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That is literally the drug in the article (ritonavir).

So much of this is hindsight bias though. There were no shortage of people with ideas and companies pursuing obesity drugs through a number of different pathways. Only in hindsight does it seem "genius" that Thomsen persisted and succeeded where nobody else did. But there are dozens, hundreds, of other smart people who were pursuing other pathways who did just as much stubborn work but didn't get a result. That's just pharmaceuticals.

Take, for example, another high profile disease - Alzheimer's. First there was the beta amyloid theory, then there was the p. gingivalis theory (this one was talked about so highly on this very forum, but ended in an equally high profile failure* of a pivotal clinical trial by Cortexyme). Now there are viral and metabolic theories. Each of these theories have a few dozen companies and armies of PhDs stubbornly pursuing a miracle drug, but so far it remains elusive.

* We also like to talk about "failures" of clinical trials, which is technically correct language, but evokes in the public imagination the wrong idea. A clinical trial failure doesn't mean there was something wrong with the idea or process (long before it ever gets there, a drug candidate would have been proven to be very effective in lab tests and animals). It's just that 90% of clinical trials don't end up working due to complex disease pathways and numerous unknown factors. It would help if we talked about "negative proofs" (i.e. proving something doesn't work is also valid), but it's not quite as catchy.


> First there was the beta amyloid theory

First? Isn't the beta-amyloid cabal still blocking all Alzheimer's research unless the researchers find a way to even tangentially support that long disproven theory?


It was not a cabal. It was scientific fraud.

Karen Ashe and Sylvain Lesné at Minnesota published a fake paper that redirected billions of research into the trash bin. https://www.science.org/content/blog-post/faked-beta-amyloid... Amazingly both still have their jobs for life, both still publish, Ashe is still a member of the National Academy of Medicine, both are still getting grants.


This is a mischaracterization of the scope of the fraud. Lesné clearly committed fraud, but his work was not foundational. The fraud did not "redirect billions".


Yes it very much did lead to billions of wasted dollars and that's if you count us public funding alone. Tens of billions of you count non us and private funding.

From https://www.science.org/content/article/potential-fabricatio...

The Nature paper has been cited in about 2300 scholarly articles—more than all but four other Alzheimer’s basic research reports published since 2006, according to the Web of Science database. Since then, annual NIH support for studies labeled “amyloid, oligomer, and Alzheimer’s” has risen from near zero to $287 million in 2021. Lesné and Ashe helped spark that explosion, experts say.

The paper provided an “important boost” to the amyloid and toxic oligomer hypotheses when they faced rising doubts, Südhof says. “Proponents loved it, because it seemed to be an independent validation of what they have been proposing for a long time.”

This is also a fun read https://www.nytimes.com/2024/07/07/opinion/alzheimers-missed...


From your description, it sounds like a large complex ecosystem (of which Lesne and Ashe were important parts) redirected billions. I think it’s a bit overselling it to say that their results alone redirected billions


As unavoidable mentioned, there are viral theories.

In Science, from July, "Can infections cause Alzheimer’s? A small community of researchers is determined to find out. Following up tantalizing links between pathogens and brain disease, new projects search for causal evidence", https://www.science.org/content/article/can-infections-cause...


Yet another reason to get your shingles vaccine.


I mean, that's the point - in pharmaceutical sciences there's _so much noise_ including fraud that it's really only easy in hindsight to pick out "the guy" who was the "genius". It's hard to take one story like this and make it a repeatable success.


> So much of this is hindsight bias though. There were no shortage of people with ideas and companies pursuing obesity drugs through a number of different pathways. Only in hindsight does it seem "genius" that Thomsen persisted and succeeded where nobody else did. But there are dozens, hundreds, of other smart people who were pursuing other pathways who did just as much stubborn work but didn't get a result. That's just pharmaceuticals.

Exactly.

There are plenty of examples where the opposite choice was made - argue for continued development despite high uncertainty.

The CETP inhibitors is a good one. Pfizer flushed several billion dollars down the drain with the decision to push it through phase 3.


Brutalism actually comes from the French word for concrete, "beton brut"; not English "brutality".

https://en.wiktionary.org/wiki/Brutalism


Unfinished concrete, specifically. I would translate "brut" as "bare" or "unrefined" here. English brutality is related to French brut, but in French it means more like crude, unrefined, raw, blunt, with no particular sense of animalistic or violent.


Perhaps we should be right-click->view-source'ing for the true brutalist experience.

e: ah, in this very thread https://secretgeek.github.io/html_wysiwyg/html.html


Brut is raw. Brute or brutal is related to violence.



Am a lawyer. This is correct. Drafting subpoenas, motions, applications, convincing a skeptical judge that Twitter posts are "real" evidence, or explaining how DNS records work, not to mention actually scheduling a damn hearing, then multiply that by 4 or 5 jurisdictions (therefore 4 or 5 sets of lawyers), and you got yourself easily a few years' worth of work.


It's not quite that simple. If you've ever lived in a tall building and heard/seen/smelled stories of sewer pipes backing up, well you'll know what I mean. The bottom floor of a 50 storey building needs much more sewage space than the bottom floor of a 5 storey building. Anyway, there are considerations about venting, as well as increased capacity for lower floors versus higher floors, and the whole thing has to be designed in conjunction with the rest of the plumbing anyway.


I see this sentiment a lot, and as an engineer-turned-lawyer, I've always found this to be intriguing but unsatisfactory. Certainly lots of transactional type work (contracts, estates) and maybe even basic adversarial work (parking tickets and fines?) could be greatly enhanced by AI/ML.

But I've asked clients this question and while they would love to not have to pay lawyers - if you ever put the thought in front of them and asked whether they actually want an AI to represent them in court, when stakes are high and there's a chance of losing... well, I've never met anyone who has said they willingly take that chance.

Some fields will also certainly never be AI-ified. Not a snowball's chance in hell (and I know it sounds like a cranky person talking) that lawyers and judges in criminal/constitutional trials will ever be "replaced" by AI. It has nothing to to with the possibilities of present and future technology, but everything to do with optics. Society is almost certainly never going to accept being judged and/or losing to AI and algorithms. Even if a person has a losing case they would want to make sure to hear it from a human rather than a machine.


> Not a snowball's chance in hell (and I know it sounds like a cranky person talking) that lawyers and judges in criminal/constitutional trials will ever be "replaced" by AI. It has nothing to to with the possibilities of present and future technology, but everything to do with optics.

Ha, you might like Pohl and Kornbluth's classic dystopian science fiction novel "Gladiator at Law", which I think was from the 1950s. There is a trial scene near the beginning where the prosecutor and defense spend a page or so addressing the jury box. Then (spoiler) the jury box flashes and whirs, and spits out the verdict.


I think you're failing to consider the selection bias in those who have had the chance to ask the question of. By definition your clients are people who are able to hire lawyers. They aren't the target market for robot lawyers, not for a long time.


> ever be "replaced" by AI.

I believe you have a rude awakening ahead.. resolve the roles in court to authority roles, and yes, none of the professionals will give up any authority; but the "work" of law, that is to study, consider, refute and prescribe, especially with citations and written works.. absolutely yes they are top on the list to be replaced by AI.


"To be or not to be, that is the question." -> "Or not."

That settles it then.


Haha, tried the same and got:

"Even if this is a problem."


I got: "The question is different"

I can't stop laughing, this is treasure


"To be or not to be, that is the question." -> "No questions."


Europe and Canada approved AstraZeneca's vaccine while the FDA didn't (not debating whether it was a "good" decision, just that it did). Canada also approved of vaccine dose mixing (out of necessity, but nonetheless it was clearly not following the FDA). Plus, by and large Europe and Canada's leaders did not actively harm Covid treatment and vaccine efforts (many policy missteps, but nobody was actively politicizing the virus itself).


Relatedly, a great primer on this concept has been written up by the Bank of England and IMO is a must-read for anyone who wants to know how money is "created".

https://www.bankofengland.co.uk/-/media/boe/files/quarterly-...


I love something like this but something about having to log in to a proprietary service to read/comment/view markups just doesn't sit right. I wish this kind of stuff was built in more easily to PDF readers/writers. The modern state of commenting/annotating documents despite a decade of tablet computers is sad.


I first checked out Fermat's Library on account of the email list (the "Journal Club") that features a different paper each week. Even that is designed for maximal vendor lock-in: You can't download the paper. They don't even link to the paper's DOI so you can find another copy.

Additionally, like many social sites, the idea is to collect user-created value for free, centred solely within their control. That aspect echoes of the great problem with scientific publishing: Scientists produce information, and give it away to some corporation for free, which then charges the public to access it. The user comments, even if informative, are stuck on the site; you have to return to the site to access those comments.

Even if "All team members have an academic background and share the desire to make science more open and widely distributed" [0], there is no guarantee that the user-populated database of annotations will remain free or accessible in the future, since again, it's stuck on that site.

[0] : https://fermatslibrary.com/about


Could you elaborate more on what and why document annotation is in a "sad" state? Even with a regular PDF file there are many ways you can annotate it: highlighting, adding text box, adding comments, drawing shapes, freehand writing -- without resorting to third-party software. So either your need for offline annotation is pretty advanced, or that you are yet to update your OS/software to take advantage of those.

As for the online part you may be conflating your point about offline annotation. Fermat's Library is about annotation sharing: implementing this functionality without any sort of identity management appears to me that it would basically be asking for trouble (imagine you could send e-mails to anyone without logging into anything).

It's easy to casually throw around phrases like "log in to a proprietary service" to criticise something. Perhaps that sentiment is understandable, but it doesn't really move the conversation forward or lead to better solutions. In this case I think it's just simply missing the point: at least at this point in time Fermat's Library's mission doesn't appear to be about grabbing your identity for profit. So unless there is something particularly fishy about what they are doing, that sort of criticism seems unfounded.


> without resorting to third-party software

What would be the "first-party software" in that case?


If that's your concern then have a look at Semantic Scholar who are backed by Paul Allen's AI For The Common Good [1]. They are as open as it gets and do interesting things with NLP.

That said I wish Fermat every success. Any way that helps you drink from the firehose of publications is a much needed step forward. Even if there is so much more you can still do in this respect...

[1] https://www.semanticscholar.org/


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