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Charles Fain Lehman Newsletter
The the words it uses that this site has seen least often elsewhere. Posts are matched on those words alone — nothing here is a summary of this one.
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21 September
19 September
13 September
12 September
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Their words
This is the first time a debate over whether a model ‘was AGI’ felt non-silly. I do not think it is AGI, and I would warn against the dangers of using that label prematurely, but I would not laugh at you for disagreeing.
11 September
10 September
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Their words
I put the probability of complete extinction as being so low it isn't worth discussing, but the probabilities of AI caused disasters - e.g. cyber attacks on critical infrastructure or bio-risks - as being worth debating.
5 September
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Their words
We can’t count on surrogate blood markers to guide the results of cardiovascular clinical outcome trials.
The Coronary Artery Inflammation Controversyerictopol.substack.com
3 September
2 September
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Their words
You definitely will NOT get a body you see on fitness Instagram or in Hollywood 99% of those people are on gear and not natty!
31 August
27 August
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korrents.com
Killing suspected drug smugglers at sea without trial is murder, because smuggling is not a capital offence.Their words
Even if it turned out that they were drug smugglers, as claimed, and even if it turned out that they were bringing drugs to the United States, a dubious proposition, the penalty for smuggling drugs is not summary execution.
25 August
24 August
20 August
From one piece From Restoring Sight to Reimagining the Brain, with Max Hodak 3 beliefs, in the piece's order there
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korrents.com
Humanity is not good enough at molecular biology to make drugs that restore vision or hearing or stop Parkinson's.Their words
People have spent huge amounts of time and money looking for drugs to restore vision or to restore hearing or to stop Parkinson's or to to help paralyzed people move again. Understanding the like the biology and the molecular detail required to make a drug has been very difficult. Humanity just isn't that good at that, to be totally honest.
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Their words
Yeah, I mean I think BCI is a category kind of like how pharma is a category. I think sometimes you I I'll talk to VCs and like, "Oh, we have a BCI bet." I'm like, "Do you have a drug bet? You made one bet on a drugs? Like that's that's how you think about the category?"
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korrents.com
Putting a device into the brain works in an hour, which makes it far more amenable to biology than drug discovery.Their words
It's like if I put electrodes in M1, you will probably be using a computer in an hour. Um and so it's just it's easier, it's more amenable to biology in many ways.
17 August
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Their words
open models are still incredibly useful, but fill a long-tail ecosystem relative to the closed counterparts that have monopoly ownership stakes in the most valuable areas like knowledge work collaboration, drug discovery, SWE, etc.
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Lovedrcmnd.app
Music Copyright, Creativity, and CultureTheir words
Jenkins understands it, though. I've been reading, writing, and debating about this stuff since the late 1990s, and I learned something new on every page of this delightful book.
12 August
10 August
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korrents.com
Developers today mostly plan, debate, implement and review with AI agents rather than write code themselves.Their words
Nobody writes the code anymore. Instead you're basically planning, debating, implementing and reviewing with Agents.
7 August
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Their words
It gives you these effect sizes that you just don't really see in medicine. Like if you have a patient on on a dopamineergic drug for Parkinson's that works for some period of time, but it's a it's a relatively small effect after a little while. You turn on a deep brain stimulator and a patient goes from not being able to hold a cup of water to being able to write cursive in like 10 seconds.
6 August
29 July
21 July
From one piece Intelligence is not the main bottleneck 4 beliefs, in the piece's order there
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korrents.com
Drug companies pile onto the same few already-validated targets, so far less of biology gets explored than could be.Their words
In biomedicine we have a problem called target herding: most companies chase the same biological targets because they are de-risked, which means we explore far less of the biological space than we could.
Intelligence is not the main bottleneckwritingruxandrabio.com
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Their words
That is mostly in the realm of chemistry and is intrinsically far more tractable and predictable; given a validated target, good teams usually reach a decent molecule.
Intelligence is not the main bottleneckwritingruxandrabio.com
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Their words
The patent system then further disincentivizes companies from taking target risk, because it rewards novel chemical matter, not novel biology.
Intelligence is not the main bottleneckwritingruxandrabio.com
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Their words
Take Eroom’s Law: the number of new drugs approved per dollar of R&D has fallen for decades, even as our scientific tools have grown vastly more powerful, the exact opposite of what the existence of more raw capability would predict.
Intelligence is not the main bottleneckwritingruxandrabio.com
13 July
From one piece The Black Markets Fallacy 2 beliefs, in the piece's order there
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Their words
What’s fallacious is to argue that this fact necessarily means the prohibition does not “work,” or is not better than legalization.
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korrents.com
Prohibition reduces how much of a product is consumed rather than merely moving the same consumption underground.Their words
Quantity consumed under prohibition is almost always smaller than quantity consumed under legalization.
8 July
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korrents.com
Recorded crime partly measures policing: a neighbourhood policed harder produces more crime in the statistics.Their words
Particularly with gun and drug crimes, communities with more aggressive policing tend to produce more crimes in part because law enforcement polices them more aggressively.
A guide to racism in the criminal justice systemradleybalko.substack.com
4 July
From one piece Metformin and cancer: active surveillance needed 3 beliefs, in the piece's order there
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korrents.com
Metformin is not a general-purpose anti-cancer or anti-ageing drug, and healthy people should not take it as one.Their words
MAST adds to a growing body of evidence suggesting that metformin is not a general-purpose anticancer drug.
Metformin and cancer: active surveillance neededpeterattiamd.com
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Their words
we now have multiple trials confirming that metformin interferes with your ability to reap the adaptive benefits of exercise, which is the most powerful broad-based longevity intervention available to us today
Metformin and cancer: active surveillance neededpeterattiamd.com
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Their words
That’s a lesson we could all learn about our approach to supplements and even drugs: not to fall for hazy promises that a single molecule will deliver vaguely-defined benefits for all aging persons, but to demand rigorous evidence for well-defined benefits for well-defined problems in well-defined populations.
Metformin and cancer: active surveillance neededpeterattiamd.com
30 June
27 June
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Their words
These failures are a strong signal that HDL-C is not the variable we should be trying to manipulate.
20 June
13 April
28 February
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Their words
Trials serve two distinct functions: validation — confirming whether a drug works and is safe — and learning, or generating biological data to refine our understanding of a disease, a compound, and the relationship between the two.
21 January
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Their words
Sleep – high quality sleep is the world’s #1 longevity drug.
17 January
29 November 2025
9 November 2025
19 September 2025
From one piece Norman Ohler: Hitler, Nazis, Drugs, WW2, Blitzkrieg, LSD, MKUltra & CIA | Lex Fridman Podcast #481 5 beliefs, in the piece's order there
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Their words
So the Navy hired the shoe runners unit from the SS, paid them money, and then gave them drugs, different kinds of drug combinations, methamphetamine combined with cocaine and chewing gum and all kinds of things. So this is a big thing, you know. And there are documents to it.
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korrents.com
The Neanderthals lost to us because they had no drug culture — they were too sober for the future.Their words
And I think, a lot of evidence kind of points to it that we were able to develop our consciousness in a better way than the Neanderthals, who did not have a drug culture. They were basically too sober for the future. We assimilated them.
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korrents.com
LSD is not a truth drug and never could be — it takes you toward your own truth, not out of it.Their words
They miserably failed because LSD… Is not the truth drug. LSD maybe leads you closer to your own truth, because when suddenly the default mode network receives less energy and other parts of the brain think more, and the neuroplasticity of the brain is enhanced and stimulated, you might understand something about your life.
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korrents.com
An entire army was prescribed methamphetamine by written decree, with dosages, intervals and side effects specified.Their words
And he gave lectures in front of the officers, and he wrote a stimulant decree where a whole army is prescribed a drug, in this case methamphetamine. How much should be taken? At what intervals? What are the side effects?
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Their words
One thing that changed was that Eukodal was not available anymore, so the drug that Hitler actually had become physically addicted to was suddenly not available anymore. This had to do with the bombardment of the Merck company, the factory in December 1944. British bombers destroyed the production facilities.
11 June 2025
28 May 2025
From one piece What Was The War on Drugs? Part V 2 beliefs, in the piece's order there
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korrents.com
Drug enforcement cut casual use and barely touched heavy users, who account for most of the drugs consumed.Their words
But by the available evidence, the War on Drugs was far less successful at reducing use among the “hard core” of users, mostly meaning people addicted to their drug of choice.
What Was The War on Drugs? Part Vthecausalfallacy.substack.com
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Their words
Drug offenders never accounted for a particularly large fraction of the U.S. prison population, peaking at about 22 percent of state prisoners in 1990.
What Was The War on Drugs? Part Vthecausalfallacy.substack.com
20 October 2024
17 September 2024
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Their words
Another challenge for Class II biotechs is that even if you have a nifty computational drug discovery platform, you are still often bottlenecked by the rest of the drug development process. It takes 1,000 (or more!) small steps to advance a drug through discovery, development, and past the regulators.
23 December 2023
From one piece The pharma industry from Paul Janssen to today: why drugs got harder to develop and what we can do about it 4 beliefs, in the piece's order there
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Their words
Because patents have fixed term lengths, with small extensions to compensate for the year or so when the drug is under regulatory review, drug developers are incentivized to go after conditions where clinical trials can be completed quickly, all else being equal.
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Their words
Biology is unpredictable, especially when the immune system is involved, and there is no guarantee that a drug that appears safe in animals will be safe in humans.
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Their words
The most significant factor preventing us from taking better molecules into clinical trials is not our ability to design arbitrary molecules, but our (lack of) understanding of underlying disease biology. In other words, we often know how to make something, but not what to make.
+ 1 more
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Their words
In reality, the productivity crisis in the pharmaceutical industry is the culmination of decades of just about every aspect of drug discovery and development getting gradually harder and more expensive.
30 October 2023
1 October 2023
25 May 2023
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Their words
But we do not have enough data and we do not have enough insight to use AI/ML to pick better targets that have a higher chance of succeeding in the clinic.
9 July 2021
28 October 2020
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Likedaffiliate linkrcmnd.app
DecodedTheir words
Decoded is a semi-autobiographical book that tells Jay-Z's story growing up and finding success in hip hop. It also helps you deeply understand the inner-city ghetto struggles (Jay was actually a drug dealer until age 27). In organized sections of hand picked songs with RapGenius-style lyric explanations (note: Decoded came first), you see through his eyes the difficult choices he and so many others faced while listening to some of his best tracks.
1 May 2020
From one piece Why Are Clinical Trials So Complicated? 2 beliefs, in the piece's order there
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Their words
You cannot wing it when you're giving a drug to human beings.
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Their words
The procedures that have grown up around drug development are a sort of Chesterton's Fence: we shouldn't pull them down without considering the reasons why they were put up.
15 March 2020
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