The Year After the “CRISPR Babies” Bombshell
A year ago, this November 25, the world was told that two genetically modified babies had been born. We have no idea how those babies are doing; in fact, we know very little about them, not even their birthday. The scientist who edited the babies' DNA, Dr. He Jiankui, did not actually work in secret, we discovered later, but he did wait until he could present the world with a fait accompli.
Dr. He is a biophysicist turned biotechnologist who, at the time, was an associate professor at the Southern University of Science and Technology in Shenzhen, China. His story — “world’s first CRISPR babies” — was published as an unauthorized scoop by Antonio Regalado in MIT Technology Review; it was quickly confirmed by the Associated Press, which had been working on the story for weeks. Hours later, Dr. He’s American public relations company released previously prepared interviews and videos. Clearly, his plan had been to make a splashy announcement at the Second International Summit on Human Genome Editing, scheduled for November 27–29 in Hong Kong. On the 27th, he gave a presentation there and faced questions in front of the hundreds of scientists and reporters gathered at the Summit.
The “CRISPR babies” announcement made headlines around the world, and the response to it is still developing. Here, in roughly chronological order, are key events related to the announcement and to the debate about human germline genome editing that ramped up over the past 12 months.
INITIAL REACTIONS, November–December 2018
The first response to the announcement was unanimous condemnation. But, before long, it became clear that there was a divergence between those who were seriously alarmed by the prospect of heritable genome editing and those who qualified their outrage by describing Dr. He’s experiment as “premature.” Given a day or two to catch their breath, the Summit organizers transitioned from making a noncommittal statement to suggesting that “it is time to define a rigorous, responsible translational pathway toward such trials” of germline editing. They called for “an ongoing international forum,” which the US National Academies of Science and Medicine and the Royal Society of the UK (henceforth NAS/RS) subsequently set up.
Chinese scientists condemned the experiment (full statement in Chinese), as did He’s university. China’s Genetics Society and the Chinese Society for Stem Cell Research stressed that He’s work posed “tremendous safety risks for the research subjects.” Chinese authorities immediately began an investigation; the Deputy Minister of Science asserted that the experiment was “prohibited under Chinese laws.”
An analysis of 125 news articles and commentaries from November 25 to December 3, most but not all from the US, showed no one not involved in the experiment who unequivocally supported it. Some prominent scientists, including Robin Lovell-Badge of the Francis Crick Institute in London, “worried about a knee-jerk reaction that might … make it unnecessarily hard to do this research.” Others, such as CRISPR pioneer Jennifer Doudna, saw “a potentially positive outcome,” if the reaction led to clear criteria for “responsible germline editing.”
The Center for Genetics and Society (CGS) and the UK’s Human Genetics Alert organized a Civil Society Statement, which was presented at the Summit before its close. The statement called for condemnation of the "rogue actions" and for "governments and the United Nations to establish enforceable moratoria prohibiting reproductive experiments with human genetic engineering.”
On December 18, the World Health Organization (WHO) announced “a global panel to study human gene editing and the scientific, legal, social, and ethical challenges that surround it.”
Where did the balance of sentiment lie? Regrettably, some people, notably the Summit organizing committee, preferred to ask when and how rather than whether such interventions should take place. But there has been significant push-back against this techno-enthusiasm from a range of stakeholders, including scientists, biotech companies, ethicists, public interest groups, and social justice advocates. There have also been some useful suggestions for how to proceed with inclusive, robust public conversations about whether heritable genome editing should ever be permitted.
DISCUSSIONS AND DEVELOPMENTS, January–February 2019
One of the first formal civil society convenings to discuss the future of germline editing was organized by CGS and held in Switzerland on January 14–16, 2019, under the auspices of the Brocher Foundation: “Engineering Future Generations? The New Debate about Societal Governance, Public Engagement, and Human Gene Editing for Reproduction.”
On January 17, Bioethics Forum published an article by leading ethicist Françoise Baylis of Dalhousie University and CGS Executive Director Marcy Darnovsky titled “Scientists Disagree About the Ethics and Governance of Human Germline Editing.” They pointedly critiqued the growing assumption that the scientific community was unanimously predicting the advent of germline engineering.
By then, it was common knowledge that the editing performed by Dr. He was a scientific failure (as some scientists had noted very quickly) as well as an ethical one. Even if it had successfully reduced the babies’ risk of contracting HIV, it would have done so at the cost of increased susceptibility to the West Nile and influenza viruses.
Also in January, the Chinese government confirmed that Dr. He, who was by then under house arrest, had initiated a third pregnancy (something He had announced the previous November but was, to this point, unconfirmed). The due date was thought to be early July, but there have been no updates on this pregnancy since.
As time went by, the involvement of American scientists as co-conspirators was becoming clearer. By the end of February, an article in Nature was asking, “Why were scientists silent over gene-edited babies?”
CALLS FOR A MORATORIUM, March–April 2019
On March 13, Nature published a call for a “moratorium on heritable genome editing.” What made this significant was not just the content of the article or the popularity of the journal, but the extremely distinguished list of 18 authors; led by Eric Lander (president of the Broad Institute), the authors also included Feng Zhang and Emmanuelle Charpentier (both leaders in the discovery of CRISPR gene editing) as well as Nobel Prize winner Paul Berg. It seems unfair to omit the rest, but suffice it to say that they were all major figures in the field. CGS responded cautiously with “A Step in the Right Direction—But We Can’t Stop Here.”
Much of the response to this high-level call for a moratorium was favorable. Carrie D. Wolinetz and Francis S. Collins of the National Institutes for Health (NIH) strongly, for example, supported it. CGS collected a number of reactions along the lines of "a welcome step" and "a good start." However, the proposal was criticized as “part of the problem, not part of the solution” by the British activist group Stop Designer Babies, and called “a step backward when the relevant science, developmental biology, is brought into the picture” by Professor Stuart Newman, who predicted “a consensus to proceed with caution on a form of human experimentation that should never be undertaken.” Advocates of human germline modification mostly kept their heads down.
On March 19, the WHO’s advisory committee on developing global standards for governance and oversight of human genome editing announced the results of their first meeting. They proposed to establish a global registry “for both germline and somatic cell editing research” that was intended to list all experiments related to the human genome. (The registry was officially launched in August.) However, they rejected a “vague moratorium” in favor of a “more comprehensive, stepwise approach,” which critics found even vaguer.
At almost the same moment, scholars Sheila Jasanoff of Harvard and Ben Hurlbut of Arizona State University called for a “global conservatory” in hopes of changing the way that problems are framed by including “voices and concerns that are currently inaudible to those in centres of biological innovation.” As a conceptual approach to the issue, the conservatory idea may, in the end, be influential.
On April 24, 62 scientists, bioethicists, and biotechnology executives — including several prominent members of the American Society of Gene & Cell Therapy (ASGCT) — signed a letter to the US Department of Health and Human Services supporting “a binding global moratorium until serious scientific, societal, and ethical concerns are fully addressed.”
A PATHWAY TO GERMLINE? May 2019
Support for some kind of a moratorium was growing, but there was often a catch. On May 9, the German Ethics Council issued a report titled Intervening in the Human Germline, which concluded that germline interventions were “currently too risky, but not ethically out of the question.” Given that Germany has strongly opposed eugenics since World War II and prohibited human germline modification in 1990, this conclusion was surprising. Moreover, they attempted to flip a major argument back on opponents by suggesting that
the question also arises as to whether the renunciation of germline intervention, which could spare the people concerned severe suffering, would not violate their human dignity, too.
The Council did call for “a binding international agreement, preferably under the aegis of the United Nations,” which George Annas of Boston University’s School of Public Health called “a major take-home” since the distinction between voluntary and binding agreements is significant.
The Washington Post editorial board supported a moratorium on May 21, but recommended outsourcing the discussion to the NAS/RS or perhaps the WHO; the headline rather gave the game away: “We have the technology to customize our babies. It needs regulation.”
On May 22, the NAS/RS announced its International Commission on the Clinical Use of Human Germline Genome Editing, which was tasked “to develop a framework for scientists, clinicians, and regulatory authorities to consider when assessing potential clinical applications of human germline genome editing … [that] could inform the development of a potential pathway from research to clinical use — if society concludes that heritable human genome editing applications are acceptable.”
Ominously, a report by Sharon Begley in STAT at the end of May suggested that fertility clinics around the world had asked the disgraced Dr. He to teach them how to use CRISPR on embryos. One from Dubai put it in writing; He told Stanford ethicist William Hurlbut that there were several others. This is shocking but not surprising since many fertility clinics already market sex selection, a few claim to provide embryo selection for eye color, and one start-up purports to test IVF embryos for IQ.
ENTER REBRIKOV, June–July 2019
The summer got significantly worse when, on June 10, Nature published this article by David Cyranoski:
Denis Rebrikov was first reported as intending to make the same kind of edits as Dr. He the year before but soon changed his objective to correcting a mutation that leads to hereditary deafness. This provoked outrage and accusations of ableist assumptions, but it kept his name in the press. (For those unfamiliar with discussions of germline editing within the disability community, this page is a useful, well-linked introduction.) A little later, Rebrikov’s name surfaced yet again due to speculation that this proposal might put the future of heritable genome editing into the hands of Vladimir Putin. The Russian president was reportedly skeptical, at least about enhancement technologies, but it was speculated he might be swayed by claims of medical applications.
Nature published an editorial in the same issue as Cyranoski’s article that tut-tutted and wrung its hands:
The scientific community now has an opportunity to do what they couldn’t with He — work with Rebrikov to identify and discuss the risks. That’s better done by engaging with him than by branding him a maverick. And Rebrikov must listen to the concerns and the critics, and not move forward until the dangers are assessed.
That doesn’t seem to have been an effective deterrent.
SELF-REGULATION, August–October 2019
The concept of scientific self-regulation — a mantra of many advocates of heritable genome editing – took a major hit at the beginning of August with the revelation by reporter Jon Cohen in Science that there were “five dozen people who were not part of the study but knew or suspected what He was doing before it became public.” They constituted a “circle of trust”:
That circle included leading scientists — among them a Nobel laureate — in China and the United States, business executives, an entrepreneur connected to venture capitalists, authors of the NASEM report, a controversial US IVF specialist who discussed opening a gene-editing clinic with He, and at least one Chinese politician.
Many, probably most, of those involved thought that Dr. He's plans were wrong, and told him so. Dr. He, in contrast, was of the opinion that he was following guidelines set out by the NAS in 2017. He was not, though the report did recommend that heritable genome editing could be ethical under certain conditions. The entire episode ought to — but has not — put to rest the idea that scientific self-regulation is anywhere close to being adequate.
On August 13, the first meeting of the NAS/RS international commission took place in Washington, DC. Their charge, cited above, was conditional: to identify a “potential pathway” for human germline editing “if society concludes that [such] applications are acceptable.” At this meeting, “if” might as well have been “when.” For example, an item described on the Commission’s August agenda as “Translational Pathways from Laboratory to Therapy: Somatic Genome Editing” was actually a presentation titled:
Technical Challenges to Achieving Safe and Effective Human Germline/Heritable Based on Data from Somatic Cell Editing
Some of the presentations listed on the agenda as focused on somatic gene editing were, in fact, about that, but in another, the “way forward” clearly envisaged heritable genome editing. Hence the title of this CGS review of the meeting: Rigorous Pathway or Runaway Train?
In contrast, on August 27, the Alliance for Regenerative Medicine, an international organization of biotech companies, research institutes, and others, released a Statement of Principles on Genome Editing that strongly endorsed somatic applications but asserted that “germline gene editing is currently inappropriate in human clinical settings.” It was signed by 13 major gene-therapy companies. It may be that they don't want the controversy to hurt their business, but some do have a history of opposing germline interventions.
In September, NAS launched a disastrous attempt at public education that seemed to be pushing heritable genome editing as if it were advertising an online dating platform. The Twitter-, video- and web-based components were roundly mocked and ridiculed and have all since been deleted.
Rebrikov complained in September that “Everyone is just yammering. I want the rules to be set, but nobody is doing this.” President Putin may or may not approve. Incidentally, there are also reports that the Russian military is trying to understand “at the genetic level … who may be more prepared to become a paratrooper or a tankman.”
Of course, “the rules” are exactly what’s being debated. The maverick is just impatient. His ambitions had been condemned by WHO in July and again in August when they announced “a new global registry to track research on human genome editing.” This criticism was echoed in October by the Ministry of Health of the Russian Federation. But once again, the keyword was "premature"—not yet but not never.
ONE YEAR LATER, November 2019
Francis Collins, director of the National Institutes of Health (NIH), reaffirmed his support for a moratorium on heritable genome editing on November 6 in a keynote presentation at the ASGCT Policy Summit in Washington, DC. Collins delineated “three main reasons for a moratorium: safety, medical, and ethical,” while lauding advances in somatic therapies. Many of the other speakers at the policy summit agreed.
Regrettably, the second public meeting of the NAS/RS initiative, on November 14–15 in London, was no better than the first. It did include attention to “how to prevent risk havens for germline editing,” but even that assumed the reality of germline editing and demonstrated that their concern was all about how to manage it.
As the anniversary approached, Nature published an editorial endorsing the WHO recommendation that it would be "irresponsible at this time for anyone to proceed with clinical applications of human germline genome editing” and urging the NAS/RS Commission to agree. It also noted, with remarkable understatement, that:
It isn’t entirely clear why separate initiatives are needed, and it is unfortunate that representatives of people with disabilities are not part of the decision-making process.
This has been a year of discussions and proposals but very little action beyond the naming of committees. For some advocates of germline genome editing, that is doubtless quite acceptable, since almost all of them agree that the technology is (so far, at least) not safe. For those who consider it to be inherently unsafe, essentially unethical, or unacceptably dangerous from the perspective of social justice and human rights, the year has overall been disappointing. Although increasing awareness of the failures of self-regulation provides some encouragement, the mission of the NAS/RS doggedly creeps toward assessing when and how heritable genome editing should happen, instead of if it should move forward at all. And although gestures to “broad societal consensus” continue, little material support for enabling meaningful public engagement has been secured.
Next year may see better and more concrete proposals, both for public engagement and regulation at both national and global levels. If not, the window for heading off more bombshells will continue to close.