There are many safe choices of targets, simply reverting a known mutation that causes a well-studies genetic illness is such an obvious choice. Mutating the wild-type to a non-functional version that has known benefits but also drawbacks, and almost certainly has unknown drawbacks as well is such an insane choice for the first experiment of this type.

Not that making a better choice there would have saved this experiment. The lack of informed consent, the highly experimental nature of the work and going ahead even when you know that you did not achieve exactly the mutations you intended damn this experiment in any case.

It's likely that parents had misconceptions about modes of HIV transmission. Transmission is of course possible but not very likely. https://www.cdc.gov/mmwr/preview/mmwrhtml/00030972.htm

"He said his goal was not to cure or prevent an inherited disease, but to try to bestow a trait that few people naturally have -- an ability to resist possible future infection with HIV"

Hasn't it been clear that the goal was from beginning to build a stronger race ? They never said it was to save baby from a inherited disease but to make them more resistant to potential future infection

> A: It struck me as bold choice to do CCR5. In some ways it doesn’t make sense, but in another way it makes more sense than β-thalassemia or sickle cell, both of which you can prevent with preimplantation genetic diagnosis. [These genetic diseases are two prime targets of many CRISPR researchers.] The real issue is what’s the best first case.

I think it's certainly possible to get mixed or even bad results with gene editing by trying to push the technology farther than we really understand.

That being said, the basic priority for gene editing is probably to prevent/reverse bad genetic conditions that we understand well. No more downs syndrome.

That seems to be an unmitigated win to me.

DNA looks mightily like an extreme and profoundly complicated, complex piece of programming, with unnecessary redundancies removed, and useful redundancies left in, as well pieces of code that call lots of other pieces, as well as being called by others.

If the genome is analogous to a computer binary... we don't understand the file format, and how it is read and interpreted.

Nature knows far-and-away better than we do how to make it all work 99.99% of the time, with occasional errors due to radiation, poisoning, interbreeding being accounted for so that things don't get out of hand.

Well, these assumptions held... until we intelligently stupid creatures came along, using our intelligence to create dangerous tools that are most abused by those least worthy to wield them...

Nature does not ‘know how’ to make it work 99.99% of the time. Nature very frequently aborts pregnancy’s when any number of things go wrong. Getting all the way to birth is a huge checksum that validates the majority of critical DNA.

Which gets it the larger point. Evolution focuses more on species propagation than individuals.

We may understand a lot, but nowhere near enough to be able to confidently edit DNA, and know that it won't causes a ton of unforeseen issues down the line.

We don't know what we don't know ~ that is, as much as we like to believe that we understand a lot about DNA and how it works, odd things pop up all the time that prove us wrong. I dare say that there are far deeper mysteries about DNA that we have no current understanding of.

> Nature does not ‘know how’ to make it work 99.99% of the time. Nature very frequently aborts pregnancy’s when any number of things go wrong. Getting all the way to birth is a huge checksum that validates the majority of critical DNA.

This is merely an example of nature getting it right ~ abort if there are serious issues.

> Which gets it the larger point. Evolution focuses more on species propagation than individuals.

It is about both ~ the individual matters most ~ species propagation doesn't even register in importance to a majority of individuals. Having children does. They're subtly different ideas.

That’s a question of code not file format. I may understand C, but that does not mean I can edit any C program safely.

> abort if there are serious issues.

That stance suggests there is no way to fail as death is the worst option. But even that fails as a significant number of women died due to pregnancy or birth before modern medicine. Even now pregnancy’s are higher risk than most things people do.

People with personalities also have neurons and wonder of wonders a centural nervous system.

PS: It’s hard to get good numbers for this stuff as but many things like drug use my pregnant mothers can cause significant developmental issues. But, everyone has several random mutations and mental problems from them seem to be far less common than other issues. Especially when you exclude things getting passed down over time and just look at new mutations.

Cell division is one of those things you need or get right or you don’t get a pregnancy.

It’s not like the mother needs or do anything at that point, the result is just death by default.

I would add that PheWAS is often performed with specific genetic instruments of interest, and can be performed with aggregate measures such as a genetic risk score. This lets you see association across a slew of traits at once.

And it's good we are sharing this info. But we are far from having high-powered GWAS for all of human's traits and diseases. And often what we do know is from a single demographic (fwiw mostly caucasian, not chinese). How gene variants influence outcomes in different genetic backgrounds, or within certain environments (think developmental nutrition in africa vs asia) is typically a big questionmark. So IMO performing CRISPR edits to mitigate a problem that was completely avoidable by other means was unethical at best.

For UK Biobank, there is a GWAS of ~everything: http://www.nealelab.is/uk-biobank/

The lack of diversity in genetic studies is a huge problem. This one isn't just moral, either: we're ignoring the richness of allelic diversity that is found in people throughout the world (particularly in Africa, which has the most genetic diversity because of its pre-bottleneck status). There is an awareness and I think you'll see big changes here in the next few years.

Many people are interested in seeing CRISPR push forward, and mention something like you have: but what about the "knowledge it will provide us for the next iteration". Trust me, I'm just as eager as anyone. However, if this mavrick experiment fails, and something is remotely off about these little girls (u can bet they will be under a constant magnifying glass), this will end up being a huge setback. It will spook the public, and the legislation factory will churn out regulatory policy that nobody wants.

    CRISPR Twins Aborted

My calculation goes like this: Most of the things we get up-in-arms today about aren't that bad numerically. When those come our science is the ONLY thing that can save us (be that mars, be that a preventative technology, be a genetic adaptation).

I think if we handwring over the ethics of individual testing for decades on end, all-the-while millions die because of the technology we didn't build then, by a utilitarian ethics at least, that was a bad call.

The whole point of "civilized" countries is to guarantee some basic individual rights by not fall into this pure utilitarian vision. Otherwise you can justify all the most dystopian-dictatorish-nazish horrors you want.

If you or your children were dying because some scientists did non-consenting & non-needed test on them to make sure "we build the technology to save million others" you wouldn't find this fair.

We still do wars

1. Your country A doesn't allow genetic enhancement because of some "equality" concerns.

2. Another country B decides to go ahead with it anyways, gets a number of competitive advantages, eventually gains an upper hand economically and any other spheres.

http://www.sciencemag.org/news/2018/11/i-feel-obligation-be-...

Well, he would say that. Can I read statements of those 4 professors?

https://www.theatlantic.com/science/archive/2018/12/15-worry...

> 4. There were problems with informed consent.

> It’s not clear if the participants in He’s trial were actually aware of what they were signing up for. He relied on an AIDS association to reach out to the patients and falsely described his work as an “AIDS-vaccine development project.” He told delegates at the Hong Kong summit that he personally took the volunteers through the informed-consent process, along with another professor. But taking consent is a specific skill that requires training; He had none.

> The consent document that he used describes CRISPR and gene editing, but it does so in heavily technical language. He has said that his patients were “very well educated” and already knowledgeable about gene-editing technology. But according to a news report from the Chinese magazine Sanlian Life Week (which has since been removed, but not before a digital copy was saved and translated), one of the people who dropped out of the experiment had only a high-school understanding of biology, and only heard the term “gene editing” when news stories about He’s experiment broke. The man claimed that he was not informed about the risks of off-target effects, or about the fact that gene editing was a prohibited and ethically controversial technology.

> Also, the consent form “is not a consent form,” says Kelly Hills, a bioethicist at Rogue Bioethics. “It’s a business form, of the kind that a company might use when subcontracting.” For example, the section about possible risks says nothing about any negative consequences of deactivating CCR5, and is instead more focused on absolving He’s team of legal responsibility for problems arising from the procedure. The form also gives He’s team rights to use photos of the babies in magazines, calendars, billboards, propaganda, product packaging, and posters in cars and elevators.

> I dont think anyone has evidence that he did not do it.

The burden on proving he did it, not on proving he didn't. Of course, doing what he did the way he did it is much worse than lying about doing it, but logic is logic. As for your link:

> 14. A leading geneticist came to He’s defense.

> In an interview with Science, George Church, a respected figure from Harvard and a CRISPR pioneer, said that he felt “an obligation to be balanced about” the He affair. Church suggested that the man was being bullied and that the “most serious thing” about his experiment was “that he didn’t do the paperwork right.” “[Church’s] comments are incredibly irresponsible,” says Alexis Carere, who is president-elect of the Canadian Association of Genetic Counsellors. “If someone contravenes the rules that we have laid down, we are very justified in speaking out about it. The unfortunate effect of this is that it makes it seem like there is some kind of balance, and George is just in the middle. There is not.”

> Carere was also dismayed at the rest of the interview Church gave, where “every sentence was a new ethical maxim that I had never heard of,” she says. For example, Church noted that “as long as these are normal, healthy kids it’s going to be fine for the field and the family.” But unethical actions are still unethical, even if nothing goes wrong. Arguing otherwise gives a pass to scientists who blow past ethical norms, provided that they find something interesting. “It’s bizarro-land consequentialist ethics,” Carere says.

I do want to emphasize that this may not be the most relevant discussion for the gene editing adventure that actually occurred, where off-target effects are also at play, where ethical considerations like informed consent seem not to have been appropriately undertaken, etc.

While it's true that, in theory, unknown edits could cause novel gains of function, and while it's true in theory that there might be undetected off-target effects, these sorts of outcome are unlikely. Mutating one byte of /bin/ls will almost certainly not transform it into a C compiler. Criticism of He Jiankui's work plays up almost-impossible negative side effects while ignoring the beneficial applications of this technology; it emphasizes the remaining areas of genetic ignorance while ignoring the massive strides in understanding from the past decades; and it suggests that we'll never have sufficient understanding to apply these techniques routinely. That is, it's FUD.

Human genetic editing is likely one of the most profoundly beneficial technologies ever developed, and to see its use delayed saddens and disappoints me. If the mainstream scientific community will block the development of this technology, using public condemnation, binding "ethics" panels, and (as I predict will come soon) censorship of research, then the ethical thing to do is to bypass the mainstream scientific community, as He Jiankui did. This work is too important to delay on the account of obsolete, non-utilitarian, and ultimately irrational disgust.