George Church, PhD: Rewriting Genomes to Eradicate Disease and Aging

Since Dr. Church pioneered direct DNA sequencing in 1984, sequencing has become over 10 million-fold cheaper. This exponential reduction in cost has made personal genome sequencing widely accessible and has advanced the field significantly.

Comparing genomes across species is almost as effective as an experiment and provides richer data for exploration. This comparison helps in discovering new biological tools, creating a positive feedback loop: sequence genomes, find tools, use tools to read and write genomes, and find more tools.

Biology offers atomic precision in manufacturing, allowing for reproducibly made molecules with exact atomic configurations. Additionally, biological systems can replicate themselves, a capability currently ludicrous for non-biological machines, offering exponential scalability.

Yes, Dr. Church's lab has successfully demonstrated changing the genetic code in industrial organisms like E. coli to make them resistant to all known viruses. This involves making many thousands of changes that viruses cannot easily mutate around, potentially applicable to plants, animals, and human stem cells.

While AlphaFold primarily predicts protein 3D structures, computer-aided design, especially with machine learning and large synthetic molecule libraries, helps explore the 'landscape of functionality.' This allows for rapid testing of millions or billions of subtle genetic variations to understand their functional consequences.

CRISPR is a revolutionary tool but not the only one. Older, precise methods like homologous recombination and SSAPs (Lambda red) exist and are still in use. Dr. Church suggests that reading genomes and considering wider integrated approaches, including delivery and testing, are equally vital, and that public focus on CRISPR might be an oversimplification.

One school of thought, favored by Church, views aging as a programmed process, possibly modifiable by addressing a 'small core set of systems biology systems medicine.' Strategies include rejuvenating environments (like eggs in cloning), transcription factors (Yamanaka factors), and blood-borne factors that reset the age clock.

Dogs are large mammals with closer similarities to humans than rodents, living in similar environments, eating similar food, and exhibiting similar emotions. Their owners can also detect subtle positive and negative consequences of treatments earlier, making them a particularly good conduit for translating therapies to humans.

The distinction between enhancement and therapy is often fluid, as many common technologies (smartphones, cars) are already enhancements. Dr. Church argues that biotechnologies like vaccines are enhancements that protect us, making the obsession with defining a 'perfect human' or avoiding enhancement seem odd and inconsistent with other accepted technologies.

Dr. Church opposes explicit moratoriums on germline editing, arguing that existing regulatory bodies like the FDA already provide caution and oversight for new drugs. He believes preventing careful data accumulation through bans is counterproductive and that a compelling medical need would eventually lead to public acceptance, similar to IVF.

Promoting conversation through common media like books, movies, and television can help frame complex science in an entertaining and educational way, allowing for exploration of both positive and negative scenarios without avoiding concerns. This helps make scientific advancements more accessible and understandable to the broader public.

There's often a double standard where random, uncontrolled mutations (e.g., from UV radiation in plants) are accepted, but precise, controlled genetic edits are viewed with suspicion. This is akin to accepting IVF but rejecting germline editing, or chemotherapy but not gene therapy for germline concerns.

Dr. Church describes finding himself in a 'limbo between dreaming and awakeness' when super bored, excited, or facing difficult problems. He often falls asleep and wakes up seconds later with solutions to abstract or practical problems, experiencing a heightened state of awareness, which he attributes to aiding his creativity.

After reviewing a paper where authors encoded their names in a tiny genome, Dr. Church decided to encode his entire book, 'Regenesis,' into DNA. He used a generalized binary code that could encode text and later images, creating 70 billion copies and inadvertently launching an industry for digital encoding in DNA that can record vast amounts of data in living organisms.