杏吧原创

WHEN it comes to studying our earliest existence, how far are we willing to go? Growing human embryos in the lab beyond the seventh day after fertilisation 鈥� the moment when embryos normally implant in the wall of the uterus 鈥� has been a long-standing challenge for biologists, but the latest research is allowing us to extend past that.

Earlier this year, a team led by , New York, and another group at the University of Cambridge managed to keep embryos alive for longer than seven days, but they stopped the experiments two weeks in.

It鈥檚 not that the embryos perished. Guidelines set by national medical societies in the US prohibit growing embryos in the lab for more than 14 days. In the UK and 11 other countries, that limit is enshrined in legislation, and embryos must be destroyed before they develop further.

Until now, this restriction wasn鈥檛 an issue, but as science has caught up with the law, many researchers are eager to revisit the rule. Clearly, experimenting on well-developed embryos (or fetuses, past the 12th week from conception) would be ethically unacceptable to almost everyone, but that doesn鈥檛 mean we shouldn鈥檛 go beyond the first two weeks. The question is, how far, and to what end?

, who led the Cambridge group, wants to open the 鈥渂lack box鈥� surrounding this period of our lives. 鈥淚t鈥檚 one of the most critical phases of our early development and we don鈥檛 know anything about it,鈥� she says. By extending the limit we could learn why many pregnancies are lost in the early stages, for example, and improve the current one-in-three success rate of IVF.

At present, our understanding is limited by growing embryos in the lab only up to day 14. Brivanlou鈥檚 and Zernicka-Goetz鈥檚 embryos are not organised exactly like human embryos that attach to the uterus, in part because they grow in a flat environment. 鈥淭he next stage is to be able to grow these embryos in a more three-dimensional structure,鈥� says Janet Rossant, a developmental biologist at the Hospital for Sick Children in Toronto, Canada.

鈥淚t鈥檚 one of the most critical phases of our early development and we don鈥檛 know anything about it鈥�

Brivanlou argues that many genetic and neurodegenerative diseases start early in embryonic development. Observing how organs grow naturally might let us cure these diseases, or make new organs from scratch, he says.

So there is much to be gained from revising the 14-day limit, given its origins are more pragmatic than scientific. Little was known about the timing of human development when the rule was first proposed in 1979, though studies of other animals hinted at its importance (see 鈥淏aby steps鈥�).

After two weeks, a feature called the primitive streak appears in the embryo, the first indication of bilateral symmetry. And before this point, two embryos can fuse into one, or one embryo can split to form identical twins. Because of this, policymakers argued that an embryo cannot be considered an individual person before 14 days.

But this limit was not supposed to be philosophical. The Warnock Committee, which advised the UK government on human embryology in 1984, noted that 鈥渂iologically there is no one single identifiable stage in the development of the embryo beyond which the in vitro embryo should not be kept alive鈥�.

Nevertheless, the committee felt a time limit was appropriate, 鈥渋n order to allay public anxiety鈥�. By drawing the line at 14 days, policymakers in the UK and US hoped to permit research while showing respect for those with strong views about when life begins.

, chair of the UK鈥檚 Nuffield Council on Bioethics, says although the limit was passed into British law in 1990, it鈥檚 still fair to question it. 鈥淲e shouldn鈥檛 think that somehow 14 days was a line at which Parliament had previously decided the embryo was sacrosanct,鈥� he says. If scientists make a strong enough case for revisiting it, Parliament could consider changing the law.

Beyond the limit

Discussion among researchers is well under way. Earlier this month, Harvard Law School hosted a , and another the rule in London in December.

One of the speakers at the Harvard meeting, , a bioethicist at Case Western Reserve University in Cleveland, Ohio, says there may be no need to extend the limit just yet. 鈥淭hey鈥檙e just starting getting up to this time point,鈥� he says. 鈥淭here鈥檚 still so much more to learn about day 13, for example.鈥�

More urgently, grey areas need to be clarified on the fringes of the rule. Brivanlou鈥檚 group has shown that human embryonic stem cells can grow into structures that resemble post-implantation embryos. These could be a useful model for studying early development, but no one is sure if the rule applies to them.

It might be too soon to shift the 14-day line, but it鈥檚 worth beginning the conversation, says Rossant. 鈥淭here are lots of inputs that need to be considered, ethical, legal, societal, as well as the scientific.鈥�

For those who believe life begins at conception, any research on embryos is unacceptable. 鈥淚 think the basic question still comes down to what sort of moral worth do we want to give to various human beings,鈥� says , a geneticist at Georgetown University, Washington DC, who is also a Jesuit priest.

, a bioethicist at George Washington University in Washington DC, thinks the current rule is overly accommodating of those holding strong beliefs on when life begins. By comparison, abortion law is much less accommodating of conservative views, he says.

鈥淭his is not a decision for scientists, it鈥檚 a decision we must make as humans鈥�

If not 14 days, where else could we draw the line? From a philosophical point of view, the crucial matter for moral status is sentience, and the capacity to have feelings, says DeGrazia. That comes much later, perhaps early in the third trimester 鈥� far beyond the stage we can imagine embryos reaching in the lab, and what many people would be comfortable with.

So a more realistic suggestion is a smaller change, such as a three-week limit. After that, the precursors of vital organs become identifiable, including beating heart cells and the beginnings of the central nervous system.

Setting the limit at this stage would allow the current trajectory of research to continue, without ruffling too many feathers. 鈥淚f you can do all the science you want without alienating people with moral concerns so that they鈥檙e firebombing clinics, it鈥檚 good politics, and it鈥檚 respectful,鈥� says DeGrazia.

Hyun argues that we shouldn鈥檛 swap the 14-day rule for another arbitrary line in the sand, given we might wish to cross it in future. 鈥淩ather than one rule for all research across the board, it needs to be more nuanced,鈥� he says. 鈥淲e have to look at real specifics about what the research is trying to do and if there鈥檚 no other way to answer that question.鈥�

The political reality is that there must be a cut-off point to reassure the public that the research is being tightly regulated. 鈥淚 strongly think it鈥檚 important to have boundaries beyond which we cannot go,鈥� says Zernicka-Goetz.

She and Brivanlou hope the limit will be extended by one or two weeks, but both are adamant that people of all backgrounds and cultures should have their views heard. 鈥淭his is not a decision for scientists,鈥� says Brivanlou. 鈥淚t鈥檚 a decision we must make as humans.鈥�

This article appeared in print under the headline 鈥淭he limits to growth鈥�