hypertension

Article

hypertension is a recurring concept in the Astral Codex Ten archive, appearing 3 times across 3 issues between November 24, 2022 and July 31, 2025. The archive places it in contexts such as “with hypertension and ACE inhibitors,”; “and most of the other things they measured… hypertension”; “two bright orange squares (gallstones vs. hypertension and hypothyroidism)“. It most often appears alongside Europe, US, 23andMe.

Metadata

Category: Concepts
Mention count: 3
Issue count: 3
First seen: November 24, 2022
Last seen: July 31, 2025

Appears In

- Europe (2 shared issues)
- US (2 shared issues)
- 23andMe (1 shared issues)
- 23andme (1 shared issues)
- 9-11 (1 shared issues)
- ACE inhibitors (1 shared issues)
- ACE inhibitors (1 shared issues)
- Adderall (1 shared issues)
- Alex Young (1 shared issues)
- Americans (1 shared issues)
- Americans (1 shared issues)
- anorexia (1 shared issues)

External Links

Source Context

Recovered passages from the original issue text. When the raw archive preserved outbound links inside the source passage, they are listed directly under the quote.

Semaglutidonomics

November 24, 2022 · Original source

Semaglutide is now as searched-for on Google as Prozac or Viagra. Even if this is a temporary Musk-related spike, even pre-Musk it was getting a little above half their level. But Google Trends doesn’t exactly track awareness; few people search for Prozac these days precisely because everyone already knows what it is. So all this tells us is that there’s a lot of buzz around semaglutide. Suppose for the sake of argument that 5% of obese people have heard of this drug. Step 2: Prescription Accessibility The FDA says Wegovy is indicated for obesity, defined as BMI ≥ 30, or for people with BMI ≥ 27 and certain medical conditions. Does that mean that if you have that BMI, your doctor will give you a prescription? I think most doctors will want patients to try diet and exercise first. My experience as a doctor is that most obese people have already considered diet and exercise. Sometimes if you have a very compelling reason and a very well-thought out plan you can get them to try again. But usually they are obese because diet and exercise are hard for them, or don’t work for them, or some other reason besides “they never thought of it”. Still, I hear lots of stories about patient-doctor fights here. I assume this will happen with Wegovy too. Every doctor will have their own threshold for what amount of “already tried diet and exercise” is enough to justify a Wegovy prescription, and sometimes patients won’t meet that threshold. The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy. …except that this time, Silicon Valley is short-circuiting the process with fly-by-night telemedicine companies that guarantee you’ll get the drugs you want. For example, NextMed charges $138/month ($99 first month only!) for a guaranteed GLP-1 agonist prescription, plus “support and messaging with expert doctors”. The DEA sometimes shuts these groups down when they start playing around with controlled substances (eg addictive drugs like Adderall), but Wegovy isn’t controlled, and the government probably doesn’t care that much here. These services guarantee that people with money will be able to circumvent conservative doctors and access a prescription. Only 75% of Americans have PCPs at all. If we assume half of them will eventually be able to get a Wegovy prescription from their doctor, that’s 37.5%. Step 3: Affordability Semaglutide costs $15,000/year. Well-off people like Elon Musk might be able to pay that out-of-pocket, but most people will probably need insurance coverage. Right now this is spotty. Medicare doesn’t cover obesity drugs. This isn’t a reaction to the threat of semaglutide-related cost explosions - they’re not that smart. I think Medicare laws were just written in the old days when people were less likely to think of obesity as a disease. Is it time for change? Some Congressmen have proposed a very noble-sounding law telling Medicare and Medicaid to start covering weight loss drugs. I‘m sure this is out of deep compassion for America’s obese population and not because it would make pharma companies one billion zillion dollars. One of the Congressmen even has the last name “Kind!” Some pharma lobbyist probably got a bonus for that one. Private insurers mostly have to cover whatever Medicare does, but they can choose whether or not to include extra non-Medicare-covered drugs. Some have chosen to cover semaglutide under some conditions. Others would prefer not to cover it, but can be scared into covering it by the magic words “medical necessity”. Overall I don’t understand the laws here beyond that maybe they’ll cover it and maybe they won’t. Here, too, it might be time for change. The New York Times is publishing articles trying to convince us that private insurances not covering semaglutide is an outrage. Here in the tiny gray text, I want to take a second to complain about this article. It notes that Wegovy (semaglutide for obesity) costs more per prescription than Ozempic (semaglutide for diabetes), and calls this “a gross inequity”, accusing Novo Nordisk of “charg[ing] people more for the same drug because of their obesity”. But the obesity prescription is higher dose than the diabetes prescription! Milligram per milligram, Wegovy costs *less* than Ozempic! A steelmanned version of the NYT might object - don’t most of the costs come from the intellectual property and not the manufacturing, so that dose shouldn’t matter? Yes, but if you made the obesity version cost too much less per milligram than the diabetes version, then diabetics would cheat the system by buying the obesity version and splitting it into smaller doses! Insurances that do cover it may require extra documentation that the patient has tried lots of diet and exercise, maybe including some official diet-and-exercise program like WeightWatchers. They might also want documentation that patients have tried cheaper earlier-generation weight loss drugs without success. Even when insurances do cover semaglutide, copays may be very high. I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my out of pocket limit. Harsh. People with better insurances might get hit less hard, but I don’t think anyone will be picking this up for cheap. Let’s say only 5% of people who clear all previous hurdles can afford the drug. How Many People Get Semaglutide? 140 million obese Americans * 25% interested * 5% know of semaglutide’s existence * 37.5% can get prescriptions * 5% can afford it = 33,000, which is a pretty good match for the 50,000 estimated prescriptions. I didn’t even fudge the numbers to come out right, it just happened. The Coming Decade As a service to pharma investors, Morgan Stanley modeled the economic future of obesity medications over the next decade. Their headline result: semaglutide and various semaglutide-copycat-drugs will be a $30 billion market by 2030. That’s less than the $500 billion disaster I was afraid of! But still almost 10% of all US drug spending! Here are two core analyses from the report: The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%

Inline links: NextMed, a very noble-sounding law, https://substackcdn.com/image/fetch/$s_!l_X7!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2F1dbb9e98-6e07-4237-988e-3b7a61af3e5a_1381x834.png, is publishing articles, https://substackcdn.com/image/fetch/$s_!R-zS!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2F0f24b293-27de-462a-84fd-bed2ba7cf07f_1723x831.png, modeled the economic future of obesity medications over the next decade, https://substackcdn.com/image/fetch/$s_!zSOS!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2F0906b28a-1ad4-421d-a055-87ed95db59ce_918x261.png, https://substackcdn.com/image/fetch/$s_!QJj9!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2Fb966f730-6b24-48e1-98b1-e710cda9264c_903x656.png, this is mysteriously not how things work in health care, https://substackcdn.com/image/fetch/$s_!5poy!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2Fc201f05a-7d1f-4738-911f-11d0d051adf9_2880x1562.png, Institute for Clinical and Economic Review, don’t think there are technical barriers, offers a Savings Card, This startup, about the same amount for Ozempic, This article in Drug Discovery Trends, Everyone else seems as confused as I am, NHS will, private clinics

The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want. I’m not sure this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%

Inline links: this is mysteriously not how things work in health care, https://substackcdn.com/image/fetch/$s_!5poy!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2Fc201f05a-7d1f-4738-911f-11d0d051adf9_2880x1562.png, Institute for Clinical and Economic Review, don’t think there are technical barriers, offers a Savings Card, This startup, about the same amount for Ozempic, This article in Drug Discovery Trends, Everyone else seems as confused as I am, NHS will, private clinics

Response to Hanson On Health Care

April 30, 2024 · Original source

…and the same is true of hypertension and most of the other things they measured.

I find it unfair to present this claim without presenting my reasoning, which is that there’s a whole other paper, How Free Care Reduced Hypertension In The RAND Health Insurance Experiment, which does various sanity checks to this result, finds that it holds up, and finds related claims with lower p-values.

Inline links: How Free Care Reduced Hypertension In The RAND Health Insurance Experiment

Suddenly, Trait-Based Embryo Selection

July 31, 2025 · Original source

Aside from two bright orange squares (gallstones vs. hypertension and hypothyroidism - I don’t know what’s up with this and it doesn’t seem to be a widely-appreciated result) we see that most correlations are zero or positive - that is, selecting against one disease selects against another or at worst does nothing. In this ocean of blue, worrying about those few orange squares feels a bit motivated. Hans Jonas-ism says that no medical intervention may ever cause any harm, no matter how much benefit it produces. By this standard, perhaps slightly raising the risk of gallstones in the process of preventing various cancers and psychoses and other forms of human misery is unacceptable. To anyone with the more normal perspective where something with large benefits and tiny downsides is still pretty good, I don’t think the antagonistic pleiotropy argument carries much weight. Ethical Objection: Cost No way around this one: if these products work, they mean that rich people can have healthier/smarter/taller/prettier kids than poor people. One might object that at least they’re in good company: other products which help rich kids get healthier/smarter/taller/prettier than poor kids include private tutors, gyms, hair salons, health insurance, clothing, books, and food. Is this really the time to declare ourselves against this kind of thing? But maybe we should fight against expanding this already-bloated category. Or maybe there’s something more final about a genetic advantage. Maybe a stronger argument is that rich people get first crack at every new technology, but poor people usually follow close behind. The first cellphone, in 1982, cost $12,000 in today’s dollars. Now you can get something a thousand times better for $50, and Kenyan pastoralists use cell phones to call up the local shaman. The trajectory of genetics has been even more striking: sequencing a single genome cost about $100 million in 2000 and is somewhere around $100 today. Polygenic embryo selection has the potential to follow a similar path. There are two associated costs - sequencing the embryos, and running the analysis. Sequencing costs are decreasing and may eventually be comparable to the sorts of genetic screening (for e.g. Down Syndrome) that most families get anyway. Analysis costs are mostly the one-time expense of inventing the predictor; we might expect these to follow the same pattern as generic medications, where cutting-edge technology is jealously guarded and expensive, but last decade’s technology has made its way off patent and is cheap-to-free. A few groups have already created free open-source predictors; so far these are much worse than the private companies’ versions, but one of last year’s ACX Grantees is working on a better one. Also, it would be crazy for any forward-thinking government not to cover this; it could save hundreds of thousands of dollars in future health care expenses. In countries with public health care, this comes directly out of the government treasury; even in the US, it’s covered by Medicare after age 65. The government should be begging people to select embryos. The most persistent cost barrier is likely to be in vitro fertilization itself, a necessary precursor. In the US, 2-3% of babies are born through IVF. For those kids, this is a no-brainer - even if the cost never comes down, the cheaper products are only a fraction of total IVF expense. What about the other 98%? If those parents feel like they have to get embryo selection (and therefore IVF) to keep up, this could be a significant burden. IVF isn’t fun - it requires pumping a woman full of mind-altering hormones for weeks, extracting eggs in a minor surgery, and then implanting embryos in another minor surgery, all with a decent chance that some step will fail and you’ll have to do it all again. It also costs $15,000 in the US (less in poorer countries), and unlike the genetics, the cost has barely gone down in the past twenty-five years. Some countries, including Israel, offer free IVF for anybody who wants it. And universal basic IVF is surprisingly popular even in the usually government-phobic United States - Donald Trump made it part of his campaign platform. So there’s a plausible path to embryo selection for everyone who wants it. But it’s still going to take a while, it will hit different people at different times, and so far11 there’s no way around the month or two of various miserable medical procedures for women. Ethical Objection: Personhood Is it really correct to say that you have reduced someone’s risk of breast cancer by 46%, if what you’ve really done is closer to replacing them with a different person who is 46% less likely to have breast cancer? I cover this one in more depth here. Ethical Objection: Race This one is awkward: right now the technology works best for white people. Most genetic data available for research/commercial use comes from the UK, US, and Europe - areas which are mostly white. Asian biobanks, and those serving US minority communities, have been more reluctant to share data. So we know a lot about the genetics of white people, and only a limited amount about the genetics of anyone else. Companies are suitably embarrassed about this, and researchers in the field are working hard to wring every ounce of information out of the minority data they have. But for now, white people are the clear winner. Here’s data from Herasight: A European family with five embryos and no family history can cut their diabetes risk by 47%, and an African family 29%, with everyone else in between. As usual, all companies say that they adjust their scores based on the couple’s genetic ancestry. As usual, Herasight challenges them to publicly release data on exactly how they performed the adjustments and how well they work. All companies say they are working as hard as they can to improve cross-ancestry portability, but that progress will remain limited until governments collect/release better genetic data on non-white populations. Ethical Objection: Selection At some point, you’ve got to choose. Genomic Prediction and Herasight offer scores that aggregate overall health risks. Some people will follow them slavishly. Other people will try to second-guess them - would you prefer your child have lower cancer risk, or less chance of heart attacks? And this is the best case scenario! Herasight offers predictors for IQ, height and BMI; Nucleus offers those plus eye color and hair color12. A parent might encounter a situation where the embryo with their favorite eye color also has the highest cancer and schizophrenia risk, and choose to doom their child to cancer and schizophrenia because they really want pretty eyes. On average, even if everyone in the world selected for eye color, it wouldn’t raise cancer and schizophrenia risk. No not-deliberately-perverse polygenic selection choice can make your child worse off in expectation. Still, suppose you got cancer, and your mom admitted that she selected you for pretty eyes and didn’t even check the cancer column of the embryo selection report. How would you feel? And would you feel better or worse than someone whose parents didn’t do embryo selection at all, and spent the money on a Caribbean vacation? What if they selected your brother for everything great, then had you naturally? What if they selected you for IQ, but actually you are very stupid, and you were one of the 20% of cases where a predictor that’s right 80% of the time gets it wrong? Mark my words, one day there will be entire subfields of therapy dedicated to these issues. Going Nuclear Even as outsiders criticize the whole field, Herasight has launched a full-scale attack on competitor Nucleus. Herasight’s white paper compares its own predictors (favorably) to those of Orchid and Genomic Prediction… …but refuses to acknowledge Nucleus at all. In a supplementary note, the authors explain why: they accuse Nucleus of being so bad that it would “not yield a reliable or meaningful addition to our analysis”. They say Nucleus has inflated the accuracy of their scores. This is most dramatic for a few conditions like ADHD, where the leading published polygenic score is based on 2,300,000 variants but explains only ~1% of variance in the condition. Nucleus’ score is based on 12 variants13 and (implicitly) claims to explain 3-6%. This doesn’t make sense. Some of Nucleus’ other scores do use millions of variants. But many of these are 5-10 year old scores downloaded from open-source catalogs, whose accuracy statistics are easily available and far less than Nucleus claims. Here is what Herasight finds when they double-check Nucleus’ numbers: On their Substack, Herasight also criticizes Nucleus’ monogenic screening product. They point out cases where it fails to properly screen for the conditions it claims. For example, the Nucleus website advertises screening for spinal muscular atrophy: But on their gene list… …they don’t screen for SMN, which causes 95% of spinal muscular atrophy cases. They only screen for UBA1, which causes a distinct and much rarer condition called x-linked infantile spinal muscular atrophy. Professional organizations publish guidelines for what genes need to be screened in a screening product, and Nucleus does not appear to be following them. In further discussion, Herasight continued with exhaustive criticism of essentially everything Nucleus had ever done down to the smallest detail. Nucleus reports list the same baseline disease risk regardless of patient ancestry, but different ancestry groups should have different risks14. Nucleus’ physician reports sometimes list lower-than-average risk for patients with positive polygenic scores15. Nucleus’ age-based risk tables don’t distinguish between age and cohort effects (is this bad? see footnote16). My favorite critique is that Nucleus wrote a blog post criticizing competing company Orchid… …which included a section on how Orchid is a polygenic selection company, and polygenic selection companies are inherently “sketchy” and “honestly should be illegal”. But Nucleus is also a polygenic selection company! This is like Marlboro attacking Camel on the grounds that cigarettes are addictive and should be banned! Obviously something went wrong here - my guess is AI - and it’s a really bad look, especially when these scientific issues are so hard to litigate, and so many of us will have to go off gestalt impressions of corporate culture. Nucleus states that they validate their models internally and intend to make their results public soon. A Foothill Of The Future It’s hard not to love this technology. Lots of people (and the aforementioned professional organizations) manage anyway, but it’s hard. If this were a single-use medical treatment, delivered by a doctor after someone got the relevant condition, it would be one of the biggest advances of the decade - imagine a drug that cures 10 - 40%17 of breast cancers with no side effects! But in fact, it works for breast cancer, and schizophrenia, and heart attacks, and approximately everything else. The only things comparable are antibiotics and GLP-1RAs. And then there’s the IQ effects. Even after studying the literature, people have wildly different opinions about the importance of IQ. One of the most important debates is to what degree IQ differences are a cause of poverty, a consequence of poverty, or both. I lean towards both - a country with limited access to schools and medical care will have low average IQ, but as a consequence it probably won’t become the next big semiconductor hub. This technology could close half the IQ gap between poor and middle-income countries, or between middle-income and rich. Or it could give rich countries average IQs that have never been seen before, and let us see what kind of O-ring technologies (and new forms of social cooperation) lie just beyond the frontier. (this is the nice quantifiable argument in favor of IQ enhancement, but I find myself more convinced by fuzzier things - how much is it worth to be able to enjoy great art and literature? To fully comprehend what we know of nature, and be able to fully appreciate the mystery of the rest? To have a sense of why society works the way it does, instead of feeling like you’re being blown back and forth by institutions you don’t really understand? Amateur psychoanalysts like to say that the only people who care about IQ are those looking for an excuse to boast about how high their own is, but my experience is the opposite: I care about IQ because I bang up against the limits of my own a thousand times a day, and I hate it. I fantasize about ways to make my children smarter than I am for the same reason a dog confined in a tiny crate might fantasize about getting her puppies adopted out to a nice house with a big grassy yard.) My biggest qualm is that it might not matter. This is such a tiny foothill, flanking such a vast and foreboding range of mountains, that it might be a mistake to care about it at all. Selecting the best of five or ten embryos is not a very effective way to get the genes you want. There are things in the pipeline that will make this look like Hippocrates draining black bile. By the time the first polygenically selected children are adults, they’ll be old news. And then there’s AI. The average age at diagnosis for Type II diabetes is 45 years. Will there still be people growing gradually older and getting Type II diabetes and taking insulin injections in 2070? If not, what are we even doing here? Many people in the transhumanist community are still bullish on this technology. They think - well, there’s still an outside chance that something comes up and AGI takes another few decades. If we can enhance humans to be smarter, healthier, and more determined by the time it arrives, maybe we’ll have a better chance. Or maybe, if there’s a positive optimistic vision of a human-based high-tech future, people will be more willing to delay AI in the first place. I like this argument, but I also think it’s worth stepping back. What’s the point of anything? Why have kids at all in a world that’s changing this fast? Why save for the future? At some point your answer has to be romantic and aesthetic - it’s never been clear whether anything you do matters in any ultimate sense, but you’ve got to act as if it does and hope for the best. From that perspective, this is the most romantic technology of all. You’re not just giving a better life to your kids. Genes travel from generation to generation; you’re giving a better life your grandkids, your great-grandkids and so on to the point 1.77*log₂(population) generations from now when you are the ancestor of everybody and nobody. Somebody in Macaronesia in 3525 AD will avoid getting breast cancer because of you (if there is still cancer; if there are still breasts). Some combination of reasonable cost-benefit analysis and romantic/aesthetic commitments makes me want to have children despite the uncertainty, and the same combination made me sign up to use this technology despite the same. More later on how that’s going. 1I’m slightly mixing up two different things here - Down Syndrome can be detected with an aneuploidy test, but cystic fibrosis takes a more involved PGT-M test. 2There are two separate questions here. First, how much would diabetes risk decline if you selected the embryo with the lowest risk for diabetes - something you have no reason to do, since you have no reason to privilege diabetes risk over risk of any other disease? Second, how much would diabetes risk go down if you selected the embryo with the lowest health risk overall? Genomic Prediction’s their risk calculator calculator shows, seemingly paradoxically, that you get -38% relative risk by selecting against diabetes alone, but -41% relative risk by selecting against everything at once. Over email, they stand by this surprising result, saying that “for a couple of diseases (type II diabetes and CAD), the EHS actually accomplishes a larger risk reduction than the individual predictors. The explanation is that the EHS takes into account multiple PRS of diseases with high comorbidity”. See eg Figure 3 here: …and the section of the post called “Antagonistic Pleiotropy” for more. However, this paradoxical benefit is only true for a few conditions like diabetes - for everything else, selecting on health index does better than you would naively think, but still does not decrease the risk of a given condition as much as selecting against that condition directly. 3That is, new mutations in that particular baby, as opposed to older mutations already present in the parents. 4Conflicts of interest: I have used Orchid’s and Herasight’s products on my own embryos (not the ones used to conceive my existing kids, but for a potential third child), employees of Genomic Prediction and Herasight have been extremely helpful in contributing expertise to ACX posts on genetics, and I might invest in this field at some point (though haven’t done so yet). This post started as Herasight asking me to write about their white paper, then spiraled out of control. There were some unexpected time pressures and the result is that I didn’t get a chance to run everything in Herasight’s white paper by their competitors as thoroughly as I would like. Although I talked to representatives of all four companies profiled here, I feel like this probably reflects Herasight’s perspective better than other companies’, and that this is a major flaw. If other companies have responses, I’ll publish them. Thanks to all companies involved for their assistance on this article. Finally, I am favorably disposed toward Herasight because of how I learned about them: a professor named Jonathan Anomaly got cancelled from Penn for being too gung-ho about genetic enhancement, and used his newfound freedom to join a very-early-stage Herasight, raise their ambitions, and sell everyone (including me) on the idea. I grew up on a diet of books and movies about mad scientists, and I’m a sucker for a story about a guy named Doctor Anomaly pursuing revenge against the small-minded fools who destroyed his career by creating a race of superbabies. 5The version of the tool I looked at said 5.9 points for five embryos, up to 9 points for twenty embryos. The version of the tool on their current said says 5.3 - 9, so they might have recalculated after I finalized this article. 6Used in quotation marks because these scores were fine for the predictive tasks they were applied for - they just weren’t finding genes that directly caused the outcome of interest. 7Conflict of interest notice: this table was originally unadjusted. A representative of Herasight claimed that this was unfair, because each company used slightly different reporting conventions, and offered to correct for this in a neutral way. I retraced their reasoning, confirmed that the correction did not especially benefit Herasight at the expense of other companies, and accepted the correction. The original unadjusted table is below: Herasight was insufficiently comfortable with Nucleus’ methodology to even be willing to posit a corrected value, so I left their self-reported value in gray. 8Zagorsky (2007) says an extra IQ point means $234-$616/year in higher salary. The midpoint of $425 equals $670 in today’s dollars; assuming a forty-year career, Nucleus’ +1 point estimate is worth $26,800 (vs. $9,249 Nucleus cost) and Herasight’s +6 point estimate is worth $160,800 (vs. $53,250 Herasight cost). 9As part of researching this article, I asked all four major companies about their within-family validation strategies. Here are some details: Genomic Prediction discusses their strategy in this paper. The results are complicated to interpret - the within-family numbers often have such wide error bars that they overlap with both the across-family numbers and with zero - but looking qualitatively it seems like most scores on average lose about 25% of their risk reduction ability (though averages might not be the right way to do this, and some might be much more affected than others). Their website reports unadjusted, not within-family validated numbers; GP says they say this clearly on their site (which is true), Herasight counters that they still present their numbers as applicable to embryo selection (which is also true). To get the most applicable-to-embryo-selection numbers, you might want to adjust GP’s stated numbers down somewhat; it’s hard to say exactly how much, but maybe 20 - 25%?

Astral Codex Ten

Table of Contents

Atlas

hypertension

hypertension

Article

Metadata

Appears In

External Links

Source Context

Backlinks

Astral Codex Ten

Table of Contents

Atlas

hypertension

hypertension

Article

Metadata

Appears In

Related Pages

External Links

Source Context

Backlinks