Things We Are (Nearly, Perhaps) Able to Do with Human Embryos

At least five separate studies involving human embryo research are raising fresh versions of old questions about science, ethics and regulation. On March 17, Nature published two peer-reviewed papers about generating in vitro, with slightly different methods, “blastoids” or “human blastocyst-like structures.” (One team, perhaps trying to be cute, called them “iBlastoids” but the Nature summary article sensibly eschews this.) One process involved developing from human embryonic stem cells, the other used cells reprogrammed from adult tissues. A few days earlier, two preprints were posted that also described generating blastoids (1, 2), though they have not yet undergone peer review. Notably, none of these groups of scientists grew their blastoids beyond the equivalent of 14 days of human development. All of them, however, clearly have that in their sights.

Also on March 17, Nature published “an unedited manuscript that has been accepted for publication” describing a mouse embryo grown in an artificial womb, “Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis.” Lead author Jacob Hanna told Antonio Regalado of Technology Review that they “collected 5-day-old embryos from pregnant mice and moved them into the incubator system, where they lived another week,” taking them about halfway through mouse gestation. (Nature publishing an unedited manuscript is not unknown but did the editors actively want this limited result to be coupled with the blastoid papers?) Hanna hopes to develop the procedure so the entire process is in vitro.

He also wants to grow human embryos in vitro and to do so well beyond 14 days:

We need to see human embryos gastrulate and form organs and start perturbing it. The benefit of growing human embryos to week three, week four, week five is invaluable. I think those experiments should at least be considered. If we can get to an advanced human embryo, we can learn so much.

Suddenly it is clear why there has recently been a push to change the 14-day rule. We still await the formal update to the research guidelines of the International Society for Stem Cell Research (ISSCR), which describes itself as “The Voice of the Stem Cell Research Community.” The guidelines currently include the 14-day rule, but bioethicist Alta Charo, who is on the ISSCR steering committee, seems to be confirming the widespread rumors that the rule will be dropped or changed. She told Regalado:

Before, you didn’t have to measure a loss in knowledge against other concerns, because we didn’t know how to culture things that long. That is what has changed. It’s easy to say no when it can’t be done.

And Hanna, who is based at the Weizmann Institute of Science, in Rehovot, Israel, says he has no need to consult ethicists or religious figures, because “the ISSCR is my rabbi.”

This smacks of choosing the authority that will give you the decision you want. Research scientists want to do research and are inherently conflicted in these decisions. That includes those who run the ISSCR. They should certainly be involved in decision-making, and they should certainly not be the only people involved. As Daniel Sarewitz wrote in 2015, “risk is more a political and cultural phenomenon than it is a technical one.” Government regulation is clearly appropriate, and Israel does regulate human embryo research, though it does not specify a particular limit.

Several jurisdictions, including the UK, Canada, South Korea, and Sweden, have enshrined the 14-day limit into law; Australia has already decided that blastoid development beyond 14 days is banned by existing law, though it “may need to be rewritten to fully address them.” Some countries ban human embryo research completely; others, including the US, largely rely upon the scientists’ professional associations. What gives them the authority?

The New York Times report on this work concludes:

Of course, even the suggestion of this science fiction scenario is bound to horrify many. But it is early days, with no assurance human fetuses could ever develop entirely outside the womb.

Even assuming they could, Dr. Tesar [a developmental biologist at Case Western] noted, “whether that is appropriate is a question for ethicists, regulators and society.”

Are you reassured?

Where these technologies may lead remains unclear; there is even speculation about growing organs for transplants. Some people are certainly excited by the prospects, sometimes with a nod to “adequate ethical and societal reflection.” Others are more wary: Fyodor Urnov, a long-standing expert on gene editing tweeted that “this freaks me out as an editor.” Stanford University bioethicist and law professor Hank Greely questions how valuable the information gleaned about human embryonic development would be because of his skepticism “about how well ex vivo embryos, weeks past the time they normally must implant or die, will model implanted embryos.”

Greely points out that a naturally implanted embryo has tight communication via a placenta with … a woman! All too often, it seems that women’s roles are undervalued if not entirely ignored in these discussions. Pregnancy is something more than a growth medium and the developing physical relationship between the embryo and the woman gestating it is vital. It’s hard to imagine that an artificial environment might adequately replace that.

Stuart Newman, New York Medical College developmental biologist and author, whom I asked for comment, took a broad view of the issues ahead:

The one comment I have come up with that brings all the developments together is: “Humanity will become something else — an industrial or consumer product — if we start manufacturing people with tenuous, uncertain connections to other members of society.”

Newman and Tina Stevens wrote about closely related issues in their book Biotech Juggernaut: Hope, Hype, and Hidden Agendas of Entrepreneurial BioScience.

Bioethicist Ben Hurlbut emailed a similar response:

For starters, and for a kind of general thought, the ex vivo mouse culture experiment and the blastoid experiments are each contributions to a growing repertoire of tools and techniques that allow manipulations of life that will sooner or later stray into zones where they should not go. …  Developing deepened consideration of what is at stake in such research, particularly when mouse is replaced by human, is going to take a lot more than the ISSCR’s ethics and policy committees rewriting its own rules behind closed doors.

Hurlbut was recently interviewed by Christopher Lydon for Open Source, which bills itself as “the world’s longest-running podcast.” That interview followed one with Walter Isaacson, who seems to worship at the altar of biotech and has canonized the redoubtable Jennifer Doudna in his recently published biography of her. Hurlbut seemed to be talking on an entirely different plane than Isaacson, reckoning that this developing technology is “a solution in search of a problem.” He referenced Hannah Arendt, noting that the question “How would we do it?” distracts from the more important question, “Why would we do it? In the name of what?” Indeed, Arendt suggested that in the modern scientific world:

It could be that we ... will forever be unable to understand, that is, to think and speak about the things which nevertheless we are able to do.