This is 100% correct.
(COI: Kiran was my postdoc while I was a student in the lab a decade ago.)
Some theists believe that we shouldn't tamper with God's perfect creation, because everything happens for a reason (including miscarriages, birth defects, and genetic diseases.) Atheists might believe that natural selection has got us this far, so it must be a pretty good process. A scientist shouldn't change anything, because they will be adding unnecessary risk to the natural process of evolution.
But you have to think about the "baseline". Natural selection is actually a brutal and horrific process where genes are just mutated at random. 50% of all pregnancies end in a miscarriage. Birth defects occur in 3% of all live births, and they account for 21% of all infant deaths. Nature is already a mad scientist that runs random experiments on babies.
I read that humans have about 30 genetic mutations per generation [1]. So imagine if a scientist picks 1 gene at random, and they use CRISPR to randomly change that gene. Now the embryo has around ~31 random mutations. Isn't that basically the same result as natural selection? You probably wouldn't even be able to tell that the scientist had changed anything.
Is that an accurate way of looking at it, or am I missing something?
We already know a lot about certain genes and what they do. For example, mutations in the HBB gene cause sickle cell anemia. Removing the mutation in that HBB gene is a good idea 100% of the time. You can just look at the 99% (?) of healthy people who have an HBB gene without that mutation.
Maybe the CRISPR process is risky and can cause lots of unexpected mutations. In that case it's not so black-and-white. But if you can edit a gene to prevent a disease, and it can be done in a safe way, then I don't think it's inherently unethical. (Although you could argue that it might be more ethical for parents to adopt a baby and donate money to charity, instead of spending a lot of money on gene-editing and IVF.)
If you can reach a high certainty level through other kinds of tests, then that would be another story.
I didn't realize that CRISPR gene editing can cause damage to other genes [1], so it might not worth it yet. If there was a perfect CRISPR procedure that had no other side effects, then it would be hard to argue against that.
[1] https://www.sciencedaily.com/releases/2018/07/180719165032.h...
I sure hope you are pro-life, otherwise making "consent" and "individual rights" a foundation of your view would be pretty hypocritical.
In my view, if you aren't even a fetus yet, you can't possibly have any rights. You're not a human being. During IVF, you select the embryo with the best health prospects - the rest may be destroyed.
Keep in mind I only disagree with the foundation, I still think the procedure is unethical because the scientific basis is poor.
That does not imply that a doctor or researcher has the right to risk causing debilitating life-long symptoms to another human being at any stage of development without a clear medical justification.
By your reasoning, because an embryo has no rights whatsoever, it would be fine to experiment wantonly for the sake of producing circus attractions. I presume you wouldn’t actually support this?
I also fail to see how the scientific basis is relevant to the ethical question. Whether the science is good or not, we’re talking about unnecessary procedures with inherent failure rates that can have brutal life-long consequences. I can’t see how someone can support this unless they are fundamentally lacking in empathy. As I asked another poster elsewhere in the thread, do you really think you would feel the same if something like this had been done to you and caused you to live with a painful deformity? Would you care then whether the science was good?
> That does not imply that a doctor or researcher has the right to risk causing debilitating life-long symptoms to another human being at any stage of development without a clear medical justification.
It's not the doctor making the decision to go ahead with this procedure, it's the mother. So, according to you, a mother has the right to kill an unborn child in the womb because it's the wrong gender (not uncommon in China) and that's "agency over her body" but then she can't attempt to mitigate the HIV risk it has given her child by procreating with an HIV-positive male. This is absurd.
> I also fail to see how the scientific basis is relevant to the ethical question. Whether the science is good or not, we’re talking about unnecessary procedures with inherent failure rates that can have brutal life-long consequences.
Nobody knows if there will be "inherent failure rates that can have brutal life-long consequences". That's why the science is bad. If the science was good, you'd know if the procedure is really that risky or not. If the procedure was 100% safe and effective, it would be unethical not to perform it.
Good or bad science has nothing to do with the outcomes--that's good or bad medicine. There's plenty of 'good science' practiced on lab rats that would immediately become horrifyingly unethical if practiced on humans, but that has nothing to do with how well the scientific method is being applied and what can be learned.
Anyway, this discussion doesn't seem to be going anywhere productive, so I will bid you good day.
No, I am not arguing that. That's an embarrassingly absurd conclusion to draw.
These babies have a risk of life-long HIV impairment. This intervention may prevent this. With any medical intervention, you need to trade off risk and reward. Obviously, for an unborn child, there can not be any consent here.
It would be unethical to not give the babies the treatment if there wasn't any risk associated. What makes it unethical is that the risk profile isn't even known. The scientific foundation is poor.
> Anyway, this discussion doesn't seem to be going anywhere productive, so I will bid you good day.
I agree and let me say this: You're by far the worst discussion partner I have ever had on HN.
Woe is me!
I somehow doubt you're very high on anyone's list yourself :-/
You're assuming it's riskier, in terms of lives, to try this technology. But it could be -- and obviously it's up in the air, which is my point -- that without such technology many more people will end up dying.
The status quo is never neutral with respect to risks.
What if it was used to provide immunity to malaria, as a hypothetical example?
Steady with the generalisations there. Your polarised US and various other places might be home to fewer liberal religionists, but that is not necessarily an accurate statement.
Excellent way of putting it. I'm adding that quote to my arsenal..
There is strong evidence that high mutation rates are selected against, to the point that some have speculated that driving down mutation rate is one of the key functions of selection[1].
Point being that increasing the number of germline variants is an extremely important consideration. The fact that the underlying biological replication mechanisms are not 100% perfect does not alter this point, and certainly doesn't mean that when you artificially increase the number of mutations that "this isn't a worse situation".
Maybe if you were seriously ill because of a genetic experiment we did on you (and that you did not need) as you were an embryo, then you would not hold the same view.
I don't think you get where the morality problem is... It's not about being Amish that say "we shouldn't temper with God's perfect creation".
It's about a country doing human experimentation on innocent people that do not need it, it's not to cure them from an heridetary problem but to breed a stronger race. China will only show the success of their experiments and will hide from the eyes of the world all the failures, handicapped babies, secondary effects of their human experiments. They'll make experiments on babies with lots of failure (it's science, you never get it right at the first experiment) and once in a while they'll put a video on YouTube like they just did saying "Aw look how healthy they are". But behind there going to be a lot of guinea pig children with serious secondary effects. And the worth part is how they'll make sure the rest of the world never see those "failed" children. This might be Nazi-level stuff that's going to happen and this is what people with a glimpse of ethics left are concerned about, it's not about "not tempering with God's perfect creation"
I'm not arguing for that, and I don't think it's the only possible situation.
> "it's science, you never get it right at the first experiment"
> "there is going to be a lot of guinea pig children with serious secondary effects"
I don't think so. If this does happen then it would be extremely sad, but I don't think it's very likely. Scientists are far more careful than that. A new drug has to go through many stages before it is ever tested in clinical trials, and these human trials are generally very safe. So I'm just trying to say that if this is done properly and with a lot of safeguards, then gene-editing is not inherently unethical.
But you're probably right about China. They have a horrible history of human-rights abuses, and I think they are much more likely to get this wrong. Even if it's not a government program, Chinese companies don't have a great track record [1]. I wouldn't be surprised if they were already performing some reckless experiments, and all of these people should locked up.
[1] https://qz.com/1323471/ten-years-after-chinas-melamine-laced...
I'd also argue that non-natural selection can be worse. We have crude forms of it through pet breeding, and cats come to mind. The Scottish Fold in particular:
https://en.wikipedia.org/wiki/Scottish_Fold
I worry non-natural selection could follow the path of the fold and various toy breeds.
Also pet breeding is a great example. But I think that's one of the advantage of CRISPR over selective breeding. Selective breeding results in lots of genetic problems like hip dysplasia, arthritis, etc. because the gene pool is too small. But I think CRISPR could probably fix most of these issues by splicing in the healthy genes from other dog breeds.
Although I just found this article: https://splinternews.com/meet-the-guy-biohacking-puppies-to-...
I didn't realize there was a DIY bio-hacking community just playing around with CRISPR in their backyard shed. This is concerning.
What is the relevance of "Asian nations?" to this conversation?
Also, we're talking about a specific experiment that was allegedly conducted in human beings with (good but error-prone) genome editing mechanisms, outside of the purview of peer review or, from what I can tell, an IRB.
Gene editing is mandatory, if only because we've managed to turn many previously lethal mutations into livable, and reproducible, ones.
I would assume it's because the article describes genetically-engineered babies in China, so obviously it's not outlawed there (or if it is, the law is not enforced). Grandparent poster is pointing out that if genetic engineering gives survival or competitive benefits to those who do it, it doesn't matter what your personal ethical, moral, and legal standards are, because your whole society will be outcompeted by societies without those strictures.
Or maybe a cozy cage in a zoo, with a little sign next to the bars which reads: "homo sapiens inferior".
Evolution is blind to such concerns. Those who "experiment" might be wiped out because of their experiments gone wrong, and evolution wont care at all.
A creature inventing tools might have an evolutionary advantage over others. A creature inventing e.g. biological warfare and nuclear weapons might have less an advantage, it can easily wipe most of its own kind and even collapse its civilization (losing even more advantages).
(1) IQ is very polygenetic - a big IQ gene might be 0.1 IQ, and there aren't a lot even that large, if I recall the large genome wide association studies done on this. As GWAS studies get larger we find more, but they're all super small effects.
(2) Having an extra 0.1 IQ point is easy to lose in the noise of other effects on having offspring.
So even if we assumed IQ was perfectly correlated with more surviving offspring in modern societies, it might take an extremely long time (even longer than a whole planet and a thousand years) to make a detectable difference.
(Note I am not advocating for gene editing)
Also I don't think we have reached a local maximum, human society kind of fucks with natural selection so I imagine there is room for improvement.
I didn't do good at school but i had many friends! I never felt i was less intelligent than my friends which make me question the IQ score thing.
My Dad has high IQ (135) and he's a mathematician.
So how did i inhert low IQ? My mom's score is average at best, 102.
I've sold 3 companies, i am married and I've managed to be quite wealthy.
You don't need to posses high intelligence to survive and reproduce in this world that's why it's not selected for.
We don't walk out of womb and given a puzzle to solve where if we fail, we are instantly killed.
https://www.gwern.net/Drug-heuristics
Here’s a brief snippet
> the intervention may be simple, give major enhancements, but result in a net loss of reproductive fitness The famous Ashkenazi theory of intelligence comes to mind. According to this theory, the Ashkenazi were forced into occupations demanding intelligence, and micro-selected for high intelligence. Except the high IQ genes were not previously prevalent among either Jews or gentiles because - like sickle-cell anemia - when they became too prevalent, they result in horrible diseases like Tay-Sachs. In 2007, a unique mutation in a Scottish family was found to increase verbal IQ in afflicted family members vs non by something like 25 points; this would be great for them - except for how that mutation starts causing blindness in one’s 20s or later. (In general, it’s much easier to find mutations or other genetic changes breaking intelligence than helping in cases of retardation26 and autism27.)
Based on all the GWASes and additional studies which have been done since 2007 and a continued absence of confirmed examples of IQ-boosting variants with negative pleiotropic effects, I now would explain the lack of optimization of intelligence as being an example of 'too complex for evolution because too many little changes to do simultaneously', that is, mutation load: essentially, there are too many little effects (which sum up to make us far stupider than we have to be), which have been created & maintained by too many demographic bottlenecks and genetic drift and other effects, too much background selection, and too much selection on other traits (plus some level of dysgenics), for the various harmful variants to have been meaningfully selected against over the past 50kya. And that's why we could boost intelligence a lot with few harmful and many beneficial side effects.
> The average human genome appears to be close to a local maximum.
Absolutely, but it's maximized for the environment we lived in 10-100 generations ago.
https://www.scientificamerican.com/article/bad-news-for-the-...
You join Mensa if your IQ is a large part of your identity. Individuals who have a high IQ but also have a lot of other things going on in their lives (like career success or fulfilling personal relationships) tend to concentrate on those things rather than join Mensa. Therefore, membership in Mensa tends to overselect for individuals whose self-conception is both narrow and focused on their intelligence. There's a lot of other evidence in psychology that a narrow self-conception correlates highly with mood & anxiety disorders. You can also get correlations with physical ailments like environmental allergies and asthma as well, because someone who doesn't have these physical ailments is more able to get outside or pick up sports rather than go to meetings of a high-IQ society.
So the way they designed their experiment, they introduced tons of conflating factors that may or may not actually have anything to do with IQ. It's certainly possible that high IQs are associated with mental and physical disorders - but what the experiment shows is that membership in Mensa is associated with mental and physical disorders.
In a population that got carefully selected traits for high IQ, these tradeoffs could over time be understood and the effects minimized.
IQ predicts health and longevity.
https://journals.sagepub.com/doi/abs/10.1111/j.0963-7214.200...
Intelligence Predicts Health and Longevity, but Why? Linda S. Gottfredson1, Ian J. Deary
Low iq is a risk factor for several mental health disorders.
https://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.20...
> Results: Lower childhood IQ was associated with increased risk of developing schizophrenia spectrum disorder, adult depression, and adult anxiety. Lower childhood IQ was also associated with greater comorbidity and with persistence of depression; the association with persistence of generalized anxiety disorder was nearly significant. Higher childhood IQ predicted increased risk of adult mania.
Childhood IQ and adult mental disorders: a test of the cognitive reserve hypothesis
Karestan C Koenen
Some problem areas are no longer as such because today's environment is much better at compensating for them than the environment that we actually evolved-for.
Energy efficiency comes to mind prominently: we've never been better at producing human-consumable energy in our entire history, yet we can't actually use the stuff because our bodies still interact with energy much like children-of-the-Depression interact with money.
Editing hundreds of alleles may sound incredible to you now, but I don’t think it will sound so incredible for long.
Even ignoring GM, embryo selection can get us pretty far with current technology: https://www.gwern.net/Embryo-selection
That paper does not imply what you think it implies: that editing all these variants in an individual embryo would have a small effect.
An individual with the top 200 IQ-enhancing variants edited in (and an otherwise normal genome) would be far, far smarter than than than you seem to think, even though the variants edited only explain 5.2% of the differences within the population.
Since they have an average effect size of ~0.05-0.1 IQ points or so, a few hundred of those would in fact be many SDs. You can download the PGS, grab the top few hundred or thousand betas, and sum them if you don't believe me. (I show this with Benyamin et al 2014 in that section above, but no reason one couldn't redo it with a better PGS; the results won't change much.)
And yes, Hsu really does believe this, he is quite explicit in that 2014 paper that that is how it would work (in addition to countless places on his blog & Twitter) and I've discussed it with him in the past.
(As other comments point out, the real problem with this logic is that the hits are usually not causal but tag the causal variant, even if you had some magic CRISPR which could make hundreds of arbitrary edits. That's soluble, but not easily. It is, however, not a problem for selection procedures.)
This could change if the tech improves, but it would need to improve A LOT.
This looks totally unlikely.
Not to mention generally undesirable (people with IQ over 150 or so often have severe problems in their social life, and a lot of them don't ever even create or discover much, not to mention the insufferable part whose main accomplishment is to be members of MENSA).
Sure, that won't stop progress by people who do not follow your flavor of morality or ethics, though.
It's a very real threat and believing that The West has a head start and is more intelligent/better funded/other excuse is not going to end well for us.
China achieves goals though brute force with very little regard for ethics or norms.
Also note the differences in culture: the chinese parents consented to it. I m not sure how easy it would be to find this in the west.
Based on whose ethics and morals? Eventually a country is going to go all in on robotics and genetic engineering, ethics be damned, and the rest of the world is going to be left in the dust -- economically and militarily.
please, spare us the "100% correct" and certified ethical positions
It's not black and white.
So in this case experimentation is a first step in preventing disease.
(The answer is none.)
You and I could very well find arguments for defending it, even while fitting the current morale.
Clearly those moral and ethical frameworks are not shared by at least one Chinese scientist.
You can show with empirical evidence that climate change is true.
However no matter how hard you try you can't show with evidence that your moral framework or ethics are somehow the "one true moral/ethical truth".
Is that a fact, or an opinion? :-)
(Straight question, that really isn't obvious to me at all.)
Seriously why? We do so many unnatural things to us through technology. The article discusses editing genes to try and prevent viruses.
Ethicists are experts in talking about ethics. They have no special expertise in acting ethically, compared to other philosophers[1].
Ethicists have expertise in what amounts to a body of administrative law, like rabbis, imams or canon lawyers.
And we have strong evidence of actual harm caused by them. If bioethicists can’t get their shit together enough to defend compensated kidney or gamete donation they aren’t even broadly neutral. There are people being paid to argue against saving lives, and against helping to bring into the world new lives that are actively wanted. There are ethicists who argue that poor people can’t really consent because the offer of some good to sufficiently poor person qualifies as duress.
The Nuremberg Code is good. The system of IRBs and bioethicists built up around it is not just bad, it’s genuinely awful.
[1]The moral behavior of ethics professors: Relationships among self-reported behavior, expressed normative attitude, and directly observed behavior Eric Schwitzgebel & Joshua Rust
If your point is that "IRBs could be improved in various ways", I'd be happy to agree in many cases. But also, there are some shining examples of enlightened IRBs that make human research at scale quite practical.
http://emilkirkegaard.dk/en/?p=7193
https://kiej.georgetown.edu/carl-e-schneider-the-censors-han...
IRBs do not have a problem. They are a problem. If we must have IRBs they should be deprofessionalised to the fullest extent possible rather than staffed by people whose job and motivation is to find problems where none exist and add more bureaucracy to prove they are actually doing some work. IRB as jury service seems like it could be acceptable. Twelve people, a three hour course on the Nuremberg code and the scientist presenting their application. And absolutely no bioethicists.
If you’re interested in the book put it on an Amazon wish list and email me the link at barrypcotter at iCloud. I’ll buy it because more doctors and scientists should know IRBs are a cancer on society and science.
If you had to live your entire life with a painful deformity because someone experimented on your genes, do you think you’d find this argument convincing?