Addressing gene editing with “thin” bioethics

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

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

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

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

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

Humanoid Mass Production

Henry Ford would be proud.

We now have the ability to mass produce humanoids, embryonic cells derived from human embryonic stem cells or induced pluripotent stem cells (the latter can be made from adult cells). These cells are specifically designed by researchers to have some but not all of the necessary elements to be fully human. The goal is to grow these humanoids beyond the current 14-day limitation imposed on research studies on human embryos that ARE fully human.  In theory, these humanoids are physiologically similar enough to humans that by observing their growth and development, scientists hope to learn about human development. By design, the claim is that humanoids are different enough from humans that they would not/could not /should not live outside the Petri Dish. The original report in Nature may be found here.

I use the Henry Ford analogy on purpose. He revolutionized the automobile industry by standardizing the manufacturing process such that less skilled laborers could sequentially assemble an automobile. This allowed the cars to be built faster, at higher volume and far less expensively. Previously, higher skilled craftsmen machined each unique part for each unique car. Though the cars looked the same, their parts were not interchangeable. The process was painstakingly slow, resulting in a very low production volume at a very high price. With mass production, cars became far more common,  much less expensive and, to some extent, disposable.

Moving toward a standardized “mass production” process will have the same effects for humanoid production. Standardizing the manufacturing process will reduce the variance of a given humanoid, making the scientific study of its growth more reliable, reproducible and less expensive, all good things from a scientific standpoint. Will it also cause us to view the humanoids as more disposable?

I continue to want more discussion on the moral status of humanoids before more experimentation is permitted, particularly as we extend their lifespans. Whatever they are, at minimum, they are living entities.  Humanoids must be more than the sum total of their individual cells otherwise we humans would not have so much interest in their development. How human-like does a humanoid have to be before we should consider additional human-like moral/ethical protection in humanoid experimentation?

Or their mass production?

Screening that benefits the screener

I teach it course on human diseases for students in a public health program. One of the things that we talk about is asymptomatic disease. If a disease has no symptoms the only way that we can detect it is by screening. For screening to be beneficial it needs to be able to detect asymptomatic diseases accurately and there needs to be something which can be done that will help those in whom the asymptomatic disease is diagnosed. Many times, a screening test will only be accurate if the test is used to screen a selected population which is at risk. Sometimes there are asymptomatic diseases which we can detect accurately, but the people diagnosed do not benefit because there is not something we can do to make their life better than it would be if the asymptomatic disease had not been diagnosed. Since the purpose of screening is to help people, there is no reason to do it if the people being screened will not be helped. That idea is based on the principle of beneficence. Everything that we do in medicine should be done for the benefit of the person being treated.

Some people do not follow that moral principle. There have always been some who have used the practice of medicine to benefit themselves more than those they were treating. That is why the Hippocratic physicians had to put a statement about beneficence in their oath. One of the ways that the principle of beneficence can be violated is for some people to encourage other people to do screening that will not benefit those being screened but will benefit the one doing the screening. One of the examples I see most often is supposedly low cost ultrasound screening for such things as carotid stenosis. Those doing the screening can make a significant amount of money by screening everyone who will accept their pitch but the people being screened do not benefit. It is currently not recommended to screen for asymptomatic carotid stenosis because there is no evidence that intervention is beneficial for those who are diagnosed and some evidence that intervention may cause more harm than good.

As new technology is developed it is subject to being used in a way that violates the principle of beneficence. One of the new ways to do that is with genetic screening. A recent article in the health news section of Reuters.com describes the fraudulent promotion of genetic screening to older adults in the US. Again, this is screening being done to benefit screeners who have collected huge sums from Medicare while providing no benefit to those being screened.

These abuses do not mean that we should not do screening. It simply means that screening should be done the right way. We should choose which screening tests we use and which people we screen with those tests based on how the screening will benefit those who are being screened. We should not do it to benefit those who are doing the screening.

Why do we do this?

Many of the posts on this blog involve cautions that there are things in medicine which we are capable of doing and which some want to do that we should not do. Much of the time those cautions go unheeded by our society. For fifty years we have been saying that we should not perform abortions, but many unborn human beings continue to lose their lives. We give reasons why we should not do euthanasia, but PAS becomes legal in state after state. We write about why we should not alter the genes of human embryos, but the research continues. Is it just that we are anti-medical science and like telling people what they should do?

No. We do it out of love. Sometimes it is love and concern for people who are powerless and cannot speak for themselves. It is because of our love for the person who is aborted as a fetus or comes into being as the result of a genetic manufacturing project rather than being accepted unconditionally as a gift. It is out of love for the Canadian man who chooses euthanasia because he cannot obtain the 24 hour a day care he needs to live life with ALS.

It is also out of love for those who do things that are wrong. Love for the physician who performs abortions or euthanasia. Love for the researcher who uses human embryos as research subjects destined to die. We do it for the sake of the gospel which tells us that we have all done wrong and are destined for judgment unless someone intervenes. The gospel that tells us Jesus did intervene by his death and resurrection and has made forgiveness and restoration available to all who confess their wrongdoing and put our trust in him. We do it for those who will miss out on the amazing grace of the God who died for us if they listen to a culture that says that anything you desire to do is right and there is no need to ask for forgiveness for anything.

“Velvet Eugenics”

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

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

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

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

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

Two developments

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

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

[note to reader: subscription required]

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

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

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

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

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

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

At least for now.

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

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

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

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

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

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

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

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

Much going on about heritable genome editing

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

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

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

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

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

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

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

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

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

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

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

“Safe” gene editing

The New England Journal of Medicine carries a brief article about “Controlling CRISPR-Cas9 Gene Editing” (subscription required).  The upshot: RNA used as a medicine, as in the case of “CRISPR” to edit genes, can hang around well after administration, and alter genes other than the ones intended to be altered.  These “off-target” effects could lead to unwanted clinical side effects.  You’d like to be able to shut the RNA medicine off.  Pharmaceutical companies that make and develop medicines from short RNA sequences have been doing just that—creating “antidotes,” if you’ll pardon the expression (bad use of the word, really—an antidote is to a poison, and the medicines are not poisons)—to reverse unwanted off-target effects of their medicines, should such effects occur.

Using CRISPR for gene editing to treat known genetic disease raises a similar concern, and the NEJM article cites a recent experiment indicating that such a “reversing agent” for CRISPR, if needed, might indeed be feasible.  So, suppose you are trying to treat someone with genetically-caused blindness, and there’s a risk that other genes might be affected.  You could give the “reversing agent” to block that.  Cool.  You’d want to get it into the right tissues—the right parts of the body—but the work described in NEJM suggests that might all be reality eventually. 

One challenge is: these RNA-based agents don’t always get into the parts of the body, or into cells, all that well.  The NEJM writer says that this new work into “controlling” CRISPR-based gene editing “of course, depends on the [reversing agent] delivery problem being solved, but that is a topic for another day.”

It’s been some time since your correspondent worked for a drug company making RNA-based drugs, and I’m not close to the work these days, but I would say that is most definitely a topic for another day.

So, why bring this up in a bioethics forum?  Because it’s one more matter that would need to be considered and addressed before charging into gene editing that can be inherited from generation to generation.  This, as the present writer has repeatedly held, is something that that the human race should never do.

But it’s bowling along.  The latest reports are that attempts to edit genes babies of deaf couples to prevent them from being born with genetic deafness are nigh in Russia.  Understandable, laudable goal, but we should not think that control of the process is nigh.   edium

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.