who find themselves falling asleep during difficult problem-solving, consider allowing for short naps, as some, particularly those with narcolepsy, report waking with solutions to abstract or practical problems.

33. Harness Hypnagogic State for Creativity

For creative individuals, consider experimenting with methods to capture ideas from the hypnagogic state (the transition between wakefulness and sleep), as it can be a source of unique inspiration, similar to Salvador Dali’s technique.

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38. Share the Podcast with Futurism Enthusiasts

Share this podcast with anyone interested in futurism and the cutting-edge scientific advancements discussed, to spread knowledge and spark further interest in the field.