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.

Selective data collection – what do we know about the risks of IVF?

A recent article in Newsweek reports on a physician, Dr. Jennifer Snyder, who is calling for the formation of a registry of egg donors to help determine the risks to women who “donate” eggs to other women undergoing IVF for monetary compensation. Her motivation in calling for this registry was the death of her daughter at age 31 from cancer after donated eggs on three occasions. She points out that egg donors are commonly told that there are no known long-term risks of egg donation, but that the reason that there are no known long-term risks is that the risks of egg donation have never been studied.

The article reports that Alan Penzias, chair of the practice committee at the American Society of Reproductive Medicine, agrees that such a registry is needed, and states that “national reporting on IVF, including data on both mothers and babies, is required by law.” It is good that this representative of those who practice reproductive medicine is in favor of a registry to assess the risks of egg donation, but there is a problem with his statement about the current reporting that is done on IVF in the United States.

That reporting on IVF is done under the authority of the CDC by the National Assisted Reproductive Technology Surveillance System. According to their National ART Surveillance website what they measure to comply with the Fertility Clinic Success Rate and Certification Act is data about patient demographics, patient stature: medical history, parental infertility diagnosis, clinical parameters of the ART procedure, and information regarding resultant pregnancies and births. The outcomes data is limited to information about the percentage of IVF cycles that achieve pregnancy and achieve live birth and information on how many of those pregnancies are single or multiple gestations and how many are delivered prematurely or at term. No data is collected on the complications or ill effects that women who undergo IVF may experience, and no data is collected on either birth defects or any other adverse consequences other than prematurity, birth weight, and plurality for the infants born by way of IVF.

Dr. Snyder’s call for a registry for data on adverse effects experienced by women who donate eggs is absolutely necessary to be able to give women the information needed to be able to make an informed decision about being an egg donor. There is an urgent need for the same type of registry of adverse outcomes for women who undergo IVF and the children produced by IVF. It is inexcusable to expect women to consent to these procedures without knowing the risks because those who perform the procedures have failed to collect data about those risks.

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?

Fetal tissue and commerce

You may have seen in the general press that Indiana University is asking a federal judge to declare unconstitutional that state’s law banning research on the remains of aborted fetuses.  I noticed an article in the Wall Street Journal (subscription required).  An open-access account can be found here.

I oppose abortion, but I can imagine for the sake of argument that, if one allows for abortion, that it might be claimed that the tissue of an aborted unborn human could ethically be donated for research.  It seems to me that such an argument would construe this donation to be similar to donation of organs for transplantation.  In this case, the mother would be speaking for her (newly-deceased) unborn to make the decision, since the aborted one would not have decision-making capacity.

For such an action to be remotely ethical, donation of tissue could not in any way influence the decision to have an abortion–as, indeed, federal restrictions on fetal tissue research currently require.  There should be no profit to the donor or the abortion provider in the process.  In light of the Planned Parenthood brouhaha over this subject, I might suggest that the researchers seeking the tissue for research be required to bear any costs for the preparation of the tissue.  And something like the dead donor rule for organ transplantation would have to apply.  But that’s probably a trivial point in this case.  Never mind that the dead donor rule itself is under attack these days.

I imagine it’s clear that I don’t find this argument very persuasive.  For one, in organ donation, assuming the dead donor rule applies, one is not killing the donor on purpose, as is the case in abortion.  (Then again, maybe I speak too soon.  Maybe as euthanasia advances we will see it practiced explicitly to facilitate organ harvesting.  But I don’t want to believe that will get much traction.)

For another, scientists should seek alternate approaches to their research.  If we afforded unborn humans the same protections generally afforded to human research subjects, seeking such alternatives would be unescapable.  But in a time when it is far from agreed that we should not create human embryos solely for the purpose of medical research, extending protections to cover the new being in a pregnancy would appear a stretch for us.

Whatever the law allows, it is hard to square respect for human life with performing research on electively aborted babies, no matter how “important” the research appears.

The WSJ report says that other parts of Indiana’s law have been blocked in court, including a ban on abortions because prenatal diagnosis has detected Down syndrome–part of my subject last week.

Two other points about this case that I find painfully telling about how our society reflexively thinks of human life.  First: Indiana University’s key argument against the Indiana law is that it blocks commerce, it violates the commerce clause of the Constitution.  The argument is that aborted fetal tissue is an “article of commerce,” similar to–and these are the precedents being cited– margarine, or meat slaughtered more than 100 miles from the point of sale.

Second:  the university contends that the law does not advance a legitimate public interest.  All it does is express “moral disdain for abortion.”  So: the protection of unborn human life is not a legitimate public interest.  What other human life lies outside the public interest, I wonder?



Is Involuntary Temporary Reversible Sterilization Always Wrong?

Ever since Janie Valentine’s blog post last week I have been thinking about the problem of repeat drug offenders and their children. My home state is also Tennessee so I read Judge Sam Benningfield’s order (to reduce prison sentences by 30 days for any drug offender willing to “consent” to voluntary temporary sterilization) with particular local and regional interest.

My office practice is on a street with more than one suboxone treatment clinic (a synthetic opioid designed to be used to assist in narcotic withdraw or as a substitute for pain management with less potential for abuse). It is not uncommon for me to see the parking lots of these clinics full of cars, with unsupervised children playing with other unsupervised children in the parking lot while their parents are inside the clinic receiving their treatment. No doubt some of these patients are opioid dependent and not necessarily opioid impaired. My point here is simply to point out the sheer volume of the opioid problem and also to highlight that this represents the families that are doing well. The children are still with their parents and the parents are not (obviously) under the jurisdiction of the court system.

One partner in my practice and his wife are foster parents and have opened their home to children of repeat drug offenders. These children have often been ordered by child protective services to be temporarily removed from their homes because of their parent’s incarceration related to a drug offense or court ordered treatment. The usual placement is a group of 2 or 3 siblings, often with one of the foster children a newborn baby in the throngs of opioid withdrawal. After seeing several iterations of this pattern, I can certainly sympathize with the judge’s moral outrage and frustration at seeing multiple children, often within the same family, born with opioid withdrawal, though I must agree with Janie Valentine and Steve Phillips that in the case of the judge’s court order (now rescinded), such consent is, at best, coerced given the incarceration.

This brings me to the point of today’s blog. Can there be any condition in which it is right to prevent repeat opioid drug offenders from conceiving a child while impaired by opioid addiction? No one will claim that conceiving a child while addicted to opioid drugs results in a desirable outcome for the parent or child. Choosing to avoid conception requires the very planning that opioid addiction frequently impairs. The current epidemic of opioid-addicted newborns proves that expecting voluntary conception avoidance by the opioid impaired is a non-starter. Voluntary reversible forms of sterilization (none are 100% successful at preventing conception) are available but have non-zero barriers (access/cost/side-effects/compliance/efficacy). Reducing the barriers for those willing to choose temporary sterilization seems reasonable. But what about individuals not willing to voluntarily avoid conception while opioid impaired? Does society have any right to temporarily (reversibly) prevent conception for some time frame in someone impaired by opioids? Should this happen after the first birth of an opioid-addicted newborn? Can it happen after the fourth such serial opioid-addicted newborn birth? At what point should autonomy of the opioid impaired yield to avoiding maleficence to a child?

Let me additionally be clear about what I am not asking or claiming. I am not making some eugenics claim that opioid impairment is genetically determined such that eliminating offspring of individuals suffering from opioid impairment somehow reduces the future risk of opioid dependency within the larger population. I am also not claiming that individuals who are currently opioid impaired will always be opioid impaired. I am not claiming that opioid impaired individuals are necessarily permanently bad parents; when not opioid addicted, they may in fact be wonderful parents. Finally, I am not asking that the sterilization be permanent, as I do not think that opioid impairment is permanent.

Again: Can there be any condition that makes it permissible to involuntarily temporarily reversibly sterilize repeat opioid drug offenders to avoid conceiving a child while opioid impaired?

More about Charlie Gard

Dr. Robert Truog, the bioethicist and transplant physician who has pushed the envelope on the definition of death, has weighed in on the Charlie Gard case in a “Perspectives” piece that is generally available (i.e., without a subscription) from the Journal of the American Medical Association (JAMA).   By all means read it.

Dr. Truog approaches the case from the standpoint of limiting medical research—indeed, that’s in the title of his article.  He says the case is about “the best interest of the patient, financial interest, and scientific validity.”  On the first point, he is cautious about the British courts’ assertions that it can assess how much pain and suffering Charlie is experiencing, and whether the courts know this better than the baby’s patients.  This caution seems wise.  As I have reflected further on this case it strikes me that I may be missing a legal distinction between Britain and the US; frankly, I am not well-versed on British law in these cases.  I do tend to think of the Gard case in terms of substituted decision-making in the case of severe or terminal illness.  My thought process runs through the checkpoints.  First, the patient’s wishes are paramount.  In this case, the patient cannot express wishes and may not be able to form them.  In that case, second, a surrogate decision-maker should speak for the patient using “substituted judgment” or “substituted perspective” to express how the patient might have approached the case if able to express wishes.  Here, the parents are available to speak for the patient.  It would be only in the absence of a decision surrogate that “the best interests of the patient,” as judged by the physicians or the courts, would control.  Apparently British law grants rather more primacy to third parties, other than the patient and any surrogate decision-maker.  Under the rubric I’m used to, the parent’s wishes would control.  Here, the British authorities argue, they do not.

The columnist William McGurn took exception to this attitude in The Wall Street Journal earlier this week.  “This is our call, [the doctors and courts] say,” he writes.  And this is the necessary attitude of single-payer healthcare, he claims: “at the heart of single payer is single authority.”  The hospital, McGurn charges, “even wants the last word on love: ‘In one respect, Charlie is immensely fortunate” to have such loving parents, but that respect apparently has nothing to do with this decision, for which their love apparently disqualifies them.  (BTW, perhaps you have seen the report that the court-appointed “guardian” for Charlie chairs an organization that is a sister organization to one that promotes doctor-assisted suicide.)

Dr. Truog’s second point is that distributive justice trumps (my word, no political pun intended, honest) the money Charlie’s parents have raised for his experimental care.  In fact, justice demands we disqualify that fundraising effort, because to allow them to pay is to elevate their ability to pay over others who may be in need of scarce resources.  He says that public funds have stood up the hospital and British health system overall, so the Gard family does not, as it were, “own” it or lay privileged claim to access.  I find this argument of Dr. Truog’s specious.  There is no certainty at all that Charlie would block other needed care—unless, I suppose, it is allowed that Britian’s National Health Service already rations care to the point of extreme scarcity!—and they harm no one by possibly paying for experimental care.

That leaves the third issue—is treatment, admittedly experimental in this case, ethical?  Dr. Truog says no, because the chance of success is so low and “does not meet a threshold of scientific plausibility.”  He argues that the rationale is theoretical only, and complains that the proposed experimental treatment has not been tested in animals or humans before.  But again, this is at least partially specious.  Charlie suffers from an extremely rare condition, animal models may be lacking or entirely unpredictive (medical researchers operate with this general conceit that animal studies DO predict—boy can I tell you how often we are wrong about that!), and when a condition is rare, EVERY individual case provides the opportunity to learn something.  Medical history is replete with work based on the careful observation of clinicians, even apart from the randomized clinical trial, which could never be done in such a rare condition as Charlie’s.

It is of course possible to object that the risk-benefit ratio for giving Charlie the experimental treatment is a judgment call that should be made against treatment.  If the doctor is truly being reckless with the proposed treatment, is profiteering, or if there is no reasonable possibility, at acceptable risk, for direct benefit to Charlie or for useful knowledge to be gained, then the proposed treatment should be deemed unethical.  In the U.S., that would be a call for an IRB and the FDA.  And again, they might say “no,” in which they would be speaking more to the doctor than the patient’s parents.

But in this case I think the British courts should defer to the parents and allow them to pursue that question in the U.S.

The Semantics of Therapy, Part II

A previous blog post of “The Semantics of Therapy” posed three questions about the human genome being a “patient” to be treated. One reader found the post “provocative and disturbing” and called for further explanation and discussion of the questions posed. That will take some time and several postings.

The first of the questions to be considered is this: If the “patient” is a genome, to whom does the researcher answer?   An answer from recent history may shed some light on this important issue.

33 infertile couples underwent a novel procedure at New Jersey’s Saint Barnabas Medical Center during the years 1996-2001. Embryologist Jacques Cohen used cytoplasmic transfer–ooplasm from the oocytes of fertile women was transferred into the eggs of infertile women–in the hope of establishing pregnancies in the latter. The outcome was 13 pregnancies and 17 babies from the Saint Barnabas experience (see accounts here and here).

According to a 2014 BBC article, one resulting pregnancy, which ended in miscarriage, revealed a missing X chromosome in the fetus. The same anomaly was noted in another child: one of a set of twins from a different pregnancy. Later, one child showed evidence of developmental delay. In 2014, Cohen estimated that the worldwide experience of cytoplasmic transfer between oocytes had resulted in the births of 30-50 babies, although the FDA had effectively stopped the procedure in the U.S. in 2002.

What had the follow-up on the babies born through cytoplasmic transfer been in 2014?

Due to a lack of funding, Cohen says, it hasn’t been possible to find out about how any of the children like Alana who were born from cytoplasmic transfer are doing. But the St Barnabus Institute is now starting a follow up study to check their progress (BBC).

In October 2016, Chen, et al, published “A limited survey-based uncontrolled follow-up study of children born after ooplasmic transplantation in a single centre,” in Reproductive BioMedicine Online.  Twelve of thirteen couples responded; parents of quadruplets did not:  “One couple disclosed the use of egg donor to their child. One reported intention to disclose; six were undecided and four reported they would not disclose.” (Article here.)

This admittedly biased study and a few newspaper-based profiles appear to constitute the follow-up of significant genetic intervention in babies-turned-human-subjects. So what will the future hold?

The recent committee report on human genome editing had this to say about heritable genome editing:

As with any new procedure, carefully monitored clinical trial protocols would be required for germline genome editing, with attention to monitoring off-target events as well as the efficiency and correctness of the specific edit. Unlike conventional clinical trials, germline genome editing trials would likely require long-term prospective follow-up studies across subsequent generations. This follow-up would entail study of the future children affected by the intervention, none of whom would have been party to the initial decision to participate in a research trial. . . . Even those who have volunteered to be research subjects cannot be compelled to participate in long-term follow-up. Nonetheless, encouragement is permitted. . . . (download available here)

Should we be comforted by the “long-term prospective follow-up” and the permitted “encouragement” that may be necessary?  Presumably the long-term prospective follow-up will be dependent upon the monies allocated for same (when the money runs out, so does the interest?).  When the State is involved, what kind of “encouragement” might be involved?

On the other hand, what about any anomalies that may be caused by these procedures?  Will pregnant women be “encouraged” to abort such offspring?  If born, will the resulting children be treated, or only followed like any other long-term science experiment?  Who explains to these, and indeed, all of the children born through germline genome editing, that they are indeed long-term experiments?


— D. Joy Riley, M.D., M.A., is executive director of The Tennessee Center for Bioethics & Culture.

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.

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.