International commission: go slow with heritable human genome editing

The international commission on heritable human genome editing (HHGE), formed by the US National Academies of Medicine and Science and the Royal Society of Great Britain, has issued it report.  The 224-page report is freely available for reading here, and a summary news report can be accessed here.

The upshot:  not too fast.  The commission’s 11 major recommendations, briefly reworded and rearranged in order, are:

  • Before attempting any pregnancy with a gene-edited human embryo, “a significant cohort” of edited human embryos should be studied in the laboratory to ensure that the desired gene edit(s) “can be performed with sufficiently high efficiency and precision to be clinically useful.”  (No attempt would be made to bring these embryos to birth, and they would exist solely for research purposes, after which they would be destroyed.)
  • This efficiency and precision have not been demonstrated yet, and “no attempt to establish a pregnancy” with an edited human embryo should be made until they have.
  • Even then, the attempt should come only after “extensive societal dialogue” within any country whose leaders are considering endorsing the attempt.  This dialogue would include medical and scientific concerns, which the report addresses, and also “societal and ethical issues that were beyond the Commission’s charge.”  (Your correspondent has just begun reading the report, so cannot say yet whether the Commission considered how to proceed if one country green-lights edited human pregnancies while others do not.)
  • The only conditions that should be considered for editing are those of a serious disease caused by a single gene abnormality, for which the prospective parents have a less than 25% chance of having an unaffected child using current preimplantation genetic diagnosis (PGD).  Further, the resulting edited gene would be common and non-disease causing in the general population, and no embryos without the diseased gene would be edited. (This would seriously limit the use of HHGE—not permitting it for genes that increase the risk of cancer, for example—but, like the first point, would also raise concerns for conservative ethicists who consider all human embryos, from conception, to be human beings with the right to life.  If you’re troubled by PGD in general, this recommendation won’t satisfy you.)
  • The above would need to be followed for every proposed “treatment” of genetic disease—there is no “one-size-fits-all” approach to setting up a regime for heritable gene editing in general.  (This would have the effect of limiting the “industrialization” of HHGE, it appears.)
  • The actual transfer of an edited embryo to a woman’s uterus should be subject to (future) “rigorous” regulatory review and approval—that is, the edited embryo would be checked, in the laboratory, before transfer, to be sure that the edit had succeeded.   After transfer and through pregnancy, birth, and the life of the individual, close medical monitoring would be mandatory to learn what medical problems may have arisen.
  • A potential work-around should be studied in the laboratory: making human eggs and sperm from stem cells, with the intent of being able to use them for in vitro fertilization to give rise to an embryo without the abnormal gene.  However, the Commission recognizes that there are other canned worms, so to speak, to be dealt with here—such as whether this approach to begetting children is ethical at all, apart from any use of gene editing.
  • Any country embarking on HHGE in actual pregnancies should first put in place “mechanisms and competent regulatory bodies” to oversee standards and adherence to them, publication of results, and oversight in general.
  • An International Scientific Advisory Panel should be established in advance to oversee the progress of the science overall, before pregnancies are attempted—essentially, a single point of review to prevent intrepid scientists from “going rogue,” as it were.
  • An international body (presumably a different one from the above) with appropriate expertise should review every new proposed medical application of HHGE before pregnancies with the relevantly-edited embryos are established.  So, presumably, attempts to edit the gene for Huntington’s disease would be assessed separately from attempts to edit the gene for sickle cell anemia, for example.
  • An international mechanism should be established to adjudicate cases of alleged deviation from received guidelines or standards, and its’ results should be transmitted to individual governments and publicly released.

It looks like a careful report, welcome in its caution, although, as noted, those who hold that human life begins at conception will still likely object to the endorsement to continue with laboratory-based research.  “Just say no” to the prospect of HHGE—a position your current correspondent has consistently advocated on this topic—does not appear to be in view.  One might also be forgiven for skepticism over the effectiveness of any international body, given the controversies that arise from our existing international bodies for medicine and health, not to mention other endeavors.  Some such efforts, such as the regulatory harmonization of human clinical trials and drug development that governs the US, the EU, and Japan, work pretty well, but arguably are limited.

It is also worth mention that the California Institute of Regenerative Medicine (CIRM), established with Proposition 71 in 2004, ostensibly to translate embryonic stem cell research into cures (with creation and destruction of human embryos for the purpose), is proposed for renewed public funding in California with Proposition 14 in this November’s election.  Nothing approaching a cure was achieved under the CIRM, and even proponents of human embryonic stem cell research argue a renewal is unnecessary, because there is plenty of private money supporting related work already.  Further, the CIRM came under charges of insider dealing, because it needed to draw its leaders from the small pool of experts who tended to have career or monetary interests in the field to begin with, raising repeated concerns about a conflict of interest.  Would such potential conflicts plague the national and international bodies proposed by the HHGE Commission?  (Full disclosure: your correspondent will eagerly vote “no on 14” on his mail-in ballot this fall.)

Finally, so-called “somatic” gene editing—a fundamentally ethical undertaking by which a person’s cells may be altered to make them into a treatment for disease—is here to stay, as are certain forms of gene therapy that don’t involve heritable changes.  Expect to hear about those more in the future; they are subject to standard human subject research concerns, and to justice concerns like the eventual costs of the treatment.  Those topics for another day.

Humanoid Mass Production

Henry Ford would be proud.

We now have the ability to mass produce humanoids, embryonic cells derived from human embryonic stem cells or induced pluripotent stem cells (the latter can be made from adult cells). These cells are specifically designed by researchers to have some but not all of the necessary elements to be fully human. The goal is to grow these humanoids beyond the current 14-day limitation imposed on research studies on human embryos that ARE fully human.  In theory, these humanoids are physiologically similar enough to humans that by observing their growth and development, scientists hope to learn about human development. By design, the claim is that humanoids are different enough from humans that they would not/could not /should not live outside the Petri Dish. The original report in Nature may be found here.

I use the Henry Ford analogy on purpose. He revolutionized the automobile industry by standardizing the manufacturing process such that less skilled laborers could sequentially assemble an automobile. This allowed the cars to be built faster, at higher volume and far less expensively. Previously, higher skilled craftsmen machined each unique part for each unique car. Though the cars looked the same, their parts were not interchangeable. The process was painstakingly slow, resulting in a very low production volume at a very high price. With mass production, cars became far more common,  much less expensive and, to some extent, disposable.

Moving toward a standardized “mass production” process will have the same effects for humanoid production. Standardizing the manufacturing process will reduce the variance of a given humanoid, making the scientific study of its growth more reliable, reproducible and less expensive, all good things from a scientific standpoint. Will it also cause us to view the humanoids as more disposable?

I continue to want more discussion on the moral status of humanoids before more experimentation is permitted, particularly as we extend their lifespans. Whatever they are, at minimum, they are living entities.  Humanoids must be more than the sum total of their individual cells otherwise we humans would not have so much interest in their development. How human-like does a humanoid have to be before we should consider additional human-like moral/ethical protection in humanoid experimentation?

Or their mass production?

Stem Cell Rx No Longer For Sale on Google

Perhaps once a week, I will be asked by a patient about the potential benefits of stem cells for reversing the normal affects of age, particularly with respect to arthritis of the knee joints, hip joints or the degenerative discs in the lumbar spine. I believe one of the reasons for this interest has come from increasing advertisements by various clinics in my region of East Tennessee claiming stem cells are the answer for these problems. My region is not unique. A simple Google search on “stem cells for knee pain” yields ads for clinics offering such treatment.

Stem cells are cells that have potential to become any type of cell in the human body such as a new blood cell, nerve cell or bone/cartilage cell. Scientists are rapidly learning how to find or create stem cells, as well as how to safely use them to replace old or missing cells, thus restoring function in worn out, damaged or diseased areas of the body. In fact, stem cells are presently used to replace the bone marrow for some individuals with certain cancers and disorders of the blood and immune system, and in many of these cases, the results are lifesaving.

The problem is that stem cell treatment remains yet unproven in all other medical conditions, including the age-related arthritis conditions which I treat. This lack of efficacy has not stopped clinics from offering and patients from receiving stem cell injections with the hope of achieving improved function or cure. I am willing to grant that many offer these treatments with the sincere hope and belief that they are acting in their patient’s best interest, though I suspect not all have the patient’s best interest in mind. Unfortunately, there have been severe adverse events. Examples include blindness following an injection of stem cells into the eye, and loss of function with development of a spinal cord tumor following stem cell injection into the spine.

The FDA is trying to educate the public and prevent stem cells from being offered for unproven treatments. The FDA has the authority in the US to stop these unproven treatments and take punitive action if needed. This is not to suggest that the FDA is in the business of preventing legitimate investigation into the potential benefits of stem cells, such as this Mayo Clinic Phase 1 study looking at the risks of injecting stem cells in to the cerebrospinal fluid of patients following a spinal cord injury to see if this particular stem cell technique causes harm (with future studies needed to determine benefit).

The FDA is recently getting some help from Google. On September 6th, Google announced it would stop accepting ads for unproven medical treatments, including stem cell therapies. It is early in the effort and the initial link above still has four ads for non-bone marrow stem cell treatments returned with the Google search. Maybe by the time you read this blog entry, the stem cell ads for unproven treatments will be gone.

I am hopeful that stem cells will eventually provide patients with safe therapies that repair injury and return patients to normal health. Offering that promise without the studies that prove such benefit is unethical and potentially harmful. It is good to see Google favoring human welfare over financial profit.

Two developments

A new effort at “somatic” gene editing in China is reported this week.  The key summary:

“As the researchers report in the New England Journal of Medicine,

[note to reader: subscription required]

they transplanted [blood stem] cells that had undergone CRISPR-based editing [of a gene that encodes for a receptor, or “docking station”] into a patient with HIV and acute lymphoblastic leukemia. While [the edited cells lasted for a long time in the bloodstream of the HIV-infected recipient], they only made up between 5 percent and 8 percent of blood cells. A higher percentage is needed for this to be an HIV cure…”

In “somatic” gene editing, mature cells, such as “adult stem cells” or diseased tissues, are gene edited for the purples of treating a fully-formed individual with a disease.  That is what appears to be in view here.  Similar efforts are in progress to treat sickle cell anemia and other genetic diseases.  The ethical issues are relatively well-understood, and fit within the regime of regulating cells-as-medicines in clinical trials of humans, under the ethical and regulatory regime that governs the latter.

That’s in contrast to “heritable” gene editing, which attempts to edit genes in embryos, fertilized eggs (zygotes), or gametes (sperm or eggs) with changes that would be passed on through the generations, as recent entries on this blog have been addressing.  The Chinese twin girls who were reported to have undergone gene editing late in 2018 are examples of an attempt at “heritable” gene editing.

A second report from Nature describes efforts to use human “reprogrammed” stem cells, aka pluripotent stem cells, to make human “embryo-like structures.”  This is distinct from making a human embryo, for example in IVF, then removing cells, likely destroying it, for use in research or to develop medical treatments.  In conservative commentaries in recent years, these “reprogrammed” stem cells are considered the “ethical embryonic stem cells,” because they can’t form a full individual and they don’t require creation and destruction of an embryo, that would under normal circumstances form a full individual.

Thing is, these “embryo-like structures” can still form something called a “primitive streak,” which, in normal embryos, is the first sign of formation of a nervous system.  The primitive streak usually forms 14 days after fertilization, so, to try to avoid concerns about research on embryos, scientists who think such research is ethical in limited circumstances have operated under a “14-day rule”–voluntary in the US, mandated by law in the UK–after which embryos would not be destroyed for research.  These “embryo-like structures” may form a primitive streak, it appears.  The situation is similar to “synthetic human entities with embryo-like features,” or “SHEEFs,” which may bypass the primitive streak but raise similar issues of whether something too like a natural human being is being engineered by this work for it to be ethical.

A developmental biologist at Caltech says, the California Institute of Technology in Pasadena. “We will have to confront ourselves with the question of what is a human embryo, and whether these models really have the potential to develop into one.”  The researchers making these synthetic embryos argue that they lack a placenta and other cells needed for development, so could not develop into a person.

At least for now.

Embryonic Legerdemain?

Developmental biologist Lewis Wolpert is credited with saying, “It is not birth, marriage, or death, but gastrulation which is truly the most important time in your life.” Gastrulation, simply put, means the embryo develops an axis and distinctly different cell layers. In the human embryo, gastrulation takes place during the third week post-fertilization. Formation of endoderm occurs over days 14-15, and the mesoderm begins to appear on day 16 (see Figure 1-11 here).  Ali Brivanlou, of New York’s Rockefeller University, identifies gastrulation, or the breaking of symmetry in the embryo, as the “major Holy Grail of developmental biology.”

Why is this so? During the third week after conception, the embryo has burrowed into the mother’s womb, and the peering eyes of scientists cannot visualize the events there. With the 14-day rule in place regarding embryo research, laws or guidelines in various locales outlaw or discourage (as in, do not fund) laboratory culturing of embryos beyond that point. So, Brivanlou’s lab “came up with a model of human embryos that is developed outside of the womb and is not the product of sperm and eggs, but the product of human embryonic stem cells that self-organize into complicated structures.”  These embryonic stem cells have formed what appears to be an embryo, but in Brivanlou’s terms, “could never become a baby.”

Dehumanizing the embryo is one of the essential components of making research on embryonic humans more palatable to the public. It will also be en essential step in a workaround of the 14-day rule. It appears that “model embryo” will join other terms such as “embryoids,” “gastruloids,” and “SHEEFs” as some element of humanity that scientists do not recognize as humans worthy of legal protection. Regarding Brivanlou’s “model embryo,” Harvard Medical School’s Dean George Daley calls it a “remarkable tool in a petri dish.” The “tool” with which Brivanlou and others concern themselves is both human and alive; otherwise, would they be interested?

Let’s think about this, using an analogue. If well-trained scientists could produce men and women without chests, what would be allowed? Would they have to call such men and women without chests “human”? Could they use men and women without chests for experiments?  Would the experiments have to be approved by institutional review boards?  Would the rest of us pay the scientists – handsomely – to do this? Could they win prizes?

Raiding the CRISPR


A couple of gene-editing news items from this week’s science literature:

First, Nature reports that a group in my “back yard,” at the University of California San Diego, has tested gene editing using the CRISPR approach in mice.  Recall that CRISPR is an acronym for a particular molecular mechanism, first discovered in bacteria, that is particularly efficient—though not perfectly so!—at editing genes.  The idea is to find a “bad” gene that you’d like to replace, for example to prevent or treat a disease, and edit it to be the normal version of that gene.

The kicker in this particular case in mice is that it tested something called “gene drive.”  In classical genetics, humans (and other higher organisms) have two copies of each gene.  In sexual reproduction each parent passes one copy of the gene to offspring, so the chance of a particular gene being handed down is 50%.

“Gene drive” is a technique designed to change those odds, and make a particular gene “selfish,” and much more likely to be passed on.  In fact, the idea is that transmission would be 100%, or nearly so.  If that worked, then a new gene would soon take over a population of organisms, and every member would, in a few generations, have that gene.

Why might that be a good thing?  Suppose you are interested in pest control, and you could use the technique to make, say, mosquitoes infertile.  Then they would soon all die off.  Or if you had some other “desirable” characteristic, you could make it so all members of a species (rodents?  Cattle?  People?) have that characteristic.  Assuming it’s determined by one gene, that is.

And assuming that the technique works.  In the mouse experiment, efficiency was only 73%.

That’s probably good news.   This is one of those techniques that could have serious unintended consequences if tried in the field.  Scientists have been warning about that.  It looks like it’s a way off, but something else to fret about.

The second item involves a clinical trial to treat sickle cell anemia.  In this one, blood stem cells from a person with the disease are removed from the bloodstream and gene-edited outside the body to make hemoglobin that is not as damaged as in the disease (SCA is an inherited disease in which the red blood cells have abnormal hemoglobin that doesn’t carry oxygen well).  Then the altered cells become the therapy, and are given back to the patient.

The FDA has put a “clinical hold” on this clinical trial.  Exactly why has not been publicly disclosed (it doesn’t have to be), and it sounds like the trial itself hadn’t started yet, but that the company developing it was getting ready to start.  This is, in my view, an approach to gene editing that does not pose special or particularly worrisome ethical issues, because the genetic changes are done on “adult” stem cells to treat an existing individual with a disease in a way that would not entail transmission of altered genes to future generations.

And, probably, it’s a case of “this too shall pass,” and the FDA’s concerns will be answered and the trial will proceed.

But check out the sidebar reporting this in Nature Biotechnology.  If you follow the link you will probably get a prompt asking for payment but I was able to sneak a free read on my screen.  If you go there, read below the separate quote (itself picked up from The New York Times) from Dr. George Church of Harvard:  “Anyone who does synthetic biology [engineering of biological organisms] should be under surveillance, and anyone who does it without a license should be suspect.”  Apparently he said that in response to “the publication of an experiment recreating a virus that has engendered fears that such information could be used to create a bioweapon. ”

The old “dual use problem,” eh?  We should really fret about that.

Labs are growing human embryos for longer than ever before


That’s only a slight paraphrase of a news feature article this week in Nature.  The clearly-written article is devoid of scientific jargon, with helpful illustrations, open-access online, and readily accessible to the non-specialist.  Check it out.

Key points include:

  • Scientists who do not find it ethically unacceptable to create and destroy human embryos solely for research purposes continue to follow the so-called “14-day rule,” by which such experimentation is limited to the first 14 days after fertilization. At that point, the human nervous system starts to form and the time for twinning is past.
  • The 14-day rule is law in some nations, but until now has not been a practical issue because scientists have been unable to grow human embryos that long in the laboratory.
  • That technical limit has been sufficiently overcome that embryos are now surviving for almost 14 days. Scientists have not directly challenged the 14-day rule yet, but might, and would like to revisit it.
  • Experiments on human embryos in that time have included editing of critical genes to see what happens (sometimes they stop growing), and making hybrids of animal embryos with human cells whose purpose is to “organize” embryonic development rather than remain part of the developing individual.
  • Embryo-like structures, referred to as “embryoids” in the article, and sounding similar to “SHEEFs” (“synthetic human entities with embryo-like features”) are also being created. These entities don’t necessarily develop nervous systems in the same way as a natural embryo, prompting questions of just how much they are like natural embryos, whether the 14-day rule applies, and whether they raise other ethical concerns.

The last paragraph of the article, reproduced here with emphases added, is striking and more than a little ironic in light of arguments that embryos are “just a clump of cells”:

As the results of this research accumulate, the technical advances are inspiring a mixture of fascination and unease among scientists. Both are valuable reactions, says [Josephine] Johnston [bioethicist from the Hastings Center]. “That feeling of wonder and awe reminds us that this is the earliest version of human beings and that’s why so many people have moral misgivings,” she says. “It reminds us that this is not just a couple of cells in a dish.”

A safety concern with gene editing


Hat-tip to Dr. Joe Kelley for bring this to my attention…

As readers of this blog will recall, there is keen interest in exploiting recent discoveries in genetic engineering to “edit” disease-causing gene mutations and develop treatments for various diseases.  Initially, such treatments would likely use a patient’s own cells—removed from the body, edited to change the cells’ genes in a potentially therapeutic way, then return the altered cells to the patient’s bloodstream to find their way to the appropriate place and work to treat the disease.  How that would work could differ—make the cells do something they wouldn’t normally do, or make them do something better than they otherwise do (as in altering immune cells to treat cancer); or maybe make them work normally so that the normal function would replace the patient’s diseased function (as in altering blood cells for people with sickle cell anemia so that the altered cells make normal hemoglobin to replace the person’s diseased hemoglobin).

Or maybe we could even edit out a gene that causes disease (sickle cell anemia, Huntington’s disease) or increases the risk of disease (e.g., BRCA and cancer) so that future generations wouldn’t inherit it.  Or maybe we could edit genes to enhance certain health-promoting or other desirable qualities.

The recent scientific enthusiasm for gene editing is fueled by the discovery of the relatively slick and easy-to-use (if you’re a scientist, anyway) CRISPR-Cas9 system, which is a sort of immune system for bacteria but can be used to edit/alter genes in a lot of different kinds of cells.

It turns out that cells’ normal system to repair gene damage can and does thwart this, reducing the efficiency of the process.  The key component to this is something called p53, a critical protein that, if abnormal, may not do its repair job so well.  When that happens, the risk of cancer increases, often dramatically.  In cancer research, abnormal p53 is high on the list of culprits to look out for.

Two groups of scientists, one from the drug company Novartis and one from the Karolinska Institute in Sweden, have published on this.  P53’s thwarting of gene editing is particularly active in pluripotent stem cells, that are some, but not the only, candidate cells to be edited to create treatments.  These cells are also constituent cells of human embryos.  If the CRISPR-Cas9 process is used on these cells, p53 usually kills them off—unless it’s lacking or deficient, in which case it doesn’t, but also in which case it means that the altered cells could themselves become cancers, later on.

This is something that has to be monitored carefully in developing cells as medicines, so to speak, with genetic editing.  One does not want the patient to appear to be healed, only to develop a cancer, or a new cancer, later on.  One certainly would want to know the risk of that before editing an embryo—an unborn human, a future baby if placed in the right environment—to create a gene-edited human being.

Yet, as I’ve written here in the past, it appears that experimentation in heritable gene editing is pressing on.  I’ve argued, and continue to argue, that heritable human gene editing is a line that must not be crossed, that would place too much trust in the providence of the scientists/technologists who are the “actors” exerting power over fellow humans who become “subjects” in a deep sense of the term; that the risks to the subjects are undefinable; that it would enable perception of humans as “engineering projects”; that the gift of life would tend to be replaced by seeking to limit birth to “the people we want”; that the people acted upon are unable to provide consent or know what risks have been chosen for them by others, even before birth.  Rather than press ahead, we in the human race should exercise a “presumption to forbear.”

A counter argument is that, in limited cases where the genetic defect is limited and known, the disease is terrible, treatment alternatives are few or none, that the risks are worth it.  The recent papers seem to expose that line as a bit too facile.  How many embryos created (and destroyed) to develop the technique before “taking it live?”  Could we work things out in animals—monkeys, maybe?  How many generations to alter, create, and follow to be sure that a late risk—such as cancer—does not emerge?  Or maybe our animal rights sensibilities stop us from putting monkeys at such risk—maybe mice will do?

The new papers are dense science.  Frankly, I can grasp the topline story but have trouble digesting all the details.  More sophisticated readers will not be so impaired.  The news report, in the English of the general public, can be read here, the Novartis and Karolinska reports read (but not downloaded or printed) here and here, respectively.

DIY CRISPR Kits – Gene Editing for the Rest of Us

One might think with the amazing advance of technology and easy access to nearly infinite data via the Internet that we, as a society, would see a reduction in false claims of benefit for novel medical procedures and untested medications. Sadly, it seems to be just the opposite. I seem to be spending gradually more time with my patients reviewing the results of their internet research for new solutions for their chronic back pain. Their efforts are laudable even though the “hoped for” benefits claimed in their researched solutions are woefully lacking. Unfortunately, often this exercise in reviewing the outside data takes valuable time away from the remainder of the office visit.

Reviewing false or confusing information is one thing but preventing patients from self-experimentation with untested medications or unproven treatments is another. Enter the biohacker and companies offering do-it-yourself (DIY) kits claiming to allow anyone to experiment with CRISPR (a method of genetic editing) for self-administration. Emily Mullin covers biohacking and DIY CRISPR very nicely in her recent article in the December Technology Review. To me, this has the feel of the 1980s when a curious kid with some basic programming knowledge, an inexpensive computer and a modem can access previously forbidden government systems, potentially unleashing havoc on the rest of us (WarGames, anyone?) After all, now that we know the human genetic code, all we need is for someone to just provide the instructions and tools for editing that code, then anyone could tweak their own DNA. Easy peasy lemon squeezy, right?

Recently, the FDA has been busy trying to prevent medical clinics from administering untested stem cell treatments (see Neil Skjoldal’s recent November blog entry on (Stem Cell Clinics & the FDA). Imagine the significant increase in the scope of the regulatory problem if individuals can order a DIY CRISPR kit off the Internet!

While we might chagrin at the naiveté required to believe the street-side pitch of the Old West Carter’s Little Liver Pill salesman, that same pitch via a modern tech savvy YouTube video (complete with separate internet links) somehow offers a new level of legitimacy. The Technology Review article speculated that one of the featured companies was preparing not a vaccine but a treatment for herpes. In less than 8 weeks from the article’s publication, Aaron Traywick, CEO of Ascendance Biomedical, publically self-injected himself with his firm’s untested and non-FDA approved “treatment” for herpes. The linked article by Reegan Von Wildenradt in the popular magazine Men’sHealth offered an excellent counter as to why this type of “science” might be suspect, including quotes from ethicist Arthur L. Caplan at NYU in support of the standard FDA process for screening medical treatments.

We often lament in this blog that technology is advancing so rapidly that we fail to have a fair public hearing and discussion of the ethics involved in a particular biomedical advance. Now it seems our time may be better spent speaking out first about the basic risks of the new technology and doing our best to support the FDA in their massive task of policing the Internet to prevent a DIY CRISPR kit from falling into the wrong hands – ours.

P.S. – I’m accepting names for the title of the future Hollywood blockbuster where the son of Matthew Broderick and Ally Sheedy injects himself with his own DIY CRISPR-modified DNA and …

“Nervy” SHEEFs, pain, and moral status

In May of this year, my brief essays (literally, “attempts”) on synthetic human entities with embryo-like features, or SHEEFs for short, sought to ask what sort of human cellular constructs might or might not enjoy full human moral status; to wit, the right to life.  Some experimenters with SHEEFs have suggested that, since they may bypass the early (14 days of life) markers that normal, or (if you will) canonical, human embryos demonstrate, a different moral approach is needed to determine ethical boundaries for these experiments, and the suggestion was that the capacity to feel pain would be a good substitute.

In my May 11 post, I suggested that a SHEEF with even part of a human nervous system must be accorded the right to life.  I made what is, I confess, a breezy connection between said nervous system, however rudimentary, and the identification of a human soul, on the grounds that bodily expression of human capacities commonly is through the effects of the nervous system.  The capability of any such capacities, I wanted to hold, would mark a SHEEF as a “human being” deserving of moral status.  This would distinguish it from, for example, a tissue-engineered trachea, or a kidney, or maybe even a heart, although human heart have, in their automatic conduction systems, a sort of “nervous system” capacity, I suppose.  Still, it didn’t seem to me (Edgar Allan Poe notwithstanding?) that a tissue-engineered heart would be considered a “human being,” the sort of being with “the intrinsic capacity to develop sentience, to ponder the universe, to comprehend the inevitability of mortality, to seek purpose, to yearn for love, and to suffer?”

That last quoted phrase is from a welcome essay by Dr. William Cheshire in the Fall 2017 edition of the journal Ethics & Medicine.  In his essay, “The moral significance of pain for synthetic human entities derived from embryo-like cells,” he argues, to put it all too briefly, that the ability, the realized capacity, to feel pain is an inadequate marker of human moral status.  Why?  Because some humans are incapable of nociception—physical responses to noxious stimuli.  Indeed, local anesthetic makes an otherwise fully-thriving human numb, for a while.  To say that all SHEEF experiments are OK as long as the entity doesn’t feel pain is to reduce meaning to pain, pleasure, and happiness.  Dr. Cheshire muses about a hypothetical creature, designed and bred in the laboratory, that is “sentient…possessing a complete brain composed of human neurons, yet lacking critical genes necessary for the capacity to experience pain…Rather than ask, what does it mean for a human organism to experience pain, a better question is, what does it mean to be the kind of being that experiences pain?  What does it mean to be the kind of being who has “the intrinsic capacity to develop sentience,” etc?

I was surprised when I saw that Dr. Cheshire chose for an epigram to his essay this sentence from my May 11 post:  “A moral boundary is approached when a human nervous system is brought into the plan.”  I read his essay as a criticism of my approach, but I still think the latter has merit.  I still think that some human tissue engineering with some SHEEFs might be ethical.  At the same time, I think that attempts to make too complete, too complex a SHEEF—for example, one with a whole human body except the head—would be monstrous.  I suppose that such a being would have to have a fair amount of human autonomic nervous system to function at all, and so would fall under my criterion.  And I also think that a quest for a “minimal human genome” or a “minimal human” would be frankly unethical.  (I understand synthetic biologists to be interested in the former but nobody to be suggesting the latter.)  To be ethical, experiments would have to observe serious limits from the concept stage.  And a concept of “how far can we go before we truly have the kind of being with the intrinsic capacity…?” would be out of bounds.

Check out this June 15, 2017 cartoon from the New Yorker