Growing embryos could lead to "ethical firestorm"
Researchers at the Rockefeller University in New York and the University of Cambridge, England, have managed for the first time to develop two-week-old human embryos, sparking a fierce ethical debate. The traditional cut-off point for using human foetuses has been 14 days, after which the first distinctions of a foetus appear. Until recently, no one had developed an embryo beyond nine days. Jonathan Moreno, a bioethicist at the University of Pennsylvania said he was not troubled by the 14-day rule, but said questions needed to be asked as to whether it was “permissible to move those goalposts”.

At what point should a scientist stop doing experiments on a human embryo in a Petri dish?

For decades, the answer has been clear: 14 days after fertilization. The cutoff is protected by law in 12 countries, including Canada and the United Kingdom, and by scientific guideline in five others, including the United States.

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But the discussion has been a moot point because no lab had ever succeeded at growing human embryos past nine days.

On Wednesday, though, two different research teams reported a scientific first: watching embryos develop in the lab all the way to the two-week mark.

Both groups — one from the Rockefeller University in New York, the other from the University of Cambridge in England — saw how these balls of cells become riddled with holes and tunnels so that they can attach themselves to the nourishing vasculature of the mother’s uterus.

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They saw populations of cells that have never before been identified, which appear after the embryo implants itself but disappear long before birth. And they tracked the minute chemical changes from one day to the next.

But alongside the new science comes a fierce ethical debate about whether the advance warrants reconsidering the “14-day rule.”

The dispute isn’t just about the stage of development at which research on a human embryo becomes unethical. It’s also about how involved the public should be in deciding what happens in research labs — an explosive question in an era when CRISPR gene-editing has sparked fears about “designer babies.”

“I don’t see anything sacred in the 14 days,” said Jonathan Moreno, a bioethicist at the University of Pennsylvania and a senior fellow at the Center for American Progress. “What’s really more important than whether it’s permissible to move those goalposts is how we make that decision.”

The 14-day rule was first proposed in 1979 by the precursor to the Department of Health and Human Services. Two weeks after fertilization, a small streak of cells faintly appears, the first distinction between the embryo’s front and back ends. Because it’s also the moment when the embryo can no longer split into identical twins, it was chosen as the point where embryo research had to stop.

The rule was a compromise, explained Josephine Johnston, a bioethicist at the Hastings Center, who coauthored a commentary in Nature alongside one of the new papers. (The other was published in a sister journal called Nature Cell Biology.) “This was a policy tool that was designed to allow research to happen but to place limitations on it,” she told STAT.

This debate bears a parallel to that over when abortion is permissible. In 1973, the US Supreme Court decided in Roe v. Wade that abortion was allowed until the fetus could possibly be born and survive, and in 1992 defined that point as 23 or 24 weeks. Meanwhile, recent medical advances have made it possible for babies born even more prematurely to survive, which has prompted debate in many state legislatures about moving up the time stamp at which abortions should be banned.

Yet to Johnston, abortion and Petri dish embryology research are fundamentally different issues: “We might prohibit research at a point even when a woman should still have the right to choose,” she said.

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To the scientists who made the advance, extending the 14-day embryo research rule could benefit patients. Already, by observing what happens at the developmental stage when the embryo attaches itself to the wall of the uterus, researchers can begin to try to help women who keep losing pregnancies.

“Fifty percent of the embryos that are fertilized do not attach. That’s a tremendous waste for couples who are trying to have kids and are not successful,” said Ali Brivanlou, an embryologist at Rockefeller University who led one of the teams. “For the first time, we can try to dissect the cellular and molecular bases when things do not work out for attachment during pregnancies.”

And, he said, understanding how the embryo uses stem cells to create organs could allow for unprecedented new treatments for birth defects.

Labs in Sweden, China, and the United Kingdom have begun using CRISPR to edit the genomes of human embryos in the lab. Some are hoping to better understand the genes involved in early development, which could lead to improved fertility treatments, while others have been trying to engineer resistance to certain diseases. These experiments have stopped before two weeks, but longer studies could yield a deeper understanding — and potentially new therapies.

Many ethicists aren’t convinced, though. To Stanford Law School’s Hank Greely, extending the 14-day rule is a slippery slope: “I don’t know where you stop.”

“I do know that I would feel very concerned about a 20-week fetus being used as an experimental object, because it’s too damn close to being a baby,” he said. “And people should not be treated as objects.”

For some, like Kevin Fitzgerald, who is both a Jesuit priest and a geneticist at Georgetown University, the 14-day rule already isn’t restrictive enough — and was established without true public consultation. He would be happy for the discussion to be reopened, as long as the lay community’s values are taken into account.

“Is the goal to make the public comfortable with this?” he asked. “Or is the goal to actually find out what an engaged, empowered public actually wants?”

“Maybe the 14-day rule should be changed. But who gets to make the rules and who gets to decide when it’s time to remake them?” said Marcy Darnovsky, executive director of the Center for Genetics and Society, a nonprofit in Berkeley, Calif.

She said that the decision needs to be more inclusive of disability rights groups and racial justice organizations, and that it can’t just be “a few advisory bodies that are representative of no one and that set themselves up, that consist of scientists and professional bioethicists who are making these decisions in closed door meetings and issuing recommendations.”

Governments and scientific advisory boards may well decide to reopen discussions about the 14-day rule. But in the meantime, there is still plenty of research that can be done within the current limits. As Magdalena Zernicka-Goetz, a physiologist at the University of Cambridge who led one of the studies, told STAT, she has no intention of pursuing research beyond 12 or 13 days. She already has her work cut out for her.

“It’s incredible,” she said. “For the very first time, you can look at our own development in the lab, at that very mysterious stage at which the embryo develops the first contact with the mother.”