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

Stem Cell Clinics & the FDA

When any business over-promises and under-delivers, it is well on its way to failure.   Does this principle also hold true in the world of stem-cells?  In the last few months the promise of stem cell treatment has met the reality of government oversight.

Does the government have the responsibility to rein in the larger-than-life claims of stem cell treatment clinics? In a letter dated August 24, 2017 to US Stem Cell of Sunrise, Florida, the FDA cited at least 14 failures relating to the facility’s compliance with federal regulations. It is a powerful letter that makes one wonder what is happening in some of these clinics throughout the country. US Stem Cell responded quickly, re-asserting their claim that they were simply treating consenting patients with their own cells and not subject to the same sorts of regulations that drug manufacturers are.

Is there a place for government oversight over stem cell clinics? At the very least, it could easily be argued that some of their claims are over-the-top and should be subject to false advertising laws.  Michael Joyce makes this point clearly.  He cites the concerns of stem cell researchers Paul Knoepfler and Jeanne Loring. Dr Loring puts it bluntly: “[Stem cell clinics] don’t want to talk to real scientists . . . Because 99 percent of them know they’re pulling the wool over people’s eyes. This is marketing, not science.”

Joyce makes an important point. There are real people with real physical problems who are turning to stem cell clinics as a last resort. If one buys a faulty product from the mall, one has the opportunity to return it for a refund. However, if one receives a faulty medical procedure, how can they be repaid for their loss? In these cases, shouldn’t stem cell clinics be held accountable for misleading the public?

The New York Times describes what happened to some unfortunate individuals who suffered at the hands of US Stem Cell: “The women had macular degeneration, an eye disease that causes vision loss, and they paid $5,000 each to receive stem-cell injections in 2015 . . . Staff members there used liposuction to suck fat out of the women’s bellies, and then extracted stem cells from the fat to inject into the women’s eyes.” They “suffered severe, permanent eye damage…”

Desperate people will try desperate things in order to receive desirable results. It is my opinion that the FDA is acting properly by providing at least a level of protection from those who would exploit the desperation of suffering people.

Human gene editing marches on

Nature has recently carried two new reports of human gene editing.  In one, embryos donated from an IVF clinic had a gene critical to very early development altered, to study what happens when you do that, and try to understand early human development more than we now do.  In the other, scientists studied editing of an abnormal recessive gene, specifically the one causing a type of blood disorder called thalassemia, by using cloning to create a new embryonic version of an adult with the disease.  (This made it technically easier to start in the laboratory with an embryo that has the disease, because it is genetically recessive, meaning that both copies of the gene are abnormal.)  This follows earlier publication of similar work to edit dominant mutation-causing genes, in which the embryos arose because of new IVF, done in the lab, by the scientists, using donated eggs fertilized with sperm from a male donor who carried the abnormal gene.

In all three cases, the main biologic approach, and the main ethical issues, are the same.  The main differences were which genes were being edited, and how the embryos were obtained.

This prompted Nature to run an editorial to say that it is “time to take stock” of the ethics of this research.  Read the editorial here.  The key points:  This is important work that should be undertaken thoughtfully.  Accordingly, donors of any embryos or cells should be fully informed of the planned research.  Only as many embryos should be created as are necessary to do the research.  Work on embryos should be preceded by work on pluripotent, or “reprogrammed,” stem cells, and if questions can be fully answered by work with those cells, then it may not be necessary to repeat the studies on whole, intact human embryos, and if that is not necessary, perhaps it should not be done.  Finally, everything should be peer reviewed.

I agree that editing work in non-totipotent cells should be at all times favored over work on intact embryos, but if one holds that an embryo is a human being that should have the benefits of protections afforded human research subjects, then Nature’s ethical principles are rather thin, little more than an extension of animal use provisions for studies in which early humans are the raw materials for the development of new medical treatments.

Included was a link to the journal’s policies for considering for publication any reports of experimentation on living organisms.  Those policies include this paragraph regarding modification of the human germline:

“In deciding whether to publish papers describing modifications of the human germline, we will be guided by safety considerations, compliance with applicable regulations, as well as the status of the societal debate on the implications of such modifications for future generations. We have established an editorial monitoring group to oversee the consideration of these concerns. (The monitoring group includes the Editor-in-Chief of Nature publications, the Nature Editorial Director, the Head of Editorial Policy, Nature Journals and the Executive Editor, Life Sciences.) This group will also seek advice from regulatory experts to ensure that the study was conducted according to the relevant local and national regulations. In this evaluation, we will be strongly guided by the guidance issued by the International Society for Stem Cell Research: Guidelines for the Conduct of Human Embryonic Stem Cell Research (http://www.isscr.org/home/publications/guide-clintrans ).”

I want to be reassured by their invoking “the status of the societal debate on the implications of such modifications for future generations,” but the weaknesses are first, that debate is just not very robust, and “society” is generally in a position of accepting, more or less uncritically, the ongoing technical push; and second, that the ones considering the status of the issues will more or less naturally view them through the relatively narrow researchers’ scope I describe above.  To be sure, the goals at a minimum appear to be to ensure that the research is not reckless, that it meets technical standards, that obtaining and creation of embryos is relatively limited in scope, and that nobody, for now, is trying to bring gene-edited embryos to human pregnancy, much less birth.  At least, not until the scientists and regulators tell us they think it’s time to try that.

Is Obfuscation Ever Helpful in Science or Ethics?

Obfuscation and science would seem to be polar opposites. The scientific method hinges upon correctly identifying what one starts with, making a single known alteration in that starting point, and then accurately determining what one ends up with. Scientific knowledge results from this process. Accidental obfuscation in that three-step process necessarily limits the knowledge that could potentially be gleaned from the method. Peer review normally identifies and corrects any obfuscation. That is its job. Such peer review can be ruthless in the case of intentional obfuscation. It should be. There is never any place for intentionally misrepresenting the starting point, the methods or the results.

Until now?

In an excellent article in Technology Review, Antonio Regalado describes the current status of research where human embryonic stem cells “can be coaxed to self-assemble into structures resembling human embryos.” The gist of the article is that the scientists involved are excited and amazed by the stem cells’ ability to self-organize into structures that closely resemble many features of the human embryo. Perhaps more importantly, per Regalado:

“…research on real human embryos is dogged by abortion politics, restricted by funding laws, and limited to supplies from IVF clinics. Now, by growing embryoids instead, scientists see a way around such limits. They are already unleashing the full suite of modern laboratory tools—gene editing, optogenetics, high-speed microscopes—in ways that let them repeat an experiment hundreds of times or, with genetic wizardry, ask a thousand questions at once.”

This blog has reported on Synthetic Human Entities with Embryo-like Features (SHEEFs) before (see HERE and HERE for starters). The problem from a bioethical standpoint is this: is what we are experimenting upon human, and thus deserving protections as to the type of research permitted that we presently give to other human embryos? Answering that ethical question honestly and openly seems to be a necessary starting point.

Enter the obfuscation. Consider just the following three comments from some of the researchers in the article:

When the team published its findings in early August, they went mostly unnoticed. That is perhaps because the scientists carefully picked their words, straining to avoid comparisons to embryos. [One researcher] even took to using the term ‘asymmetric cyst’ to describe the [amniotic cavity-like structure] that had so surprised the team. “We have to be careful using the term synthetic human embryo, because some people are not happy about it,” says [University of Michigan professor and lab director Jianping] Fu.

“I think that they should design experiments to focus on specific questions, and not model everything,” says Insoo Hyun, professor and ethicist at Case Western University. “My proposal is, just don’t make the whole thing. One team can make the engine, another the wheels. The less ambiguous morally the thing is that you are making, the more likely you can do your research unimpeded.”

“When Shao presented the group’s work this year, he added to his slides an ethics statement outlined in a bright yellow box, saying the embryoids ‘do not have human organismal form or potential.’”

This last comment seems to contradict the very emphasis of the linked article. As Regalado nicely points out: “The whole point of the structures is the surprising, self-directed, even organismal way they develop.”

Honestly, at this point, most are struggling to understand whether or not the altered stem cells have human organismal form or potential. I suspect everyone thinks they must or else researchers would not be so excited to continue this research. The value of the research increases the closer a SHEEF gets to being human. If our techniques improve, at what point does a SHEEF have the right to develop as any other normal embryo? Said differently, given their potential, and particularly as our techniques improve, is it right to create a SHEEF to be just the engine or the wheel?

Having scientists carefully picking their words and straining to avoid comparisons is not what scientists should ever be doing. Doing so obfuscates both science and ethics. Does anyone really think that is a good thing?

Bioethical Jets and Sharks

Recently, Professor Craig Klugman called on the President to set up his Presidential Bioethics Commission. He provides a nice history of Presidential Bioethics Commissions dating back to President Ford. The link to that article is HERE. Other than the usual implication that the President may not be intellectually up to the challenge, I agree with Professor Klugman that there are many pressing bioethical issues that will or ought to affect policy in the not-too-distant future, so I also join the chorus to call for the President to set up his bioethics commission.

Professor Klugman’s plea for such a commission followed an earlier one by Wesley Smith, who called for a “populist” bioethics commission. He admits to desiring a less intellectual or less philosophical commission so we are not limited to receiving only “arcane advice”, preferring instead to have “the verbal equivalent of West Side Story’s knife fight between the Jets and the Sharks.” I admit that a commission with that type of energy would be fun to follow and certainly generate more public awareness of bioethics.

This got me to wondering: What do the readers of this blog consider to be the most pressing bioethics issue? Specifically, if the President listens to Wesley Smith and appoints you to the populist Presidential Commission on Bioethics, what is the one issue you want to make sure makes the list for 2017-2020?

For me, I favor a robust re-examination of what we as a country will permit or proscribe in embryological research, particularly within the first 28 days of the life of the embryo. Within this blog, Jon Holmlund has outlined nicely the technological advances outpacing bioethical consensus in the area of Synthetic Human Entities with Embryo-like Features (see SHEEFs Part 1 and Part 2) and Steve Phillips recently highlighted similar issues in the field of IVF (HERE) just to name a few.

So what is the number one bioethical issue on your list?

And remember, if Wesley Smith’s description of the potential energy in those future debates is accurate: You may want to bring more than a knife to the fight (verbal equivalently speaking, of course…)

All we like SHEEFs (?)

So, how should we address the moral status of synthetic human entities with embryo-like features (“SHEEFs”)?

First, we should consider that these are human, as opposed to non-human, if they arise entirely from cells of human origin.  Human/non-human hybrid creatures are just that, and partially human, biologically.  But are any of these human beings, as in, in California the crime of murder is described as against a “human being?”  Or as in, a being that natural rights, most fundamentally a right to life?

Scientists make human/non-human hybrids now that clearly do not have the same moral status as a human being, e.g., immune-deficient mice whose immune systems are reconstituted with human blood cells (SCID-hu mice).  And, collections of human tissues that are far from a whole individual are still human, but not human beings.  That’s easy.

Ultimately, the question at the top of this post will be irredeemably tangled if one holds, as many if not most in the West today do, that human life with the right to life begins only sometime after the conception of a new human being; if a human being’s moral status, privilege, or rights vary depending on how much that being is able to exercise common human capacities, like choice or conscious self-reflection; if all moral questions turn on calculi of benefits and harms that must weigh individual human rights against the rights of groups of humans; if there is no natural moral law and all moral principles are fluid depending on the shifting consensus of a community.

If one holds, as I do, that human life begins at conception and that there are at least some foundational moral laws, and that a right to life is not dependent on varying realization of human capacities, then it seems that any human entity that is capable of developing into an entire human organism bears a full right to life from the first moment it comes into existence; i.e., conception, whether in the lab or arising from that process accessible even to educated fleas; or first existence of a totipotent cell, be it cloned, from an extended pluripotent stem cell, from in vitro gametogenesis with induced pluripotent stem cells, or from a future “manufacturing” process.   To name a few.  The right to life of such human beings is more dependent on their ultimate capacities than on the passage through 14 days of embryogenesis, or, for that matter, even on whether it might prove capable of skipping certain day 14 markers like the primitive streak.  In a sense, the “potential” or nascent human enjoys the right to life precisely because of what it (he or she?) is capable of becoming.  Maybe to say this is to extend Louis Pasteur’s comment that when he saw a child he was filled with “compassion for who [s]he is and respect for who [s]he will become.”

This implies that SHEEFs that are engineered to be very like regular embroys—“embryos in a dish”—deserve the same protections that pro-lifers defend for embryos made the old fashioned way, or by the more new-fashioned approach, IVF.  They should not be created or destroyed for research.  If they are created it should be with the intent of bringing them to term after a gestation (still, and one hopes, forever, in utero).  If that cannot be the intent and the extreme likelihood of a normal human being cannot be established, “embryos in a dish” should never be produced.

What about SHEEFs that combine features in novel ways, e.g., a human beating heart and a brain incapable of pain or sensation; or SHEEFs engineered to develop a nervous system without passing through a primitive streak?  My current thought is that insofar as the development of a human nervous system is “morally relevant,” something that likely would enjoy near-universal agreement, then the SHEEF acquires a right to life at the point of conception.  What is the point of conception?  The design on the drawing board, in the laboratory.  This would imply that such SHEEFs also should never be produced solely for research.  It also seems to imply a difficult, counterintuitive conclusion that if produced, any such SHEEF must be brought to “birth,” if possible.  But what would be the purpose of that except to create such SHEEFs solely for the purpose of some level of experimentation?  So SHEEFs like this also ought never be produced—and, I would argue, should not be drawn up.  The experiment should not be designed or pursued.

What about SHEEFs with recognizable human form and a beating heart but no brain?  Here, I would argue that by “conceiving” of such things one intends an entity that is a severely disabled human being.  Moral commitments would be similar to concerns raised by, for example, anencephalic babies.  They should be cared for.  If they are “created,” what is the purpose?  Solely for research or observation?  Why would we need to do this, in this way?  Just to show we can really do it?

What about human/non-human hybrid SHEEFs?  These, like pigs engineered with human hearts, may pose the most difficult cases.  Here, the issues raised by human/non-human hybrids in general seem germane.  I might suggest that prudence, guided by a concern for “where will it lead?” should pertain, rather than the instrumental question of “what benefits might I make of it?” and “how far shall I push the envelope?”  We should decline to participate rather than embrace pieties about how a regime of regulation will “prevent abuses,” when the fundamental premise of the work is to enable said abuses.

I end this post confessing, as I believe I have in the past, that these are musings of a part-time, less-than-eminent bioethicist, offered to provoke reflection.  I admit they are only partially developed, not fully argued, perhaps flawed.  In invite others to offer constructive criticism and rebuttal, and suggest refinements.  That’s what the comments section is for.