By Barbara Pfeffer Billauer
A synthetic embryo can now be constructed from very early pre-embryonic cells – without the need for an egg or sperm. These were initially created in mice. In April, researchers in China published about their creation of synthetic monkey embryos. In June, it was reported that the first synthetic human models were apparently created. This development throws a moral monkey-wrench into the current moratoria on embryonic research after 14 days. But there are more problems ahead.
Two weeks – the 14-day Rule
Of immediate concern are the ramifications of the 14-day rule, which imposes a (voluntary in the U.S.) moratorium on experimentation on human embryos older than 14 days; after that, they must be terminated. Strictly speaking, at this point, the fertilized egg (zygote) is called by various names, e.g., blastocyst and a “morula” (“little cherry”) because depending on the stage of development, that’s what the entity resembles. This zygote does not achieve full “embryo” status until day 14 after fertilization, the beginning of “gastrulation.”
In biological terms, the 15th day of embryo development is the point when the primitive streak forms: that is, the beginning of gastrulation when three layers of germ cells differentiate. The 14th day is therefore notable, because the embryo is then individuated and can no longer become a twin.
At this point, an identifiable humanoid entity begins to form, most notably the spinal column (the “primitive streak”) and the origination of nerves. The origin of nerve cells triggers concern the entity might feel pain; the spinal column signals the development of a bilateral organism, bifurcated longitudinally.
Dame Martha Warnock, the British Bioethicist who conceived the first formal ethical construct to deal with these problems, considered gastrulation the point where “moral grounds of sentience and individuality” first appear.
When I first wrote about this topic, the discussion was purely theoretical, as the synthetic version of the human zygote was purely a hypothetical construct. No longer. We now have to address the ramifications in real-time.
Synthetic embryos?
These synthetic human embryos, or SHEEFs (synthetic human entities with embryo-like features), are created from very early (actually pre-embryonic) zygotic cells called stem cells. The stem cells are called “pluripotent” because they have the potential to develop into almost every cell of the body. [1]
Because they theoretically don’t have the potential to grow into viable organisms, legally speaking, these entities are not considered embryos. And because an egg and sperm are not involved in its creation, technically, experimentation on the synthetic embryo escapes the 14-day moratorium’s literal restraints. There is no specific regulation governing such research in the U.S.; it’s just that the federal government won’t fund the research. To date, most, if not all, U.S. scientists comply with the voluntary moratorium, but there is no way to be absolutely sure. In the U.K., the Warnock Commission strictly banned experimentation after 14 days, but no ban exists on experimentation beforehand.
Indeed, of the two scientists reporting the breakthrough in human synthetic embryos, one was from the U.K., the other from the Weizmann Institute in Israel. In other countries, the research is explicitly banned. The International Society for Stem Cell Research advises the ban be relaxed on a case-by-case basis if good scientific cause can be shown for its use. So far, no country has adopted this rule.
At present, researchers can keep these synthetic humanoid organisms alive for almost nine days; the mouse version can be kept alive for twelve days, half the full mice gestation period, which might translate to four and a half months in humans. Even at these early stages, the syn-pre-mice developed the ability to “form all regions of the brain, beating hearts, and so on.”
The importance of this research, say scientists working in the area, is to give us more information regarding early human pregnancy failures, furnishing knowledge, currently unavailable, on how human embryos develop post-gastrulation. This research could also benefit children with congenital disabilities, genetically derived malignancies, and other disorders and assist in creating cell-based therapies to treat disease.
On the flip side, knowledge of early human development empowers those who are pro-life, opposing abortion even at the earliest stages of gestation, when nascent structures of to-be-organs first appear.
The blurring line of legality and ethics
Another concern, from a legal standpoint, is identifying who owns these cells. Legally, once one parts with or donates pieces of our anatomy, they are no longer “ours.” To protect against individuals or corporations utilizing these cells for profit, ála the Henrietta Lacks story, sophisticated informed consent, and licenses should surely be developed, along with directives on responsibility for maintenance, warehousing, and disposal., Bailment theory is a theory of contracts generally applied to safeguarding property and has been applied to lost or damaged gametes from laboratory misfeasance. It might find another home here.
Perhaps the most frightening consideration, however, is the possibility of using this research to develop human tissues and organs for transplantation. While no actual human would be created, it is highly realistic to presume that early lineages of human cells could be “cloned” from these synthetic models. At what point we decide to ban such research along the developmental continuum should be decided before we begin to embark on this journey. [2]
As opposed to embryos that can develop into a complete human, the potential for stem cell development is far more limited and can be seen as “morally safer.” On the other hand, once we remove the lid from Pandora’s box, we have no guarantee where we will be headed.
And consider this: we are not limited to creating synthetic pre-humans from early embryos, The technology of induced pluripotent stem cells allows for an adult human to harvest their cells, regress or rejuvenate them to the pre-embryonic state, and then redirect their growth into a new person-oid. (This “rejuvenation” of mature cell types was the revolutionary discovery of the Japanese biologist Shinya Yamanaka, which won him a share of the 2012 Nobel Prize in Physiology or Medicine.)
Rejuvenated or induced pluripotent stem cells do not even involve the use of an embryo, let alone an egg or sperm, even at its earliest stages, and therefore bypasses any existing regulation. Surely, one can foresee some wealthy megalomaniac billionaire (of which our society has a few) with a fatal disease or needing a new body part commissioning some scientist to use this technology privately.
Science fiction has arrived. We need to start planning now.
[1] “Pluripotent cells are capable of giving rise to nearly all cells in an organism (i.e., all tissues in the fetus- brains, bones, guts) except the ones that form the placenta and supportive structures that link the fetus to the mother).” See Siddhartha Mukergee, The Cell p. 319. The supportive cells, however, are necessary for the creation of the synthetic embryo and are derived from totipotent cells, which have the capacity to morph into all cells of the human, including the trophoblast stem or TSCs and the yolk sac progenitors, or XEN cells).
[2] For a frightening fictional depiction of replica humans created for organ transplant, read Never Let Me Go by Kazuo Ishiguro.
This article is lightly edited and reprinted, with permission, from the American Council on Science and Health. The original article can be found here.
