
Baby Gene Edits Could Affect a Range of Traits - subroutine
https://www.nature.com/articles/d41586-018-07713-2
======
fabian2k
The choice of gene to edit is absolutely baffling. There are plenty of other
major issues with this work, but this part is the most surprising.

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.

~~~
nabla9
Each family had HIV positive father.

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](https://www.cdc.gov/mmwr/preview/mmwrhtml/00030972.htm)

~~~
asituop
[http://mainichi.jp/english/articles/20181126/p2g/00m/0fe/047...](http://mainichi.jp/english/articles/20181126/p2g/00m/0fe/047000c)

"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

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subroutine
This was the immediate concern shared by me and several genomics researchers -
gene variants that are often shown to be good for one thing may be bad for
another. However, the way genome wide association studies (GWAS) currently
works, is that gene variants are identified that have unexpectedly high
frequencies in 'case' group compared to a control group; but follow-ups to see
what other phenotypes are associated with those variants are rarely done.

~~~
trashE
The same thing happens with IVF babies. It shakes up their epigenetics and
causes a wide range of health problems which are less common in natural born
populations.

~~~
im3w1l
People get IVF babies because they can't get normal babies. Wonder if it would
happen the same if you did IVF with normally fertile people.

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alexandercrohde
I wonder if I'm the only one here who thinks this probably a good thing, from
a utilitarian ethics.

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.

~~~
asituop
I'm not sure to understand are you basically saying " it's okay to do human
testing because we can save million of others " ?

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.

~~~
buboard
> it's okay to do human testing because we can save million of others " ?

We still do wars

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jdpigeon
This article takes for granted that the Jiankui has actually edited human
embryos. I haven't been following this story closely, but I'm inclined to
believe the guy is fraudulent until proven otherwise. Has it been established
that he's not just lying about what he did?

~~~
buboard
Other scientists had seen the data even before his announcement / knowledge of
the matter. He said that even his informed consent was reviewer by 4
professors , including one from the US. I dont think anyone has evidence that
he did not do it.

[http://www.sciencemag.org/news/2018/11/i-feel-obligation-
be-...](http://www.sciencemag.org/news/2018/11/i-feel-obligation-be-balanced-
noted-biologist-comes-defense-gene-editing-babies)

~~~
PavlovsCat
> He said that even his informed consent was reviewer by 4 professors

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

[https://www.theatlantic.com/science/archive/2018/12/15-worry...](https://www.theatlantic.com/science/archive/2018/12/15-worrying-
things-about-crispr-babies-scandal/577234/)

> _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._

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carbocation
Very broadly, this article gets into a future time where our gene editing
technology has been perfected so that you can feel confident that there are
~no off-target effects. So, this is a worthwhile discussion to begin now.
Basically, if the tech worked as we hoped, what are the considerations even
when things are on-target?

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.

------
quotemstr
I expect to see a great deal of FUD surrounding human genetic editing the
future. One gets the sense, reading the commentary from the scientific
community following He Jiankui's announcement, that the outrage and
condemnation didn't come from any details of the edit, but instead from a
certain disgust at the idea that anyone would attempt to edit human genomes at
all.

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.

~~~
subroutine
The situation at hand is not like that. The intended edit _will_ change the
function of the gene and its coded protein, that much is known. However, (1)
some reports are saying the intended edit may not have gone as planned and the
gene will actually be completely silenced, and (2) assuming the edit doesnt KO
the protein, it will produce a variant that 90% of the population doesnt have.
Sure this allele may confer protection against HIV infection, but it may also
result in undesirable traits. For comparison the e4 allele of the APOE gene is
thought to confer protection against parasites. But it's also found in only
14% of the population. Why might these pathogen protecting alleles not be
dominant? Well, wrt the APOE e4 allele, it increases your risk for memory
decline and is associated with a 14x rate of Alzheimer's disease. In the 1700s
in the South American rainforest u may have opted for the e4 allele, but if
you live in a modern society in 2018 where pathogens like parasites and HIV
aren't killers, wouldn't you want to avoid the more pertinent risk?

