For the first time, scientists have managed to grow human embryos to at least 14 days old inside a petri dish. Their work has the potential to revolutionize our understanding of what makes us human—and it's the next step on the road to completely artificial, womb-free reproduction. In fact, it's possible that these embryos might even have kept growing past two weeks, if the scientists did not have to terminate them for ethical reasons.
One of the most crucial, yet poorly understood, phases of life is the time from when a seven-day-old embryo burrows into the wall of a woman's uterus—a stage of development called implantation—and the moment, seven more days later, when the embryo becomes a self-organizing ball of cells destined to become a baby. This is when problems with pregnancy, or the first appearance of developmental disorders, can occur. But it's a black box that's very hard to study, as it's too early to see much on an ultrasound, for example.
Previous attempts have been made to understand the first days of life in lab animals like mice. Very limited data from monkeys show the biological processes underway during post-implantation are substantially different in primates like us. So why not study the genetics of human embryos directly?
""The embryo itself, in these very early post-implantation stages, is undergoing the critical cell-cell interactions that establish the body plan—and we do not have any easy way of studying those early stages," Janet Rossant, senior scientist of developmental and stem cell biology at Toronto's Hospital for Sick Children, told Motherboard. (She was not involved in this study.)
Using a technique originally developed in mice, and reported in Wednesday's Nature and Nature Cell Biology, researchers in the US and Europe grew viable human embryos, created via artificial insemination, in a completely artificial environment. They had to turn off the switch after 13 days because of a moratorium that limits this type of research.
"The key [to] the success of our research was our previous knowledge [of] mouse embryo development at the equivalent developmental stages," said study author Marta Shahbazi, a postdoctoral fellow at the University of Cambridge, in an e-mail to Motherboard.
"During the last five years, [we] developed a culture method that allows mouse embryos to develop beyond implantation in a dish," she continued. This special brew of nutrients, oxygen and growth factors, it turns out, can promote the development of human embryos as far as day 13, maybe even longer.
It's a big deal. Extended growth time gives researchers the ability to study physical and genetic changes in the developing embryo. It will underpin the design of new drugs to treat infertility, and help researchers understand more about developmental disabilities.
But the research can't go much farther, at least among scientists who abide by an international agreement stating that 14 days is the point when it must be terminated. That's when the embryo develops a structure called the "primitive streak"—a row of cells that go on to form all of the body tissues in the developing fetus. Only 17 countries subscribe to this self-imposed deadline. What could scientists in other nations do with this discovery, where ethical guidelines are more relaxed? What about private companies?
"We do not know the limit to the self-organising capabilities of human embryos," Shahbazi told Motherboard. "It is indeed very difficult to say whether human embryos would develop in vitro beyond the stages we have characterized."
The ethics have not crystallized as neatly as the ability to grow human embryos, apparently. "What this clearly shows is that we've got to a point where people believe they have the ability to step over that line," Françoise Baylis, holder of the Canada Research Chair in Bioethics and Philosophy at Dalhousie University in Halifax, told Motherboard.
"As is wont to happen when people think they're about to do something that will raise controversy, the strategy is to float the idea and see how long it'll take for people to become accustomed to it—and then move forwards."
It was a surprise for these researchers to see that a human embryo could direct its own development, even after it reached the point where it should have implanted into the uterus, without any input at all from the mother. This begs the question: would an artificial womb, if it had the right ingredients, be capable of bringing a developing human to term?
"[We] allow[ed] human embryos to develop on their own, without any interactions with maternal tissues," said Shahbazi. "Previous reports had tried to culture human embryos [on uterus] cells, with limited success. Based on our knowledge of mouse embryo development, we reasoned that human embryos could also have the ability to self-organise … to generate specific structures without the need for an external maternal input. By doing that we discovered the remarkable self-organising properties of human embryos."
One day, under the right conditions, this means we might be able to grow a human to the point when it can be "born" in a completely artificial environment. It also highlights the futility of the 14-day rule, in a new era where embryos can be grown past that artificial deadline.
"So, a crucial question for us today is, 'Do we have new and compelling ethical or scientific justification(s) to change the 14-day rule?'" wrote Baylis in a commentary that accompanied the Nature paper. She finds it "ironic" that, just when this agreed-upon limit might become relevant, the suggestion is being floated to change it.
The 14-day rule was agreed upon in Canada in 1995, when the idea of growing an embryo for that long was wishful thinking. Not so much anymore.
If materials science advances as fast as biology, the ability to develop advanced biomaterials to build an artificial womb may be just over the horizon. Researchers are working on the problem now. Once we reach that milestone, regulations like the 14-day rule will seem as quaint as a world without this reproductive technology.