How will technology transform humanity? From gene editing to AI, five big thinkers

“A geneticist, an oncologist, a roboticist, a novelist and an A.I. researcher walk into a bar.” That could be the setup for a very bad joke — or a tremendously fascinating conversation. Fortunately for us, it was the latter.

This is the beginning of the New York Times article in which a transcript of a three-hour dinner is published, with five brilliant scientists and thinkers: Catherine Mohr, Siddhartha Mukherjee, Regina Barzilay, George Church and Jennifer Egan. The table was moderated by Mark Jannot, editor of journal articles and former editor-in-chief of Popular Science, and they discuss the future of medicine, health and humanity. It’s worth reading it entirety. I’ll leave you a small fragment of it:

Mark Jannot: For years, many pregnant women have undergone amniocentesis to test for rare metabolic disorders and other fetal issues. And couples who use in vitro fertilization can screen the embryos for genetic abnormalities. What sorts of advances in genetic screening and manipulation are coming, and where do you see that taking us?

Catherine Mohr: When I was pregnant with my daughter, my husband and I were joking, “Well, if she gets the best of both of us, she’ll be a superhero, and if she gets the worst of both of us, she’s not going to make it out of first grade.” And so we were rolling the genetic dice, which you do when you choose to have a child. It’s not totally random, of course; there’s all kinds of great things about your mate — that’s why you chose them — and hopefully there’s some pretty good things about you, too. But the temptation to engineer what you think of as the best combination, as we become more capable of doing it, I think it’s going to be irresistible for a lot of people. You’re investing so much of your life into this little being, and you’re going to love this child, and you want to give them every advantage in life. We are already screening for diseases to avoid passing on our “bad” genes, but this same technology will let us start screening for our “best” genes — the ones we really want to pass on. As screening becomes cheaper, easier and more reliable, and more people are using assisted-reproductive technologies, I see us, as a society, sliding down that slippery slope pretty far, one couple at a time, each trying to do what’s best for the child they are hoping to bring into the world.

Siddhartha Mukherjee: It’s certainly a tempting path, toward a potentially terrifying slope. But that only works if you do in vitro fertilization and create a pool of testable embryos. Then you have to biopsy those embryos-in-dishes, sequence their genes, identify and interpret the gene variants that you want to select (Variant A and B and C and D) and implant the “desirable” ones.

George Church: Or we may turn to gene editing. If, for example, you have a dominant-allele disorder, like Huntington’s disease or Marfan syndrome, and you want to have children, you could edit the sperm, change that allele so that all sperm are healthy and your offspring will be fine. All sperm come from spermatogonial stem cells in the man’s testes. You can use editing tools and work on stem cells in Petri dishes so that you’re removing the bad allele and replacing it with DNA that has been designed and synthesized on computer-controlled machines. And then you can implant a pure population in which you’ve checked that the edit is what you wanted it to be, with all cells with only the desired “on target” changes. This has been done in mice. It’s a great opportunity. It’s only one time, and they’re good for life. In principle.

Jannot: And why is that not being done now?

Church: Until recently, we didn’t have good methods for doing gene therapy that we could apply to editing stem cells, sperm cells.

Jennifer Egan: How hard is it to edit genes?

Mukherjee: Well, that’s one of the surprises, is how extraordinarily easy it is. There are still technical challenges, and some of them may be hard to surmount, but the protocol is quite simple. We recently edited a gene in human blood stem cells to enable therapy for some forms of leukemia. We’ve sequenced the genomes of the edited cells and have not found a single “off target” effect thus far, although we are still looking. For other genes, off-target effects have been reported, so it seems that it’s case dependent. But over all, the fidelity of the system seems quite remarkable.

Church: At this point, there’s nothing published in the literature demonstrating successful editing of human sperm stem cells, the germline. But if you want to edit the DNA of, say, pigs, it’s very easy with Crispr, which is a set of editing tools that uses enzymes, guided by RNA and proteins, to make a change at a precise location in your DNA. You’re injecting a small thing in that changes as little as one base pair out of six billion, in each cell. So it’s nanosurgery — very precise and automatically in many cells at once.

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