Previously: #1 It feels so long ago that Covid and health were my beat, and what everyone often thought about all day, rather than AI. Yet the beat goes on. With Scott Alexander at long last giving us what I expect to be effectively the semi-final words on the Rootclaim debate, it seemed time to do this again.
"A ‘vaccine-like’ version of Wegovy is on the drawing board at Novo Nordisk (Stat+). If you are convinced you need this permanently it would be a lot cheaper and easier in this form, but this is the kind of thing you want to be able to reverse, especially as technology improves."
It sounds like the "vaccine-like" version is just the same sort of GLP-1 molecule, but it would just last a year instead of a week. So it's not permanent, and there's no real need for it to be reversible.
Re the sock. Out of desperate necessity, I've developed a talent for getting accurate oxygen readings on babies and children with adult pulse oximeters.
Step 1: if you can't get the kid to be still, you usually don't need to worry as much and can drive to ER.
Step 2: Use the foot or entire hand.
Step 3: If your child is unfortunate enough to be admitted to the hospital and monitored, use the opportunity to get the adult pulse oximeter to match their reading.
(But first order something yummy for yourself to eat)
"Sulfur dioxide in particular is a huge deal. The estimate here is that a 1 ppb drop in levels, a 10% decline in pollution, would increase life expectancy by a whopping 1.2 years. Huge if even partially true, I have not looked into the science."
My priors on most health effects of low levels of pollution is that this is exactly the sort of area I expect bad science to rule the day. Good studies are somewhere between difficult and impossible to do, and I would expect that all the right people will be lining up to say how awful the effects of pollution are and how good the science is, even when that's not true. And there is really no strong interest group on the other side to point out how the entire field is nonsense. So I'd be interested in someone like you or Scott Alexander doing a deeper dive and investigating how good the evidence is for things like this.
"Of all the low hanging fruits in health care, ‘lots of capable people want to be doctors and we should train more of them to be doctors’ has to be the lowest hanging of all."
Oh no, there's a lower one. Lots of capable people are *already* doctors and want to be doctors in the US, and we should let them do that.
"So yes, assuming this is a full cure then this does seem worth it for America, on the principle that a life saved is worth about $10 million. In theory we should be willing to pay at least $5 million for this drug, possibly up to $10 million, before it would cost more than it is worth."
I think this is missing out a key component of the cost/benefit analysis. A relatively small portion of the benefit is the lives saved over the next ~15 years, at a cost of $4 million each. But a much bigger portion of the benefit is the lives saved over the next several decades, at whatever the marginal cost of the drug is. And then there's all of the medical advances that will build on drugs like this that can be used to treat other disease.
Overall, I'm skeptical that, at a societal level, saving a toddler's life is worth it at $4 million each, at least under a cold-hearted cost/benefit analysis. But factoring in those other benefits, I think the calculus could change quite a bit.
On the "people used to eat much more" part I strongly feel like this is misled.
We have a large body of litterature suggesting the reason for weight gain is essentially "calories in - calories out" along very strong mechanistic plausibility.
We also know even modern nutritional epidemiology is extremely flawed and prone to methodological errors.
In this context I don't think a handful of decades old studies constitute sufficient evidence to infer that "it seems improbable that too many calories in and too few calories out are the cause of modern obesity" as the author does.
Even at a quick glance one can easily find flaws in many of the studies he cites, highlighting how he things they're "more evidentiary than the usual [...]".
Children being served given amounts of food? But they don't measure how much they actually eat.
Soldiers supposedly eating upwards of 5500 kcal not gaining weight on a mere "3 hours of moderate activity a day" ? Give me a break ....
> Someone should buy 23AndMe purely to safeguard its data
Has anyone managed to demonstrate a credible attack vector that results in significant damage to a persons life due to their DNA being leaked? I can only think of super rare edge cases, such as an a sperm donor who wants their DNA sequenced but doesn't want their 15 bio kids to find them.
> You have something that is 95%-99% to be essentially fine (depending on your threshold for fine) but will sometimes kill you
It was ~99.9% fine if you were under 30 with a BMI under 30 and no respiratory problems. And yet ~nobody in the government was saying this publicly or saying that night clubs should remain open as long as they don't admit people older than 40. Instead, high school students and retirees were treated as if they're in the same risk group.
> America utterly failed to make tests available in reasonable fashion
Yes, but in 2021 they've also failed to tell people to stop getting tested if they're only hanging out with people under 40 or with vaccinated people. I've seen plenty of people waste time getting tests in summer 2021 when everyone in their social circle had the vaccine.
> ‘I’m 28. And I’m scheduled to die in May.’
I do wonder if this person has considered/tried any illicit substances before choosing to commit suicide. If you're going to die anyway, why not first spend a month or two doing acid, smoking weed and doing lines of ketamine? Heck, if death is the only other option, I'd try opiates as a measure of last resort.
> My actual impression is that the elite therapists largely do not market themselves at all. They instead work on referrals and reputation. So you have to know someone who knows.
This is an underrated reason to give therapy a try. Having the direct contact info of a few therapists who know and trust you personally can be incredibly helpful. Even if you end up not needing the help of a therapist for long, think of it like any other professional relationship; maybe they'll be a better fit in the future and they can always open their network to you if you need it.
The actual problem with the sock was that it had way too high a false positive rate of emergency. Kid kicks sock off a bit, it fire off an alarm, you wake up in a panic and get your sleep disrupted.
However, it did absolutely let us know when our baby with RSV needed to go into the hospital vs convalescing at home. And for 1st time parents it was a nice little bit of piece of mind.
Yes, Johnson is definitely not taking the right approach to living forever. He needs to go into harder approaches like genetic engineering and synthetic biology, but that could go wrong rapidly (if he is very unlucky), so there is that. He does seem to look 'better' than most 46-year-olds. I am not sure that shocking his body with precise waves is the same as the kind of stressors your body needs to become resilient (as also said in a comment in the interview article you referenced). On the other hand, it is likely that there are shock routines that mimic natural stressors, so I do not fully agree with the doctor there, plus Bryan is a multimillionaire, so he will be able to afford this forever. However, he could experiment with occasional sleep deprivation to get his circadian resilience going.
The difficulty with his approach is that he is the only subject. We would need thousands of people on this regimen to get useful data. I do not think this approach alone will give him more than 100 years of total life or so, if he can even maintain such a boring routine and lifestyle until then. If we want to push the envelope, we need to bring synthetic biology, gene therapy, robotics, and nanotechnology into the picture, but bioethicists won't let that be researched easily, and it will probably lead to creepy results before it is mastered.
Based on my brief reading now, it seems that size is a huge issue as we age, so obviously bone density and mass seem to suffer (some genetic upregulation and maybe micro-delivery of ions over a template might help with that, but sounds extremely painful to install), eye health (same, and maybe biocoatings to protect the surface), and hearing (that seems challenging, but maybe hybridizing our hearing with a computer, or replacing it by a computer, seems like the best bet). Anything else that does not make us look extremely decrepit at, say, 150 and beyond will have to be invented. Ideally, we will converge the process backwardly to be able to start it earlier in life as research progresses. Thus, ideally and eventually, we'll slow down aging to the point where 100 years feels like just a decade of current aging (and so on, incrementally, through some advanced exploration process, kind of like having deep reinforcement learning being applied to yourself all the time, in a broad sense, of course, where the goal is not dying but maintaining homeostasis as the main ideal or irrefutable basis).
We will probably eventually converge on preserving our brain and major organs and designing a body around them. The connection between the peripheral nervous system, the endocrine system, the cardiovascular system, and the immune system to our brain is crucial and delicate, and will probably require iterative replacement in order for us to maintain an image and memories of our identity as we transform (i.e., the body-brain connection is obviously crucial to identity, and just replacing everything but the brain for some reservoir is likely going to create a sudden change of who you are and thus the importance of iterativeness). Even major organs will probably be replaced soon after the body is robotized. I hope to be around for all of this in a few decades. The question is how to start the process and convince politicians that these lines of research are crucial and that becoming immortal is probably the point of life. Maybe this is all too crazy, but it sounds feasible and better than dying. The problem again is the initiation of the process and the subjects (volunteers) and the suffering (minimize suffering). Ideally, we should start lobbying for this type of idea as soon as there is a clear sign of 'AGI', so we can be alive by the time the developments arrive and have enough time for volunteers to try processes out and processes to improve steadily.
Zvi writes: "Also, they are going to put each person on each diet for only two weeks? What is even the point? This does not seem like $189 million well spent." Perhaps the researchers simply could have each rented and watched Morgan Spurlock's "Super Size Me" to get 80% of the learnings.
"90% of junior doctors in South Korea strike to protest against doctors."
Not to jump up and down on this soapbox, as you kindly quoted me once, but the US is way, way worse on this. Docs in the US don't have to protest, because the AMA, CMS, and the federal healthcare government in general spent most of the 90s/2000s throttling residency spots (which CMS literally pays for only a limited # of) in order to forestall an upcoming terrible disaster of oversupply of doctors. The shortages we have right now - and the push for more and more independent practice from non-MD's - are a direct consequence of that.
I am 100% for less restrictive legal barriers to people practicing medicine, but there's at least a small story to be told about how we have been relaxing the practical, educational (i.e. the hours of study, and times of practice) barriers to practice specific subsets of medicine in order to route around the lack of docs. And that obviously US nurses/etc... have a much stronger lobby than foreign medical people.
Even though longvid having a disease burden like cancer or cardiac disease is Obvious Nonsense, the narrower claim that covid has meaningfully raised disease burden in general seems clearly true. Like I don't personally know a single person who's been long-term debilitated by covid - even finding cases of real bad cases is hard - but attendance data from my workplace shows a clear pattern. In the Before Times, the average number of absences to trigger a "you're maybe not getting a raise" each half-year was 7 or so. After covid...that's roughly the number of sick days an employee averages in a month or two. Sure, some of those are probably "mental health days" or other not-strictly-covid things. People also aren't gonna get a test every time, so that increases the odds of generic cold and flulike symptoms leading to calling out Just To Be Safe. But from a business POV, the actual cause doesn't really matter - a sick day is a sick day, the absenteeism exists either way. So it's still a useful approximation to blame the curve shift on "Covid". I'd imagine it's the same situation in schools as well. Hopefully they've likewise updated their policies on absenteeism to grade a bit more on a curve.
(Still want that damn pan-coronavirus intranasal vaccine. It's really annoying not being able to work, even if the actual illness is mild. Written while home sick.)
Skeptical @ that blag arguing against CICO. Especially if they're citing SMTM's obesity series approvingly - I thought the "It's Probably Not Lithium" LW post pretty thoroughly dismantled that argument. Doesn't really grapple with measurement error, either - it's not just a methodological issue with surveys, it's that accurately measuring both CI and CO is harder than it first appears. All models are wrong, some models are useful...
It's also weird to have a section on the metabolism hypothesis, but neglect the obvious standout from the data, which is that basal metabolism is the bulk of CO even at "heavy" activity level. An appropriately intense workout/sports/whatever might be able to get a higher percentage, if it's sustained long enough...conversely, the amount of calories burned from modern intentional exercise is less than one would think, while also stimulating appetite, quite possibly ending in a net caloric gain. (I'm a fan of thermogenesis, personally - shivering and other subconscious involuntary movements are an easy way to passively burn calories. Much happier dryly chilling than wetly sweating in spandex. Have heard there's ice vests and such for people who don't happen to work in walk-in freezers.)
"A ‘vaccine-like’ version of Wegovy is on the drawing board at Novo Nordisk (Stat+). If you are convinced you need this permanently it would be a lot cheaper and easier in this form, but this is the kind of thing you want to be able to reverse, especially as technology improves."
It sounds like the "vaccine-like" version is just the same sort of GLP-1 molecule, but it would just last a year instead of a week. So it's not permanent, and there's no real need for it to be reversible.
Re the sock. Out of desperate necessity, I've developed a talent for getting accurate oxygen readings on babies and children with adult pulse oximeters.
Step 1: if you can't get the kid to be still, you usually don't need to worry as much and can drive to ER.
Step 2: Use the foot or entire hand.
Step 3: If your child is unfortunate enough to be admitted to the hospital and monitored, use the opportunity to get the adult pulse oximeter to match their reading.
(But first order something yummy for yourself to eat)
"Sulfur dioxide in particular is a huge deal. The estimate here is that a 1 ppb drop in levels, a 10% decline in pollution, would increase life expectancy by a whopping 1.2 years. Huge if even partially true, I have not looked into the science."
My priors on most health effects of low levels of pollution is that this is exactly the sort of area I expect bad science to rule the day. Good studies are somewhere between difficult and impossible to do, and I would expect that all the right people will be lining up to say how awful the effects of pollution are and how good the science is, even when that's not true. And there is really no strong interest group on the other side to point out how the entire field is nonsense. So I'd be interested in someone like you or Scott Alexander doing a deeper dive and investigating how good the evidence is for things like this.
"Of all the low hanging fruits in health care, ‘lots of capable people want to be doctors and we should train more of them to be doctors’ has to be the lowest hanging of all."
Oh no, there's a lower one. Lots of capable people are *already* doctors and want to be doctors in the US, and we should let them do that.
"So yes, assuming this is a full cure then this does seem worth it for America, on the principle that a life saved is worth about $10 million. In theory we should be willing to pay at least $5 million for this drug, possibly up to $10 million, before it would cost more than it is worth."
I think this is missing out a key component of the cost/benefit analysis. A relatively small portion of the benefit is the lives saved over the next ~15 years, at a cost of $4 million each. But a much bigger portion of the benefit is the lives saved over the next several decades, at whatever the marginal cost of the drug is. And then there's all of the medical advances that will build on drugs like this that can be used to treat other disease.
Overall, I'm skeptical that, at a societal level, saving a toddler's life is worth it at $4 million each, at least under a cold-hearted cost/benefit analysis. But factoring in those other benefits, I think the calculus could change quite a bit.
On the "people used to eat much more" part I strongly feel like this is misled.
We have a large body of litterature suggesting the reason for weight gain is essentially "calories in - calories out" along very strong mechanistic plausibility.
We also know even modern nutritional epidemiology is extremely flawed and prone to methodological errors.
In this context I don't think a handful of decades old studies constitute sufficient evidence to infer that "it seems improbable that too many calories in and too few calories out are the cause of modern obesity" as the author does.
Even at a quick glance one can easily find flaws in many of the studies he cites, highlighting how he things they're "more evidentiary than the usual [...]".
Children being served given amounts of food? But they don't measure how much they actually eat.
Soldiers supposedly eating upwards of 5500 kcal not gaining weight on a mere "3 hours of moderate activity a day" ? Give me a break ....
> Someone should buy 23AndMe purely to safeguard its data
Has anyone managed to demonstrate a credible attack vector that results in significant damage to a persons life due to their DNA being leaked? I can only think of super rare edge cases, such as an a sperm donor who wants their DNA sequenced but doesn't want their 15 bio kids to find them.
> You have something that is 95%-99% to be essentially fine (depending on your threshold for fine) but will sometimes kill you
It was ~99.9% fine if you were under 30 with a BMI under 30 and no respiratory problems. And yet ~nobody in the government was saying this publicly or saying that night clubs should remain open as long as they don't admit people older than 40. Instead, high school students and retirees were treated as if they're in the same risk group.
> America utterly failed to make tests available in reasonable fashion
Yes, but in 2021 they've also failed to tell people to stop getting tested if they're only hanging out with people under 40 or with vaccinated people. I've seen plenty of people waste time getting tests in summer 2021 when everyone in their social circle had the vaccine.
> ‘I’m 28. And I’m scheduled to die in May.’
I do wonder if this person has considered/tried any illicit substances before choosing to commit suicide. If you're going to die anyway, why not first spend a month or two doing acid, smoking weed and doing lines of ketamine? Heck, if death is the only other option, I'd try opiates as a measure of last resort.
Bryan Johnson's interview reminds me of this New Yorker cartoon:
https://glasbergen.b-cdn.net/wp-content/gallery/stress-management-cartoons/thumbs/thumbs_stress3.gif
> My actual impression is that the elite therapists largely do not market themselves at all. They instead work on referrals and reputation. So you have to know someone who knows.
This is an underrated reason to give therapy a try. Having the direct contact info of a few therapists who know and trust you personally can be incredibly helpful. Even if you end up not needing the help of a therapist for long, think of it like any other professional relationship; maybe they'll be a better fit in the future and they can always open their network to you if you need it.
The actual problem with the sock was that it had way too high a false positive rate of emergency. Kid kicks sock off a bit, it fire off an alarm, you wake up in a panic and get your sleep disrupted.
However, it did absolutely let us know when our baby with RSV needed to go into the hospital vs convalescing at home. And for 1st time parents it was a nice little bit of piece of mind.
Typo: "charing" → ?
Yes, Johnson is definitely not taking the right approach to living forever. He needs to go into harder approaches like genetic engineering and synthetic biology, but that could go wrong rapidly (if he is very unlucky), so there is that. He does seem to look 'better' than most 46-year-olds. I am not sure that shocking his body with precise waves is the same as the kind of stressors your body needs to become resilient (as also said in a comment in the interview article you referenced). On the other hand, it is likely that there are shock routines that mimic natural stressors, so I do not fully agree with the doctor there, plus Bryan is a multimillionaire, so he will be able to afford this forever. However, he could experiment with occasional sleep deprivation to get his circadian resilience going.
The difficulty with his approach is that he is the only subject. We would need thousands of people on this regimen to get useful data. I do not think this approach alone will give him more than 100 years of total life or so, if he can even maintain such a boring routine and lifestyle until then. If we want to push the envelope, we need to bring synthetic biology, gene therapy, robotics, and nanotechnology into the picture, but bioethicists won't let that be researched easily, and it will probably lead to creepy results before it is mastered.
Based on my brief reading now, it seems that size is a huge issue as we age, so obviously bone density and mass seem to suffer (some genetic upregulation and maybe micro-delivery of ions over a template might help with that, but sounds extremely painful to install), eye health (same, and maybe biocoatings to protect the surface), and hearing (that seems challenging, but maybe hybridizing our hearing with a computer, or replacing it by a computer, seems like the best bet). Anything else that does not make us look extremely decrepit at, say, 150 and beyond will have to be invented. Ideally, we will converge the process backwardly to be able to start it earlier in life as research progresses. Thus, ideally and eventually, we'll slow down aging to the point where 100 years feels like just a decade of current aging (and so on, incrementally, through some advanced exploration process, kind of like having deep reinforcement learning being applied to yourself all the time, in a broad sense, of course, where the goal is not dying but maintaining homeostasis as the main ideal or irrefutable basis).
We will probably eventually converge on preserving our brain and major organs and designing a body around them. The connection between the peripheral nervous system, the endocrine system, the cardiovascular system, and the immune system to our brain is crucial and delicate, and will probably require iterative replacement in order for us to maintain an image and memories of our identity as we transform (i.e., the body-brain connection is obviously crucial to identity, and just replacing everything but the brain for some reservoir is likely going to create a sudden change of who you are and thus the importance of iterativeness). Even major organs will probably be replaced soon after the body is robotized. I hope to be around for all of this in a few decades. The question is how to start the process and convince politicians that these lines of research are crucial and that becoming immortal is probably the point of life. Maybe this is all too crazy, but it sounds feasible and better than dying. The problem again is the initiation of the process and the subjects (volunteers) and the suffering (minimize suffering). Ideally, we should start lobbying for this type of idea as soon as there is a clear sign of 'AGI', so we can be alive by the time the developments arrive and have enough time for volunteers to try processes out and processes to improve steadily.
Zvi writes: "Also, they are going to put each person on each diet for only two weeks? What is even the point? This does not seem like $189 million well spent." Perhaps the researchers simply could have each rented and watched Morgan Spurlock's "Super Size Me" to get 80% of the learnings.
"90% of junior doctors in South Korea strike to protest against doctors."
Not to jump up and down on this soapbox, as you kindly quoted me once, but the US is way, way worse on this. Docs in the US don't have to protest, because the AMA, CMS, and the federal healthcare government in general spent most of the 90s/2000s throttling residency spots (which CMS literally pays for only a limited # of) in order to forestall an upcoming terrible disaster of oversupply of doctors. The shortages we have right now - and the push for more and more independent practice from non-MD's - are a direct consequence of that.
I am 100% for less restrictive legal barriers to people practicing medicine, but there's at least a small story to be told about how we have been relaxing the practical, educational (i.e. the hours of study, and times of practice) barriers to practice specific subsets of medicine in order to route around the lack of docs. And that obviously US nurses/etc... have a much stronger lobby than foreign medical people.
Even though longvid having a disease burden like cancer or cardiac disease is Obvious Nonsense, the narrower claim that covid has meaningfully raised disease burden in general seems clearly true. Like I don't personally know a single person who's been long-term debilitated by covid - even finding cases of real bad cases is hard - but attendance data from my workplace shows a clear pattern. In the Before Times, the average number of absences to trigger a "you're maybe not getting a raise" each half-year was 7 or so. After covid...that's roughly the number of sick days an employee averages in a month or two. Sure, some of those are probably "mental health days" or other not-strictly-covid things. People also aren't gonna get a test every time, so that increases the odds of generic cold and flulike symptoms leading to calling out Just To Be Safe. But from a business POV, the actual cause doesn't really matter - a sick day is a sick day, the absenteeism exists either way. So it's still a useful approximation to blame the curve shift on "Covid". I'd imagine it's the same situation in schools as well. Hopefully they've likewise updated their policies on absenteeism to grade a bit more on a curve.
(Still want that damn pan-coronavirus intranasal vaccine. It's really annoying not being able to work, even if the actual illness is mild. Written while home sick.)
Skeptical @ that blag arguing against CICO. Especially if they're citing SMTM's obesity series approvingly - I thought the "It's Probably Not Lithium" LW post pretty thoroughly dismantled that argument. Doesn't really grapple with measurement error, either - it's not just a methodological issue with surveys, it's that accurately measuring both CI and CO is harder than it first appears. All models are wrong, some models are useful...
It's also weird to have a section on the metabolism hypothesis, but neglect the obvious standout from the data, which is that basal metabolism is the bulk of CO even at "heavy" activity level. An appropriately intense workout/sports/whatever might be able to get a higher percentage, if it's sustained long enough...conversely, the amount of calories burned from modern intentional exercise is less than one would think, while also stimulating appetite, quite possibly ending in a net caloric gain. (I'm a fan of thermogenesis, personally - shivering and other subconscious involuntary movements are an easy way to passively burn calories. Much happier dryly chilling than wetly sweating in spandex. Have heard there's ice vests and such for people who don't happen to work in walk-in freezers.)