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

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.

Are AI Ethics Unique to AI?

A recent article in Forbes.com by Cansu Canca entitled “A New Model for AI Ethics in R&D” has me wondering whether the ethics needed for the field of Artificial Intelligence (AI) requires some new method or model of thinking about the bioethics related to that discipline. The author, a principal in the consulting company AI Ethics Lab, implies that there might be. She believes that the traditional “Ethics Oversight and Compliance Review Boards”, which emerged as a response to the biomedical scandals of World War II and continue in her view to emphasize a heavy-handed, top-down, authoritative control over ethical decisions in biomedical research, leave AI researchers effectively out-of-the-ethical-decision-making loop.

In support of her argument, she cites the recent working document of AI Ethics Guidelines by the European Commission’s High-Level Expert Group on Artificial Intelligence (AI HLEG). AI HLEG essentially distilled their AI ethical guidelines down to the familiar: Respect for Autonomy, Beneficence, Non-Maleficence, and Justice, as well as one new principle: Explicability. She downplays Explicability as simply the means to realize the other four principles. I think the demand for Explicability is interesting in its own right and will comment on that below.

Canca sees the AI HLEG guidelines as simply a rehash of the same principles of bioethics available to current bioethics review boards, which, in her view, are limited in that they provide no guidance for such a board when one principle conflicts with another. She is also frustrated that the ethical path researchers are permitted continues to be determined by an external governing board, implying that “researchers cannot be trusted and…focuses solely on blocking what the boards consider to be unethical.” She wants a more collaborative interaction between researchers and ethicists (and presumably a review board) and outlines how her company would go about achieving that end.

Faulting the “Principles of Biomedical Ethics” for failing to be determinant on how to resolve conflicts between the four principles is certainly not a problem unique to AI. In fact, Beauchamp and Childress repeatedly explicitly pointed out that the principles cannot be independently determinant on these types of inter-principle conflicts. This applies to every field in biomedical ethics.

Having an authoritative, separate ethical review board was indeed developed, at least in part, because at least some individual biomedical researchers in the past were untrustworthy. Some still are. We have no further to look than the recent Chinese researcher He Jiankui, who allegedly created and brought to term the first genetically edited twins. Even top-down, authoritative oversight failed here.

I do think Canca is correct in trying to educate both the researchers and their companies about bioethics in general and any specific bioethical issues involved in a particular research effort. Any effort to openly identify bioethical issues and frankly discuss potential bioethical conflicts at the outset should be encouraged.

Finally, the issue of Explicability related to AI has come up in this blog previously. Using the example of programming a driverless car, we want to know, explicitly, how the AI controlling that car is going to make decisions, particularly if it must decide how to steer the car in a no-win situation that will result in the death of either occupants inside the car or bystanders on the street. What we are really asking is: “What ethical parameters/decisions/guidelines were used by the programmers to decide who lives and who dies?” I imagine we want this spelled-out explicitly in AI because, by their nature, AI systems are so complex that the man on the Clapham omnibus (as well as the bioethicist sitting next to him) has no ability to determine these insights independently.

Come to think about it, Explicability should also be demanded in non-AI bioethical decision-making for much the same reason.

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. 

Then a Miracle Occurs…

If a picture is worth a thousand words, then a single-paneled comic is worth a thousand more. Sydney Harris is a famous cartoonist who has the gift of poking fun at science, causing scientists (and the rest of us) to take a second look at what they are doing. My favorite of his cartoons shows two curmudgeonly scientists at the chalkboard, the second scrutinizing the equations of the first. On the left side of the chalkboard is the starting equation demanding a solution. On the right is the elegant solution. In the middle, the first scientist has written: “Then a Miracle Occurs”. The second scientist then suggests to his colleague: “I think you should be more explicit here in step two” (the cartoon is obviously better).

Recently, in my usual scavenging around the internet for interesting articles on artificial intelligence (AI), I came across a Wired magazine article by Mark Harris describing a Silicon Valley robotics expert named Anthony Levandowski who is in the process of starting a church based on AI called Way of the Future. If their website is any indication, Way of the Future Church is still very much “in progress”. Still, the website does offer some information on what their worldview may look like in a section called Things we believe. They believe intelligence is “not rooted in biology” and that the “creation of ‘super intelligence’ is inevitable”. They believe that “just like animals have rights, our creation(s) (‘machines’ or whatever we call them) should have rights too when they show signs of intelligence (still to be defined of course).” And finally:

“We believe in science (the universe came into existence 13.7 billion years ago and if you can’t re-create/test something it doesn’t exist). There is no such thing as “supernatural” powers. Extraordinary claims require extraordinary evidence.”

This is all a lot to unpack – too much for this humble blog space. Here, we are interested in the impact such a religion may or may not have on bioethics. Since one’s worldview influences how one views bioethical dilemmas, how would a worldview that considered AI divine or worthy of worship deal with future challenges between humans and computers? There is a suggestion on their website that the Way of the Future Church views the future AI “entity” as potentially viewing some of humanity as “unfriendly” towards itself. Does this imply a future problem with equal distribution of justice? One commentator has pointed out “our digital deity may end up bringing about our doom rather than our salvation.” (The Matrix or Terminator, anyone?)

I have no doubt that AI will continue to improve to the point where computers (really, the software that controls them) will be able to do some very remarkable things. Computers are already assisting us in virtually all aspects of our daily lives, and we will undoubtedly continue to rely on computers more and more. Presently, all of this occurs because some very smart humans have written some very complex software that appears to behave, well, intelligently. But appearing intelligent or, ultimately, self-aware, is a far cry from actually being intelligent and, ultimately, self-aware. Just because the present trajectory and pace of computer design and programming continues to accelerate doesn’t guarantee that computers will ever reach Kurzweil’s Singularity Point or Way of the Future Church’s Divinity Point.

For now, since Way of the Future Church doesn’t believe in the supernatural, they will need to be more explicit in Step Two.

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

Human germline gene editing is not a solution for genetic diseases

By Steve Phillips

I have said this before (see post on 12/5/18), but since otherwise intelligent people continue to say that we should pursue human germline gene editing because it can be used as a means of eliminating the transmission of genetic diseases to future generations, I need to say it one more time. There is no reason to expect that editing the genes of human embryos will ever be a practical and effective way to eliminate the transmission of genetic diseases to future generations.

There are several reasons for this. One is that the elimination of genetic diseases in future generations would require the widespread screening of all potential parents to identify everyone who would need to use this technique for it to actually eliminate a genetic disease. There is no reason to think that that will ever be practically possible and if it were possible it would require an extreme limitation on personal liberty (think Brave New World). If genetic diseases cannot be eliminated using this technique, then what those who take this position must be advocating using it as a means for a particular couple to avoid passing on a genetic disease when they know that they are carriers of that disease. There are additional reasons why gene editing will not be practical and effective for that.

If the couple’s sole priority is to eliminate the possibility of passing on the genetic disorder that they carry to a child, the simplest and most effective way to accomplish that is to choose not to conceive children. That means that their desire to have and raise children would need to be fulfilled through adoption, but it is the most effective way of achieving the goal of not passing on the genetic disorder that they carry. If this method is not chosen, the couple must recognize that they are trying to accomplish two goals, both having their own biological child and not transmitting the inherited disease.

For the large majority of couples trying to accomplish both of those goals the method with the least risk and highest likelihood of success would be creating a child through IVF and using preimplantation genetic diagnosis (PGD) to choose an unaffected embryo to be implanted in born. However, this method carries significant moral concerns related to the creation and elimination of embryos who have the genetic disorder. Some might think that this moral concern would be a reason to choose gene editing instead, but it is not that simple. The development of the technique of human embryonic gene editing will require using human embryos as research subjects who will be destroyed as an essential step in the research to establish the effectiveness of this technique. This means that it is not a morally superior technique for those who are concerned about the value of the life of a human embryo.

If a couple would choose to pursue embryonic gene editing for the purpose of having a biological child who did not suffer from a genetic disorder that the couple carries, there are still other problems. If gene editing is being used to transform an embryo with a genetic disorder to an embryo without that genetic disorder, it would be necessary to be able to determine that the embryo actually has the disorder before doing the gene editing. Except for the case of two potential parents homozygous for a recessive disorder, some diagnostic test would be needed. We can currently diagnose many genetic disorders in a multi-cell embryo produced by IVF by using PGD. However, for embryonic gene editing to be effective in completely removing the genes for a genetic disorder and replacing them with normal genes the best time to do the gene editing is at the single cell stage. Even if it is established that gene editing can be done effectively and safely, it is hard to see how we would be able to establish that a single cell human zygote has the genetic disorder prior to treating that single cell.

For all of these reasons, the situations in which human embryonic gene editing would possibly be the preferred means of creating a child without a genetic disorder would be quite rare. It is much more likely that the technique would be used for enhancement.

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

Informed Consent and Genetic Germline Engineering

By Mark McQuain

I recently read, with admittedly initial amusement, an article from The Daily Mail that described a young man of Indian decent who was intending to sue his parents for giving birth to him “without his consent.” Raphael Samuel, a 27 year-old who is originally from Mumbai, is part of a growing movement of “anti-natalists”, who claim it “is wrong to put an unwilling child through the ‘rigmarole’ of life for the pleasure of its parents.” While he claims he loves his parents and says they have a “great relationship”, he is bothered by the injustice of putting another person through the struggles of life “when they didn’t ask to exist.”

While I was amused at the absurdity of asking a non-existent entity for permission to do anything, I began to wonder whether my position against germline genetic engineering should continue to include the lack of informed consent by the progeny of the individuals whose germline we are editing.

I have made the claim on this blog previously that one of my arguments against germline genetic engineering is that it fails to obtain the permission of the future individuals directly affected by the genetic engineering. Ethical human experimentation always requires obtaining permission (informed consent) of the subject prior to the experiment. This goes beyond any legal issue as many would consider Autonomy the most important principle of Beauchamp and Childress’s “Principles of Biomedical Ethics”. Informed consent is obviously not possible for germline genetic engineering as the future subjects of the current experiment are presently non-existent at the time of the experiment. While I believe there are many other valid reasons not to experiment on the human genetic germline, should the lack of informed consent continue to be one of them?

In short, if I am amused at the absurdity of Mr. Samuel’s demand that parents first obtain their children’s permission to be conceived prior to their conception, is it not equally absurd to use the lack of informed consent by the progeny of individuals whose germline we are editing as an additional reason to argue against genetic germline engineering?