Interviewed by William Leonard Pickard
George Church, PhD, is the Robert Winthrop Professor of Genetics at Harvard Medical School, Professor of Health Sciences and Technology at Harvard University and the Massachusetts Institute of Technology. He is a founding member of the Wyss Institute for Biologically Inspired Engineering at Harvard.
His research efforts include the first direct genome sequencing method, collaborating in initiating the Human Genome Project, and creating the Personal Genome Project. He co-founded over 50 biotechnology companies as spin-offs from the Church Lab, including Veritas Genetics, Rejuvenate Bio, and Nebula Genomics. Church began Colossal Biosciences to de-extinct the woolly mammoth.
Dr. Church’s research published in Science Translational Medicine pointed to lower immunogenicity in gene therapies, and in PNAS to simultaneous treatment of obesity, type II diabetes, heart failure, and renal failure.
How does an external group that wants to do something approach your lab? In these spin-offs, does one approach the Church Lab with a request for licensing or are there collaboration agreements with the Harvard Office of Technology Review?
GC: Both are possible. For collaboration, it’s typically a sponsored research agreement. We’ve got two or three of those right now. The most notable recent ones were making human gametes for in vitro fertilization.
Andres Sandberg, a bioethicist at the Future of Humanity Institute at Oxford, asks how you manage your risk-benefit profile.
Almost every technology that I’ve been involved in could have dual-use. Sequencing by 20 million-fold, that seemed like an appropriate time. Another one was gene drives, where we proposed how to contain them. And then when we improved synthesis by about 10,000-fold, now probably a million-fold, we’ll dash back from lawyers saying it could be an invasion of privacy of the pharma companies that were placing DNA orders, and that if we look at our orders, we’ll be responsible for them in some sense. But anyway, eventually we overcame those objections.
Can you comment on BGI Group’s – formerly Beijing Genomics Institute – search for ultra-intelligent individuals across China, and sequencing of their genomes to identify genes for educational attainment or intelligence?
GC: BGI currently is blacklisted by State, so I am not involved. In terms of intelligence, Steven Hsu was involved in one of these studies. There have been a few; they tended to come up with very little. Now, that said, I maintain a website of all kinds of enhancements, mainly as an inspiration for pharmaceuticals. In fact, some of them have now become pharmaceuticals.
You’re a small molecules fan when it comes to cognitive enhancement?
GC: No, not particularly. I tend to think that gene therapy is a more powerful method, but some of my companies do work on small molecules. But it’s mostly gene therapy and cell therapy.
You’re involved in the Supercentenarian study with James Clement.
GC: Quite a while ago, we helped sequence organisms which live exceptionally long relative to their close relatives. The bowhead whale lives a lot longer than other cetaceans. The capuchin monkey, more than other monkeys. The naked mole rat, more than other rats. So I would say we’ve got a few hints. There are a few genes that we add to the list. We already have a list of 300 from cell biology. It hasn’t really impacted our choice of gene therapies yet. There were lots of different information streams feeding together, and I think that was a fairly minor one so far, but I’m glad we did it.
Is cognitive enhancement through genomics too speculative for you? Do you think that the 50-100 genes identified in Genetic Wide-Association Surveys (GWAS) as involved with educational attainment could be expressed?
GC: I don’t think that GWAS has necessarily been that fruitful, as I mentioned earlier. But what has been fruitful is synthetic biology. What’s happened is if you do experiments on mice, you can identify genes that help them perform a variety of cognitive tasks. Oh, yes. If you’re not too fussy about what combination of tasks and things like that, it’s really quite impressive. There’s going to be a lot of gene therapies and other therapies that are in line. Some of them will actually cause augmentation.
Some will cause augmentation?
GC: Yes, people will start using them younger and younger and longer and longer before the onset of symptoms. And then a whole market will get good at it, maybe, or maybe more general. I think cognitively advanced “computers” are more likely to be human than they’re going to be silicon. Silicon computers can do Jeopardy and chess very well, but I think there still are some things that are more in reach for synthetic biology than they are for synthetic von Neumann silicon.
Will we see this lifestyle-enhancing cognitive therapy?
GC: I think that most of our technologies are enhancing in some sense or other. Cell phones are enormously enhancing. Vaccines are making us have no fear of dozens of diseases. And I think the same thing is certainly true of anything cognitive. You know, coffee is just the tip of the iceberg.
Why not go ahead right now, with a project that bypasses treating neurodegenerative diseases, and go directly to improving cognitive function in normal humans?
GC: It has piqued my interest for many years. The practicality I’ve noticed over the years is that no matter what we aim at, there’s the very severe, shorter-term FDA trial. If you look at gene therapies, I’ve been kind of a vocal opponent and advocate of gene therapies for rare diseases. The only exception that I know that’s getting close to the beginning of clinical trials is a trial that does aging reversal. That’s not a rare disease. That’s going to kill 90% of us. But it’s easier to get approval for a rare disease.
If you can improve cognitive skills with Mild Cognitive Impairment (MCI) patients, would it augment normal humans?
GC: I think it has some possibilities. We’ve been kind of moving in that direction. I maintain this list of potential enhancements, a huge fractional list. And so those are the genes that we could start on. There are problem to be solved but it’s achievable. I would love to go in that direction. I don’t even think it’s going to be that controversial, frankly. The only thing that’s controversial is starting with healthy adults.
Yet enhancement might lead to a personality shift away from the social connection, and you could have a dangerous smart person?
I agree. Even the military would like to have people that are very sociable and easy to talk to in between missions. I mean, they can’t be on the battlefield every minute of every day. So you want something you can switch on and off. I count myself in this, to be able to turn these things on and off. In other words, I wouldn’t want to be barely functioning autistic all the time. But if you could turn it on and off, that would be great. And some people say we can’t engineer these until we understand them but that flies in face of most engineering. Most engineering is done with a very primitive level of understanding. I think you could increase oxytocin levels or what have you. I mean MDMA is a temporary small molecule for the space of seven or eight hours.
If it’s reversible I think that’ll make it easier to get approval and easier to market and also easier to evaluate. You can see both sides of the coin, and if there’s any deleterious longer-term effects.
How does your lab handle ethical issues that might arise?
I routinely accompany each potentially transformative paper with a paper addressing the ethics (safety, security, equity, or stigmatization). In 2004 this was chip synthesis of pathogen DNA. In 2005 the topic was consent for public release of human data. In 2014 CRISPR gene drives. And other papers covering germline editing, artificial intelligence, arctic carbon release, etc. I have also enabled and listened carefully to dialog via journalists, pged.org and teaching the required HMS discussion course on ethics, the responsible conduct of science.
