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.


The moral problem of manufacturing children

Mark McQuain’s post yesterday about the moral concerns raised by some of the new things such as in vitro gametogenesis in conjunction with human induced pluripotent stem cells being developed in the field of artificial reproductive technology made me think of something that Leon Kass had written in the early days of in vitro fertilization. In the early years when in vitro fertilization was being hailed as an advance which would provide the ability to have their own biological children to many couples who were suffering from infertility for whom no effective treatment had previously been available, he and others warned that we needed to be morally cautious about this new technology because it would lead to us thinking of children as something that we could manufacture. A significant part of what he and others were saying was that up until that time the conception of children had always been something that was shrouded in a certain degree of mystery. There was an understanding of the miraculous nature of the creation of a new human being, and by those who had a sense of the divine origin of human beings it was understood that every child was a gift from God. This was something that impacted how children were viewed in society and individually by their parents. If each child was a gift from God, made in his image, and received through the natural consequence of the expression of the love the couple had for each other, we could understand that each child should be loved unconditionally. Gilbert Meilaender expressed this love in the words of Joseph Pieper: “Love is a way of saying to another, ‘is good that you exist; it’s good that you are in this world!’”1

While I believe that this concern about how IVF changes how we think about children is a very significant one, it never gained much traction in the society around us. The use of IVF has continued to increase and technology has allowed it to be used in ways that increasingly lead to children being made in a way that is more and more like manufacturing them. We are able to incorporate quality control in this process by the use of preimplantation genetic diagnosis. We can manufacture a child with nuclear DNA from one mother and mitochondrial DNA from another. Soon we may be able to manufacture a child whose DNA may come from two parents of the same sex or four or more parents. That makes me think even more about what it means to manufacture a child. When we manufacture something we do so because of our desire to have the product that we manufacture and to have it meet our own desires for what that product should be and do for us. This is very different than receiving a gift given to us because of the love of the one who gives it. The thing that we make is intended to fill our own desires, which in our society is frequently expressed as a right to reproductive autonomy. Reproductive autonomy is focused on the value of the maker and not the value of the child. A gift that we receive puts our focus on the one who has given it to us and makes the gift valuable just as it is. We need to be careful as a society that the making of children does not turn into a process that is so focused on satisfying the desires of the makers that the value of the children who are made depends on their ability to satisfy those desires and the intrinsic worth of every human child is forgotten.

1 Meilaender, Gilbert, Bioethics: a Primer for Christians, third edition, p.50

Do Extended Pluripotent Stem Cells Raise Ethical Issues?

On April 6, the journal Cell published work (subscription or online article purchase required) from the Salk Institute in San Diego, in which scientists have created a new “reprogrammed” stem cell.

These cells are called “extended pluripotent stem cells” or “EPS” cells.  They are different from embryonic stem (ES) cells, which are removed from intact embryos that arise from fertilization—typically requiring specific creation and destruction of an embryo.   Of course, ES cells can be human or non-human, depending on the source.

EPS cells are similar to “induced pluripotent stem cells,” or iPSCs, invented in 2006.  The latter are generated from adult skin cells that have been reprogrammed, using genetic alterations.

EPS cells may be made by reprogramming ES cells or skin cells or, if I understand the work correctly, iPSCs.  In this case, the reprogramming is done with a cocktail of chemicals in the lab.

But EPS cells are more capable than iPSCs.  Unlike iPSCs, which can give rise to many different types of cells but not all—including not a placenta and not an entire intact new individual—EPS cells can do all of that.  They are totipotent, meaning they can make all the cells of an individual from their species.  Moreover, they are quite long-lived in the laboratory.  EPS cells from one species—e.g., humans—can be placed into non-human (e.g., mouse) embryos to make hybrid animals that, it appears, survive quite well and can breed.  And, remarkably, the authors of the Cell paper report (again, if I understand correctly, and I think I do) that they were able to use a mouse EPS cell to give rise to a whole new mouse, not “just” a laboratory tissue hybrid.

Upside?  A remarkable, easy source of totipotent cells that appear easy to derive, without requiring production or destruction of embryos, and use in the laboratory, enabling a wide range of research into embryonic development.

The downside?  To read a report in my local paper, the San Diego Union-Tribune, apparently not much.  That paper quotes a couple of stem cell experts, one also a Roman Catholic bioethicist, as saying that EPS cells really don’t pose much of a moral issue.  The other quoted expert says that it would be a “misconstrual” to think this work poses an ethical problem “(i.e., creating whole ‘designer’ organisms from a single cell…).”  These statements are printed a couple of columns after the statement, remarkably breezy in my view: “[The Salk scientists] have even created human EPS cells.  But legal and ethical considerations have prevented them from trying to turn those cells into babies.”

Say what?

It seems that EPS cells are another step toward eventual synthetic organisms.  The Salk scientists successfully, and stably, made mouse-human hybrids by injecting a single human EPS cell into a mouse embryo.  At a minimum, that work would seem to raise similar ethical issues as those raised by animal-human chimeras more broadly.  Indeed, the senior scientist on the recent paper has been working on human-pig hybrids, with growth of human organs, in pigs, for transplantation in eventual view.  “It will be very interesting,” his colleague said, “to test [EPS cells] in the pig.”

And, if mouse EPS cells can be used to give rise to (dare I say “make?”) a whole mouse, what in principle would prevent using human EPS cells to give rise to a baby?  This prospect would seem to invoke ethical concerns substantially similar to those posed by human cloning.  And, because EPS cells can also give rise to non-embryonic tissues, including placenta, needed for reproduction, then ex vivo gestation could be envisioned, although one certainly could not say that it “can’t be far behind.”  There would be rather some distance yet to cover.

So, readers, please set me straight—if this development is indeed not troubling, then what am I missing?  Where am I going wrong?  Or am I raising concerns that “used to be considered germane,” but maybe are not anymore, because we’ve gotten used to the ideas involved…

The comments line is open.

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.


Equipoise and Caution Regarding “Ethical” Stem-Cell Therapy

You may have seen one of the many news reports this week about an “adult” stem cell treatment gone bad.  In it, doctors, not working in regulated industry or in the bounds of a clinical trial, injected stem cells derived from a person’s fatty tissue into the eyeballs of three people in an attempt to treat a vision-destroying condition called macular degeneration—and all three lost what remaining vision they had.  T

In a separate experience, two people received “reprogrammed” stem cells, also called “induced pleuripotent stem cells” or “iPSCs,” for the same condition, and they did not appear harmed, and may have been showing early signs of improvement, one year later.  In this second case, the cells are described as having undergone rigorous quality testing before being injected into the patients’ eyeballs.

The two cases are described in this week’s New England Journal of Medicine.  The links above are to those reports; subscription may be required to read them.  NEJM makes some of its editorials and perspective pieces generally available, other articles not.  Two such articles, one from FDA and one from a physician at Boston Childrens’ Hospital, address these cases.  In both opinion articles, the authors argue that careful regulation and quality control of stem cell studies is critical to their ethical testing.

To say this position is hard to argue with is a gross understatement.  I will confess that on this blog, in the past, I have wondered whether some use of “adult” or “somatic” stem cells is over-regulated, as, for example, when such cells are obtained from a woman’s fatty tissue, and reinjected into her in an attempt at breast reconstruction after surgery.  I’ve seen proposals in the past for work like that, and it seemed pretty straightforward—recovering a cell layer from a centrifuge, and reinjecting, all under sterile conditions.  The doctors in question in the case I saw were not in any way trying to cut any corners.  But existing regulation would have prevented their proposed breast-surgery work without a couple million dollars’ worth of the kind of work needed, and usually funded by industry, before commencing human trials of a new treatment.

The macular degeneration cases do indeed push one back in the direction of regulation.  Injecting into the eye is rather riskier than some other uses.  There are established clinical uses of adult stem cells—notably in bone marrow transplantation, potentially in other cases.  But it can be too easy to miss risks.  We should have our “hype detectors” well calibrated when it comes to stem cell therapies, even with those that use ethically-derived cells (i.e., not from the creation or destruction of human embryos).

Heritable human gene editing and the public

The recent report by the National Academies of Science, Engineering, and Medicine includes a chapter dedicated to public engagement.  Scientists leading gene editing efforts have actively sought broader public engagement, and point out that they desire this input, including from people who disagree with them about it.  They may push to win any arguments, but for the most part they don’t seem to be hiding.  I say “for the most part” because there have been apparent exceptions, such as the closed door meeting described last May that ostensibly was to discuss industry involvement in so-called “HGP write,” a proposal to synthesize an entire human genome in the laboratory and put it into a cell within 10 years.

The recent report from the National Academies points out that any ethical restriction in the U.S. on human genome editing would require legislation.  FDA does not have authority to apply restrictions other than lack of safety or efficacy.

Effective public engagement, according to the report, should address the widest possible range of effects, options, and facts and values surrounding gene editing, permitting the general public to ask questions and suggest solutions that may not have occurred to the experts.  Processes should also be transparent and, of course, lawful.  This would ensure the best, most legitimate decisions possible in a free society.  The best process would communicate, educate, consult with, and draw participation from not only interested insiders and advocacy groups but the wider public.  But the processes should also be efficient, not overly drawn out.  And what is in view is not just “selling” the idea to the public.  Rather more equipoise is envisioned.

So are there examples of public engagement processes that work?  The report cites examples in the U.K., Denmark, and France of government initiatives actively to recruit the broader citizenry in ethical policy discussions.  Denmark’s comes in for more detailed attention: a serious report is produced by actively involved citizens, but the process is still too top-down and open to gaming that tends to guarantee participation by interested insiders.  I would say we shouldn’t be surprised by this.  In the U.S., the report comments that most of the venues (government regulatory rule-making, FDA advisory committees, Presidential bioethics panels) are too passive from the public’s standpoint.  Amen to that.  The report also states that “[t]o the extent that some policy can be formulated at the state

level, as has happened in some states with respect to embryo research, cloning, and funding for

stem cell research, the states themselves can be stakeholders that engage with the federal

agencies (albeit with complex goals that include concerns about state power and independence).”  For real?  They suggest that America’s political culture war regarding embryo and stem cell research is a good model?  To my mind, that is just a case in point for how hard it is to get meaningful public engagement on big bioethical matters.

“Lessons learned” include a need to realize that public engagement is not public opinion research, and a commitment to developing information resources that are developed not only by technical experts, but by people who use “empirical social science” to minimize bias.  How one asks the question goes a long way toward determining the answer.  And one can only think of the difficulties in defining informed consent for human research subjects to imagine the many pitfalls.

The report’s recommendations suggest that actually trying heritable gene editing in a (preborn) person should NOT be attempted until a better, formal public engagement process is developed that ties directly into policy-making.  The recommendations include more research and information-gathering on effects of heritable gene editing and public attitudes about it.  To some degree, the report throws the onus back onto the medical scientists—“your grant should include money and a project to obtain/assess public engagement.”  That’s easy to say, hard to do—something that creates the risk of making it up as one goes along, with attempts that really aren’t feasible.

This chapter in the report includes a lot of good reflection.  But its recommendations are unavoidably overoptimistic.  The sheer magnitude and complexity of the effort suggested, and the difficulty in obtaining and adjudicating input from a wide range of people, many of whom simply aren’t engaged in current affairs to begin with, is staggering.  Add to that how television and social media have degraded anything resembling public discourse, and one is tempted to respond to this part of the report “Nice try, but when pigs fly.”

Anywhere to start?  For readers of this blog, maybe in the churches and with pastors.  The current issue of Christianity Today includes a game but all-too-brief essay by a pastor in Cambridge, Massachusetts who was approached by Harvard biotechnologists seeking public input into the ethics of human genome editing.  And the pastor-author, heavily degreed in economics and theology, writes that he concluded he simply would have to try to learn something about the matter.  Were there members of that congregation who could have helped brief him and the other clergy and laypeople?  We don’t know.  But readers of this blog know some people like that, don’t we?


Still further on heritable human gene editing

I want to spend a little time—several consecutive posts—on the subject of heritable gene editing in humans, and on the recent report by the National Academies of Science, Engineering, and Medicine on it.  The topic bears more attention than a single blog post, written in a bit of a rush, based on only the initial release of the report, pending a deeper dive.  That is where I have been until now.

At the link above, one can download for free a pre-publication pdf of the full, book-length report.  (Last week I had found a 4-page summary that I can’t seem to locate again this week.)

Less than 15 months ago, in early December 2015, the Washington Post was reporting that “experts” were saying “It’s too early for gene-editing of human reproductive cells.”   Some, like Nobel laureate David Baltimore of Caltech, drew the line at attempting to establish a human pregnancy with an implanted embryo that had been gene-edited.  Others working in the field were writing that even a moratorium on laboratory studies of editing human sperm or egg cells was wise.  Then, as now, these experts (and they truly are experts, providing careful reflection for public benefit and guidance) were calling for more public input before pushing ahead.

Still, in a separate brief summary of the new report’s key points, the committee that prepared it says, first, that laboratory studies of editing human egg or sperm cells, the cells that produce them, or early human embryos “is essential to the advancement of science and should continue with[in] existing regulatory structures.

What has changed in less than 15 months?  May I suggest, nothing?  Last week, I used the words “runaway train.”  To be sure, I hear something of the same worry behind the experts’ just-released report.  In the 4-page summary I have, they write, that developing policies around human genome editing is “pressing, in large part, because of the…growing use of the CRISPR/Cas9 system.”  Growing use, as in, exploding.  I think we can concur with the committee about the urgency of the matter.

But, again, the experts seem to have moved from “don’t proceed with any pregnancies from this” to “clinical research trials could be permitted” only under a set of circumstances that are carefully controlled, at least to the extent possible.  In my post last week I copy-pasted their full list, the shorter form of which includes the following critera:

  • Absence of reasonable alternatives
  • Restriction to editing genes that have been convincingly demonstrated to cause or to strongly predispose to a serious disease or disabling condition
  • Availability of credible pre-clinical and/or clinical data on risks and potential health benefits of the procedures
  • Ongoing, rigorous oversight during clinical trials of the effects of the procedure on the health and safety of the research participants
  • Comprehensive plans for long-term, multigenerational follow-up while still respecting personal autonomy
  • Continued reassessment of both health and societal benefits and risks, with broad on-going participation and input by the public

IF one were going to allow attempts to, for example, prevent or “genetically cure” sickle-cell anemia prenatally, one would want to meet these criteria.  But suppose we could meet them all, except for of course the multigenerational follow-up, which would take time.  Suppose we knew beyond a shadow of a doubt that, in this case, the sickle hemoglobin gene mutation, a single point mutation, were definitively and selectively repaired in a new unborn human being, and we could treat a small but sufficient number to know that, at least into their young adulthood, they had no other adverse health consequences whatsoever, and maybe even had begotten unaffected infant children.  Would we consider this an unambiguous good?  I’m not so sure.  For one, we would have formed, in the first instance, an absolute dependence on in vitro conception—not that such is not the state of affairs in many cases, anyway.  But a mindset that “procreation the old fashioned way” is too dangerous would be fostered.


For another, the past and ongoing basic research would have included creation and destruction of human embryos—nascent human beings—for research purposes.  Well, maybe the horse would have left the barn, as is argued for the development of certain vaccines now widely in use.


The National Academies’ report focuses on human uses of gene editing—“gene therapy,” enhancement, and heritable changes.  Meanwhile, on the European continent, apparently they are not so sure whether they want to permit gene editing in plants.


And, of course, where there’s cutting edge science, there are patent applications, with an uncertain outcome in part because the techniques are already moving beyond CRISPR/Cas9.


More to follow on this.  In the meantime, interested readers may also want to revisit this short treatment of the topic.

Can We Be Okay With Chimeras?

In a post yesterday, Jon Holmlund, in typically erudite fashion, addressed the ethical issues that arise from the findings of a published study which looked at the potential use of genome technologies to (someday) produce human organs in animals. I will begin by saying that I have no particular disagreement with Jon’s assessment. There is a lot that is troubling in this research, as much good as it could eventually do, and we need not embrace it just because it has the chance to help people. Many of us have have taken an ethical stand against embryonic stem cell research, for example, because it ultimately violates the dignity of human beings, regardless of its intended benefits.

Yet I do find myself troubled, aesthetically and emotionally, at least, by the contention of the esteemed Charles Krauthammer that this research would ultimately provide “spare parts.” I suspect that, to the parent of a child with a congenital liver disease, a donor organ would hardly be considered such. That doesn’t constitute an ethical argument, for there are many unethical ways to procure organs and we invent more all the time. But it is a reminder that these discussions aren’t restricted to the theoretical firmament of the molecular biologists.

It’s in the public forum now. A recent article in the New York Times addressed this research and spoke to the continued disparity between the tremendous need for healthy human organs in waiting patients and the great scarcity of those organs available from donors. The article estimates 76,000 people are currently on a waiting list. Stem cell therapy, for all its successes in treating a host of diseases by way of human adult stem cells, has not had success with in vitro development of human organs for transplantation. Enter “chimeras.”

To be honest, there is much about the very notion of “chimeras” (which are a blend of the cells of two or more species, in this case: human and non-human animal, which this post addresses) and “human-animal hybrids (a blending of the DNA of both species) that I find troublesome, or even “creepy,” in an Island of Doctor Moreau-kind of way. And concern is warranted. Much of the research for which some scientists are seeking advocacy would do exactly what Jon (and Dr. Krauthammer) expressed: place pluripotent stem cells into another species (likely pigs or, less likely, sheep) and “pull the trigger.” In the article there is an implicit assumption that we must be cautious. The Times tries to be clever here: “No-one wants a talking pig.” But even a slight risk that this could place human cells into the central nervous system or reproductive germline of animals should be chilling.  And yes, we need to have a compelling explanation of this concern to offer the suffering and those who wait with them for new organs.  This is a risk not worth taking.

But I am also haunted by a bit of an escape clause: there is technology that could avoid the bulk of what I find ethically problematic. I have less fear of some mix of human and animal tissue…certainly “xenotransplantation,” like implanting a pig’s heart into a human being, whatever its successes or failures, isn’t really an ethical problem to most. What if the use of  the “CRISPR-Cas” gene editing system, which would allow for specific genes that code for targeted organs, could be used?

This technology, to which the original Cell (and NYT) article alludes, would mean that the animal embryo with implanted human stem cells did indeed avoid involving any human tissue in the non-specific organs of the host animal, particularly the brain and reproductive systems. Could that blunt much of our argument against this…one that says that the brain and germline are “off-limits,” but that we could find ethically-acceptable ways to provide organs for waiting patients using animals we already use for human food?

To be honest, I have my own qualms about CRISPR-Cas, largely because I don’t know a lot about it. It may indeed involve its own ethical problems, despite any protestations from its proponents. And once we go down this road, it makes it harder to say that, in particular, brain tissue is “off limits.” I get that. I would need to be convinced that this technology would do exactly what it is supposed to do. But I want to be sure my acceptance or rejection of any technology is soundly rooted in a consistent ethic that is appropriately nuanced.

I say all this to open the conversation…perhaps more to have the wiser inform me. But I do wonder…in this very specific way, are we able to keep the door slightly ajar without rejecting the technology outright? Does that keep us in the conversation? Within strict boundaries, can we be, indeed, be okay with chimeras?

Last week’s “Loser of the Week”: the Human Race

Every Friday, on the Fox News “Special Report,” anchor Bret Baier asks his panelists to choose a winner and loser for the week.  Last week, Charles Krauthammer’s “loser” choice was “the human race.”  Why?  Because of the first peer-reviewed publication (in the journal Cell, freely available online via the link) of work to produce pig-human hybrid embryos—pig embryos with human stem cells implanted, making a creature that is part human, part pig.  The eventual goal is growing human organs in pigs for transplantation in humans.

Now, good things arguably could come from this work, and it looks like they did not use embryonic stem cells obtained from destroyed human embryos, and the process is still inefficient so that “clinical use is years away.”  And when Baier asked Dr. Krauthammer, “Do you have a picture?” which, as we know, is what television demands, the response was no, it’s tiny, not grown to a size where it could be born.  (Yet.)  So if we can’t see it we can’t appreciate the implications—it doesn’t connect, kind of like a lot of folks see embryos as less than human because they don’t look like people…

Dr. Krauthammer said, “The implications of this are simply staggering.  We shouldn’t be doing anything near this, despite the fact that it holds out some promise for making spare parts.

“If you’re not scared by this, you don’t understand what’s going on.”

So he said in 30 seconds what I’ve been arguing, most recently in an August 4, 2016 post about changes in U.S funding for this research.

There are some avenues of work that simply should not be pursued.

Fetal tissue research furor continues

At the end of 2016, the Select Investigative Panel of the House Energy and Commerce Committee published its report—all 485 pages—of its investigation into procurement of tissue from aborted fetuses for research.  The investigation had been prompted by the 2015 undercover videos from David Daleiden and his “Center for Medical Progress,” which was adduced to support charges that Planned Parenthood clinics, in particular, had violated existing federal law in the performance of abortions and transactions to provide tissue from aborted fetuses to firms supplying medical research.

The Committee’s majority, of course, was Republican.  The Democrat minority on the Committee published a rebuttal.  The Executive Summary of that can be found here, and one link to the full minority report is here.

The majority report, as publicized, takes Planned Parenthood and several entities to task, and the minority rebuttal not only defends those groups but decries the majority’s tactics in the hearings.  I don’t intend to comment on those here.

Rather, I want to make limited remarks about the scientific contentions between the majority and its critics.  The journals Nature and Science have pushed back on several fronts.  In particular, the editors of Nature called the report “fantasy politics” that revised “the long history of the role of fetal-tissue research in vaccine and therapy development.”  The editors, writing, I suppose, under space constraints and the assumption that their audience knew that history as they know it, did not recount details.  The majority report does go into considerable detail, on pages 376 and following.  As I read the report, the majority admitted that fetal cells have been used in vaccine research and production, but their argument was that such cells need not be.  (Another Nature writer helpfully points out that the cells in question are cell lines, particularly two called WI-38 and MRC-5, used most notably in the development of vaccines against Rubella.)  The majority claims that the science of vaccine research has moved beyond the need for new fetal tissues.

Science took this point on directly, listing several vaccines that are still produced in WI-38 or MRC-5, rebutting statements in the majority report that fetal cells had “never” been used to produce a polio vaccine, and that “none” of the currently-licensed vaccines in the US are produced using fetal cells.

On the face of it, Science appears correct, but here’s a more extended excerpt from the majority report (pages 379-380, references eliminated from post for brevity but present in the original):

“The fetal-derived cell lines WI-38 and MRC-5 were adopted by the pharmaceutical industry as tools for the production of vaccines shortly after they were developed in the 1960s.And for a small minority of vaccines, these tools are still used today. However, these historic fetal-derived cell lines are still in use today for primarily economic, not scientific reasons. Obtaining FDA approval for a new vaccine is very labor intensive and costly. Consequently, once FDA approval has been secured for a particular method of producing a vaccine, Pharmaceutical companies tend to rely on this method, to avoid incurring new costs associated with “validating” the safety and efficacy of new procedures. Three major Pharmaceutical players (Merck, GlaxoSmithKline and Sanofi) adopted the fetal cell lines MRC-5 and WI-38 in the 1970s, shortly after they were developed. These companies were successful in gaining FDA approval for vaccines produced in these cell lines, and have continued using them ever since. However, viable alternatives exist and are used by other pharmaceutical companies for production of very similar vaccines (see Exhibit 9.3). [Blogger note:  I have not reviewed  “Exhibit 9.3.”]…

“Of the nearly 75 vaccine formulations currently approved by the Food and Drug Administration for use in the United States, only 11 (directed against Zoster, Varicella, Rabies, Rubella, Hepatitis A, Polio and Adenovirus) are produced using historic, fetal-derived cell lines, and none are produced using freshly isolated fetal tissue. Importantly, alternative vaccine formulations that do not rely on fetal-derived cell lines are available or all but five of these diseases (Adenovirus, Hepatitis A, Rubella, Varicella and Zoster), and there is no scientific reason these vaccines could not be produced using animal cell lines. For example, although vaccines against Hepatitis A are produced using the historic fetal-derived cell line MRC-5, modern vaccines against the related Hepatitis B virus are produced using genetically engineered yeast cells. In fact, the vast majority of modern vaccines are manufactured using bacteria, yeast or animal cells—and all of them could be manufactured in this manner. Human fetal tissue is outdated technology that is not necessary for modern vaccine production or research. For example, current vaccine research for HIV/AIDS, Cancer, Malaria and Ebola does not rely on human fetal tissue (see Exhibit 9.3.).”

Now, I am not an expert in vaccine production.  I will say that the majority report did seem thoughtful on this point.  Review it and the rebuttals for yourself.

The scientists otherwise complain that the Committee majority—clearly and admittedly opponents of abortion—wrongly discount the scientific merit of fetal tissue research, and the need for fetal cells, not replacements or surrogates, in that research.  The majority, they say, was too breezy about the possibility of using alternate cells or laboratory models.  Fetal tissue is more useful in certain research into HIV/AIDS, other infectious diseases, and especially to try to understand fetal development.    And fetal cell transfer is being studied again as a potential treatment for Parkinson’s disease.

But, as I have argued in the past, the empiric arguments from potential utility miss the ethical point.  Maybe cells procured a certain way will “work better” than alternatives, but have they been ethically procured?  And if not, we should limit the kinds of experiments we’re doing to what can be done within ethical boundaries.  If you don’t think unborn children warrant projection of life, or as human research subjects, except on the variable decision of someone else, then the expediency needs of the researcher win out.  If you do, there are limits.

And you should.