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.

Future new CRISPR baby in Russia?

Nature reports that Russian scientist Denis Rebrikov has started experiments intended to lead to editing a gene, in human oocytes (egg cells) associated with human deafness.  Prior reports had claimed that he was working on eggs from deaf women in an attempt to repair the defect and, presumably, provide a normal egg for IVF.  This apparently is not the case—yet.  At the moment, he is using eggs donated by women who can hear, to do experiments on editing the gene in question and ferret out what might go wrong in the process—that is, is the right gene edited, is only the right gene edited, and related questions.   

He says he has had discussions with deaf women, but has not yet sought approval from the Russian regulators to try IVF with a gene-edited egg.  The regulators appear reluctant, and Rebrikov says he will not proceed without prior approval.  He had previously said he wants to edit the same HIV-susceptibility gene that was edited in twin babies born in China last year, but it looks like there aren’t too many candidates for that approaching him, and that attempt has not gone forward—yet.

He’s clearly impatient.  Other scientists working in the gene editing field—which has broad applications short of making “gene-edited babies”—are urging patience, and saying that it is at a minimum rashly irresponsible to rush ahead with the effort, particularly for non-fatal conditions like deafness.  And they are right—too little is known to justify the effort—yet—even if one thinks there are conditions for which it ethically could or even should be attempted.

But “the field” is working hard to define a path forward.  The second meeting of an international panel discussing how to move ahead meets in London November 14-15.

Nature includes a brief Q+A with Dr. Rebrikov.  Forgive me, but some of it is chilling, reflecting blindness to the deeper issues.  Paraphrasing selected questions, quoting the answers, offering italicized commentary:

  • Question:  don’t the risks of trying this outweigh the benefits, for a non-life-threatening condition like deafness?  Answer: “Any new drug carries certain risks. The deafness model is the most appropriate for applying genomic editing at the zygote [newly fertilized egg] stage. And it is only for deaf parents to decide whether … deafness is enough to not expect the same for their child.”  Beg pardon:  heritable gene editing is NOT A DRUG, and the risk-benefit decision is NOT solely the province of private decisions about reproductive-related risks.
  • Question:  the regulators point out that editing people is currently not permitted.  Answer: “Laws are written to change them. As soon as we demonstrate the safety of technology, the rule will change.”  Ahem: some laws are enduring, even eternal—cf. divine law. Recognizing that the regulators’ judgment is not divine, eternal law, reverent attention to the latter should be a paramount concern.  And ‘safety’ appears to be narrowly defined here, blissfully ignoring the deeper human questions posed by modifying people’s genes permanently.
  • Question: people trying to build a regulatory framework for human genome editing think researchers should slow down until the framework is agreed upon. What do you say?  Answer: “Are you serious? Where did you see the researcher willing to slow down?”  Hello!  McFly!  We are not ASKING you to slow down.
  • Question: Russian regulators and the World Health Organization say it is too soon to create edited children.  What do you say?  Answer:  “What does it mean, too soon? Lenin said ‘yesterday was too early, tomorrow it will be too late.”.

Lenin?? LENIN?!  For real??

Addressing gene editing with “thin” bioethics

Yesterday’s post on this blog, by Steve Phillips, warned that a narrow, “rules limited” approach to bioethics reduces ethics in science and medicine to matters of regulatory compliance and risks making thoroughly logical conclusions based on faulty premises that are adopted without regarding “deeper ethical thinking” for which scientists’ thinking must be brought under the discipline of broader humanitarian reflection if correct basic notions of what it is to be human, and what humans should be up to, are to be arrived at.

A different but closely related way to look at this was suggested by John Evans of the University of California, San Diego in his contribution to Human Flourishing in an Age of Gene Editing, a new collection of essays, edited by Erik Parens and Josephine Johnson.  In brief, Prof. Evans commented that too much of bioethics is “thin,” reduced to the Belmont principalism (respect for persons/autonomy; beneficence/nonmalificence; justice) governs human subject research.  This “thin” bioethics is convenient for regulators to use to derive a manageable set of rules, and for scientists to, if you will, hide behind (my expression, not Prof. Evans’s).  Rather, he writes, we must be willing to criticize the assumption that all we need to ask about technology is how to use it, and seek a deeper wisdom about what is a good or worthy human life, for individuals or communities.  In making this argument, he appeals to “critics of technology,” both politically conservative (Leon Kass) and politically liberal (Jacques Ellul).  Jacques Ellul!  How often does anyone hear him mentioned anymore?  How many of us have read him?  (I venture fewer than should!) 

This criticism of worshipping at the Belmont altar, if you will, is hardly new, but it’s critical, especially when something as profound as heritable human gene editing is being considered.  You see, Belmont principalism is quite robust when asking how to deal with clinical trials.  But it really most closely applies to things like regulated drug development, and germline gene editing goes far beyond drug development.  It isn’t drug development at all, and cramming it into the conceptual framework of drug development is fundamentally misguided.

Nonetheless, the International Commission on the Clinical Use of Human Germline Genome Editing appears to be proceeding merrily along the drug development path. The second meeting, in London, is next month; one can sign up for a webcast. Just check out the agenda, especially day 2’s planned sessions on risk-benefit analysis and defining “a translational pathway.”  That language applies to new therapy development, not fundamental alterations of human inheritance.

One should keep in mind also that the assumption one can assess risks and benefits is only as good as one’s data.  This week it is reported that scientists have retracted an analysis suggesting that babies edited for an HIV-susceptibility gene might be at risk of relatively short life spans, something this blog poster readily jumped on in his June 6, 2019 post.   But, then again, so did the prestigious journal Nature Medicine, so I guess I shouldn’t beat myself up too much.  Seems the researchers didn’t define matters carefully enough.  Even if this particular analysis, from a large database of human genetic data, was flawed, similar analyses in the future might be helpful, it is argued.  Until more is known, it is further argued, one should not seize on a retracted analysis to infer a full “green light” to edit unborn babies’ genes.  But that may take “thicker” bioethics than whatever risk-benefit analysis we think we can muster now.

Fewer U.S. Twins and the Development of IVF

Readers of this blog may have seen the report in the general press that, after three decades of increases, the rate of twin births in the U.S. has declined by 4% from 2014 to 2018.

Those three decades correspond to the era of IVF, since the birth of Louise Brown in England in 1978.  It seems likely that changes in IVF practice contributes at least in part, if not substantially, to the trend in twin births.

Specifically, doctors at IVF clinics are more commonly implanting only one, rather than more than one, embryo back into a prospective mother’s womb with each attempt at a live birth.  Multiple pregnancies—even twins, not just “Octomom” scenarios—carry increased risk for mother and babies.  Previously, two or more embryos were implanted in an effort to increase the chance that at least one would make it to live birth.  Sometimes, “selective abortion” was practiced to reduce the number of initially multiple pregnancies to one.  Now, it appears that gradually increasing success rates of IVF are supporting single-embryo transfer as a standard practice.

The Centers for Disease Control and Prevention (CDC), which provides a substantial amount of information on the current status of IVF on its website, summarizes the changes in the percentage of single-embryo transfers in recent years—increasing from 11.6% of non-donor-egg transfers in 2007 to 39.9% in 2016.

To the extent that this reduces the practice of selective abortion and, one hopes, decreases the number of embryos created but kept frozen, never to be born, at IVF clinics, this is a welcome development.  The Christian Medical Dental Association takes the position that, in IVF, the number of embryos should be kept to a minimum, and all embryos created should be so created with the intent of having the genetic mother carry all of them in pregnancy, to live birth one hopes.

IVF remains a transformative enabling technology that facilitates contractual arrangements for reproduction, profound changes in the structure of families, and the use of pre-implantation genetic diagnosis to control what sort of people are allowed to be born.  One might view these developments as non-physical harms, that alter our overall experience of being human in ways that may properly be subject to question.

And: the rate of twin birth is still twice what it was in 1980.  If one sees a mom or dad pushing a stroller with fraternal twins, chances are they are IVF kids.

“Velvet Eugenics”

Human Flourishing in an Age of Gene Editing is a new collection of essays, edited by Erik Parens and Josephine Johnson.  In the introduction, the editors explain they are concerned with “nonphysical harms” of human gene editing.  That is, these harms would not affect bodily systems, but harm “people’s psyches…[their] experiences of being persons,” and could impair human flourishing.  These harms could be incurred not only by gene editing but also by use of other “reprogenic” technologies such as preimplantation genetic diagnosis (PGD) and prenatal diagnosis.

Your correspondent has just begun to read this collection.  In the first entry, “Welcoming the Unexpected,” bioethicist Rosemarie Garland-Thomson of Emory University, takes the view that flourishing is not a matter of proximity to some ideal of health or human excellence, but is, for each person, a growing into expression of that person’s unique capabilities.  Accordingly, rather than embrace a project of eliminating disabilities, society should work to make the environment more welcoming to people with those conditions—many of which, after all, need not impair a person’s ability to live a life of happiness and contribution to others.  Communities have an obligation, she says, “to support the distinctiveness of its members according to the egalitarian principles of justice, liberty, and equality,” and “build environments that…support the widest spectrum of embodiments…in which human embodied existence can successfully thrive as it is.”  Put another way, we should not be building a regime in which we are deciding what sort of people we will allow to be born, but we should be ready to welcome and embrace the ones who are.  In this, Professor Garland-Thomson sounds a “caution against an aggressive normalization imperative…an outlook of humility about the human capacity to control future circumstances through present action…against the arrogance of [what one writer called] ‘the danger of a single story.'”

We should, she writes, adopt a stance of “growing” rather than “making” human beings, and “reconsider the logic of a velvet eugenics that would standardize human variation in the interest of individual, market-driven liberty and at the expense of social justice and the common good.”  In this, she embraces the argument of contemporary German philosopher Jurgen Habermas that rejects “a liberal eugenics regulated by supply and demand.”  One can be forgiven for hearing in this an echo of C.S. Lewis’s worries about “conditioners” in The Abolition of Man.

This is set in the author’s description of her ongoing friendship with three other women, all, like her, married PhD’s who like good wine, good food, and are amply supported by technology and community.  One of her friends is congenitally deaf, another has hereditary blindness, the third has a genetic muscular condition, and the author herself was born with what is now called “complicated ectodactyly,” with “asymmetric unusual hands and forearms.”  The sort of thing your correspondent understands the Chinese to be trying to eliminate through the use of PGD.

A remarkable essay to lead off a collection that appears worthy of careful consideration.

Two developments

A new effort at “somatic” gene editing in China is reported this week.  The key summary:

“As the researchers report in the New England Journal of Medicine,

[note to reader: subscription required]

they transplanted [blood stem] cells that had undergone CRISPR-based editing [of a gene that encodes for a receptor, or “docking station”] into a patient with HIV and acute lymphoblastic leukemia. While [the edited cells lasted for a long time in the bloodstream of the HIV-infected recipient], they only made up between 5 percent and 8 percent of blood cells. A higher percentage is needed for this to be an HIV cure…”

In “somatic” gene editing, mature cells, such as “adult stem cells” or diseased tissues, are gene edited for the purples of treating a fully-formed individual with a disease.  That is what appears to be in view here.  Similar efforts are in progress to treat sickle cell anemia and other genetic diseases.  The ethical issues are relatively well-understood, and fit within the regime of regulating cells-as-medicines in clinical trials of humans, under the ethical and regulatory regime that governs the latter.

That’s in contrast to “heritable” gene editing, which attempts to edit genes in embryos, fertilized eggs (zygotes), or gametes (sperm or eggs) with changes that would be passed on through the generations, as recent entries on this blog have been addressing.  The Chinese twin girls who were reported to have undergone gene editing late in 2018 are examples of an attempt at “heritable” gene editing.

A second report from Nature describes efforts to use human “reprogrammed” stem cells, aka pluripotent stem cells, to make human “embryo-like structures.”  This is distinct from making a human embryo, for example in IVF, then removing cells, likely destroying it, for use in research or to develop medical treatments.  In conservative commentaries in recent years, these “reprogrammed” stem cells are considered the “ethical embryonic stem cells,” because they can’t form a full individual and they don’t require creation and destruction of an embryo, that would under normal circumstances form a full individual.

Thing is, these “embryo-like structures” can still form something called a “primitive streak,” which, in normal embryos, is the first sign of formation of a nervous system.  The primitive streak usually forms 14 days after fertilization, so, to try to avoid concerns about research on embryos, scientists who think such research is ethical in limited circumstances have operated under a “14-day rule”–voluntary in the US, mandated by law in the UK–after which embryos would not be destroyed for research.  These “embryo-like structures” may form a primitive streak, it appears.  The situation is similar to “synthetic human entities with embryo-like features,” or “SHEEFs,” which may bypass the primitive streak but raise similar issues of whether something too like a natural human being is being engineered by this work for it to be ethical.

A developmental biologist at Caltech says, the California Institute of Technology in Pasadena. “We will have to confront ourselves with the question of what is a human embryo, and whether these models really have the potential to develop into one.”  The researchers making these synthetic embryos argue that they lack a placenta and other cells needed for development, so could not develop into a person.

At least for now.

Heritable genome editing: a too-short list of 12 questions

Last week, I discussed efforts by a US/UK commission formed to recommend a framework for regulating and monitoring heritable human gene editing.  This commission has called for “expert evidence” to assist them in the task “to develop a framework for considering technical, scientific, medical, regulatory, and ethical requirements for human germline genome editing, should society conclude such applications are acceptable.”  The deadline is September 27, 2019 to make recommendations.  The website to do so appears open to the public. 

Now, I suppose the commission will ultimately decide who qualifies as an “expert,” and several of the questions are decidedly technical.  But I submit that many who read this blog qualify as experts in bioethics or in some aspect of biomedicine, and will be able to offer considered responses to at least some of the questions.  So I encourage readers of this blog to access the link and weigh in.

I have yet to complete my effort.  I started last week, then pulled back in the middle.  Responses to each question appear to be submitted in real time, and the possibility to save work (there are ‘”back” and “next” buttons) for future editing seemed unclear.  And these questions merit careful responses.  So I decided to wait for another day—before the September 27 deadline!

If you would like to mull over possible responses in advance of trying to offer them online, I have copied them here, for advance thinking before submitting at the online portal, or to inform reflection and discussion otherwise:

  1. Which diseases and conditions, if any, do you see as appropriate for human germline genome editing?
  2. If there were to be an appropriate use case for human germline genome editing, what evidence would be needed to proceed to first in human use?
  3. What is the status of editing mechanisms for early stage human embryos (e.g., using different editing techniques, improving homology directed repair, etc.)? What are the factors that predict whether single nucleotide changes or other intended modifications in human embryos will be correct? To what extent will genome editing affect the viability of embryos?
  4. What is the status of the technology for validating that a correct edit (on target characterization) has been made and that unintended edits (e.g., off target effects, mosaicism, etc.) have not occurred in a range of cell and tissue types? If possible, please provide evidence drawn from work on induced pluripotent stem cells, embryonic stem cells, and/or early stage human embryos.
  5. What is the status of generating cell lines from human and non-human germline stem cells?
  6. How might animal models inform the editing in human embryos (inclusive of analysis of phenotypic correction)?
  7. To what extent do different genetic backgrounds affect success and phenotypic outcomes after genome editing?
  8. What is the success rate of full-term pregnancies following pre-implantation genetic diagnosis? What affects this (e.g., age, number of oocytes harvested, technique used, etc.)?
  9. What are the appropriate mechanisms for obtaining informed consent, long-term monitoring of the future children, assessing potential effects in subsequent generations, and addressing untoward effects? Are there best practices from: a) assisted reproductive technologies; b) pre-implantation genetic diagnosis; c) gene transfer research for children; d) mitochondrial replacement therapy; and e) somatic genome editing?
  10. How should we think about the inter-generational medical (e.g., genetic changes to the genome) and ethical implications of human germline genome editing (e.g., potential harms and benefits)? How should the rights of future generations and the wider human population be taken into account?
  11. What international oversight structures would need to be in place to facilitate, in a responsible way, a path forward for germline genome editing?
  12. Are there any topics or issues that are not covered by the above questions that you think the Commission should attend to during its deliberations?

This last question, of course, is the most pregnant of all.  The list of questions is so technical, so question-begging about whether heritable gene editing should be done at all, that the commission should receive carefully-considered reflections on the meaning of the potential enterprise, how the future practice of heritable genome editing should not be a foregone conclusion, and how and why the right answer to “when should we edit human genes heritably” might well be “never.”

By all means, reader of this blog, go online and offer what you reasonably can to this important discussion!

Much going on about heritable genome editing

The first meeting of the International Commission on the Clinical Use of Human Germline Genome Editing was held in Washington, DC on August 13.  This is a US/UK commission convened by the UK Royal Society, the US National Academy of Medicine, and the US National Academy of the Sciences.  Space for in-person attendance at these meetings appears limited, but information is freely accessible on the internet.  For example, the meeting materials and videos from the August 13 can be accessed here, and one can register to be on the Commission’s mailing list at this link. 

It is challenging for anyone with a “day job” whose work is not dedicated to the field of gene editing to try to keep up with developments, so the open access to information is welcome.  The August 13 meeting included numerous basic science discussions as well as some from biotechnology companies seeking to develop gene editing approaches.  As discussed often on this blog and elsewhere, so-called “somatic” gene editing—that is, gene therapy of fully-formed individuals by editing an undesirable gene such as one known to cause disease–appears generally to fall within the existing regime of human research ethics and regulation and pose relatively few unique ethical issues.   The day included industry presentations regarding somatic gene editing, either “in vivo”—involving injecting the gene editor into a person—or “ex vivo”—involving removing cells from a person, editing the cells in the medical lab, then re-injecting the gene-edited cells into the person’s body as a form of treatment.  In neither case is the editing inherited across generations, avoiding the larger issues of manipulating human beings more fundamentally, and, as your present correspondent has consistently argued, unacceptably.

Even for somatic gene editing, however, “getting it right” in the form of editing the genes intended, and only those, and developing approaches to assess and control for longer-term or unintended risks is still a substantial set of tasks, as was described in a presentation by an official from the FDA.

The day also included a presentation from the separate World Health Organization multidisciplinary advisory panel, which held its first meeting in March 2019 with another one having been due this week in Geneva, Switzerland.  At the March meeting, the WHO panel adopted three main recommendations for developing oversight of human genome editing:

  • Establish a structured mechanism for collecting and curating details about proposed and ongoing research;
  • “it would be irresponsible at this time for anyone to proceed with clinical applications [they mean trying to establish a pregnancy or birth] of human germline genome editing”
  • Establish approaches to obtain input from the “broadest possible range of stakeholders” and “explore opportunities for an open, online mechanism for seeking input.”

All that said, the Salk Institute in San Diego is working on a new technique of editing, called SATI (short for intercellular linearized Single homology Arm donor mediated intron-Targeting Integration [say THAT three times fast!], which is expected to be more versatile than the current “preferred” technique called CRISPR-Cas9.  Biologic details between the two differ, but the ethical issues mainly apply to applications, and are therefore the same for both.  But don’t be surprised if you hear about “SATI” for 5-10 minutes in the news sometime.

And scientists at Cornell Medical Center in New York City are trying to gene-edit human sperm to alter the characteristics of children conceived using them.  Pressing ahead with getting ready for the WHO panel’s “clinical applications.”

Mildred Solomon of the Hastings Center has recently added her voice to those pointing out that whether heritable human genome editing should ever be done is not just a matter of weighing benefits vs risks, but involves much more momentous possibilities that should give us pause.  The key graphs:

“Even as [the WHO and US/UK commissions] regroup to produce clearer guidance, however, I sense a shift in the debate. For a very long time, the scientific and bioethical consensus was that we must not do human germ-line modifications—that we should not change gametes and embryos in ways that would be permanent, affecting all future generations. In contrast, somatic modifications, which affect only the person in whom the edits are made, have been mainly uncontroversial.

But that border between germ-line and somatic genome modification is blurring; the zeitgeist feels different. There is a growing sense of inevitability that we will eventually do human germ-line modification and that our only obligation is to wait until it is safe. When that day comes, we may want to make permanent heritable changes to the human species to eradicate otherwise intractable diseases. We should, however, enter this discussion with eyes wide open, considering each application on its own merits and anticipating a wide range of issues that go well beyond safety. Many of these issues are explored in Human Flourishing in an Age of Gene Editing, which will be published by Oxford University Press on August 28, 2019.”

I’m willing to forgive the plug for a book from people at Dr. Solomon’s institution, which is where the editors of the book in question work.  It looks worth checking out.  In the meantime, the US/UK commission has called for “expert evidence” to assist them in the task “to develop a framework for considering technical, scientific, medical, regulatory, and ethical requirements for human germline genome editing, should society conclude such applications are acceptable.”  Follow this link to have a look at their questions.

Contraception, Climate, and Population Control

This week’s New England Journal of Medicine (NEJM) carries an opinion piece (subscription required) pressing the concern that human-caused climate change should prompt a concerted effort to develop new methods of contraception and increase the ready availability of all forms of contraception worldwide.  About 222 million women in the lowest-income countries need family planning services, the author says.  About 40% of pregnancies (80 million out of a worldwide annual total of 210 million) are unintended, with similar rates in higher- and lower-income nations, it is said.  Past Malthusian fears about overpopulation had subsided with improved agriculture and a leveling, or even declining, fertility rate in many countries, but that appears now to have created a false sense of security, because the world’s population continues to grow, global warming and resource depletion are threatening sustainability of the ecosystem, and “naturalists” warn that half of all species living today may be extinct by 2100 because of human activity.  While the number of people the earth can support has been estimated at between 2 and 100 billion, the author prefers a more conservative “modern estimate” of 1.5 to 5 billion, as opposed to the current 7.7 billion.

Leaving aside the question of why the earth’s carrying capacity is a proper topic within the purview of the NEJM, the author says that currently available contraception is inadequate.  Sterilization “is not suitable” for people who want to have children, hormonal methods have side effects, and barrier methods are not reliably used.  (In case the reader wonders, abortion is not listed.)  Moreover, side effects notwithstanding, needing a prescription for much contraception limits availability and increases costs.  Development of newer methods, including some that would also protect against sexually transmitted diseases, could meet a large need, limit population “growth,” and have the further advantage of giving people more choices.

Unless one is fundamentally opposed to contraception on moral grounds, these suggestions may seem attractive on the surface.  Better, effective, preferably reversible, affordable, widely available, low-risk contraception would be welcomed by most people.  But the primary aim of this particular piece does not seem to be the well-being of individuals, but limiting the number of them overall.  One might object that pursuing limits on population is an invitation to tyranny, just in more sophisticated forms than one-child policies or forced sterilization.  One could not trust full reproductive freedom to “limit the excess population,” as Ebenezer Scrooge famously advocated.  Rather, controls would have to be instituted on who could have children, how many, and under what circumstances, not to mention trying to control what sort of people are brought into the world.  I do not think this is a farfetched concern.  After all, the NEJM writer thinks there are too many people already.  Might not someone (someone else, not the writer of the piece in question) think that some culling would be for the good of the ecosphere overall?  Getting back down to 5 billion from 7.7 billion would be a reduction of about 35%–an apocalyptic figure, to be sure.  I must confess that it would not entirely surprise me to see a future NEJM piece addressing population reduction.