Reining in the SHEEFs

Consider the human embryo…

Ordinarily, it arises from the union of a sperm and egg to form a zygote, which is totipotent, that is, able to develop into a full individual.  In our time, fertilization can happen artificially, as with artificial insemination or in vitro fertilization, or naturally through the process that is accessible even to educated fleas.  But the zygote develops into a multicellular embryo, which in its earliest stages, can be the source of embryonic stem cells.  Fourteen days after fertilization the embryo develops a “primitive streak,” a sign that more advance development is imminent.  A few days later, nerve cells begin to develop, and things mature and get more complicated from there.  A cloned embryo, at least in principle, can do the same thing.  Also, in the first few days, the embryo can be invaded or destroyed to yield human embryonic stem cells that are also totipotent.

The so-called “14-day rule,” reviewed by Mark McQuain in his March 21 post to this blog, limits research on human embryos to that first few weeks of life.  The idea was to try to stay away from the development of those first nerve cells, when it might be argued the embryo can begin to feel pain.  People who disagree with, for example, the present writer that the embryo should enjoy full human moral status from the time of protection reasoned that the beginnings of a nervous system constitute the acquisition of “morally relevant” qualities by the embryo.

As Mark reviewed, arguments are being advanced to relax this 14-day rule, to facilitate embryo research of interest.  If one objects that moral status is not something emergent, not dependent on the acquisition of degreed properties, then one will resist relaxing the 14-day rule.  I put myself in that camp and imagine most other contributors to and readers of this blog would agree.

But now, synthetic biology—the fusion of engineering and modern biology—poses new problems for the 14-day rule.  These are reviewed in an article, “Addressing the ethical issues raised by synthetic human entities with embryo-like features,” or “SHEEFs” for short.  The authors, Harvard geneticists John Aach, Jeantine Lunshof, Eswar Iyer, and George Church, point out that SHEEFs are not like your regular embryo, your “non-synthetic” embryo as they call it, because the development of SHEEFs is different.  (I object to using the term “non-synthetic” here, because it seems to make “synthetic” the reference standard, but that’s for another time.)

SHEEFs are made from the “ethical” stem cells, induced pluripotent stem cells, or iPSCs, which are considered not to be totipotent.  However, it turns out that under certain conditions human iPSCs can be used to make something that is not a fully human embryo but can look like one in various ways.  Work to make clumps of cells with iPSCs has been reported to lead to something with a primitive streak and with other differentiation of cells into the basic early cells found in an embryo.  The work is still fairly early on, but technically, numerous possibilities can be envisioned.  An example of a goal would be “tissue engineering,” growing, if not full organs in the lab, then cells that could be used to regenerate damaged organs.

The key technical point is that SHEEFs can leapfrog the 14-day primitive streak to develop more complex, higher functioning characteristics.  Some examples raised by the authors:

  • SHEEFs that are engineered to be very like regular embroys—“embryos in a dish”
  • SHEEFs that combine features in novel ways, e.g., a human beating heart and a brain incapable of pain or sensation
  • SHEEFs with recognizable human form and a beating heart but no brain
  • SHEEFs engineered to develop a nervous system without passing through a primitive streak
  • Human/non-human hybrid SHEEFs

The geneticists, concerned about the emergence of “morally relevant properties” in such SHEEFs, argue that rules should be added to the 14 day rule to govern what sort of SHEEFs should or should not be produced in the course of research.  Research limits should be addressed, they say, to “give precise definition to how SHEEFs must be configured to avoid making them morally equivalent to embryos…SHEEFs could be generated using [iPSC] that are specifically engineered in ways that will prevent the SHEEFs from developing a cell type or function essential to a moral status signifying feature, but which would follow embryonic development in every other respect…[there will be an increase in] demand for experiments with non-synthetic embryos that go up to the permissible boundaries of embryo research…entities created from mixtures and animal cells would raise moral concerns similar to those raised by chimeras…synthetic biology methods might be used to generate post-embryonic human cerebraland nural tissue organoids that likewise present complete and active pain pathways, possibly even in childhood or adult forms,” with the further challenge that “very sophisticated brain organoids” could be made that arguably are not just sentient but conscious and self-aware.

How far shall we go in the name of treating disease or understanding human biology?  What strange beasts shall we create?  Who will help the church understand and respond?  The authors call for a serious, wide ranging ethical discussion that includes not only scientists and bioethicists, but also those who do not endorse moral developmental emergence, to foster negotiation between the two viewpoints in search of a common agreement.  Whether such an agreement would be possible remains to be determined.

The article discussed here should be read by anyone remotely interested in bioethics, or the future of the human race—frankly, by anyone who can read and will spend 30 minutes.  Strange, mind-blowing things are knocking at the door.


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Mark McQuain
Mark McQuain
4 years ago

Thanks for your post and the heads-up on the advances in SHEEFs.

I read the article you linked (took me much longer than 30 minutes) and share your concerns with the authors’ chosen terminology of “synthetic” as the default, such that “non-synthetic” mean regular embryo development. I appreciated their analogy of the primitive streak being currently the “stop sign” of the present 14-day rule “highway of normal development” and how the current limit of the primitive streak clearly won’t work if one can use synthetic methods to bypass the normal development of the primitive streak and potentially create SHEEFs with features that have neural development well beyond the primitive streak. I would extend their highway analogy to suggest the synthetic embryo engineering is indeed turning the car “off-road” to bypass a reasonable “stop sign” and effectively amounts to reckless driving. Seems fitting…

Perhaps most concerning is their preference for considering human moral status an emergent phenomena. Though it does sound as if they are resigned to include individuals on a future commission who may have opposing views – so when that time comes I enthusiastically nominate you to present one such opposing view.

Finally, the theme in their article and in their discussion of their revisions with their reviewers was that SHEEFs are clearly “entities” but are they “human”? Can they become “human”? If it is determined that SHEEFs never arrive at a human threshold,then “Katy bar the door” – all experiments will be permissible.

Jon Holmlund
Jon Holmlund
4 years ago
Reply to  Mark McQuain

Watch for more–I intend a series on this. Will not try to start that in this comment. Not sure I would qualify to be on any of their envisioned commissions but there are others, as we know.

You may have noted that they do NOT think that SHEEFs necessarily require a re-visiting of the 14-day rule for natural/canonical/conjugal (none of the terms seems exactly right) embryos. That despite the clear pressure on that rule that you and others have commnented on.