Dare we edit the human race? Star geneticists wrestle with their power

WASHINGTON — The International Summit on Human Gene Editing is wrapping up on Thursday after three days of formal talks, panel discussions, and audience questions on altering the DNA of sperm, eggs, or early embryos — the human “germline” — so that the repairs are passed down to any future children. The prospect of altering human heredity in this way is controversial, to say the least, but it has become a real possibility because of the development of the CRISPR-cas9 gene-editing system.

The meeting has had its share of Tweetable moments: One participant said China will spend $400 million over the next five years on genome-editing research. George Church of Harvard Medical School said the dread prospect of “genetic enhancement” of embryos (a.k.a. designer babies) might come creeping through the back door — as patients with muscle-wasting diseases get their in vitro fertilization embryos engineered to prevent that disease in their children, and then other prospective parents will want that strong-muscle gene so that their embryo can grow into an Olympian. And it became clear that genome editing will likely reopen the bitter debate over embryo creation and destruction.

If there is a divide at the meeting, it is between patients with genetic disease (themselves or in their family) and the doctors who treat them, on one side, and basic scientists like Eric Lander, director of the Broad Institute in Cambridge, Mass., on the other. Dr George Daley of Boston Children’s Hospital sees his patients and thinks, “If I can help them via germline genome editing, I have a moral duty to do so.” Columbia University neuropsychologist Nancy Wexler, who lost many family members to Huntington’s disease and who decided not to have children for that reason, said, “If you have it in your capacity to make a difference you owe it to us to do it.” In contrast, many of the academic scientists at the meeting are focused more on the safety and ethical arguments against germline genome editing.

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In case you weren’t glued to the webcast for 20 hours, here’s what you missed:

What has the summit accomplished?

It aired many different points of view, which was one of the goals, from scientists, ethicists, legal scholars, regulatory experts, patient advocates, and critics of genetic technologies. Some were on the official program, some spoke from the floor during Q&A sessions. In a surprise to some participants, summit committee chairman David Baltimore of the California Institute of Technology announced on the first morning that the committee would issue a summary statement at the end of the meeting “and suggest a path forward.”

What will that “path forward” be?

The committee — composed of 10 scientists and 2 bioethicists — isn’t telling until Thursday afternoon, but there are hints. Some committee members have gone public with their views. Lander told the meeting on Tuesday that “before making permanent changes to the human gene pool, we should use great caution,” a conclusion he said was based on “humility” about how much we don’t know. For instance, even “bad” genes aren’t always all bad, he pointed out; one gene that increases risk of HIV/AIDS reduces risk of West Nile virus.

Committee member Jennifer Doudna of the University of California, Berkeley, whose pioneering work on the CRISPR-cas9 genome-editing system led her to propose such a summit, also made her position clear. On the day before the summit began, she had an essay in the journal Nature arguing that the science and ethical implications of human germline editing are too poorly understood for now that it should not be allowed for the purposes of treating people, such as by changing the genes of an IVF embryo. But she argued against a total ban on germline-editing research, partly because CRISPR-cas9 is out of the bag: the technology is so ridiculously easy to use that telling scientists the world over that they can’t investigate whether it might be used to prevent genetic diseases in embryos would never work.

So the committee has already decided, no germline genome editing for medical as opposed to research uses?

One possibly, and quietly, contrarian view came from committee member Daley of Boston Children’s. “If we overweight the possibility of misuse, we might deprive ourselves of legitimate medical uses,” he said.

What does the smart money say about the committee’s recommendation?

STAT won’t out people who spoke confidentially. But one scholar who chaired a panel predicted that the committee would note the potential promise of germline genome editing and, therefore, call for research to continue, as Doudna advocated, but call on scientists not to go rogue and try this on the genomes of sperm, eggs, or soon-to-be-implanted embryos for clinical purposes — that is, to treat or prevent genetic diseases. One staffer who works with the summit said the committee is likely to call for further study (the go-to position for scientists) and, simultaneously, for work on figuring out how germline genome editing should be regulated. For instance, the Food and Drug Administration, under current guidelines, could classify genome editing as a drug or a device. How FDA handles this will make a huge difference to what happens. The National Institutes of Health announced earlier this year that it wouldn’t fund any research on germline genome editing.

So all political landmines will be avoided?

Hah. Even basic research on editing the human germline genome will require very early human embryos, said one expert on IVF. How early? So early that the “spare” embryos in fertility clinics probably won’t work. “It will probably be necessary to create embryos” to develop germline genome editing, said developmental biologist Janet Rossant of the University of Toronto. No one in the audience (which was largely subdued, reflecting its makeup of mostly scientists, some government officials, and a few patient advocates) reacted to that. But remember the stem cell debate, which centered around the ethics of creating and sometimes destroying human embryos for purposes of research? Get ready for Round 2.

What ethical concerns were discussed?

Eugenics — trying to “improve” the human species. Although the Nazis get all the blame for that, eugenics was a respectable, mainstream scientific position in the United States and Europe early in the 20th century, historian Daniel Kevles reminded the summit: “Eugenics was not unique to the Nazis; it happened everywhere.” While government-sponsored eugenics seems unlikely today, there are other forces that might push for genetic “improvements.” If CRISPR offers the possibility of forever eliminating a disease gene from a family, Kevles asked, “How will couples respond?” NIH isn’t funding anything like that, but “research conducted in private labs is wholly out of government control.”

Were there any fireworks?

It was an extremely low-key meeting, with more and more empty seats as it went on. But on the first day, two ethicists faced off. John Harris of the University of Manchester made the ethical case for research on human germline editing. “We, the world, our descendants need genome editing to be pursued,” he said, arguing that a moratorium on the research would go against the “inescapable moral duty to continue with scientific investigation” of a technique that could eliminate disease-causing genes in an embryo “to the point at which we can make a rational choice. We are not yet at that point. . . . Research is necessary.” But Hille Haker, chair of Catholic Moral Theology at Loyola University, called for a two-year, worldwide moratorium on such research. After more back and forth, Sarah Gray of the American Association of Tissue Banks went to the microphone. Her son had died of a fatal genetic ailment six days after he was born, but not before he was constantly tortured by seizures, she said between sobs. She implored the meeting, “If you have the skills and the knowledge to eliminate these diseases, then frickin’ do it!”

Is that a widespread view?

Many families who have been afflicted by a genetic disease for generation after generation seem pretty gung-ho about using germline editing to wipe disease genes off their family tree forever. When Sharon Terry, president of the Genetic Alliance network of patient-advocacy and similar organizations, asked her members what they thought, responses ranged from “Hell, yes!” to “We want to figure out how to mitigate suffering” to “Don’t let’s think about it yet.”

Ethics aside, what was the most intriguing trait mentioned as one whose gene might be edited into human embryos one day?

STAT votes for the short-sleep gene, which lets people thrive on six or even four hours of sleep, though the gene for green fluorescent protein brought to mind intriguing images of glow-in-the-dark children. There was more serious mention of genes for lactose or gluten tolerance, perfect pitch, and longevity, and semiserious mention of genes for tolerance to heat (the Paris climate change meeting is going on, too).

Was anyone there in a position to make policy?

Lander chairs President Obama’s panel of science advisors. Representative Bill Foster, who has a doctorate in physics, kicked off the summit by pleading for scientists to be proactive and responsible: “It’s very important” that the first use of CRISPR in people “be positive. We need to avoid a reaction that might jeopardize research.” He also said that if CRISPR yields nongermline therapies (most uses would change just blood or other kinds of cells, and the change would not be passed on to descendants), we “must make sure they’re not reserved for the rich and well-connected.”

Once there’s a policy, we’re done, right?

There’s policy, and then there are patients and parents. “There may be applications” of human germline editing “driven by consumer demand that will occur outside the regulatory framework,” said Daley. Read: if people want this, and have the money to pay for it, they’ll find a scientist to do it. See: rogue stem cell clinics. Marcy Darnovsky, executive director of the Center for Genetics and Society, which is critical of many genetic technologies, said once germline genome editing is possible, it “will escape from any regulatory limits,” with “fertility clinics offering the latest upgrades” to IVF embryos.

Where was industry?

Mostly saying as loud as it could that it has no interest in editing germline genomes and please, please don’t let fear of that get in the way of genome editing for diseases like cataracts, muscular dystrophy, blindness, and more. In a statement released as the meeting began, Intellia Therapeutics and CRISPR Therapeutics said genome editing “provide[s] an unparalleled opportunity for treating, or even curing, patients with serious genetic disorders” by targeting nonreproductive cells, and warned that “unnecessarily modifying existing regulations” out of fear of germline genome editing (which they have no intention of pursuing) “would adversely impact patients.”

Would editing the germline genome help many people?

There’s the rub. Using it for basic research could shed light on how a fertilized egg becomes a baby and other important questions. The value for patients — that is, of clinical use — is less clear. The most likely germline use of genome editing would be to repair single genes that always and alone cause devastating diseases, such as Huntington’s. But most of those 4,000 or so “Mendelian diseases” are exceedingly rare, Lander pointed out. For many other diseases, it would be just as effective to correct genes once a child is born and only in the relevant tissue, or to do genetic diagnosis in IVF embryos and implant only healthy ones. “Germline genome editing is not required to help these patients,” said MIT’s Rudolf Jaenisch. For other uses being proposed, he said, germline genome editing “may have limited if any therapeutic applications.”

As the second day of the meeting drew to a close, biochemist Dana Carroll of the University of Utah made a prediction: “Germline applications [of gene editing] will be done, probably before anyone in this room is ready for it.”

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