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.”

Pandemic Priorities in the Face of Uncertainty

Last week, this space on this blog addressed concerns about overconfidence in judgments about the COVID pandemic, and intimated that some humility is in order, especially on the part of the experts doing the advising and opining.

Now turn the perspective around—humility is in order on the part of us non-experts, receiving and reacting to the experts’ advice.

At this writing, while precision is ever-elusive, it is clear that the number of infections is increasing at an accelerating rate in several states and localities across the United States.  How many of these infected people will require hospitalization, or will die, remains to be seen, but concerns are raised that hospital systems in some areas will be stressed—perhaps not to the degree that New York City or northern Italy saw earlier this year, we certainly hope not—but stressed nonetheless.

And there is a rush to apportion blame, especially to “the other side” of our current, apparently intractable political split.  But, again, humility is in order.

First, hindsight is 20-20, as the old saw goes, and it’s easy to find misjudgments among various public officials.  Some may prove to have been honest, some less so, but scapegoat-hunting seems of little use, except to try to win the next election.

Second, the public health officials have not been purposefully lying to us.  They have generally made their best efforts.  We might rightly take them to task for letting certain value judgments bleed into their scientific assessments.  But there remains much that we just don’t know. 

Third, wearing masks is not principally an issue of rights.  It’s a matter of prudence and neighborliness.  We should wear them in public.

Fourth, we can’t say exactly why the infection rate is increased.  More contact between people, sure.  But which ones?  That remains to be determined.  My local newspaper says today that in my county (San Diego County, CA), family parties of 10-20 people gathered in households appear to be the source of outbreaks.  And maybe gambling casinos. 

Fifth, what is really “essential?”  People need to be able to work and earn a living.  Perhaps we can grant them that, do everything we can to protect them and the rest of us in the process, and voluntarily limit exposures that really aren’t critical.  Some calls may be contentious, I know—should we limit hip replacements while folks can get their nails done, or buy marijuana of dubious medical need?  In a free society we don’t have a Platonic philosopher-king to walk us through that, but we might be willing to offer some tradeoffs and continue to try to help those who suffer loss because of it.

Sixth, we don’t know what outdoor group gatherings have or have not promoted spread.

Seventh, while there is merit from a civics standpoint in asserting that churches ought to be able to meet, there is also merit from a Christian citizens’ standpoint in bearing delays in meeting patiently, and laboring, as the hymn says, to “preach Christ, as love knows how, with witness true and virtuous life” (emphasis mine).

The above are only the opinions of your correspondent.  And the larger priority questions—of health care disparities, priorities of high-tech vs low-tech ethical issues, of different areas of medical care that are being “rationed” from time to time these days—are for future posts here.

Uncertainty, Arrogance, and Mourning in the time of Pandemic

As I write this I have been fielding messages from a friend and interlocutor who, a knowledgeable health industry professional, seems quite confident that had President Trump been successfully impeached—or, better, never elected—the COVID-19 pandemic would not have been such a trouble for us. 

And there may well be something, more than a little something, to this.  Catalogued charges of missed opportunities and willful neglect are well known.  At the same time, in some quarters anyway, Trump’s adversaries have not escaped criticism.

Of the first 100,000 or so deaths from COVID, about 40% are said to have occurred in nursing homes and assisted-living facilities for elderly people.  Joy Riley discussed the situation in a fine post on June 6.  But how accurate is the count?  We don’t know. The government can’t quite get the data, or its rules block collection of the data, or something. 

All the counts are imprecise.  The self-declared uncertainty in the IHME estimates appears rather narrower now than it did in April—it should, with more data—but it still gets wide after a while.  One doesn’t hear much about that uncertainty, unless you consult a site like five thirty-eight.  Lack of certainty does not mean that the modelers are purposefully misleading us, but, although they are making their best estimates to help guide public decision-making, it does guarantee that their projections will be “wrong.”  (The National Weather Service forecasts thunderstorms for Omaha next Monday night, June 22.  I think they are more likely to be accurate.)

How much of a greater outbreak will there be this fall?  We don’t know.  We can and should be concerned, and prudent, and considerate of our neighbors, but we don’t know.

Right now we’re overrun by people of all political persuasions, not just at one “end of the spectrum,” who are quite certain they are right and the other guys and gals are knee-walking stumblebums of the apocalypse.  Add in a dash of ulterior motive or hastiness and you get a lot of folks who, as President Reagan said, “know so many things that aren’t so.”  And then you get high-profile retractions

The pandemic is a poor topic for a bioethics blog because so much of bioethical discourse is about logical argument rather than decisions under uncertainty, or judgments unencumbered by data, and because there is a temptation to get on rather a high horse about matters.  Your correspondent confesses he is all too familiar with the latter.

When the humble (we hope), uncertain, doing-their-best public health forecasters speak, it would help if they would take care to sort value judgments from judgment calls, if they would stay in their lane and point out where their expertise ends and their opinions begin, and if they would resist expanding their remit to make every social concern, as great as those may be, a “public health” issue, and therefore a matter of science, with the attendant risk of false precision and, indeed, category error.  As readers of this blog have recently been reminded, what is “essential,” or more important than something else, is not subject to measurement and experimental verification.

And the rest of us should give those forecasters some grace.

Gerald Seib of the Wall Street Journal recently wrote that there is no goodwill in America anymore.  Sixty percent of people in each major political party think the opposing party is “a serious threat” to the nation.  Forty percent of each party think that the opposing party is “evil.”  About 15 percent (give or take a little) of each party think that violence would be “somewhat justified” if the other side wins the next presidential election.

I once heard a story—no doubt apocryphal, I can’t find it, but it serves my purpose—that Abraham Lincoln, at a friend’s funeral, listened to several people speak then rose to eulogize his dead friend—and just cried and sat down without uttering a word.

Maybe there’s a lesson there.

“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.