A new genetic testing company called Nebula Genomics wants to help people profit from their own genomes. The Observer talks to Harvard University DNA sequencing pioneer George Church about his latest venture, what’s cooking in his lab and how falling asleep on the job can sometimes be a godsend.
What is the value of getting your genome sequenced? Why do it?
One very compelling argument that I think justifies almost everybody in the population getting sequenced is reproductive decision making: who to date, who to marry, whether or not to have gamete [egg/sperm] donors. Anybody that is of reproductive age, whether they intend to or not, are at risk of producing 5% of babies that are very severely affected with genetic disorders. Longer term, sequencing can enable the development of therapies that could provide years of enhanced quality of life.
Why aren’t people getting their genome sequenced and how will Nebula Genomics change that?
Cost and concerns around privacy are putting people off. Even as the price has fallen, most people don’t see the value. Nebula may get us enough people doing it so that it spreads. Right now, genome sequencing is like the internet back in the late 1980s. It was there, but no one was using it. Then the first browser came and commerce started – it was the tipping point. The same thing could happen here. We have been waiting for the right technology tipping point.
What does the new approach bring? How can it change people’s attitude?
The drive will come from three areas: can people help their family? Can they do something altruistic for everybody? And can they do it so inexpensively that they can brag to their friends that they got their genome sequencing done for free, or are even getting paid for their genome [information]?
You founded the nonprofit Personal Genome Project, which since 2005 has gathered genomic and health data from around 10,000 volunteers. Why not stop there?
That is for people who are feeling particularly altruistic, or have a disease in their family that they want to receive high priority research, and are willing to give up some privacy. Our new blockchain model allows it to be done without people giving up their privacy, and getting paid to do something they would probably want to do anyway.
You’ve cofounded more than 20 companies and advised many more. But you also have a lab where you work on noncommercial projects. What are you are working on in your lab right now?
The shortlist: reversal of ageing using gene therapy, which we are testing in pre-aged mice and dogs; making species resistant to multiple viruses – if you have hepatitis and you need a liver transplant, you might as well have that liver be resistant to hepatitis; and making organs, including growing human brains. For the organs we use human stem cell lines created from my skin cells. It is unethical for me to do experiments on my students (in case of any potential coercion), but it is apparently ethical for them to do experiments on me!
You have been instrumental in the development of gene editing tools such as Crispr and there are many clinical and pre-clinical efforts under way to use these technologies to correct human genetic diseases in nonreproductive cells. But what about using them on the germline [human eggs, sperm, or early embryos], where the fixes can be inherited by future generations?
In the US, germline engineering won’t happen until Congress allows the Food and Drug Administration (FDA) to evaluate applications to begin clinical research. [Regulation in the UK is more permissive.] Right now, even if you submit a very promising, well-researched proposal to the FDA they are not allowed to accept it. I think part of it is the misunderstanding that such therapies put embryos at risk – when instead, you are probably saving embryos because otherwise they would be aborted. The alternative is editing sperm and we are working in that direction in my lab. The technology hopefully will be ready by the time that Congress has the dialogue that will result in them allowing the FDA to accept clinical research applications.
You recently argued (in the New England Journal of Medicine) that there shouldn’t be a hard line between editing human germlines for diseases and editing them for enhancement or other traits, though in a report last year the US National Academies of Sciences, Engineering and Medicine concluded there should be. You aren’t against enhancement per se. So where do we stop?
We stop, at a minimum, based on safety and efficacy – keeping in mind the long term. But it is a continuum and it needs to be regulated appropriately. There has to be a broad dialogue as to what the actual risks are for a particular thing, not blanket prohibition. What is the worst thing likely to happen if people made hair blond or cells resistant to viruses? And if that’s acceptable, then we should say so. Generally, regulation is very desirable. It is not a permanent ban, but guidance and protection.
Garnering a lot of attention has also been your research efforts to resurrect the woolly mammoth from extinction, albeit in a revised form. Last February you said you believed you were just a couple of years away from creating a hybrid elephant-mammoth embryo. With a year left, how is it going?
We have had hybrid cells for quite a while and we have made a great deal of progress on making embryo-like structures. Hopefully, this year we will publish four papers of relevance. I think the problem of getting them fully grown in the lab [Church’s plan is to use an artificial womb rather than a female elephant as a surrogate] is more challenging, and I am not making any predictions about when that will happen.
In mid-2016, you launched a 10-year nonprofit project to synthesise the human genome. How are you doing it?
The key thing is developing enough technology to bring the price down a million-fold – and then it is trivial. I don’t want to just synthesise the human genome, by the way: I want to be able to do every organism that is of industrial, agricultural or medical significance. Goals and applications greatly influence the choice of technology: there is no need to synthesise DNA that you don’t need to change. And I consider the most common reason to do it is to make virus-resistant cells and organisms, and that might actually be done most cost-effectively by highly multiplexed editing.
Another of the companies you have cofounded, eGenesis, is focused on using pig organs to overcome transplant shortages. Last year the company reported a breakthrough using Crispr to knock out a key virus in piglets that might cause disease in humans. What’s still to sort out?
We need to ensure human immune systems don’t reject the pig organs and then test how safe and effective these organs are in humans. There already are preliminary experiments involving transplants of partially engineered pig organs into primates. I think probably within a couple of years we will be realising organ transplants this way.
You have attributed your visionary ideas to your narcolepsy. How so?
I don’t think it is my only source of innovative ideas… but it doesn’t hurt. I am surprised sometimes how quickly things come to me when I am in and out of sleep. I have solutions that might have otherwise taken days! I probably wouldn’t fix my narcolepsy, even if I could… It illustrates that we need to be very cautious about eliminating certain genes.