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Comment by netizen-936824 | Hacker News Reader

Sounds like you and your colleagues could start your own company, there may be enough people. I wonder if a nonprofit pharma company is viable.

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I have been reading a book recently: The Story of Taxol: Nature and Politics in the Pursuit of an Anti-Cancer Drug, and one of the most fascinating parts was the way they discovered this molecule. Long story short, Taxol is a molecule they isolated from the bark of the Pacific Yew. The interesting part for me was learning about the Cancer Chemotherapy National Service Center [1]. They went around collecting samples of random plants, then tested them for anti-cancer properties very systematically. So in the U.S., at one point, we had a publicly funded drug discovery program targeted at a specific disease, and this is what jump started Pharma research in anti-cancer drugs. I would say we need to restart a program like this, and of course we should also focus on rare diseases--we stand to learn a tremendous amount, and it's difficult to convince industry to do it.

Personally, I'm a computational/mathematical biologist and I work on single cell data targeting multiple myeloma, I'd really like to see serious non-profit Pharma. Drug repurposing seems like the most feasible avenue. What I know of right now is open Pharma [2].

[1] https://dtp.cancer.gov/timeline/flash/milestones/M3_CCNSC.ht... [2] https://www.ospfound.org

Out of curiosity, what does your work entail with single cell stuff from a computational perspective? I've been doing some research into molecular docking as a drug discovery method, but its all single protein.

There are a lot of modalities being integrated, things like spatial/temporal, ADT/protein, etc. Integrating all of this data is a computational challenge, and of course there are lots of methods for analyzing it that vary in computational demands. It's not simulation, but still a lot of processing.

So you're taking all wet bench data and analyzing or integrating it rather than modeling? That's interesting!

Are there any possibilities that you see from your experience in using modeling or other in silico methods to reduce time in the lab, find new leads in drug development, or otherwise enhance research capabilities?

Yes, essentially, though you may create models of interactions etc., but the main idea is to extract information from various aspects of the cell.

As far as in silico, I think absolutely there are probably opportunities here. Generative models might be useful for some type of counterfactual (automated) reasoning with respect to disease course/treatment. I think we're in the relatively early days of collecting high resolution cellular data, so I think in silico approaches like this will be more and more relevant.

The Broad Institute hosts a very interesting transcriptomic dataset called CMap [1] that was intended to facilitate rapid drug repurposing. Having studied this dataset and worked with the data generators and software teams, I can say that drug repurposing is NOT as straightforward as people think. However, I agree that as a strategy drug repurposing is a useful tool in the arsenal generally.

[1] https://clue.io

Interesting....I'll have a close look at this, thank you. I didn't mean to imply drug repurposing was straightforward, certainly as you say this is very challenging. I guess my thinking was that there might be relatively lower hanging fruit here (if Pharma companies have very little incentive to exhaustively search for repurposing targets for off-patent meds, maybe only a non-profit would be willing to do this) than say de-novo development.

This is one of the many reasons that causing plant and animal species to go extinct is bad for humans. We really have no idea how many potentially live-saving/health-enhancing/etc. medicines we are annihilating!

What I find interesting is that most western countries have this kind of government funded programs of one kind or another... and yet they hardly produce any medical breakthroughs.

Perhaps the interesting thing would be to ask what particular thing makes the US different to other western countries, rather than cherry picking one particular thing that happens to agree with whatever ideology is popular today.

I wish there was a way to crowd fund or crowd source a push for new therapeutics. I have a rare cancer at the moment and the overwhelming majority of drugs used for it were developed for other cancers. I wish there was a way we could establish an open source community or project around creating novel drug targets as a small moon shot funded by donations from the lives that it effects.

From a software developer perspective: A github like service where every incremental research step is recorded&visible. A build management system like travis where each experiment is built and held accountable to unit tests. Something like github actions where you can trigger an automated lab trial instantly. Somehow opensource SW development communities have so much they can teach to medical researchers in terms of how to scale development.

Sage Bionetworks Synapse https://www.synapse.org/ was conceived as a github-based research collaboration ecosystem.

This is what I'd like to see. There should be some kind of system where in-progress research being done by pharma companies can be published. This would reduce the massively redundant amount of studies (e.g. CRISPR screens, xenograft studies, etc.) and help scientists more quickly converge on the mechanistic underpinnings of disease and how best to address them therapeutically.

Obviously this can't work in the current pharma industry configuration; what financial incentive is there for big pharma companies to publish their results for another company to beat them to a new drug? I don't have a solution to this problem, but I hope someday we as a society can find one. This would absolutely revolutionize biopharmaceutical science.

I've thought about things like the patent/ip problem, the structure of biomedical research, Pharma research, etc. This is an area where I don't actually see competition as a net benefit, however....it's the reality. The only thing I can come up with is a version of 'data rental'. Rather than Pharma companies locking this data away from others indefinitely, is there a way they could profit from it somehow, while still retaining ownership and not divulging trade secrets? Maybe not.

I've thought that a type of cryptographic data commons based on multi-party communication [1] could possibly be deployed with some effect. Basically you need algorithms that can compute on encrypted data, and a way to securely communicate encrypted data. There might not be huge incentive to use something like this, but maybe a version of this idea could work.

[1] https://en.wikipedia.org/wiki/Secure_multi-party_computation

I agree that the system is just "reality" right now. I think the idea of a cryptographic data commons is an interesting idea, I'm just trying to imagine how it'd play out in my day-to-day research. If a system would tell me that my hypothesis is correct, but I couldn't look at (and share with colleagues) the raw data being computed, it'd be tough to believe that system. Maybe there's some type of zero-knowledge proof system that could facilitate this, though.

I only have a rudimentary understanding of blockchain technologies, but a system where pieces of a research puzzle are stored on chain and each user can claim ownership of those findings, a resultant drug's profits could be proportionally split by every entity which contributed to the research.

Another idea would be to completely socialize all biopharmaceutical research, but that type of system would require an extremely radical societal shift.

Yes, it's admittedly an incredibly tough problem (how do you get those competing to cooperate?), and how to compute on data that is trustworthy. Ultimately, in biotech/pharma you have to ultimately know what an underlying gene or say pathway actually is, it can't be totally obfuscated. Still not sure how to set this up (if it's really even possible) that solves for this use case.

> but a system where pieces of a research puzzle are stored on chain and each user can claim ownership of those findings, a resultant drug's profits could be proportionally split by every entity which contributed to the research.

I think ultimately this is how a research cooperative could work. If distributing and re-allocating fractional ownership is efficient enough, it seems like something like this might be feasible. The idea with multiparty communication (MPC) is that in this setup a research entity would contribute their data in an encrypted fashion, and any parties would be granted access to compute on it based on some set of rules/buy in etc.

This is a really difficult technical approach, as MPC is really only in it's infancy, made only to seem easy by the far more difficult and distant prospect of socializing medicine, which would seem to be of the greatest benefit.

It's hard to imagine that working in a way that was free from scammers. People with rare conditions are already targeted by con men, internet fundraising is targeted by con men, I think it would implode.

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