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Life After Eroom’s Law

refoundable.com

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Re: Life After Eroom’s Law

#31

Post by MichaelZuo »

refoundable wrote: post #28
bfieidhbrjr wrote: post #24

Earlier quoted context omitted.

Well, are you aware that the common model of cancer (genetic) is almost certainly wrong? And that we've wasted 50+ years, and something like an infinite amount of money on it? https://www.amazon.com/Cancer-Metabolic-Disease-Management-P... https://www.amazon.com/Tripping-over-Truth-Overturning-Entre...

It's worth noting that the most effectives breakthroughs against cancer in recent decades (Immunotherapy, angiogenesis-suppressing drugs) have largely been based on ideas that were first dismissed and widely ridiculed by senior scientists working on cancer research. I suspect that in another 50 years, when the war against cancer is (finally) over, we will end up with a completely different perspective on the history…

Just how radical were these ideas you speak of from the accepted dogma?

Re: Life After Eroom’s Law

#32

Post by refoundable »

titanomachy wrote: post #30
beloch wrote: post #29

Earlier quoted context omitted.

The way your website handles font-size and zoom is really weird.

I feel like there should be a named law of hacker news for this. There's sometimes more discussion about how the page doesn't work without javascript, font colors are bad, page is slow, whatever, than about the content of the article. Although in this case most people are talking about the article. Agreed though, there's some weird responsive CSS going on here that makes it impossible to resize fonts on a desktop.

I echo both observations and urge you to name that law.

Will look under the hood at the CSS.

Re: Life After Eroom’s Law

#33

Post by andrewjl »

refoundable wrote: post #8

Author here. I interviewed Jack Scannell on the hypothesis that the man who wrote the now famous paper on Eroom's law would likely have many more insights to offer that didn't necessarily make it into print. One of the oddest things about biotech and pharma is that cures trail improvement in technology by at least a couple of decades. That's terrible news if you're a patient/consumer though maybe great news if you're…

The article mentions poor incentive structure around development of better disease models as an obstacle for some of the drug categories, is that an area where either the federal govt or the industry as a whole can step in and develop a collective solution?

Re: Life After Eroom’s Law

#34

Post by refoundable »

MichaelZuo wrote: post #31
refoundable wrote: post #28

Earlier quoted context omitted.

It's worth noting that the most effectives breakthroughs against cancer in recent decades (Immunotherapy, angiogenesis-suppressing drugs) have largely been based on ideas that were first dismissed and widely ridiculed by senior scientists working on cancer research. I suspect that in another 50 years, when the war against cancer is (finally) over, we will end up with a completely different perspective on the history…

Just how radical were these ideas you speak of from the accepted dogma?

On angiogenesis, see Judah Folkman: https://www.tobinproject.org/about/judah-folkman

On cancer immunotherapy, see Fran Visco's story as partially told by Daniel Sarewitz (section titled "War on Cancer"): https://www.thenewatlantis.com/publications/saving-science

Re: Life After Eroom’s Law

#35

Post by refoundable »

Dysseus wrote: post #23
refoundable wrote: post #16

Earlier quoted context omitted.

The FDA does not allow Pharma companies to create safe and slightly less effective drugs than the best-in-class, even if such drugs were 10-100x cheaper and would thus alleviate most people's complaints about outrageous drug prices. Scannell's observations are focused on the problem of finding drugs that are more effective than the current best-in-class, the so-called Better than the Beatles problem. This turns out t…

First, really appreciate the engagement here. This is a hugely important problem and this interview and your presentation of it is a great contribution. I think one of the things that gets lost when we talk about Eroom's law is that the original data points were established before congress passed the Kefauver-Harris amendments in 1962 which set standards for clinical trials, iNDA process, and basically required that…

No disagreement on the skewed stats. And I won't dispute the need for a minimum standard of efficacy.

However, if anything, the problem that we've had over the last 60 years is setting the standard of efficacy too high. This caused the Better than the Beatles problem, and placed Pharma companies in an impossible situation where they have to run faster and faster just to stay in the same place.

Moving forward, if we're not going to lower the efficacy standard, then the questions that Scannell raises about model validity and the search problem writ large become even more pressing and important.

On the other hand, if we're not going to solve the search problem, then the pragmatic solution would be to lower the efficacy bar somewhat so Pharma companies can at least create slightly less effective but way cheaper drugs.

In theory, we should be able to do both. In practice, we're likely to get one way before the other. The current path we're on of fewer drugs and higher prices is simply unsustainable.

Re: Life After Eroom’s Law

#36

Post by refoundable »

andrewjl wrote: post #33
refoundable wrote: post #8

Author here. I interviewed Jack Scannell on the hypothesis that the man who wrote the now famous paper on Eroom's law would likely have many more insights to offer that didn't necessarily make it into print. One of the oddest things about biotech and pharma is that cures trail improvement in technology by at least a couple of decades. That's terrible news if you're a patient/consumer though maybe great news if you're…

The article mentions poor incentive structure around development of better disease models as an obstacle for some of the drug categories, is that an area where either the federal govt or the industry as a whole can step in and develop a collective solution?

That's certainly what's implied by Scannell's answer to Question 8, but such a solution comes with its own set of limitations related to design by committee.

Small startup teams are still the most effective way to solve hard problems in our society, and so I suspect that any definitive solution would likely be built and sold to the industry by such a team.

Re: Life After Eroom’s Law

#37

Post by jhayward »

refoundable wrote: post #32
titanomachy wrote: post #30

Earlier quoted context omitted.

I feel like there should be a named law of hacker news for this. There's sometimes more discussion about how the page doesn't work without javascript, font colors are bad, page is slow, whatever, than about the content of the article. Although in this case most people are talking about the article. Agreed though, there's some weird responsive CSS going on here that makes it impossible to resize fonts on a desktop.

I echo both observations and urge you to name that law. Will look under the hood at the CSS.

Thanks for looking. I use the "zoom" feature of Chrome to make fonts more readable. The CSS on this page does not permit resizing of the type - a major faux pas for accessibility.

This is a fascinating article, and is even better with the conversation here added. Thanks for your efforts.

Re: Life After Eroom’s Law

#38

Post by eganp »

refoundable wrote: post #8

Author here. I interviewed Jack Scannell on the hypothesis that the man who wrote the now famous paper on Eroom's law would likely have many more insights to offer that didn't necessarily make it into print. One of the oddest things about biotech and pharma is that cures trail improvement in technology by at least a couple of decades. That's terrible news if you're a patient/consumer though maybe great news if you're…

Hey refoundable - great interview! Love Jack's characterization of Alzheimers as chemical roulette.

Just wanted to let you know there's a typo in your first figure. "Thalyidamide" should be "thalidomide" [0]. It's also been sold as Thalomid.

[0] https://en.wikipedia.org/wiki/Thalidomide

Re: Life After Eroom’s Law

#39

Post by eganp »

contravariant wrote: post #21

The current Covid-19 vaccine seems a crucial example of how important model validity can be. The mod-mRNA vaccines can apparently be created in a matter of hours and validated on animal subjects within days/weeks, yet it has taken us almost a year with extensive testing to be sure it will work and be safe. And even that is considered a record breaking time. It cannot be overstated how big an advancement in medical sc…

It's a tough lift to demonstrate that all such modified-mRNA vaccines are safe and likely effective. This trial is a good validation of off-target safety, and that's a huge achievement. However, you still have on-target safety concerns (e.g. cross reactivity). Then, for each pathogen, the selected antigen expressed needs to 1. generate an antibody response and 2. provide protection from infection.

Antibody titers can de-risk 1 pretty effectively. But, without human challenge trials, you're stuck waiting for nature to test 2. Even using non-human primates as the model to test infection has many pitfalls as the species barrier is often strong with infectious diseases. Human immunology is often idiosyncratic when compared with closely related primates.

Re: Life After Eroom’s Law

#40

Post by MichaelZuo »

refoundable wrote: post #34
MichaelZuo wrote: post #31

Earlier quoted context omitted.

Just how radical were these ideas you speak of from the accepted dogma?

On angiogenesis, see Judah Folkman: https://www.tobinproject.org/about/judah-folkman On cancer immunotherapy, see Fran Visco's story as partially told by Daniel Sarewitz (section titled "War on Cancer"): https://www.thenewatlantis.com/publications/saving-science

Thanks! They certainly like very illuminating insights. From my viewpoint epigenetics seems like the forerunner to many future revelations too.
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