COUNTDOWN TO AGE-REVERSAL
GENOMIC PATHWAYS TO A BETTER FUTURE - WITH GEORGE CHURCH
Affordable age-reversal. Xenotransplants to eliminate organ shortages. Rewriting health economics. De-extinction. Keeping methane sequestered under the tundra. Editing livestock and crops to be resistant to ALL viruses …
What are the genomics pathways to a better future? Which are closest? Where could we be in twenty years?
I asked George Church, the greatest genomic pioneer in the world.
GREATEST GENOMIC PIONEER
George Church is a professor of genetics at both Harvard and MIT, the developer of the first direct genomic sequencing method, an initiator of the Human Genome Project and the Personal Genome Project, inventor of molecular multiplexing and tags, homologous recombination methods, array DNA synthesizers and many many more tools that help us investigate, analyze, edit and synthetize LIFE, as well as co-author of 684 scientific papers and 156 patent publications and counting, co-founder of more than 50 biotech companies, and mentor and inspiration to hundreds and hundreds of world-leading biochemists who have passed through his lab.
Or, perhaps this is a better introduction: George’s contributions, both directly and indirectly via the accomplishments of all the students and colleagues who have passed through his lab, have improved the lives of hundreds of millions on this planet and will soon improve the lives of billions, because he’s still contributing, STILL pushing the frontiers of science in all directions.
Who better to clarify how genomics can create a better future for HUMANITY?
No one, that’s who.
MEETING GEORGE CHURCH
Quick segue: this connection came, as always, though the kindness of others – or in this case, a chain of kindnesses:- the wonderful Tom Whitehead connected me with Michelle Berg at the Emily Whitehead Foundation, who connected me with Elizabeth Wood and the amazing Julie Norville at JURA Bio who, after learning what I did, made a point of connecting me with George Church, who said yes! All these important people made time to help for no other reason than they believed spreading the word about pathways to a better future is a good thing to be doing. I share this as a small way to say ‘thank you’, and because it’s a reminder of the generosity in people, and because it makes me happy.
Back to George:
First thing I learned, he’s as nice as his reputation suggests. Nice in manner and nice in motive. He has an easy sense of humor and consistently emphasizes the contributions of others over his own. He willingly shared his thoughts on absolutely every question I raised.
Second, he’s a born communicator. He knows how to translate complex science, when to dive deep and when to summarize, and when a metaphor is better. We talked for an hour and when we pushed ‘stop’ on the recording, we happily went on swapping thoughts on the relative merits of podcasting and presenting. I could have happily continued our conversation for three hours, I enjoyed it so much.
Third, he is ‘cross-disciplinary’ in the extreme. I asked where his early inspirations came from and I’m so glad I did, because I discovered that engineering, and the possibilities in building things came first, and the science that followed was a means to that end – and not just one discipline; pretty much all of them.
Fourth, he thinks BIG. Big about possibilities, big about opportunities, big about solutions. He identifies truly meaningful contributions and goes after them. Unquestionably, he is a scientist dedicated to making this world a better place.
Enjoy the podcast (you can either click below, or download it from your favorite podcast app). As usual, I’ve added some of my post-conversation reflections below, but I strongly recommend listening; there really is no substitute for hearing it in George’s words.
CHECK OUT THE PODCAST TRANSCRIPT →
THE AGE-REVERSAL GAME-CHANGER
Before our conversation, here’s where I was at with respect to age-reversal and the future of healthcare:
A range of drugs ARE coming to both extend cellular healthspans and to reverse cellular ageing, with the former being easier and therefore predominant.
They WILL significantly reduce the incidence of ageing related diseases, thereby significantly extending healthspans and average human lifespans.
They WILL include targeted drugs to rejuvenate specific organs (eg restore function in kidney, optic nerve, auditory nerve, cilia).
They MAY extend maximum human lifespans, perhaps in the order of 10 or 20 years, although with some doubts about this, especially after my conversation on age-reversal with the wonderful Jan Vijg at the Albert Einstein School of Medicine.
Future prices are unknowns, but very large economies of scale are LIKELY to make prices reasonable, which will translate to wide accessibility.
All of the above WILL revolutionize healthcare economics.
Other consequences of the above include the obvious shifts in workforce demographics, a rethink of retirement planning, aged care, work participation, and more (it’s a long list!).
Runaway overpopulation is NOT an outcome (global population is much more closely tied to fertility rates -- big subject which I may write about another time).
George reinforced most of the above, but his generously-shared insights also updated and corrected my expectations.
‘EXTENDING CELLULAR HEALTH’ VERSUS ‘REVERSING AGEING’
Essentially, until now I have conceptualized slowing the cellular aging process (by slowing the accumulation of epigenetic errors) as a simpler goal than outright reversal (rolling back accumulated epigenetic errors). George challenged my differentiation:
“I don't think they're that different, really ... The main reason that young cells repair better is epigenetics, they think they're young. So for example, you can actually repair a damaged heart if you're a fetus or a newborn, but you can't if you're my age, not easily … if you make the cells think they're young, they have the wherewithal to repair almost everything, proteins and nucleic acids, lipids, and so forth.”
MAXIMUM LIFESPAN NOT A BARRIER
George agreed with Jan Vijg’s views on a biological maximum age limit ‘built into’ our design as an evolutionary outcome …
“I totally agree with the concept that there's a programmed death date, with of course a standard deviation. There are some rats that live a year and a half, that's when they die. A little bit of variation, whether they're dying in the wild or in the lab. And then there are bowhead whales that last 200 years, and that's clearly in their, built into their evolution and DNA. That I agree with.”
… but disagreed with the notion that this programming was some kind of fundamental barrier we couldn’t break through. George was clear that, in his view, multiple pathways are necessary to achieve this, multiple edits if you like, with still much complexity to overcome to do them correctly, but equally clear that he considered extending maximum lifespan do-able:
“[It] doesn't mean that you have to change radically. I don't have to become a bowhead whale in order to live 200 years. That I don't agree with. I think that there are a small number of pathways we need to get right … to a certain extent we can change our species definition through gene therapy, somatic gene therapy on adults. We can't change everything, but we can change a whole lot of things.”
Henceforth, I’m modifying my position on maximum lifespan extension to “likely.” Impact timeframe? Beyond 2040 for now, but I’m still listening and learning. Watch this space.
I have to admit, that last paragraph feels slightly surreal, even to me. Honestly, who would have thought we would be contemplating such a future?
AGE-REVERSAL CHEAPLY AND AT SCALE
On the accessibility issue, George was unequivocal: age-reversal therapies most definitely CAN be supplied cheaply, for the simple reason that we’ve already done it – we’ve supplied mRNA vaccines to billions at a few dollars per dose, and the manufacturing processes are essentially identical. With R & D costs fixed, “the main difference between the $3.5 million a dose and the $2 a dose or $20, is the economies of scale.” Ergo, with scale-up, there are no technical reasons why we cannot supply age-reversal therapies at similar price points.
REVOLUTIONIZING HEALTHCARE ECONOMICS
Again, stop for a moment and consider the implications. I meant what I said on the podcast: when we extend healthspans and thereby lower the incidence of all diseases, the economic payoff in healthcare will be IMMENSE – probably the biggest humanity will ever see.
XENOTRANSPLANTS: SOONER THAN YOU THINK
After our conversation, I feel more confident than ever that Xenotransplants are now our first, best pathway to ‘organs on demand’ which have long been part of my future of medicine.
George emphasized the flexibility of the process to produce different organs and skin and blood cells, the advantages this method offers, such as fully testing and ‘debugging’ candidate organs before they go into a human, and the opportunity for enhancements (organs less likely to fail, blood transfusions and hematopoietic stem cell transplants that are cancer resistant or pathogen resistant, immunologically privileged, senescent resistant, and so on).
Non-human primate trials have been very successful. We have learned much from the brave first human patients, such as David Bennett Sr. Human trials are now at a stage where they are ready to go with “a big human cohort,” which George expects “not 10 years from now, much sooner than that.”
DE-EXTINCTION TO SAVE THE TUNDRA
The biggest negative feedback loop in climate change awaits as the permafrost thaws and progressively releases 1,400 gigatons of trapped methane, the most potent greenhouse gas of all. The process has already started. As I’ve explained previously, the atmosphere is now pumped and primed and carries momentum, and the ocean sinks are full, so additional global heat increase is now ‘baked into’ our future, no matter what. Even if we could magically zero all anthropogenic greenhouse emissions tomorrow, it would not stop the thawing.
As George explained, all the CO2 emitted by humans is as nothing compared to the impact of that methane release, hence his motivation to keep the tundra frozen via his famous woolly mammoth de-extinction project, which is often misunderstood to be ‘just’ about restoring a bygone species. The idea in a sentence: cold-resistant hybrid-elephant populations will help revitalize grasslands and restore the tundra biome which will keep the ‘perma’ in permafrost and the methane locked away.
Whether or not you find this biome-scale geoengineering intimidating (I admit I struggle with it, and foresee some pretty formidable socio-political resistance to the rollout), and whether or not you ‘believe in’ climate change or prefer to ‘wish it away,’ know this: the physics won’t change. The warming is here. The thawing is happening. Do nothing, and that methane is coming.
DOUBLING YOUR CORNFIELD EVERY NINETY MINUTES
George: “The doubling time of our fastest organism that we've discovered is 17,000 times faster than corn, so just imagine your cornfield, you've got a mature cornfield and then 80, 90 minutes later, you've got two cornfields …”
Is there a more vibrant mental picture of the genomic potential in the future of agriculture? This is why “editing life” is still one of my top two technological drivers of change through the next 20 years (along with exponential AI) with daylight to third place.
You can explore more about gene-editing and the future of agriculture in my interview with Rodolphe Barrangou, and about keeping future CRISPR use responsible in my interview with Jennifer Kuzma.
Oh, and that company George is involved in with Rodolphe Barrangou, to improving yields and pest resistance and drought resistance in standard crops like corn and soybeans, is Inari.
As exciting as the possibilities in agriculture are, I appreciated the way George emphasized the overwhelmingly greater importance of addressing climate change as an objective, and his pragmatism when balancing aspirations against the reality of farmer incentives/behaviours.
GENOME RECODING AND SUPER-LIVESTOCK
What would it mean to the world if livestock was resistant to ALL viruses? What would it mean to farmers? Just imagine for a moment: all those foot and mouth, mad-cow and swine flu outbreaks, all those many thousands of destroyed and incinerated animals … gone. History. Imagine the improvements to farmer’s lives. Imagine the reduction in waste. Imagine all the agriculture testing and monitoring requirements and associated bureaucratic overheads we could get rid of.
This is the power of genome recoding.
And that’s just animals. What about crops? How about eliminating viral risks in all those pigs hosting organs for xenotransplantation we talked about? It keeps going …
Genome recoding is the frontier George nominated that he wished more people knew about. What a frontier! What possibilities!
BIOFUELS FROM BACTERIA
I’ve long been excited by the potential of next-gen biofuel projects that employ tanks of genetically engineering cyanobacteria to ingest sunlight and CO2 directly and excrete ethanol and other hydrocarbons as products in situ, thus solving the truly appalling problem of displacing precious arable land from food production, and simultaneously zeroing out the very significant carbon emissions associated with biofuel harvesting and processing (today’s biofuels are far from climate friendly!)
This is an especially interesting pathway to better future for the aviation industry, where electrification of long-haul requires battery energy densities that are still a way off, and hydrogen is problematic because of the added systems complexity, volume trade-offs and associated packaging requirements.
Unfortunately, the next-gen projects haven’t scaled, and when I asked George for his thoughts, he pointed to the economics, not the technology. The technology works for diesel and gasoline and jet fuel and “was perfectly scalable – the problem is that it's very hard to compete with pulling stuff out of the ground and sending it through pipes ... especially when the costs to the environment are not really factored in.”
Same old story. The ultimate arbiter of energy behaviour is the dollar. And yet another reminder that we’ll have to embrace significantly more top-down regulation, especially via pricing carbon costs properly and fully into all energy sources, to get to net-zero.
RE-THINKING INTERSTELLAR EXPLORATION
That interstellar exploration paper we discussed is Picogram-Scale Interstellar Probes via Bioinspired Engineering. Did I mention that George thinks BIG? Oh. My. God. The perfect demonstration of his always curious, always problem-solving mind. And while the crippling economics of interstellar exploration might not be on your priority list, I’ll bet fostering positive innovation is, and it’s a great reminder that if you truly want to “think differently” about big solutions to big problems, then a great way to do it is to be brave and cross disciplines.
EXPONENTIAL OPPORTUNITY
George reminded me that he and his colleagues operate in a world of exponentials. When they sequenced the first human genome it cost $3 billion. Now it's $300 and becoming part of standardized personalized medicine for everybody, with a return probably ten times the investment.
And of course, it isn’t stopping. As George put it, “what seems very hard for us today, two years from now will seem plausible, and five years from now will be seem routine.”
There is a LOT of upside embodied in that statement. When I revisit this post in a couple of years, there will be twenty new headings.
INNOVATION AS A COLLECTIVE ACHIEVEMENT
Notice George’s steadfast deflection of my praise in favor of his students and colleagues and all their contributions to the future this planet? Notice how he said, “I'm very proud of my alumni, the graduate students and postdocs that have gone off and either started companies or started their own academic labs. It's a wonderful crew. And they're very nice [my emphasis] to each other. I mean, that's one of the fundamental things that we encourage, so it's lovely to see them populate the world.”
Looking for the magic? The diverse community, the shared values, innovation as a social outcome and a collective achievement, the generosity, all the other definitely-not-secret ingredients that power impactful innovation? There. Right there.
Bravo, George. And thank you. And please take those anti-aging therapies, so we can enjoy another sixty or seventy years of your breakthroughs!
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