Scientists push to reconsider human embryo research limits

An international research team has just announced that they have succeeded in “cultivating” human embryos for 13 days, compared to the preceding record of nine days. Notably due to a rich artificial nutritive medium resembling that of the human uterus, they were able to keep them alive, past the point when they would normally implant in the womb.

This work was published May 4, 2016 in two British reviews, Nature and Nature Cell Biology. Professor Zernicka-Goetz from the University of Cambridge stated that this new limit «actually allows us to understand the very first steps in our development at the time of implantation where the embryo, really for the first time, reorganizes itself to form the future body”.

Afterwards, the embryos in this experiment were purposely destroyed in order to respect the current legal limit of 14 days in several countries. This 14-day limit is often adopted since it marks the point when the individuality of an embryo is assured, because it can no longer split into twins. At the same time, embryos form what is called the “primitive streak”, which marks the distinction of the head from the tail of the embryo.

This piece of news has caused a number of reactions. The question to prolong the 14 day limit has been raised, and is already being debated by the scientific community. By prolonging the legal limit by two days (thus 16 days) one would be able to study the third phase of the in-vitro embryo development, called «gastrulation». This is the development period during which the 3 fundamental (or primitive) layers of the embryo are being put into place, together forming the tissues and organs of this new human being.

According to Professor Zernicka-Goetz : “This new technique gives us a unique opportunity to better understand our own development during the critical phases (in the first days of life) and what happens for example during a miscarriage”. But this professor who is responsible of the part of the study carried out in the United Kingdom says: it’s not for us to decide now whether we should do it or not. Rules are useful, we must adhere to them, and they should be set out by the wider community”.  

Three of the researchers involved in the study, Insoo Hyun at Case Western Reserve University in Ohio, Amy Wilkerson at Rockefeller University in New York, and Josephine Johnston at the Hastings Center in New York, call for the 14-day ‘rule’ to be revisited, and for international discourse to amend the laws and research policies.

For Allan Pacey, Professor at the British University of Sheffield: “This could be a revolution in our understanding of the early stages of human embryo development”. Robin Lovell-Badge at the Francis Crick Institute in London questions: “Does proposing the extension of the 14-day limit open Pandora’s Box or would it be a wealth of information? (…) If the decision was not to extend, I can certainly live with it, and I suspect most scientists can”. However for Azim Surani, research director at The Gurdon Institute in Cambridge, is in favor of reviewing the rule: “In my opinion, to allow culture beyond 14 days was justified even well before these publications”.

The Nuffield Council on Bioethics has announced their wish to organize a meeting later this year to discuss the possibility of modifying the limit. Considering the initiative for extending this limit raises serious questions, the Chair of the Council, Johnathon Montgomery declared: “The Council intends to bring together participants with different points of view on embryo research in order to evaluate whether, after 25 years, there may be persuasive reasons to review this legal limit, or whether the reasons for setting this limit remain sound.”

Thus these embryos developed without any contact with maternal cells. Yet, after fertilization, in the natural process, the fertilized egg usually implants itself in the mother’s uterine wall about 6 days following fertilization. In the ART centers, embryos are implanted before the 7th day.

This raises a number of questions, in particular: is the development of the embryos studied in-vitro perfectly similar to that of embryos developed in a woman’s uterus? Ideed, the “natural” process is interrupted since these embryos have developed without being implanted in the womb and with no interactions with the maternal mucous membrane.

This is why Henry Greely, Genetics Professor at the American School of Medecine, questions the interest of prolonging the life of in-vitro embryos to obtain “details on early human development”, whereas we “do not have detailed information” on the embryo in the uterus at the very beginning of pregnancy. Dr Donovan at the University of California however states: “We could perhaps (…) study the potential causes of autism and find out how chemical products in the environment may affect the embryo’s development.”

This research study also involves the development and use of embryonic stem cells. If the in-vitro development stages are prolonged, it’s possible to imagine genetically modifying more differentiated tissues (for example by using CRISPR-Cas9) without these modifications becoming hereditary.

This breakthrough, by re-launching the debate on the legal limit for embryo experimentation, gives rise to renewed pressure to extend the manipulation of human beings conceived in-vitro outside the woman’s body.