I drink about 400mg of caffeine daily through coffee and Coke Zero. It helps me process complex ideas quickly, consider alternatives, and lifts my mood.

Without it, I get frustrated when I can’t follow arguments or understand ideas, often rejecting them or settling for “good enough.” Caffeine gives me the clarity and energy to stay open to new ideas and better solutions.

Stable is not a virtue, nor is our equilibrium well-tolerated. The problems it causes in terms of health, cost and homelessness are central political issues and have been for a long time.

I also have no idea why you assume I’m “ignoring” these “lessons” you’re handwaving at. It’s a pretty annoying rhetorical move.

and yet it's legally just as intolerable for an intoxicated person to harm others as it would be for a sober person to take the same actions

Even America hasn't been able to solve drug abuse with negative consequences. My hope is mainly on GLP-1 agonists (or other treatments) proving super-effective against chemical dependence, and increasing their supply and quality over time.

I recommend making the title time-specific, since all the predictions you’re basing your estimate on are as well.

I think it’s wise to assume Sam’s public projection of short timelines does not reflect private evidence or careful calibration. He’s a known deceiver, with exquisite political instincts, eloquent, and it’s his job to be bullish and keep the money and hype flowing and the talent incoming. One’s analysis of his words should begin with “what reaction is he trying to elicit from people like me, and how is he doing it?”

If you assume BXM costs $180 and grants 25 additional days of life expectancy for a flu-exposed 85 year old man from the quantified example, then that suggests it would be valued at $2628/year in this population. Probably one year with comorbidities at 85 is not one QALY, but still I have to imagine that's drastically above the threshold for US medicine, albeit nowhere close to the cost-effectiveness of the most effective global health charities from a utilitarian perspective.

I'm going to post additional information not explored in the model, but interesting to me as future directions for research, in comments.

Drug resistance can be studied in viral kinetics/dynamics studies. These studies focus on two aspects of viral biology:

• Mutations vs. drug resistance
• Mutations vs. replication efficiency

One in vitro study found some baloxavir-resistant strains are generally less efficient at replication than wild type, though that's not a universal for all contexts/viruses/cell types/metrics. Also, these studies typically control the genome of the virus, whereas in the wild, viruses can develop compensating mutations for the decreased fitness induced by the resistance-conferring mutation.

The mutations linked to resistance are currently rare (<1%) in flu patients. This study measured resistance in terms of cell death +/- baloxavir and viral yield +/- baloxavir at different concentrations of drug and different strain mixtures. In some cases, only small fractions of resistant strains were needed to reduce susceptibility. I'm curious if this may be because the resistant proteins are being "shared" among the population of resistant and non-resistant viruses in the cell, but don't have enough knowledge of influenza biology to know if that's plausible.

There are a whole bunch of interesting looking in vitro studies on various drugs/strains/cell types.

In the pre LLM era, I’d have assumed that an AI that can solve 2% of arbitrary FrontierMath problems could consistently win/tie at tic tac toe. Knowing this isn’t the case is interesting. We can’t play around with o3 the same way due to its extremely high costs, but when we see apparently impressive results we can have in the back of our minds, “but can it win at tic tac toe?”

I upvoted for the novelty of a rationalist trying a bounty based career. But also this halfway reads as an advertisement for your life coaching service. I wouldn’t want to see much more in that direction.

Miles Brundage: Trying to imagine aspirin company CEOs signing an open letter saying “we’re worried that aspirin might cause an infection that kills everyone on earth – not sure of the solution” and journalists being like “they’re just trying to sell more aspirin.”

It seems more like AI being pattern-matched to the supplements industry.

• Marketed as performance/productivity-enhancing
• Qualitative anecdotes + suspect quantitative metrics
• Unregulated industry full of hype + money
• Products all seem pretty similar to newcomers, aficionados claim huge differences but don't all agree with each other
• Striver-coded
• Weakens correlation between innate human capability and measured individual performance