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The Fundamental Ethical Flaw in Jiankui He’s Alleged Gene Editing Experiment

By Julian Savulescu

Chinese researcher Jiankui He of Shenzhen claims to have gene edited two healthy embryos, resulting in the birth of baby girls born this month, Lulu and Nana. He edited a gene to make the babies resistant to HIV. One girl has both copies of the gene modified while the other has only one (making her still susceptible to HIV).

On July 29, 2017, He uploaded a copy of his lecture on YouTube, “Evaluating the safety of germline genome editing in mouse, monkey and human embryos“. He finishes the lecture (see 11:22) arguing that experimentation in humans should be “slow” and with “caution”, remarking that “a single case of failure might kill the entire field”, as in the case of the death of Jesse Gelsinger. He closes with a picture of Gelsinger.

Gelsinger died during a somatic (not germline) gene therapy trial nearly 20 years ago. Early gene therapy trials were conducted with an emphasis on participant consent. A somatic cell gene therapy was developed for ornithine transcarbamylase deficiency, a disorder of nitrogen metabolism. The condition comes in two forms: mild, with normal life expectancy and management by diet, and severe, which is lethal in the first year. Researchers, acting on the advice of ethicists, decided to conduct the first trials in adults with the mild form of the disease as they were capable of consenting. Gelsinger consented at age 18 and died due to a catastrophic immune reaction. He would have had a normal life expectancy in the absence of the intervention.

At the time, I wrote this paper. I argued the main failing of that experiment was failure to minimise expected harm. The design of the trial was flawed; it should have been conducted in infants with the severe form of the disease, as this would have resulted in less expected harm.

Few people read that paper. Twenty years have passed and the same mistakes are made again. He Jiankiu mentions Gelsinger but appears to have missed the major lesson. It is precisely the failure to understand the basic principles of research ethics that makes this experiment so monstrous, not the mere fact it employs gene editing. As I have argued, any first in human trials should begin with embryos which have lethal single gene disorders, not otherwise normal healthy embryos.

The message is clear for the gene editing community: any trial of gene editing with the intention of bring a live born baby into existence should first be tried on embryos disorders that would be fatal in very early life.

  1. The basic principles of research ethics are:
    Risk should be reasonable (See Savulescu & Hope, The Ethics of Research). This includes that risks are minimized and that there are proportionate benefits. There would have been less expected harm if embryos with lethal disorders were used. Any child produced would stand to derive a very significant benefit: having their life saved. Lulu and Nana derive no direct benefit: HIV can be prevented in numerous ways, including by protected sexual intercourse. Yet they were exposed to significant risk of off target mutations and cancer. The benefits to them are not proportionate to the risk.
  2. Consent should be obtained. Clearly embryos cannot consent. Research on incompetent participants can be ethical if it is minimal risk or the benefits are proportional to the risks. This would only be the case if the embryo had a lethal disorder, and not when the embryo and future child only stands to be harmed with no direct benefit.

People have been puzzled as to why I have been such a vigorous and vocal critic of this experiment since I have a track record of supporting gene editing. Gene editing will likely be one day safe and of both clinical and non-clinical utility. But at present, it is still experimental. There should be further work on embryos which do not develop into babies into reducing off target mutations and assessing whether they have occurred.

But most importantly, any first in human trial potentially giving rise to a live born baby should conform to basic principles of research ethics. This requires that the risk is reasonable. This requires that such gene editing trial use embryos with a catastrophic lethal single gene disorder.

The problem with this study is not that it involves gene editing. It is that it has an unethical design.

It is too early to try gene editing in humans. But when it is appropriate, let’s design the trial ethically.

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10 Comment on this post

  1. Not sure I agree entirely here, Julian. Of course, it is a problem that risk minimization is not applied. But even if there had been such minimization, this kind of gung-ho, one-off stunts are basically scientifically useless, so there will be no confirmable benefit to outweigh even minimal risks.

  2. I saw Nobel Laureate David Baltimore criticised He’s defence of his work as irresponsible. He apparently stated it would make more sense to use embryos with Huntington’s Disease or Tay Sach’s disease. They would be better candidates ( This repeats the kind of mistake I am describing though to a lesser degree. Huntington’s Disease is very different to Tay Sach’s Disease. People with Huntington’s Disease have an adult onset of the disease and are likely to have 40 years or so of good life. Tay Sach’s starts early in life: they have less good life to lose. We should not do first in human trials in Huntington’s Disease. Tay Sach’s might be a candidate but there are likely even more severe, lethal single gene disorders which would be even better candidates.

  3. My view is that the fundamental problem with applying the CRISPR technology outside the laboratory is that our present understanding is gravely inadequate in relation to the vast complexity of living systems, human and nonhuman, organismic and ecosystemic. But the uproar over this particular application just underscores the myopia of our vision: it’s always “all about us,” the sacrosanct _human_ organism. If it’s “playing God” to try to prevent the development of a single disease in a human being because it entails manipulating the fetal genome, why isn’t it “playing God” to allow our single species to drive thousands of others into extinction and destabilize the entire Biosphere? The serious danger of CRISPR lies in the plans to create a slew of un-evolved organisms and release them into the environment, as if there weren’t enough problems already with naturally evolved but nonindigenous species creating havoc in ecosystems where they don’t belong.

  4. The question is not...

    “so monstrous” … “It is too early to try gene editing in humans.” … “used as genetic guinea pigs” (from Savulescu’s previous post on the same topic at this blog)

    Meanwhile millions of non-human animals are forcibly subjected to extreme suffering, bodily harm and killings in medical experiments and billions more in factory farms. How can putative utilitarians like Savulescu spend time so sharply denouncing this *one* single human germline gene editing while implicitly accepting the millions of other harms done to non-humans that in aggregation are massively larger?

  5. That is so true. Have you noticed how common it is to read, in the introduction to a scientific experiment (which I do a lot of, just to keep track of what’s going on in various biological fields), something along the lines of “because it would be unethical to perform this experiment on human beings, we are using _______ (fill in the blank with your favorite lab animal) as a model . . .” — AS IF somewhere it has been decreed what is ethical and what is not, and this researcher can’t be bothered to think any more deeply about the matter than that. And what does it mean to be a “model” human? Does it mean that, whatever the animal that is standing in for the human, that animal is of no value in and of itself? One thing it clearly means, of course, is that it isn’t really a human being, and so any results obtained in the experiment are necessarily applied to the human case only by extrapolation. But if what is of interest is what happens in the human case, why not design the experiment in such a way as to be something a human being would be willing to take part in? If we’re not clever enough to figure out how to do that, perhaps the experiment shouldn’t be done. If it’s for “our” benefit, shouldn’t it be those of “us” running whatever risks it might entail?

  6. The question is not...

    Reply to Ronnie Hawkins:

    I can partly understand why individual biomedical researchers goes along with extremely harmful, coercive experiments on countless animals without much thinking. After all they’re trained primarily to go for medical discoveries and all the research protocols that they’ve been taught to follow give them the go ahead to harm non-humans.

    What is supremely depressing though is when people like Savulescu, a prominent academic bioethicist, drones along the same lines.

    Based on the most recent posts by Savulescu here he seems to be an ultra-speciesist who thinks extreme suffering experienced by millions or billions of non-humans is insignificant compared to the risk of harm to two human animals.

  7. Animal suffering is a monumental problem. Our treatment of animals will probably be looked upon by future generations as we now look upon slave owners. I have just written a chapter on animals for a new book by Tom Beauchamp and David Degrazia.

    But there are also many other monumental issues: child labour, domestic abuse, war, climate change, biological weapons, and many others. As an academic bioethicist, I see my role as trying give some insight into how to identify ethical issues and think about ethical about them, so people can do that for themselves about any issue. The bad arguments, misapplication of concepts or principles and other ethical mistakes in the gene editing debate are as good a place as any to try to show how ethical deliberation is possible.

  8. The question is not...

    Julian Savulescu: “Animal suffering is a monumental problem. Our treatment of animals will probably be looked upon by future generations as we now look upon slave owners.”

    I was glad to read those words. But then you added:

    “there are also many other monumental issues: child labour, domestic abuse, war, climate change, biological weapons, and many others.”

    First, non-humans are also harmed through many of those other issues, so the contrasting is peculiar.

    Second, the number of humans harmed by all of those other issues combined is magnitudes smaller than the number of non-humans harmed by humans. Yet your writings here, and the issues that this practical ethics blog more generally attends to, are overwhelmingly human centric.

    You also used the expression “used as genetic guinea pigs” to object to He’s experiment on two human animals.

    That objection seem to work only through a tacit speciesist premise that using humans as “genetic guinea pigs” is wrong while using non-humans, such as guinea pigs, as “genetic guinea pigs” is permissible.

    Perhaps I’m misinterpreting what you meant by that expression though. A clarification would then help.

    “The bad arguments, misapplication of concepts or principles and other ethical mistakes in the gene editing debate are as good a place as any to try to show how ethical deliberation is possible.”

    If it is *only* as good a place as any then that is no reason for choosing to devote time to this issue in particular. You might then as well from now on instead focus on showing how ethical deliberation is possible with regard to non-humans. That many more non-humans are harmed by humans is a reason for making that shift.

  9. I can “partly understand” why biomedical researchers do what they do–I’ve been there. But it was like being one of those “four eyed” fish that can see both above and below the water; on the surface I could see what was expected of me, and even appreciate the intellectual fascination of the “search for knowledge,” but below it I could resonate with the monkeys and other animals I had to treat as “objects” in the process. There was a social circle of people who could relate to what the animals were experiencing, mostly composed of animal caretakers and other students as yet minimally indoctrinated, and a separate circle reserved for medical residents and the principal investigator, who worked very hard to avoid thinking about the ethics of what we were doing as we operated on the monkeys’ brains. I can also “partly understand” the philosophers, bioethicists whose graduate education is largely an immersion in self-enclosed anthropocentrism–I’ve been there too. But by that time I was also studying animal behavior, wildlife ecology and conservation biology, and so I had another “four-eyed” experience, learning the major milestones in western philosophy at the same time I was seeing from the outside the narrow arrogance of Cartesianism and the detached flatness of reductive analysis, conceptual as well as scientific.

    Now, however, I sense that we are verging on two major paradigm shifts. One is a matter of shifting out of the extreme reductionism of the last couple hundred years, a reductionism that led us to see nonhuman nature as dead, passive, without agency and lacking in intrinsic value (a state from which we strangely exempted ourselves, evolutionary continuity be damned), to a new holism that permits us to perceive the living world as active, aware, and in multifaceted relationship with us—awakening in us a new sense of appreciation and awe. The other is a matter of grasping the stark realization of what our human actions have done and are continuing to do to the other life all around us, at many levels—one level is that of the huge numbers of individual animals undergoing tremendous suffering purely for the purpose of our human “preference satisfaction”; another is that of wild populations of nonhumans being decimated and species exterminated as we increasingly humanize the planetary surface; and yet another is that of the entire biosphere, rapidly destabilizing because we just can’t give up our bloated industrial lifestyles. I’m hearing a big collective oops! going up now, as we begin to come out of our planetarily destructive trance and desperately try to figure out how we can mend our ways before it’s too late for any of us evolutionary cohorts. And so my major criticism of the bioethicists is this: if the stability of the Holocene biosphere goes, we all go with it, and the latest new drug or emerging technology won’t matter a damn at that point. So until that happens, it might be a good idea if some of the best and the brightest minds among us were occupied trying to undo the shackles imposed by recent western philosophy on our innate human compassion and creativity, that we might yet act to save Life on Earth.

  10. “This includes that risks are minimized and that there are proportionate benefits.”

    This sentence sums up everything wrong Suvalescu’s technocratic fantasies.

    You have no concept of risk or benefit that doesn’t come down to warmed-over sentimentalism dressed up in the wardrobe of “decision theory”.

    But you’re happy to lecture everyone on “risk” from the ivory tower, safely free of any consequences for your mistakes.

    Rationalism is fraud and it always has been.

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