Scientists break record for lab-grown human embryos, raising questions over research rules

Two separate research teams publishing in Nature and Nature Cell Biology have reported culturing human embryos up to 13 days, going well beyond previous achievements and reaching the internationally agreed 14-day limit on human embryo research. Writing in a separate Nature comment piece, three US researchers raise the question of whether the 14-day rule should now be revisited.

 

Dr. Vittorio Sebastiano, Assistant Professor, Department of Obstetrics and Gynecology, Stanford School of Medicine (webpage):

Expertise: Molecular mechanisms that regulate the development of human embryos from fertilization to the formation of the blastocyst, right before it implants in the uterus.

“In these studies the researchers have shown for the first time that human embryos can be successfully cultured for approximately 12-14 days, way beyond previous attempts. Most importantly the embryos could be cultured on a three dimensional matrix and mimic the process known as implantation. Implantation occurs when the embryo ‘invades’ the maternal uterine wall to initiate fundamental processes of development that will lead to the formation of both the fetal tissues and of the tissues (for instance the placenta) that will sustain the growth of the fetus during pregnancy. This apparently trivial achievement is a rather remarkable milestone in the field.

“While studying rodent embryos can approximate some of these events, many features are human specific and necessitate a model that is based on human embryos.

“These studies pose the basis for future work that will allow dissecting, at the functional and molecular level, a fundamental and thus far inaccessible window of development with important repercussions on the elucidation of human specific characteristics of implantation. Recent achievements in genome editing for example can be combined with this novel technique to investigate how different genes control and fine-tune implantation. In addition novel tissue-specific cell lines could be generated with the potential to develop cell therapies that will impact the survival of defective embryos. Lastly we could start developing therapies for the treatment of pathologies where it is the maternal tissues that impede the implantation of embryos.”

 

Henry (Hank) Greely, Director, Center for Law and the Biosciences; Professor (by courtesy) of Genetics, Stanford School of Medicine (webpage):

Expertise: Ethical, legal, and social implications of new biomedical technologies, particularly those related to neuroscience, genetics, or stem cell research.

“In the past few decades, bioscience has made several promises it couldn’t be called on. ‘No human germline engineering,’ ‘no human reproductive cloning,’ ‘no embryo research more than 14 day after fertilization.’ None were possible at the time of the promises; all have started looking plausible in the last few years.

“The latest is embryo research. It was easy to promise not to do research past 14 days (or the appearance of the primitive streak) because no one could keep ex vivo human embryos alive past at most nine days, usually seven.

“But now two groups have kept human embryos alive on ‘in vitro implantation platforms’ for 12 or 13 days. At least one of the groups destroyed its embryos to abide by the 14-day limit.

“At the same time as the scientific publication comes a call to ‘revisit’ or ‘reconsider’ this limit. Frankly, I am not convinced.

“What is the benefit from keeping human embryos alive in vitro for extra days? It is said it can ‘lead to scientists being able to study all aspects of early human development with unprecedented precision.’ Yet is an in vitro embryo attached to an ‘implantation platform’ really a model for ‘early human development’? Who knows – and, perhaps more importantly, who can know barring unavailable detailed information about early embryos inside women’s wombs?

“On the other side, if we do not use a 14 day rule, what limit will we use? Twelve weeks or so as in many European abortion laws? Viability (at around 23 weeks) as in U.S. abortion law? Human development is a seamless process, but ultimately lines need to be drawn even when – especially when – they do not naturally exist. 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.”

 

Dr. Françoise Baylis, Professor and Canada Research Chair in Bioethics and Philosophy, Dalhousie University (webpage):

Expertise: Bioethical aspects of women’s health, human embryo research, and novel genetic technologies.

“Scientific and political elites have long known the day would come when scientists would challenge the 14-day limit. Indeed, Sir Robert Edwards, one of the pioneers of IVF, suggested that the limit should be 21 days. More generally, as far back as the mid-90s there were those who insisted that the internationally accepted norm of 14 days ‘should be subject to modification should there be new and compelling ethical or scientific justification to do so.’

“So, a crucial question for us today is: do we have new and compelling ethical or scientific justification(s) to change the 14-day rule? What we certainly do have is technological prowess:  scientists appear to have mastered keeping human embryos alive in vitro up to 14 days. 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?

“In December 2015, the US National Academy of Sciences, the US National Academy of Medicine, the Chinese Academy of Sciences, and the UK’s Royal Society jointly hosted an international summit on human gene editing.  At the close of that meeting, the organizing committee (of which I was a member) issued a final statement that endorsed basic and preclinical research in human embryos ‘subject to appropriate legal and ethical rules and oversight’.  The statement also championed a commitment to international consensus-building. As such, I am very pleased to see Insoo Hyun, Amy Wilkerson, and Josephine Johnston encourage ‘processes aimed at consensus-building involving experts, policymakers, patients and concerned citizens.’ However, these authors may have reached the right conclusion, but for the wrong reason.  Their primary concern seems to be with preventing ‘a public backlash and the implementation of reactive, or restrictive limits on research.’  This smacks of political expediency.”

 

Dr. Paul Root Wolpe, Asa Griggs Candler Professor of Bioethics & Director, Center for Ethics, Emory University (webpage):

Expertise: The social, religious, ethical, and ideological impact of technology on the human condition.

“New scientific techniques sometimes challenge existing definitions and standards.  The ability to sustain embryonic stem cell development further and further are beginning to put pressure on the ’14 day rule,’ and future developments will only increase that pressure.  Temporary or piecemeal changes are not going to solve the broader problem of differing standards of the moral status of embryos and proper scientific posture towards embryonic cells as research tissues.  Also, different policies in different countries may lead to inability to do cross-cultural work, or refusal of some countries to use products developed in countries with different standards. 

“I believe the solution is to differentiate reproductively viable embryos from embryos or other cellular simulacra that are non-viable.  For viable embryos, we should retain a 14 day standard or negotiate some other internationally negotiated time limit (14 days is just a convention).  Scientific advances are allowing the creation of either non-viable embryos or embryo models.  For non-viable models, with some rare exceptions, there should be fewer ethical challenges to the research.”

 

Dr. Peter Donovan, Professor of Biological Chemistry and of Developmental and Cell Biology, University of California, Irvine (webpage):

Expertise: Molecular genetics of germ cell and stem cell development.

“Two important messages emerge from these studies. First, advances in technology have allowed the growth of embryos in a lab past the time which many scientists thought possible. Second, the studies demonstrate many of the events of embryo development (cell differentiation and shape changes) can be recapitulated in the lab, which indicates that these events are autonomous to the embryo. In other words, these events aren’t strongly influenced by being attached to the maternal tissue. So now science has a method to study a key period of human development that up until now has largely remained a black box.

“Of course, major advances like this often raise questions that go beyond the science. In many countries, growth of human embryos in the lab is prohibited past 14 days. In the past this has been of little issue because it was technically not feasible. Why is the 14 day limit important? At this time in development the embryo forms a structure called the primitive streak that marks the time at which the embryo has a definitive head and tail end. Before this time the embryo could split to form two individuals. So this marks the time at which an embryo could be considered an individual, as well as the time just before the embryonic brain begins to develop.

“What if scientists could culture the human embryo for longer than 14 days? Perhaps we could begin to understand the consequences of fetal alcohol syndrome, study the potential causes of autism and find out why some environmental chemicals can affect development. Perhaps we might, for examples, be able to more quickly understand what the Zika virus does to embryos to cause major problems with brain development. There could be major benefits for society, but if the 14-day line is crossed then society has to fully understand the science and come to an informed decision about the use of the technology.”

 

Declared interests (see GENeS register of interests policy):

No interests declared.

 

Reference:

  1. Self-organization of the in vitro attached human embryo‘ by Deglincerti et al, published in Nature on Wednesday May 4, 2016
  2. Self-organization of the human embryo in the absence of maternal tissues‘ by Shahbazi et al, published in Nature Cell Biology on Wednesday May 4, 2016
  3. Revisit the 14-day rule‘ by Hyun, et al, published in Nature on Wednesday May 4, 2016
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  • Dulcinea67

    Scientists with research dollars on the line will undoubtedly beat their drums that they absolutely must extend the 14-day rule because their research will save lives. Just like they beat their little drums about needing embryonic stem cell to save people from Alzheimer’s and Parkinson’s disease. They drummed out all the scientists who said that adult stem cells are a more feasible approach to disease fighting, which in the end was absolutely correct. Embryonic stem cell research has been a waste compared to adult stem cell research, even though billions more were spent on embryonic research.

    The science is clear, a new life is created when an egg is fertilized by sperm and if left to its own devices, barring any interference (natural or human), it will become a breathing human. All these lines scientists and activists try to draw in human development (when cells differentiate, when the primitive streak emerges, when the brain stem develops, when the fetus can feel pain, when it becomes a “person”) are completely artificial and only serve to create the appearance of ethical consideration for human life. There are only three bright lines in human development: fertilization, first breath, last breath. For females you could add first menses, but the rest of human development is an ongoing process.

    As far as I’m concerned, a woman who is gestating has the right to do whatever she wants with her body, so this isn’t about being pro-life or pro-choice. This is about being a scientist and accepting the reality that a human embryo is a human being at its appropriate stage of development. It doesn’t suddenly become a human at a magic moment or get ensouled at some point that turns them into humans; it’s always a human being and it’s anti-scientific to use political processes to cover-up that fact. This latest call to revisit the 14-day rule only serves to move the imaginary line that separates “a bunch of cells” from a human being and confirms the slippery slope we’re on to get to breeding human fetuses for experimentation. If anything, given what we scientifically know about human development, the 14-day rule should be pulled back to the point of cell differentiation, i.e., when the blastocysts form after 4 days. Scientists are not saints and many will feel no hesitation about experimenting on humans if released from such rules. The trend has been towards scientists demanding to do more human experimentation with the justification that human embryos aren’t humans. When they come up with a way to keep a cadaver uterus viable for implantation, they’ll demand that fetuses aren’t human either and argue they should be able to grow them until the first trimester. When will it end? What’s the point of this experimentation? Do we really need more ways of increasing population growth? Isn’t it likely that we’ll develop the technology to learn more about human development by observing it in its natural environment? Let’s wait until then. They are creating artificial urgency around this issue just as they did with embryonic stem cells.

    • Slicer

      “Isn’t it likely that we’ll develop the technology to learn more about
      human development by observing it in its natural environment?”

      This statement shows how much you actually care about ethics.

      Yes. Let’s subject women to recurring experimental pregnancies. That’ll work well.