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Human embryos created through in vitro fertilization are ethically sensitive research material.

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Stem cell guidelines open door to more permissive research on human embryos

The world’s largest stem cell society this week signaled a willingness to reconsider a long-standing restriction on laboratory efforts to grow and study human embryos. In new guidelines, the International Society for Stem Cell Research (ISSCR) also spotlights a possible alternative to using embryos that might be less ethically fraught: emerging methods to model stages of human development with stem cells. ISSCR’s influential guidelines previously put the culture of human embryos beyond 14 days postfertilization in its most restrictive category three: “prohibited research activities.” The new guidelines, drafted by a task force of scientists and ethicists, omit longer embryo culture from this category and encourage a public discussion about allowing it.

The guidelines aren’t legally enforceable. Laws limiting embryo research to either 14 days or formation of a structure called the primitive streak exist in several countries, including the United Kingdom, Sweden, and South Korea. But ISSCR “has an important soft power,” says Annelien Bredenoord, a bioethicist at the University Medical Center Utrecht who is a member of ISSCR’s ethics committee but not part of the guideline task force. “It can be the one that fuels the discussion.”

Until recently the 14-day rule had little practical effect because embryos didn’t survive that long in the lab. But recent advances have allowed some researchers to run experiments up to that limit.

Observing embryonic development after 14 days could help scientists better understand the origins of miscarriages and birth defects, and many scientists and bioethicists have advocated softening the restriction. In a commentary in Science, researchers and ethicists including Bredenoord urged policymakers and ISSCR to “consider a cautious, stepwise approach to scientific exploration beyond the 14-day limit.”

The new guidelines don’t explicitly move extended embryo culture into ISSCR’s less restrictive category two, which describes research permissible after scientific and ethical review. “The ISSCR has not abandoned the 14-day rule,” says Amander Clark, a stem cell biologist at the University of California, Los Angeles, and a member of the guideline task force. But the guidelines call for “national academies of science, academic societies, funders, and regulators to lead public conversations” about the “societal and ethical issues raised by allowing such research.”

Those groups will have to decide whether changing current restrictions is “really worth the political capital and the legal battles,” says cell biologist Martin Pera of the Jackson Laboratory. The 14-day limit “has given the public a good deal of reassurance around the boundaries of human embryo research,” he says, “but probably merits a careful reexamination.”

Pera notes that human embryos begin to degenerate as they approach the 14-day limit. Even as scientists get better at keeping embryos alive past 14 days, only a minority will survive in a dish, he says, and the number that remain healthy will diminish as development proceeds.

To study developmental processes beyond 14 days, Pera is more optimistic about embryo models created from human stem cells, which in recent years have become increasingly complex and powerful. These lab-grown structures can be made in unlimited quantities, he notes, and enable researchers to study the role of particular mutations in development and disease. In a commentary this week in Stem Cell Reports, members of the guideline task force and other scientists say the need to validate stem cell–based embryo models by comparing them with natural embryos is one reason to remove the 14-day limit.

Some of these stem cell–based models carry ethical sensitivities of their own. ISSCR’s updated guidelines propose a distinction between nonintegrated models—which re-create only certain features of an embryo and lack supportive “extraembryonic” cells crucial to survival in a uterus—and more complete integrated models.

The new guidelines say research on nonintegrated models can proceed without special review. But such review is necessary for integrated models such as recently reported “blastoids,” which closely resemble the human blastocyst—a stage about 5 days after fertilization when an embryo implants in the wall of the uterus. Such models could eventually reveal why many pregnancies fail at this stage and could help researchers refine in vitro fertilization techniques.

But integrated models should be “maintained in culture for the minimum time necessary to achieve the scientific objective,” ISSCR says, and no embryo model should be transferred into a uterus to develop further.