General Science Thread

Um, what?

There is no indication anywhere I can find that the experiment was unsuccessful. In fact, the whole reason why this study is relevant is because it was successful.

"For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled." - Richard Feynman

Well it did do what it set out to do: it did end up protecting the children involved against HIV. It just lowered their life expectancy too thanks to unforeseen side-effects.

As somebody living with the unexpected (well, they actually had some idea) consequences of Lariam on an "interesting" Northern European genome, allow me to remind you that the "side effects" are likely to intrude massively on their entire quality of life for the duration of said lives. Likely requiring medical attention at points throughout until the cumulative effects finally kill them.

Yay: swapped one life-impacting, medically intense immunological issue that can shortens life expectancy that they may never have run into for a bunch of mystery others they got given that likely will shorten their life expectancies. Success! They won't catch HIV! And didn't spontaneously abort!

Edited by Euodiachloris on Jun 5th 2019 at 12:34:07 PM

What has that to do with anything? The statement I am questioning is In the end the CRISPR editing didn't even work not whether the experiment had an overall positive effect.

"For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled." - Richard Feynman

If by "worked" you use the narrow definition of "won't get HIV according to standardised tests", sure. It worked.

But, that's going to be huge icebergs of cold comfort when symptoms eerily akin to having the effects of catching the virus will very likely be your assigned lot in life, regardless.

That's not success. That's a sentence of a shorter lifetime of physical, mental, social and financial shackles — potentially in an entire germline. You know... making what is, in effect, a genetic condition. Because "ethical practice? wazzat?".

Oh, and nothing says that out in the wild, some strain of HIV or its cousins won't manage to wriggle around this costly immunity, anyway.

Edited by Euodiachloris on Jun 5th 2019 at 9:42:30 AM

I don't think you're understanding their point.

The trial was successful in that its objective was achieved. That does not mean that it was good for the subjects, but their lifespan wasn't the point of the trial.

Successful in this context is value neutral.

Edited by Fourthspartan56 on Jun 5th 2019 at 1:40:16 AM

"Sandwiches are probably easier to fix than the actual problems" -Hylarn

I'm saying that an ethical trial would have that as part of the win condition. Up there with the nul.

That's the whole friggin' point of medical ethics. You are working on a whole patient, not just a tiny part of them taken from the whole and viewed in disconnected isolation.

Which is why I congratulate them on the tricky (and still somewhat fudgy) bit of coding. But flunk 'em on the ethics.

Not. A. Success.

Success was not achievable because an invalid, unethical definition of success was used from the outset.

We may as well applaud the resounding experimental successes of Unit 731. Use the data, sure. Acknowledge breakthrough, fine.

Not. A. Success.

Edited by Euodiachloris on Jun 6th 2019 at 10:47:17 AM

I'm saying "it didn't work" as "the desired form of the edited gene was not achieved". So sure, they managed to edit something, but what they ended up editing did not match the desired final result. If the result is no better than a random mutation, then it's a pretty big failure in my book.

EDIT: So for clarification, the gene they attempted to modify is CCR5, inducing a mutation referred to as CCR5-Δ32, meaning that it's missing a 32-base-pair segment of DNA that HIV binds to, resulting in higher resistance to HIV. Of course, it also possibly results in higher susceptibility to West Nile and Zika, but details, right?

Except the gene-editing, rather than deleting the segment that results in CCR5-Δ32, deleted some random other segments of DNA, meaning now we don't even know what kind of mutations it might have caused.

Edited by danime91 on Jun 5th 2019 at 4:40:15 AM

Captain (all the way back in April): I would expect that life expectancy shows rather strong socio economic differences within developing nations. (Jeez, I need to check this thread more often).

@Ethics: This is actually precisely the purpose of the "Do No Harm" principle, FYI. It's possible for a doctor to technically "successfully" cure or treat a disease in a way that causes unjustified "irrelevant" damage to the patient, and this is a textbook example of that.

To use a logically extreme metaphor: You technically can cure someone of cancer, AI Ds, or most other infections by shooting them or injecting them with botulinum. The problem is, that kills the patient, too.

Actually, on a tangent, this is basically the issue with a lot of diseases in general. Like, with bacterial resistance, the problem is that antibiotics need to be lethal to bacteria, but safe for human consumption. You have less of an issue with something like hand-sanitizer, since that only has to be safe enough to touch skin. A good metaphor is that an antibiotic is an assassin that has to figure out its target and snipe them, whereas hand sanitizer is a nuclear warhead that kills everything within a few mile radius, including your target.

Edited by Protagonist506 on Jun 5th 2019 at 4:21:37 AM

"Any campaign world where an orc samurai can leap off a landcruiser to fight a herd of Bulbasaurs will always have my vote of confidence"

danime91, I can't find evidence of that course of events either. It also isn't consistent with the concerns stated here - the claim that CCR5 deletions shorten the life expectancy is based on empirical/statistica observation of people who have the CCR5 mutation. If the deletion didn't happen the shortened life expectancy won't happen either.

The principal problems here aren't that the change didn't work, but that it was done with little awareness of the risks and with sundry ethics violations.

Edited by SeptimusHeap on Jun 6th 2019 at 9:15:16 PM

"For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled." - Richard Feynman

The cure is worse than the disease and all that.

Disgusted, but not surprised

I'm pretty sure everyone already agrees on the lack of research into possible side-effects and the gross ethics violations. I'm just addressing the part where, even if we were to ignore those, the procedure very likely didn't work anyway.

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000224

Examination done of the experiment shows that He was very shoddy in establishing control groups and adequately studying the possible results of the procedure, as well as highlighting the likelihood of off-target mutations and possible effects of the embryo's own DNA repair on the edited genes. One of the babies only had 15 base pairs removed compared to the 32 base-pair deletion.

What I'm saying is that even if the ethical problems were addressed and the side-effects adequately researched, the whole process itself is still a failure and shouldn't be performed on anyone anyway.

That article doesn't say the procedure didn't work (verbatim: For Lulu, one allele remained WT, and the other allele had an in-frame deletion (−15 bp). For Nana, the two CCR5 mutant alleles represented 100% of all sequencing reads at the CCR5 target region), it says the whole procedure was shoddy on top of dangerous and unethical.

IMO, this seems like a case where someone wanted to be the "first" to do something and rushed ahead.

Edited by SeptimusHeap on Jun 6th 2019 at 6:59:24 PM

"For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled." - Richard Feynman

Don't really know what the rush was for, not like CRISPR human testing is exactly a bustling field of research right now.

It was about getting the first genetically modified (sorta) HIV-resistant human out, I believe.

"For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled." - Richard Feynman

If YouTube has taught me anything, it's that bragging about being first ain't a win.

Russian biologist plans more CRISPR-edited babies

Si Vis Pacem, Para Perkele

What if instead, we spend this research funding on creating functional cures for HIV, and on identifying the multiple functions of genes such as CRISPR than on the ethically questionable and potentially harmful modification of human DNA? What if?

I'm not opposed to DNA modification on general principles, but clearly more research needs to be conducted into the multiple purposes that various genes serve before we try and go messing around with them in human beings.

Edited by Pseudopartition on Jun 11th 2019 at 3:54:43 AM

The main objection to experimenting with gene editing on humans is that we're messing with, well, humans. The science isn't solid enough that anyone can ethically consider applying those techniques lest a life be seriously and irrevocably harmed. It runs squarely into the Hippocratic Oath.

On the other hand, "Why don't we spend this time and effort on X instead," is a form of the Appeal to Worse Problems fallacy. We can work on multiple things at once, and diversifying lines of research can lead to unexpected synergies. For example, if we find a cure for HIV that requires gene-editing, it'll be helpful to have the latter techniques at a level of maturity where we can apply what we've learned rapidly.

Edited by Fighteer on Jun 11th 2019 at 4:57:05 AM

"It's Occam's Shuriken! If the answer is elusive, never rule out ninjas!"

Exactly. I just want to clearly differentiate this from DNA modification in the case GMO crops, which are perfectly safe for consumption (notwithstanding some issues with things like terminator seeds and biodiversity, but they're only a problem if people make them a problem), because boy am I tired of hearing the conspiracy theories about those.

I know this. And the aforementioned Russian scientist is obviously going to be focused on working within his area of expertise. I don't see how 'appeal to worse problems' applies to what I'm saying. I just don't think this specific effort should be funded right now, because it seems ethically... kind of fucked. Also, according to the article, he's just planning to disable the gene, while according to the article linked on the last page, mutations on CRISPR are linked to higher death rates (it encodes for numerous other proteins in the body). There doesn't seem to be much more to his strategy beyond "the same, but slightly different."

Which is why I said that spending time further researching the effects of the CRISPR gene would be more beneficial right now, instead of trying to apply it to human test subjects. Or at the very least, further animal testing.

Edited by Pseudopartition on Jun 11th 2019 at 4:14:13 AM

Is it actually an appeal to worse problems? The problem is still HIV. It's just that the current considered solution of CRISPR editing doesn't seem very safe or effective. So let's fund research efforts into other solutions.

No, it absolutely is.

By bringing up HIV they were using it to argue against CRISPR by bringing up a worse problem that we should focus on, ignoring that we already focus on HIV quite a bunch. In other words, it's literally Appeal to Worse problems.

We can and should do both. Yes, CRISPR editing can be dangerous if done hastily by sole scientists who clearly want glory but that doesn't say it's a dead-end. That assumption is entirely flawed.

Edited by Fourthspartan56 on Jun 12th 2019 at 6:04:34 AM

"Sandwiches are probably easier to fix than the actual problems" -Hylarn

On top of everything else, this is also likely to fuel more anti-science rhetoric and propaganda, thus making it harder to do legitimate research.

Aren't selfish glory-hounds the best?

"Sandwiches are probably easier to fix than the actual problems" -Hylarn