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

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

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

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

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

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

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

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

Much going on about heritable genome editing

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

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

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

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

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

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

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

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

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

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

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

Contraception, Climate, and Population Control

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

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

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

Embryonic Legerdemain?

Developmental biologist Lewis Wolpert is credited with saying, “It is not birth, marriage, or death, but gastrulation which is truly the most important time in your life.” Gastrulation, simply put, means the embryo develops an axis and distinctly different cell layers. In the human embryo, gastrulation takes place during the third week post-fertilization. Formation of endoderm occurs over days 14-15, and the mesoderm begins to appear on day 16 (see Figure 1-11 here).  Ali Brivanlou, of New York’s Rockefeller University, identifies gastrulation, or the breaking of symmetry in the embryo, as the “major Holy Grail of developmental biology.”

Why is this so? During the third week after conception, the embryo has burrowed into the mother’s womb, and the peering eyes of scientists cannot visualize the events there. With the 14-day rule in place regarding embryo research, laws or guidelines in various locales outlaw or discourage (as in, do not fund) laboratory culturing of embryos beyond that point. So, Brivanlou’s lab “came up with a model of human embryos that is developed outside of the womb and is not the product of sperm and eggs, but the product of human embryonic stem cells that self-organize into complicated structures.”  These embryonic stem cells have formed what appears to be an embryo, but in Brivanlou’s terms, “could never become a baby.”

Dehumanizing the embryo is one of the essential components of making research on embryonic humans more palatable to the public. It will also be en essential step in a workaround of the 14-day rule. It appears that “model embryo” will join other terms such as “embryoids,” “gastruloids,” and “SHEEFs” as some element of humanity that scientists do not recognize as humans worthy of legal protection. Regarding Brivanlou’s “model embryo,” Harvard Medical School’s Dean George Daley calls it a “remarkable tool in a petri dish.” The “tool” with which Brivanlou and others concern themselves is both human and alive; otherwise, would they be interested?

Let’s think about this, using an analogue. If well-trained scientists could produce men and women without chests, what would be allowed? Would they have to call such men and women without chests “human”? Could they use men and women without chests for experiments?  Would the experiments have to be approved by institutional review boards?  Would the rest of us pay the scientists – handsomely – to do this? Could they win prizes?

Technical steps to gene-edited babies

This blog has carried several comments about the prospect of heritable human gene editing.  While nearly no one currently supports bringing such babies to birth—and condemns those who would rush ahead to do so—it appears a distinct minority think that we the human race should, if we could, agree never to do such a thing.  The most cautious perspective is to advocate a moratorium.  Others in favor of proceeding argue that, in essence, with the technologic genie (my term, not necessarily theirs) out of the box, a moratorium, much less a ban, is futile; the “rogues” will press ahead, casting off restraint. 

Advocates of research in this area have argued that a clear, careful, regulated pathway is needed to guide the work through necessary laboratory experiments that should be done first, before making a woman pregnant with a gene-edited embryo, in an attempt to be sure that the process is safe and highly likely to yield the intended result.  Even a moratorium would be, by definition, temporary, leaving the question, “when we will know to remove the moratorium?” to be answered.

A feature article in Nature, accessible without a paid subscription, asks “When will the world be ready” for gene-edited babies.  It walks through scientists’ understanding of what the technical issues are.  It is longer than a blog post, so I can only list key points here.  It is worth a reading by anyone interested, and it is written in sufficiently non-technical language that it’s accessible to the general, non-scientist public.

Key concerns are:

  • How would we be sure that genes that were NOT intended to be edited, in fact were not?
  • How would we be sure that genes that ARE intended to be edited are edited correctly?

These two matters have been addressed to some degree, or could be, in animals, but that would be faster and easier than in human egg cells or human embryos, and the results in animals may be different from what is found in the embryos.  (A further question is how many embryos, observed for how long, would need to be studied to support confidence.)

  • Even if the intended gene edit is made, is it clear that doing so is safe and does not induce other health risks? 

This blog recently reported the UK study that suggested that changes in the gene edited in the twin girls born in China last year might eventually reduce life span.  A criterion promulgated in 2017 by the National Academies of Sciences, Engineering, and Medicine was that the edited gene should be common in the population and carry no known risk (including, presumably, no increased risk) of disease.  Such knowledge is lacking for human populations, and what is believed known about the association of genes with risk of future disease has often been developed in Western populations, and may not apply to, for example, Africans.

  • At least some embryos would include some edited and some non-edited cells.  It would not easily be possible, if possible at all, to tell how many of which were present, or needed to be for the editing to work and not cause risks to the embryo’s development into a baby and beyond.  And what answers were obtained would require manipulating healthy embryos after in vitro fertilization.  The outcomes could not be predicted from first principles.
  • What should a clinical trial look like?  How many edited children would have to be born, and their health (and, most likely, the health of their progeny) observed for how long to get provisional answers before practicing the technique more widely?  Or, would the work proceed as IVF did—with dissemination in the general public, and no regulated research?

A US and UK committee is planned to address these questions, with the intent of proposing guidelines in 2020.  This will be important to follow, but with no chance to affect.  Most of us will just be watching, which leads to the last concern:

  • Is the world ready?

If that means, is there an international, or even a national, consensus, then the answer is clearly “no.”  That almost certainly remains “no” if one asks whether there is a future prospect for consensus.  It’s hard to envision something other than different groups and nations holding different judgments, and, most likely, remaining in some degree of irresolvable conflict.

More gene-edited babies on the way

It is reported this week that a Russian scientist plans to edit the genes of more human embryos intending to bring gene-edited babies to birth.  As with the case in China last year, the intent is to edit a gene called CCR5 that is responsible for a receptor that facilitates initiation of HIV infection.  The stated reason is to prevent transmission of infection from the mother, not the father, as in the Chinese case.  Maternal transmission of HIV is a real risk, but there are other ways to prevent it, with medications.  And, as recently reported on this blog, the risks of editing this gene are not understood, nor are the long-term risks of heritable genome editing.

The science press is saying that someone should put a stop, now, to bringing edited embryos to pregnancy and birth.  But it is unlikely that effective action can be taken.  The public will has not been engaged, necessary medical research controls are not in place, and no one can say just who would have the authority to take what sort of action.

So for the moment there is little else to say.  We will hear of more cases.  We will find out later how we will respond.  Clarity and consistency of that response seem unlikely. https:/

Proposed moratorium on human germline: Asilomar analogue?

The Editorial Board of The Washington Post (WaPo) recently published their opinion  on regulation of heritable genetic changes in human eggs, sperm, and embryos. The authors expressed some measure of relief that organizations such as the National Academies in the U.S., the Royal Society in Britain, and the World Health Organization are beginning to consider the daunting topic of human heritable genetic changes. The board advised, “The goal must be a framework that will enable genuine scientific advancement but avoid reckless fiddling with the source code of life.”

The WaPo editorial board further recommended “something of similar scope and power” to that of the Asilomar Conference on Recombinant DNA Molecules, held in February 1975. Asilomar, as that conference came to be called, was convened to evaluate the risks posed by the novel technology of genetically modifying organisms. The public perception of Asilomar has been primarily one of scientists shouldering the “social responsibility of science.”

Further, the WaPo article pointed out that one of the authors of the March 2019 Nature commentary calling for a “global, temporary moratorium on clinical uses of human germline editing” was Paul Berg, a Nobel laureate, and one of the organizers of the Asilomar conference. The Nature commentary, authored by Eric Lander, Françoise Baylis, Feng Zhang, Emmanuelle Charpentier, and Paul Berg, described the consensus for a moratorium thusly:

The 18 signatories of this call include scientists and ethicists who are citizens of 7 countries. Many of us have been involved in the gene-editing field by developing and applying the technology, organizing and speaking at international summits, serving on national advisory committees and studying the ethical issues raised.

This description appears to differ substantively from one Berg gave of the Asilomar analogue. In an 18 June 2011 video interview by Larry Goldstein, Berg had this to say about the success of Asilomar:

We made some decisions that were smart in retrospect. For example, one of the things we did not do – and did not include in any way in the agenda was the ethics. We didn’t talk about genetic testing… we talked about real experiments, and what the impact of those experiments would be in the field (10:40-10:58)

Of the five authors calling for a moratorium on human heritable genetic changes, only Françoise Baylis is an ethicist. A 2004 article penned by Baylis and Jason Scott Robert, “The Inevitability of Genetic Enhancement Technologies,” gives insight to her views. The paper concludes with

. . . we maintain that accepting the inevitability of genetic enhancement technologies is an important and necessary step forward in the ethical debate about the development and use of such technologies. We need to change the lens through which we perceive, and therefore approach, the prospect of enhancing humans genetically. In recognising the futility of trying to stop these technologies, we can usefully direct our energies to a systematic analysis of the appropriate scope of their use. The goal of such a project would be to influence how the technologies will be developed, and the individual, social, cultural, political, economic, ecological, and evolutionary ends the technologies should serve. It is to these tasks that bioethical attention must now fully turn.

It appears that 1) Paul Berg’s previous concerns about “ethics” being involved is not a problem to date in this enterprise; and 2) the called-for moratorium is truly only a “speed bump” on the road to converting future generations into our own laboratory experiments. The “individual” ends such experiments will serve are likely to be the individuals who are paid handsomely to do such experiments or who hold the patents to the processes utilized – not the individuals formed. Despite the extensive embrace of heritable human genome editing by the principals cited here, we need to remember that this is not a road that we must travel. Future generations are not our playground. We need to rethink this “moratorium”:  It should be an outright ban.

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.

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.