International commission: go slow with heritable human genome editing

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

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

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

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

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

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

Pediatric Fertility Preservation for Hormone Suppression in Transgender Youth

Last week, I received an e-mail update on current research and treatment being performed at the institution where I did my residency training. One of the interesting research areas was in the discipline of pediatric fertility preservation. Pediatric patients who undergo cancer treatments often take medications which cause destruction of their testicles or ovaries, not uncommonly resulting in infertility problems when the patient reaches adulthood. Advances in cryopreservation techniques of reproductive tissues are offered as a solution to preserving one’s fertility after pediatric cancer treatment.

The cryopreservation technique in the pediatric population is not limited to cancer treatment. There have been advances in providing fertility to non-cancer medical conditions that previously caused infertility. Two such conditions are Klinefelter syndrome and Turner syndrome which affects sex chromosome anomalies male and female patients, frequently resulting in infertility problems in those patients. By cryopreserving these patient’s testicular or ovarian tissue when they are children, when the number of the reproductive cells are in larger number and/or have the best potential for future reproductive function, in vitro fertilization techniques using these preserved cells when these patients reach adulthood can improve fertility.

The same pediatric fertility preservation treatment is now being offered prior to the hormone medication used to assist pediatric transgender youth transition from their birth sex to the opposite gender. Hormone treatments are used to intentionally suppress the transitioning person’s natural sex hormone production. This causes body habitus transformation to the desired gender. Continuous hormone suppression severely reduces (and can eliminate) baseline anatomic testicular or ovarian function causing permanent infertility in the transitioning patient. There is additional concern that the infertility persists even if that hormone treatment is later discontinued. Limited data exists to make conclusive statements on this subject as studies on long-term physiologic effects of hormone treatment used to transition pediatric patients are lacking; this is true even in the adult population where the number of patients who have transitioned is much larger.

Bioethically, we have moved beyond the question of whether we should be doing hormone suppression to assist in gender transitioning in the pediatric population and begun to discuss whether that child’s fertility ought to be preserved following such hormone administration. A simple Google search for non-hormone treatment of gender dysphoria in the pediatric population shows mostly hormone-based treatments for the first pages of results. With more effort, non-hormone options can be found.

The Mayo Clinic update that I received describes the transgender fertility preservation treatment along with a constellation of other pediatric medical conditions whose treatments potentially cause infertility (i.e. the cancer chemotherapy treatment causing infertility described earlier) as if all of these programs should be considered medically (and ethically) equivalent.

Are they?

If they are not, shouldn’t we be debating the medical and ethical pros and cons of pediatric transgender hormone administration more thoroughly before we consider how (and why) to preserve the very fertility of the pediatric patients we are altering by intentional hormone suppression?

Human Fetal Tissue — Considerations

The NIH Human Fetal Tissue Research Ethics Advisory Board met on 31 July 2020 to “make recommendations regarding the ethics of research involving human fetal tissue (HFT) proposed in NIH grant and cooperative agreement applications and R&D contract proposals, as set forth in the NIH Guide Notice NOT-OD-19-128.” The meeting agenda included a brief time set aside for public comment. Additionally, written comment could be submitted within a prescribed time frame prior to the meeting.

It is my hope that the advisory board seriously considered the following comment penned by this writer, on behalf of the educational non-profit Tennessee Center for Bioethics & Culture:

All human beings belong to one another.  Whatever our genetic constitution, our ethnicity, our color, our femaleness or maleness, our geographic location, or stage of life:  we are part of the human family.   That membership is not bounded by a cradle-to-grave timeline.  As human mammals, our beginnings begin before the exodus from our mothers’ wombs.  From the fertilization of the egg by the sperm, a new human being arises (and sometimes, multiples).  How we treat that human zygote, embryo, fetus, newborn, baby, toddler, preschooler, child, adolescent, adult, and elder, has effects on that human being – as well as on ourselves.  How we treat other human beings, especially vulnerable ones, tells future generations and civilizations about what kind of people we are.

In 1993, President Bill Clinton signed into law the NIH Revitalization Act.  That Act charged the NIH to conduct or support research that reduced the number of animals used in research, and that produced less pain and distress in those animals (https://grants.nih.gov/grants/olaw/pl103-43.pdf). Those are laudable goals.  That same 1993 NIH Revitalization Act authorized the use of human fetuses for research, including fetuses from induced abortion (www.hhs.gov/ohrp/regulations-and-policy/guidance/public-law-103-43/index.html).  The same law that sought to reduce pain and suffering in animals opened the door wider to using nascent human beings as research subjects.  Utilizing tissue that becomes available by virtue of spontaneous abortion (miscarriage) does not actively convert living beings into research subjects/objects.  It is not a planned procedure that can be scheduled around tissue procurement firms.  That is not the case, however, with the use of fetal tissue from induced abortion.  The willful taking of tiny, live human beings from their mothers’ wombs, followed by the use of them in whole or in part, as research subjects/objects, sets up a human market.  Abortionists and abortion facilities are paid to render a living being into products or parts.  Then they are paid again to yield up these beings or parts to research.  Money is exchanged for parts or labor, even if said payment is labeled “handling charges.” This is a market, and it is a market in human flesh:  a stain upon our culture and our civilization.

Property rights, payments, and urgent public health needs

Greed is a common concern—a risk, from one perspective, an indictment, from another—raised regarding medical care and the people who profit from providing certain aspects of it.  Nurses don’t get rich.  Doctors, in rich nations, often do.  Public hospitals generally don’t; private, for-profit ones do, and manage their work to make sure they do. 

There’s a much richer ethical tradition than can be recounted here that doctors should not be about profit.  Indeed, key tenets underwriting the understanding of medicine as a learned profession are that the physician enters a covenantal, not transactional, relationship with the patient, and that the physician is duty-bound to efface his self-interest when the patient’s care so requires.  One can argue about the precise boundaries of that, but the principles, even with today’s corporate medicine, still seem generally accepted.   The ancient Christian church gave us the “holy unmercenaries,” saints (generally physicians) who lived in extreme poverty and did not accept payment. 

But the most relevant collective culprit in out time seems to be the Western pharmaceutical industry, which is, to be sure, lucrative, providing high-tech medicines at often high prices.  The principle that the inventor has a right to profit from his invention has led to the standard practice of issuing and protecting patents, which prevent cheap alternatives from becoming available for a number of years.  The idea is that the inventor has those years to make a reasonable profit before the right to praceice the invention becomes more generally available—unless the inventor grants a license to the patent, which of course comes at a price.

The most common remedy for proposed is to limit the price that can be charged.  This is an issue of policy and justice, but not so much one of ethics as of public policy.  The old search for the “just price”—what should something cost—foundered, because the most workable answer turned out to be the market price, assuming that seller and buyer are on equal footing.

A related proposal is that drug companies ought to be non-profit.  The challenges here are that the modern drug industry employs many people, most of whom cannot be considered under the same terms as physicians—they have not taken a covenantal oath to society.  They’re doing jobs, making a living.  Also, being not-for-profit doesn’t eliminate the need for large amounts of money to develop and make drugs.  Countering this is the charge that the prices could or should be lower, that the real costs are not so high to justify pricing, and so on.  These are complex matters that will not be solved on principle but will be the source of ongoing policy disputes that will take on the form of a negotiation, of sorts.

But if one grants that the drug maker is due a reasonable, or even a handsome, profit, then one can still ask, if the medical need is sufficiently acute, when does just, merciful care of suffering people–some rich, many not so much, some from rich countries, many not so much so—demand that the product not be considered a proprietary invention, but a public good?

This question is surfacing as the prospect of one or move COVID-19 vaccines becomes more likely.  The general press has recently reported on various prospective pricing plans from the manufacturers.  Some intend prices that are a bit higher than others, some are discussing charging poor countries less than rich countries, and so on.

A more provocative proposal is to eliminate the property protection from COVID drugs or vaccines.  Recent arguments have held that in no circumstance should patents be enforced, so that inventions would be immediately open on a broad basis, and that one nation should not be able to prefer a product made by a native country be available first to its own citizens; or that, perhaps more simply, that all COVID-related inventions should be placed in an open-access repository for widespread availability.  The fundamental argument is that all such inventions are, and should be, global public goods.

Counter arguments are that people who create new drugs, vaccines, or other products to meet critical needs should be reasonably rewarded, and that not allowing this creates a disincentive to them to make the attempt in the first place.  A government that supports such work has a reason for claiming some consideration when it comes to pricing, and also arguably has a greater moral responsibility to its own citizens than to those of other nations.  Part of that government support arguably includes a duty to provide incentive to the inventors and producers in the first place.

Expect to hear more about this in the general press in the months ahead.

A new cautionary tale for heritable genome editing

A fundamental concern about applying gene editing to human embryos is how to limit the risk of errors, or “off-target” effects.  One makes an edit to change a bad gene’s defect, and presumably prevent the disease the defective gene would cause.  But the current methods to do that, although apparently highly selective, might still make other, unwanted changes as well—with possible deleterious, even disastrous, consequences.

Heretofore, the attention to these “off-target” effects has largely been directed to changes in genes that are separated from the target gene.  However, a recent news item in Nature describes three recent experiments with human embryos in the laboratory, in which large defects were induced in the chromosomes bearing the target gene—that is, right next door.  The difference is a bit like the difference between damage by shrapnel (distant effect) and blowing a 6-foot hole instead of a pinhole (near effect).  The latter is now the new concern.  Apparently, and, for one who does not live the scientific details daily, amazingly, prior analytic techniques were missing the possibility of these big, close-in errors.  “CRISPR gene editing in human embryos wreaks chromosomal mayhem,” the headline reads.  Geez Louise…

The technical details are still to be worked out, but one possibility is that, after the targeted gene is cut by the editing mechanism, the way that repair of the genes is done by the human embryo creates the possibility of introducing errors by copying or shuffling of a big chunk of the gene.  These processes are not fully understood in human embryos, and may be different from what pertains in mouse or other animal embryos, or in single human cells such as egg cells or newly-fertilized eggs.

The big technical message is that a lot is poorly understood and will take a ton of work to sort out before one can be confident that a pregnancy carrying a gene-edited to-be-born human will birth a healthy baby, in the immediate outcome, never mind consequences later in life.  It further suggests that no amount of animal work may lay the matter to rest.  From that it’s hard to avoid the conclusion that many embryos will need to be created, altered, and destroyed for research purposes if heritable human genome editing is to proceed with some assurance of safety.  How long would those embryos have to be kept alive to test?  Quite possibly longer than the few days currently possible and accepted by the scientific community.

Absent that, trying to birth gene-edited children would mean, as this blog said some time ago, that “the babies are the experiment.” 

And, even if one does not grant moral status to the human embryo from the point of conception, one is compelled to seek an accounting of the compelling unmet medical need that supports a careful benefit-risk analysis.  Risks to human subjects—embryos, fetuses, eventually-born babies, women donating eggs, perhaps even women carrying partial pregnancies (to allow study of results from a later point in utero?)—seem substantial, overall costs of the effort raise questions of spending the money better elsewhere in the overall health care of society, and alternative approaches to the diseases in question must all be considered.

Geez Louise.

One other point: the Nature article cites preprints posted, prior to peer review of the science, on the website bioRxiv.  Operated by the outstanding Cold Spring Harbor Laboratory, the website offers authors the chance “to make their findings immediately available to the scientific community and receive feedback on draft manuscripts before they are submitted to journals.”  Open access and public feed back are good, but the general press often picks up these preprints, whose quality may not have been fully vetted, and runs with headlines—kind of like I am doing here, following Nature.  So we must watch this space to be sure that the research is being accurately described and interpreted.  For the moment, the topic of this post can be taken as another example of “something to watch out for.”

Coronavirus 2019: A case of fear as a harm from technology

One of the ethical concerns in modern medicine is whether new technology developed out of a desire to help people may cause more harm than good. Most of the time we think about this in relation to therapeutic technology, but it may also be true of diagnostic technology. It is usually good to be able to diagnose diseases more accurately but learning about a diagnosis can cause significant stress and anxiety. When that is not balanced by significant benefit to the person learning the diagnosis, diagnostic information can cause more harm than good.

I think we are currently experiencing this type of harm from new diagnostic technology in the current outbreak of Covid-19, and it may be a while before we know whether our ability to diagnose this new virus has actually resulted in more benefit than harm.  Prior to the development of rapid viral DNA testing this new virus would not have been recognized early in the course of its spread. 3000 or 4000 additional deaths from viral pneumonia in China where there are 100,000 deaths from influenza annually might not have been noticed at all. However, there might have been more deaths if the relatively extreme limitations on movement had not been up imposed on the Chinese people in the region where the outbreak began. There has undoubtedly been benefit from being able to identify those who are infected with this new virus and isolating them to help prevent increased spread of the virus. However, knowing that this new virus exists has led to significant fear and panic. Some of the response has undoubtedly been excessive, and those excesses can cause harm. Locking down the entire nation of Italy, restrictions on travel that may be more than what is necessary, and the closing of workplaces does more than just impact the stock market. People are impacted by an overreaction to this new disease. Those of us who are more affluent have enough margin to get by, but there are those who live week-to-week and even day-to-day may be severely impacted by things that are being done more due to fear and panic than well-established public health strategies.

There are hopeful signs that the number of deaths in China from Covid-19 are rapidly decreasing, and if the impact in the rest of the world is no worse than what it has been in China, the deaths from this virus worldwide will be about 3 or 4% of the number of deaths from influenza each year. That is significantly less than the normal fluctuation in influenza deaths from year to year. It is not good that those people have died, but it is not the end of the world. The ability given to us by DNA technology to identify this virus will have helped through proven public health measures to decrease the impact of the disease, but will the overreactions due to fear and panic cause as much or more harm than the virus? We may never know.

A principalist argument against heritable genome editing

In May of 2019 The New Bioethics carried a paper (purchase or subscription required) by Jennifer Gumer of Columbia and Loyola Marymount Universities, summarizing an argument against heritable genome editing (the kind in which an embryo’s genes are edited so that the change will be passed down to the subject’s descendants), based on Belmont principalism.  A brief outline of the argument:

  • Uncertainties about the safety of the procedure make it highly unlikely at best that the principle of nonmaleficence (“first, do no harm”) will be satisfied.  Even if the technique substantially eliminates unintended, “off target” gene changes or mosaicism (some cells have the change, others do not), uncertainty will remain about whether interactions between genes may be altered, potentially beneficial positive effects of the “bad” genes may be lost, or the edited gene may have different effects in different environments.  Further, the edited gene will persist in the human population. 
    • At least, this concern would appear greatly to limit the number of genetic conditions that would be appropriate for heritable editing, to a few where a very discreet genetic abnormality that causes a devastating disease is well understood.  Such limits would almost certainly be unenforceable, as efforts to edit genes that clearly cause disease would be expanded to edit genes that predispose to or increase risks of disease, or event to insert or add genes thought to protect from disease.  The additional complexity of the tasks would further confound attempts to calculate risks.
  • The justice of heritable genome editing could well be limited by:
    • The costs, either in the individual case or more broadly on the health care system because in vitro fertilization would almost certainly be required to carry out the heritable editing;
    • Diversion of resources from dealing with environmental or socioeconomic conditions with greater overall impact on the health of the human population;
    • A bias against people with disabilities may be fostered.
  • If heritable gene editing included efforts to enhance traits perceived desirable, harms could arise from miscalculations about whether such enhancement truly yields a better life (e.g., if one could be genetically altered to require less sleep), or pressures on the offspring to perform up to enhanced expectations, again violating the principle of nonmaleficence.
  • Efforts at enhancement would create eugenic pressure to extend the enhancement widely through the population, and/or create a split-class society of (presumably wealthy) genetically enhanced “haves” and unenhanced “have nots,” violating the principle of justice.
  • Limiting heritable genetic editing to the few cases of single-gene-caused serious diseases would benefit only a few affected individuals and their parents, by helping the latter to have genetically-related, unaffected offspring, while risks such as those outlined above could affect many, either by creating direct risks in the population or indirect risks of lost opportunities from deferral of attention to other health and societal problems.
  • Likewise, an appeal to autonomy fails.  Procreative freedom has not yet been held to include a right to bear a genetically-related child, much less one free of undesired traits, and even if such a right were recognized, it would not be unbounded, but would be subject to limits set by concerns such as well-being of the resulting child and societal concerns.  Moreover, parental exercise of autonomy for heritable gene editing would limit the autonomy of society by potentially exposing others to unintended risks without their consent, and would limit the autonomy of gene-edited descendants, whose genomes would be determined at least in part by the decisions of their ancestors.

Thus, in brief, runs the argument.  Like the utilitarian argument summarized in my February 6 post, these contemporary discussions are important to review from time to time.  Further perspectives and analysis to follow in future posts.

An argument for heritable genome editing

Some weeks ago, a utilitarian perspective in favor of heritable genome editing was published (purchase or subscription required to read).  In it, the author, Kevin Smith of Abertay University in the United Kingdom, begins with a general defense of utilitarianism, the ethical philosophy that what is morally good is what produces the greatest good for the greatest number, as opposed to alternative ways of judging that invoke duty, principles, God’s law, or virtues.  In the process, he comments that ethicists who do not consider themselves utilitarian often employ risk-benefit or cost-benefit analyses in making particular judgments.  “We’re all utilitarians now,” as it were.   Smith then proceeds to make a case by a utilitarian, for utilitarians, in favor of pursuing heritable genome editing.  Key points:

  • Genetic editing will technically improve, reducing if not eliminating risks and broadening the ability not only to eliminate genetic disease but also to enhance complex genetic traits and correct mutations that increase risk for disease.  He envisions a day when correcting gene editing errors will readily be reversible by further editing (an “undo” function, as it were).  Consequently, we should anticipate that heritable genome editing will provide many benefits but few harms.
  • Early adoption of technologies is generally beneficial in the end, as, he argues, was the case with IVF, because to delay is to put off the benefits.  In the case of heritable genome editing, we won’t know how well it works without forging ahead.  Nonetheless, the editing of embryos leading to the birth of the edited twins in China in late 2018 was a bit reckless, and the reaction threatens to regrettably and unnecessarily retard progress.
  • Preimplantation genetic diagnosis (PGD) is not a preferable option because some genetic diseases cannot be avoided with PGD (i.e., if all IVF embryos are affected, so there is no unaffected embryo to select) and, more importantly, any additional risk from heritable genome editing is likely to be limited to a relatively few cases in the relative short term, while ultimately yielding much larger benefits to a larger number, justifying the greater risk to some.  (This, I suppose, could be considered crudely analogous to the accepted human research principle that risks to subjects may be acceptable if potential benefits to society—e.g., in development of a candidate new medicine—are possibly greater.  It’s OK for some people to get sick from too high a dose of an experimental drug, for example.)
  • Heritable genome editing should be used soon, because doing so will hasten the first celebrated successes, which will supercharge public support to expand the use of the technology.
  • Adoption is an important alternative, because it increases the happiness of an existing individual, the adoptee, instead of the more speculative prospect of a healthy new person without disease from a mishap from the gene editing.  But if a couple chooses not to adopt, preferring to have a genetically-related offspring, they should not be denied the opportunity if one is possibly available.
  • In general, more new people means more overall happiness for the human race in general, because the new people are more likely to be happy and not, and at least not diminish the happiness of other existing people in the progress.  (This seems to take for granted that heritable genome editing will not cause a detrimental population explosion—which, indeed, seems pretty unlikely.)
  • Having a child produces more happiness for all involved than not having one.
  • Having a genetically related child is better than having one that is partly unrelated, as would be the case with a child conceived using sperm or egg donation from a donor without a genetic disease to be avoided.
  • In cases where a couple simply could not avoid their naturally-conceived child having a bad genetic disease, to go ahead and conceive such a child would entail suffering for the child and parents, and the moral benefits of suffering are overrated.
  • The upside of heritable genome editing—i.e., the potential for human enhancement—is huge.

Many of these points are reasonable as far as they go.  Where this sort of argument leaves one unsatisfied is in the high optimism for technical success without unintended consequences; conceiving the risk-benefit relationship as if it can readily be calculated with confidence; disregard for broad consequences for how we understand ourselves, our begetting, and how we should receive fellow humans who are less than fully whole, physically; and, in some cases, the potential for alternative treatments.

Smith rejects a “precautionary” approach as too timid, but still concludes that maybe we should wait a bit, for the reaction to the Chinese twins’ birth to wear off and for scientist to be able to marshal further their technical case. 

Discussion to follow in future posts.

Twenty-first Century Divorce: Who Gets Custody of the Embryos?

A recent CBS news story provides yet another example of the technology and legal cart pulling the ethical horse.

In short, in 2014, an Arizona couple used in vitro fertilization (IVF) to preserve her eggs after she learned she had breast cancer and would require chemotherapy. The woman’s then boyfriend originally declined to be the sperm donor but later agreed when the woman, perhaps desperate to preserve her eggs, considered using a former boyfriend as the donor (fertilized eggs survive cryogenic preservation far better than unfertilized eggs). The couple executed a contractual agreement, provided by the clinic, as to the disposition of the frozen embryos (“their joint property”) should their relationship divorce or dissolve prior to implantation. They married several days later, underwent IVF yielding 7 embryos, which were cryogenically preserved and the woman underwent successful chemotherapy.

Unfortunately, after 2 years of marriage but prior to implantation, the husband filed for divorce. The pre-IVF contract stipulated that both husband and wife had to mutually agree on the disposition of the embryos – if not, they agreed a court could decide the embryos’ fate. Recently, the Arizona Supreme Court determined that the embryos should be put up for adoption, siding in one sense with the ex-husband to prevent the ex-wife from “using” the embryos. The decision upset many in Arizona to the point where the Arizona Legislature enacted a law to award the frozen embryos, in the future cases of divorce, to the spouse who “intends to use them to have a baby.” The new law will not benefit the ex-wife so, at the time of this blog entry, she was considering whether or not to appeal her case to the US Supreme Court.

There is a lot here to consider. I want to focus on just a few issues. First, I left scare quotes around several of the terms used in this case. The frozen embryos are indeed legally “joint property”, much like children in other cases of divorce. The couple could have just as easily checked the box on the contract to select “Destroy the Embryos” in case of their divorce. This same choice is one that many married (and unmarried) couples make regularly in IVF absent divorce when deciding the fate of unwanted or unused embryos following successful pregnancy and birth from prior IVF cycles. So asking a court to decide the fate of the frozen embryos is similar to children of divorced couples (though their “destruction” is not currently an option.)

“Using the embryos” is terminology that further emphasizes the commodification of frozen embryos as we consider them as a convenience for, or, for the sole benefit of, the parent(s). While I can empathize with the ex-wife’s desire to preserve her ability to have future children in the face of cancer treatment, her choice of an ambivalent (then) boyfriend over an ex-boyfriend as the father of her future children has proven disappointing, if not disastrous, for her in the present. It is harder for me to grasp the rationale of the ex-husband, who, though previously agreeing to father his ex-wife’s children, now (vindictively?) refuses to allow her to mother them, particularly since (continuing with my horse analogy) that fatherhood horse left the barn years ago.

As we allegedly advance our technical and scientific skills by increasing the various situations in which women can become pregnant, we are demanding more legal decisions when these new situations cause conflict rather than discussing and agreeing beforehand whether or not to permit these situations from occurring in the first place.

New technology, old moral problem

Many of our discussions in bioethics are about whether the things that are possible to do with advances in medical technology are things that we ought to do. However, some of the moral concerns in medicine are much more basic. They have to do with the idea that dates back at least to the Hippocratic oath that physicians should use their knowledge for the benefit of the people they treat. Patients should not be used by physicians in ways that are harmful to the patient in order to increase physicians’ income.

Medscape recently reported on a study presented at the American Society for Reproductive Medicine 2019 Scientific Congress which looked at how well fertility clinics across the US complied with the Society’s online advertising policy. They found that many clinics were not following the policy. The major concern was that there were a significant number of clinics that were advertising success rates without revealing the additional information needed to make that rate meaningful. The most serious concerns had to do with clinics that advertised high success rates without revealing that they also had higher than recommended rates of transferring more than one embryo per cycle and had significantly higher than expected rates of twin pregnancies. It is well known that twin pregnancies have a higher risk of complications for both the mother and the babies. Transferring more than one embryo increases the chance of achieving pregnancy and live birth with a cycle of IVF but also increases the likelihood of twin or other multiple gestation pregnancies and the risk to the mother and babies. By transferring more than one embryo in situations in which it is not generally considered justified, these clinics are increasing the success rate that they advertise to obtain patients by doing something which causes harm to their patients.

When the physicians at a fertility clinic prioritize their income above doing what is best for the people they are treating, they have gone beyond unethical business practices. They have abandoned one of the main things that makes the practice of medicine a moral profession.