A pressing question, said Rudolf Jaenisch, an M.I.T. biology professor, is why anyone would want to edit the genes of human embryos in order to prevent disease. Even in the most severe cases, involving diseases like Huntington’s in which a single copy of a mutated gene inherited from either parent is enough to cause the disease with 100 percent certainty, editing poses ethical problems. Because of the way genes are distributed in embryos, when one parent has the gene, only half of the parent’s embryos will inherit it. With gene editing, the cutting and pasting has to start immediately, in a fertilized egg, before it is possible to know if an embryo has the Huntington’s gene. That means half the embryos that were edited would have been normal — their DNA would have been forever altered for no reason. “It is unacceptable to mutate normal embryos,” Dr. Jaenisch said. “For me, that means there is no application.”
If I were grading an undergraduate philosophy class, I am not sure Dr. Jaenisch would exceed a C minus with that answer (the source article is here). Besides I have never known a normal embryo. Then there is the all too obvious question as to why it should be acceptable to abort embryos, but not to modify or mutate them. Oops.
The better arguments are surely the slippery slope worries that embryo tinkering will change the nature and future of humanity in dangerous ways, perhaps producing too much conformity, too much zero-sum competition (“buy the Harvard splice”), too much discrimination against various “types,” too much induced family loyalty, legal discouragement of rebellious genes, excess advantages for elites, too many decisions which too explicitly lower the social status of some groups of people, and perhaps ultimately too much drift from the world we know (and love?).
Those are my worries. Whether or not they are valid, they would seem to merit at least a C+. But many commentators wish to ensure these issues are not actually argued. Will this prove the new face of anti-scientific, anti-philosophical thinking? Check out the closing quotation from Professor Daley at Harvard, and his use of the word “deranged.”
A lot of parents will strongly desire some future version of this product, and I believe a number of countries are going to be willing to proceed with such innovations, if and when they become possible. They’ll also be willing to live with the costs of the failures in the meantime. So I don’t think the strategy of shutting down debate is going to fare so well in this case.
Given the remarkable human history of using essentially all technologies for suppression of somebody somewhere, it is truly naive to think that “a number of countries are going to be willing to proceed with such innovations” is any less true than “countries will have taxes” or “countries will have armies.” Can we really believe that some autocrat, finding a path to breeding a race of super people loyal to him wouldn’t pursue this? If you claim no, have you read any 20th century history?
A much more substantive fear is “we don’t know how to do this” and therefore there’s a high risk of “curing” hunington’s whilst giving the baby no feet and no knees, or of “assuring” an IQ that will get the child into Harvard, at the cost of the being profoundly deaf, or of “enhancing” the child’s physical prowess so they’re a great professional athlete but also riddled with arthritus.
“Mom, you are going to watch me slowly die in my forties of the same neurological disorder that killed dad. Why didn’t you have this gene edited out of me?”
“Because mutating a normal embryo was unacceptable, but watching you die in what should be the prime of your life is just dandy. Pass the popcorn while I watch. Oh wait, you can’t because you shake too much.”
Given its so easy to test and abort and then do the old in-out and repeat until the test is negative for the hereditary disease, the question is how often is your hypothetical occurring in reality now.
We cannot at the moment safely edit out the allele for Huntington’s, so it is currently a fantasy. But if we could, then it wouldn’t even be a “cake or death” choice, it would be a no “measurable effect vs death” choice. They wouldn’t even get cake out it.
note that I summarize the “we do not know what we are doing” argument, I do not actually make it.
and of course a 100% accurate screening program that could tell people before they formed couples could end that particular scourge.
but even that frightens people – society arranges that noone is conceived with hunington’s or even downs. where does it stop?
We don’t know what we are doing yet. You remember Dolly but you forget all the sheep you died before her in the attempt to clone her.
I can buy that the United States is far too risk-averse where human lives are concerned, while China is far too risk-accepting where human lives are concerned.
And you Dan, you remember Dolly… but not that she died of a common sheep problem or the lives of all the sheep *after* Dolly: http://news.bbc.co.uk/local/nottingham/hi/people_and_places/newsid_9217000/9217340.stm So whose memory yields a more accurate belief about the safety of cloning?
Someone woke up on the wrong side of the Dual-N-Back bed this morning. 🙁
Given what we understand concerning the (limited) role of genetics, it appears unlikely to impossible that genetic modification could offer “a path to breeding a race of super people loyal to him”.
If I were the autocrat I don’t see why members of any “super race” I might breed would chose to be loyal to a genetically inferior troll like me.
Meh, my bet is on the exo-skeleton autocrat crushing the gene-mod autocrat.
Pretty sure Bruce Sterling wrote in the 1980s about that war.
DNA edited right after fertilization means said edits can be propagated through offspring. Your concerns are valid and important, and are being discussed among scientists. After all, deciding what is (or isn’t) a desirable trait (i.e. “mutation”) is a VERY slippery slope… And who gets to make those decisions, anyway?
“Who gets to make gene editing decisions?” <– Parents paying for gene editing services.
"Ethical discussion" is just op-eds and parlor debates. What matters is that the core gene editing technology is in heavy use and getting better every year. Two major areas it will develop are with making better strains of livestock and with humans, treating diseases like Tay Sachs which result in death of small children by the age of four, are genetically very simple, and currently have no treatment options. Saving a child's life will trump ethical concerns about gene editing.
+1
Assuming we can gather the requisite data (see the shutdown of 23andMe) editing of embryos will be performed by most parents that have access.
Many of the diseases which could be prevented through relatively simple genetic modification could also be prevented through preimplantation genetic diagnosis (i.e. IVF plus genetic testing of embryos and then selection).
Yes, there are some truly terrible monogenic diseases. It wouldn’t hurt my feelings to see them go. But that’s the low-hanging fruit. I’m more interested in other areas, such as height and intelligence. At least those examples are highly complex and polygenic.
Still, your point about people (or governments) with means seeking out and finding people with expertise is correct. It’s just that germline editing of people amounts to directed human evolution. And I don’t think that should be a free-market decision. I’m just not sure where one draws the line.
What if not free markets has driven human evolution up to now?
Hahaha, good point!
> And I don’t think that should be a free-market decision.
Even though you seem to have conceded the point in your comment above, I want to drive a stake through the idea.
If it isn’t free-market then who makes the decisions? Who enforces the decisions? That is a lot of power, are you sure it won’t be bent to someone’s will? And finally, why do you think it will lead to better outcomes?
I see that you read my tweet about the costs of too much conformity.
I would predict that cultures more accepting of plastic surgery would be more willing to proceed with genetic alteration.
If so, the South Korean-Venezuelan-Argentinian Axis of Plastic Surgery will rule the world in the 22nd Century.
Colombia.
I don’t see blue anywhere in Tyler’s post. Here it is: http://www.nytimes.com/2015/04/24/health/chinese-scientists-edit-genes-of-human-embryos-raising-concerns.html?hp&action=click&pgtype=Homepage&module=second-column-region®ion=top-news&WT.nav=top-news&_r=0
Shouldn’t we need voluntary informed consent before modifying another person’s genome? It might be argued that an embryo is incompetent to give such consent so it falls to the parents to give it. However, that seems legally and ethically dubious unless a medical emergency or threat to a third party exists. Embryos have a right to refuse genetic modification in the same way any person has a right to refuse any medical procedure, and this right should only be violated if absolutely necessary, otherwise we head down the road of female genital mutilation and other similar elective procedures forced on children. Modifying an embryo to cure a disease it does not actually have is a violation of this ethical principle, which is Prof Jaenisch’s point.
We don’t require consent for conception, so why would we require it for genetic modification? If a person never knows what it would have been like to live without the modification, he has nothing to complain about. Additionally, as it is, there are numerous epigenetic heritable changes that we inevitably inflict on our offspring.
And the epigenetic inheritance might be tens times as powerful for all we know.
Even if you find it inconsistent, to most conception and genetic modification (and the genetic legacies thereof) occupy different worlds legally and morally. One is an intrinsically necessary sin of omission, the other an unnecessary sin of commission. That perception can change, but for now that justifies different rules for them, including regarding consent.
Would Huntington’s of Tay Sachs constitute a medical emergency?
If, and only if, there was a way to determine a particular embryo suffered from those.diseases, then yes for only that embryo. And that’s the problem, because we need to act while it’s still a single cell, but we have no way to test a single cell nondestructively.
Unborn babies have a right to refuse abortion? Crimethink!
+1 A logical statement if you accept the above.
In this case it’s a balance between the rights of the embryo and the rights of the mother. The mother’s right to bodily autonomy trump the embryo’s for now, but that does not mean the embryo has no rights.
You can, in theory, do the gene therapy on the fertilized eggs, so that it ends up in every cell, but it isn’t activated until exposed to a very specific virus. So you can prepare the child, and then give the child the option to activate the gene therapy when they are of majority.
This is all theory, of course. Using a virus to deliver gene therapy to adults has killed a person despite theory. And one of the big ethical hurdles now is that we cannot do this safely.
You could also do the gene therapy on an adult, it just wouldn’t be transmissible to the next generation.
The whole point of gene-editing on embryos is to make the trait heritable. Not because it’s impossible to do it on adults.
If the gene therapy hits my gonads (so to speak), it’s going to get passed on.
Gene therapy is harder in an adult, because you have to hit so many cells. Especially for toxic gain-of-function diseases like Huntington’s.
Most hilarious troll I have seen in weeks.
How is a 5-day old blastcyst supposed to give consent? It doesn’t have mouth yet, or even any nerve cells.
It’s not a person, it’s a clump of undifferentiated stem cells.
And what if the gene modification would result in it having a 120 IQ instead of a 60 IQ. The latter perhaps never being considered competent to give informed consent about a technical matter?
Talking about embryos giving consent really just exposes the ludicrous nature of treating embryos as people.
Maybe we should hire mediums to try to communicate with the embryo’s “soul”. Maybe it can tell us about it’s past lives.
It’s not black and white like that. Bioethics is generally many shades of gray. It is not a question of whether embryos are people and have rights, or are not people and have no rights, but the *extent* to which they are people and have rights. It is generally accepted that the rights of the unborn are often subordinate to those of the born (e.g. in the case of abortion where the mother’s right to control her body and health trumps the embryo’s), but that has limits. The Odierno convention for example bans the creation of embryos specifically for experimentation and choosing the sex of embryos, because those just go too far. It’s not a settled question, but it is generally recognized that there have to be some limits to what we can do to embryos, because they do have some rights, even if not the same as a full person.
That’s why I pointed out that the embryo is legally incompetent to make these medical decisions for itself, so its parents are trusted to make them for it. However, the powers of such substitute medical decision makers are legally circumscribed.
If I were to fall into a coma, for instance, my family would have the power to make whatever medical decisions and order whatever medical therapies were necessary to resolve the medical emergency, but not to give me unnecessary cosmetic surgery or a sex change. Their power to make medical decisions for me while I am incompetent is not unlimited. The same should apply to parents making medical decisions for their children, born or unborn.
Of course, there are a lot of grey areas here. Whether a particular genetic modification constitutes a necessary or unnecessary therapy can be very hard to decide. Prof Jaenisch’s point is precisely that determining necessity even for life saving genetic modifications is impossible with currently conceived methods, because we must use them on a single cell, yet cannot test that cell nondestructively. If we are unable to determine necessity, then therapies must be extremely safe with rare side effects to apply them as a precaution even on undiagnosed zygotes, but we are not anywhere near the required level of safety.
It’s okay. We’ll genetically modify their personalities so that they would consent.
I think you are being too hard on Dr. Jaenisch. First, how do you know what he fells about abortion? Second, surely when we speak of a “normal” embryo we never mean that it is perfect: surely, we mean that its defects are within the range of what would produce a “typically” healthy baby today, even if the kid might have an extra mole on his back and–upon reaching adulthood–discovers that one leg is shorter than the other. Third, there is no indication that his answer comprises an exhaustive list of his concerns: Indeed, he describes it as “A pressing question” and it could well be that among his other pressing questions is the slippery slope issue.
A quick Google search revealed nothing on Jaenisch’s position on abortion itself, but he does engage in human embryonic stem cell research, implying that he supports some instrumentalization of human embryos. Of course, it would not be wholly ethically inconsistent to also oppose abortion.
Given the productive capacity to pump out billions of embryos per year, merely sorting them and tossing out the bad ones would make more sense. No one suggests repairing tomatoes and apples that are defective in formation or that get bit by a bug or hit by a hard object. The bad ones are just juiced while the select few are delivered to market.
Where technology has been employed to increase the yield of apples and tomatoes using gene editing of some sort, the result is bland and uninspired.
Not quite: The analogy is more like this. You want one perfect apple (let’s suppose the perfect apple is 1 in 1,000). You can test all the apples for defects you want, but each test costs on the order of $10K to perform (and requires you to get anesthetized…). Apples degrade, too, so you can’t really keep around the ‘top-level’ of apples in the hope of getting a better one in the future. Suppose it costs $1m to fix a bad apple.
You can either spend $1.01m to find a random apple and fix it, or
You can test 1K apples at $10K apiece for $10m.
If perfection weren’t the goal, and testing were much easier and cheaper, yours may be the better way. I’m admittedly not an expert, but if my back-of-envelope is correct, the scientists are doing it the right way, due to the cost (in time and money and invasiveness) of testing.
Tyler,
Two quick questions:
1) What do you think of movies such as Gattaca in this context? Do you think that these provide a good or a bad view of the future of gene editing from the economic point of view?
2) If there is a probability p of the invention of gene editing materializing every year, do you think it’s sensible to postpone having children a few years if you’re planning to have children in the near future? I would guess there is at least some justification to postpone having children by a few months? Will the announcement of this technology lead to inter-temporal substitution when to have children?
You assume that there is (or ever will be) such a thing as a “Harvard splice”. I would not take that as a given, as we are far from the point where we can reliably posit that it is possible to improve humans in the “smart and handsome” category. I think it is more likely that we will move into a world where gene editing (not justified by medical reasons, such as Huntington), is similar to today’s parents’ choice about vaccination, i.e. dogma above reason. There will be parents who will make the arbitrary (and probably expensive) choice to provide their kids with “better genes”, while others will be strongly opposed on the basis that the true “genetic algorithm” gives them the better result. And I also do not believe that it will be obvious anytime soon that one or the other group is right.
Excellent post, thanks Tyler.
“But many commentators wish to ensure these issues are not actually argued…”
Indeed, that NYT article didn’t make even a cursory effort to find any counter-arguments.
But Oxford’s Julian Savulescu has been long making a cogent defense in favor of gene editing. He also makes some good points about the cowardice of Nature and Science for rejecting the recent Crispr study: “It is the Chinese scientists led by Huang, not our leading scientific journals, who occupy the real ethical highground.”
http://blog.practicalethics.ox.ac.uk/2015/04/the-moral-imperative-to-research-editing-embryos-the-need-to-modify-nature-and-science/
I think the moral questions and concerns about societal impact are justified, but we are very far off from this being tested and checked for consistency and long-term safety. So far off, as in I think the only way we begin to see this in the next 20 years in the US is via some underground capacity or something.
Yes, this touches very quickly on the issue of abortion.
The still unresolved questions of neuroscience and genetics in issues of morality and religion also are involved.
Let’s posit that Haight’s 5 base/2 base moral systems include some genetic predisposition. We can take at face
value some of the atheists’ calls to remove children from the families that will provide any religious education.
This leads pretty quickly to a scenario of artificial selection in a positive feedback loop driven by and driving a
particular morality (and religion and theology). Hard to get much more problematic than that.
>too much discrimination against various “types,”
If Rudolf’s answer gets a C-, this answer is somewhere around H.
The entire point of this process is to discriminate against various types. Putting the word in quotes, in order to give it “meaning,” is both inane and cowardly.
Genes are regularly mutated and embryos regularly destroyed by the standard machinery of life. Is nature immoral, and perhaps a monster? It appears so.
red in tooth and biotech lab
Many humans want to live in something better than the nasty, brutish, and short terms that nature has set for us.
Will those opposed to eugenics prove the new face of anti-scientific, anti-philosophical thinking?
With gene editing, the cutting and pasting has to start immediately, in a fertilized egg, before it is possible to know if an embryo has the Huntington’s gene.
I’m not sure if this is true. It is currently possible to do genetic testing on day-5 blastocysts, these services are commercially available.
Or does he mean that CRISPR will only work on one cell at a time? I’m not sure that’s true either …
I was under the impression that CRISPR would spread the edited genes to the entire organism, but couldn’t reach germ-line cells because of something about how egg cells are all generated by birth and encapsulated, making the DNA impossible to reach.
But they should be able to reach every cell in a day-5 blastocyst, so you could test and do the gene editing at the blastocyst stage before embryo
transfer. Admittedly, it’s a compressed time-scale, but there’s no reason it’s technically impossible.
I was under the impression that CRISPR would spread the edited genes to the entire organism,
I am not a biologist, but my understanding is the gene drive of CRISPR in sexually reproducing animals is that it causes you to pass on the gene to each child with 100% chance, instead of each gene having a 50% chance.
I would love it if Tyler got a guest-blogger who knows all this stuff cold to answer all our basic questions.
If that was the case, there would be no reason it has to be done on embryos. I thought there was something about the egg cells already being created at birth so to get the germ line the only way was to edit embryos.
The big lesson of bioethics as it appears in mainstream media: There’s not some IQ above which you stop being tempted to backfill moral arguments for your visceral reactions to new technology. (I have no idea if this also describes bioethics that doesn’t get quoted in the MSM.)
ISTM that there’s a short-term issue w.r.t. risks vs benefits of the technology, and a long-term set of social issues which Tyler kind-of minimally sketches out.
The short-term issue is that the bugs haven’t been worked out of this technology yet, so using it on humans would be taking some awful risks with those humans’ lives. It will presumably take many years of work to get to the point where human genes can be edited in a controlled and safe way, but my understanding (this isn’t remotely my field) is that this is probably going to happen–it’s engineering difficulties, not bumping up against physical laws or anything. (I gather the same thing is true of cloning humans–it’s probably possible, and maybe someone’s even done it already, but it’s not something that’s understood well enough to be safe to do on people.)
The social issues come later, and are really hard to untangle, and probably very hard to even come to consensus on. In our world, parents move heaven and earth to get their kids into the best schools; it’s pretty much guaranteed that lots of parents would shell out some extra money to give their kids a prenatal IQ burst if that was available. (How many parents bought those Mozart tapes, breastfed, etc., in hopes of getting smarter kids? And yet, right now, mostly what you’re able to do in that regard is choosing the kid’s other parent well.
Hazel:
They use other technniques (engineered viruses) for gene therapy in whole organisms (and I think they worry a bit about whether they might somehow affect the patient’s germline cells). I gather a general problem with gene therapy is that you can alter the genes in some cells, but not all of them (or all of any one kind of cells). I’m pretty sure the CRISPR techniques are done on individual cells or small collections of cells. (But I’m not any kind of expert on this stuff–hopefully someone who knows more will come along and correct me if I’m wrong.)
How is this so different than deciding with whom to mate? It will be more targeted to specifics “fixes” but the basic idea of trying for certain characteristics is the same.
A philosopher will assume that the gene editing will have the desired effect. Anyone involved with medicine will know, have pounded into them by teaching and experience, that it won’t work much of the time and will more than likely have unknowable side effects.
So the question isn’t whether we do something knowing for certainty that it will solve the problem, but will we do something where the side effects may or may not be severe in a situation where there is a 50% chance of not doing something ending in a very nasty illness.
If the gene editing has no effects other than the disease isn’t there any more, there is no question. But that isn’t the case. It is the same question when it comes to vaccines. There is a very small chance of a harmful side effect from the vaccine. There is a much larger chance of harmful effects from the disease. So the treatment of healthy children makes sense. But if the numbers were the other way or equal, or as in this case undetermined, then treating a healthy embryo would not be ethical.
It isn’t an abortion issue. It is a pretty basic cost benefit analysis. Do no harm is an ethical matter.
The level of desire for validation required to become a Harvard professor is the goldilocks level. The desire to be any more important-famous is deranged.
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