Genome-Edited Babies: The Latest Report and Reactions to It

Biopolitical Times
Cover of the Report

On September 3rd, Heritable Human Genome Editing was published. This Report was the work of a multinational Commission organized by the U.S. National Academies of Sciences and Medicine and the U.K. Royal Society. Its explicit conclusion, as described in the press release, is two-fold: first, that heritable genome editing is not yet safe or effective enough for human application; second, that the first clinical uses of it should be restricted to serious diseases caused by a single aberrant gene. 

The Report also provides a noteworthy implicit conclusion: For the specified circumstances, it defines “a responsible clinical translational pathway from rigorous preclinical research that determines whether and how editing can be performed efficiently and with high accuracy, to clinical application.”

Marcy Darnovsky, the Executive Director of the Center for Genetics and Society (CGS) immediately noted in a press release that:

The idea that now is the time to set aside the deeply controversial question of whether heritable genome editing should be done at all in order to iron out the nitty-gritty details of how it might someday move ahead is completely backwards.

The Report does include a substantial and very useful analysis of the scientific and technical challenges that such editing would entail. More controversially, it consistently mentions and then passes over the equally tricky ethical and societal challenges involved. Essentially, as Katie Hasson, CGS Program Director for Genetic Justice, pointed out

The Report says that public discussion must take place, but that someone else will have to be responsible for it.

All the principal news organizations that include a scientific focus covered the news, many of them noted below. Most quoted one or both of the Commission co-chairs, Richard Lifton, president of the Rockefeller University in New York, and Kay Davies, professor of genetics at the University of Oxford, and other members. Many also quoted prominent scientists and academics, including Jennifer Doudna, Fyodur Urnov, Hank Greely, David Liu and Benjamin Hurlbut. There were also informative Twitter threads from @PeterFRMills, @CohenProf, and @ewanbirney, among others. 

However, neither the New York Times nor the Washington Post assigned their own reporters; both ran the Associated Press story, with the AP headline:

Still too soon to try altering human embryo DNA, panel says

Other news organizations covered the story, of course, including STAT, both as news and with a valuable opinion column by Josephine Johnston of the Hastings Center; the Wall Street Journal; The Scientist; GEN; Science News; Axios; OneZero; Biospace; AFP; and the BBC. Special mention should go the UK Daily Mail, which went to town with an extensive feature.

Both proponents and opponents of the technology, as well as the Commission itself, may be disappointed that the papers of record did not treat this as an important story.

Governance Issues

As described in the Report (p. 22 of the pre-publication version currently available) the Commission was tasked with

developing a framework for scientists, clinicians, and regulatory authorities to consider when assessing potential clinical applications of heritable human genome editing. This framework could be used in the development of a potential pathway from research to clinical use, should a country conclude that HHGE applications are acceptable.

The reference at the end to “a country” arguably represents a significant change from the original remit, which was:

to develop a framework for considering technical, scientific, medical, regulatory, and ethical requirements for germline genome editing, should society conclude such applications are acceptable.

The assumption implied by that subtle shift — that global governance is impossible — might be seen as running counter to the Commission’s origins. It was set up in early 2019, as Benjamin Hurlbut pointed out

to salvage the damaged reputation of the genome editing field by showing how to do responsibly what [He Jiankui] did irresponsibly.

He Jiankui, we subsequently learned, was in close touch with several American academics. This not only suggests a disastrous failure of scientific self-regulation, it emphasizes the international nature of modern cutting-edge scientific research. 

As frequently noted in the Report, the World Health Organization (WHO) has also convened an Advisory Committee on Human Genome Editing. The WHO committee was formed to focus on “appropriate oversight and governance mechanisms, at the international, regional, national and local levels,” while the Commission “is more concerned with the scientific and technological questions” and “limited to issues inextricably linked to research and clinical practice.” Nevertheless, all of Chapter 5, the last in this Report, is about “National and International Governance of Heritable Human Genome Editing” as are Recommendations 8–11. Also, the scientific discussion itself raises “societal and ethical issues that were beyond the Commission’s charge” (as noted in Recommendation 2) but receive significant consideration, for example in Chapter 3, “Potential Applications of Heritable Human Genome Editing.” 

The Report does rather vaguely call for international oversight, noting that: “Citizens from different countries seeking access to HHGE will travel to countries where it becomes available” (p.159), though it makes no attempt to consider the consequences of such travel. Darnovsky told The Guardian she agreed that it was “unlikely that any boundaries would hold”:

“We could see gene editing for embryos marketed as an enhancement technique, and from there the emergence of a market-based eugenics that would exacerbate already existing discrimination, inequality, and conflict.”

The Pathway Assumption

Despite the Report’s caveats about developing a “potential pathway from research to clinical use, should a country conclude that HHGE applications are acceptable” (p. 22), to be implemented only after “extensive societal dialogue” (p. 2), many people asked for comment noted that the pathway seemed rather too sure of its destination. Stanford lawyer and bioethicist Hank Greely told Wired:

The large amount of discussion of the pathway may cause casual readers to think it is endorsing its use, if proven safe and effective.

Peter Mills of the Nuffield Council pointed out on his personal Twitter account:

The pathway is a powerful organizing metaphor for technology. The pathway drives traffic to its destination. If you have not asked for a pathway, or if you don’t want a pathway, being presented with fully drawn-up plans for a pathway may seem a little presumptuous.

Australian bioethicist Jackie Leach Scully agreed, in Nature

There’s a risk that [the Report] will be perceived as saying, ‘Because we’ve got this focus on scientific and technical issues, we have already made the decision to go ahead with it.’

Katie Hasson summed up this concern in an interview with Science News:

“There’s no reason this should be inevitable. Laying out this path in advance makes it seem more inevitable and pushes us toward that conclusion.”

The Technical Challenges

What is clearly explained by the Report, in great detail, is just how far scientists are from demonstrating safety and effectiveness. Davies noted that “There are a lot of gaps in our knowledge and further research is necessary.” CRISPR pioneer Jennifer Doudna (who was not involved) emphasized this:

It underscores what really I think most researchers who think about this are aware of: There must not be any use of germline editing for clinical purposes at this time. And the reason is the technology is just too early-stage and we don’t understand well enough how it works in human embryos.

Paul Knoepfler, a UC Davis professor of Cell Biology and Human Anatomy, applauded the Report in general but remained concerned about the technical challenges:

I wonder whether the technical hurdles like mosaicism and reducing the risk of deleterious on- and off-target effects can ever be overcome satisfactorily. In my view, the report summary should have been more direct about just how difficult these challenges will be and raise the possibility that they may never be resolved.

Knoepfler supports a temporary moratorium on heritable genome editing. In practice, if the Commission’s recommendations are followed, there may be one. Eric Lander, president of the Broad Institute and a member of the Commission, who along with other scientists and scholars has advocated for a moratorium, told Technology Review that

the group’s conclusion that genome-editing technology needs several more years of research amounts to an extended moratorium on further CRISPR babies. 

The same practical effect is likely to result from the rather stringent specifications for what could be the first applications. In brief, they specify several criteria: a serious monogenic disease for which the pathogenic variant can be changed to one that is common and known not to cause disease; a process in which no embryos would be edited that did not have the bad allele; and where the parents have essentially no other option for having a healthy child who is genetically related to both of them. (Many have noted that full genetic relationship is a matter of fulfilling parental desires, not a medical criterion.)

All this, after the technology has been proved safe and efficient, and assuming it would be applied in a country with a good regulatory structure, after an International Scientific Advisory Panel has been established, with a proper oversight mechanism. (See pp. 4–5 of the Report.) This should follow a societal debate, for which the Report considers the WHO responsible (p. 1). Incidentally, the target of He Jiankui’s attempts, the CCR5 gene, would be ruled out on several grounds (pp. 107–8).

Fyodor Urnov, a colleague of Doudna’s at the Innovative Genomics Institute, has long opposed heritable human genome editing as impractical and unnecessary. Urnov also considered that the detailed guidelines in the Report offer “a strong reason for any aspiring embryo editors to turn their efforts elsewhere.” 

Harvard’s David Liu told Science that the Report was “thoughtful, balanced, and well-bounded,” but still had misgivings about allowing heritable human genome editing at all:

I continue to struggle to imagine plausible situations in which clinical germline editing provides a path forward to address an unmet medical need that cannot be provided by other options.

Liu also told the Associated Press about his concerns that if a disease can be treated, “then it doesn’t make sense to me to layer the additional medical and ethical risks” of editing embryos to try to prevent it. 

Advocates of Heritable Human Genome Editing

Some concern about the Report was expressed by advocates of heritable human germline editing. Oregon Health and Science University issued a press release with a statement from Shoukhrat Mitalipov, who concurred with the commission’s finding that it’s premature to use gene-editing tools to establish pregnancies, but also believes that “responsible scientific research in early human embryos is necessary now more than ever.”

Sarah Norcross, director of the Progress Educational Trust, told Science Media Centre (whence the quote was picked up by several outlets) that 

The criteria the report sets out, for the first acceptable clinical use of germline genome editing in humans, are far too narrow. 

The would-be rogue Russian Denis Rebrikov agreed. Indeed, he told New Scientist that “We are still planning to correct the inherited hearing loss mutation in [the gene] GJB2, so that a hearing baby is born to a deaf couple.” In this, he goes further than Norcross, who “would not be supportive of it being used first for deafness.” 

Preventing Rogues

According to Lifton, the Commission “was very concerned about the potential for rogue scientists.” The one (so-called) rogue who so far actually has edited embryos with the intention of them developing through pregnancy to birth is not named in the Report, which consistently refers to him as “a scientist” or “the researcher” (pp. 20–21). His name is He Jiankui. We have learned since He’s 2018 announcement that he had created “CRISPR babies” that several notable American scientists were aware of his work, including Michael Deem, Craig Mello, Matthew Porteus, William Hurlbut, and Stephen Quake. Some of them helped, others urged him not to proceed, but all of them observed the scientific omertà that developed over years of informal discussions.

The word “rogue” is not in the Report, though it does refer to “unapproved uses” and “unpermitted uses” (once each) as well as twice to “misconduct” (pp. 14, 157) and twice to “illegal” (pp. 29, 137), both in the context of current legislation that would need to be replaced to perform heritable human genome modification. 

The word “treaty” does not appear either, and the most significant international agreement is mentioned only in a footnote and without any details (p. 159). The 1997 Oviedo Convention on Human Rights and Biomedicine has the force of law in its 29 ratifying countries, and it bans heritable human genome editing. (The ban is not mentioned.) According to bioethicist Françoise Baylis, at least 67 countries currently prohibit the procedure.

Without global governance, arising from a fully informed public debate, it is all too likely that someone will try — and very likely fail — to edit embryos.