Emerging attempts to control gene editing

Recently, it was reported that the panel convened by the World Health Organization (WHO) to develop standards and guidelines for gene editing will ask the WHO to establish a registry for any projects on heritable human gene editing.  The idea is that, to get research funding, a project would have to be registered, and there would be a required review in order to get on the registry in the first place.  The net effect would be to control the flow of money to such projects.

Also, according to Nature, the Chinese government is looking at amending its civil code, effective March 2020, to in essence make a gene editor liable for health outcomes by declaring that “experiments on genes in adults or embryos that endanger human health or violate ethical norms can accordingly be seen as a violation of a person’s fundamental rights.”  The idea here appears to be to make gene editors think twice about whether they are sure enough of their work to accept essentially a permanent risk of being sued for all they are worth if anything goes wrong in the future.  Your correspondent knows nothing about Chinese civil procedure, but in the litigious U.S., the risk of really big, unpredictable lawsuits at some entirely unpredictable time in the future, with no limit, can make even big companies shy to pursue something. 

So maybe these approaches, by “following the money,” as it were, would at least slow down heritable genome editing, short of a ban.  Skeptics of the utility or wisdom of a ban argue that the “rogues” will just find work-arounds anyway, and that entire states can “go rogue,” limiting the effects of the ban to only the nations willing to enact and enforce it.

That’s a reasonable argument, but it still seems that, by only requiring a registry—with noncompliance always a risk—or trying to up the ante in court—a risk that some entities might take if the perceived reward is big enough to warrant it, and they can hire enough expansive lawyers to limit the risk—there is an admission that heritable genome editing is going to go forward.  And, indeed, maybe there’s no stopping it.  But it seems like promoting a stance toward human life that refuses to accept heritable gene editing is still something we should do.

Brain resuscitation (?) in pigs

By Jon Holmlund

The latest mind-blowing (seriously, no pun intended) report from the science literature is that a team of scientists at Yale Medical School have been able to use an artificial preservative solution to recover electrical activity in some of the cells of the brains from the severed heads of pigs that had been slaughtered for food.  This is absolutely stunning because the understanding—so widely accepted that the term “conventional wisdom” is trite in this case—that the brain’s need for oxygen, nutrients, and the blood flow that provides them is so massive, so constant that an interruption of even a few minutes means irreversible death of brain tissue.  This can be in part of the brain (as in a stroke), or the whole brain (as in brain death).  Your correspondent is not a neuroscientist, but understands that recent research is showing the human brain, anyway, to be more adaptable than historically understood, meaning that after an event like a stroke, function can be restored over time with rehabilitative efforts that support the remaining, undamaged brain tissue adapting to the damage.

In this case, it was four hours after the pigs’ deaths that the researchers isolated their brains and put them into the solutions.  Besides the electrical activity in some nerve cells, the researchers also found evidence that blood vessels could support circulation, and that there was metabolic (energy-using) activity in the isolated brains.  Evidence that the whole brain was working, and able to, for example, “feel” pain or detect stimuli, was not evident, but the researchers were not trying to do that.  Their immediate goal was apparently to understand how long brain cell function might be preserved.

Before we rush to invoke the immortal Viktor Frankenstein, it should be said that the researchers in this case appear to have carefully followed existing ethical guidelines for the research use of animals.  And it is tempting to speculate about this work leading to new treatments for brain injury.

Still, many ethical issues are raised.  What constraints should proper ethics of experimentation on animals put on future, similar experiments?  Is it acceptable to pursue a model for whole animal or even human brains preserved outside the body to study preservation and restoration of function, perhaps even to the point of trying to “jump start” the whole brain, as the current researchers speculate might be necessary.  Or, such a recovery might be impossible; they say they might just be observing an evitable process of brain death and decay.  Maybe it takes rather longer than previously appreciated.

That last point raises further concerns about how we understand when death has occurred.  Do current approaches toward harvesting human organs for transplantation, that may require that blood flow to the brain be interrupted for only a matter of minutes before declaring death of the donor, effectively jump the gun?  Might some people who are thought brain dead in fact have better chance of recovery than appreciated?  These questions already trouble ethicists thinking about how to determine when a person has died.

These are only a few of the concerns, and some authors this week are calling for an international review of the ethics of this work, before proceeding further with research on mammals—never mind humans, that’s not in view, yet.

A summary of the work for the non-specialist is openly available.  Summaries of related ethical issues, also openly available, can be found here and here.  The full scientific report in Nature requires subscription or purchase.

Human brain genes in monkeys

By Jon Holmlund

This week’s news is that a group of Chinese researchers have birthed and studied a small number of rhesus monkeys that were “transgenic” for a human gene associated with brain development.  In this work, monkey eggs (oocytes) were altered by adding the human form of a gene that is believed important to the development of the brain.  This gene is one of the relative few that is different between humans and primates (monkeys, as in the work described here, or apes, such as chimpanzees or gorillas).  That gene is abnormal in cases of human babies with small heads and brains, making it a good candidate for a gene that is critical to normal human brain development.

The gene was added to the monkeys’ egg cells using a viral delivery mechanism.  The monkey genes were not, in this case, “edited” to the human form using CRISPR/Cas9.  (Presumably, that experiment is coming.)  Using the altered eggs, 8 monkey embryos were then conceived and implanted in females.  Six of these survived to birth, and 5 of them lived long enough to do tests on their brains.  These monkeys’ brains looked, on imaging studies and under the microscope, more like human brains than normal monkey brains do, and these monkeys’ brains developed more slowly than normal, mimicking the human situation, in which brain development occurs largely in late pregnancy and then a lot more in infancy and childhood.  The five surviving monkeys also did better on some short-term memory tests than did “natural” monkeys given the same tests side-by-side.  How strong this finding is appears debatable; the number of monkeys tested was small, and your correspondent cannot say how useful the tests are.

The scientists also took sperm from these transgenic monkeys and conceived three other monkeys (again, using IVF, they apparently did not try to breed the animals), all of which were sacrificed before birth, and whose brains apparently showed some of the same features as their “parents'” brains.

Genetically modifying non-human primates is generally frowned upon in the West, largely on grounds of the animals’ welfare, but in China, it’s full-speed ahead.  The Chinese scientists apparently agree with Western scientists that the brains of apes (chimpanzees) should not be genetically altered because they are too much like us humans for comfort.  Monkeys are not so close, in the Darwinian schema.

The investigators in this case think they are learning important lessons about the genetics of human brain development in a model that is enough like humans to be informative.  They also think they are shedding light on human evolution (assuming that the evolutionary model is correct).  Those conclusions seem to be a reach.  The gene in question had already been identified as a candidate of interest, and its association with brain development arguably could be studied in other ways, within the ethical bounds of human subject research.  And it seems unlikely that a creature such as created in this work would ever have arisen from random mutation.  Rather, these transgenic monkeys seem to be an artifact of the investigators’ design, with uncertain relevance.

In any event—off to the races.  Anticipate more work to alter monkeys’, if not eventually apes’, brains genetically.  They might get something really interesting—and hard to know quite what to do with.

Another example of work that seems unethical on its face, done not because they should, but because they could.  The full paper can be found here.  A description for general readership is here. 

The (at least, an) other side of the argument about heritable human gene editing

By Jon Holmlund

Last week’s New England Journal of Medicine (subscription required) included four articles addressing heritable human gene editing (HHGE, if you’ll allow the acronym).  All assumed that it would or should go forward, under oversight, rather than seeking a moratorium.  One took the position that a moratorium is a bad idea, because the “rogues” would press ahead anyway, and the opportunity to create meaningful partial barriers to at least slow down what could easily be a runaway train.

This week, a group of prominent scientists in the field, representing seven nations, take the other side in Nature.  They call for an international moratorium on HHGE.  This is not a permanent ban, nor is it an international treaty banning HHGE until a subsequent action removed the ban.  Rather, they propose that for a fixed time (they suggest 5 years), nations as a group agree to block, and scientists and clinicians agree to abstain from, any attempt to bring a gene-edited baby to pregnancy or birth.  The scientists writing this week would allow research on human embryos to proceed, as part of a broader effort to define the reliability and safety of the editing—something they say has clearly not yet been established. 

During the moratorium, hard work would need to be done for societies to define what people should be edited.  The scientists suggest that HHGE would rightly be limited, pretty strictly, to “genetic correction,” meaning cases in which a defect of a single gene known to cause, or almost certainly to cause, a serious disease would be corrected.  They would not permit genetic enhancement absent “extensive study” into long term and unintended effects, and even then, they say, “substantial uncertainty would probably remain.”  Genetic enhancement, in their view, would include altering genes that increase the risk of diseases.  They don’t cite examples, but it appears that abnormalities like BRCA1 mutations that increase cancer risk are in view here.  Further, which medical conditions would have no alternative to HHGE must be determined.  In most cases, IVF and preimplantation genetic diagnosis would likely suffice, obviating the need to take the profound additional step of HHGE (whatever one may think of the moral status of the human embryo).  The cases eligible for HHGE, they suggest, would be “exceedingly rare,” limited to essentially unavoidable situations for which a “small minority” of genetic diseases is caused by a genetic abnormality that is frequent in the population.  (It seems like such situations would be rare indeed.)  In such cases, they say, “legitimate needs” of couples seeking to have unaffected, biologically related offspring would need to be weighed against “other issues at stake.”

Most critically—and, hardest to achieve—the scientists envision a broad, intensive effort, that is not limited to or driven by scientists and physicians, and that goes beyond current regulatory regimes to include all aspects of society in an effort to achieve broad consensus—neither simple majority nor unanimity, but a situation in which the clear, large majority opinion exists on when and how HHGE should be countenanced.

Whether these tasks could be pulled off in five short years is something to wonder about, and even allowing planning for HHGE under these constricted circumstances raises questions about how we understand our humanity, whether embryos should be treated as raw materials in development of new treatments, and other matters that go deeper than discussions of medical, scientific, and population risks and benefits.  Were the tasks achieved under a moratorium, the authors envision that individual nations would be sovereignly free to go separate ways, with some allowing HHGE, but perhaps others not.

The editors of Nature, without taking a side about a moratorium per se, call for rules to be set, broad societal conversations to take place, research to be carefully overseen to be sure it is on a “safe and sensible” path and to identify and stop the “rogues,” and journals to refuse to publish work that transgresses limits in place at the time.

With something this big, a “presumption to forebear,” rather than a proactive drive to progress, should be the dominating sentiment.  The details are too complex to address in a few articles, a few short blog posts, a few minutes on cable news, or a few passing conversations wedged into the cracks of busy lives.  We should slow down.  We should ALL call for a moratorium. b

One side of the argument about heritable human gene editing

The current issue of the New England Journal of Medicine (subscription required) includes four new articles addressing heritable human gene editing.

George Daley (who was also discussed in a post on this blog last December 6) argues that work must proceed to find a responsible way of editing the human germline for people with genetic diseases that are devastating, untreatable, and largely unavoidable unless affected people forego having children.  This would be a limited use of heritable gene editing, he holds, although it may ultimately become attractive to the 1-4% of offspring of unrelated people who have genetic diseases, who seek to eliminate risk of passing on those diseases, or risk of them, to future generations.  He thinks that “our ignorance” regarding genetic complexity will ultimately prevent attempts at begetting genetically enhanced, “designer” children.

Matthew Porteus reviews “the new class of medicines” becoming possible due to DNA editing.  These include genetically modified cells as drugs, other attempts to treat existing people with known genetic disease by editing genes in part of their bodies, and, eventually, editing humans so that the genes they transmit to future generations are permanently altered. 

Lisa Rosenbaum reviews several of the objections to heritable gene editing that can stand in the way of scientific and social consensus.  Among these, she points out that people with disabilities often live very fruitful lives—lives that may never have come to be if their parents had the chance to edit their genomes, or not brought them to birth in favor of another embryo selected, without editing, through preimplantation genetic diagnosis.  But some disabilities are too severe to allow fruitful lives.  In such cases, she asks, “who is qualified to decide whether it is ethical to alter these children’s fate?”  If you think you can edit a baby destined to suffer severe genetic disease, are you obligated to try?  In that case, there’s “no such thing as an ‘informed decision’…you can’t know until you know.”

Alta Charo, who has co-led several recent prominent international conferences on human gene editing, argues that the “rogues” will proceed to edit people irresponsibly, even—and perhaps especially—in the face of a moratorium.  A more effect approach would be an “ecosystem” of restrictions, including formal regulation, restriction on supplies of raw materials (that is, human eggs, sperm, and embryos) for experimentation, patent and licensing restrictions, health insurance policies, liability for lawsuits, and the like.  Broad, international consensus is an unlikely prospect, she argues, but individual nations may enact their own regimes.  Whether this would really stop a black market is questionable, and heritable editing would become the province of favored entities (government or industry), I suppose—perhaps slowing the whole process down but leaving objections to the practice unsatisfied.

Each of these authors condemns He Jiankui’s claimed editing of Chinese twin girls who were born late last year.  Each of them also clearly takes the position that human gene editing should be regulated, either because it should proceed or because it will, inevitably, proceed. 

None of the authors suggests that heritable human gene editing should “never” be done, the position Francis Collins, the head of the US National Institutes of Health, took on Gerry Baker’s WSJ at Large on the Fox Business Network on Feb 22, 2019.  (I would link it but it appears that the clip has not been preserved on the network’s website.)

This blog recently recounted some reasons why heritable human gene editing should not be pursued.  But the train appears to have left the station.

The new WHO advisory panel on human gene editing

By Jon Holmlund

The World Health Organization (WHO) has empaneled an expert advisory committee to propose standards for governance and oversight of human gene editing.

This group is to meet in Geneva on March 18 and 19 to review the state of the field, broadly, and formulate a plan for its work, over the ensuing 12-18 months.  Sounds like your basic organizational meeting. 

The WHO website does not specify a more detailed charge for the committee, which no doubt will determine its goals.  It is said to have been formed “after an open call for members,” implying, I suppose, that the members volunteered, as opposed to being invited or otherwise prevailed upon.

The co-chairs are Edwin Cameron, former Justice of South Africa’s Constitutional Court, and Margaret Hamburg, who, among her other positions, was FDA Commissioner under Barack Obama.

A review of the full list of biographical sketches for the members shows that they are a truly international group, representing nations from the developed and developing world, and from all continents (except Antarctica, of course).  They are a mix of physicians, biologists, and ethicists.  None appears immediately recognizable from the recent media coverage of human gene editing.  If there are members with a specific interest in promoting technology, that is not obvious from the list, which WHO further says was limited to people screened carefully for conflicts of interest.

One can tell but little from such bio sketches, but in this case it at least appears that a broad range of cultural perspectives will be represented.

There is no clear representation for a theistic or religious perspective.  Also, because the work of such a group naturally draws and involves scientific specialists, the broader, non-scientific, “lay” public is not represented.

Past work by these members addressing gene editing will be of interest to review, which your present correspondent has not, yet.

One hopes that this group will offer wise counsel that, as discussed in prior posts to this blog and elsewhere, goes beyond the usual, limited “benefit-risk” estimates that characterize Western bioethics.

But it will unavoidably not constitute the broad, cosmopolitan, multinational and multiethnic, naturalistic and theistic dialogue that is hoped for—probably too much to hope for, too much to ask of a group of 18 people—in advance of broad adoption of heritable human gene editing, which appears inexorable.

Godspeed and best of success to this group—follow its work as closely as possible. ity51 \lsdl

Summarizing ethical issues with heritable human gene editing

By Jon Holmlund

A brief recap of reasons why we should not pursue heritable human gene editing:

It seems unlikely that risks to immediately-treated generations can be predicted with the accuracy we currently and reasonably expect from human subject research and medical practice.

Risks to later generations, that is, to the descendants of edited people, would be incalculable, and the informed consent of those later generations would be unobtainable.

To allow heritable gene editing even in the uncommon cases of untreatable, devastating genetic illness is to place too much faith in the ability of human providence to identify, and human behavior to observe, firm boundaries on its eventual use. 

Eventual use will become unavoidably subject to a eugenic approach in which the key decision will be what sort of people do we want, what sort of people should be allowed to receive life.

There will be no end to the disagreement over what edits should be permitted, and to the vilification of those considered to have been illegitimately edited, from those who object to their existence, perceived unfair advantage, or other characteristic.

Human populations will become stratified into the “edited” and the natural, introducing deep new justice concerns.  The main issue will be not will humans be gene-edited, but what should be the social status of those who are. 

To reduce heritable human gene editing to a reliable practice requires submitting it to the paradigm of manufacturing, as in drug development, with children seen as quality-controlled products of choice, not gifts of procreation.   To develop the practice, a “translational model,” again analogous to drug development, is necessary, with human embryos serving as raw materials, and, of necessity, a large, indeterminate number created and destroyed solely for development purposes, for the benefit of other humans yet to be born, and of those who would raise them.

Quite possibly, the translational model will demand great license on the extent to which embryos and fetuses may be experimented on; to wit, longer and longer gestations, followed by abortion of later and later stage, to further verify the success of the editing process.

In the extreme situation, the degree of editing may change the human organism in ways that will create a “successor” species to homo sapiens whose nature and desirability cannot be reasonably envisioned at this time.  In the extreme situation.

Even granting that this last scenario may never really arrive in ways that fiction writers can easily imagine, the other reasons should be enough that we simply don’t move heritable gene editing forward.

National Public Radio recently reported on the gene editing of human embryos—one day old—in the laboratory, in an attempt to correct and eliminate the inherited cause of blindness, retinitis pigmentosa.  The end is laudable.  The means is not.  We should not race ahead without considering why, first.  Then, we should not move ahead, but seek alternate means to the medical ends.

Edited embryos should not be created and brought to term—certainly not now, and I would say, not ever.  To be outraged over the former but not the laboratory creation of edited embryos is insufficient.  Both are outrages, although outrage over the recently-claimed birthing of edited babies in China is real, not “faux,” as one reaction held.  Still, the authors of that reaction are correct that one’s condemnation of the China event somehow justifies the laboratory work.  It does not. One last point: The Economist carried an essay decrying the birth of the edited twins in China as a case of “ethical dumping,” the practice of carrying out human subject research that would be disallowed in the West in other, perhaps less advanced (although China is certainly not backward), nations with fewer ethical scruples.  A valid point—but not one to cloak oneself in, while trying to justify the efforts to edit humans in ways that can be passed on from generation to generation.

Human organ harvest

By Jon Holmlund

The ethical practice of human organ transplantation entails consent from a donor to donate an organ while still living (e.g., one of the donor’s two kidneys), or after dying (e.g., the heart).  In the latter case, it is still generally accepted that the donor must be dead first, and that the harvesting of the vital organ to be transplanted not be the cause of the donor’s death.  This is referred to as the “dead donor rule,” the interpretation of which is open to some controversy (about which more in a future post).  But it is still generally followed.

Periodically, one reads of suggestions or practice that violates this.  In 2006, the bioethics observer Wesley Smith posted comments about proposals in the medical ethics literature to the effect that some had said that patients permanently comatose but not dead, in what is known as a “permanent vegetative state” (PVS), could ethically not only have their organs harvested for transplant, but be human subjects for experimentation involving the transplant of animal organs into them, to try to learn how to improve that practice, called “xenotransplantation.”  Presumably, these “donors” would have previously “consented” to have their organs harvested—essentially, to be killed—if they became persistently comatose.  The validity of such “consent” is of course questionable, and the prospect of the practice should be seen as abominable.  An argument in favor seems to rely on the notion that it’s too risky to transplant animal organs into humans who have full brain function and seem to be more clearly alive than PVS patients (suggesting they be seen as dead), or that there is some envisioned state where a PVS patient could potentially benefit from the animal organ and give consent in advance.  The former is disturbing, and the latter implausible.  A link to one proposal that appears to be in favor is here, and to arguments raising concerns, here and here.

(More to follow in a future post on comments about xenotransplantation from the recent Hastings Center conference on the 50th anniversary of the development of brain death criteria.)

More recently (again with the blogger’s “HT” to Smith), not only is organ harvesting after euthanasia apparently performed, on occasion, in countries that permit euthanasia, but a transplantation medical journal has carried an article arguing for “organ donation euthanasia,” wherein someone who had previously requested euthanasia could also “request” organ donation while still alive—essentially, authorizing the removal of the heart as the means of active euthanasia.  Now, what is first in view is harvesting a kidney, which would not cause death, but if someone is in a state where euthanasia is perceived as a preferred option, why would someone want to undergo invasive surgery first? 

If euthanasia is accepted, then this troubling stance on organ donation will be difficult to resist.

At least the above pay lip service to “advance, informed consent.”  This week, an article in the Wall Street Journal calls attention to the covert but well-attested practice in China to accommodate demand for organ transplantation without the encumbrance of a waiting list, by harvesting organs from prisoners of conscience, such as political dissidents, who are given a mortal but not immediately fatal wound, then have their organs removed before they are dead—satisfying the “need” for a donated organ while finishing the prisoner off.  Because of this practice, several countries have prohibited their citizens to travel to China for “transplant tourism,” just going there to get their transplant.  What the Chinese seem clearly to be doing should not be supported, by anyone.

Gene-editing public discussions: looking ahead

By Jon Holmlund

Passing along word that the National Academies of Medicine and Science are planning an international commission on human gene editing, the editorial board of the New York Times has issued a welcome call to make the public discussion of the issues as broad as possible.  Read the whole thing, but this key graph is particularly important (emphases mine):

“As gene-editing technology advances toward the clinic, scientists will need to do more than listen to the concerns of bioethicists, legal scholars and social scientists. They will have to let these other voices help set priorities — decide what questions and issues need to be resolved — before theory becomes practice. That may mean allowing questions over societal risks and benefits to trump ones about scientific feasibility.”

See the 29 March 2018 post on this blog regarding two calls—the Times linked to one, and quoted from the author of the other—for broader discourse.  This discourse is urgently needed, but must go beyond risk-benefit discussions to the broader meaning of, and issues raised by, heritable human gene editing in particular.  (Somatic human gene editing, to treat a known disease in an existing individual in a way that cannot be passed on to the next generation, is less troublesome ethically, except insofar as it enables the heritable version of gene editing.)

The challenges to effective public deliberation of heritable human gene editing are formidable: getting truly wide participation; getting the scientists to inform and educate non-scientists without trying to lead them to a set of preferred conclusions; engaging the developing, as well as the developed, world; obtaining “religious input” that is more than token; and sustaining the conversation as long as necessary to hold attention in our short-attention world.

It seems that to execute on that will take a pretty large group of dedicated people engaged in a focused, full-time effort to make it happen.  Existing science and ethics groups, like the National Academies, may be the default nominees, but it also seems like a broader group of facilitating entities is needed.  The “global observatory” mentioned by the Times editorial would, as proposed, be established by an “international network of scholars and organizations…dedicated to gathering information from dispersed sources, bringing to the fore perspectives that are often overlooked, and promoting exchange across disciplinary and cultural divides.”

Hear, hear.  One hopes that this happens—and that individuals can find a way to help make it happen.  Spread the word—people should be encouraged to set aside time, energy, and mental space to consider this revolution for the human race.

Revisiting the definition of death

By Jon Holmlund

The Hastings Center shows Christmas Day 2018 as the date of publication of its report, “Defining Death: Organ Transplantation and the Fifty-Year Legacy of the Harvard Report on Brain Death,” arising from a 2018 conference of the same title at Harvard Medical School.  The full contents are freely available at the link above.  The occasion for the conference was the 50th anniversary of the 1968 report that defined brain death as one way to determine, alongside the more traditional use of cessation of the heartbeat and breathing, whether a person had died.  Report contributor Robert Truog puts it this way: brain death can be thought of as “permanent apneic [absence of breathing] unconsciousness.”

Subsequent to the 1968 report, the Uniform Determination of Death Act, formulated in 1981, stated that a human has died if there is either irreversible cessation of circulatory and respiratory functions, or irreversible cessation of all functions of the entire brain, including the brain stem.

Initially, according to one retrospective, the 1968 report was motivated mostly by a desire to determine when intensive medical care of a comatose person could be stopped and still be consistent with the aims of medicine, and, indeed, avoid a murder charge.  Nowadays, we often associate the use of the brain death criteria with the decision to harvest the decedent’s organs for transplantation, but that is said to have been a secondary concern in 1968, probably reflecting the state of organ transplantation at the time, as opposed to after the ensuing 50 years of development.

One reviewer in the report worries that concern about the use of brain death criteria has become “too philosophical,” as it were; the 1968 conferees were not trying to define death analytically, but prudentially, to guide the practice of medicine.  So contemporary critics shouldn’t be too harsh in their hindsight.  However, Robert Veatch counters that to ask whether the brain has irreversibly stopped functioning is not the same as to ask whether we should treat individuals with dead brains and beating hearts as dead humans.  He further comments that, since the brain also acts in some sense as a gland, secreting hormones, the current ways of determining brain death may not take that into account.  He identifies three broad approaches to defining death:  circulatory/somatic, whole-brain, and higher brain.  He lists at least six current significant disputes about brain death: whether patients and families should have the right to refuse treatment; which criteria to use to determine brain death; whether those criteria actually assess all the functions of the brain; whether doctors apply the criteria accurately and consistently, without excessive error; whether brain death as currently determined is truly irreversible; and whether whole-brain criteria should be favored over criteria around blood circulation or criteria that focus, more narrowly than whole-brain death, on higher-brain functions including loss of consciousness and associated loss of integrated function of body and mind.

Sections of the new report include essays reviewing and offering a contemporary critique of the concept of brain death, a discussion of whether “donation after [brief] circulatory determination of death” (DCDD) is an acceptable approach to obtaining vital organs for transplantation, whether the “dead donor rule”—briefly, the idea that one’s organs should not be removed from one’s body for transplantation into another person until that one (the proposed donor) has died—should be followed, using brain death to inform law and public policy, the future of xenotransplantation (specifically, transplanting animal organs into humans, known as xenotransplantation), and reflections on the case of Jahi McMath, the girl who was declared brain dead in 2013 after complications of a tonsillectomy, but whose body was subsequently kept alive at her parent’s behest until bodily functions finally failed to the point where she was declared dead to the agreement of all concerned in mid-2018.

There is much to consider here—particularly alongside the 2008 report, “Controversies in the Determination of Death” by the then-President’s Council on Bioethics.  Candor requires that your correspondent has in the past argued on this blog for the dead donor rule and has expressed concern about potential overzealous use of the “DCDD” approach by transplant surgeons in a hurry to procure organs for transplant to a needy, waiting recipient.  But a revisiting of the matter is in order, and a matter for future posts.  In the meantime, the cited reports are readily available on the internet for review by all interested parties.