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Posted by AnodicElegy 13 hours ago

AI in drug discovery – what it is, where we stand and the path forward(www.science.org)
https://www.nature.com/articles/s41573-026-01496-2
136 points | 73 comments
plaidfuji 7 hours ago|
> “…the focus of AI in drug discovery must shift from doing what can be done - such as modelling data that is readily available, but that is unlikely to move the needle - to doing what should be done, even if this requires, for example, substantial data generation…” It’s a worthy goal, but I think that many involved in this work might be thinking, even unconsciously, “You first”.

This is the problem with AI for all of science - not just drug discovery. Applied ML has spread like wildfire through academia over the past decade - this started well before the LLM hype. It’s the perfect honey trap: research is painstaking and slow, ML offered a shortcut, and best of all, it just needs data. Research produces lots and lots of data! Surely this will be a match made in heaven.

I’ve watched the same pattern play out at least four or five times now in various roles.

(1) Propose an ML-guided approach to material/chemistry discovery/optimization.

(2) Gather existing data (real, experimental data).

(3) Realize there’s less than about 50 true rows of data on the outputs of interest.

At this point, you either: (4a) revert to traditional methods but keep the veneer of using ML to save face, or (4b) pivot to computational/simulation work or a high-throughput system that’s very far removed from your original problem, but allows you to keep playing with ML toys

It’s really bad. I left the industry. I don’t know how long it will take for people doing real science to take back the reins (and the funding).

rdedev 5 hours ago||
Here is an article by Pat Walters on the usefulness of ML in drug discovery. This article is a response to another one making the case that utility of ML models are very limited in drug discovery

https://patwalters.github.io/Response-to-Peter-Kenny/

> (4a) revert to traditional methods but keep the veneer of using ML to save face

I haven't worked in the industry side of things but in academia everyone kind of agrees that gradient boosting trees are some of the best models to do these things.

colingauvin 4 hours ago|||
The real value right now is in figuring out how to generate robust data cheaply and quickly. I'd wager that the effect of a good model on marginal data is small, but the effect of a marginal model on great data is probably quite large.
whatever1 1 hour ago|||
It was always easy to come up with new molecules/drugs/materials. The thing that changed is the scale that it can happen with the new ml-based approaches.

What hasn’t changed is finding ones that are manufacturable/synthesizable.

Even if you find 1 million new stable molecules, there no guarantee that even one of them is manufacturable.

aragilar 2 hours ago|||
The obvious question is what limits getting more data? Astronomy (especially in Australia) has been quite good at designing surveys to answer multiple scientific questions with reasonable amounts of data (and then fed into ML systems like the cannon). Sadly one of the consequences of the LLM hype is the increasing cost of doing this, so "AI" is actually making things worse not better.
eru 6 hours ago||
(3) seems like a problem in its own right? Basing science, traditional or newfangled ML, on such small amounts of data looks pretty weak.
hibikir 4 hours ago|||
I worked on some of the very best funded plant research out there. When it comes down to it, there's enough variation caused by confounding factors, and it takes so long to capture more data, that almost everything anyone tries cannot be called a success or a failure for years, because the individual measurements for one small plot of land somewhere just don't mean anything. Once you do an entire experiment for a season, which takes months, and you grab the little noisy data you have, and turn it into real rows, we were down to very little.

You can do more tests on smaller things, like checking if some protein will kill some cells of a pest, but making sure a plant produces it enough that it actually does something significant to the real, live pests, that it's not toxic, and it doesn't harm the plant's yield massively (as it's now spending time producing your pesticide) is still going to take years. We might be able to fold proteins, but the kind of things we'd need to really simulate plant biology well enough to not need years of failures are still very far away.

And it's far worse in medicine, as with plants at least nobody has ethical concerns if they fail and die, and nobody needs to get consent from a corn seed. Getting to 50 actual data points from many medical studies is already a lot of effort. And imagine when it's a long term study, and you need to follow patients for 30 years, as theym move, or die, or decide to stop participating, or who knows what.

bharatsuthar 1 hour ago||
Ethical concerns might become an even bigger bottleneck in the future. It's sad what we're doing with millions of rodents each year.
plaidfuji 5 hours ago|||
In chemicals and materials, 50 rows of good data is a really solid study. That’s e.g. a 3x4x4 experimental design (assuming replicates for each condition get averaged into a single row). If you managed to prep that many samples correctly and obtain consistent characterization data across all properties of interest, you’ve easily got a paper. It’s also kind of malpractice to jam this type of data (few samples, wide rows) into modern ML models. There are plenty of simpler statistical methods that will tell you what’s going on, and even then a well-made plot might be good enough. The difficulty is not in drawing insight from the final numbers, it’s almost always in how those numbers came to be in the first place.

Thus the reticence of science-oriented companies to invest heavily in these mass data-gathering exercises to feed ML. It’s damn expensive, and almost always leads you back to raw data issues, not breakthrough discovery. Doing it without a set purpose in mind is even more likely to yield garbage.

colingauvin 11 hours ago||
I'm a structural biologist at a mid-sized biotech. I use AI tools daily. They make accomplishing the same things I was able to accomplish before quite a lot faster and easier. They don't help me magically accomplish new things that I couldn't previously.

For example, it helps me install academic software, debug things. It helps me take a large dataset and write scripts to ask questions. It helps me go through experiment drafts to see if I'm missing things. It helps me remember obscure formulas I use every 6 months. It has not, at least in my experience, come up with anything truly novel.

A concrete example: AlphaFold is great...to come up with a starting model for a chimeric fusion or something. What would have taken me 1-2 hours fumbling around in PDB or CIF files is now a quick prompt.

sm2 6 hours ago||
Serious question - have you tried applying AI tools to more of your job, and in a goal-seeking fashion? Have you hit roadblocks?
colingauvin 5 hours ago||
Yes, and it's relatively good for on-rails data collection and data processing pipelines that would have previously needed occasional human intervention. Especially now that I can run something like DeepSeek v4 Flash on a couple of RTX 6000s and just script an API to hammer away without having to worry about racking up a huge bill.
iririririr 10 hours ago||
do you feel this is the same trade off of UI builders like android studio (or msvb6). you do in minutes what you previously did in 2, 3 hours.

is it all the work? no, but it's a part that's early on and have high perceived impact.

then, as you progress, that tool actually gets in the way and a new feature that would take 2 hours, now is around 2 days.

colingauvin 9 hours ago||
In some ways, but it's tough to say if that's my ADHD or not. It's far too easy to leave one branch of reasoning now and jump to another whenever progress gets difficult.

Though in some areas where I can sustain interest, AI is helping me go deeper. For instance, I've been putting myself to sleep at night by just asking it questions about expectation maximization and Bayesian statistics. This has seriously boosted my understanding of cryo-EM alignment algorithms in a way I couldn't do in grad school because there was no professor that understood enough to help me when I got stuck reading literature.

So it's a double edged sword for sure.

calvinmorrison 6 hours ago||
> In some ways, but it's tough to say if that's my ADHD or not. It's far too easy to leave one branch of reasoning now and jump to another whenever progress gets difficult.

I have a co-worker who doesnt feel like ADHD helps him because he sits down and just starts... doing work and typing. Assign him a complex task, he will just start on it. Mind blowing he does this day in and day out. an absolute machine.

arionhardison 8 hours ago||
I think the real win here is for idiots like me:

A) no education

B) no resources

C) not smart enough to be a self-taught bio-hacker

Everyone hears "AI is going to cure disease" and pictures some cure-all pill from a bio lab which is what I feel this paper is hinting at is missingb but that's the top of the funnel; I'm at the bottom where patients live and that is where AI is already quietly working. Its just not being benchmarked.

I built https://crohns.ai. I set out to make an AI-native clinical-trial manager with a feedback loop (DDP) and ended up somewhere completely different: instead of chasing a new "drug" which is totally out of my grasp; financially, intellectually etc... I used it to codify a care protocol that helped me avoid a flare after I got laid off, lost my insurance, and lost access to Skyrizi.

dmix 7 hours ago|
> Skyrizi

How are those biologics? Did you have to visit the doctor to get injections frequently?

arionhardison 6 hours ago||
Hands down the best drug I have been on EVER; but its 11k a month with no insurance.

The 1st 2 injections where done by a nurse that came to my home, the others were done as self injections using their njection kits.

arionhardison 6 hours ago||
Ironically, now I have several people that are on it tracking their infusions etc...

Intent: https://wiki.crohns.ai/agent/posts/ibd-biologic-switch-decis...

Program: https://crohns.ai/program/71168-biologic-therapy-initiation

Protocol: https://crohns.ai/protocol/71168

If given the chance, I might go back on it because my protocol can be a little strict at times but either way I do see a significant shift to tools like this given the state of the US Healthcare system.

tim333 11 hours ago||
Derek Lowe discusion of the paper https://www.science.org/content/blog-post/so-how-ai-drug-dis...

I think that was originally linked but got changed to the £30 to Elsevier version for some reason.

murphyslab 11 hours ago||
Derek Lowe as a science communicator, and others like him, is sorely needed to understand the real meaning and significance of the study and others. I say that as someone with a PhD in chemistry who's been to plenty of presentations on drug discovery topics.

It's difficult to calibrate statements made by other scientists unless you're well embedded within a field: Is this someone whose opinions matter? Are they the subject matter expert they make themselves out to be? Is this research itself truly impactful? Is it really 5 years until it will be realized outside of academic labs? Etc...

It's difficult to decipher questions around credibility because they rely on real-world interactions and associations that extend beyond the physical tokens of paper counts, publication venues, citations, and author lists that typically lag behind the front of human knowledge which is generated from real-world interactions. It can be simple things, like the insightful question a grad student, with minimal publication history, asks in a seminar.

Of course, the paywall is also unhelpful too, but a good, brief commentary by an appropriate commentator is a better link for 99% of prospective readers compared to most "peer reviewed" (scare quotes because that's a real question nowadays) articles.

joe_the_user 9 hours ago||
Not that I'm a Derek Lowe fanboy or anything but the entirety of your comment is like "that guy needs to check himself" without, like, any specific context, any specific argument he's wrong on this specific question or like anything. It's like "deciphering questions around credibility" is hard ... all the way down. Where's yours? What are you saying?
bogzz 8 hours ago|||
Isn't the comment in fact praising Derek Lowe as a science communicator? In the second paragraph OP is just posing the questions that one might have when reading about a field not your own, that highlight the importance of reliable science communicators.
bigDinosaur 7 hours ago||
It's a very confusing comment since Derek Lowe is a chemist working in pharma but is being referred to only as a science communicator which I suspect most people would consider to be an implicit insult.
murphyslab 1 hour ago|||
Derek Lowe is someone whom I greatly admire and his work as a science communicator is a true service to the profession and to science at large. It is not intended as an insult in any way. I've known a great number of competent chemists, but few are as effective as communicators as he is.
Gangway0829 7 hours ago|||
I think it says more about the person reading it as an implicit insult than it does OP. I am, I think, a fairly competent scientist, and know many great scientists. I know very few great scientific communicators.
murphyslab 1 hour ago|||
My apologies for the lack of clarity in my prior comment; it was composed in haste. To be clear, I am a bit of a Derek Lowe fanboy. I value the work that he does in offering insight on his areas of expertise to the public at large because he has both the necessary understanding and the ability to communicate clearly. Few people have his level of background knowledge alongside the capacity to wade into the depths of pharmaceutical chemistry and then communicate that information and his personal perspective to enrich the commons.

What I was getting at with the issue of credibility is that I (or most others) would have time determining if a particular scholarly author in pharma is a good person to listen to on the subject. But having evidence that Derek Lowe is an honest broker of information in that domain, given his long history of commentary as well as other chemists I know who eagerly read his commentary, I'm willing to defer to his assessment.

AnodicElegy 9 hours ago||
OP here: the title of the thread still links to Derek Lowe's blog post, but the article discussed in the blog post was added to the body of the original post (not by me).
murphyslab 1 hour ago||
NB: The post was updated twice. The first changed the link to the Nature Reviews Drug Discovery article; the second changed it back to Derek Lowe's blog post with the NRDD article in the body.
Xenoamorphous 13 hours ago||
Need one for hair loss ASAP.
xX_Hacker_Xx 12 hours ago||
there is a AI designed drug for hair loss that i know of.

its slow-release oral minoxidil formulation called MINX. AI helped with the formulation [1].

its in in similar category as VDPHL01. Hundreds of millions if not a billion dollars has been invested into Veradermics, and their main product is VDPHL01 (also an extended-release oral formulation).

[1] https://x.com/anagenxyz/status/2071601868841595082

kridsdale1 11 hours ago||
I’m on 0.5 to 1mg oral minoxidil daily for a few years now and it’s working great. Blood pressure benefits too.
Scoundreller 33 minutes ago|||
> Blood pressure benefits too.

Speak for yourself, if mine goes any lower I’m going to pass out

rubicon33 4 hours ago|||
Any other side effects? I’ve never even heard of this.
mjmj 3 hours ago||
I’ve taken low dose oral min for a few years and it’s systemic, meaning it’ll make all your hair grow. I now have body hair where before it was never noticeable. “I’m hairy like monkey” as my kids say.
newsomix9xl 13 hours ago|||
Indeed. My plans for a youthful Mohawk are being stymied by the lack of AI promised medical breakthroughs.

Wheres my follicles dammit?

piskov 8 hours ago|||
Track KX-826, clascoterone, and VDPHL01
Z_I_F_F 5 hours ago||
PP-405 too
SoftTalker 10 hours ago|||
A good set of clippers.
asxndu 13 hours ago|||
Already exists (finasteride), only problem is that it castrates you chemicallym
gradus_ad 13 hours ago|||
For everyone struggling with hair loss but concerned about side effects of Fin. Look into topical fin. It produces higher concentrations of the medication in the scalp and lower systemic concentration. Not perfect, but better.
skepticATX 13 hours ago||||
About 2% of finasteride users experience these side effects, and they are reversible after discontinuation.
pton_xd 13 hours ago||
Apparently some users report persistent side effects even years after stopping the medication (post-finasteride syndrome).
debugnik 12 hours ago|||
How many of them can be accounted for by the natural rate of sexual dysfunction?

I've been taking it without significant side effects for ~15 years, so I'm not worried, although at this point it's losing its main effect as well.

xX_Hacker_Xx 12 hours ago||||
yep that would be me
pstuart 13 hours ago|||
Yep. Not everybody but enough to warrant vigilant monitoring and titration.
alpineidyll3 13 hours ago|||
Absci has a good asset coming out pretty soon that you could try to get on the trial.
codemax98 5 hours ago||
Absci is bullshit
rubicon33 13 hours ago||
[flagged]
redox99 5 hours ago||
Obviously the missing part (which we already have for software and math) is that we need agents to be able to run automated loops in the real world. That basically requires robots. I think we'll be there in less than 5 years.
p-o 13 hours ago||
We're all about to come face to face with this reality. This dance can only last so long.
GolfPopper 13 hours ago||
>We're all about to come face to face with this reality. This dance can only last so long.

Only for values of 'all' that exclude well-connected members of the billionaire class and their select associates.

alpineidyll3 13 hours ago||
if you think the state of the art in this area is something you'll hear about from a guy that looks like santa in an academic journal, your investments deserve what's about to happen to them.
Oarch 12 hours ago||
[AI drug discovery] was never the hard part.
techpression 7 hours ago|
This made me laugh, more than expected, but I did visit LinkedIn just before so that could explain it. Thanks!
bharatsuthar 2 hours ago||
Yeah it's [x was never the hard part] all the way down. It's a very human thing and I bet we'd keep saying that even after we've solved the hardest mysteries including consciousness, the origin of life or the true nature of reality.
largbae 11 hours ago||
How refreshing was this article vs. all the slop?

The lack of comparable data and testability really does seem to be a challenge. I wonder if people would be more willing to collect and share lots of health data if the collecting company was a non-profit dedicated to anonymizing it.

cryptographical 12 hours ago|
need one for brain plasicity. it would be nice to be able to easily learn a foreign language or musical instrument naturally.
bothers 11 hours ago||
Easily? Have you ever actually learned a second language or an instrument as a child?
fragmede 9 hours ago||
Vs as an adult. Yes it's hard as a kid, but as an adult it's even harder.
KellyCriterion 12 hours ago|||
There is one!

Ketamin should have huge impacts on neuro/brain plasticity when used properly (i.e. in therapy)

immmmmm 12 hours ago|||
Psychedelics are several orders of magnitude stronger on the plasticity front.

In therapy as well.

bharatsuthar 2 hours ago||
So is ketamine but we haven't explored it more for other brain functions where it can act as a psychoplastogen eg reopening critical periods of visual learning.
consensus1 11 hours ago||
Psilocybin has this effect. Source: I can't remember where I read it, so low confidence.
bharatsuthar 2 hours ago||
Sure, but what kind of protocol are you going to use to actually reap the benefits of these transient neuroplasticity effects, especially for learning something new like math or piano as an adult?

Same with ketamine. It's not like you can take it a couple of times and open some magic window where everything suddenly becomes easier to learn. From my personal experience and surface-level understanding of the current research, psychedelics(including ketamine) seem to temporarily relax hardened beliefs/priors and rigid neural pathways, which can help you see things from a fresh perspective. But learning something substantial like math or a new language after you've passed the most plastic stages of development is still going to take much longer than what these drugs can realistically help with.

They might make you see something differently or even get you extremely interested in it, but sustaining that interest and consolidating the knowledge or skill is still slow compared with childhood/adolescence. Of course, it depends a lot on what you're learning. For example, crystallized intelligence and sufficient motivation can make some things much easier to learn as an adult, but many useful things are also just boring to learn when you no longer have a childlike plastic brain or an environment built around constant learning.

Edit: Theoretically, you could accelerate learning by taking psychedelics/ketamine at a set frequency but it's a huge gamble because of their risk profile. eg. HPPD/trauma risk with classic psychedelics and bladder/neurotoxicity risk with ketamine if you get addicted or take it too frequently.

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