The 1000 Faces of George Church
He's Everywhere—a geneticist whose science fiction visions of the future tend to become real | Plus, from my archives a Church profile (NYTimes); and how to make a synthetic human (Wired); and more.
In this issue of FUTURES
Theme: The Visionary
New Essay: The 1000 Faces of George Church, by David Ewing Duncan.
Q&A: George Church, PhD
Articles from my archives: A Profile of George Church, by David Ewing Duncan, The New York Times; and “How to Build a Synthetic Human (Using My Own DNA),” by David Ewing Duncan, Wired
What I’m reading now: A list of recent reads for you to check out
FUTURES is a column and a newsletter about possible futures at a pivotable moment in history, where the future could turn out wondrous—or not. We’re seeing a flurry of innovations and fresh ideas in technology, health, science, art, policy, and matters of the heart even as we face existential threats like climate change, authoritarianism rising, a crisis of misinformation, and anxieties about powerful new technologies like AI. I’m asking the most interesting people I can find what they are most excited about and most afraid of for the future, and why.
For more check out my website: www.davidewingduncan.com
To view past “Futures” columns and to subscribe or to ask your friends to subscribe, click here.
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New Essay
I interviewed George Church during Future in Review in La Jolla, California, in 2019.
The 1000 Faces of George Church
He's Everywhere—a geneticist whose science fiction visions of the future tend to become real.
By David Ewing Duncan—June 28, 2024
During the pandemic, George Church declared on a Zoom call that he was no longer three-dimensional. For real. That he had taken the plunge, Max Headroom style, and given up his corporal existence to become purely digital.
Church was kidding. But unlike most people worried they were becoming 2-D during lockdown, you almost had to take George Church seriously given the decades he’s spent pushing the boundaries of biology, physics, AI, and things digital, and what it means to be human. More often than not he’s made his far-out ideas actually happen.
An important figure during the human genome project and in the early days of genetic sequencing, the 69-year-old Church has been at forefront of everything from editing DNA to cure diseases and genetically altering animal organs for human transplantation to efforts to epigenetically reverse aging and bringing back extinct wooly mammoths.
Just this year Church made headlines as the primary scientist behind the first ever pig kidney transplant into a human. The organ was developed by eGenesis, a Boston-based company that Church co-founded. Earlier this year, eGenesis gained FDA approval to surgically tuck their bioengineered tissue into a man dying of kidney failure. With 69 modifications to its DNA to mostly help prevent rejection, the new kidney allowed the patient to leave Massachusetts General Hospital and spend a few weeks with his family before he died of complications unrelated to his new kidney.
Last March, Colossal Biosciences, another Church company made a splash when they announced they had successfully created an induced pluripotent stem cell for the mammoth’s closest living relative, an Asian elephant. Church says this was a big step towards the company’s goal to deextinct mammoths.
In 2010, I profiled Church in The New York Times. In the article I described walking down the main corridor of his lab on Avenue Louis Pasteur at Harvard Medical School in Boston, and how it felt like taking a tour of everything cutting edge at the time in life sciences—improving DNA sequencing; experiments focusing on gene therapy and the use of stem cells; the development of advanced computing tech for biology; projects to manipulate microbes and to tinker with DNA to fight disease, create biofuels, and more.
“I’m a polyglot who believes in integration,” he told me for the Times. “That’s my specialty.” Fourteen years later, the polyglot’s lab remains a showcase of bio on the edge, even as Church’s lab and ambitions have gotten bigger.
Church is also a polyglot in the business of biotech. He has spun out, founded, and co-founded over 50 companies, including eGenesis and Colossal—plus Editas (gene editing), Rejuvenate (aging reversal), Nebula (DNA testing), Warp Drive Bio (genome mining), and more. These businesses have collectively raised hundreds of millions of dollars, and possibly more. Some have failed; but many others are thriving. For an exhaustive (and exhausting) list of Church’s companies, projects, titles, and more check out his personal webpage here.
Over the years, Church has generously shared with me what he is working on and thinking about, patiently explaining things to a nonscientist and flashing his wry smile at times when I ask a dumb question, or I finally get what he is talking about.
Not that George Church is a poor communicator. Part of his success comes from being an excellent explainer, and for having a distinctive and erudite but very approachable style that includes his long, Methuselah beard that over the years has turned snowy white. This gives him a Santa Claus meets crazy uncle meets Albert Einstein aura and look. He also is chronically so unruffled that in that in the New York Times profile I quote him describing himself as “pathologically calm.”
One of my favorite George Church stories came in 2019 when he agreed to be interviewed for my book, Talking to Robots, about the future of AI and robots and people. For the book I asked him and several other prominent thinkers the following question: What robot or AI system would you be excited to meet, or afraid of meeting in the future, and why?
Church didn’t hesitate. He answered that he would want to meet himself—not as a robot, but as a modified, improved and relatively ageless synthetic human. In the book I called this Church bot Homo syntheticis. Check out this chapter (excerpted in Inc. magazine) here.
Below is a recent conversation I had with George Church edited for space and clarity. Like everyone I profile in this Futures column, I start out by asking him what he’s most excited about and most afraid of for the future.
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Q&A: George Church, PhD.
What are you most excited about and what are you most afraid of for the future and why?
They're usually the same thing—a new discovery that could go well or could have serious downsides. Almost every technology that comes out of my lab is something I feel is important; that I believe is very positive. But I also feel an obligation to explore whether there's anything negative. I try to do a preemptive ethics essay before we do the hardcore science and engineering, rather than acting like I'm just a blind advocate. I did that for when we improved DNA synthesis by 10,000-fold. I did a paper in 2004 on how we need to have a surveillance system to be sure nothing bad happens. When we brought out gene drives, our first three papers were on how to contain them, how to reverse them.
What are you excited about that you’re working on right now?
I'm excited about engineering mammalian genomes, which includes human genomes and making that affordable.
You're talking about gene therapy, like CRISPR?
CRISPR is actually still a side show. All the improved gene therapies, with the exception of one or two, are adding a gene and not necessarily precisely edited it.
There are two gene therapies that are well on their way into clinical use thanks to my company, Editas. One in collaboration with Vertex, and another one Editas initiated.
What has been done to make gene therapies safe? For many years there were problems—in the 90s, people died.
The technology has really moved along, and the FDA is good at assuring these are safe and effective therapies. But we’re doing more than just safety. We’re requiring the additional ethics of making this affordable and non-stigmatizing. One of the ways to do both is make it affordable so that people who are poor can get it, too.
What about the work you and others are doing with gene therapies to impact age-related diseases?
We're probably right on the cusp of having therapies going into clinical trials. Gene therapies that address multiple age-related diseases that will probably address 90% of what kills us or that makes us feeble for a decade before it kills us.
What are the specific edits or fixes that you’re working on to mitigate age-related diseases?
In almost all cases, it's a set of genes that were high when you were young and are low when you're old. So you just boost them back up. It's not introducing foreign genes and there's not going to be an immune response. It's not editing, so that's also good. Some of them are of the type where if you fix the cell, it will affect adjacent cells or might secrete things that go into your blood and fix your whole body. These gene therapies seem to potentially fix diseases of aging, and also have a demonstrable longevity effect in mice.
Are any of these gene therapies in human clinical trials yet?
They're not yet in human clinical trials. We have pre-clinical mouse and dog experiments, but we have secured funding to take them the next step for four different drugs. I'd be surprised if they weren't given a green light for phase one [human clinical trials] within the next year or two. That's my company, Rejuvenate.
What kinds of gains would we get from that? Is there a way to measure the impact in years or in energy levels?
In the mice, they look friskier. By a number of metrics, they're healthier and they certainly live longer. We made the changes pretty late in life. It's easier if you intervene early in life. Our work was done late in life to test the worst-case scenarios. And we extended their life by about a factor two. In humans, if you are age 80, which is your life expectancy, let’s say you expected to live 10 more years. This intervention would effectively make it 20. So that takes you to being a 100-year-old. It's not immortality. In fact, we're not even aiming for longevity with the FDA. We're just aiming for improving outcomes for age-related diseases.
Are there any side effects?
I don't know of any. Clearly mice are dying because we've applied the intervention at the point where half of them are dead already. If it works well enough, we can get it for all age-related diseases and then use it preventively as well.
You’re also working on modifying an organism’s genes to make them more resistant to viruses, right?
Yes. We have now published the first example of an organism that's resistant, we think, to all viruses. And we're now working to transfer that into our experiments on making pigs that can provide organs for transplanting into humans.
You’re using these technologies to help treat disease and maybe bump up lifespan a little bit. But can’t these technologies also be used to enhance people? The old designer human concern?
I do worry about this. But how far do you take this? Can you weaponize a kitchen knife? Yes, you can. Can you weaponize a jet? Yes, you can. It's a little hard to imagine exactly how you're going to do this because it's hard to do gene therapy without permission. You could make super soldiers, potentially. But I have to believe we will protect ourselves from this like we do with many other potentially dangerous things.
Is there anything else you’re afraid of?
Most things I'm afraid of my lab is working hard on increasing the benefit to risk ratio. But I do have some things I'm anxious about. I'm afraid that we have a strange demographic change growing worldwide—which is that the year 2050 will be the first year in human history that our population has decreased since the Black Plague. Unless we succeed at reversing aging, which would prevent age-related diseases and make everyone have youthful health.
The second thing s climate change. I think that we've passed the point where we can just tighten our belts and stop using SUVs. We actually have to do a serious reversal of the carbon in the atmosphere, and there aren't that many ideas on the table for greatly increasing carbon sequestration.
The third is artificial intelligence. There’s the paper David Baker and I just wrote. We say some of the same things I brought up in 2004 about making synthetic viruses that could target individual people as weapons, say, or other abuses should now be updated to consider AI. But I think we have a fix for that.
Pandemics are number four. We may be on the verge of a series of pandemics. We are more prepared than we were, but not as much we should be. People have short memories.
Is there anything else about AI that worries you?
Using artificial intelligence to hack through privacy. We've already got some governments that are hacking into public systems, electric grids, and so forth.
It's also already happening in warfare. There's a constant digital war going on now where we use our AI to counter their attacks, and vice-versa. It's kind of scary.
Quite frankly, if I had to choose, I'd prefer that we fought World War III digitally rather than with hydrogen bombs. But clearly lots of damage could still be done in such a world.
What worries me is human nature? The technology itself is usually is fairly neutral, but I worry about that spectrum of humans who will abuse it.
Solutions for that requires that we get much better at engineering the human mind. We could make optional drugs or gene therapies that you might be able to use to dial up and down your worst instincts. But the government should not tell us, "Oh, you've got to take your ADD meds now." It should be something that you can individually control that includes things like empathy and altruism and ethics.
Are you talking about gene editing?
Probably not. There is a lot of very complicated neurobiology that we can fix now, but not by replacing or editing a gene. For example, if I drive a nail in my hand, that's going to cause pain and the solution isn't just pulling the nail out. You can either go through the opioid pathway or the THC pathway to deal with the pain. And there are people walking around with mutations who are naturally highly resistant to pain. But that's just an example where you can fix something without addressing to the actual cause.
AI will help with this, creating sophisticated medicines and a better understanding targets, say, in neurobiology. They're going to be more sophisticated where you can control them with an innocuous small molecule, but it's a very complicated circuit that you're controlling. Or maybe it’s a pump. Can you imagine voluntarily having a pump implanted that controls anger.
I imagine Vladimir Putin having had access to drugs that dial up or down emotions and proclivities like empathy, cruelty, and rage when he was younger. Would he have volunteered to take them?
That's the interesting question because even if you only affect a few people with a few problems, you could have a big impact on the world. Because I think that once you get addicted to power, it's too late. But if you do it early enough, maybe they would've taken. But as I said, all new technologies, we think early on about how to reverse them well before bringing them out.
I hope so. We're seeing parts of the world now becoming more authoritarian. That kind of technology in the hands of the Chinese government right now is frightening to think about.
People talk about hacking into, say, your heart control device. Or they may just want to suddenly make everybody complacent, to program them to be docile.
That sounds like Soma in Brave New World.
What's important here is that we get the knobs in place where we can start talking about how we would make them work in a positive way.
And yet you remain optimistic?
I do, because it’s important we believe that things will turn out well in the end. This means being aware of the downsides and taking action to prevent them while allowing innovations that can be hugely beneficial to happen. That’s what I’ve dedicated my life to doing.
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From My Archives: George Church Profile in the New York Times
Credit: Béatrice de Géa for The New York Times
SCIENTIST AT WORK: GEORGE M. CHURCH
On a Mission to Sequence the Genomes of 100,000 People
By David Ewing Duncan, The New York Times, June 7, 2010
Traditionally, biology is about taking apart things like cells to better understand them. For the geneticist George M. Church, the main objective is to put the pieces back together.
Strolling through his laboratory, one of the larger ones at Harvard Medical School, Dr. Church, 56, points out benches where students and colleagues work on everything from basic genetics, proteomics and biocomputing to synthetic biology and the impact of the millions of microbes that inhabit our guts.
“I’m a polyglot who believes in integration,” he said. “That’s my specialty.”
Dr. Church, a tall man with a long graying beard and rumpled clothes, oversees 45 students in his lab and has co-founded or advises some 22 businesses, many of them startups that focus on things like synthetic biology, genetic sequencing and companies that provide genetic testing to consumers.
His most visible work is the Personal Genome Project, which has 16,000 volunteers, 12 of whom have had their genomes sequenced and made publicly available. These include science and technology celebrities like the Internet pioneer Esther Dyson and the Harvard psychologist and best-selling author Steven Pinker.
Eventually Dr. Church wants to sequence the entire genomes of 100,000 people nearly every one of the six billion As, Cs, Gs and Ts that occur in a human.
“The goal of getting your genome done is not to tell you what you will die from,” he said, “but it’s how to learn how to take action to prevent disease…”
Typically, Dr. Church has been at the center of the development of the technologies that are making this possible. He advises or has licensed technology to most of the companies active in this field. This makes his potential conflicts of interests almost byzantine, since many are rivals, particularly in the hotly competitive field of genetic sequencing…
“I want to move the science into application,” Dr. Church explains, “and I’ll support anything that gets it there. I won’t support one over the other. If they tell me something secret, I can’t tell anyone until it comes into the public domain…”
Go here for the complete article in The New York Times.
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From My Archives: Wired
The Next Best Version of Me
Researchers want to synthesize an optimized human genome that can be stored indefinitely and grown decades from now. So I volunteered mine.
By David Ewing Duncan, Wired, April 2018
George Church towers over most people. He has the long, gray beard of a wizard from Middle-earth, and his life’s work—poking and prodding DNA and delving into the secrets of life—isn’t all that far removed from a world where deep magic is real. The 63-year-old geneticist presides over one of the largest and best-funded academic biology labs in the world, headquartered on the second floor of the massive glass and steel New Research Building at Harvard Medical School. He also lends his name as an adviser or supporter to dozens of projects, consortiums, conferences, spinouts, and startups that share a mission to push the outer edge of everything, from biorobotics to bringing back the woolly mammoth. And on a steamy August morning last summer, he wants to talk to me about the outer edge of my life.
Church is one of the leaders of an initiative called the Genome Project-Write, or GP-Write, which is organizing the eforts of hundreds of scientists around the world who are working to synthesize the DNA of a variety of organisms. The group is still debating how far to go in synthesizing human DNA, but Church—standing in his ofce in a rumpled sport coat, behind the slender lectern he uses as a desk—says his lab has already made its own decision on the matter: “We want to synthesize modified versions of all the genes in the human genome in the next few years.”
His plan is to design and build long chains of human DNA, not solely by cutting and pasting small fixes—a now-routine practice, thanks to recent technologies like Crispr that let scientists edit DNA cheaply and easily—but by rewriting critical stretches of chromosomes that can then be stitched together with a naturally occurring genome. If they succeed, it will be a breathtaking leap in ambition and complexity from the genomes of bacteria and yeast that scientists up until now have worked to synthesize. “What we’re planning to do is far beyond Crispr,” Church says. “It’s the difference between editing a book and writing one.”
In writing the book, Church hopes to bend the human narrative to his will. By replacing select nucleotides—the ACGTs of life, which are scattered throughout the chromosomes—and changing, say, a T to an A or a C to a G in a process called recoding, Church envisions being able to make cells resistant to viruses. “Like HIV and hepatitis B,” he says.
“And the common cold?” I ask.
He nods yes, adding that they’ve already recoded bacteria to be virus resistant. “It’s in a paper we published in 2016,” he says…
Go here for the complete article in Wired.
What I’m Reading Now
New Book: Superconvergence: How the Genetics, Biotech, and AI Revolutions Will Transform Our Lives, Work, and the World,” by Jamie Metzl
MIT Technology Review: “Google DeepMind’s new AlphaFold can model a much larger slice of biological life,” by James O’Donnell, May 8, 2024
The Baffler: “Altered States,” Issue No. 74, on psychedelics, June, 2024
Aoen, “What is intelligent life?” by Abigail Desmond and Michael Haslam, edited by Pam Weintraub, June, 2024
The New York Times: “As Bird Flu Looms, the Lessons of Past Pandemics Take On New Urgency,” by John M. Barry, May 16, 2024
Wired: “My Memories Are Just Meta's Training Data Now,” by Morgan Meaker, June 24, 2024
That’s it! Thanks for reading.