Scientists call for renewed talks on human embryo research limits

The science

Context: Embryo research is affected by an international agreement that limits embryo research to 14 days, which is when the embryo starts developing the primitive streak and its neural system.

• Of note: The U.S. has adopted the international agreement as guidelines rather than as policy, as many other countries have done. However, alongside this agreement, various U.S. states have even stricter policies, with some like North Dakota banning all research.
• Several speakers at the event said the 14-day limit was not really based on scientific thought but instead chosen in 1979 when In Vitro Fertilization (IVF) first started and people became worried about test tube babies. "None of it is actually scientific, I would argue," Rockefeller University's Ali Brivanlou said.
• To be sure: At the time, the limit didn't matter since scientists didn't have the technological know-how to be able to develop embryo cells for that length of time.
• However: Technology has advanced, and a couple years ago, Brivanlou's lab was able to develop embryos that successfully developed up to the 14-day mark and had to be frozen, a move he calls "one of the hardest things I've ever done."

What's happening now: Instead of human embryos, many researchers are using animal models such as mice, according to Kirstin R.W. Matthews, Baker Institute fellow in science and technology policy. The problem is while human and mice blastocysts look similar at 5 or 6 days, they look very different by day 14, she said.

• Rice University's Daniel Wagner, who spoke at the event, also noted they've been able to pinpoint how some birth defects may originate in animal models, but "we can't really validate these detailed findings in humans."

Newest finding: Brivanlou's lab announced Wednesday in Nature they were able to confirm that humans have an "organizer structure" — a node they believe signals to newly-forming cells to differentiate into a skin cell or muscle cell, etc. Because organizers appear around the 14-day mark, they had not been confirmed in humans.

• What they did: The team developed artificial human embryonic stem cells (hESCs), exposed them to two proteins to spur growth, and grafted them onto a chicken egg, creating what's called a chimera. There, the hESCs seemed to started directing nearby cells into what type of cells were needed, acting as the organizer.
• The big question: During the first couple of days, the cells multiply quickly from 4 to 8 to 32 cells — "at what point does each of those cells know what they're going to be?" Brivanlou asks. "This is done through communication between cells." He says this applies to diseases as well, many of which start early. "Perhaps we could attack them as early as they start," Brivanlou said.

"It's pretty amazing. I spent a big chunk of my life on seeing how you make a tadpole from fertilized frog eggs," Brivanlou told Axios. "Now we're cracking the code of what it takes for making a human."

The ethics

There is a major disagreement about at what stage the human embryo can be considered a human being and where to draw the line with experimenting with chimeras.

• These views range from the moment the egg is fertilized to the moment the fetus is viable outside the womb, according to Ana Iltis, director of Wake Forest University's Center for Bioethics, Health and Society, who spoke at the event.
• Chimeras also tend to generate controversy. "For example, how many [human] cells do you put into it, and it is still a mouse?" Brivanlou said.

The discussion: The question remains on if the 14-day guidelines were to be altered, where the best point is to encourage research but respect the developing life form as well. Wagner pointed out that there are a multitude of avenues like institutional review boards that can host such discussions.

• Brivanlou said 28 days may be a good mark, since it is after organs start to develop but before many are connected.
• "If we were able to do more research, towards day 30 or so, we'd have a richer body of knowledge to go on," Matthews told Axios, adding that this topic presents difficult questions that need a national discussion, since a longer research period would need to be balanced by respect and care for the life created in the dish.

"There are good arguments for relaxing this time limit in order to study events such as [formulation of neural system] which are critical for development.  Moreover, this is a developmental stage at which many spontaneous abortions occur — we desperately need to find out more about this stage."

Go deeper: Watch the Baker Institute seminar here. Read these Axios stories on new advances in stem cell research, growing replacement human organs in sheep, and what's happening with fertility treatments. And, check out this piece in The Scientist on the first week of the embryo.