George Church Talks Age Reversal and Woolly Mammoth DNA

CHRISTIANE AMANPOUR: Now our next guest is one whose current projects range from growing human organs to resurrecting the woolly mammoth. Harvard genetics Professor George Church is at the cutting edge of genetic experimentation.

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WALTER ISAACSON: George Church, welcome to the show.

GEORGE CHURCH, GENETICIST, HARVARD MEDICAL SCHOOL: Thank you. Great to be here.

ISAACSON: You have a paper coming out on age reversal in mice.

CHURCH: Right.

ISAACSON: How do you do that? And, by the way, you going to get it done before we have to get too old?

CHURCH: Yes, so, it is aimed at — after mice. We’re already starting clinical trials in dogs. And then, after that, it will be clinical trials in humans. So, it’s on a very fast track. It’s a gene therapy. The way that it works is, it’s a gene therapy. And it’s a combination. So, we have combination drugs for cancer and infectious disease, but not so much for other things. So, this is — this will be interesting. And because there are like nine pathways of aging that are fairly well- accepted, things like telomere and calorie restriction are some sort of things that people have heard of. And we want to hit all nine pathways at once. And so we want to deal with diseases at aging and the phenomenon of aging. And we want reversal, rather than longevity, because, like, some mammals, like the bowhead whale, lives 200 years. If I went to the FDA and said we have some pills that will make you live 200 years, they will say, great. Come back in 120 years in a clinical trial, you know?

ISAACSON: Give me an example of a reversal. What does that mean?

CHURCH: Many of the proteins, the enzymes and other things in your body that are helping you repair and respond are dropping with age, because you don’t — really, you just don’t need them anymore. And so we’re just boosting them back up.

ISAACSON: Do you think any ethical, moral issues about trying to reverse aging?

CHURCH: I usually see some ethical safety moral issues on every new technology, especially the technologies that we deal with are usually quite transformative. The ones that come up here are population. Our population is decreasing its rate of increase. And, in fact, in cities, it’s going down. It’s like at 1.2 children per family, which is below the replacement rate. There’s issues of, you know, are we truly reversing aging, so that we think younger thoughts, and we’re not stuck in our ways, and we’re not like just sitting on a big pile of money and not letting anybody else have a chance? I think these are things where the problem isn’t the aging reversal. The problem is various other things in society, and we need to address those.

ISAACSON: So, at one point, when you’re doing genetics, you decide, I want to help bring back the woolly mammoth.

CHURCH: Right.

ISAACSON: I want to regenerate some species that have gone extinct.

CHURCH: Yes.

ISAACSON: And now it’s continuing to happen. You’re still involved. Tell me about bringing back the woolly mammoth.

CHURCH: Yes. Well, it’s a very popular topic. It’s a fairly small fraction of what we do, but it is very exciting. I just returned from Siberia, where we collect — I personally got to dissect six frozen mammoths that were — some of them were 40,000 years old. And we brought them back. And we used a new technology for reading them. So, the thing that’s interesting here — there are two things — is, one is that we can read that ancient DNA. In fact, we can read ancient DNA that’s up to 700,000 years old. Furthermore, that we can read it into the computer. We can figure out what the ancient genome — we can reconstruct the ancient genome. And then we can decide which genes are likely to achieve whatever it is we want to do. So, we’re really resurrecting genes, not species. And we’re putting them into a species that needs help and can help us. So, the Asian elephant is an endangered species, and it is very closely related to the mammoth. They’re almost — they’re so similar in sequence. They’re closer to each other than they are to the African elephant. So, we can help them by providing them a new place to live. And they return the favor by keeping the Arctic cold, and hence keeping the carbon there trapped. And the carbon there trapped is way more carbon than we’re worrying about in the atmosphere or even in the rest of the world’s forests.

ISAACSON: So you think there would be an impact on climate change?

CHURCH: We’re working with the Zimov family, who established two parks, Pleistocene Parks. One in is very Northern Siberia, and one’s near Moscow. And they’re trying — and they have shown that, if you bring herbivores, they can maintain the more ancient grassland, which is far better at sequestering carbon. It’s better at reflecting sunlight than these black trees are. And they allow the herbivores to stomp down the snow. So you get a conduction of the minus-40 winds, rather than this fluffy snow blanket, which protects the summer soil temperature from the low temperatures above. So, all of those things can be mitigated if you shift back from trees to grass. Now, normally, I am a big fan of trees, but in this particular case, it was not what humans want anyway, and was not what the animals wanted back then. So, the elephants are the few herbivores that can knock down trees, and they can knock them down in 15 seconds. They love doing it.

ISAACSON: So you think we may, 20 or 30 years from now, have woolly mammoths roaming the Arctic again?

CHURCH: So, I don’t know the exact tame frame. We’re trying to accelerate it. Many of the things — many of the technologies that I have worked on have arrived ahead of schedule. Like, the affordable sequencing was supposed to take six decades. It took six years. So, I don’t know. It could — I could be wrong in either direction if I predict it. But, yes, the hope is that we will have large herds of them, if that’s what society wants.

ISAACSON: What other extinct species would you bring back, if you could?

CHURCH: You know, there’s not a close second for me personally, but I’m part of a team that has a Web site, Revive & Restore, where they list about 100 different species. And there are some very ardent champions of each of these. But I think the woolly just really has it all in terms of, people like big things. It’s not a carnivore. It’s an herbivore, knocks down trees. It’s saving the environment. It just has so many things going for it, in addition to its charisma. But this is just my personal opinion. I could present arguments for some of the other species.

ISAACSON: Well, you made a little bit of news about 10 years ago, when you kind of said, hey, maybe we should bring back the Neanderthal. And you even said, maybe we should have, you know — a surrogate mother would volunteer to give birth to a Neanderthal.

CHURCH: Yes. Yes, there weren’t any shoulds in my statements. This is the problem. When scientists are asked whether you can or not, they will say, technically, you can do it. And so I was asked multiple times by multiple journalists. And I try not to dodge the questions. I try to — and I said, yes, that’s technically possible. This is what it would be. And — but I said, we’re not doing it, right? There’s no — there’s not any compelling reasons. You know, I think there are even fewer compelling reasons for the Neanderthal than there are for the dodo, and it’s so ethnically fraught. You know, we’d have to develop the technology of cloning humans. And you would have to get approval for every step of the way. And it’s just not — who’s it benefiting?

ISAACSON: You recently got caught up in this Jeffrey Epstein affair, where he was donating money to Harvard and other places. And you recently apologized for it. What did you learn from that? And do you have any comment on that?

CHURCH: Yes, I mean, I think that there’s a great tendency to — for people to distance themselves, rather than apologizing and worrying about the victims. I mean, I think the conversation really should be about how we can avoid this in the future and how we can just face — the first step is facing what we have done wrong. And I think that my role was small, but it doesn’t mean that I can just distance myself from it.

ISAACSON: You helped develop the technology for the human genome sequencing.

CHURCH: Yes.

ISAACSON: And what you really did is, you pushed down the price. You made sure it got cheaper and cheaper.

CHURCH: Yes.

ISAACSON: Now it’s almost less than $300 to get my genome sequenced.

CHURCH: Right.

ISAACSON: Should I do it? Should our viewers do it? And why?

CHURCH: Well, the should is — the should is, in order to do what, right? And I think that if you’re — if — we really, as a society — it’s a public health threat that isn’t easily understood by the public. It’s like seat belts. You had a 1 percent lifetime risk of dying or getting seriously hurt if you don’t buckle up.

ISAACSON: But if I got my genome sequenced, couldn’t I figure out a lot more than just major genetic diseases? Like, couldn’t I figure out propensities to cancer, propensities to diabetes?

CHURCH: Yes. You know, I think it’s up to the individual whether they want to learn more. I’m very curious. I wanted to see my whole genome. But, you know, I think it’s a conversation you need to have with whoever’s providing the service and your personal physician. But, at a minimum, you should be doing the very highly actionable things and making sure that next generation is not burdened with serious genetic diseases.

ISAACSON: What are the things advancing in terms of cancer treatments that excite you the most?

CHURCH: Yes. Well, cancer is entering a whole new phase now, with things like CAR T therapies. This is chimeric antigen receptor on T-cells, where you can train a T-cell — or you can program a T-cell with molecular biology to attack a particular cancer, if that cancer has a particular protein on the surface that you — that is characteristic of that cell type or that cancer.

ISAACSON: And those cell types are immune cells in our body, right?

CHURCH: Well, the attacking cell is immune.

ISAACSON: Yes.

CHURCH: The target doesn’t have to be immune. It can be, in principle, any cancer. So far, it’s been — the first target were other immune cells that were cancerous. And you can consider that a precision or personalized medicine, but it’s not in the classical sense, where we, you know, study the cancer on good genes, the things that are causing the cancer, and target them with small molecule drugs. This is more like we pick anything on the surface that has nothing to do with the cancer cell. We’re just killing all B-cells. And, also, we’re getting better at prevention, so, the genes that cause cancer, something that could be avoided, much, much earlier in life, before you actually get the disease. So, Angelina Jolie was — I thought was something that was going to be such a moving experience that everybody was going to go out there, get their genome sequenced, because she did not have cancer. She did not have any shred of, you know, a positive mammogram or lump or anything like that. She had a genetic risk factor, which she — you could only get by looking at your genome. We need more of that. So, those are the two main things that I think, the CAR T’s and the — getting your genome sequenced to see — so you can avoid cancer by preventive measures, not — because, once it starts growing, you’re kind of fighting this losing Darwinian battle.

ISAACSON: When we edit human genes, and do it in the germ line, which means it goes on to our children and our descendants…

CHURCH: Yes.

ISAACSON: … do you think that ought to be done only for therapies, like to fix things such as Huntington’s disease, or do you think it would be a good idea to make our children taller and blonder and stronger?

CHURCH: I just want to be clarify, we don’t do this right now. We don’t edit genes in germ line. There are alternatives. And you always have to consider the alternatives in medicine. Right? So, the alternatives for Huntington’s, which is practiced, is that you can go into an IVF clinic and you can pick the embryos that don’t have Huntington’s. You can even do that in such a way that you don’t even let the parents know whether they have it or not. Some parents don’t want to know whether they have Huntington’s. They just want to make sure their kids don’t. And so that’s all done. So, there’s no particular motivation to develop a new technology. All these new therapies, it costs a billion dollars to develop a new therapy, whether it’s gene therapy or some regular small molecule. I prefer things that are equitably distributed. This is — when you talk about ethics, I think this is something that should come up more than it does, is, it’s not just, is it safe and effective, but is it going to be available to everybody, so you don’t have the rich-get-richer situation and the poor get poorer? And the alternative that is very cost-effective and available today, doesn’t require new research particularly — it does require some communication — is genetic counseling, rather than gene therapy. So you just read your genome, which you kind of have to do anyway to do the therapy. Just read it, and then you can pick people that are compatible with you before you start dating. So, this — it’s only 5 percent of the people that you will miss. So, 95 percent of the people are compatible with you, so it’s not a big burden from a dating standpoint.

ISAACSON: What did you think when the Chinese doctor, though, did this type of editing that was inherited?

CHURCH: I mean, it was inevitable. And I wasn’t necessarily happy with it, the outcome, but I wasn’t surprised by it either. We did — we had not set up an adequate system for whistle- blowing. They can’t point the finger at just at the person who did it. There is also — there were dozens of people who knew about it, both in the United States and in China. None of them spoke up. We just don’t have a culture of whistle-blowing. And we should, because there — this is not the most serious things that we should be blowing whistles on, I mean, things having to do with pathogens and so forth. You know, it’s unlikely that people will die because of this particular experiment, OK. There are two children born so far, maybe a third. I think it’s unlikely they’re going to die. But we will see. And I think we should be paying attention to them. There should be some sympathy for their plight. They have at least been spared of the publicity. But, you know, there were deaths at the beginning of gene therapy. Gene therapy forged ahead. This case, I don’t even think we’re talking about life and death. We’re talking about something much more abstract.

ISAACSON: You have formed more than 20 companies, I think, coming out of the…

CHURCH: Yes.

ISAACSON: … basic science that comes out of your lab or that you have worked with. Do you think that’s a really good thing for science to be driven by trying to create biotech companies and fund it, or do you think that that can be a problem as well, which is, it drives science to do things that you wouldn’t do unless you could make a lot of money at it?

CHURCH: Well, so, I mean, I think you can be driven in that in odd ways without ever making a company. I mean, you could — and there is a problem that, if you just publish something without escorting it into the public, where it can be used, it dies. It doesn’t blossom. So, I think there’s some — you need some commitment to getting it out there. And, you know, some of these things are quite expensive. The cost of developing a drug is $1 billion. If you’re going to try to do that — if you expect somebody to read your paper and somehow it’s just going to happen, it’s unreasonable. But for the most part, most of my colleagues that I know that do this, they’re just totally motivated by the science, the cool factors, the helping society. And what they do with the money is, they just plow it right back into research, some — for either basic research or more applied research. I don’t think it warps our mission that much.

ISAACSON: George, thank you for being with us, sir.

CHURCH: Thank you very much.

ISAACSON: Appreciate it.

CHURCH: Yes, lovely.