Even before we could experiment on human embryos, we’ve gone back and forth about where we should draw the line: When does an embryo stop being a bunch of cells and start to become a person? If you were Dante Alighieri, writing in the 14th century, you would have drawn the line at the point of “ensoulment.” If you’re a scientist working in the 21st century, you might end experiments at a point called “individuation.” If you are a bioethicist trying to write policy, you might do so after 14 days — at least until Tuesday, when bioethicists in Europe argued in EMBO Molecular Medicine that it’s time to rethink the timeline of personhood.

Squabbling over dates might seem unnecessarily semantic when dealing with a concept this ethereal, but deciding on where to draw this line is crucial to navigating the ethics of embryonic research. The “14-day rule”, made official in 1985, functions as a drop-dead zone for embryonic research because after 14 days, things start to change in the embryo. Cells no longer simply copy and paste themselves and start to differentiate into three layers known as “the primitive streak,” explains the Jackson Laboratory’s Martin Pera, Ph.D., who was not involved in the new policy recommendation but has written about the implications of the 14-day rule.

“It is what embryologists call ‘individuation’, that’s the point at which there is a unique individual there,” he tells Inverse. “I mean again, that’s a sort of ethereal concept, but that was one of the concepts that was put forward.”

louise brown
After the birth of the first "test tube baby" Louise Brown, the 14-day rule was established to put some limits on how we can manipulate human embryos 

In the new opinion article, John Appleby, Ph.D., of the University of Lancaster and his co-author Annelien Bredenoord, Ph.D., of University Medical Center Utrecht argue that the time has come to extend the 14-day rule to 28 days and probe a bit further into what some researchers call the “black box” of human development. There are two reasons we need to do this. Firstly, we legislated the 14-day rule decades ago, so there are considerable roadblocks to conducting this research in the first place. Secondly, until recently, it was challenging to even keep embryos viable enough to study for that long. Now that the latter is addressed, they argue, it’s time we opened that black box.

“There are both scientific and ethical reasons to extent the 14 day rule to for example 28 days,” Appleby said. “Extending the window for embryo research to 28 days would allow scientists to reveal a new in-depth chapter of knowledge about the developmental processes that take place in embryos.”

They argue that now is a good time to probe deeper into the black box because we now have the tools to truly manipulate human biology. Techniques that allow us to “cut and paste” DNA, like CRISPR, are making it possible for parents to pick and choose genes that could eliminate genetic diseases in their children. But to do so, the authors write, we need to know more about how those genes fare during early development — that is, after the 14-day mark.

embryonic cells
An embryo with only eight cells, before the cells start to differentiate. 

Others argue that pushing for the 14 day rule might be more trouble than it’s worth, especially because it’s enshrined in law in the nations that lead genetic research, like the UK and the United States. For his part, Pera thinks that we should push for more understanding of this period in embryonic development but to also consider that we might not need embryos to study them at all. Recent developments in stem-cell research have allowed scientists to create “synthetic” embryos — collections of cells that mimic early stages of human development but can’t, at least right now, become a person.

“Yes this whole area needs consideration and debate,” Pera says of the potential move to a 28-day rule. “But to me, it’s not even clear that we can support embryonic development up to that period. What is clear is that these synthetic embryos provide a very powerful alternative.”

Pera makes it clear that because synthetic embryos aren’t made from sperm and eggs, the 14-day rule doesn’t apply to them at all. Appleby and Bredenoord acknowledge them in their opinion piece, noting that while synthetic embryos are important research tools, extending the 14-day rule would allow us to develop them technology further and determine whether they really are useful alternatives to “real” human embryos.

No matter how much more we understand the biology of a human embryo, we’re still going around in the same circles Dante did centuries ago. Whether you call it individuation or ensoulment, the debate over the origin of personhood always comes down to the question of how best to maintain human dignity. That conversation, Appleby explains to Inverse is changing.

“For the most part, attitudes towards embryo-related research remain cautious. However, now that embryos can be kept alive in vitro for longer than ever before, there is a growing discussion about the scientific, regulatory and ethical implications of not conducting research on embryos beyond 14 days,” he says.

Maybe now is the time to open the black box.