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 ( ).”

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.


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?