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Sierpiński Triangle? In My Bitwise and?

https://lcamtuf.substack.com/p/sierpinski-triangle-in-my-bitwise
71•guiambros•2h ago•17 comments

Show HN: Xenolab – Rasp Pi monitor for my pet carnivourus plants

https://github.com/blackrabbit17/xenolab
54•malux85•3h ago•17 comments

US vs. Google amicus curiae brief of Y Combinator in support of plaintiffs [pdf]

https://storage.courtlistener.com/recap/gov.uscourts.dcd.223205/gov.uscourts.dcd.223205.1300.1.pdf
310•dave1629•10h ago•503 comments

Observations from people watching

https://skincontact.substack.com/p/21-observations-from-people-watching
21•jger15•1h ago•7 comments

Why the Apple II Didn't Support Lowercase Letters (2020)

https://www.vintagecomputing.com/index.php/archives/2833/why-the-apple-ii-didnt-support-lowercase-letters
31•colinbartlett•3h ago•23 comments

A critical look at MCP

https://raz.sh/blog/2025-05-02_a_critical_look_at_mcp
305•ablekh•9h ago•181 comments

Show HN: LoopMix128 – Fast C PRNG (.46ns), 2^128 Period, BigCrush/PractRand Pass

https://github.com/danielcota/LoopMix128
24•the_othernet•3h ago•14 comments

For $595, you get what nobody else can give you for twice the price (1982) [pdf]

https://s3data.computerhistory.org/brochures/commodore.commodore64.1982.102646264.pdf
105•indigodaddy•6h ago•69 comments

Reverse engineering the 386 processor's prefetch queue circuitry

http://www.righto.com/2025/05/386-prefetch-circuitry-reverse-engineered.html
103•todsacerdoti•8h ago•29 comments

Pope Leo XIV: "AI poses new challenges re: human dignity, justice and labour"

https://www.vatican.va/content/leo-xiv/en/speeches/2025/may/documents/20250510-collegio-cardinalizio.html
87•90s_dev•5h ago•33 comments

Eagle Hunters of Kyrgyzstan

https://magazine.atavist.com/the-eagle-hunters-of-kyrgyzstan-world-nomad-games/
15•gmays•3d ago•2 comments

Comparison of C/POSIX standard library implementations for Linux

https://www.etalabs.net/compare_libcs.html
82•smartmic•9h ago•28 comments

Adventures in Imbalanced Learning and Class Weight

http://andersource.dev/2025/05/05/imbalanced-learning.html
27•andersource•2d ago•3 comments

Embracer Games Archive is preserving 75000 video games and needs contributions

https://embracergamesarchive.com/
132•draugadrotten•13h ago•61 comments

Microsoft Teams will soon block screen capture during meetings

https://www.bleepingcomputer.com/news/microsoft/microsoft-teams-will-soon-block-screen-capture-during-meetings/
101•josephcsible•4h ago•160 comments

Show HN: Code Claude Code

https://github.com/RVCA212/codesys
93•sean_•9h ago•19 comments

Private Japanese lunar lander enters orbit around moon ahead of a June touchdown

https://phys.org/news/2025-05-private-japanese-lunar-lander-orbit.html
197•pseudolus•3d ago•58 comments

How much information is in DNA?

https://dynomight.substack.com/p/dna
50•crescit_eundo•2d ago•46 comments

Email Forwarding for Your Domain

https://mailwip.com
49•codazoda•5h ago•36 comments

Weave (YC W25) is hiring a founding engineer

https://www.ycombinator.com/companies/weave-3/jobs
1•adchurch•7h ago

Intel: Winning and Losing

https://www.abortretry.fail/p/intel-winning-and-losing
77•rbanffy•13h ago•47 comments

Gmail to SQLite

https://github.com/marcboeker/gmail-to-sqlite
302•tehlike•20h ago•92 comments

The State of SSL Stacks

https://www.haproxy.com/blog/state-of-ssl-stacks
12•zdw•3d ago•0 comments

React Three Ecosystem

https://www.react-three.org/
98•bpierre•11h ago•43 comments

Not a three-year-old chimney sweep (2022)

https://fakehistoryhunter.net/2022/07/26/not-a-3-year-old-chimney-sweep/
100•nixass•17h ago•57 comments

Building Local-First Flutter Apps with Riverpod, Drift, and PowerSync

https://dinkomarinac.dev/building-local-first-flutter-apps-with-riverpod-drift-and-powersync
32•kobieps•4d ago•17 comments

Detect and crash Chromium bots

https://blog.castle.io/detect-and-crash-chromium-bots-with-one-weird-trick-bots-hate-it/
124•avastel•3d ago•35 comments

The Deathbed Fallacy (2018)

https://www.hjorthjort.xyz/2018/02/21/the-deathbed-fallacy.html
233•mefengl•14h ago•110 comments

Prolog's Eternal September (2017)

https://storytotell.org/prologs-eternal-september
73•Tomte•2d ago•57 comments

'It cannot provide nuance': UK experts warn AI therapy chatbots are not safe

https://www.theguardian.com/technology/2025/may/07/experts-warn-therapy-ai-chatbots-are-not-safe-to-use
104•distalx•8h ago•115 comments
Open in hackernews

The Price of Remission

https://www.propublica.org/article/revlimid-price-cancer-celgene-drugs-fda-multiple-myeloma
79•danso•2d ago

Comments

planck_tonne•2d ago
Crazy how they managed to restrict the competing researchers from obtaining the drug.

How did they do that?

Why is the sale of a super expensive drug used exclusively to treat a super specific type of cancer even controlled in the first place? What is even the argument?

I couldn't think of any argument before. After reading, I can only think of "to restrict competition".

throwanem•4h ago
The argument in essence is that only permitting pharmaceutical companies these outrageous profits will induce them to continue investing the likewise outrageous costs of new drug development now that all the low-hanging fruit like antibiotics, and sildenafil and other antihypertensives, has been picked. This extends (usually by implication) to trivial variations in molecular chemistry which have no functional effect on a medication but which are used to extend patent protections solely on the basis of a structural change - a practice also visible in the history of one family of drugs I have mentioned, and one which without some sort of justification might be taken for an example of a law's letter being abused to violate that same law's intent.

Look, I didn't say I buy it. But you asked for the basic argument advocates make in support of such practices, and here it is.

throwawaymaths•4h ago
it's not a great argument since iirc half of pharmaceutical company spending is on marketing; far far outstripping r&d
smt88•4h ago
And a lot of pharma research is based on publicly-funded research in the first place.
nradov•4h ago
Sure, but that's a bit of a red herring. The largest expense in bringing a new prescription drug to market is the phase 3 clinical trial, which now costs on the order of $1B each. Those often fail, so it's a huge gamble. There is very little public funding for type of research.
throwanem•4h ago
And a drug like Revlimid makes its manufacturer tens to hundreds of billions; the "legacy" portfolio in which BMS classes it pulled in a cool $5.6b just in Q1 '25, of which Revlimid itself was about a sixth, or just under a billion - down by almost half year on year. See https://www.bms.com/assets/bms/us/en-us/pdf/investor-info/do..., pp. 8-9.

It is as if VCs in the tech industry demanded the taxpayer guarantee them a healthy rate of profit, to a standard of health the VCs themselves are privileged to define. Indeed, as with Allred and the regional airlines, perhaps now we see whence Altman has cribbed his "innovation."

nradov•4h ago
I don't understand your point. Some drugs are enormously profitable. Others lose money. There are no taxpayer guarantees. Pharmaceutical companies on average don't generate higher shareholder returns than other industrial sectors. A few like K-V and Dendreon have even gone bankrupt.

One could make an argument that taxpayer subsidized health plans which include prescription drug coverage such as Medicare Part D or Medicaid should limit the prices they are willing to reimburse on a QALY basis. And Medicare has started a limited drug price negotiation program. But generally, voters have been unwilling to accept the trade-offs inherent in drug price controls.

https://www.cms.gov/newsroom/fact-sheets/medicare-drug-price...

throwanem•3h ago
My point is that if you want to provide support for the advocacy argument, you've quite a long way yet to go. A good place to start would be to pick any one claim you have made and attempt to substantiate it. Until then, I've nothing with which to attempt further to argue.

(If you want to do something else, I can't tell what it would be.)

nradov•3h ago
What advocacy argument? You're not making any sense and are just posting lazy, low-effort criticism. None of my claims require further substantiation, you can easily look up for yourself if you want to understand how the system works and the incentives involved.
mikeyouse•4h ago
Phase 3 trials don’t cost $1B - they’re more on the order of $20M.
nradov•3h ago
Sorry I should have been more specific. Average total cost to bring a new drug to market is on the order of $2B.

https://www.fiercebiotech.com/biotech/drug-development-cost-...

cogman10•3h ago
The NIH already creates grants for Phase 1 and Phase 2 trials. It's a bit insane that we don't also do phase 3 trials. Heck, even drug manufacturing is already done both by the DoD and the VA. It's crazy that we have a vision that private investment will somehow make things either cheaper, more affordable, or more available.

Big pharma is providing very little benefit and a lot of cost. We've seen their playbook with people like Martin Shkreli who'll buy up patents to existing drugs and jack up the price to make a quick buck. Do we really need that sort of "private investment"?

nradov•3h ago
I don't think anyone is seriously making the argument that private investment in drug development is making things cheaper or more available. So that's a strawman argument.

The primary claim in support of the current system is that it encourages greater levels of innovation than would happen under a socialized central planning system where government bureaucrats allocate funding for all trials. We don't have any solid evidence about that one way or the other. But year after year, US pharma companies do consistently release more new drugs than any other countries on a per-capita basis. We don't want to wreck that just because of high prices on a few patent protected drugs. Let's take a longer view and consider possible second-order effects before making any drastic changes.

cogman10•3h ago
> innovation than would happen under a socialized central planning system where government bureaucrats allocate funding for all trials.

What innovation? All the innovation with the current system happens outside the big pharma companies. They are merely swooping in at the final steps and manufacturing to benefit from the public investment.

The actual innovation is happening because of public social investment. Not because if private investment (at least in terms of medicine). Private investment here is simply leaching off of the public investment.

nradov•1h ago
You're ignoring second-order effects. While the big pharma companies do some original drug development themselves, they also commonly acquire start-ups which have promising drugs that aren't approved yet. This is tremendously risky because many of those drugs never get approved, or don't sell very well. Most of those start-ups would never have been founded in the first place if an acquisition wasn't possible.

If we want to have new a lot of new drugs every year that meet the FDA standard for being safe and effective then someone has to put in enormous capital investments. In theory I suppose we could raise taxes and socialize the whole system but so far I haven't seen any evidence that would be a net improvement. More likely just another opportunity for graft and corruption.

throwanem•3h ago
> I don't think anyone is seriously making the argument that private investment in drug development is making things cheaper or more available. So that's a strawman argument.

> The primary claim in support of the current system is that it encourages greater levels of innovation than would happen under a socialized central planning system where government bureaucrats allocate funding for all trials.

Oh, I see. You argue against the barely reanimated corpse of Nikita Khrushchev, in the breath after you accuse someone else of playing with a strawman.

Considering that I obviously disagree with the argument you've been trying to advance, I hope I can be forgiven some surprise at having presented so much stronger a formulation to argue against than you seem prepared to present in arguing for. Whom do you imagine yourself convincing in this way?

cogman10•2h ago
Meh, I'm fine with it. The general argument for capitalism is usually one of cost and market efficiency which is why I argue that doesn't happen with medicine.

But if you want to argue innovation instead, I see that as particularly worse in terms of medicine and science. Pure research is rarely profitable which is why you pretty rarely see it in an open marketplace.

It's not that it never happens. Obviously some research specifically targeted at manufacturing efficiency does happen as that will increase profits. However, outside of maybe semiconductors you'll almost never see a purely private institution invest in something like material sciences. More often than not, that research actually comes from something like the DoD contacting out to a defense agency trying to do better tank armor.

With medicine in the US, pretty much all innovation has come from public investment. The polio vaccine, for example, didn't come from a drug company, it came from a university researcher. That's the story of a large number of modern medicines.

A private company doesn't need or in some cases even want new medicines. Why would they want to make something that benefits 1/100000 of the population when something like insulin has a huge market and few competitors. Manufacturing new medicines for rare diseases isn't profitable, so why would they ever research it in the first place?

throwanem•2h ago
It is too specific an argument to be applicable here. Thalidomide was privately developed, as is the cancer miracle drug derivative of it, Revlimid or lenalidomide, discussed early in the article.

The argument is also not too well presented, in that it lacks grounding. For example:

> Why would [a pharma company] want to make something that benefits 1/100000 of the population when something like insulin has a huge market and few competitors?

Because insulin has a huge market and few competitors. That means they have defense in depth on pricing because their manufacturing will be highly specialized and high-throughput, else they could not continue to serve the market unless protected: someone would acquire them or shoulder them out. If you try to disrupt that incumbent, the same will happen to you; you'll be either acquihired, vivisected, or left to go bankrupt in peace for lack of anything novel enough to attract interest.

If, conversely, you can go to one person in every hundred thousand and offer them a pill that will make the difference between life and death - a pill that no one else, ideally, can possibly sell them - well, what can't you ask in return? The traditional rate I understand to have been in the order of one to ten firstborn sons and heirs.

We do things differently now, of course, or less overtly at least. But the business case when considered amorally, as any of that species must be to be understood on its own terms, is trivially clear. The discussion you really want to have is that of whether income inequality can and must be allowed to dictate even partially the dimensions of a human life, versus whether that can and must be prevented. I'm not going to pretend I could summarize the state of the field on that one, which has much older names even than "theodicy."

cogman10•2h ago
A fair point, but I'd point out that the research which showed revlimid was a well tolerated cancer medicine didn't happen because of private investment, but rather public NIH grants and funding. The lead author that ran the trials wasn't a pharma employee, but rather a staff member of a cancer research institution.

If someone is going to find that Benadryl can treat a new disease, it won't be a pharma company.

throwanem•1h ago
A fair point, indeed. Now we reach the question in a way that anyone can follow: if the cost of development is already sunk, and the cost of discovery is publicly defrayed, then what justifies these absurd revenue multiples of development cost when they come at a price measurable in human suffering and death? In what way is this not sheer price gouging of a particularly vicious kind?

That's the sort of question folks like my prior interlocutor, who appears now to have abandoned the effort, really don't want to answer. And no wonder! There's no way for them to do so while maintaining the usual comfortable abstraction over the essential bloodthirstiness of their philosophy.

SAI_Peregrinus•2h ago
"How can we lower the cost of phase 3 clinical trials without allowing non-functional medication (scams) to proliferate" is very important. The point of a phase 3 trial is to prove that a medication treats what it claims to treat.
tough•4h ago
the argument might be, the more profits the pharma's make, the more available cash to buy out poltiicians or create SuperPAC's or whatever they have at hand..

America, the land of the dollar

ricksunny•3h ago
>America, the land of the dollar

Correction: America, the land of the rent-seeking.

bschne•3h ago
2024 numbers -- Selling, General & Admin vs. R&D

Roche (Pharma Division): 7533 MCHF vs. 11096 MCHF

Novartis: 12566 MUSD vs. 10022 MUSD

Pfizer: 14730 MUSD vs. 10822 MUSD

Eli Lilly: 8594 MUSD vs. 10991 MUSD

AstraZeneca: 19977 MUSD vs. 13583 MUSD

Johnson & Johnson: 22869 MUSD vs. 17232 MUSD

The left side here contains more than just marketing, and already "far far outstripping" seems like a mischaracterization.

For comparison, the average R&D spend between these firms is bigger than the 2024 NSF budget (~9bn) and bigger than 1/4 of the 2024 NIH budget (~37bn).

dgacmu•2h ago
I think you meant to say NIH for the second budget number?
bschne•2h ago
correct, edited, thanks
derektank•1h ago
Also worth considering that this only includes internal R&D, not R&D acquired through acquisition of smaller biotech firms (known as in process R&D). VC investment in biotech startups is, at least in part, built around the assumption that acquisition by a larger pharmaceutical company is a viable exit strategy. To take the example of Eli Lilly, I think they spent an additional 10-20% of their R&D budget on IPR&D in 2024, though this obviously can fluctuate more year to year. They acquired Morphic, which produces a pharmaceutical that treats IBS, and Scorpion Therapeutics, which produces a precision oncology treatment, this year and I'm guessing neither spent much on consumer sales.
tptacek•2h ago
That's part of it, but pharma is also a portfolio business, like VC or music; the winners have to pay for the losers.

(I don't know how much that matters in this case, where a tiny company lucked into a blockbuster and then used every lever in the system to protect their exclusivity).

throwanem•1h ago
Yeah, nobody serious is really arguing the winners shouldn't pay for the losers. How many times over, though?
tptacek•59m ago
I sort of don't care, as long as investor value isn't being protected abusively, by anticompetitive schemes with the patent system and exclusivity. We pay lots of money for all sorts of things, most of which don't actually matter to our lives; pharmaceuticals matter a great deal, and I'm OK with the idea that advancements are incentivized by a time-limited lane for nosebleed pricing.

(Pharmaceutical costs, all in, across the board, are a relatively small component of total health spending in the US. They're not why your health insurance is so expensive.)

This is mostly a story about anticompetitive abuses, so that question isn't super relevant to the story. I'm just answering the claim that invisible marketing/SG&A costs are why drugs cost so much. They also cost a lot because most drugs fail, sometimes after billions invested.

leereeves•4h ago
> This extends (usually by implication) to trivial variations in molecular chemistry which have no functional effect on a medication but which are used to extend patent protections solely on the basis of a structural change

How does that work? Does it extend patent protection on the original molecule? Or if not, what stops generic copies of the original version?

throwanem•4h ago
I found a menu. https://www.obrienpatents.com/extending-life-patents-pharmac...
jmward01•2h ago
This is trickle down economics for healthcare. It is stupid. No, it is worse than that, it is evil.
photochemsyn•3h ago
Bayh-Dole legislation in the 1990s allowed universities to exclusively license researcher inventions to private parties. Hence:

> "Celgene had acquired the rights to thalidomide patents held by researchers at Rockefeller University in 1992."

Change Bayh-Dole law to non-exclusive licensing, but with some level of royalties paid to institution that originated the patent, and other corporations could have made the drug - and it would be a competitive market, so costs would drop due to lack of a monopoly on the drug.

This one simple change to Bayh-Dole - 'non-exclusive' - would upset the academic-corporate apple cart well beyond pharmaceuticals. Eg the PageRank algorithm created at Stanford could not have been exclusive licensed to Google - any American corporation or person could have applied for a license to the invention, entirely erasing the benefits of a monopolistic patent to the corporation.

One great benefit of this change is that corporations who wanted exclusive patents would have to finance their own private R & D divisions, instead of just capturing the output of taxpayer-financed researchers.

y-curious•4h ago
It makes me wonder, is there a way to get this drug from a Chinese or Indian lab? I'm sure there are severe legal repercussions, but purely theoretically. It reminds me of the film The Dallas Buyers' Club
the_pwner224•2h ago
Yes, it's readily available to buy online from India for <$1/pill.

In practice there aren't legal repercussions. If you import scheduled drugs (adderall, opioids, etc.) and get caught that's obviously going to be a big issue. But with most prescription medications, the worst case scenario is that Customs will just toss your package. And the likelihood of that is low; the majority of the time it makes it through undetected.

I've done this in the past with another drug. In the US it was $30/month but from India I got 1000 pills for $30 + $40 expedited shipping. For me the big factor wasn't cost, but rather the convenience of not needing to go through the process of getting a prescription.

imperfect_light•16m ago
How do you know you're actually getting what you bought?
csours•4h ago
Remember the time that Florida fought the federal government for access to socialized medicine?

https://www.flgov.com/eog/news/press/2024/florida-becomes-fi...

> "Today, the DeSantis administration received U.S. Food and Drug Administration (FDA) approval of its Canadian Prescription Drug Importation Program. The Agency for Health Care Administration (AHCA) submitted this first-of-its-kind plan to safely import cheaper drugs from Canada to the FDA nearly 37 months ago, and after filing a lawsuit against the FDA due to delays, has finally received approval. This approval will save Florida up to $180 million in the first year."

eterm•3h ago
> But Revlimid is also, I soon learned, extraordinarily expensive, costing nearly $1,000 for each daily pill.

Thanks to the bargaining power of my nationalised healthcare, my government pays around 1/5th of that, and I'll pay nothing myself.

Revlamid is listed under it's generic name Lenalidomide, price is in pence: https://www.drugtariff.nhsbsa.nhs.uk/#/00791628-DD/DD0079145...

jonplackett•1h ago
Even that is still an obscene amount if money for something that cost 20p per pill.
tptacek•22m ago
The manufacturing cost of a 20p pill has literally nothing to do with its price.
pstuart•1h ago
So $200/pill for something that costs them $0.25 to make. That's still obscene.
thrance•49m ago
Which is why there should be no patents in healthcare. Most research is already publicly-funded, production and distribution should be too. We could drown in cheap medicine, instead we artificially increase the prices by 5000% to fatten the pockets of already super-wealthy parasites.
tptacek•20m ago
Are you thinking this through? It costs billions of dollars to bring a new drug to market --- before sales, admin, and marketing costs --- and most attempts to bring drugs to market fail. In the very best case for the public, the drugs are incredibly cheap to manufacture; that's an achievement for a pharma company. Do you see how the incentives work here?
thrance•4m ago
Are you arguing this can't be achieved by the public sector too? Or that pharma companies don't make obscene margins?
Lalo-ATX•19m ago
the way I'd look at is what's the return-on-capital for pharmaceuticals as a whole.

Generally I think (this is highly subjective and irrational, of course) that I'd be comfortable with a 10%-20% return-on-capital overall. Lower than that and I'd think that risky drugs couldn't get funding; higher and I'd think there's too much rent-seeking.

Perhaps some economists have studied what an optimal ROC might be for pharmaceuticals.

In any case, the gross margin per-pill doesn't really tell you anything about ROC. 99.875% is astounding, but what was invested to get to that point - including the drugs that never made it to market?

comrade1234•2h ago
My wife’s company developed a multiple myeloma immunotherapy that is for people that have had previous treatments of other drugs but then go into remission.

It works so well that their efficacy reports have caveats like “not enough patients that were treated have died yet” to provide meaningful statistics.

The drug was initially developed in china. They presented results at a conference in the USA but no one believed them other than a skeptical Pfizer who sent a big team to china to confirm the data. Pfizer soon invested billions into the company and drug to bring it to market.

The drug’s sales are on track to be $1 billion this year but the stock is heavily depressed because of the china connection.

foundry27•43m ago
What kind of focus do biopharma companies put on their stock prices? If a company like the one you described had a great treatment option that could genuinely help people and was raking in money by the boatload, is that “enough” for them as a “winning” business strategy regardless of how outside investors might perceive it?
comrade1234•39m ago
It leaves them vulnerable to takeover, for one. They have over $1B cash right now to pay for clinical trials in other markets as well as new indications but their valuation is about 5x that. Someone could leverage the $1B as part of a hostile takeover.
A_D_E_P_T•1h ago
> But Revlimid is also, I soon learned, extraordinarily expensive, costing nearly $1,000 for each daily pill. (Although, I later discovered, a capsule costs just 25 cents to make.)

That daily pill is 25mg. You can buy 5g of Revlimid's active ingredient for $352.

> https://www.sigmaaldrich.com/US/en/product/aldrich/901558

200 doses at less than $2/ea.

If you want to get adventurous, you can probably buy 1kg from China or India for $900. Find a university or commercial lab with HPLC and LC/MS and run your own QC for a few hundred bucks. Store the powder in a vacuum-sealed container in a refrigerator. You're set for life.

I've done this sort of thing before, and a lot of people are doing it for GLP agonist drugs. (To say nothing of sports doping, nootropics, etc.)

Sometimes you've gotta take matters into your own hands.

collingreen•15m ago
We agree that, while it's nice this is an OPTION, it's a crazy state of affairs, right? I'm tired of the phrase "free market" since it isn't really either of those words.
est31•29m ago
There is some light at the end of the tunnel. I suppose the patent runs out early next year, as the drug was released in 2005 and the generic which is already available but volume limited also has that volume limitation until January 31, 2026. The press release formulates this as if Celgene did this out of graciousness but I suppose it's just that the government granted monopoly ends.

https://web.archive.org/web/20220811173542/https://ir.celgen...

> Celgene has agreed to provide Alvogen with a license to Celgene’s patents required to manufacture and sell an unlimited quantity of generic lenalidomide in the United States beginning no earlier than January 31, 2026.