DirectedEvolution

Karma: 11,112

Pandemic Prediction Checklist: H5N1

Pandemic Prediction Checklist: Monkeypox

Correlation may imply some sort of causal link.

For guessing its direction, simple models help you think.

Controlled experiments, if they are well beyond the brink

Of .05 significance will make your unknowns shrink.

Replications show there’s something new under the sun.

Did one cause the other? Did the other cause the one?

Are they both controlled by what has already begun?

Or was it their coincidence that caused it to be done?

DirectedEvolution 2 Mar 2025 17:07 UTC
17 points
0
in reply to: Alexander Gietelink Oldenziel’s comment on: Alexander Gietelink Oldenziel’s Shortform
My partner has ADHD. She and I talk about it often because I don’t, and understanding and coordinating with each other takes a lot of work.

Her environment is a strong influence on what tasks she considers and chooses. If she notices a weed in the garden walking from the car to the front door, she can get caught up for hours weeding before she makes it into the house. If she’s in her home office trying to work from home and notices something to tidy, same thing.

All the tasks her environment suggests to her seem important and urgent, because she’s not comparing them to some larger list of potential priorities that apply to different contexts—she’s always working on the top priority strictly with reference to the context she’s in at the moment.
She is much better than me at accomplishing tasks that her environment naturally suggests to her—cooking (inspired by recipes she finds on social media), cleaning, shopping, gardening, socializing, and making social plans in response to texts and notifications on her phone.
I am much better than her at constructing an organized list of global priorities and working through them systematically. However, I find it very difficult to be opportunistic, and I can be inflexible and distracted from the moment because I’m always thinking of the one main task I want to focus on.
I don’t think explore/exploit is quite the right frame in our relationship. I’m much more capable of “exploring” topics that require understanding complex abstract interconnections because I can force myself to keep coming back to them over and over again, whatever they are, in any environment, until I’ve understood them. By contrast she’s more capable of “exploiting” unpredictable opportunities as they arise. But the opportunities she and I are exposed to are constrained by our patterns of attention.

DirectedEvolution 13 Feb 2025 19:25 UTC
4 points
0
in reply to: Gunnar_Zarncke’s comment on: Gunnar_Zarncke’s Shortform
There is trust in the practical abilities. Right now it is low, but that will only go up.
Part of the learning curve for using existing AI is calibrating trust and verifying answers, conditional on use case. A hallmark of inexperienced AI users is taking its replies at face value, without checking.
I do expect that over time, AI will become more trustworthy for daily users. But that is compatible with the trust users place in it decreasing as they familiarize themselves with the technology and learn its limitations.

DirectedEvolution 3 Feb 2025 7:21 UTC
17 points
0
in reply to: Viliam’s comment on: Viliam’s Shortform
I’ve participated in several alternative communities over the course of my life, and all became mired in scandal. The first was my college, where tolerance of hard drug use by the administration resulted in multiple OD deaths in my time there. The second was in my 20s in an intentional living and festival culture, when a major community figure was accused by multiple women of drugging and raping them while unconscious. The third was the EA and rationality community, which of course has had one scandal after another for years.
My model is that drugs, extreme ideas, mental illness, economic precarity, alternative cultures and institutions, power differences, and violent behavior are mutually reinforcing. Rationalists may drastically underestimate how intensely the recruitment funnel they’ve created selects for interest by disturbed people. Or the extent to which features correlated with the movement, like lifestyle experimentation, alternative spirituality or drug use, may be the central attractions for some, using rationality as a pretext. It’s the opposite of evaporative cooling—it’s condensation of crazy.
My belief is that to counteract this, it’s necessary to promote some level of conformism and convention to the standards and norms of society at large. Think of academia in STEM. Yes, the people and jobs are unusual. But the requirement for participants to repeatedly integrate into new departments at new universities repeatedly and work with many collaborators and a constant churn of new students from around the world makes for a melting pot culture where condensation of crazy is mitigated on a per capita basis.

In short, it seems to me that it’s in the very nature of niche movements and alternative communities to generate scandal for systematic sociological reasons. There is probably no way to retain the niche alt community structure without the scandal. Individuals will have to choose whether or not they prioritize a low frequency of scandal, or having the community exist in its present form.

A question I ask when sizing up a community is “do these people seem likely to be much more scandal-prone than the average church, sports team or workplace?” I also ask this for people I am considering getting to know. I go with my intuition and choose how to engage accordingly.

DirectedEvolution 25 Jan 2025 2:50 UTC
2 points
−2
on: Mechanisms too simple for humans to design
We can do the same with living organisms. The human genome contains about 6.2 billion nucleotides. Since there are 4 nucleotides (A, T, G, C), we need two bits for each of them, and since there are 8 bits in a byte, that gives us around 1.55 GB of data.
In other words, all the information that controls the shape of your face, your bones, your organs and every single enzyme inside them – all of that takes less storage space than Microsoft Word™.
There are two ways to see this is incorrect.
1. DNA’s ability to structure an organism is mediated through its chemical mileau. It is densely, dynamically regulated through a complex and dense mesh of proteins and regulatory RNA and small signaling molecules at every timepoint in every organism throughout the life cycle. Disruption of that chemical mileau renders the organism nonviable. This is a separate issue from the fact that evolution overwhelmingly operates on DNA sequence.
2. The DNA in a particular organism/cell is one point in a very long series of complex inheretance chains going back 4.5 billion years. I’m comfortable rounding off the maximum complexity of the soma to the maximum possible complexity of the complete set of ancestral DNA sequences. But we can go further by noticing that an individual’s DNA sequence is not just the combination of their direct ancestors—the entire ancestral lineage at every step is sampled from a distribution of possible genomes that is produced from mechanisms impacting reproduction.
In a more mathematical sense, while it’s true that, conditional on a specific non-stochastic function, the number of values in the output set is less than or equal to the number of values in the input set, if the function can vary freely then there is no such constraint.
The soma might be viewed as a stochastic function mapping DNA inputs to phenotypic outputs. The stochastic aspect gives a much larger number of theoretically possible outputs from the same input set. And the fact that the ‘function’ (soma) itself varies from organism to organism increases the number of phenotypes that can be generated from a given amount of DNA still further.
All these arguments also apply to technology. MS Word ‘co-evolved’ with Windows, with programming languages, with hardware, and this context must be taken into account when thinking about how complex a machine is.

DirectedEvolution 22 Jan 2025 2:59 UTC
4 points
0
on: AllAmericanBreakfast’s Shortform
The CDC and other Federal agencies are not reporting updates. “It was not clear from the guidance given by the new administration whether the directive will affect more urgent communications, such as foodborne disease outbreaks, drug approvals and new bird flu cases.”

DirectedEvolution 17 Jan 2025 4:10 UTC
3 points
0
in reply to: Elizabeth’s comment on: Elizabeth’s Shortform
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.

DirectedEvolution 15 Jan 2025 3:15 UTC
1 point
−3
in reply to: nim’s comment on: Don’t Legalize Drugs
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.

DirectedEvolution 14 Jan 2025 17:58 UTC
2 points
0
in reply to: nim’s comment on: Don’t Legalize Drugs
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.

DirectedEvolution 8 Jan 2025 18:22 UTC
2 points
0
in reply to: Nathan Young’s comment on: Nathan Young’s Shortform
I recommend making the title time-specific, since all the predictions you’re basing your estimate on are as well.

DirectedEvolution 8 Jan 2025 7:06 UTC
29 points
24
on: OpenAI #10: Reflections
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?”

DirectedEvolution 6 Jan 2025 5:51 UTC
6 points
0
on: Estimating the benefits of a new flu drug (BXM)
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.

DirectedEvolution 6 Jan 2025 5:41 UTC
6 points
0
on: Estimating the benefits of a new flu drug (BXM)
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.

Estimating the benefits of a new flu drug (BXM)

DirectedEvolution6 Jan 2025 4:31 UTC

40 points

2 comments3 min readLW link

DirectedEvolution 4 Jan 2025 18:16 UTC
8 points
0
in reply to: Mo Putera’s comment on: RohanS’s Shortform
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?”

DirectedEvolution 30 Dec 2024 18:04 UTC
11 points
8
in reply to: Chipmonk’s comment on: Began a pay-on-results coaching experiment, made $40,300 since July
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.

DirectedEvolution 27 Dec 2024 2:12 UTC
9 points
0
on: AI #96: o3 But Not Yet For Thee
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

DirectedEvolution 14 Dec 2024 5:41 UTC
8 points
0
in reply to: J Bostock’s comment on: Biological risk from the mirror world
Acquired immune systems (antibodies, T cells) are restricted to jawed vertebrates.

DirectedEvolution 12 Dec 2024 16:42 UTC
4 points
0
in reply to: Ben Pace’s comment on: Here’s Why I’m Hesitant To Respond In More Depth
Thanks for the nice comment. I tried using it several times IIRC, but I don’t think it helped. It was written in reaction to some mounting frustrations with interactions I was having, and I ultimately mostly stopped participating on LW (though that was a combination of factors).

DirectedEvolution 11 Dec 2024 4:51 UTC
2 points
0
in reply to: Elizabeth’s comment on: Correct my H5N1 research ($reward)
Great, that’s clarifying. I will start with Tamiflu/Xofluza efficacy as it’s important, and I think it will be most tractable via a straightforward lit review.

DirectedEvolution 10 Dec 2024 5:31 UTC
16 points
0
on: Correct my H5N1 research ($reward)
I’ve been researching this topic in my spare time and would be happy to help. Do you have time to clarify a few points? Here are some thoughts and questions that came up as I reviewed your post:
1. Livestock vs. Wild Birds
  The distinction between livestock and wild birds is significant. Livestock are in much closer contact with humans and are biologically closer as well. How granular of an analysis are you interested in here?
2. US-specific H5N1 Trends
  It’s peculiar that H5N1 seems so prevalent in the US. Could this be due to measurement bias, or does the US simply have more factory farming? How interested are you in exploring the reasons behind this trend?
3. Citations and Depth
  While most points aren’t cited (which is fine), it might be valuable to compile both a list of key aspects and resources for further reading. Are you looking for a more polished, thoroughly cited document?
4. Biological Factors of Severity
  Binding to human receptors is just one factor controlling the severity and infectiousness of a virus. Would you like a deeper dive into the biology of respiratory infections and what makes them dangerous?
5. Tamiflu and Xofluza
  Wikipedia notes that Tamiflu has limited evidence of being worth the side effects. Are you interested in a detailed evaluation of its effectiveness? Similarly, how interested are you in assessing the likelihood of shortages and efficacy of Tamiflu/Xofluza during an H5N1 pandemic?
6. Over-the-counter Tests
  Is the issue a lack of over-the-counter tests specifically for H5N1, or for flu in general? General flu PCR testing is likely available—should we investigate this?
7. Trajectory of Illness
  For past H5N1 cases, is there a treatable “window of opportunity” before the infection becomes severe? How critical is it to determine whether mild cases might escalate and require aggressive intervention?
8. Historical Epidemics
  I could pull together a list of relevant modern epidemics (human-to-human airborne transmission without an animal vector). Are there any specific criteria you’d like to prioritize?
9. Cross Immunity
  While cross immunity seems important, determining decision-relevant information may be challenging. Would you like a summary of existing knowledge or only actionable insights?
10. Respiratory Infection Dynamics
  Epidemiologists suggest that respiratory infections are deadlier lower in the lungs but more infectious higher in the system. Is this a fundamental tradeoff? Would a “both-and” virus be possible? What evolutionary advantages might viruses have in infecting the lower lungs?
11. Government Stockpiles and Interventions
  What stockpiles of H5N1 vaccines exist? What options are available for increasing testing and vaccination of livestock? How are governments incentivizing medication, vaccine, and PPE production?
12. Political Considerations
  Should we examine how a Trump presidency or similar political scenarios might influence the interaction between local and federal health agencies?
13. Species-to-Species Spread
  The rapid spread of H5N1 to multiple bird and mammal species raises the question of whether humans will inevitably be affected. Is this worth exploring in-depth?
14. Mortality and Long-term Effects
  What demographics do other flu strains tend to affect most? Are there long-term side effects comparable to “long COVID”?
15. Mutation and Vaccine Efficacy
  How quickly do flu strains, especially H5N1, tend to mutate? What implications does this have for vaccine efficacy and cross-reactivity? How much asymptomatic spread occurs with flu, and how long does it remain airborne?
16. No Deaths Yet
  How should we update based on the fact that, contrary to past occurrences of H5N1 that had a ~50% CFR, none of the 58 confirmed cases have died?
Finally, I’d be interested to hear which of these questions or areas you find most compelling. Are there other questions or directions you’d like to explore? This will help me prioritize my efforts.
Epidemic Scares That Did Not Pan Out
- 1976 - Legionnaires’ Disease: Initially alarming but identified as a bacterial infection treatable with antibiotics. (Not relevant: bacterial)
- 2001 - Anthrax Attacks: Bioterrorism-related bacterial outbreak causing fear but limited deaths. (Not relevant: bacterial)
- 2005 - Avian Flu (H5N1): No confirmed US human cases despite global fears. (Relevant)
- 2014 - Ebola: Strict public health measures limited US cases to three. (Relevant)
- 2016 - Zika Virus: Local transmission limited to parts of Florida and Texas. (Not relevant: mosquito vector)

DirectedEvolution

Es­ti­mat­ing the benefits of a new flu drug (BXM)

Epidemic Scares That Did Not Pan Out

Estimating the benefits of a new flu drug (BXM)