Book review: The End of Alzheimer’s Program, by Dale Bredesen.

This sequel to The End of Alzheimer’s is an attempt at a complete guide to a healthy lifestyle.

Alas, science is still too primitive to enable an impressive version of that. So what we end up with is this guide that would overwhelm anyone who tries to follow it thoroughly, while still lacking the kind of evidence that would convince a skeptic.

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Last month, I conceded defeat in my bet (with Robin Hanson) that US COVID-19 deaths would be less than 250,000.

My biggest mistake was thinking voters would care about results, and unite against a common enemy as they did in WWII. I should have been more aware of the tendency to treat natural deaths as more acceptable than deaths due to a hostile agent. Robin clearly did better at evaluating this.

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From The problem with rapid Covid testing, Mayank Gupta writes:

The absolute number of false positives would rise dramatically under slightly inaccurate, broad surveillance testing. At least initially, the number of people going to the doctor to ask what to do would also rise. One can imagine if doctors truly flubbed and didn’t know how to advise patients accurately, a lot of individual patients would lose trust in the medical system (testing, doctors, or both). The consequence of this would be more resistance to health public policy measures in the future.

For a reminder of why rapid testing is valuable, see Alex Tabarrok. Note also the evidence from the NBA that people who need useful tests can be more innovative than the medical system.

This seems like the tip of an important iceberg.

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A new study has provided evidence that a healthy lifestyle can reverse aging, as measured by epigenetic age: Reversal of Epigenetic Age with Diet and Lifestyle in a Pilot Randomized Clinical Trial. This is the second study to show that epigenetic age can be reversed in humans (here’s a reminder to read the first).

They used the Horvath DNAmAge clock.

After a mere 8 weeks of a healthy lifestyle, the subjects’ DNAmAge was 3.23 years younger than the controls (and 1.96 years younger than the pre-trial DNAmAge of the treatment group).

The lifestyle interventions weren’t labeled as paleo, but they closely resemble the lifestyles that are recommended by Chris Kresser, Steven R. Gundry, and Dale Bredesen. The diet comes about as close as the diet of a typical paleo enthusiast to avoiding foods that have been available for less than 10,000 years. The recommended foods that I consider the least paleo are “coconut, olive, flaxseed and pumpkin seed oil”. The diet is more plant-based than the stereotypical paleo diet, but it’s well within the normal range of hunter-gatherer diets.

The study has a bunch of the usual limitations, such as a small sample size (18 people in the treatment group). There are also reasons for mild concerns about conflicts of interest, as some of the researchers work as functional medicine physicians, so their careers are mildly dependent on the popularity of the lifestyle approach being studied. As far as I can tell, that is likely to cause a level of bias that is rather ordinary for nutrition-related research. Oh, and the instructions are listed as “Patent pending”, but it’s unclear why they would meet the novelty requirements for a patent.

My main doubt comes from the difficulty of figuring out whether DNAmAge measures causes of age-related health problems, or whether it’s just measuring symptoms. I’m slightly more than 50% confident that epigenetic changes have some causal influence on aging.

This kind of trial raises questions about how well patients follow the instructions – most would find it difficult to “Avoid added sugar/candy, dairy, grains, legumes/beans”. The paper describes how they checked on patient compliance, but I didn’t see any data indicating what they found about compliance. So there’s some risk that they were especially lucky about getting patients to follow their instructions, and maybe future studies of this nature will show much weaker results due to poor compliance.

Lastly, it’s a bit odd that the control group appeared to age 1.27 years in 8 weeks. Maybe they were depressed about not getting any treatment? (This isn’t the kind of study where blinding is feasible). More likely it was just noise, but that’s a reminder that the small sample size provides lots of opportunity for luck to dominate the results. Even if we assume perfect measurement, there’s plenty of room for variation in lifestyles. Uncontrolled lifestyle changes, such as someone getting fired, could mess with the results enough to matter.

Book review: Lifespan: Why We Age – and Why We Don’t Have To, by David A. Sinclair.

A decade ago, the belief that aging could be cured was just barely starting to get attention from mainstream science, and the main arguments for a cure came from people with somewhat marginal formal credentials.

Now we have a book by an author who’s a co-chief editor of the scientific journal Aging. He’s the cofounder of 14 biotech companies (i.e. probably more than he’s had enough time to work for full time, so I’m guessing some companies are listing him as a cofounder more for prestige than for full-time work). He’s even respected enough by some supplement companies that they use his name, even after he sends them cease and desist letters.

I’m glad that Sinclair published a book that says aging can be cured, since there’s still a shortage of eminent scientists who are willing to take that position.

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Book review: Black Death at the Golden Gate: The Race to Save America from the Bubonic Plague, by David K. Randall.

Imagine a story about an epidemic that reached San Francisco, after devastating parts of China. A few cases are detected, there’s uncertainty about how long it’s been spreading undetected, and a small number of worried public health officials try to mobilize the city to stop an imminent explosion of disease. Nobody knows how fast it’s spreading, and experts only have weak guesses about the mechanism of transmission. News media and politicians react by trying to suppress those nasty rumors which threaten the city’s economy.

Sounds too familiar?

The story is about a bubonic plague outbreak that started in 1900. It happens shortly after the dawn of the Great Sanitary Awakening, when the germ theory of disease is fairly controversial. A few experts in the new-fangled field of bacteriology have advanced the radical new claim that rats have some sort of connection to the spread of the plague, and one has proposed that the connection involves fleas transmitting the infection through bites. But the evidence isn’t yet strong enough to widely displace the standard hypothesis that the disease is caused by filth.

There was a vaccine for the bubonic plague, which maybe helped a bit. It was only 50% effective, the benefits lasted about 6 months, and the side effects sound like cruel and unusual punishment. It was controversial and often resisted, much like the compulsory smallpox vaccinations of the time.

Yet the plague didn’t seem to know that it was supposed to grow at exponential rates. That left an eerie sense of mystery about how the plague could linger for years, with people continuing to disagree about whether it existed.

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New infections have been declining at an almost adequate pace (10% per week?) in most parts of the US, and probably the rest of the developed world.

The overall reported new cases look more discouraging, for two reasons.

One reason is the increase in testing. I estimate that two months ago, a bit less than 10% of new infections were being confirmed by tests, and I estimate that now it’s above 20%, maybe getting close to 25%. That means that if the new infection rate were unchanged, we’d be seeing a roughly 10% per week increase in reported cases.

Nearly all parts of the country have done a good deal better than that.

I estimate the change in new infections since the early April peak by multiplying the early April confirmed daily cases by 10 or 12, and the June ones by 4 or 5, and I get a current rate that’s about 1/4 to 1/3 of the peak.

The bad news is that there are some heavily populated areas for which the trend doesn’t look very good over the past few weeks. When the rate of new infections remains constant in some areas, but declines at exponential rates in others, the exponential declines stop affecting the total numbers before too long. E.g. much of California has suppressed the pandemic, but a few cities, such as Los Angeles and Oakland, are enough to keep the state’s total count of new infections steady.

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Elon Musk has gotten some well-deserved flack for predicting (in March) close to zero new infections in the U.S. by now.

Yet the focus on national or statewide infections has obscured a curious phenomenon: if he’d just predicted infections in Santa Clara county, he’d have been partly right – new cases peaked on April 10 at 83, were down to 23 on April 27, and appear to have dropped more since then (reporting may be incomplete for more recent days). (Santa Clara county roughly coincides with Silicon Valley; Tesla’s plants are a few miles from the Santa Clara county border, technically in Alameda county, but in most senses Tesla’s plants are part of Silicon Valley, which I’ll treat as a city, even though it’s more a city-less suburb).

Meanwhile, the statewide totals fail to show a trend of doing much more than stabilizing the rate of new cases. A good deal of that is due to Los Angeles.

What’s different between LA and Silicon Valley that would explain this difference?

It’s probably not much due to differences in government policy. California is using a mix of statewide rules and county rules, which makes it tricky to say whether there are policy differences. My impression is that most differences between county policies have relatively minor effects. I guessed that the most important difference would be in when they required facemasks use. Yet it looks like LA required facemasks on April 17, in synchrony with most of the bay area. But Santa Clara county differed by strongly urging, but not requiring, facemasks.

Maybe the reason that Santa Clara county didn’t create a formal facemask rule is that residents were sufficiently quick to adopt them that there was less need than in other counties? That fits my intuitions fairly well.

The LA area has been in the news for having crowded beaches. Outdoor activity in warm, sunny weather seems relatively low risk, but I doubt that the people on those beaches carefully evaluated the effects of ventilation, sun, and temperature on their risk, so it’s likely that the crowded beaches are at least a symptom of attitudes which cause the spread of infections.

I can see from Ohio that there are significant regional differences in people’s willingness to wear facemasks. I’m surprised that Ohio voters won’t put up with a rule to make them wear masks in order to enter stores. (Ohio’s Governor DeWine deserves much better constituents than he’s currently stuck with. Here in Berkeley, I get the impression that a majority decided that we needed to follow that rule before our government got around to announcing it).

Another relevant difference is that Silicon Valley workers switched to working from home more readily than most other places. This is likely a moderate factor, but I’d have expected a peak before April 10 if it explained more than half of Silicon Valley’s success.

Another influence might be blood types: type A blood creates higher risk of COVID-19, while type O lowers risk. Judging from the blood type differences between the U.S. and China, the large Chinese population in Silicon Valley ought to lower risk a bit.

LA’s apparently steady number of new cases can’t be very stable. People’s willingness to take precautions will decline at some point if herd immunity looks inevitable. Pushing in the other direction: increasing numbers of people will become immune, reducing the virus’ ability to spread. It seems almost impossible for these forces to balance out.

Robin Hanson sees a world polarized between regions that prevent infections and regions that get something like herd immunity. I expect that many regions, such as LA, will end up at various places in between, with maybe 10% of the population becoming immune. Since the people most likely get infected and to spread the virus will be over-represented in that fraction, it will put a sizable dent in R, enough to enable significant periods of suppression.

Robin expects that variance in R will be harmful. Zvi counters that variance is not bad, given sufficiently effective travel restrictions.

I mostly agree with Zvi here. The cost of restricting nearly all travel to commuting distance or less from home is much lower than the cost of the current drastic restrictions, so voters will typically demand a shift in that direction. My main concern is that these travel restrictions are getting lumped in with “lockdown measures” such as stay at home, and shut down “nonessential” businesses. That means that pressure to reopen activities that ought to be reopened could become pressure to remove most travel restrictions.

How many politicians will see beyond simple categories such as lockdowns versus reopening the economy, to pick and choose between the good and bad pieces of lockdowns? My impression is that at least half of the state and local politicians are on track to doing so, and have enough power to sidestep whatever problems exist at the federal level.

I sympathize with Musk’s desire to reopen Tesla plants, and it’s somewhat plausible that now is the right time for that. But I’m reluctant to side with him until he alters his tweets to be more narrowly targeted on specific, arguably safe, changes. I don’t want the world polarized between openers and closers.