Hacker News Reader

Comment by biols | Hacker News Reader

I work at a medium-sized pharmaceutical company as a computational biologist. Diseases like KS sometimes come up as potential repurposing targets (or novel drug targets), but we get a LOT of pushback from finance / leadership because we're unlikely to turn a profit working on ultra-rare indications.

It is a deeply frustrating position to be in, wanting to work on these rare diseases and help this rarified patient population and not being able to, even though me and my colleagues are poised to do so. I often get maligned for being a scientist in pharma; laypeople often assert that I "don't want to treat cancer / rare genetic disease / etc; because then I'd be out of business." I can assure those reading that all of us DESPERATELY would like to work in these indications, and often times it's tragically finance that dictates whether we are able to or not. The system feels broken.

View on HN

If you could do research that will save 10 lives, vs research that will save 1 life, which would you choose?

I understand that there are no easy choices here, and having to make a choice will always be heartbreaking.

May I suggest contacting MacKenzie Scott (Jeff Bezos' ex) who seems to be looking for worthwhile endeavors to finance.

(I have no connection to Ms Scott, I just read articles about her charitable activities in the newspaper.)

I first heard about her efforts when she donated $40M to UCF. https://www.ucf.edu/news/scott-40-million-transformational-i...

I hope we can get in touch somehow. Thank you.

Major pharma companies are all constantly competing, and very often are duplicating work because they are not sharing major experimental results. The way it feels is that there's already "too many people" working in certain areas (e.g. in cancer), while almost no attention is paid to these rare diseases.

I think that more people studying rare diseases would result in a net gain of lives saved; I don't think it's as zero-sum as "either 1 person's life is saved or 10 are" in this instance.

Research also cross pollinates across disease areas. For example, understanding altered metabolism in cancer can yield insights for non-oncological metabolic disorders. Oftentimes, though, nobody's working on translating that work out of a cancer model, because the financial incentives are not there.

On the other hand, competition has given us what, 6 covid vaccines of varying effectiveness, and in record time. What if only the least effective one was developed, and took 18 months?

The 1962 FDA effectiveness mandates have had the side effect of increasing drug development costs enormously, and that shuts down development of treatments for rare disorders.

I think the idea would have been that Pfizer and Moderna could have pooled resources and made a single optimal vaccine faster, though I'll admit I'm not sure it could have happened any faster than it did from my perspective.

The Kefauver Harris Amendment you refer to was immensely important towards the development of safe and efficacious drugs -- I do not see the connection between that act and rare disease therapeutic development. In fact, drugs that only offer marginal improvements in quality of life for rare genetic disease patients are often fast-tracked by the FDA. Requiring that a drug _works_ shouldn't inhibit drug development. Otherwise, we end up with tragedies like what happened with the use of thalidomide, which prompted this amendment in the first place.

Competition is an incredible driver of outcomes, e.g. moon landing. It's also better from a risk perspective since it decorrelates efforts and we only need 1 to succeed. It also allows evolution to operate, where the incompetent and broken and corrupt die off and the productive are given more resources, which tends to lead to overall improvement.

Sure, competition also creates waste, which is your main point here, but don't discount the upsides.

Competition has proven itself in the real world. Having only one monolithic vaccine maker (whether for-profit, non-profit, or government) would be a very bad thing. What would happen if it falls to corrupt leadership, as one of many examples of how this could go wrong? There is no mechanism to escape badness here, because we only have 1 of them.

It is possible to maintain the benefits of competition without the level of duplication and profit motives that we struggle with today.

Large scale collaborative scientific endavours like CERN show us that it is possible to both publically share knowledge and still explore multiple avenues and competing designs. There's also no financial profit motive and while CERN receives a lot of public funding, it has to pump that funding back into the economies of the funding countries so it serves more like a high-tech industry stimulus and technological incubator.

I see no reason why a similar aproach for the development of (specific) therapeutics could not work.

I agree that it's possible to preserve many of the benefits of competition under a more centralized and explicitly cooperative structure. You see this sometimes within large for-profit companies that have competing products, which are siloed from each other in the workplace. This works fine, because there is still a profit motive at work and the identical evolutionary forces that will kill a particular silo if it's underperforming, and the same competitive pressure to perform.

Much larger cooperative structures are less proven to work and are more hypothetical, though, even if CERN is an example of such a structure working. The risk, mainly, is that there isn't a good corrective mechanism if the whole thing becomes corrupted or rotten from the top. The other risk is that the cooperation is actually detrimental to progress because it correlates outcomes via group think. Some decorrelation is nice. I am happy that Musk et al. weren't forced to become cogs at NASA, and could explore their own ideas, which was easier to achieve by then being explicitly separate entities (even if they were reliant on contracts).

> This works fine, because there is still a profit motive at work and the identical evolutionary forces that will kill a particular silo if it's underperforming, and the same competitive pressure to perform.

the profit motive in a multinationally funded system is still there in the sense of 'we have a budget of X, what's the best way to spend it?'. And research avenues that fail to yield the expected results can be terminated. In my experience, disagreement between researchers or groups were also far from uncommon. But maybe that's just physicists being exceptionally knowitall^H^H^H hard to convince :)

It's not flawless, but I don't think it could be less efficient use of public money than the current system where we publically fund early research and the succesfull projects get snatched up by the industry, patented, and sold for large profits. Even if a lot of pharmaceutical research ends up going nowhere (or a competitor beats them to it), we still end up paying for it trough the profit margins of the parent companies.

Raising healthcare costs are a serious concern for many countries, and part pharmaceuticals are a non-trivial part of the cost. Researching and producing them locally might help reduce that cost and stimulate a broader healthcare industry.

I do fear that pharmaceutical research might be to politicized for a multinational approach(e.g. HIV, what disease to prioritize). And there's bound to be some backlash from certain groups over a large 'shadowy' multinational body doing human trials.

"Safety" is quite a wide concept. I heard a professional drug researcher say that aspirin wouldn't pass the trials today, and certainly not as an over-the-counter drug. Too many side effects.

If we can use a software analogy, mess like Windows 95 wouldn't see the light of the day. But they were useful nonetheless.

I’m not sure that history is going to be kind to Trump’s shortcutting[1] regulatory approval on the current vaccines.

[1] “Operation Warp Speed”

I'm beyond puzzled. The multiple COVID vaccines weren't developed so quickly because of competition. They were developed by an unprecedented worldwide effort and government support.

I wonder if you could run a pharma company that buys IP for failed cancer treatments and runs small trials in rare diseases. you have the advantage of having passed Phase I/II usually, so you know it's decently safe, and oncology hits a lot of diverse targets.

there are some examples, for instance enzastaurin being repurposed for vascular EDS, after washing out as an angiogenesis inhibitor for cancer. I don't know if it makes sense mechanistically, I sure hope it does.

You don’t know in advance how many lives will be saved by research. You may not know what you are researching at first; diphenhydramine is a moderately effective sedative, but turned out to be a strong antihistamine.

> If you could do research that will save 10 lives, vs research that will save 1 life, which would you choose?

Both. We're not even close to our limits on research capacity.

If we actually were at the limits of research capacity, and we were actually forced to make decisions between livesaving treatments to research where we couldn't do both without sacrificing something else that saves lives, then yes, of course, choose the thing with the highest number of predicted lives saved. But we're not even close to needing to make such decisions yet.

We just don't have a good system for funding cures you can't sell to millions. That's not anywhere close to "heartbreaking decisions" territory; that's "societal coordination problem" territory.

> Both. We're not even close to our limits on research capacity.

Really? From the outside it seems to me like we are beyond our limits on research capacity.

The progress seems to be slowing down everywhere while the price per discovery of a new drug skyrockets with many having rather disappointing efficacy (high NNTs).

None of those limitations seem inherent, nor are we close to the societal limits for what we can do when we actually care about accomplishing something. We may be somewhat close to the limits of what we can do with current R&D structures and incentives, but that's quite different.

> We're not even close to our limits on research capacity.

Maybe not at your stage of research, but it's my understanding that further down the pipeline (eg clinical trials) you're mich closer to the limits, simply due to financial constraints: given that a trial for something you can sell to millions isn't that mich more expensive than one you can sell to dozens,and given that you need to get payed for your job, i don't see how it doesn't make sense to prioritize the lower hanging fruit. Am i missing something?

> We just don't have a good system for funding cures you can't sell to millions

(Full disclosure: close family member works at $bigPharma)

I don't think it's about finding treatments you can "sell to millions", it's that in pharma, like in pretty much every other business, it's about ROI.

You definitely don't need millions of patients, but you do need to cover the R&D costs _and_ have enough left over to keep the shareholders happy.

This is such a fucked up incentive structure. Literally having the capacity to save lives but not doing it because otherwise people will pull out their money because Roblox is has a better ROI.

> This is such a fucked up incentive structure [..]

It may well be(!), so let's assume you're right, what better incentive structure should we put in place instead?

Increase general taxation and use that to fund more pharamaceutical R&D?

Break up the pharma companies and let them only be at-cost (!) manufacturers, move all R&D off to universities, and cooperate with other countries in said R&D efforts.

> Break up the pharma companies

For many politicians that would be seen as a "courageous decision" (hat-tip: Sir Humphrey Appleby)

> and let them only be at-cost (!) manufacturers

Won't it be hard to find investors if you do that?

> move all R&D off to universities

I think the "D" in "R&D" might be the problem in this approach. Universities are great at many things, including research, but based on my experiences (science PhD two decades ago in a research group which worked on anti-infectives) the scientists there aren't necessarily very good - or even actually interested - in development as such. We partnered fairly closely with $bigPharma at the time, and they funded a fair chunk of our work.

> Won't it be hard to find investors if you do that?

Better that than paying negative interest for German 20 year bonds, if you ask me.

> Universities are great at many things, including research, but based on my experiences (science PhD two decades ago in a research group which worked on anti-infectives) the scientists there aren't necessarily very good - or even actually interested - in development as such. We partnered fairly closely with $bigPharma at the time, and they funded a fair chunk of our work.

Agreed, universities have historically not been involved into the development part. But that is not a given dogma that can't be changed - the government could fund the establishment of development departments.

Alternatively, international governments could establish cooperative efforts to develop pharmaceutical compounds. Rare diseases and the decline of available reserve antibiotics are a global problem affecting every country on Earth just the same.

Can you illustrate for a lay person the difference between research and development in pharma context?

Research = determining a candidate compound, e.g. a new antibiotic, (e.g. by taking and tweaking an existing compound, by basing off of the actual viral/bacterial genetic code such as with the Biontech/Moderna CoV vaccines or by isolating a compound found in a plant, fungus or other natural agent which has been determined to have the effect you want), and initial checking against cell cultures and/or lab animals for effectivity.

Development = taking a lot of candidate compounds and evaluating them in the classic three-stage procedure - phase 1: determine how the compound is processed in actual human bodies to check if it is actually safe to ingest and what side effects can already be observed (n ~ 20-80), phase 2: determine effective dosage (n ~ 100-500), phase 3: check effectivity in a double-blind trial (n ~ 1k-10k), as well as the fourth phase (after-license monitoring) [1][2].

The more a compound progresses, the more expensive the trials get to conduct, not just because the participants usually get some compensation for their risk, but also because all the data has to be tracked and processed. And a lot of candidate compounds fail somewhere along the path (either because they are ineffective or because the side effects are too severe), which makes the money invested effectively wasted (from a capitalist point of view, not from a scientific!).

[1]: https://en.wikipedia.org/wiki/Clinical_trial

[2]: https://studienteilnehmergesucht.de/ratgeber/die-vier-phasen...

> Development = taking a lot of candidate compounds

At least one $bigPharma defines "research" as being everything up to and including the first proof of concept in a human [Phase I] trial. After that would be "development".

That'll mean no more drug development.

My grandmother had rheumatoid arthritis, and it made her life utterly miserable for her last 10 years. Recently, Enbrel was developed by a biotech for profit company, it is the first effective treatment for rheumatoid arthritis.

No university or government came up with it. A for profit company did.

> Increase general taxation and use that to fund more pharamaceutical R&D?

Take the US military budget and give it to life saving research instead of life taking.

Edit: Also implement a wealth tax instead of income tax. Discourage hoarding of wealth and concentration of power in the hands of top 1%.

Ah yes so China or Russia can invade and establish a totalitarian regime. Excellent idea.

You don't have to give up all of it. The total budget of US is larger than the next 6 countries combined. India, which is actually surrounded by hostile neighbors, one of which is china manages to defend itself with a tenth of the budget. My guy you are giving military money they didn't even ask for in this year's budget. Please stop repeating this line. American budget it not to stop China or Russia, its to assert their own will on the world.

> The total budget of US is larger than the next 6 countries combined.

Not in % of gdp. The only metric that matters. The US economy is massive in size so of course the budget is a big number.

> one of which is china manages to defend itself with a tenth of the budget.

Everything is cheaper in China. You can do a lot more with one million there than in the US.

I don't know why you are talking about china while the point I was making was about India defending itself against china. Also indian % of GDP for military budget is 2.8 while for US its 3.75. US has no neighboring countries actively attacking it, India does.

edit: BTW, is there any actual proof that this whole military budget dissuades Russia and China in any way?

> This is such a fucked up incentive structure.

It has produced far, far better results than communist incentive structures.

Thanks for your answer. Yes, this is not a case of lacking science, research, or even treatment capabilities. It is a case of too many hoops to jump.

Maybe twenty years from now some people with a high degree of knowledge, skills, and some resources will be able to get around these hoops illegally (by the laws of certain jurisdictions) and fix these conditions (or kill themselves or somebody else trying, but so does god/nature and doctors, with different[citation needed] probability distributions).

> If you could do research that will save 10 lives, vs research that will save 1 life, which would you choose?

The diseases like what OP is dealing with are the ones that are going to advance science for all of us. That’s where gene therapies are going to be applied first which will pave the path for more mass-market treatments.

Thanks for your comment. I'm also a computational biologist by training, but have never worked in the private sector.

I'm familiar with the idea of re-purposing drugs for rare disease treatments (most of my adjacent work has been in very early-stage academic research), but I'm curious about the financials here. Could some of the financial risk here be minimized by aggregating multiple groups of patients, all suffering from different rare diseases? From what I know about the process, the answer is yes, but I'd be curious to hear from somebody closer to the process.

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.

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.

I hope one-day things would turn around. If the regulators asked pharmaceutical companies to study for these drugs on the side so much could change. Probably less than 1% of their R&D budget would be enough to move things.

Absolutely. A lot of funding gets poured into dead end alzheimers research or similar that will never work. A fraction of that redirected to rare diseases that get zero funding will do wonders. It is a shame that academia and research are so burdened with graft and politics.

It would be cool if pharma companies had charitable rotation program for researchers to volunteer to research these types of things. So the researchers could still get paid and the company could claim the costs as a write-off (not sure if they actually need one) with the results being public use.

I want to preface this by saying I am not providing an opinion rather I am genuinely curious.

When Martin Shkreli bought the rights to Daraprim, some of his rhetoric about pharmaceutical industry sounded fair. He said that he is willing to send the drug for free to anyone who wrote to the company and he was essentially making the insurance companies pay the absurd price of the drug. He claimed no patient would ever financially suffer for the drug. He said the needed the money to pay for new research and better drugs and it was one of of lesser of evil thing he can do to R&D.

Ignoring the trickle down effect, if the government and Insurance companies in most cases ultimately pay for the price of medication wouldn't it be valid motivator to research rare diseases?

not providing an opinion on your suggestion but there is no such a thing as "government and Insurance companies paying" though, It's taxpayers.

Always has been. Through insurance, cost-pass-thru, taxes, direct medication purchase, etc. So, now that it's established that it's always the individual paying into...which is the most efficient way of allocating funds out of the system? Profit? Lives saved? Less acne?

Zolgensma comes to mind - one time gene therapy treatment for a rare disease (tens of thousands), billed at $2M.

Not sure if there's as viable for OP since only a few hundred people have been diagnosed.

Insurance companies get their money from people, companies, or governments that pay for insurance. To get him an absurd amount of money, ultimately we (individuals, companies, taxpayers) have to provide it.

How does near-welfare state do innovation and research in pharmaceuticals? How do countries with universal medical care performs in terms of research and innovation and treating rare diseases?

Shkreli's ideology was when it comes to innovation in Pharma and America's patent driven capitalist nature towards it is the reason why America leads the way in innovation.

Basic research is mainly government funded. Pharma companies build on that research to do the final phases of drug development and they fund the trials in exchange for a monopoly if the drug pays off. Shkreli wasn't interested in funding research. He looked for drugs he could buy and jack up the price of, so he was just a parasite.

This is very interesting. On a tangential note about Shkreli. I took a break and I remembered in the Facebook senate hearing a senator said to Zuck, "Who elected you to make decisions about what stays on the internet and what doesn't?" . This is tangentially related in the matters of Shkreli. Why it would be ethical for Shkreli to take this "moral burden" of doing the right thing and invest in innovation by essentially indirectly taking money from taxpayers? I am using the word ethical because the US government doesn't think price gouging illegal. He is nobody's champion and surely he is not elected. It is a very interesting idea.

I guess for decisions about pharma research like this having an elected body or representation of an elected body is a good thing.

The answer should be obvious. Countries that do use "democratic" means to decide these things produce absolutely nothing of value. Countries that let people vote with their wallet (rather than ideology) have produced just about every important medical breakthrough in the last 50 years.

In the USA the best of the best are put in charge of tomorrows medicine, and that is why they succeed while the rest of the world is just pitiful in comparison.

Just the fact that you get push back on work like that suggests to me that these companies will never cure anything. They will treat absolutely disease, but cure nothing.

Have you not had a family member or close friend cured of disease that would have killed them a hundred years ago, thanks to modern pharma drug? I sure have.

No, not personally, I do have 2 on life long treatments. But I was being too hyperbolic and I don't doubt your story.

I'm just extrapolating incentives. Is there any incentive to cure (invoice once), when they can treat (life long invoices)? Certainly scorn is irrelevant as OPs comment suggests they're unwilling to work on rare diseases. And these companies are public. They have shareholders that expect them to constantly grow.

I don't believe it's a stretch to say, at the very least, the incentive is there.

competion provides the incentive, a cure will put all your treatment competitors out of business as you get everything from everyone who doesn't like treatment.

You know many people who would have died of smallpox,measles, polio, and the like 100 years ago, you just have no idea who those people are.

That is a reassuring perspective.

To be clear, I still think this conversation goes on in the background. Bill Gates famously convinced Oxford not to give the covid vaccine IP away thus preventing poorer countries from creating their own vaccines. The deaths from this act alone should be enough to convince you that money makes medicine murkier than you clearly want to believe.

Sometimes I share this feeling, but then I think about all the loved ones who were cured of some disease that would have been deadly 50 years ago. I don't think it's the pharma companies that are responsible for this. They are for-profit entities. Our governments should create the necessary business environment which will encourage these companies to work more for the people.

How do you (eventually) do phase 2 and 3 trials for an ultra rare disease that only has hundreds of patients?

Reply on news.ycombinator.com