A Growing Chorus of Objections to Loosened Rules for Embryo and Germline Research

On May 26, the International Society of Stem Cell Research (ISSCR), a non-governmental  organization of scientists, released newly revised guidelines for research scientists. As in past iterations, they cover much more than stem cells, including heritable genome editing, artificial gametes, and growing human embryos in the lab. These guidelines are the work of a large committee of notable scientists and bioethicists, and have been translated into Chinese, Turkish, Korean, German, and Japanese; they have, or at least seek, global influence. A month later, reactions continue to be published, and for once most of them are critical, from a wide variety of perspectives.

The almost immediate CGS analysis noted several problems, as did other early reactions from the eminent Canadian bioethicist Françoise Baylis, on her own and jointly with South African bioethicist and attorney Sheetal Soni. In the week after the guidelines were released, some of the authors published explanatory pieces, as did NPR (though most other major outlets did not cover the story). A few additional expert commentators, including UC Davis stem cell scientist Paul Knoepfler, also weighed in.

That might have been expected to be that. But more commentary keeps appearing, some of it perhaps indirect.

Criticism from scientists and bioethicists in Nature

Baylis, who collaborated with CGS and others on the Geneva Statement on Heritable Human Genome Editing, and with Marcy Darnovsky, Katie Hasson, and Timothy M. Krahn on Human Germline and Heritable Genome Editing: The Global Policy Landscape, provided further thoughts in a letter to Nature published on June 15:

ISSCR guidelines fudge heritable human-genome editing

She detailed “troubling inconsistencies [implying] that, in time, research that involves making heritable changes to the human genome will be permitted.” She asks whether heritable human genome editing should rightly be considered part of ISSCR’s category 3A (“currently not permitted”) or 3B (“prohibited”), noting that the guidelines’ choice of 3A is by no means self-evident. In fact, 75 countries already prohibit it. She closed by asking directly:

So why is reference to research that is “illegal in many jurisdictions” included in the 2016 guidelines [p. 7] and not in the 2021 guidelines?

Baylis was back in Nature on June 22, this time with a pair of interesting co-authors: Josephine Johnston of the Hastings Center, who has cautiously endorsed heritable human genome editing, and Henry T. Greely, Stanford Professor of Law and, by courtesy, Genetics and author of The End of Sex (for reproduction) and CRISPR People. They acknowledge their differences:

We are researchers with differing views on the ethics of stem-cell and embryo research who nonetheless share deep concerns about the latest guidelines from the International Society for Stem Cell Research (ISSCR).

What they share, perhaps for varying reasons, is concern that the latest guidelines drop the former prohibition of experiments on human embryos beyond 14 days without proposing an alternative.

At some point, the developing human embryo reaches a stage at which it should not be used for research. There is disagreement about when that happens, but scientists need to acknowledge that it does, and reassure the public that they accept limits. … Defining and defending a new limit, and possible constraints within it, will be hard. This was the case for the 14-day cut-off, selected some 40 years ago. But setting no limit is a grave omission.

In the same issue of Nature, British zoologist Matthew Cobb and American biologist Robert Pollack refer to a letter that Pollack and Joe Sambrook drafted 50 years ago but never sent:

As early-career researchers, they decided not to risk antagonizing senior colleagues who might be hostile to the idea of limiting research.

The letter concluded: “If it is dangerous, or wrong, or both, and if it doesn’t need to be done, we just ought not to do it.” Then, as now, what is the right experiment to do should not be determined by scientists alone.

Criticism from social conservatives

More pushback along these lines has come from, among others, David Albert Jones, Director of the Anscombe Bioethics Centre at Oxford, who complains about a “shifting goalpost” and stresses that the 14-day rule had survived so long mostly because scientists had been unable to culture a human embryo for more than 13 days.

In effect, the rule has been like a speed limit that no car could physically achieve. It was a vacuous prohibition, forbidding the impossible and allowing experimentation on human embryos at every stage that this was physically possible

Jones is a Catholic and believes that any experiments on an embryo represent “a grave injustice and a form of exploitation.” So do other conservatives, including Ross Douthat in the New York Times and John Burger in Aleteia, who wrote:

We are not valuable because we have a nervous system; we are valuable because we are already the kind of being, a human being, that is capable of developing a nervous system if we have not yet not done so.

A deep analysis came from Brendan Foht, in an article in The New Atlantis titled:

Just Say No to Human–Monkey Chimeras

The piece is about much more than chimeras, and was written before publication of the revised ISSCR guidelines, which are noted in a brief addendum, but clearly anticipated them accurately. It includes a lacerating discussion of the 14-day rule focused on “why the scientific and ethical experts don’t deserve to be trusted with the responsibility of self-regulation.” We do not need to agree with every point in his (or some other) arguments about the use of human cells for research purposes to accept his conclusion on this. After a brief historical summary, he writes:

Let us not miss the gall of all this: For decades, the 14-day rule has been the way that human embryo researchers have publicly demonstrated they are placing ethical constraints on their research. In reality, the rule is arbitrary, is based on no meaningful ethical principle, has been acknowledged by ethicists as just a public-relations tool, and never placed any constraint on researchers at all. And now that it might constrain them, they’re discarding it.

That final sentence is both accurate and damning.

Criticism from the UK and Europe

The British science writer Philip Ball, who had also written about the ethical issues raised by chimeras, wrote a very substantial piece, published on June 7, in Prospect:

Replotting the human: the thorny ethics of growing babies outside the womb

Ball discusses the Warnock Committee, both Julian and Aldous Huxley, feminists such as Shulamith Firestone, and the developing state of the science, quoting Greely and Bartha Maria Knoppers. He notes that scientists lack the training and often the desire to take on the role of tracking a responsible and humane path forward, concluding:

And heaven forbid that these issues be allowed to become fresh fuel for the culture wars. If we can reconstitute the collective and pragmatic wisdom of the Warnock Committee, it won’t be a moment too soon.

Meanwhile, the Committee on Bioethics of the Council of Europe held its 18th plenary meeting on June 1–4 and took the opportunity to reconsider its position on the Oviedo Convention of 1997, which is “the only international legally binding instrument addressing human rights in the biomedical field.” Article 13 “prohibits any intervention with the aim of introducing a modification in the genome of any descendants.” The Committee issued “some clarifications but no revision of the Oviedo Convention.” It considered that:

[T]he conditions were not met for a modification of the provisions of Article 13. However, it agreed on the need to provide clarifications, in particular on the terms “preventive, diagnostic and therapeutic” and to avoid misinterpretation of the applicability of this provision to “research.”

Given that there have been explicit calls for the Council of Europe to drop Article 13’s prohibition of germline modification, the Committee’s statement is likely not just responding to the ISSCR. But it would be hard to phrase a more polite but equally pointed criticism of their revised guidelines.

More criticism

Finally, a real surprise, from Ronald M. Green, Michael D. West & Leonard Hayflick, in a letter to Nature:

Don’t abandon 14-day limit on embryo research, it makes sense

… There are 4 compelling reasons for the 14-day limit. Its clarity leaves little room for misinterpretation. It corresponds to important biological events, including the beginning of ectoderm/neural progenitors. In marking the end of the possibilities of twinning or chimaerism, it is the start of a unique biological identity. There is no later relevant nexus of events.

None of these authors could be described in any way as opposing research involving human embryos.

• Green has been described as a “libertarian bioethicist” who in 2008 wrote in the Washington Post: “Why not improve our genome?” His vision specifically included “increased life span, better cognitive functioning and maybe even cosmetic enhancements such as whiter, straighter teeth.” (CGS co-founder Richard Hayes published a rebuttal the next week.)
• West became notorious in the early 2000s for attempts at animal cloning and the clone-your-own-spare-parts theory of stem-cell research. He was the public face of Advanced Cell Technology (ACT), for which Green served pro bono as chair of the Ethics Advisory Board. West moved on to BioTime and now AgeX Therapeutics.
• Hayflick was an important pioneer in cell biology, who in 1961 conceived of what became called the Hayflick limit, which holds that human cells in a culture divide a finite number of times before reaching a maximum limit. Back in the 1990s, West invited him to join the Scientific and Clinical Advisory Board for Geron, another company that West founded.

In sum, the ISSCR guidelines are facing criticism from social progressives, from social conservatives, from bioethicists, from theologians, from scientists, and even from bioentrepreneurs.

Comments from the guidelines’ authors

Robin Lovell-Badge, who chaired the guidelines committee, clearly tried to preempt these objections, in a Nature article that accompanied the publication of the revised guidelines. He wrote of the need for “extensive public engagement, including consideration of social justice and whether experiments are an appropriate use of limited resources.” It is indeed the case that the guidelines explicitly include assertions such as (p. 42):

The decision to proceed with first-in-human clinical uses needs to be taken openly with robust consideration of informed public opinion generated through meaningful public engagement.

Note the qualifiers, and the complete failure to define “informed” or “meaningful” or to suggest any practical method of considering public opinion. Instead, on p. 13, “the ISSCR calls for national academies of science, academic societies, funders, and regulators to lead public conversations.” But the National Academies and Royal Society have already (on p. 2 of their report) shuffled off the responsibility for “societal considerations” to the World Health Organization, whose Report we await with interest. It is hard to avoid the conclusion that the references to public engagement are little more than a fig leaf behind which science can march on.

Similarly, Megan Munsie, a committee member, co-authored a piece with Melissa Little (also published on the same day as the guidelines were released) that was headlined:

New global guidelines for stem cell research aim to drive discussions, not lay down the law

On June 22, perhaps noting the public response, Susana Chuva de Sousa Lopes, coordinator of the Stem Cells Subcommittee of the European Society of Human Reproduction and Embryology (ESHRE), and her deputy Mina Popovic, attempted to “explain what lies behind the ISSCR proposals.”

In their newly updated guidelines, the International Society for Stem Cell Research (ISSCR) proposes that embryo research beyond 14 days should no longer be viewed as entirely off-limits. However, rather than offering a universal framework for extending the 14-day rule, or abolishing it, the Society proactively sets the stage for thorough public deliberation.

Great. Let’s deliberate publicly. Not spend a couple of years having private meetings, at the end of which you “explain” what you hope the public will believe.

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For more background, see also The Push to Change the 14-Day Rule (03.10.2021) and On the 14-Day Rule and Other Limits (06.29.2016).