More—with trepidation—on COVID

Let us stipulate at the outset: first, that so much—far too much? –is being written on the COVID-19 outbreak, and wisdom is a precious commodity; second, that although your correspondent is an MD, he is as bewildered as anyone by the storm of reports, claims, data, projections, arguments; and third, that whatever public comity may appear to pertain now, in due time we likely will be at one another’s throats with blame about who should have been better prepared or done what when, and there will be plenty of blame to go around.  Our leaders, national and regional, are especially to blame, but the evidence abounds that too many of us took this too lightly throughout January and February.

This being a bioethics blog, however, a few comments about some ethical issues in an outbreak, from a 2018 paper on the subject.  The paper in question raised three major topics: ethics of treatment research, triage, and the duty (by doctors and other health professionals) to provide care.

The last point first: it is well established that the covenantal duty of doctors in particular is a willingness to efface self-interest for the interests of the patient.  There is no dispute that this duty is being followed faithfully by the doctors, nurses, and others who are caring for people sick from COVID-19.  But a related duty of society is to do what it can to limit the risk to the caregivers themselves.  This is clearly pressured by, for example, the limitation on personal protective equipment (PPE) supplies.  We owe it to the medical community to provide them with what they need.

Next, triage:  try as we might, and fail as we might (and always seem to) to prepare in advance for a possible outbreak, surprise never fails to assert itself, and shortages of things that really matter loom.  At this writing, I have no idea whether New York City’s capacity to care for the sick is destined to, or is already, hopelessly overrun “under any scenario,” as Gov. Cuomo said this morning, or whether we can take any comfort in the assertion this evening by Dr. Birx that “there are still ICU beds and ventilators” in New York.  In early March, an infamous discussion at the American Hospital Association projected as many as 1.9 million people needing ICU care nationwide, and about half of those needing ventilator care, and it is further widely said that the typical ICU stay, even for someone relatively young, is 2-3 weeks.  Numbers far fewer than that would outstrip our national capacity, it appears.   Then again, the real shortage may not be ventilators, but the doctors to manage them.

These concerns also arose in the first Ebola outbreak a few years ago, and much-discussed principles of allocating scarce resources apply.  First and foremost is to try to alleviate the shortage through the best possible resource management.  Failing that, if hard choices must be made, then the likelihood of achieving clinical success is a top criterion.  But that requires clinical judgment that may be uncertain, requiring a lottery system, or a registry (as is done for organ transplantation).  Perhaps most controversial is to make an attempt to prefer treating people who are judged, if treatment succeeds, to have more life to live or more potential lifetime contribution to society to offer.  In that case, who decides, and how one decides, become very dubious judgments to make.

In the moment, there may not be enough critical care resources to go around, and doctors have to make a hard choice to treat one person but not another.  Physicians in Italy are reported to have faced exactly this choice this month.  Another principle, easy to say but hard to follow (talk is cheap!), is that triage “should not be a bedside decision,” that is, the treating doctor should not be forced to make a choice, but a previously-settled decision process should be applied.  I do not know whether that was or is possible in Italy, or in New York, or elsewhere in the U.S. or the world during this outbreak.

If we indeed are committed to care for and conserve our most precious care resource, our doctors, then that, in addition to limits on the number of available beds, might be adduced in favor of a so-called “universal” or “unilateral” decision that resuscitation (CPR) of some patients—which will increase the risk of the doctors and nurses getting infected—simply will not be attempted if their heart stops, regardless of whether the patient desires the attempt.  I know of no evidence that this is being done anywhere, but it is the subject of some speculation in the press.  The proper process is for a careful end-of-life conversation to happen between doctor and patient, before being confronted with the need, so that the patient’s wishes and the doctor’s professional recommendation can be considered.  But if that did not happen for people seriously ill with COVID-19, it may be too late when the illness strikes.  Those of us “of a certain age” are wise to consider this question in advance—viral outbreak or no.

Finally, the ethics of experimental treatment during a disease outbreak are governed by a well-defined regime of human subject research.  The key principles follow the Belmont principles reviewed by Mark McQuain on this blog on March 17, and include that risks to subjects must be limited as much as possible; that the necessary research risks not be excessive compared to the potential benefit to the subject at hand or society at large; that informed consent be properly obtained and documented; and that vulnerable people or those less advantaged not be denied access to potentially promising treatment nor be disproportionately placed at risk or have their vulnerabilities taken advantage of.

In the case of this present outbreak, research ethics also require that experimental treatments be properly studied in adequately designed clinical trials.  Implications, IMO, include that people be randomly assigned to treatment alternatives.   It is true that “off-label” use of drugs that are available for other uses is legal when prescribed by a licensed physician, and such off-label use is not on its face evidence of malpractice.  However, society stands to benefit by collection of data about the COVID-19 disease and outcomes of treatment, and so even off-label use should be done in a clinical trial, not in a “right to try” approach.  Because COVID-19 can be so severe, and the need for treatment is so great, I am inclined to think that random assignment to a placebo is a suspect requirement, I must admit that the need to learn more about the natural course of COVID-19 infection probably requires a placebo group in most, if not every, clinical trial.  There is not enough prior knowledge to rely on comparing a past group with a current, treated group, to conclude whether a new treatment works.  But requiring a placebo further requires that the trial get done fast and carefully, so results are as clear as possible, and made pubic immediately.  We should have no doubt at all that everyone doing the trials wants that.

I note that the public registry of clinical trials includes several in the U.S., including a national, 3000-person study of whether hydroxychloroquine may prevent disease in people exposed to others with COVID-19 disease.

Chastening and enthusiasm about genome editing

A writer in Nature says that China sent a “strong signal” by punishing He Jiankui and two colleagues with fines, jail times, and bans against working again in human reproductive technology or applying for research funding.  (They lost their jobs as well and may not be able to do research work, presumably in any field, in a Chinese institution again.)  It is encouraging, this writer says, that China took this action demonstrating a commitment to human research ethics.  He and other researchers doing gene-editing work that is not ethically objectionable worry that there may be collateral damage, so to speak, against ANY gene-editing research in China.

Another writer in Nature says cites progress under “appropriate caution” for using gene editing techniques for so-called “somatic” gene editing; that is, editing disease genes in an existing person with that disease, to treat it.  This is, in essence, a form of gene therapy and is ethically permissible under proper research ethical guidelines.  Some clinical trials in progress involve injecting the gene-editing apparatus into a person, while most such trials remove the person’s blood cells, edit them in the laboratory, then re-introduce them into the bloodstream, after which the edited cells are left to mature normally.  The latter approach is particularly attractive to treat genetic blood diseases such as sickle cell anemia.

Both perspectives seem correct, as far as they go—never mind whether Dr. He’s jail sentence fits the crime, as Joy Riley asked on this blog last weekend.  Never mind also whether Dr. He’s research should be published; as Mark McQuain commented, it’s a bit incongruous to want to assess the technical merits of work that should not have been done in the first place.  He linked an opinion in Technology Review that argued, briefly, that because the ethics of editing genes in human embryos is under societal debate, people trying to decide on the ethical merits should be able to assess for themselves whether Dr. He succeeded, technically at what he set out to do.  (The consensus to date seems to be, no, he did not.)   But the role of technical success in assessing the ethical merits of a medical intervention—or, better, an intervention made in the name of medicine—depends on the degree to which the ethical judgment is a matter of making a reasonably reliable of risk and benefit, and the degree to which risk-benefit is a criterion for judging the ethical merits.  And therein, as they say, lies the rub—which I hope to revisit in coming posts.

2020, or 20/20?

Near the end of 2018, He Jiankui was on the world’s stage announcing that he had edited the genome of twin girls, in the hope of making them resistant to HIV. On Tuesday, December 31, 2019, the Wall Street Journal (WSJ) printed a report that Dr. He and two others have been convicted of “illegally practicing medicine related to carrying out human-embryo gene-editing intended for reproduction.” (online version here).

A court in Shenzhen concluded that the defendants had acted for “fame and profit,” when they “deliberately violated the relevant national regulations, and crossed the bottom lines of scientific and medical ethics.” For the crime committed, He received the most severe sentence. In addition to the three-year prison sentence, He is banned for life from “working in the field of reproductive life sciences and from applying for related research grants, “ according to the WSJ.

The Xinhua News Agency also noted that a third genome-edited baby had been born, and that this child, along with the previously born twins, “would be monitored by government health departments.” The WSJ did not state for how long the monitoring would continue. Not only were the children experimental subjects as embryos, but they continue to be subjects as well. Further, these genome effects will affect their progeny, potentially into perpetuity. Additionally, the Smithsonian Magazine reports that in the summer of 2019, He met with “investors to discuss a potential commercial genetic modification clinic in Hainan, which aims to become a ‘world-class medical tourism hub’.”  One might reasonably call this “a crime against humanity,” even if it does not include genocide of humans already born. (For further reading, see David Luban, “A Theory of Crimes Against Humanity”)

In the print edition of the WSJ, alongside the article on He is an article about Pastor Wang Yi of the Early Rain Covenant Church. Pastor Wang was sentenced on 30 December to nine years in prison. His crime was “incitement of subversion of state power and illegal business operations” (online article here).

Consider that a pastor receives a nine-year sentence for an offense against the State; and a scientist, a sentence of three years for a crime against multiple generations, and indeed, humanity. In the year 2020, we could use a check of our understanding of what is important in the life of the world. Would that our vision were 20/20 also.

Experimental Subjects for Life?

More than a year after the birth announcement of genome-edited babies in China, we are only slightly more informed of He Jiankui’s experimentation, the results of which are named “Lulu” and “Nana.” Although apparently approached, neither Nature nor the Journal of the American Medical Association (JAMA) chose to publish He’s work. Antonio Regalado reported on an unpublished manuscript in “China’s CRISPR babies: Read exclusive excerpts from the unseen original research” in Technology Review on 3 December 2019. The Technology Review article includes not only excerpts of the manuscript from He, but also reactions from Stanford law professor Hank Greely; University of California—Berkeley’s gene-editing scientist Fyodor Urnov; the scientific director of Eugin assisted reproduction clinics, Rita Vassena; and reproductive endocrinologist Jeanne O’Brien, from Shady Grove Fertility.

Regalado summarizes some of the problems with Chinese experiment as follows:

 . . . key claims that He and his team made are not supported by the data; the      babies’ parents may have been under pressure to agree to join the experiment; the supposed medical benefits are dubious at best; and the researchers moved forward with creating living human beings before they fully understood the effects of the edits they had made.

Greely points out the lack of “independent evidence” of the claims made in the paper. Urnov labels the paper’s claim of reproducing the usual CCR5 variant “a deliberate falsehood,” and calls the statement about the possibility of millions being helped through embryo editing “equal parts delusional and outrageous.” O’Brien’s concerns include the possibility of coercion of the couples involved, and, noting the social stigma of HIV-positivity in China, she poses the question of whether this was a genetic fix for a social problem. Certainly, the Chinese experiment raises many questions, including how a culture views children. Are children gifts to be received or projects to be completed? Is it appropriate to subject children to experimental research because we can? One of the quotes from the paper reads, “we have made a follow-on plan to monitor the health of the twins for 18 years and hope to then reconsent for continued monitoring through adulthood.”

We would be remiss if we thought that China alone plans to remake humanity. Vassena is quoted regarding He’s study:

Unfortunately, it reads more like an experiment in search of a purpose, an    attempt to find a defensible reason to use CRISPR/Cas9 technology in human embryos at all costs, rather than a conscientious, carefully thought through, stepwise approach to editing the human genome for generations to come.  As the current scientific consensus indicates, the use of CRISPR/Cas9 in human embryos destined to give rise to a pregnancy is, at this stage, unjustified and unnecessary, and should not be pursued.

Vassena, who directs a fertility enterprise, it should be noted, appears comfortable with impacting the human genome for generations to come:  It just needs to be a “reflective” and “mindful” approach. That is chilling. Would she, or the study’s authors, or Greely, or Urnov, or O’Brien sign up to be a science experiment for the rest of their lives? I would not consent—not for myself nor for my children—no matter how “reflective” or “mindful” the researcher happened to be.

Finally, “Lulu” and “Nana” should be known as more than the results of someone’s laboratory experiment. They are human beings, not laboratory rats or cells under a microscope to be studied at the will and convenience of the experimenters.

“Why did you make me this way?!”

Recently, Jon Holmlund brought us up to date on an effort in Russia to proceed with CRISPR gene editing aimed at eliminating deafness. Coincidently, a recent MedPage article was posted regarding the ethics of using pre-implantation genetic diagnosis and IVF to purposefully select FOR an embryo with genetic deafness for a couple, both of whom were deaf. Both links discuss some of the ethical problems with using medical reproductive and genetic technology for these purposes. While we presently lack the ability to use polygene scoring to accurately “produce” the babies we want, I want to use the remainder of today’s blog to consider what obligations, if any, a genetic engineer (or parents that use their skills) may have toward future children designed using these growing array of genetic technologies.

Deafness seems to me to be rather curious in that it is considered either a serious disability or a desirable trait, depending upon your cultural worldview. No one in any culture would purposefully select for cystic fibrosis or Tay-Sachs diseases for their child. In fact, most want to use medical reproductive and genetic technologies to eliminate these diseases. On the other end of the genetic trait spectrum, some parents want to use these same technologies to purposefully select for more trivial traits for their children – hair and eye color, for instance. Given the triviality of these traits, I hear no one mounting an effort to genetically eliminate any particular hair and eye color. Perhaps I am living a sheltered life?

Nonetheless, with regard to deafness, prior to the promises of our new reproductive technologies, if you were born deaf and did not like it, you could only shake your fist at God or Nature. Now (or very soon), you can shake your fist directly at another human, such as your regional genetic engineer (or your parents who purposefully used her technological skills) and demand a direct answer as to why they purposefully made (or did not make) you deaf. Maybe this angst will be more widespread for the many more trivial traits such as eye or hair color rather than something more significant like deafness?

Building a child is about to become much harder for parents as they become directly responsible for both interior (genetic illnesses) and exterior (hair and eye color) design issues.

“Why DID you make me this way?!”

“Why did YOU make me this way?!”

I wonder how many genetic designers (or the parents that will ultimately bear the direct responsibility for having used the technology) really want that type of responsibility?

Is there already fine print in PGD-IVF contracts holding the doctors/scientists/geneticists harmless for the choices the parents make?

I can’t wait for the late night TV commercials: “Were you born with brown eyes and feel emotionally scarred because you have always wanted blue? Call our law offices as you may be entitled to financial compensation …”

The importance of premises

In an interesting article in the Hastings Center Bioethics Forum, titled “Hannah Arendt in St. Peter’s Square,” Joseph Fins and Jenny Reardon write about the importance of deep ethical reflection in dealing with the ethical challenges of biomedical research. They point out that when ethics becomes a matter of simply following a set of rules we can end up in the wrong place. Even such fundamentally good concepts as informed consent and the need to have research proposals reviewed to be sure that they are ethically sound can lead to a mindset of regulatory compliance, essentially following the letter of the law, while leading to poor conclusions about what we ought to do. In the end they suggest that in order to facilitate deeper ethical thinking regarding new areas of biomedical research we need more interdisciplinary conversation between the sciences and engineering on one hand and the humanities and social sciences on the other. I think this is quite true and is a strong argument for a liberal education in its classic sense.

However, I find it particularly interesting how the thinking of Hannah Arendt enters into their discussion. Arendt was a German Jew who fled from Europe to the US in the Nazi era. She wrote about the kind of thinking that allowed the totalitarian regimes of Hitler and Stalin to gain control. Fins and Reardon focus on her idea that logical thinking can lead from a seemingly self-evident statement to a replacement of common sense with thinking that leads in a direction that is very wrong. They see a culture in medicine and science that considers ethics as a matter of regulatory compliance rather than deep reflection an example of this.

What I find most interesting in Arendt’s thinking is the idea that logic will lead to faulty conclusions if the premise is not true. The problem that she saw in the thinking leading to totalitarian regimes was not that the thinking was illogical. The problem was that the seemingly self-evident statements which were used as the premises were false. When we apply that to ethics it means that we will only reach sound ethical conclusions when we begin with moral premises that are true. A liberal education with interplay between the humanities and the sciences is one way to seek true premises for our ethical thinking in the wisdom that can be found in the interplay of academic disciplines. Another is to recognize that the existence of common sense morality suggests a source of moral wisdom that is beyond human wisdom. Christian ethics finds its premises in that higher source of moral wisdom. A Christian liberal education integrates them both.

Stem Cell Rx No Longer For Sale on Google

Perhaps once a week, I will be asked by a patient about the potential benefits of stem cells for reversing the normal affects of age, particularly with respect to arthritis of the knee joints, hip joints or the degenerative discs in the lumbar spine. I believe one of the reasons for this interest has come from increasing advertisements by various clinics in my region of East Tennessee claiming stem cells are the answer for these problems. My region is not unique. A simple Google search on “stem cells for knee pain” yields ads for clinics offering such treatment.

Stem cells are cells that have potential to become any type of cell in the human body such as a new blood cell, nerve cell or bone/cartilage cell. Scientists are rapidly learning how to find or create stem cells, as well as how to safely use them to replace old or missing cells, thus restoring function in worn out, damaged or diseased areas of the body. In fact, stem cells are presently used to replace the bone marrow for some individuals with certain cancers and disorders of the blood and immune system, and in many of these cases, the results are lifesaving.

The problem is that stem cell treatment remains yet unproven in all other medical conditions, including the age-related arthritis conditions which I treat. This lack of efficacy has not stopped clinics from offering and patients from receiving stem cell injections with the hope of achieving improved function or cure. I am willing to grant that many offer these treatments with the sincere hope and belief that they are acting in their patient’s best interest, though I suspect not all have the patient’s best interest in mind. Unfortunately, there have been severe adverse events. Examples include blindness following an injection of stem cells into the eye, and loss of function with development of a spinal cord tumor following stem cell injection into the spine.

The FDA is trying to educate the public and prevent stem cells from being offered for unproven treatments. The FDA has the authority in the US to stop these unproven treatments and take punitive action if needed. This is not to suggest that the FDA is in the business of preventing legitimate investigation into the potential benefits of stem cells, such as this Mayo Clinic Phase 1 study looking at the risks of injecting stem cells in to the cerebrospinal fluid of patients following a spinal cord injury to see if this particular stem cell technique causes harm (with future studies needed to determine benefit).

The FDA is recently getting some help from Google. On September 6th, Google announced it would stop accepting ads for unproven medical treatments, including stem cell therapies. It is early in the effort and the initial link above still has four ads for non-bone marrow stem cell treatments returned with the Google search. Maybe by the time you read this blog entry, the stem cell ads for unproven treatments will be gone.

I am hopeful that stem cells will eventually provide patients with safe therapies that repair injury and return patients to normal health. Offering that promise without the studies that prove such benefit is unethical and potentially harmful. It is good to see Google favoring human welfare over financial profit.

Promoting vaccination with a not-too-heavy hand

This week’s Nature has a worthwhile read, “Mandate Vaccination with Care.”    The recent rise in the number of cases of measles is well-documented in the general press, and there is a strong argument that it is a social good that sufficient numbers of children be vaccinated for a range of infectious diseases.  Your correspondent considers it unfortunate, to put it mildly, that there is a persistent belief that vaccines for the standard childhood diseases are harmful.  Although some cases of vaccine harm occur, they are rare—rarer than many in the general public believe—and the cost of under-vaccination is great.  I, for one, never want to see an infant with pertussis (whooping cough) again, and, although I recall having had measles and chicken pox when I was a kid, it’s best to prevent them.  Some can even be eradicated (see: smallpox—which we should fervently hope is never purposely re-introduced, now that we don’t routinely vaccinate for it). 

In brief, the authors in this case argue for promoting vaccination in the public with such steps as ensuring supply and access, providing information and allowing public forums, monitoring safety carefully, and tracking vaccination rates.  They argue, reasonably, that mandatory vaccination that carries the wrong kind of penalties—such as, fines or even jail sentences imposed in some countries—for non-compliance actually can harm poorer, medically underserved people, and as such be counterproductive and, frankly, unfair.  They comment that harsh mandates can unnecessarily prompt a backlash, with increased resistance.

They say, further, that if mandates are deemed “politically appropriate,” then the procedures should be just, with constraints on choice as limited as possible; any penalties must be proportionate; those who do suffer complications should be adequately compensated.   They speak favorably of creating administrative hurdles to getting exemptions from mandates.  They also argue against governments mandating only some vaccines while excluding others.  They claim that making some vaccines only “recommended” can limit the uptake of all. 

This last point may be the most questionable of all in this article.  It is easier to justify mandating vaccination for highly contagious diseases that can have devastating effect (e.g. measles, rubella, diptheria, and others), than, for example, vaccination for human papilloma virus (HPV), infection with which predisposes to certain kinds of cancer but transmission of which is through sexual activity.  In this last case, the argument for a mandate is substantially weaker; vaccination at a fairly young age might be wise, but one might still reasonably accept, for oneself or one’s child, the less certain and more remote risks of the consequences of infection, and therefore reasonably object to mandated vaccination.

Again, a worthwhile read. >

Good from Evil

I was given an article by a student of mine following his one month elective rotation with me in which we spent some clinical time discussing bioethical issues. The May 2019 web article by Sharon Begley from Statnews.com had to do with an interesting medical dilemma first presented in 2016 by Dr. Susan Mackinnon from Washington University in St. Louis. I have briefly summarized Begley’s article in the first part of today’s blog and extended her point at the end.

Dr. Mackinnon had a patient who was having severe leg pain following multiple knee surgeries. Dr Mackinnon was providing the final surgical attempt to isolate the nerve presumably being compressed by scar tissue in hopes of surgically decompressing that nerve to permanently relieve the patient’s severe pain. If the surgery was not successful, the only other option at that point was to amputate the leg. During the surgery, she used an old anatomy book called The Pernkopf Topographic Anatomy of Man, which unambiguously has the best illustrations of nerves around the knee, and successfully located and decompressed the nerve in question and successfully avoided an amputation.

So, what was the dilemma?

As Begley points out in her article, it came to light in the mid-1980s that the illustrations used in the Pernkopf atlas were based in part on the bodies of people executed by the Nazis in the late 1930s. The moral dilemma for Dr. Mackinnon was therefore:

“…even now, the Pernkopf illustrations are unsurpassed in their accuracy and detail, especially their depiction of peripheral nerves…and although a few journal papers may have an equally good, single illustrations, finding the right paper takes time that Mackinnon did not have as she stood over her patient.”

Dr. Mackinnon had been given the Pernkopf atlas as a graduation gift in 1982 but the Nazi history behind the atlas was not known until the mid-to-late 1980s, the full history of which only became known to her after the surgery. Should she continue to use an atlas that contains illustrations of the bodies of people executed by the Nazis? If used, is there a duty to inform a current patient about the nature of the atlas? Can sufficient good be derived from the atlas given the unspeakable evil required to create it to permit its ongoing use?

She posed her dilemma to Rabbi Joseph Polak, the Chief Justice of the Rabbinical Court of Massachusetts, who consulted Prof. Michael Grodin of the Elie Wiesel Center for Jewish Studies at Boston University. Their opinion became known as the Vienna Protocol, due to the origins of the Pernkopf atlas. Their response may be found in this link, which I believe is better read in the full context of the Vienna Protocol than summarized by your humble blogger. For those of you who must read the opinion before reading the entire protocol, please follow the link and scroll to the 4th to last page at number 12 in section C entitled “The Protocol and Recommendations”.

The evil that created the Pernkopf atlas was the Nazi occupation of and executions that occurred in Austria during World War II. It is no longer occurring. No one in the present is suggesting that we resume executing people to gain more anatomic drawings to complete additional volumes of the atlas. Any good resulting from the current use of the atlas isn’t being offset by any ongoing evil of creating more atlas. The evil of the Pernkopf atlas is contained in the past and, in that sense, finite. Containing the evil seems to be a necessary step in obtaining good from that evil.

I mention this in closing as I believe there are current analogies of activities performed in the name of scientific good where we condone ongoing evil. Studying fertilized ova until sacrificing them on Day 14 (an evil) in the name of learning about human reproduction (a good) is one modern day example. In Vitro Fertilization done to obtain a healthy baby with genetic traits we want (a good) that results in the death(s) of other fertilized eggs we don’t want (an evil) is another. There are other examples we have discussed within this blog. I believe we need to contain and hopefully discontinue these and other practices if we want to claim the information we gain can honestly be called good.

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.