International commission: go slow with heritable human genome editing

The international commission on heritable human genome editing (HHGE), formed by the US National Academies of Medicine and Science and the Royal Society of Great Britain, has issued it report.  The 224-page report is freely available for reading here, and a summary news report can be accessed here.

The upshot:  not too fast.  The commission’s 11 major recommendations, briefly reworded and rearranged in order, are:

  • Before attempting any pregnancy with a gene-edited human embryo, “a significant cohort” of edited human embryos should be studied in the laboratory to ensure that the desired gene edit(s) “can be performed with sufficiently high efficiency and precision to be clinically useful.”  (No attempt would be made to bring these embryos to birth, and they would exist solely for research purposes, after which they would be destroyed.)
  • This efficiency and precision have not been demonstrated yet, and “no attempt to establish a pregnancy” with an edited human embryo should be made until they have.
  • Even then, the attempt should come only after “extensive societal dialogue” within any country whose leaders are considering endorsing the attempt.  This dialogue would include medical and scientific concerns, which the report addresses, and also “societal and ethical issues that were beyond the Commission’s charge.”  (Your correspondent has just begun reading the report, so cannot say yet whether the Commission considered how to proceed if one country green-lights edited human pregnancies while others do not.)
  • The only conditions that should be considered for editing are those of a serious disease caused by a single gene abnormality, for which the prospective parents have a less than 25% chance of having an unaffected child using current preimplantation genetic diagnosis (PGD).  Further, the resulting edited gene would be common and non-disease causing in the general population, and no embryos without the diseased gene would be edited. (This would seriously limit the use of HHGE—not permitting it for genes that increase the risk of cancer, for example—but, like the first point, would also raise concerns for conservative ethicists who consider all human embryos, from conception, to be human beings with the right to life.  If you’re troubled by PGD in general, this recommendation won’t satisfy you.)
  • The above would need to be followed for every proposed “treatment” of genetic disease—there is no “one-size-fits-all” approach to setting up a regime for heritable gene editing in general.  (This would have the effect of limiting the “industrialization” of HHGE, it appears.)
  • The actual transfer of an edited embryo to a woman’s uterus should be subject to (future) “rigorous” regulatory review and approval—that is, the edited embryo would be checked, in the laboratory, before transfer, to be sure that the edit had succeeded.   After transfer and through pregnancy, birth, and the life of the individual, close medical monitoring would be mandatory to learn what medical problems may have arisen.
  • A potential work-around should be studied in the laboratory: making human eggs and sperm from stem cells, with the intent of being able to use them for in vitro fertilization to give rise to an embryo without the abnormal gene.  However, the Commission recognizes that there are other canned worms, so to speak, to be dealt with here—such as whether this approach to begetting children is ethical at all, apart from any use of gene editing.
  • Any country embarking on HHGE in actual pregnancies should first put in place “mechanisms and competent regulatory bodies” to oversee standards and adherence to them, publication of results, and oversight in general.
  • An International Scientific Advisory Panel should be established in advance to oversee the progress of the science overall, before pregnancies are attempted—essentially, a single point of review to prevent intrepid scientists from “going rogue,” as it were.
  • An international body (presumably a different one from the above) with appropriate expertise should review every new proposed medical application of HHGE before pregnancies with the relevantly-edited embryos are established.  So, presumably, attempts to edit the gene for Huntington’s disease would be assessed separately from attempts to edit the gene for sickle cell anemia, for example.
  • An international mechanism should be established to adjudicate cases of alleged deviation from received guidelines or standards, and its’ results should be transmitted to individual governments and publicly released.

It looks like a careful report, welcome in its caution, although, as noted, those who hold that human life begins at conception will still likely object to the endorsement to continue with laboratory-based research.  “Just say no” to the prospect of HHGE—a position your current correspondent has consistently advocated on this topic—does not appear to be in view.  One might also be forgiven for skepticism over the effectiveness of any international body, given the controversies that arise from our existing international bodies for medicine and health, not to mention other endeavors.  Some such efforts, such as the regulatory harmonization of human clinical trials and drug development that governs the US, the EU, and Japan, work pretty well, but arguably are limited.

It is also worth mention that the California Institute of Regenerative Medicine (CIRM), established with Proposition 71 in 2004, ostensibly to translate embryonic stem cell research into cures (with creation and destruction of human embryos for the purpose), is proposed for renewed public funding in California with Proposition 14 in this November’s election.  Nothing approaching a cure was achieved under the CIRM, and even proponents of human embryonic stem cell research argue a renewal is unnecessary, because there is plenty of private money supporting related work already.  Further, the CIRM came under charges of insider dealing, because it needed to draw its leaders from the small pool of experts who tended to have career or monetary interests in the field to begin with, raising repeated concerns about a conflict of interest.  Would such potential conflicts plague the national and international bodies proposed by the HHGE Commission?  (Full disclosure: your correspondent will eagerly vote “no on 14” on his mail-in ballot this fall.)

Finally, so-called “somatic” gene editing—a fundamentally ethical undertaking by which a person’s cells may be altered to make them into a treatment for disease—is here to stay, as are certain forms of gene therapy that don’t involve heritable changes.  Expect to hear about those more in the future; they are subject to standard human subject research concerns, and to justice concerns like the eventual costs of the treatment.  Those topics for another day.

Pediatric Fertility Preservation for Hormone Suppression in Transgender Youth

Last week, I received an e-mail update on current research and treatment being performed at the institution where I did my residency training. One of the interesting research areas was in the discipline of pediatric fertility preservation. Pediatric patients who undergo cancer treatments often take medications which cause destruction of their testicles or ovaries, not uncommonly resulting in infertility problems when the patient reaches adulthood. Advances in cryopreservation techniques of reproductive tissues are offered as a solution to preserving one’s fertility after pediatric cancer treatment.

The cryopreservation technique in the pediatric population is not limited to cancer treatment. There have been advances in providing fertility to non-cancer medical conditions that previously caused infertility. Two such conditions are Klinefelter syndrome and Turner syndrome which affects sex chromosome anomalies male and female patients, frequently resulting in infertility problems in those patients. By cryopreserving these patient’s testicular or ovarian tissue when they are children, when the number of the reproductive cells are in larger number and/or have the best potential for future reproductive function, in vitro fertilization techniques using these preserved cells when these patients reach adulthood can improve fertility.

The same pediatric fertility preservation treatment is now being offered prior to the hormone medication used to assist pediatric transgender youth transition from their birth sex to the opposite gender. Hormone treatments are used to intentionally suppress the transitioning person’s natural sex hormone production. This causes body habitus transformation to the desired gender. Continuous hormone suppression severely reduces (and can eliminate) baseline anatomic testicular or ovarian function causing permanent infertility in the transitioning patient. There is additional concern that the infertility persists even if that hormone treatment is later discontinued. Limited data exists to make conclusive statements on this subject as studies on long-term physiologic effects of hormone treatment used to transition pediatric patients are lacking; this is true even in the adult population where the number of patients who have transitioned is much larger.

Bioethically, we have moved beyond the question of whether we should be doing hormone suppression to assist in gender transitioning in the pediatric population and begun to discuss whether that child’s fertility ought to be preserved following such hormone administration. A simple Google search for non-hormone treatment of gender dysphoria in the pediatric population shows mostly hormone-based treatments for the first pages of results. With more effort, non-hormone options can be found.

The Mayo Clinic update that I received describes the transgender fertility preservation treatment along with a constellation of other pediatric medical conditions whose treatments potentially cause infertility (i.e. the cancer chemotherapy treatment causing infertility described earlier) as if all of these programs should be considered medically (and ethically) equivalent.

Are they?

If they are not, shouldn’t we be debating the medical and ethical pros and cons of pediatric transgender hormone administration more thoroughly before we consider how (and why) to preserve the very fertility of the pediatric patients we are altering by intentional hormone suppression?

A new cautionary tale for heritable genome editing

A fundamental concern about applying gene editing to human embryos is how to limit the risk of errors, or “off-target” effects.  One makes an edit to change a bad gene’s defect, and presumably prevent the disease the defective gene would cause.  But the current methods to do that, although apparently highly selective, might still make other, unwanted changes as well—with possible deleterious, even disastrous, consequences.

Heretofore, the attention to these “off-target” effects has largely been directed to changes in genes that are separated from the target gene.  However, a recent news item in Nature describes three recent experiments with human embryos in the laboratory, in which large defects were induced in the chromosomes bearing the target gene—that is, right next door.  The difference is a bit like the difference between damage by shrapnel (distant effect) and blowing a 6-foot hole instead of a pinhole (near effect).  The latter is now the new concern.  Apparently, and, for one who does not live the scientific details daily, amazingly, prior analytic techniques were missing the possibility of these big, close-in errors.  “CRISPR gene editing in human embryos wreaks chromosomal mayhem,” the headline reads.  Geez Louise…

The technical details are still to be worked out, but one possibility is that, after the targeted gene is cut by the editing mechanism, the way that repair of the genes is done by the human embryo creates the possibility of introducing errors by copying or shuffling of a big chunk of the gene.  These processes are not fully understood in human embryos, and may be different from what pertains in mouse or other animal embryos, or in single human cells such as egg cells or newly-fertilized eggs.

The big technical message is that a lot is poorly understood and will take a ton of work to sort out before one can be confident that a pregnancy carrying a gene-edited to-be-born human will birth a healthy baby, in the immediate outcome, never mind consequences later in life.  It further suggests that no amount of animal work may lay the matter to rest.  From that it’s hard to avoid the conclusion that many embryos will need to be created, altered, and destroyed for research purposes if heritable human genome editing is to proceed with some assurance of safety.  How long would those embryos have to be kept alive to test?  Quite possibly longer than the few days currently possible and accepted by the scientific community.

Absent that, trying to birth gene-edited children would mean, as this blog said some time ago, that “the babies are the experiment.” 

And, even if one does not grant moral status to the human embryo from the point of conception, one is compelled to seek an accounting of the compelling unmet medical need that supports a careful benefit-risk analysis.  Risks to human subjects—embryos, fetuses, eventually-born babies, women donating eggs, perhaps even women carrying partial pregnancies (to allow study of results from a later point in utero?)—seem substantial, overall costs of the effort raise questions of spending the money better elsewhere in the overall health care of society, and alternative approaches to the diseases in question must all be considered.

Geez Louise.

One other point: the Nature article cites preprints posted, prior to peer review of the science, on the website bioRxiv.  Operated by the outstanding Cold Spring Harbor Laboratory, the website offers authors the chance “to make their findings immediately available to the scientific community and receive feedback on draft manuscripts before they are submitted to journals.”  Open access and public feed back are good, but the general press often picks up these preprints, whose quality may not have been fully vetted, and runs with headlines—kind of like I am doing here, following Nature.  So we must watch this space to be sure that the research is being accurately described and interpreted.  For the moment, the topic of this post can be taken as another example of “something to watch out for.”

A principalist argument against heritable genome editing

In May of 2019 The New Bioethics carried a paper (purchase or subscription required) by Jennifer Gumer of Columbia and Loyola Marymount Universities, summarizing an argument against heritable genome editing (the kind in which an embryo’s genes are edited so that the change will be passed down to the subject’s descendants), based on Belmont principalism.  A brief outline of the argument:

  • Uncertainties about the safety of the procedure make it highly unlikely at best that the principle of nonmaleficence (“first, do no harm”) will be satisfied.  Even if the technique substantially eliminates unintended, “off target” gene changes or mosaicism (some cells have the change, others do not), uncertainty will remain about whether interactions between genes may be altered, potentially beneficial positive effects of the “bad” genes may be lost, or the edited gene may have different effects in different environments.  Further, the edited gene will persist in the human population. 
    • At least, this concern would appear greatly to limit the number of genetic conditions that would be appropriate for heritable editing, to a few where a very discreet genetic abnormality that causes a devastating disease is well understood.  Such limits would almost certainly be unenforceable, as efforts to edit genes that clearly cause disease would be expanded to edit genes that predispose to or increase risks of disease, or event to insert or add genes thought to protect from disease.  The additional complexity of the tasks would further confound attempts to calculate risks.
  • The justice of heritable genome editing could well be limited by:
    • The costs, either in the individual case or more broadly on the health care system because in vitro fertilization would almost certainly be required to carry out the heritable editing;
    • Diversion of resources from dealing with environmental or socioeconomic conditions with greater overall impact on the health of the human population;
    • A bias against people with disabilities may be fostered.
  • If heritable gene editing included efforts to enhance traits perceived desirable, harms could arise from miscalculations about whether such enhancement truly yields a better life (e.g., if one could be genetically altered to require less sleep), or pressures on the offspring to perform up to enhanced expectations, again violating the principle of nonmaleficence.
  • Efforts at enhancement would create eugenic pressure to extend the enhancement widely through the population, and/or create a split-class society of (presumably wealthy) genetically enhanced “haves” and unenhanced “have nots,” violating the principle of justice.
  • Limiting heritable genetic editing to the few cases of single-gene-caused serious diseases would benefit only a few affected individuals and their parents, by helping the latter to have genetically-related, unaffected offspring, while risks such as those outlined above could affect many, either by creating direct risks in the population or indirect risks of lost opportunities from deferral of attention to other health and societal problems.
  • Likewise, an appeal to autonomy fails.  Procreative freedom has not yet been held to include a right to bear a genetically-related child, much less one free of undesired traits, and even if such a right were recognized, it would not be unbounded, but would be subject to limits set by concerns such as well-being of the resulting child and societal concerns.  Moreover, parental exercise of autonomy for heritable gene editing would limit the autonomy of society by potentially exposing others to unintended risks without their consent, and would limit the autonomy of gene-edited descendants, whose genomes would be determined at least in part by the decisions of their ancestors.

Thus, in brief, runs the argument.  Like the utilitarian argument summarized in my February 6 post, these contemporary discussions are important to review from time to time.  Further perspectives and analysis to follow in future posts.

An argument for heritable genome editing

Some weeks ago, a utilitarian perspective in favor of heritable genome editing was published (purchase or subscription required to read).  In it, the author, Kevin Smith of Abertay University in the United Kingdom, begins with a general defense of utilitarianism, the ethical philosophy that what is morally good is what produces the greatest good for the greatest number, as opposed to alternative ways of judging that invoke duty, principles, God’s law, or virtues.  In the process, he comments that ethicists who do not consider themselves utilitarian often employ risk-benefit or cost-benefit analyses in making particular judgments.  “We’re all utilitarians now,” as it were.   Smith then proceeds to make a case by a utilitarian, for utilitarians, in favor of pursuing heritable genome editing.  Key points:

  • Genetic editing will technically improve, reducing if not eliminating risks and broadening the ability not only to eliminate genetic disease but also to enhance complex genetic traits and correct mutations that increase risk for disease.  He envisions a day when correcting gene editing errors will readily be reversible by further editing (an “undo” function, as it were).  Consequently, we should anticipate that heritable genome editing will provide many benefits but few harms.
  • Early adoption of technologies is generally beneficial in the end, as, he argues, was the case with IVF, because to delay is to put off the benefits.  In the case of heritable genome editing, we won’t know how well it works without forging ahead.  Nonetheless, the editing of embryos leading to the birth of the edited twins in China in late 2018 was a bit reckless, and the reaction threatens to regrettably and unnecessarily retard progress.
  • Preimplantation genetic diagnosis (PGD) is not a preferable option because some genetic diseases cannot be avoided with PGD (i.e., if all IVF embryos are affected, so there is no unaffected embryo to select) and, more importantly, any additional risk from heritable genome editing is likely to be limited to a relatively few cases in the relative short term, while ultimately yielding much larger benefits to a larger number, justifying the greater risk to some.  (This, I suppose, could be considered crudely analogous to the accepted human research principle that risks to subjects may be acceptable if potential benefits to society—e.g., in development of a candidate new medicine—are possibly greater.  It’s OK for some people to get sick from too high a dose of an experimental drug, for example.)
  • Heritable genome editing should be used soon, because doing so will hasten the first celebrated successes, which will supercharge public support to expand the use of the technology.
  • Adoption is an important alternative, because it increases the happiness of an existing individual, the adoptee, instead of the more speculative prospect of a healthy new person without disease from a mishap from the gene editing.  But if a couple chooses not to adopt, preferring to have a genetically-related offspring, they should not be denied the opportunity if one is possibly available.
  • In general, more new people means more overall happiness for the human race in general, because the new people are more likely to be happy and not, and at least not diminish the happiness of other existing people in the progress.  (This seems to take for granted that heritable genome editing will not cause a detrimental population explosion—which, indeed, seems pretty unlikely.)
  • Having a child produces more happiness for all involved than not having one.
  • Having a genetically related child is better than having one that is partly unrelated, as would be the case with a child conceived using sperm or egg donation from a donor without a genetic disease to be avoided.
  • In cases where a couple simply could not avoid their naturally-conceived child having a bad genetic disease, to go ahead and conceive such a child would entail suffering for the child and parents, and the moral benefits of suffering are overrated.
  • The upside of heritable genome editing—i.e., the potential for human enhancement—is huge.

Many of these points are reasonable as far as they go.  Where this sort of argument leaves one unsatisfied is in the high optimism for technical success without unintended consequences; conceiving the risk-benefit relationship as if it can readily be calculated with confidence; disregard for broad consequences for how we understand ourselves, our begetting, and how we should receive fellow humans who are less than fully whole, physically; and, in some cases, the potential for alternative treatments.

Smith rejects a “precautionary” approach as too timid, but still concludes that maybe we should wait a bit, for the reaction to the Chinese twins’ birth to wear off and for scientist to be able to marshal further their technical case. 

Discussion to follow in future posts.

Twenty-first Century Divorce: Who Gets Custody of the Embryos?

A recent CBS news story provides yet another example of the technology and legal cart pulling the ethical horse.

In short, in 2014, an Arizona couple used in vitro fertilization (IVF) to preserve her eggs after she learned she had breast cancer and would require chemotherapy. The woman’s then boyfriend originally declined to be the sperm donor but later agreed when the woman, perhaps desperate to preserve her eggs, considered using a former boyfriend as the donor (fertilized eggs survive cryogenic preservation far better than unfertilized eggs). The couple executed a contractual agreement, provided by the clinic, as to the disposition of the frozen embryos (“their joint property”) should their relationship divorce or dissolve prior to implantation. They married several days later, underwent IVF yielding 7 embryos, which were cryogenically preserved and the woman underwent successful chemotherapy.

Unfortunately, after 2 years of marriage but prior to implantation, the husband filed for divorce. The pre-IVF contract stipulated that both husband and wife had to mutually agree on the disposition of the embryos – if not, they agreed a court could decide the embryos’ fate. Recently, the Arizona Supreme Court determined that the embryos should be put up for adoption, siding in one sense with the ex-husband to prevent the ex-wife from “using” the embryos. The decision upset many in Arizona to the point where the Arizona Legislature enacted a law to award the frozen embryos, in the future cases of divorce, to the spouse who “intends to use them to have a baby.” The new law will not benefit the ex-wife so, at the time of this blog entry, she was considering whether or not to appeal her case to the US Supreme Court.

There is a lot here to consider. I want to focus on just a few issues. First, I left scare quotes around several of the terms used in this case. The frozen embryos are indeed legally “joint property”, much like children in other cases of divorce. The couple could have just as easily checked the box on the contract to select “Destroy the Embryos” in case of their divorce. This same choice is one that many married (and unmarried) couples make regularly in IVF absent divorce when deciding the fate of unwanted or unused embryos following successful pregnancy and birth from prior IVF cycles. So asking a court to decide the fate of the frozen embryos is similar to children of divorced couples (though their “destruction” is not currently an option.)

“Using the embryos” is terminology that further emphasizes the commodification of frozen embryos as we consider them as a convenience for, or, for the sole benefit of, the parent(s). While I can empathize with the ex-wife’s desire to preserve her ability to have future children in the face of cancer treatment, her choice of an ambivalent (then) boyfriend over an ex-boyfriend as the father of her future children has proven disappointing, if not disastrous, for her in the present. It is harder for me to grasp the rationale of the ex-husband, who, though previously agreeing to father his ex-wife’s children, now (vindictively?) refuses to allow her to mother them, particularly since (continuing with my horse analogy) that fatherhood horse left the barn years ago.

As we allegedly advance our technical and scientific skills by increasing the various situations in which women can become pregnant, we are demanding more legal decisions when these new situations cause conflict rather than discussing and agreeing beforehand whether or not to permit these situations from occurring in the first place.

New technology, old moral problem

Many of our discussions in bioethics are about whether the things that are possible to do with advances in medical technology are things that we ought to do. However, some of the moral concerns in medicine are much more basic. They have to do with the idea that dates back at least to the Hippocratic oath that physicians should use their knowledge for the benefit of the people they treat. Patients should not be used by physicians in ways that are harmful to the patient in order to increase physicians’ income.

Medscape recently reported on a study presented at the American Society for Reproductive Medicine 2019 Scientific Congress which looked at how well fertility clinics across the US complied with the Society’s online advertising policy. They found that many clinics were not following the policy. The major concern was that there were a significant number of clinics that were advertising success rates without revealing the additional information needed to make that rate meaningful. The most serious concerns had to do with clinics that advertised high success rates without revealing that they also had higher than recommended rates of transferring more than one embryo per cycle and had significantly higher than expected rates of twin pregnancies. It is well known that twin pregnancies have a higher risk of complications for both the mother and the babies. Transferring more than one embryo increases the chance of achieving pregnancy and live birth with a cycle of IVF but also increases the likelihood of twin or other multiple gestation pregnancies and the risk to the mother and babies. By transferring more than one embryo in situations in which it is not generally considered justified, these clinics are increasing the success rate that they advertise to obtain patients by doing something which causes harm to their patients.

When the physicians at a fertility clinic prioritize their income above doing what is best for the people they are treating, they have gone beyond unethical business practices. They have abandoned one of the main things that makes the practice of medicine a moral profession.

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.

Can we hop the gene-editing train?

As Joy Riley pointed out on this blog on December 7, the world and the scientific community recently marked, with almost no fanfare, the one-year birthday of “Lulu” and “Nana,” the first (we think) and still only (we think) humans to have had their genes edited heritably—in a way that will be passed on to future generations.  Joy commented these children are “experimental subjects for life,” or, to use the phrase I found and discussed some time ago on this blog, “the babies are the experiment.”  To wit: it is not possible fully to assess and limit the risks of heritable genome editing before actually editing humans.  One must forge ahead.  Even if one were to edit a series of embryos, and abort them at different times during gestation to get a full assessment of their prenatal development, the questions about lifelong effects and effects on future generations would persist. 

And, as mentioned in other posts on this blog earlier this year, there is the issue of “nonphysical” harms to how we understand ourselves and our human existence.

A number of world scientific bodies are assessing, independently of each other, what regulatory safeguards should be instituted, on the assumption that heritable genome editing is something that should be pursued.  Last month, the journal Nature editorialized that efforts by the World Health Organization, US and UK scientific bodies, and a third international commission should not proceed separately (they are all due to report their findings in 2020), but should work together.  The editors apparently think that it would be straightforward, obvious, and right to adopt a moratorium on clinical applications of heritable genome editing, establish an enforced registry for all experimentation in this area, and expand the conversations to include representatives of people with disabilities.  If I read that correctly, it’s hard to disagree.

In the laboratory, things are moving fast and it is well-nigh impossible to keep up with the science or the conversations about it without that work being one’s main occupation.  A recent contribution linked by the Nature editors is called “prime editing” that appears to increase substantially the efficiency of gene editing, raising the prospect of correcting abnormalities associated with the vast majority of genetic diseases.  The relatively naïve, like your present correspondent, might wonder whether this approach could be limited to already-born people with genetic diseases, as treatment, rather than engineer the genomes of the unborn in an apparent attempt to eliminate these abnormalities from the human prospect.

Even thinking about the general public trying to influence where this work leads feels like assuming the role of an old-style hobo, trying to hitch a free ride by jumping onto a moving freight train.  One is liable to fall under the wheels.  But in the case of heritable genome editing, you’re likely to get run over anyway.

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.