For two tense weeks in mid-2013, developmental biologist Magdalena Zernicka-Goetz was chasing a world record. She and her colleagues at the University of Cambridge, UK, were attempting to grow human embryos in the lab for longer than had ever been done before. They wanted to glean insights into how a tiny blob of cells transforms itself into a complex, multipart structure. Previous efforts had stalled after about a week, but Zernicka-Goetz knew there was much more to learn about human development beyond that point.
The researchers started with embryos that had been donated by women who no longer needed them for in vitro fertilization (IVF) procedures. The team bathed the cells in a special medium and housed them in an incubator, using methods adapted from their previous work on mouse embryos. Because the samples had to stay in a strictly controlled environment, the scientists could remove them only once or twice a day to track their progress under a microscope.
The days ticked by — six, seven, eight. And still, the embryos continued to thrive and develop1. “We would hold our breath,” recalls Zernicka-Goetz. “Each day was more and more exciting.” The team reached 12 days on its first attempt, eventually stretching to 13. “This was just unbelievable. I was so delighted,” she says.
Their advance, and a similar feat by a group based in New York City is one of a few achievements in the past five years to heat up the study of early human development. Researchers’ access to the human embryo has always been limited, and they knew relatively little about its early transformations. But now, refinements in cell-culturing methods are enabling them to grow human embryos outside of the body for up to two weeks. Scientists are using gene-editing techniques, such as CRISPR, and building artificial embryo-like structures to explore the cellular signals and physical forces that shape the embryo and its supporting cast of tissues.
These techniques are illuminating key early processes, such as implantation — when the minuscule embryo embeds itself into the uterine wall and can’t be studied directly. And new high-resolution, digital images are revealing in fine detail how muscles and nerves grow a few weeks later in development. Such discoveries could lead to a better understanding of how birth defects and developmental disorders arise, as well as why some pregnancies fail.
But alongside their promise, these new techniques are pushing researchers into uncharted ethical territory. Beginning in the late 1970s, ethicists and scientists converged on the ‘14-day rule’, which limits work on human embryos to a fortnight after fertilization — a time when the first hints of the nervous system appear, and the last point at which an embryo can divide. Until now, the internationally recognized 14-day rule has been a purely hypothetical limit. “It wasn’t a rule that anybody was butting up against,” says bioethicist Josephine Johnston at the Hastings Center in Garrison, New York. “It’s now technically possible.”