“With great power comes great responsibility”
So runs the quote popularly attributed to Uncle Ben in the Spiderman comics. It also seems quite appropriate however, to mention it at a time when advances in our ability to alter the human genome and work with human embryos outside the body seem to be moving at warp speed.
Genetic techniques like CRISPR-Cas9 have made it easier than ever to edit the human genome, and a global conversation among regulators, scientists, ethicists and public representatives has already been set in motion to determine the appropriate way to use this ever growing suite of powerful genetic tools that we have at our disposal. Key milestones in the process have included scientific breakthroughs such as advances in CRISPR-Cas9 research, the first reports of gene editing carried out in human embryos and a major meeting convened by the US National Academy of Sciences last December to discuss the issue in detail.
Researchers showed, for the first time that they could culture human embryos in the laboratory for up to 13 days, a feat that had seemed impossible until now. In fact, it basically blew through the previous record set by researchers and crossed an important time point—the seventh day, which is when the embryo attaches itself to the uterus in a process called implantation.
Failure to implant properly can result in a variety of complications in pregnancy, including miscarriages. This research presents scientists with a model that mimics early human embryo development in the human uterus. The teams, led by Magdelena Zernicka-Goetz, at the University of Cambridge and Ali Brinvalou at Rockefeller University suggested that their research could provide important insights into why problems like miscarriages occur.
Importantly, in both cases, the experiments were stopped at 13 days, in accordance with international limits that precluded scientists from culturing human embryos in the lab beyond 14 days. The limit was endorsed by the UK and US in the early 90s when the technology to culture embryos was extremely limited and have been written into laws in several countries.
An accompanying opinion article in Nature written by ethicists and policy scholars provides background on why and how the rule was established, and argued that advances such as the current reports would inevitably lead to major ethical questions about the 14-day rule. It would be prudent, they said to begin a conversation that would ‘revisit’ the rule, eventually balancing the opinions of those who are concerned about such research and those who see greater benefits than risks.
Researchers who were not involved in the work were almost unanimous in their praise for the achievement by Zernicka-Goetz and Ali Brinvalou while also noting the challenges to the 14-day rule.
Commenting to the Genetic Expert News Service, Vittorio Sebastiano, an assistant professor of obstetrics and gynecology at Stanford University said, “This apparently trivial achievement is a rather remarkable milestone in the field.” He also noted that the model could now be used along with gene editing to understand how different genes control implantation and could eventually also lead to development of gene therapies in cases where “maternal tissues that impede the implantation of embryos.”
Peter Donovan, a developmental biology researcher at the University of California Irvine noted that the, “advances in technology have allowed the growth of embryos in a lab past the time which many scientists thought possible....So now science has a method to study a key period of human development that up until now has largely remained a black box.”
Commenting to the Science Media Centre in the United Kingdom about the 14-day limit, Martin Johnson, a professor at the Univerity of Cambridge:
This is a unique achievement, that potentially challenges the 14 day rule, because to stop the culture at 14 days arbitrarily prevents study of the primitive streak development which stops us asking questions about the basis of twinning, the origins of spina bifida, and how the germ cells are set aside.
Robin Lovell Badge, a group leader at the Francis Crick Institute and a member of the committee convened by the National Academy of Sciences in 2015 noted:
the process of gastrulation, where the embryo becomes organized into a basic body plan, begins shortly after [14 days]. We know little about this critical phase in human development. So it is pertinent to ask if the 14-day limit should be extended? Proposing to extend the 14-day limit might be opening a can of worms, but would it lead to Pandora’s box, or a treasure chest of valuable information ? This is not a question to be left to scientists alone.
In an interview to NPR, Avi Brivalou highlighted the potential of this model they had developed
We will learn things we cannot even imagine...It's as if you say: 'If I look at new sets of Hubble Space Telescope pictures that I haven't seen yet, what will I learn from them?' It's difficult to say until you look at them.
And therein lies an important fact. We still don’t know what we will actually learn from this advance. What the two teams have developed is a model that scientists can improve upon and study for years to come. While we can guess that some of it will be clinically relevant, this is just the first step. Even in these studies, the researchers note that while they were able to replicate several of the features of the first two weeks of an embryo’s growth they were not able to recapitulate it completely and there were still several differences with development in the uterus.
This is one of the reasons why ethicists are reluctant to consider altering the rule. Speaking to GENeS, Hank Greely, director of the Center for Law and the Biosciences at Stanford University said:
Frankly, I am not convinced [by the call to ‘revisit’ the limit].What is the benefit from keeping human embryos alive in vitro for extra days?...Is an in vitro embryo attached to an ‘implantation platform’ really a model for ‘early human development’? ...I do not see a politically, or, for most people, morally acceptable line after 14 days. Given the questionable scientific value of the research, no case has been made for even revisiting the line, let alone changing it.
Francoise Bayliss, professor of bioethics and philosophy at Dalhousie University in Canada agreed:
A crucial question for us today is: do we have new and compelling ethical or scientificjustification(s) to change the 14-day rule? What we certainly do have is technological prowess...But is this ‘scientific breakthrough’ enough to warrant a change in law or policy? Isn’t it somewhat ironic that when the agreed-upon limit might finally be practically relevant (meaning that it could function to stop scientists from doing something they might otherwise do), the suggestion is that now might be a good time to change the limit?
Regulations and policy have always played catch up with scientific advances. But a mix of the exponential rate of new discoveries and applications, and lessons learned from previous experiences with similar controversial issues such as embryonic stem cell studies or gain of function research in viruses have put forth the need for the scientific and regulatory community to be proactive rather than reactive on issues with significant ethical implications.
Indeed, independent bodies like the Human Fertilisation and Embryology Authority in the UK were set up explicitly for this purpose. The presence of a structured process allowed them to consider the controversial issue mitochondrial transfer which allows mothers with severe mitochondrial genetic defects to have genetically related children.
In the current scenario, a discussion, as suggested seems the most prudent step forward, irrespective of what the eventual outcome is.
Arvind Suresh is a science media liaison at the Genetic Expert News Service. He is also a science communicator and a former laboratory biologist. Follow him @suresh_arvind.