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.

Gene-Edited Animals as Trailblazers

By Jon Holmlund

 

The Chinese researcher who says he edited the genes of two recently-born twin girls is named He.  He’s not a deity, that’s just his name.  (I don’t think it’s pronounced with a long “e,” by the way.)  His motivation appears to have been to be the first, to show that He could really do it. 

While scorn is mostly being heaped on He, this work has been going on in livestock for a long time, in attempts to make animals with leaner meat, or more meat, or ones that are disease-resistant, or more tolerant to hot or cold weather, or ones that have softer or more durable fur for shearing and making into cloth.  Or, cattle could be altered so they don’t have horns, and don’t have to be dehorned after birth.

Proponents consider this work to be just like crossbreeding, only a lot faster.  That’s an oversimplification, of course, since cross-breeding follows naturally occurring processes of genetic modification, not the synthetic editing of specific genes, but for the moment that’s beside the point.  The agriculture industry is keenly interested in it—the potential could be large.  Some governments want to push it.  Which ones?  You guessed it—China—but also the US, as part of the current administration’s efforts to reduce regulation and foster innovation.

Reportedly, some of these animals’ meat has been tested, and found safe.  (No claim, yet, that it’s delicious.)  But nothing commercial, at least not yet in the U.S.

One problem, though:  the animals have unpredicted other abnormalities.  Some pigs edited to be meatier also had an extra vertebra in their spines.  Some rabbits similarly edited had unusually large tongues.  And the edited animals often don’t make it to live birth, or even implant into adult females to cause pregnancy.  The process sometimes uses cloning to create the animal embryos in the first place, and it’s speculated that the cloning process, not the specific gene editing, is causing the problems with pregnancy.  But that’s not for certain.

In recent decades there has been a hue and cry over the safety of genetically modified plant foods, but they appear to be safe for human consumption, and they don’t fundamentally alter the biosphere.  The meat or milk or fur of genetically engineered animals would seem likely to be safe for human use, also, and if the animals really are created just for human use, some bizarre deformities may not be so objectionable.

Of course, that prompts questions of animal use and welfare that require more than a short blog post.  But in the case of humans, we would anticipate living with and caring for gene-edited offspring.  We would not be producing them solely for use or consumption.  Or would we—for example, for organs to transplant?  Probably not.

Proponents of limiting the use of artificial human reproductive techniques sometimes argue that it is good for children to be received as gifts, and that, rather than being “ordered to specification,” their specific characteristics be welcomed as something of a surprise.  I suppose that off-target effects of heritable human gene editing could prove to be surprises, indeed.

One scientist quoted in the general press says that, regarding editing animals, ‘if we don’t try, we will never learn.” Another, an animal advocate, says, again about the animal work, “I think it would be an understatement to say we should be more cautious…I think we’ve already gone over the line with animals, and now humans.”

For sure, and now, with humans, a major question will be, how will we regard and handle the mistakes?

“The Babies are the Experiment”

By Jon Holmlund

 

The Thursday, Dec 13 edition of the Wall Street Journal carries this headline:  “Doubts Arise Over Gene-Editing Claim.”  The work behind the recent report that the world’s first two gene-edited babies had been born has been publicly discussed, but the details have not yet been published for full scientific review.  Apparently scientists in the gene-editing field are reviewing the public presentation and finding it lacking:

  • Some, but not all, of the cells in the children may have been edited. One would expect changes in all of the cells, and this should be necessary for the overall stated medical goal (protection from HIV infection) to have a chance of having been met.

The edited babies may have variants of the edited gene that have not been fully studied and could have unforeseen health consequences.

The technique used to confirm the gene changes may not be sensitive enough to detect whether other, unintended and potentially undesirable gene changes had been made.

And perhaps most notably, the studies done in mice to demonstrate the feasibility of the technique, before editing the embryos that grew into the full-term babies, involve a different change in the target gene in mice than the change sought in the children. In other words, the animal studies appear not to be representative of the human situation.

This is a common problem for development of new treatments for cancer and other diseases.  Tests are initially done in animals—usually mice—to determine whether the putative new treatment appears to be working.  The animal models used never entirely reflect the human disease.  Some come closer than others.  But the way of handling that uncertainty is to define and limit the risks to people who subsequently have the new treatment tested on them in clinical trials.

In the case of the gene-edited babies, there’s really no way to limit the potential risks, at least not yet, if ever.  Ultimately, one has to strike out and make changes that could backfire for the recipient humans, or be propagated into their descendants with unpredictable effects. 

Accordingly, without good animal models, and appropriately extensive testing in them, then, as professor Sean Ryder of the University of Massachusetts Medical School is quoted as saying, “the babies are the experiment.”  Ultimately, heritable gene editing may just require a leap of biomedical faith.

We should just say, “no, we shall not.”

Human Embryos as Raw Materials

By Jon Holmlund

 

This past Tuesday, the Presidential Symposium at the 2018 Annual Meeting of the American Society of Hematology (ASH) addressed human gene editing.  The speakers included NIH Director Dr. Francis Collins, who spoke about somatic gene editing.  That’s the attempt to edit disease-causing genes in existing, fully formed individuals who have the disease in question, as treatment.  It’s generally well-addressed by our current ethical principles for human subject research, and it’s easy to agree that it is an appropriate use of gene editing technology, which has become so widespread—and, indeed, largely uncontrollable—because of the recently-discovered, highly efficient, easy-for-scientists-to-use CRISPR-Cas9 system.  The NIH has a specific Somatic Cell Gene Editing program.

Dr. Collins was followed by Dr. George Daley of Harvard, who presented a thoughtful case for proceeding with heritable gene editing—i.e., of germ cells (eggs and sperm) or, more likely, embryos, specifically during in vitro fertilization.  The recent editing of twin babies, announced in Hong Kong, was highly irresponsible, he said—in agreement with the vast majority of expert and general public commentators.  Fundamental principles of human subject research had been disregarded.  We must do what we can to guard against “hubris.”  Nonetheless, he agreed with the U.K.’s Nuffield Council opinion of earlier this year that ethical uses of human gene editing can be imagined.  Specifically, rare, serious genetic diseases untreatable by other means would qualify.  But rarity should not be a rigid requirement; there might be other genetic diseases for which future research would identify heritable gene editing as a viable if not preferred approach.  A “stop sign” or “red light” should be erected at enhancement—e.g., trying to edit genes to get more muscular or smarter people.  But this seems like a distant prospect.  Dr. Daley ended by endorsing a statement of the recently-concluded international symposium on gene editing in Hong Kong:  a “rigorous translational path” should be defined for human gene editing.  In everyday English:  steps to refine the technique in the laboratory should be taken, and steps needed to bring that work to the editing of people should be identified, in much the way that current regulated new drug development follows a series of well-defined steps.

But the actual translation should not go forward until there has been serious consideration of the societal and ethical concerns.  Some such efforts are happening now, he said.  I’ve blogged over the last few years about some of these, but you may not have heard of many, much less had a chance to contribute or had any way of thinking that concerns you might have would be properly represented.  Indeed, as I have said on this blog earlier this year (see my March 29 post, for example), it’s hard to imagine how to conduct social deliberation of the scale required by the utterly revolutionary prospect of human gene editing.  In a Q+A panel session, Dr. Collins asked Dr. Daley whether the answer to such deliberations might be “no”—might there be a decision not to proceed at all with editing human embryos?  Dr. Daley said, “yes, of course,” but I wonder.  For his part, Dr. Collins had sounded a highly cautionary note:  Embryo editing raises serious safety concerns, issues of informed consent, and questions about what it is to be human, he had said.  Perhaps its proper use would be so narrowly circumscribed that it really is not worth the trouble.  “Bad cases make bad law,” as it were, he had said.

After my post of last week, an inquirer had wondered aloud whether someone contributing to this blog might be able to figure out how many embryos had been destroyed in the run-up to the Chinese twins’ birth, or, for that matter, for the other laboratory experiments done so far in human gene editing.  Skeptical that such data exist anywhere, your correspondent nonetheless asked Dr. Daley in the Q+A whether there was any way reliably to estimate the “supply need” (I used that phrase) for human gametes or embryos in the course of the “rigid translational path.”  Dr. Daley of course could not make any more precise estimate than “very many embryos” would have to be destroyed in the process.  I must concur; I cannot see how a quantitative estimate could be made.  He allowed that moral objection to this would be one of the issues with this work, and commented that in the U.K., plans are to issue licenses for the necessary embryo experiments as part of an attempt to regulate them.

But the emerging picture is that human embryos are “raw materials” supporting the “translational” development of heritable gene editing, much as starting chemicals are raw materials for the production of a new drug.  That production process is governed by a panoply of regulations collectively referred to as “Good Manufacturing Practice,” a term that was applied to human gene editing more than once in the aforementioned ASH symposium.

I also asked whether the so-called “14-day rule” that scientists voluntarily follow as a time limit on human embryo research—i.e., don’t let them get more than 14 days old before killing them—would have to be relaxed.  Dr. Daley thought not.  I must say I wonder.  If embryos could be maintained in the lab for more than 14 days—something that still is not technically feasible, but is being actively contemplated by scientists in the field—might someone not insist that their development be followed as long as possible before taking the step of trying to bring them to term—that is, to full pregnancy and birth?

Perhaps not.  Unless more sophisticated “hatcheries” are developed, edited embryos would have to be implanted in a woman’s womb, after which there would be a progressively stronger presumption against aborting them, the older their gestational age.  But such a presumption would not be absolute under current American law and jurisprudence.  To be sure, the later a research abortion—currently prohibited in the U.S.—the greater a risk to a pregnant woman, not just the fetus being aborted.

And other intrepid actors, somewhere in the world, might well try to proceed outside a fully-regulated framework, purposefully setting up assessments at various gestational ages.

I must add that one liability of the line of thinking I have been taking here is that it might promote the misconception that the principal or even only reason to object to heritable human gene editing is a “pro-life, anti-abortion, religious” concern about the moral status of human embryos.  Not so, although the status of the embryo is a critical consideration.  There are lots of other reasons to object to this revolutionary development, and to say, as Dr. Collins suggested that “the answer should be ‘no.'”

About which more, much more, in the coming weeks.

 

The Genie is Out of the Bottle

By Jon Holmlund

 

Much has already been written and said—mostly in condemnation–about this week’s announcement of the birth of the first gene-edited baby (or, better, babies—there are twins).  A gene was altered in embryos created through in vitro fertilization, and then the embryos were transferred to their mother, who carried them to term and, reportedly, normal delivery.  The babies are said to be in good health.

A couple of good summary articles, written for non-specialists, are online from Science News and the science journal Nature. Follow those links to read more than your correspondent can write here in a short blog post.

The scientist who did this used the CRISPR-Cas9 system to alter a gene called CCR5, which is a receptor, or docking post, for the HIV virus.  Presumably, altering CCR5 would reduce the risk of HIV infection if not prevent it altogether.  The twins’ mother is reportedly not infected with HIV, but the father is.  How much risk this placed the babies at is questionable—usually, babies infected with HIV become infected because of transmission from an infected mother.  HIV can cause infection through other receptors, and altered or disabled CCR5 can increase risk of other infections.  So, overall, the medical need was questionable, there were (actually, are, one needs to see how their health is in the future) potential correlative risks to the babies, and there were likely other means to avoid what appears to have been an unlikely prospect of these babies getting HIV from their father.  Because of concerns like this, ethicists have been arguing that the action violates human research ethics, in which risks to subjects must be minimized, and benefits must outweigh risk.  Any ethics board reviewing a proposal would assess this rigorously, and ask whether there are safer alternatives to the research.

The experiment is said to have worked in this sense—analysis of their DNA shows that the target gene, and no other genes, was altered as intended.  Clearly, the rationale for the editing was to show that it could be done.  George Church, ever the risktaker in the name of “advancing the field,” argued in an interview that because HIV is incurable and there is no vaccine for it, that constituted an unmet medical need in this case.  He also argued that the scientist in question only failed to complete the proper “paperwork,” and that there might be long-term safety issues with heritable gene editing but that would not be dispositive because he is quite confident that those risks will be small, like the risks of diagnostic medical imaging.  To all of which we must respond, “rubbish.”  We do not know what the long-term risks are, ethics boards are rigorous about risk assessment for any and all experimental procedures, and the medical need in this specific case was dubious.

Nature reports that this work “has prompted an outcry from scientists, who are concerned that [the scientist] leap-frogged international discussions on the ethics of such interventions and has put the children at risk of unknown long-term health effects. ‘This experiment exposes healthy normal children to risks of gene editing for no real necessary benefit,’ says bioethicist Julian Savulescu.”  For those who are not formal students of bioethics, Julian Savulescu is hardly a Luddite or a God-fearer who is nervous about new technologies.  He’s right, in this case.

Note the concern about “leapfogging” discussions of the ethics.  This point is also well-taken.  Scientists have been arguing that broad, public discussion of the ethics of human gene editing is urgently needed.  On March 29 of this year, your correspondent—who is scrambling to catch up even to this week’s commentary—posted about two such arguments.

But the genie is out of the bottle, and things are moving faster than most folks can keep up with.  The work reported this week was from China, but was not part of some Chinese government effort—it appears to have been entirely on private, intrepid initiative.  As a writer in the San Diego Union Tribune wrote this week, Pandora’s box has been opened and can’t be closed.

This week’s announcement came at the international conference on gene editing, in Hong Kong.  The two days’-plus of proceedings, including a session with the scientist who did the work discussed here, can be accessed online.  The conference main web page is here.  The proceedings archived on webcast appear to be accessible here.  A summary of the Q+A with the scientist is here.

Oh, BTW—at the end of the Nature summary linked at the top of this post was a chance to vote on whether this application of gene editing was justified.  I voted “no,” as did 82% of respondents at the time I voted.  That left “yes” at 18%.

18%?? For real?