“The Science” and Moral Judgments

Some common mislocutions are simply insufferable.  One is, “It’s in my/our DNA,” implying that a commitment or habit or practiced behavior is genetically hard-wired.  No, it isn’t.

Another is, “I/we will follow the science” to make judgments.  If by this is meant, “I will face facts rather than engage in wishful thinking,” then hear, hear.  If by it is meant, “I will heed experts to explain data that I am less equipped then they to interpret,” then again, hear, hear.

But it seems that all too often what is really meant is, “I will be objective but we all know that you are not,” or some other means of asserting certitude and foreclosing argument and discussion.  In this sense, appeals to “the science” take the place of bygone appeals to Holy Writ.  And when so invoked, “the science” is sometimes, I fear, misused.  There are at least three errors to which we should be alert.

First is failure to account for uncertainties in measurement or assessment.  This has been on full display in discussions of epidemiologic forecasts of the effects of the COVID-19 pandemic.  All empiric measurement and analysis carry uncertainty, which must be assessed and reported, especially when forecasting complex events.  Readers who doubt this are referred to Nate Silver’s excellent and entertaining 2012 book, The Signal and the Noise.  Forecasts are only as good as the data that go into them, and always have some degree of uncertainty.  The forecaster should account for that, and, in fact, to the degree possible, should also assess how sensitive the forecasts are to changes in the input assumptions.

Forecasters such as Dr. Murray at the IHME do indeed report their uncertainty (look at those wide shaded bands with the forecasts), but these are often lost in discussion, much less their sources and underlying assumptions reviewed and sensitivity to changes in those assumptions described.  (Listening to his interviews, I wonder whether Dr. Murray is not somewhat pessimistically oriented in his assumptions, but that is not a point for this blog post.)  Then again, as more data are collected, the forecasts should be more refined, and they are.  Some policy makers in the current outbreak chose to risk erring on the side of caution—a reasonable approach—but that does not mean either that they were entitled to a claim of certainty in the predictions or that the forecasts themselves were somehow suspect or illegitimate in retrospect.  It was just the nature of the uncertainty.  But recognizing that demands some humility in prospective judgment and in retrospection.

Second is confusion of facts with values. It is one thing to say, “if we do X, then my best estimates suggest there is serious risk of Y,” and quite another to say, “because of my forecasts, X is out of the question because of the risk of Y,” without also assessing the real costs of both X and Y and their relative likelihood.  That is, there are tradeoffs.  Now, epidemiologists and economists both clearly are aware of tradeoffs, but the former seem to be viewed as somehow purer in aims and methods than the latter.  Yet a prominent bioethicist who has counseled extreme caution regarding relaxing mitigation efforts in the pandemic offered on television that schools might be opened soon as long as parents were informed of the risks of sending their children back to school.  This is a defensible position.  It’s just not one that falls out of scientific assessment.  It involves value judgments, and no one in a position of authority approaches the current situation value-free.  If we forget that, then our medical professionals might come off as, or be viewed as, scolds.

Third is the stubbornness of the ad hominem.  We should accord properly-credentialed experts their place of honor and authority in complex discussions, but their expertise does not confer on them certitude even of their prognoses (see above), much less certitude about all the consequences for action that might ensue.  To wit:  last month, when Governor Cuomo asserted, quite energetically, that New York State needed 30,000 ventilators to care for people who had fallen gravely ill, he was challenged by one citing a countervailing forecast that suggested the state’s true need was substantially less.  But that challenge was articulated by Mr. Kushner, citing forecasts the White House was looking at, and a common public response was that the White House stance must be incorrect or corrupt precisely because Mr. Kushner (who, one friend has recently told me with confidence, is “a clown”) was making it.  I don’t know exactly what Mr. Kushner said, or whether he was right, or whether even his projection was more or less accurate or prudent at the time.  The actual number of ventilators needed by New York for this phase of the outbreak, with more data, now appears less than 30,000.  Why?  The answer is not clear.  One can think of several possible explanations.

Still—someone once wisely told me that the merits of an argument depend on its quality, not on the identity of who is advancing it—or on one’s opinion of that person, or on one’s opinion of one’s own intelligence.  The current crisis demands calm assessment of “the science,” properly interpreted, as well as of the very difficult tradeoffs that appear to be in the offing.  And, in this, the experts are not the only ones who should have a voice.  We demand that last point in the relatively small matters of human subject research and use of biomedical technology.  How much more so in the current moment.

More—with trepidation—on COVID

Let us stipulate at the outset: first, that so much—far too much? –is being written on the COVID-19 outbreak, and wisdom is a precious commodity; second, that although your correspondent is an MD, he is as bewildered as anyone by the storm of reports, claims, data, projections, arguments; and third, that whatever public comity may appear to pertain now, in due time we likely will be at one another’s throats with blame about who should have been better prepared or done what when, and there will be plenty of blame to go around.  Our leaders, national and regional, are especially to blame, but the evidence abounds that too many of us took this too lightly throughout January and February.

This being a bioethics blog, however, a few comments about some ethical issues in an outbreak, from a 2018 paper on the subject.  The paper in question raised three major topics: ethics of treatment research, triage, and the duty (by doctors and other health professionals) to provide care.

The last point first: it is well established that the covenantal duty of doctors in particular is a willingness to efface self-interest for the interests of the patient.  There is no dispute that this duty is being followed faithfully by the doctors, nurses, and others who are caring for people sick from COVID-19.  But a related duty of society is to do what it can to limit the risk to the caregivers themselves.  This is clearly pressured by, for example, the limitation on personal protective equipment (PPE) supplies.  We owe it to the medical community to provide them with what they need.

Next, triage:  try as we might, and fail as we might (and always seem to) to prepare in advance for a possible outbreak, surprise never fails to assert itself, and shortages of things that really matter loom.  At this writing, I have no idea whether New York City’s capacity to care for the sick is destined to, or is already, hopelessly overrun “under any scenario,” as Gov. Cuomo said this morning, or whether we can take any comfort in the assertion this evening by Dr. Birx that “there are still ICU beds and ventilators” in New York.  In early March, an infamous discussion at the American Hospital Association projected as many as 1.9 million people needing ICU care nationwide, and about half of those needing ventilator care, and it is further widely said that the typical ICU stay, even for someone relatively young, is 2-3 weeks.  Numbers far fewer than that would outstrip our national capacity, it appears.   Then again, the real shortage may not be ventilators, but the doctors to manage them.

These concerns also arose in the first Ebola outbreak a few years ago, and much-discussed principles of allocating scarce resources apply.  First and foremost is to try to alleviate the shortage through the best possible resource management.  Failing that, if hard choices must be made, then the likelihood of achieving clinical success is a top criterion.  But that requires clinical judgment that may be uncertain, requiring a lottery system, or a registry (as is done for organ transplantation).  Perhaps most controversial is to make an attempt to prefer treating people who are judged, if treatment succeeds, to have more life to live or more potential lifetime contribution to society to offer.  In that case, who decides, and how one decides, become very dubious judgments to make.

In the moment, there may not be enough critical care resources to go around, and doctors have to make a hard choice to treat one person but not another.  Physicians in Italy are reported to have faced exactly this choice this month.  Another principle, easy to say but hard to follow (talk is cheap!), is that triage “should not be a bedside decision,” that is, the treating doctor should not be forced to make a choice, but a previously-settled decision process should be applied.  I do not know whether that was or is possible in Italy, or in New York, or elsewhere in the U.S. or the world during this outbreak.

If we indeed are committed to care for and conserve our most precious care resource, our doctors, then that, in addition to limits on the number of available beds, might be adduced in favor of a so-called “universal” or “unilateral” decision that resuscitation (CPR) of some patients—which will increase the risk of the doctors and nurses getting infected—simply will not be attempted if their heart stops, regardless of whether the patient desires the attempt.  I know of no evidence that this is being done anywhere, but it is the subject of some speculation in the press.  The proper process is for a careful end-of-life conversation to happen between doctor and patient, before being confronted with the need, so that the patient’s wishes and the doctor’s professional recommendation can be considered.  But if that did not happen for people seriously ill with COVID-19, it may be too late when the illness strikes.  Those of us “of a certain age” are wise to consider this question in advance—viral outbreak or no.

Finally, the ethics of experimental treatment during a disease outbreak are governed by a well-defined regime of human subject research.  The key principles follow the Belmont principles reviewed by Mark McQuain on this blog on March 17, and include that risks to subjects must be limited as much as possible; that the necessary research risks not be excessive compared to the potential benefit to the subject at hand or society at large; that informed consent be properly obtained and documented; and that vulnerable people or those less advantaged not be denied access to potentially promising treatment nor be disproportionately placed at risk or have their vulnerabilities taken advantage of.

In the case of this present outbreak, research ethics also require that experimental treatments be properly studied in adequately designed clinical trials.  Implications, IMO, include that people be randomly assigned to treatment alternatives.   It is true that “off-label” use of drugs that are available for other uses is legal when prescribed by a licensed physician, and such off-label use is not on its face evidence of malpractice.  However, society stands to benefit by collection of data about the COVID-19 disease and outcomes of treatment, and so even off-label use should be done in a clinical trial, not in a “right to try” approach.  Because COVID-19 can be so severe, and the need for treatment is so great, I am inclined to think that random assignment to a placebo is a suspect requirement, I must admit that the need to learn more about the natural course of COVID-19 infection probably requires a placebo group in most, if not every, clinical trial.  There is not enough prior knowledge to rely on comparing a past group with a current, treated group, to conclude whether a new treatment works.  But requiring a placebo further requires that the trial get done fast and carefully, so results are as clear as possible, and made pubic immediately.  We should have no doubt at all that everyone doing the trials wants that.

I note that the public registry of clinical trials includes several in the U.S., including a national, 3000-person study of whether hydroxychloroquine may prevent disease in people exposed to others with COVID-19 disease.

More notes on suicide—assisted or not

As one with the letters “M” and “D” after my name, I get emails from a service called Medscape (subscription generally required), with links to a variety of articles on things medical.  This week brings a link to a piece under the title “Inexact Science: is Patient Eligible for Medical Aid in Dying?”   The upshot: physicians who provide assistance in suicide for their patients struggle with two common features of laws around assisted suicide: a requirement that the prognosis for survival be 6 months or less, and the requirement to confirm—usually with concurrence of a second doctor—the patient’s capacity to make decisions.

In the first case, it’s no secret that saying how long any one person, even one with a terminal illness, has to live cannot be done precisely, and there are many mistakes.  A doctor can try three approaches: guess how long she thinks a patient will live, ask whether she will be surprised if the patient is alive after 6 months, or guess the probability of the patient’s living 6 months.  These are three very similar, but logically non-identical, questions.  Doctors’ estimates tend to be more accurate for patients with cancer than for other cases, but they still can be wildly inaccurate.

In the second case, patients’ limited ability to communicate can make it hard to tell whether they have the capacity to freely choose death, or they may have that capacity when the doctor provides the assistance, by prescribing a lethal dose of a drug to be taken later, yet the patient’s decision-making capacity may not be so good at the time the drug is actually taken. 

Readers of this blog will know that the present writer is a staunch opponent of doctor-assisted suicide.  One can sympathize with the difficult cases faced by physicians who disagree on the subject, yet still argue that their best course of action would not be to assist a patient’s dying, but focus on caring for the patient and alleviating symptoms and distress to the end.  A poignant essay in this week’s New England Journal of Medicine (prescription also required) by a palliative care doctor whose patient, with bone cancer, had truly intractable pain, is a case in point.  Here, the doctor did everything she could to control her patient’s pain, using higher doses of narcotics than she ever had or probably ever will again, with no success.  Seeing her patient’s joy in interacting with his family and friends, she resisted sedating him to the point of unconsciousness to death—the last resort for controlling his pain.  “Terminal palliative sedation” comes about as close as possible to active euthanasia without, I would argue, crossing the line because the primary intent is to alleviate suffering, not cause death, although the latter, because of suppressed breathing, may prove unavoidable.  In the case in point, the patient was not sedated, but died over a weekend when the doctor was off; on reviewing his last moments when she returned on Monday, she learned that he had been able to “clink a glass of beer” with visiting friends before he died.  She wondered whether she had treated him too much, tried to be too much of a hero(ine), because she wanted to preserve what was left of his consciousness.  She thought she might be to blame for treating her patient too aggressively in the end.  Reading her account, one must be reluctant indeed to level a charge like that at her.  Her writing makes it clear that she discharged her duties admirably, in a difficult situation.

Finally, I note a headline in today’s USA Today: “Suicide prevention: Many not ready.”  Who is not ready?  Therapists.  Psycohologists.  Practitioners who do not know how to talk to someone who is suicidal, or who are worried about liability if a patient/client actually kills himself, or who are more concerned about assessing how likely a suicide attempt is than positioned to take on the burdens of identifying and addressing the underlying emotional pain.  Better training is called for, the article says.  Perhaps more awareness and caring from folks in general would help.  Ten and a half million people seriously thought about suicide in 2018, it says.  About a third of those made a plan to kill themselves.  About a third of those actually tried.  Over 48,000 died from suicide. Our goal should always be to care for suffering people, but in the process we should reject actively ending their lives.

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.

Controlling gene editing

The title does not mean societal or legal control of gene editing technology.  Rather, it speaks of controlling, or shutting off, a specific gene editing process.  In retrospect, it had to be the case that there is a resistance, or control, mechanism for the CRISPR system, the gene-editing machinery that functions as a way for bacteria to resist invasion by viruses.  An engaging essay in Nature this week discusses this on a level accessible to one who, like me, is not a technical specialist in the field.  Briefly, a few years ago a grad student at UC/San Francisco discovered cases in which the CRISPR system was ineffective in certain bacteria.  Following up led to the discovery of some 50 proteins that can act as “kill switches” for CRISPR.

On a surface level, the implications are clear—learn how to deploy these proteins and one can monitor one’s gene editing efforts for unwanted effects, or for spinning out of control, and if things haven’t gotten too far out of hand, one could turn things off—have an antidote, as it were.

Suppose at some future date that someone were being treated with a gene editing approach for a genetic disease, and things start happening suggesting that other genes than were intended to be the target were being altered.  Presumably one could intervene to treat or prevent the consequences.  Or suppose that genes were being edited to control a certain pest, like malaria-causing mosquitoes.  Presumably there could be an intervention to try to stop the process.

That’s a pretty superficial discussion, but technical experts in the field are trying to learn how to use these “kill switches” to control their gene-editing efforts. 

The also-superficial implication seems clear: these efforts should be understood, and applied in laboratory systems, then perhaps in “somatic” gene editing (treating an existing person for a genetic disease) BEFORE attempts are made to edit human embryos, whether the embryos are intended for gestation or birth or not.  Until things are MUCH more fully understood, there should be no direct work on heritable genome editing.

Chastening and enthusiasm about genome editing

A writer in Nature says that China sent a “strong signal” by punishing He Jiankui and two colleagues with fines, jail times, and bans against working again in human reproductive technology or applying for research funding.  (They lost their jobs as well and may not be able to do research work, presumably in any field, in a Chinese institution again.)  It is encouraging, this writer says, that China took this action demonstrating a commitment to human research ethics.  He and other researchers doing gene-editing work that is not ethically objectionable worry that there may be collateral damage, so to speak, against ANY gene-editing research in China.

Another writer in Nature says cites progress under “appropriate caution” for using gene editing techniques for so-called “somatic” gene editing; that is, editing disease genes in an existing person with that disease, to treat it.  This is, in essence, a form of gene therapy and is ethically permissible under proper research ethical guidelines.  Some clinical trials in progress involve injecting the gene-editing apparatus into a person, while most such trials remove the person’s blood cells, edit them in the laboratory, then re-introduce them into the bloodstream, after which the edited cells are left to mature normally.  The latter approach is particularly attractive to treat genetic blood diseases such as sickle cell anemia.

Both perspectives seem correct, as far as they go—never mind whether Dr. He’s jail sentence fits the crime, as Joy Riley asked on this blog last weekend.  Never mind also whether Dr. He’s research should be published; as Mark McQuain commented, it’s a bit incongruous to want to assess the technical merits of work that should not have been done in the first place.  He linked an opinion in Technology Review that argued, briefly, that because the ethics of editing genes in human embryos is under societal debate, people trying to decide on the ethical merits should be able to assess for themselves whether Dr. He succeeded, technically at what he set out to do.  (The consensus to date seems to be, no, he did not.)   But the role of technical success in assessing the ethical merits of a medical intervention—or, better, an intervention made in the name of medicine—depends on the degree to which the ethical judgment is a matter of making a reasonably reliable of risk and benefit, and the degree to which risk-benefit is a criterion for judging the ethical merits.  And therein, as they say, lies the rub—which I hope to revisit in coming posts.

Can we hop the gene-editing train?

As Joy Riley pointed out on this blog on December 7, the world and the scientific community recently marked, with almost no fanfare, the one-year birthday of “Lulu” and “Nana,” the first (we think) and still only (we think) humans to have had their genes edited heritably—in a way that will be passed on to future generations.  Joy commented these children are “experimental subjects for life,” or, to use the phrase I found and discussed some time ago on this blog, “the babies are the experiment.”  To wit: it is not possible fully to assess and limit the risks of heritable genome editing before actually editing humans.  One must forge ahead.  Even if one were to edit a series of embryos, and abort them at different times during gestation to get a full assessment of their prenatal development, the questions about lifelong effects and effects on future generations would persist. 

And, as mentioned in other posts on this blog earlier this year, there is the issue of “nonphysical” harms to how we understand ourselves and our human existence.

A number of world scientific bodies are assessing, independently of each other, what regulatory safeguards should be instituted, on the assumption that heritable genome editing is something that should be pursued.  Last month, the journal Nature editorialized that efforts by the World Health Organization, US and UK scientific bodies, and a third international commission should not proceed separately (they are all due to report their findings in 2020), but should work together.  The editors apparently think that it would be straightforward, obvious, and right to adopt a moratorium on clinical applications of heritable genome editing, establish an enforced registry for all experimentation in this area, and expand the conversations to include representatives of people with disabilities.  If I read that correctly, it’s hard to disagree.

In the laboratory, things are moving fast and it is well-nigh impossible to keep up with the science or the conversations about it without that work being one’s main occupation.  A recent contribution linked by the Nature editors is called “prime editing” that appears to increase substantially the efficiency of gene editing, raising the prospect of correcting abnormalities associated with the vast majority of genetic diseases.  The relatively naïve, like your present correspondent, might wonder whether this approach could be limited to already-born people with genetic diseases, as treatment, rather than engineer the genomes of the unborn in an apparent attempt to eliminate these abnormalities from the human prospect.

Even thinking about the general public trying to influence where this work leads feels like assuming the role of an old-style hobo, trying to hitch a free ride by jumping onto a moving freight train.  One is liable to fall under the wheels.  But in the case of heritable genome editing, you’re likely to get run over anyway.

More on Physicians’ Conscience Rights

Yesterday’s post to this blog addressed physicians’ conscience rights.  The standard shape of arguments about preserving individual physicians’ conscience rights goes, broadly, like this:  certain actions now sanctioned by society (e.g., abortion, assisted suicide) have been embraced by the medical profession as standard medical care which all physicians should be willing to perform, but this stance runs counter to the long tradition of medicine and to the proper ethical stances of some individual physicians.  Therefore, objecting physicians should be free to decline to perform them, without fear of professional or legal reprisal.  In this vein, the current U.S. Administration had promulgated a regulatory rule in May of this year attempting to ensure that, consistent with existing statute, such conscience rights are protected.  This week, a federal judge struck down the rule in its entirety, arguing that a) the propose rule, which, like all regulations, would have had the force of law, went beyond the statute behind it by making unwarranted interpretations and expansions of the statute’s wording; b) the government’s process of promulgating the rule violated other laws governing such rule-making; c) that it was unconstitutional, violating not only the separation of powers but also the Fifth Amendment because the rule was too vague, and the First Amendment because it would have “required employers to conform their business practices to the religious practices of their employees.” 

One might wonder whether at least some of the court’s reasoning—especially the separation of powers and Fifth Amendment arguments, and the concern (“a” above) about bureaucratic overreach—might not in fact apply to a wide range of government regulations.  That notwithstanding, the Christian Medical and Dental Associations, which has been particularly vigilant to protect conscience rights when it comes to abortion and assisted suicide, vowed to fight on.

The Journal of the American Medical Association (JAMA) cites a different case, involving assisted suicide in Colorado.  There, assisted suicide was made legal, with only limited restrictions, by a public referendum.  Notably for the present case, while health care organizations such as hospitals may opt out, and decline to provide assisted suicide, they may not enforce a blanket prohibition against their physician-employees doing so on their own initiative.  Such a prohibition could only be enforced on the organizations’ actual premises. 

So apparently a physician who worked for a Catholic hospital wrote (on her own time, outside hospital premises, and of her own volition) a prescription for a lethal prescription for a cancer patient.  The physician cited judgment of her own conscience.  The hospital cited its moral reasoning, its own freedom of religion, and, it appears, a claim that the physician was, or should have been, considered to be acting as an agent of the hospital.  The matter is the subject of a lawsuit.

The hospital fired the physician.  It is said she found another job.  But that of course is not the point, is it?  If a physician, who has a covenantal relationship with the patient, finds in her moral judgment that, in a given case, assisting suicide is ethically permissible, why does the hospital system have a right to override that judgment—especially if it was exercised, as it is argued here, in accordance with existing civil law?  One can certainly argue, as I would, that the physician has erred in her moral reasoning, and misapplied the physician-patient relationship. 

But I wonder whether, as the saying goes, “what is sauce for the goose is sauce for the gander,” in this case.  We might consider: the hospital could employ the physician based on an upfront, written agreement that the latter would act in accordance with certain moral stances of the former.  Absent such an upfront agreement, it’s hard to agree with disciplining the physician as was done in this case.  But even then, such insistence on upfront agreements seems to run counter to much of the spirit of much discussion about conscience rights, setting up a regime in which the relative power of available employers of physicians determines the constraints on medical practice.  Even then, if medicine remains a learned profession at all, perhaps insistence on conscience rights should be understood to cut both ways.

Drs. Stephanie Harman and Abraham Verghese seem to lean in this direction in an accompanying editorial in JAMA—but by emphasizing physician autonomy.  Their examples betray their preferred value judgments, but the overarching concern still seems relevant and valid.

Skepticism about polygene scores to select for IQ and height

One caution when objecting to the prospect of heritable human gene editing is to take care not to overestimate what it technically possible.  That is, an all-too-easy argument is that attempts to edit a disease gene will lead, by momentum if nothing else, to “designer babies,” with children not just being genetically selected but in fact engineered in great detail for traits like attractiveness, athletic prowess, height, and intelligence.  This contributor to this blog has repeatedly taken the position that heritable human gene editing is a project that fundamentally alters the way we see ourselves and each other; that divides the human race into “actors” and “acted upons;” that has no prospect of prospectively assessing long-term, unintended consequences, to an individual subject, subsequent generations, or society at large; and that fortifies a perspective of admitting to the human race only those members we want to admit.

Along the way, we must keep in mind that “designer babies” are not likely to be feasible in the foreseeable future.  One recently-reported case in point is a study by scientists at the Hebrew University of Jerusalem.  A preprint (in advance of publication in a peer-reviewed journal, it is said) is publicly available here.  I daresay the details will be inaccessible to all but specialists in genetics, but a summary of key points is provided by a technical writer at a website called GenomeWeb.  In brief, some of those points:

  • A score based on assessment of multiple genes has previously been suggested to explain only about 5% of the difference between individuals in IQ (300,000 people genetically tested) or 25% in height (700,000 people tested).
  • These researchers tested about 1000 people, and considered about 15,000 genetic variations.
  • They looked at offspring of actual couples and also “simulated” matches for about 500 would-be couples made from individuals for whom they had genomic data.
  • Of note, they appear to have looked at “SNPs,” or “single nucleotide polymorphisms,” which are relatively easy to catalog across the 30,000 or so human genes, and which themselves run into the hundreds of thousands across those genes, but SNPs are far from the whole genetic story.  Larger differences in genes, or how those genes are translated into biological traits, is much more complex to assess.
  • They surmised that, if their score were used to try to predict height, the average gain would be about 2.5 cm (about one inch), with a range of 1-6 cm.  If used to predict IQ, the average gain would be about 2.5 points, with a range of 1-7 points.
  • Then they also looked at 28 actual families with lots of kids, from 3 to 20 (!).
  • For the actual families, the score predicted to cause the tallest child did so for only 7 of the 28 families, and the highest scoring child was actually shorter than average in the family in 5 of the 28 families.  No attempt to assess IQ for these real families, apparently.
  • They point out other reasons why trying to select for IQ might be problematic—potential association with autism and anorexia, for example, as well as just general complexity.
  • They suggest that for most people undergoing IVF, and creating fewer than 10 embryos in the process with less than 100% success after implantation in the womb, the odds are not good for making a reliable forecast of an offspring’s height or IQ.
  • They make these points without commenting more broadly on the ethics or policy wisdom of allowing or encouraging heritable genome editing to proceed.

A complex story, and a developing one, to be sure, but one should not be too quick to accept grandiose promises for predicting complex traits based on genetics.  At least for now, those appear to be rather “ahead of the puck,” shall we say.