14-day rule under review, raising ethical questions

For more than 30 years, scientists have followed a rule they imposed on themselves to avoid growing a human embryo in a lab dish for more than 14 days.

Until recently, the “14-day rule” was largely academic. Scientists couldn’t grow them for that long if they wanted to.

But in 2016, two teams of researchers reached 12 days, and in 2019, another group grew monkey embryos for 19 days.

These advances have spurred some scientists to argue in two recent papers that the 14-day rule should be modified or dropped. There’s a lot to be learned by pushing embryos out to 28 days, they say.

The regulatory committee of the International Society for Stem Cell Research, which lays down guidelines for the scientific field, has been debating the issue for months and is expected to issue its final decision this month.

Some ethicists and scientists are concerned that revising the rule just as it becomes technologically feasible to break it is ridiculous and morally repugnant. 

March 5 opinion piece arguing for a careful, stepwise extension of the 14-day rule. 

“You have to really make your case for it,” Hyun said. “You have to explain what you want to do and why, have a very clear picture of where the next stopping point is.”

Women generally don’t know they’re pregnant before 28 days, so historically, there has not been tissue from aborted or miscarried fetuses available for research.

In this Aug. 14, 2013 file photo, an in vitro fertilization embryologist works on a petri dish at a fertility clinic in London. In vitro fertilization involves surgically removing eggs from a woman’s ovaries, combining them with sperm in a laboratory, and transferring the days-old embryo to the woman’s uterus.

The central nervous system, heart and other organs begin to develop during this crucial two-week period. The body plan is established. Cells that will become eggs and sperm start to form. Aspects of the placenta are set up.

In many ways, days 14 through 28 are the most interesting period of human development, Lovell-Badge said. “You can do a whole lot of incredibly valuable research,” in that timeframe, he said.

And it’s in that window that many things can go wrong in a pregnancy, such as miscarriage or abnormalities. 

Perhaps there are treatments that could be developed to fix these problems, if they are better understood, Hyun said, just as pregnant women now take vitamin supplements to prevent spina bifida, in which the spine doesn’t develop properly. 

Developing embryos for another week “will thus illuminate this poorly understood period of our development and bring greater understanding of pregnancy loss and developmental disease,” said Magdalena Zernicka-Goetz, the British scientist who developed the technique for growing human embryos for nearly two weeks. Zernicka-Goetz, author of a 2020 book on human development called “The Dance of Life,” would like to extend the 14-day rule out one week to 21 days.

“This will enable the scientists to study a period of development that are highly susceptible to developmental failure, something that happens quite frequently in human pregnancy,” she wrote in an email, stressing work should be closely regulated “to achieve these potential biomedical advances within an appropriate bi-ethical framework.”

Despite their differences, most scientists seem to agree there’s no reason to push development past 28 days.

By one month after conception, embryonic tissue is easier to obtain and study and the organs have formed, leaving fewer questions to answer. 

“You wouldn’t need to take them much beyond that point anyway,” Lovell-Badge said.

The moral counterargument

Pacholczyk, of the Catholic Bioethics Center, said there’s simply no justification for 14 days or any other time limit.  

“Researchers have been feigning for a long time that the 14-day rule was somehow an ethical tenet grounded in biological facts – while in reality it has been little more than a ceremonial ‘line in the sand’ – and it should come as little surprise that they are now seeking to move that line beyond 14 days,” he wrote in an email. 

Even some who strongly support scientific research are uncomfortable extending the 14-day rule.

Henry Greely, who directs the Stanford Center for Law and the Biosciences at Stanford University in California, said there should be a hard-stop endpoint for embryo research.

“Even though I do not personally give strong moral status to embryos, the idea of doing research on 18-day-old human embryos is disturbing,” said Greely, author of the new book “CRISPR People: The Science and Ethics of Editing Humans.”

This sequence of images shows the development of embryos after correcting for a genetic error that would otherwise cause a type of inherited heart disease.

This sequence of images shows the development of embryos after correcting for a genetic error that would otherwise cause a type of inherited heart disease.
OHSU

“I’d like to see an endpoint that had some rationale that would make it likely to stick,” he said.

Growing an embryo in a lab dish instead of a woman’s womb is necessarily different, Greely said, and may not represent a “real” embryo anyway. 

“Does a 14-day embryo that is not implanted deep in a woman’s uterus tell us anything meaningful about a 14-day embryo that is?” he asked.