I'd argue the reason we’ve spun our wheels on Alzheimer's for decades isn't just about a flawed amyloid model. It’s a symptom of a much larger, dying paradigm in biotech.
For decades, the industry standard was to hunt for targeted small molecules to solve singular biological issues. And to be fair, I don't think this was because of a lack of vision as it was simply the strict limit of our technological capabilities at the time. But attempting to treat a cascading, systemic disease like Alzheimer's with a single targeted molecule is like hoping replacing one pipe will solve the problem when the issue is that the entire plumbing system is corroding.
This fundamental mismatch is exactly why clinical progress has stalled, and I believe the future of treating Alzheimer's will instead closely mirror how our approach to oncology has evolved.
We spent years searching for a universal molecule to cure cancer before we accepted reality. We now know that effective treatment often requires sequencing a tumor's mutanome to develop a highly personalized intervention for the individual. As neurodegenerative systems fail with age, we face that exact same biological complexity. A traditional small molecule is not going to rescue a globally failing network.
My personal take is that we won't see a true breakthrough in Alzheimer's until capital fully rotates out of these legacy, single-target pipelines and into programmable biological systems.
What Andreessen is hinting at, albeit still largely surface level, is 无心 or no mind.
Popular in martial arts and Buddhist philosophy, I think practically what you should take away is that body and mind are fundamentally intertwined.
Introspection is a practice of the mind, specifically cognition centered around portions of the brain like the prefrontal cortex. There’s a lot more to who you are and areas you can hone / cultivate.
We’re going to see all talk of AI 2027 quietly disappear as folks realize how out-of-touch with reality it is. I have no idea why people take that crap seriously.
This piece totally misreads the temperament of actual builders imo. The author confuses a malicious will to power with a genuine, if sometimes naive, optimism that code/crypto can solve human coordination problems.
I think both things can be true simultaneously. Like in the Russian Revolution, there can be a mass of people motivated by a sincere, if naive, optimism in a new way to organize society, but they can get used by people like Lenin and Stalin who were primarily motivated by their thirst for power.
Although that may be a lack of historical knowledge on my part, Lenin does not strike me as suffering from a thirst of power but as sincere ideologue (in rare combination with a good dose of pragmatism, see his critique and later repression of "leftists" and his adoption of the NEP)
But that "pragmatism" as you put it is exactly my point. A true ideologue would have realized the revolutionaries in Kronstadt had created a system more in line with the ideals of the revolution than what he had created and woouldn't have set the army out to destroy them. nor would he have introduced the NEP (basically a limited re-introduction of capitalism to save the faltering Soviet economy). In the end, the important thing to Lenin was Lenin -- not any ideology.
For decades, the industry standard was to hunt for targeted small molecules to solve singular biological issues. And to be fair, I don't think this was because of a lack of vision as it was simply the strict limit of our technological capabilities at the time. But attempting to treat a cascading, systemic disease like Alzheimer's with a single targeted molecule is like hoping replacing one pipe will solve the problem when the issue is that the entire plumbing system is corroding.
This fundamental mismatch is exactly why clinical progress has stalled, and I believe the future of treating Alzheimer's will instead closely mirror how our approach to oncology has evolved.
We spent years searching for a universal molecule to cure cancer before we accepted reality. We now know that effective treatment often requires sequencing a tumor's mutanome to develop a highly personalized intervention for the individual. As neurodegenerative systems fail with age, we face that exact same biological complexity. A traditional small molecule is not going to rescue a globally failing network.
My personal take is that we won't see a true breakthrough in Alzheimer's until capital fully rotates out of these legacy, single-target pipelines and into programmable biological systems.
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