This frequently comes up as a critique of my article, but I don't claim to be disrupting the field as a smart outsider. Rather, I looked at the field and concluded that the experts seem to know what they're doing. Derek Lowe is very much in the minority on this matter.
No, he's not (I work in pharma at a company that does basic and applied research on Alz). It's more correct to say there are several camps, but the camp promoting amyloid plaques as the causative/driver for Alz has struggled greatly to come up with evidence supporting its position.
Is your view that amyloid is actually a minority view among researchers? That seems completely wrong based on basically every conference proceeding I've viewed and the volume of papers and citations I've examined.
If your view is merely that there is a "camp" of experts that disagrees, then sure, but in that case, I do not think it is honest to frame this as a choice between believing in the authority of a single expert from that camp, vs. the (lack of) authority of me, a non-expert.
(I also think your read of the evidence is wrong, but I won't restate the arguments in my article.)
My opinion is that amyloid-as-cause moved from a majority to a minority view over the past few years, but it's not yet reflected in the literature (the entire amyloid establishment isn't going to give up its dominant position easily).
Also, I didn't say anything about the evidence (I don't have a "read" on the evidence, because I don't read Alz literature). My point is entirely that my priors indicate that Derek is a more reliable reader than you.
>My opinion is that amyloid-as-cause moved from a majority to a minority view over the past few years, but it's not yet reflected in the literature
>I don't have a "read" on the evidence, because I don't read Alz literature
these two sentences seem contradictory to me. i am not sure how you would keep up on the research (to know it's moved from majority-held to minority-held view), and know that the move is not reflected in the literature, without reading the literature.
Most scientists who are not experts in their field don't read the literature for a field directly. Instead, they synthesize their opinions about the field by consulting experts, and weighing various sorts of evidence. In my case, I work in an adjacent field and see presentations from scientists, have casual conversations with them, and read the news articles in major journals.
The raw literature for alzheimer's, as well as biomed in general, is not really easily interpretable. It's rife with errors, misleading statements, and intentional obfuscation.
You said the camp promoting the amyloid hypothesis has struggled greatly to come up with evidence to support its position. What did you mean by that if not a read of the quality of the evidence?
Why do you continue to frame this as a choice between a single cherry-picked expert's opinion, and my own non-expert opinion? Either fairly represent the spectrum of experts' views, or decide based on the actual evidence and arguments.
My estimate of the quality of the evidence is based on daily discussions with people who work in that field and reading summary articles in major journals. I typically don't read raw scientific articles directly- those are aimed at people in the field. Instead, my understanding comes from a synthesis of expert opinions weighted by my own priors (based on 30+ years in the field). Derek's opinion is now the prevailing one that I hear from a wide range of researchers.
I've seen this happen before, btw- overturning establishment paradigms, especially ones where the underlying etiology is complex- is extremely hard and often takes decades of experimental results.
What started as an argument to ignore arguments and evidence and instead rely on authority, seems now to have morphed into an argument that we should ignore the authority of the establishment, because of your own personal assessment of the evidence (which you have not yourself read) and your own personal synthesis of conversations you've had with researchers you've personally come into contact with (despite this being apparently unrepresentative of objective measures of typical researcher opinions).
Arguing from authority really only takes you so far when it ends up as an appeal to your personal experience. I'd rather you either address the arguments directly, or drop the dubious appeal to authority.
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Wow, it sure didn't take long to show a complete lack of familiarity in the field. It seems like that's going to be a real weakness with LLMs based on volumes of material that are later discovered to be semi-fraudulent and unmotivated by scientific principals.
https://stanforddaily.com/2023/12/31/blockbuster-alzheimers-...
As noted elsewhere in this thread, which you seem not to have read, I discuss that matter in the article, which you also seem not to have read.
Let's put all of that aside for a moment.
When the first drugs targeting HIV arrived the results were undeniable. Yes the drugs sucked for various reasons and yes HIV would evolve resistance. But the data demonstrated a very clear link that these drugs suppressed HIV and suppressing HIV made people live longer. Or consider mRNA and COVID, a great success story where the technology was put to good use and the results are obvious.
On the flip side we have certain cancers like certain breast cancers, melanoma, etc that never had a "wow" moment where some miracle turned them from highly fatal into treatable but we have seen decade after decade treatments improve and survival rates march ever upward such that what were once almost guaranteed death sentences are now often very treatable.
These are two disease treatment models worth keeping in mind. Sometimes major leaps are made. Sometimes progress is slow.
Now if we consider amyloid beta therapies: we have treatments that target amyloid beta with varying degrees of success but at least some show definite reductions in amyloid beta plaques. To the best of my knowledge that has not shown to improve outcomes in Alzheimer's patients to any meaningful degree.
That concerns me and I think justifies some skepticism of the amyloid hypothesis. The data is messy but if amyloid beta were a symptom not a cause that could certainly fit the results we are seeing. That doesn't mean the amyloid beta hypothesis is wrong but I think skepticism of the "state of the art" in the field is warranted given the pathetically ineffective progress made to date.
Now if we consider amyloid beta therapies: we have treatments that target amyloid beta with varying degrees of success but at least some show definite reductions in amyloid beta plaques. To the best of my knowledge that has not shown to improve outcomes in Alzheimer's patients to any meaningful degree.
This is false. They slow down disease progression by about 30%, as measured by cognitive outcomes. This is discussed in the article.
“Derek Lowe is very much in the minority”
Is putting your thumb on the scale against Lowe. When a few replies down from here some commenters have provided an article demonstrating the exact fraudulent science in favor of what Lowe is saying.[0] It seems you may very well be disrupting it because he has a minority opinion. So you’ve possibly spent 6 months understanding an incorrect and fraud supported thesis. That seems like an outsider trying to disrupt it by using their “Google/SpaceX” creds to claim authority on the work of insiders.
[0] https://news.ycombinator.com/item?id=48544407
1. I don't say Derek Lowe is wrong because he's in the minority. Minorities are sometimes right. But since the parent comment was arguing on authority and my lack thereof, I point out only that one shouldn't cherry-pick one's choice of authorities. Either accept the majority opinion of the experts, or come to your own opinion based on the quality of the arguments and evidence.
2. I would never want anyone to believe what I say because of "Google/SpaceX creds" (I didn't even write that line, Scott added it, and only to provide a brief biography and acknowledge that I do not work in the field, not to lend an air of authority to my words).
3. There's no need to cite the fraud to me, since I already discuss it in my article. You are welcome to read that article and form your own opinion about the arguments therein.