545 Comments
Comment deleted
Expand full comment

It's really not.

Expand full comment
Comment deleted
Expand full comment

I believe the conventional wisdom is that, at least in humans, living longer has been selected for. See the Grandmother hypothesis. Because infant and children humans are so much weaker and fragile than infants of other species, we have adapted to live longer to provide support to our children as they rear their own children.

Expand full comment
Comment deleted
Expand full comment

I don't think there's a clear answer, this hypothesis was developed to help explain why human beings lived significantly past the age of menopause. Though I am by no means an expert in this field. That being said, given the number of genes you share with each subsequent chain of your lineage exponentially decays, I would expect the fitness benefits of aging longer to rapidly dwindle.

Expand full comment

I think it is important for people to become weaker and infertile as they grow old, because otherwise they would be competing with their own offspring for status, resources and mates. That kind of cross-generational strife would be terrific for tearing apart families, tribes and societies. Perhaps we evolved to age as we do because those proto-humans that did not tore each other to pieces?

Expand full comment

I believe there is a strong difference between selection for lifespan and the grandmother hypothesis, which is really needed not because of long life, but because of long (well, relatively long) life past menopause, where you really needs some special kin selection (advantage not on yourself, but on multiple individuals sharing part of your genes.) because normal selection predict the fitness after reproduction to be 0, by definition. So only indirect effects are present, in the form of helping (GM hypothesis) or hurting (consuming their resources).

For the reproduction lifespan, it should always be a positive in term of fitness, because living longer allows to produce more offspring, trivially....Kin selection may interfere, indeed, but for it to select shorter life there should be a pretty big hit on fitness of many offsprings (1/2 of your genes) or grand-offsprings (1/4) just by your existence. I do not think this is a likely explanation, because your own consumption of resource is no greater than the one of your competitors, so I thing dying off to let your used resource go to your kin does not work out mathematically. It does only makes sense in group selection, but group selection is not considered a valid explanation anymore. The only example I see where dying off is directly selected because of kin selection is some animals dying off to feed off their (very numerous) offsprings. This happen in some spiders iirc (sometimes with a twist, where the male feed off the female some of the time), and there I can see how death pays off in term of amount of offsprings succesfully reaching reproduction age, so in term of fitness....

The "short" lifespan is mostly explained (and I think this is a very convincing explanation) by tradeoff of extended lifespan vs other things, like added fitness at young age (faster growth, or other short-term advantage at the price of lifespan), because there is always a time preference linked to "accidental" death: the biological lifespan is longer than the actual one, because of all the non-age-related deathcauses (sickness, predation, accident). So a long biological life always have diminishing return in term of fitness, which means any tradeoff will defavor immortality. The equilibrium (average biological life expectancy) depends on the actual set of tradeoffs in a particular organism (I guess it depends on general organisation, so past evolution, which often put a lot of contraints on future possinble adaptations), but also on the rate of "accidental" death and offspring production rate: low offspring production rate and/or low accidental death rate means longer life. This is one explanation for the longer lifespan of flying creatures, compared to non-flying ones with similar size. Less accidental death rate because flying is a very efficient escape mechanism, maybe lower offspring production rate (because flying usually take more time, as half-flying may be dangerous) -> longer lifespan. The prime example is Bats vs non-flying small mammals.

Humans have quite low offspring production rate and accidental death compared to similar-sized mammals (and, but it's far less clear, compared to close apes). We also have longer lifespan, but not hugely so (compared to chimps)...So it kind of make sense. This also makes me believe there will likely be tradeoffs linked to "easy" anti-aging drugs, because the current lifespan is already a tradeoff...

Expand full comment

It seems like evolution _should_ select for a thousand years and pumping out a baby every year. But instead we cease to be able to reproduce decades before we actually die.

One theory I've heard is that it's parasite-related and the same reason that most complex organisms reproduce sexually rather than asexually. If you live long enough with the same DNA then eventually parasites will become very good at targeting you, specifically. Better for your genes to keep swapping around as much as possible to stay a moving target.

I'm not convinced that this quite makes sense.

Expand full comment

Women cease being able to reproduce after menopause. Men can reproduce at very advanced ages.

Expand full comment

Women stop being able to reproduce because of aging. The female reproductive system has to function better than the male one in order to bring a viable fetus to term, and it also is much more dangerous to the woman when it malfunctions. women die from reproductive tract issues more frequently than men do for a reason.

Expand full comment

>Women stop being able to reproduce because of aging.

You sure about that? Isn't it still controversial if women are born with all the ovuli for their entire life or they keep producing it every month?

Expand full comment

There were a handful of papers at one point that suggested adult female mice might be capable of neo-oogenesis but that didn’t pan out. We do appear to be born with as many oocytes as we will ever have.

Expand full comment

Does menopause also exist for other long-lived species like elephants or tortoises?

Expand full comment

I’m not sure this is precisely correct. A woman’s body could stop aging and she’d still reach an end to her reproductive lifespan at some point. Women can’t make more eggs, so once you run out of what you were born with, that’s the end. Technologically this might change at some point and we might be able to make more oocytes for someone in vitro, but naturally we have what we have.

Expand full comment

If that were the case, we don't grow old and keep pumping out babies until we die, we would probably not live much longer than we already do - especially prior to modern medicine. As others have mentioned, dying in childbirth is a real thing and a real problem. Having thousands of babies would simply increase the death rate to a point where it's certain what (barring something else happening sooner) women would die from in their lives. Once women consistently lived to the point where they died in childbirth, there would be no point in women having any greater lifespan at all. Therefore, evolution should prioritize what gets a reasonable number of births per woman, and then prioritize other things (like the grandmother hypothesis or whatever).

Expand full comment

Are humans actually a good example to look at when considering the general question of the evolutionary value of longevity and reproductive windows? I could be mistaken of course but I thought that a confluence of strange selective pressures resulted in the rather extreme difficulty of reproduction for human women and that the vast majority of mammals have a much easier go of it.

Expand full comment

I think that just raises the question to another level - why do humans die in childbirth? For lack of a better alternative explanation, we are presuming that there is a tradeoff involved that selected for what we have now, and that by going a different direction we would have lost out on some other metric.

That does presume that rabbits (or name your highly fertile mammal) wouldn't hit the same wall we are talking about with humans. Most mammals in the wild have very high likelihood of dying to various non-birth causes. If those other causes went away, maybe more would die in childbirth as well. Meaning, it would be more advantageous for them to get better at basic survival than to continue increasing their ability to procreate.

Expand full comment

A lot of variation in natural lifespan seems to be based on "how good is this creature at avoiding being killed and eaten?"

Creatures that are bad at that generally have a short lifespan.

Creatures that are good at that tend to live significantly longer.

This suggests that living a longer period of time is beneficial, all other things being equal, but it can't be selected on if you aren't living that long.

So mice don't live very long at all because they all get killed and eaten.

Humans notably have extremely long lifespans for creatures their size, and indeed, in general, which suggests living longer has a significant biological advantage for them.

Expand full comment

Indeed. You just have to add some biological tradeoff between decreased aging, and increased fitness/unit of time to see that in case of many non-age related deaths, increased fitness/unit of time will be selected against decreased aging. And such tradeoffs are easy to find: scars heal wounds faster but prevent perfect regeneration, faster growth to reproductive age vs more controlled growth, increased energy efficiency vs better waste cleaning, better immune response vs more autoimmune problems,....

Expand full comment

extremely long lifespans, well, it depends. Compared to the other apes, we live longer, but not crazily longer. Longest living chimps reached 65-70 years in captivity....and they weight 50 kg. So we are not that special compared to our nearest cousins. the bodysize->lifespan scaling seems to be 0.15-0.3, so if humans are 75 kg, chimps 50, and lives 65y, taking a 0.2 exponent you expect a human to live 65*(75/50)^0.2=70.5. I guess with the relatively small chimp sample, and captivity conditions, humans would be recorded having a 75-85 max lifespan. Maybe about 15% than you would expect...

Expand full comment

I fear that we won't get to find out promptly (read: while I could benefit) because of the FDA's stubborn insistance that aging itself isn't a disease (making it harder to meet ethical critera are a were).

More generally, I'm furious at the many bio-ethicists who are complicit in the game where something bothers ppl in the population but it doesn't seem like a coherent worry so the bio-ethicists compete to see who can offer a theory of why that worry should be taken seriously.

I'm a fan of exploring these ideas but it's not cool when bio-ethicists work to justify our emotional impulses rather than working to correct them when they disagree with our best rational reconstructions of morals.

Expand full comment

Nir Barzilai, the scientific director of the American Federation for Aging Research (AFAR), seems to be much more optimistic about FDA support. He is currently leading the TAME trial, whose end goal is to get the FDA to approve aging as a treatment indication. He and Jamie Justice said in an interview with the Foresight Institute that the FDA had been very helpful in establishing trial guidelines that would lead to this goal.

Expand full comment

I just interviewed Nir Barzilai for my Live Longer World podcast! And yep he mentioned how the TAME trial is meant to serve as a template to get the FDA to approve drugs to target the biology of aging itself.

Expand full comment
Comment deleted
Expand full comment

Goddammit, she's got italics.

Expand full comment

"More generally, I'm furious at the many bio-ethicists who are complicit in the game where something bothers ppl in the population but it doesn't seem like a coherent worry so the bio-ethicists compete to see who can offer a theory of why that worry should be taken seriously."

I'm less harsh on this intellectual habit than I used to be, given that tinkering with human biology and social relations in particular can have long-term side-effects that no-one predicted. e.g, contraception and abortion paradoxically made it easier for men to keep mistresses, which led married women to retaliate with 2nd-wave feminism in the 60s/70s and was most likely a huge contributor to the soaring divorce/illegitimacy rates we've been seeing ever since.

The consequences of our currently rapidly ageing population and shrinking birthrates (most especially in the developed world and China but rapidly becoming a global issue) are so potentially terrible that I'm not going to turn down anything that helps offset those problems, but I think it's naive to imagine that radical longevity won't have significant long-term drawbacks as well, even if we can't logically nail them down right now (and a few plausible downsides have already been proposed.) A lot of the time, these conservative instincts are actually right.

Expand full comment

(To be clear, I'm not suggesting the pill and abortion-access had no benefits or that it would be practicable to roll them back- that genie is out of the bottle and it's quite possible the net benefits to human well-being outweighed the erosion of marriage norms. But I don't think the people who were/are worried about the social consequences had no valid perspective, even if they couldn't quite nail down the why beforehand.)

Expand full comment

I would like a citation on the idea that 2nd wave feminists where primarily motivated by an increase of misstress having.

Expand full comment

Maybe using Eugenics as an example would've been better, since it is more obviously bad.

Expand full comment

Perhaps... but I honestly consider the stigma surrounding eugenics to be fuelled entirely by selective remembering and double-standards (20,000 lobotomies in the US alone prior to the 1960s didn't cause us to ban psychiatry or spend most of a century insisting that the brain was not the seat of intelligence.)

Expand full comment

While I agree that eugenics as concept probably didn't deserve to be tossed out wholesale by the post-WWII world order, the idea that the stigma is fueled "entirely" by selective memory strikes me as a bit fatuous. Likewise, comparing the ill-effects of popularized and politically charged eugenics to those of early psychiatry is...well, disproportionate in the extreme is probably the polite way to put it. Practical eugenics has been a major factor in the biggest genocides and the nastiest caste systems of the last couple of centuries. Literally some of the worst things that have happened to humanity in recent memory.

So the scope of the atrocities in question (psychiatric motivated vs. eugenics motivated) is out of whack. Additionally, the comparison of the rejection of eugenics to "insisting that the brain was not the seat of intelligence" doesn't fit. This would only make sense if the anti-eugenics contingent insisted that genes don't play a role in life outcomes (granted, some people do make this argument, but most don't). The more common and, I think, more serious argument against eugenics is this: while genes have a huge impact on life outcomes, we aren't at a point yet as a species where we can confidently say whether certain genetic traits are desirable or not (excluding those which cause disease, obviously). And if we were to start identifying particular genes as desirable or undesirable, our social structures may not be secure enough to prevent our species from sliding towards a genetically homogenous Gattaca-style dystopia.

Anyway, with all that said, I more or less agree with your point.

Expand full comment

"This would only make sense if the anti-eugenics contingent insisted that genes don't play a role in life outcomes"

This was more-or-less the practical position of the academy for most of the last century whenever any specific divergence in gender, class or racial outcomes was discussed, and it is effectively an assumption that most of our social policy regarding education and welfare is still predicated on. To this day, any politician suggesting a moderate and humane version of a eugenics program, such as paying meth addicts to use long-term birth control, altering tax structure to favour middle-class fertility, or subsidising access to embryo selection or sperm banks, would be committing career suicide- certainly if he or she explicitly justified this on genetic grounds.

"...comparing the ill-effects of popularized and politically charged eugenics to those of early psychiatry is...well, disproportionate in the extreme is probably the polite way to put it."

I don't accept that charge. Roughly 70,000 people were forcibly sterilised under eugenics programs in the united states. Lobotomisation is arguably worse than sterilisation, and when you add in other therapies such as early forms of electroshock, insulin shock or heroin medication, I think one can make a completely plausible argument that psychiatry destroyed as many lives as formal eugenics movements in the US and most of the developed world.

Comparisons with 20th century genocidal regimes- most obviously the Nazis, Imperial Japan and the like- also fall under the heading of double standards. If we had reacted to Trofim Lysenko and the Holodomor, or the Killing Fields and Great Leap Forward, in the same way as Mengele and Auschwitz, we would have spent most of century insisting that class did not exist, banning all public policy based on the idea that people are shaped by their environment, and demonising the notion that the rich might be exploiting the poor. I have no idea why the left gets to impose these lunatic double-standards on the conversation.

I would also point out that genocidal regimes have been as frequently motivated by resentment of a more-successful ethnic group as by the demonisation of a less-successful ethnicity, precisely based on the idea that- in the absence of genetic ability differences- the more-successful group must owe their pre-eminence to conspiracy or exploitation. The Nazis disowned IQ tests (a separate but not totally unrelated concept) precisely because the data from such tests kept contradicting their notions of jewish and slavic inferiority. If a belief in genetic advantage can lead to atrocity, and the *absence* of belief in genetic advantage can lead to atrocity, what exactly is the risk-free belief system we are supposed to adopt?

Lastly, while historical caste systems can certainly be nasty and much of the data here remains unclear, there is the outside possibility that some of the religiously-motivated marriage practices and sexual mores of pre-modern human societies effectively functioned as a kind of 'soft' eugenics program, and may even have helped make the Great Divergence possible. I don't want to jump to conclusions, and I'm not saying we don't have more liberal alternatives for tweaking the gene pool today, but it can't be dismissed on technical grounds either.

"Anyway, with all that said, I more or less agree with your point."

I appreciate that, and I don't mean to jump down your throat. It's just that I really think our society has a screw loose on this topic.

Expand full comment

" And if we were to start identifying particular genes as desirable or undesirable, our social structures may not be secure enough to prevent our species from sliding towards a genetically homogenous Gattaca-style dystopia"

Sorry, missed this part, but I have a few extra comments here- there seems to be a common assumption that the use of embryo selection or gene-editing would lead to higher genetic uniformity, and I want to push back on this in three ways.

1. If we were to identify every locus in the genome where a minor allele was beneficial or a major allele was harmful, it would in some sense be mathematically trivial to flip the frequencies around- 'make every common bad gene rare and every rare good gene common.' The result? Identical genetic diversity. Massive gains in fitness.

2. Most genetic diversity is either useless or bad. This follows from the simple observation that 80% of our DNA is junk and most mutations that affect function are harmful (absent other selection pressures, entropy always increases.) There are certain kinds of *phenotypic* diversity we want- a diversity of talents and personalities to solve different economic and social problems, and perhaps a diversity of skin tone, hair colour and body types for either aesthetic reasons or to adapt to different climates (which is why they evolved in the first place.) We don't particularly want a diversity of crimes or a diversity of cancers.

3. In principle, exotic options like horizontal transfer or designing genes from scratch could allow humans to add brand new material to their gene pool- either borrowed from elsewhere in the kingdom of life or synthesised from first principles. (This could potentially be useful when colonising places like Mars, so that colonists can tolerate higher CO2 levels, radiation, or perchlorate contamination. Just a thought.)

In other words, I think these concerns about 'loss of diversity' are overblown.

Expand full comment

There is nothing wrong with Eugenics itself. What's bad is the methods. Yes, it's obviously bad to kill off / sterilize\* "wrong" kind of people (nevermind the criteria weren't even sensible). It's bad because it's murder.

That doesn't imply gene therapy, designer babies and such are bad "because this is Eugenics, which is bad". This reasoning doesn't make any sense.

\* On topic, IMO it'd make sense to make anti-aging drug conditional on giving up rights to unrestricted procreation in order to deal with population explosion - certainly a better solution than killing people, which is what opposition to anti-aging proposes, pretty much.

Also, some solution to balance political power. Because while Scott says it's not a problem... eh, it might be. Plenty of people today claim "boomers" control politics.

Expand full comment

"Also, some solution to balance political power. Because while Scott says it's not a problem... eh, it might be. Plenty of people today claim "boomers" control politics."

Yes, I've made this point in another thread. Your suggestion for making immortality conditional on childlessness... I mean, in principle it could work, but I suspect the necessity of this measure won't become obvious until society is already close to some malthusian wall, and at that point it's probably too late. Unless our species gets a lot more rational over the coming centuries, which I suppose isn't impossible.

Expand full comment

At 73 I've yet to find that Boomer Button that controls politics. Maybe I'm just not trying hard enough...or slept through that day in school....

Expand full comment

Eh. I don't know if obtaining that level of evidential rigour is even possible in our current academic climate, but I think I first heard the idea put forward here.

https://www.youtube.com/watch?v=5wuBQa86nj0

Expand full comment

By a citation I did not mean literally a Chicago style citation or something alike. Just evidence. It is possible that such evidence is present in the video you included but i fear I do not hve the time to watch 50 minutes of video just to be sure there is. Is there any way you could direct me to some direct evidence? Maybe a number of notable feminist claiming their motivation was misstress related for example. Or failing that could you summerise the point.

If you claim that the climate is so bad that you wouldn't be abble to give any evidence whatsover, that would be too convienient to be true at all I believe. That would imply your claims are unfalsefiable.

Expand full comment

I'm struggling to try and dig up something more concrete, but I know this is a fairly widespread argument among conservatives and the theoretical arguments seem fairly sound. There's a specific rundown on the topic here coming from an academic thesis, if it's any help.

https://www.youtube.com/watch?v=EHNiBAjZq_0

Expand full comment

I suppose it's possible I'm just wrong about this, but the odds that the pill and abortion-access had no impact on the general culture or that those cultural effects were purely good seem slim to me.

Expand full comment

Seems like a product of advanced anal fact finding to me, but that's me...

Expand full comment

Two quick counter-arguments against that line of reasoning:

1) For every new technology, there are dozens of "predictions" about negative side effects. It is extremely difficult, even impossible, to determine which of those predictions will come true, and to what extent. That general argument could have been used to suppress all beneficial changes and progress in the history of humankind. Just think of all the negative long-term side-effects that this new-fangled bipedalism could bring!

2) The societal benefits from contraception and, to a lesser degree, abortion, are so much higher than the supposed drawbacks from more men keeping mistresses, that I can't even call this a "tradeoff" with a straight face. So even if this negative effect would have been reliably predicted, it was worth it.

Besides: Is the proportion of men "keeping mistresses" really higher than, say, 100 years ago?

Expand full comment

I'm fairly sure the incidence of adultery and illegitimacy is indeed higher, and one of the negative side effects of the breakdown in marriage (or at least a coincident trend) has been a collapse in birthrates below sustainable levels. The side-effects of the latter could be potentially catastrophic over the next few decades (which is part of the reason why I'm tentatively in favour of anti-ageing therapies to try and offset the other side of the demographic equation.)

https://www.youtube.com/watch?v=b1IJ9kqBilE

https://youtu.be/UkEwHQTv9IY?t=972

I realise all technologies carry risks as well as rewards- even things like the printing and social media, which might have seemed likely purely technical engineering developments at the time, have had seismic ramifications on the social fabric. It's tough to draw the line. I'm just saying that blind optimism is a little unwarranted.

Expand full comment

> one of the negative side effects of the breakdown in marriage (or at least a coincident trend) has been a collapse in birthrates below sustainable levels

Countries' fertility rates going negative is a cross-cultural phenomenon that is seen in pretty every single developed country worldwide, and is most highly correlated with decreased infant mortality and economic opportunities. Basically, people have more interests than just popping out babies which detract from those interests, and they don't need to have a lot of kids they no longer die before they reach maturity.

Expand full comment

"Countries' fertility rates going negative is a cross-cultural phenomenon that is seen in pretty every single developed country worldwide"

Yes? And which of these countries have not seen increasing divorce and illegitimacy?

"...they don't need to have a lot of kids that no longer die before they reach maturity"

As I have already pointed out and videos I linked to explain in excruciating detail, these birthrates have gone way below replacement fertility, and there are reasons to expect this to result in economic stagnation at best and catastrophic social collapse at worst.

Expand full comment

> Yes? And which of these countries have not seen increasing divorce and illegitimacy?

Plenty. Italy and Malta, for example. Below mean divorce rate, extremely low fertility rates (near 1). Plenty of representatives among developed nations, including Ireland, Greece. Compare for yourself:

https://worldpopulationreview.com/country-rankings/divorce-rates-by-country

https://worldpopulationreview.com/country-rankings/total-fertility-rate

> these birthrates have gone way below replacement fertility, and there are reasons to expect this to result in economic stagnation at best and catastrophic social collapse at worst.

Maybe. Social security depends on growing populations, but immigration can make up the difference for now. At some point we may have to reckon with the fertility rate issue, but I still don't see a significant causal association between the breakdown of marriage and the collapse of fertility rates, which is the only point I was disputing.

Expand full comment

> given that tinkering with human biology and social relations in particular can have long-term side-effects that no-one predicted

Yes, large changes have consequences. Still, last 200 years or so should make us want changes rather than stagnation.

Expand full comment

"which led married women to retaliate with 2nd-wave feminism in the 60s/70s"

The Female on Male spousal homicide rate decreased sharply in the US over that period.

"The consequences of our currently rapidly ageing population and shrinking birthrates are so potentially terrible"

I don't follow. Is the global population supposed to increase forever? Unless space travel and energy become very cheap, that sounds like it could have a problematic end. A lot of human problems go away if the population is smaller. And that will be even more true as automation replaces the need for manual labor.

Expand full comment

"The Female on Male spousal homicide rate decreased sharply in the US over that period"

Homicide rates in general decreased over this period, but this was coincident with large increases in incarceration and also improvements in medical technology (which turn a lot of potential murders into aggravated assaults.) One can plausibly argue that present-day homicide rates would be much higher otherwise.

"I don't follow. Is the global population supposed to increase forever?"

I think you misunderstand. Birth rates are far below replacement levels across much of the developed world at present. (Conversely, if death rates drop to near-zero due to perfect anti-ageing therapies, this actually will cause global population to increase forever unless birth rates drop to near-zero, which will create some of the problems you mention.)

I already mentioned some of the problems with ageing demographics in a previous post, but there's a video on the topic here. Automation can address some of these issues but not others, and relying heavily on automation will arguable exacerbate problems like income inequality and unemployment (moving a shrinking workforce into high-skilled professions assumes that all your workforce can be retrained to do high-skilled jobs, which is rarely true.)

https://www.youtube.com/watch?v=b1IJ9kqBilE

Expand full comment

Yes homicide rates decreased in general, but I'm pointing to a trend in spousal homicides apart from that. (Though charts which break out victims by race as well as gender seem to show a different trend, so I'm not certain exactly what's going on.)

http://1.bp.blogspot.com/__cLfPbhhwmw/SfHO8f_AfxI/AAAAAAAAB08/RQY5iaDd4zY/s1600-h/00+Intimate+Homicide.jpg

Expand full comment

Do you have a link to the full article? Male intimate homicides declining faster than women's is interesting, but I'm not seeing a comparison with homicide more generally.

Expand full comment

I believe this is the original source (results from the National Crime Victimization Survey.) I have not had time to read it, admittedly.

https://bjs.ojp.gov/content/pub/pdf/ipv.pdf

Expand full comment

Wow! That's a really interesting statistic. Do you have any theories about what might have caused that?

The obvious explanation is that the new easy availability of divorce meant that women could more easily escape abusive marriages and so weren't driven to kill their husbands in self-defense. (The majority of wife-on-husband homicides are at least claimed to be cases of self-defense against abuse.)

This would match up with the significant decline in suicides by married women in states that liberalized divorce laws.

But the very surprising result that husband-on-wife homicides *didn't* significantly decline to remotely the same extent would seem to argue against this.

Maybe the fact that abused wives are most likely to be murdered *when they attempt to leave* meant that more divorces exerted a counteracting pressure which increased the husband-on-wife homicide rate?

But in that case you would also expect the wife-on-husband homicide rate to increase, if there were an increased number of attempted lethal attacks on wives thwarted by wives killing husbands in self-defense.

It does seem, though, that most cases of abused-wife-on-abusive husband homicide that I've read about aren't self-defense in the narrow sense of fighting off an immediate lethal attack, but more attempts to escape a generally unbearable situation by attacking when the husband is off-guard.

And then one has to consider the striking fact that America is the only country on earth where wives kill (or at least *used* to kill, before the recent divergence you pointed out) husbands at a rate remotely comparable to the rate at which husbands kill wives. The obvious explanation here is that America has more guns and "God made man and woman, Colonel Colt made them equal"--but this utterly unique gender similarity applies even to non-firearm homicides.

Given that societies where wives are proportionately much less likely to kill husbands include both those that are equally or more gender-egalitarian than the US (NW Europe, the rest of the Anglosphere) and those that are less gender-egalitarian (everywhere else), as well as both societies that are less violent overall (Western Europe, the rest of the Anglosphere, East Asia) and those that are more violent overall (Latin America), it seems really hard to come up with a cultural explanation for this.

Expand full comment

I don't have that much more to contribute in terms of understanding root causes, except that It seems there's a stark divergence between trends as they apply to black men and caucasian men. Black men saw a decrease in homicide victimization at least comparable to women. With black men removed from the picture, the caucasian male victimization rate is nearly constant from 1976 to 2002, if smoothed out.

https://www.researchgate.net/profile/Susan-Sorenson/publication/7102593/figure/fig1/AS:667181570334750@1536079890729/Intimate-Partner-Homicide-Victims-by-Sex-and-Race-United-States-1976-2002-SOURCE-US.png

None of this is what I would have predicted, so I hesitate to speculate.

Of course, the two graphs give different total victimization rates, such that the two studies must have different definitions of what constitutes 'intimate partner violence.'

Expand full comment

I'm not sure I can comment on these trends in more detail, but I will point out there is a mountain of evidence for gender symmetry in domestic violence (despite predominant aggressor policies that assume the opposite and can make it quite risky for men to call police to deal with violent women.)

Expand full comment

I think "the problem without a name" -- educated women expected and expecting to be content with running households-- was a major driver behind second wave feminism.

Expand full comment

Oh, absolutely! The 1950s was particularly rigid, recovering from WWII, and prompted a backlash. And with appliances and industry replacing a fair bit of housework (who darns their socks these days?) and educated women having fewer children then... yeah. Means, motive, and opportunity. ;-)

There may have been a kind of tipping point, also. Housewives live better lives if there are other stay-at-home parents for them to work and socialize with. Working women do better in the workforce if women working in the workforce is common and some women are in management. So there are probably some collective interests at play as well which could develop to critical mass.

Expand full comment

There are perfectly reasonable arguments to be made that some recalibration of gender roles was both feasible and desirable in the wake of the medical and labour-saving innovations of the early-to-mid 20th century, but women's life-satisfaction peaked in the 1970s and has declined steadily ever since despite enormous legislative and economic changes in women's favour.

Feminists have predictably ascribed this to 'increasing awareness of patriarchy' and dismissed a mountain of evidence that, on the average, conservative women, married women, and part-time-working or stay-at-home mothers are happier than liberal, unmarried or full-time-working women. But 80% of women preferring less workforce participation doesn't make GDP go up in the next fiscal quarter.

Expand full comment

Source for married women being happier?

I've always heard that, according to surveys, marriage made men happier but women less happy.

Expand full comment

Reasonable summary here. I'd expect the picture changes somewhat if you look at how women feel about it at 25 vs. how they feel about it at 60- it's more of a long-term investment strategy than instantly hedonic- and there could be various selection effects going on.

https://ifstudies.org/blog/are-married-people-still-happier

There are some women who just aren't cut out for marriage and kids and conversely there are some women who positively love kids from day 1, but that doesn't mean you can't formulate policy based on averages.

Expand full comment

>I'm less harsh on this intellectual habit than I used to be, given that tinkering with human biology and social relations in particular can have long-term side-effects that no-one predicted. e.g, contraception and abortion paradoxically made it easier for men to keep mistresses, which led married women to retaliate with 2nd-wave feminism in the 60s/70s and was most likely a huge contributor to the soaring divorce/illegitimacy rates we've been seeing ever since.

I'm not certain what caused stage 2 feminism, but it's conspicuous that it caused the 2 income trap. This indicates that the leaders may have not been powerful women, but rather corporations seeking to cheapen labor.

At any rate, to whatever degree birth control contributed to the ideas of powerful people, you have left elitism out of the analysis. It didn't happen because of middle class housewives being unhappy or something.

Expand full comment

The two-income-trap is something I have mixed feelings about, since it's probably a real effect and there's no question that short-sighted economic minmaxing pressures have a huge effect here (aside from supplying corporate labour, women also contribute much more to luxury goods consumption than men do.) At the same time, the only way around those pressures is to bar women from the workforce, which feels a bit procrustean.

I think Nancy Lebovitz pointed out in a nearby comment that educated women wanting to have some career outside the household was probably another factor once infant mortality reductions and labor-saving devices made it practicable. It's just that Moloch keeps eating our fertility to make GDP go up.

Expand full comment

Yes, that was me.

_Sex and Destiny_ by Germaine Greer may be of interest. It's about Family-centered cultures compared to commercial cultures, and part of her point was that commercial cultures pull labor out of families.

She spent some time among Italian peasants and was very favorably impressed. If you read with attention, you'll find some drawbacks to Family cultures. If your Family is bad, you have no alternatives. Barren women are badly treated.

Still, I'm wondering whether part of what's happening in the modern world is damaging institutions which work well some of the time to protect people against the failure modes of their institutions.

Expand full comment

No system is perfect, but I think the modern welfare state and some attention to individual variation would compensate for the drawbacks you mention. But I think it's pretty hard to refute the idea that some reversion to family norms is going to be needed to keep our societies sustainable, unless those anti-ageing therapies kick in in a big way.

Expand full comment

The welfare state is based on the premise that systems are better than personal loyalty. Is this sustainable for the long haul? Damned if I know.

Expand full comment

"This indicates that the leaders may have not been powerful women, but rather corporations seeking to cheapen labor. "

Why not both? Movements are a confluence of interests. There were plenty of midwestern housewives who wanted careers and independence. It's not like 2nd wave feminists don't exist. I've talked to them. Haven't you? The fact that some of their interests matched up with corporate interests likely made the movement much more likely to succeed.

Results and intentions are different things, in any case. I don't think that we can say "because the War on Drugs was disproportionately harmful to African Americans then that means no powerful African Americans advocated for it." African American leaders did support the War on Drugs and then saw their communities bitten by that movement.

Expand full comment

My impression is that the war on drugs as it pertains to afro-american neighbourhoods is one of those problems where you have to dig through multiple levels of cynical obfuscation to get at anything like the truth, but roughly, it's a chicken-and-egg situation where residents who mistrust and fear the police (and/or can be intimidated by local drug gangs- "snitches get stitches") refuse to cooperate with the justice system, which makes the justice system malfunction, which in turn prompts the police to get creative about securing arrests and convictions (in which respect the somewhat flexible application of US drug law is, ah, helpful.) And around it goes.

This particularly generates mistrust when residents see people being locked up over relatively minor drug offences while murder and rape cases go unsolved. (In reality, many of the perps being put away for drug offences are in fact responsible for murders and rapes, and the police often have reasonable evidence to this effect, but it's easier to make a drug charge stick than a murder charge, and the former can get perps off the streets long enough to break up criminal orgs and buy a few months of peace before some other drug gang emerges to fill the gap in the market.)

Liberals often complain that these drug laws were formulated in order to artificially increase arrest rates in black neighbourhoods and that black americans are much more likely to be put away for drug offences despite similar levels of drug use compared with whites- in a sense this is true, but it glosses over the fact that whites can sell drugs to eachother without committing murder at 5 times the national average (even in desperately poor areas like white appalachia.) The squeaky wheel gets the grease.

Another popular suggestion is to just legalise drugs entirely, but the truth is that the social effects this change in legislation would have are deeply uncertain. No-one really knows what percentage of violent crimes are prevented by using drug laws to periodically sweep gang members off the streets vs. what percentage of violent crime would be prevented if the black-market drug trade didn't funnel so much money in the direction of criminals. The results could be net positive, net negative, or a complete wash (setting aside the possible effects of drugs themselves being more easily available.)

Failing that, your options are (A) massively improve equipment, training and manpower available to police, and focus on both street presence, witness protection and prosecuting murders and other serious crimes, which will probably require federal funding since a lot of these cities are skint broke, (B) identify individuals with a high risk of violence (i.e, psychopaths) early in life and use some combination of diagnosis and monitoring to minimise their criminal entanglements, (C) create stable, respectably-paying jobs that don't require advanced academic skills so that non-psychopaths are less tempted by the money in crime and less like to use drugs to self-medicate depression, and (D) start taking anti-dysgenic policies seriously, because that's likely to be an accumulating problems over multiple generations (gene therapies, sperm banks, project prevention, middle-to-upper-class fertility incentives, et cetera.)

But of course, none of this will happen as long as the right's only acceptable response is By Your Bootstraps and the left's only acceptable response is Education Conquers All.

Expand full comment

> so the bio-ethicists compete to see who can offer a theory of why that worry should be taken seriously.

This is how the trolley problem worked for self-driving cars. Something that would hardly ever come up in the real world, and if it did there was an obvious solution[1], but millions of man-hours wasted on it.

[1] the solution is "hit the brakes and hope for the best"

Expand full comment

Yeah, so far as self-driving cars are concerned I'd agree. "Drive slowly enough to not hit people in the first place" is what they'll effectively be obliged to do regardless.

Expand full comment

bonus "don't make vehicles that are so heavy that they can kill people on impact".

Expand full comment

Well that's a total non-starter, it's not like the mass of cars is ballast, it's necessary for them to function. Altering bonnet shapes to make pedestrian collisions less fatal is definitely an area worth investigating thoroughly, though.

Expand full comment

You could make cars lighter. Particularly if there were regulations requiring cars to be lighter, so that you didn't try to be extra heavy to protect your occupants from the even heavier other vehicles ramming into you.

Expand full comment

> "Drive slowly enough to not hit people in the first place" is what they'll effectively be obliged to do regardless.

I doubt it. If we cared enough about that outcome, we'd already be requiring people to do it. The speed limit shows the places we do care: school zones have very low speed limits comparatively.

Expand full comment

I think the current default is sensible in principle - cars are required to drive slowly and cautiously near pedestrian crossings, and pedestrians are otherwise assumed to stay out of the road. Children can't be assumed to behave sensibly, and so roads with many children expected have lower limits.

Now, as to the actual detail, car braking technology has improved dramatically over the last decades but speed limits have tended to go down, and (at least where I live) speeding fines are a substantial source of revenue for the state government... One begins to suspect that safety is no longer the sole or even primary motivator.

Expand full comment

> More generally, I'm furious at the many bio-ethicists who are complicit in the game where something bothers ppl in the population but it doesn't seem like a coherent worry so the bio-ethicists compete to see who can offer a theory of why that worry should be taken seriously.

I think anti-aging people should be silent about their focus on curing aging, and instead point to the symptoms directly. Population is... bad... enough to be anti-anti-aging once there's hope of actually solving the problem IMO.

Expand full comment

Bioethicists are downstream from that common-meme bullshit.

Expand full comment

> fear that we won't get to find out promptly (read: while I could benefit)

The National Lampoon did a bit in 1970 about Science being on the verge of solving all the ills of aging. Not in time for their readers - presumably teens and twenty somethings - of course.

I guess that satirical prediction didn’t pan out.

Expand full comment

I've never understood this argument. A cure for aging would cure all aging related diseases and would be approved easily. Statins had an easy path to approval for just putting a small dent in one aging related disease. The FDA is terrible, but it's not the bottleneck in curing aging.

Expand full comment

There is something repellent about the idea of professional ethicists, bio- or otherwise. A biologist who cares a lot about being ethical ? -- sure, I love that guy. But someone who calls himself a bio-ethicist? Seems like making a career out of claiming the moral high ground. Prigs.

Expand full comment

Bioethics is just a name for a particular kind of philosophical ethics concerned primarily with the human body, medicine, and biology.

Mostly, they’re not claiming any moral high ground. Like all ethicists, they’re just trying to think through difficult moral dilemma’s and determine the optimal outcome.

We all engage in bioethics. Abortion is a bioethical debate. So is human experimentation, or the FDA approval process, or the COVID vaccine.

Expand full comment

I think bio-ethicists specialize in "this why people shouldn't have what they want" without considering that what people want might have some good points.

Longer healthy lives, threat or menace?

Expand full comment

I think it's spelled "resveratrol."

Expand full comment

Yes!

Fix it, Scott, before it spreads! :P "Resveratrol"!

Expand full comment

Yup

Expand full comment

'Reservatrol' is my new app for helping social media celebs find a better class of troll 👹😅

Expand full comment

That weirdly sounds like a viable idea, although recruiting high-quality trolls might be challenging (how do you know they're not trolling you with their applications?).

Expand full comment

This is clearly the first hurdle in the interview process. Seems like a winning strategy is to let all the extreme ones through.

Expand full comment

Amazon is reputable. They can have MTroll. It'll be an easy spinoff of MTurk

https://www.mturk.com/

Expand full comment

> using what template?

Show me a hundred copies of a string with a random error and I tell you the original.

Expand full comment

Hmmm, Hamming codes (et al) for the genome... coding theory could be valuable for anti-aging, if this shakes out. Shame I don't really know any.

Expand full comment

Look, you just take the most common DNA letter at every place. If there were enough random errors to make that come out wrong you'd be a puddle of goo.

Expand full comment

But there's no mechanism that allows a hundred cells to pool all their DNA together and compare them. How does a cell know what to repair when the nearest reference copies are locked behind two layers of membranes?

Expand full comment
Comment deleted
Expand full comment

My original comment was a reply to the "using what template?" in the section about DNA.

Expand full comment

I'm vaguely aware of methods to allow far fewer checks than one might expect to obtain very good accuracy. Of course, that does nothing about the *physical* problem

Expand full comment

Stem cell potential declines with age even with induced pluripotent stem cells. The right thing to do if you're paranoid about this is freeze some of yours ASAP, like some people do with umbilical cord, and then take the most common DNA on a base pair basis *there*

Expand full comment

If you're going to be paranoid about what parts of yourself are irretrievably lost to time, don't freeze cells that can be deduced later, keep a diary.

Expand full comment

You take a hundred samples from the patient, sequence a hundred DNAs, and custom-synthesize your treatment to restore that template.

Expand full comment

This essentially already how your cells repair their own dna damage.

Expand full comment

I have a lot to respond here, but don't have time to write a full response tonight, so here's a shorter one. I might revisit this later.

David Sinclair is definitely a hype machine, but some of what he's hyping might actually work. Resveratrol is not one of those things (pharmacologically it sucks), but partial epigenetic reprogramming (with OCT4/SOX2/KLF4 or other transcription factors) is. In particular there was a very cool paper recently about restoring vision in aged mice: https://www.nature.com/articles/s41586-020-2975-4

Anyway, I'll believe he can reverse aging when he shows me a 5 year old mouse.

Expand full comment

Also, messing with mTOR is generally not worth the side effects.

Expand full comment

I think messing with mTOR will be necessary, but not by simply down-regulating it. Rather, we need to strategically break links in the entangling of the mTOR and FOXO3a networks, and add ways we can turn subsets of both networks on and off ourselves.

The mTOR network activates mostly things that take lots of energy, like growing, reproducing, and fighting off disease. The FOXO network activates mostly defensive things. It's very hard for genes deep inside your body to know what's going on outside, and evolution likes to accrete things onto existing systems, and bistable switching systems are simpler and more stable than tristable or multiple switches. So we have dozens of major functions whose activation have all been dumbed down to "energy high => mTOR active" vs "energy low => FOXO3 active". We have to turn on all the energy-wasting, damage-producing mTOR systems every time we need any one of them, AND to turn off lots of repair and stress-resistance systems. And we have to turn off fun things like growth and libido every time we need to activate any FOXO3 system. It's a dumb design. We'd probably win a lot of lifespan if we could switch some things on and off ourselves, say by ingesting a chemical that will flip a genetically-engineered regulator on or off, instead of flip-flopping the whole network.

Expand full comment

Thoughts on NMN?

Expand full comment

It's very safe (unlike rapamycin), but benefits (if any) are likely small.

Expand full comment

I get the impression that mice are really weird, and most of the things that work on mice don't work on large mammals. Is anyone trying these things on animals which are a closer analogue to humans? (I realise of course that sitting around for fifty years waiting for chimpanzees to die of old age isn't really a convenient experiment either.)

Expand full comment

I mean, one obvious problem with the mouse argument is that mice probably haven't evolved to have long lifespans to begin with, whereas humans have. So it's possible many of the things we "fix" in mice are things that are already fixed in humans.

Expand full comment

Have we really evolved to have long lifespans? Or are we just better at not dying? Evolution didn't really fix us; we did that ourselves. We stopped dying from polio, fever, parasites, appendictitis, and even kidney failure, and no genes are responsible for that. The fact that we get decrepit and senile in our old age suggests that if anything, evolution *doesn't* want us to have a long life.

I think it's more likely that smaller animals are more vulnerable to aging. All the damage of aging accumulates in small bodies at the same rate as large bodies, so it catches up with them far sooner.

Expand full comment

The natural, ancestral environment human lifespan is one of the longest lifespan in the animal kingdom, a record that stands even when compared to all now-extinct life. Most animals do not live to 30. Hunter gatherers frequently lived to 70.

Expand full comment

Considering our children are not capable of caring for themselves till multiple generations of mice have died, I think we can say we've evolved to live long.

Note also that people happily lived the best part of a century throughout history (and got senile). It was less frequent due to illnesses but the underlying point that a human who stays healthy to that point can easily live over three quarters of a century suggests we did evolve to allow long lives. Evolution probably optimised surviving to a younger age (past childhood, to the grandparent stage maybe) but it therefore allowed a long lifetime.

As for senility, elderly dogs and cats get this, at a much younger age than humans (including the breeds of dog that are as large as people), which suggests it's a common late-life failure mode in mammals living beyond their prime. It's probably not evolved so much as not been evolved away as so few mammals at that stage of life have children that there's no real evolutionary driver to not be senile.

Expand full comment

I thought our children aren't capable of caring for themselves because if they gestated to when they would be, they'd no longer fit through the birth canal. We've evolved to have unusally long childhoods, sure, but I don't think that's the same thing as evolving an unusually long lifespan.

Senility in large dogs is a fair point, but I'm more curious to aging in similar primates. Chimps live to 50-60 years in captivity, with the oldest living chimp being about 77, which is not that much different from humans. Did the same evolutionary pressures apply to them, or did we further evolve to get that 10-20 years extra?

Expand full comment

According to project chimps, for chimpanzees in captivity the mean life expectancy is only 32.5 years for males and 40.1 years for females.

Expand full comment

Apparently, chimpanzees have a pattern of mortality that's distinctly younger than that of all human hunter-gatherer populations except for Pygmies.

This paper argues that abnormally short average lifespans in Pygmies--closer to those seen in chimpanzees than in any other hunter-gatherer group--is what lies behind the selection they faced for early puberty, which in turn led them to stop growing early.

Now, this paper attributes high Pygmy mortality to the greater dangers of their jungle environment--high disease burden and poor nutrition--rather than to any genetic tendency to early senility.

Reading it, I was very curious to learn if Pygmies taken out of the jungle and given a modern Western standard of health care and nutrition would still age faster and die younger than other humans, but they said nothing about that possibility.

Also, Pygmy life expactancies, while much lower than for other hunter-gatherer groups, actually seem pretty comparable to the life expectancies of some pre-modern agricultural populations that faced extremely poor nutrition and high disease burdens--and yet none of these populations underwent anything like the same selection for early puberty.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2154411/

Expand full comment

As I understand it, larger dogs don't live as long as smaller dogs. I don't know about lifespans for different sizes of wild canines.

I believe part of the extended lifespan for children is grandmothers (perhaps especially maternal grandmothers) helping to care for children.

Longer lives are associated with not resembling a prey animal. Large size, communal living, poison, armor, and flight correlate with longevity. Bats are very long-lived for small rodents.

You can't combine all of the longevity factors, but I wouldn't mind some sf about about long-lived flying poisonous communal turtles, maybe on a low gravity planet.

Expand full comment

Considering how little care (most?) turtles show their young, could they be communal? Although I have read about a sci-fi amphibian race who like frogs lay and fertilise eggs without sex, and therefore with minimal concern for parenting. They aren't portrayed as having families but rather select factions to join, and I think are suggested to have high childhood mortality. Christopher Nuttall's Ark Royal saga from memory. Do I suppose alternative models of community might apply.

Expand full comment

Mammals with a long maturation period tend to have long life spans, because the parents need to be around to raise their offspring long after they're born. Humans have one of the longest maturation periods of any animal out there, if not the longest, hence, we also have evolved to have relatively long lifespans.

Expand full comment

It's been tried in monkeys for calorie restriction (less cumbersome than primates but still lots of trouble) https://www.nature.com/articles/ncomms14063 you will notice the effects are much more noticeable for healthspan (morbidiy curve) than lifespan but sample is anyway small

Even if we did manage to avoid people raising fake ethical concerns the problem is that there aren't that many compared to mice, specially when you get to actual primates. We'd have to get everyone to agree on the best experiment (epigenetic? stell cell reprogramming? organ replacing?) and then if something goes wrong and we get a fake conclusion because of some quirk or incomplete experiment that could anchor us away from potentially good solutions

Expand full comment

Mammal lifespan is very much a factor of mammal size, plot age and size on a graph and the results are uncanny. All mammals are basically the same system scaled to a different size, at the extremes limited by elements of the circulatory system. Shrews couldn't be any smaller because a heart can only be so small and still be viable; if blue whales were any larger, their aorta couldn't handle the pressure required to maintain bloodflow. Yet both of them (and us humans) over the duration of our lives experience on average the same number of heartbeats!

Expand full comment

Is there an actual scientific proof of this? I've vaguely accepted it as true for much of my life, but it is such a just-so fact that I think I'd like to have my willingness to accept the idea bolstered by some actual evidence.

Expand full comment

Here's a site that crowdsources people digging through biological documents to verify this. They have 175 species plotted, and humans are by far the biggest outlier.

http://robdunnlab.com/projects/beats-per-life/

Expand full comment

I get the impression that mice are peculiarly susceptible to dying of cancer, such that "curing cancer" and "extending lifespan" correspond much more closely in mice than in humans.

Expand full comment

A five-year old mouse is still short of reversing aging though it's going in the right direction.

I'd want to see a decrepit 2 year old mouse eventually become a healthy 5 year old. Yes, I know, good security to prevent substitution.

Expand full comment

Why did you use 40 and 70 in "If a 70 year old man marries a 40 year old woman.."? I think I'm missing the point and would like to understand.

Expand full comment

Oh! Did you mean woman who was not very young either, but still able to have babies?

Expand full comment

A 70 year old man plus a 40 year old woman is just about the oldest combination of humans that could plausibly have a baby.

Expand full comment

I believe in the book when Sinclair was talking about the Yamanaka factors, he asked the reader to imagine that you start getting into your 40s or 50s and are diagnosed with age. You go in to a clinic for treatment and they use the Yamanaka factors until you become 20 again and you do this over and over. I'm not sure that is possible but that idea got me really excited when reading this book.

I'm interested in taking resveratrol and NMN but I don't really know about this stuff and it seems so speculative. How badly can you hurt yourself with these?

Expand full comment

>How badly can you hurt yourself with these?

Resveratrol and NMN are quite safe. Resveratrol doesn't do anything though so I don't recommend it. NMN might so you can take it if you want.

Stay away from rapamycin though, its side effects are too dangerous.

Expand full comment

Thank you!

Expand full comment

Low dosage and once a week rapamycin may not be dangerous! In fact, it is one of the drugs that has consistently shown lifespan & healthspan benefits in mice. People in the industry like Matt Kaeberlein and Peter Attia take Rapamycin. I asked Matt about it in my podcast with him.

Expand full comment

@metaclesus is right. Resveratrol doesn't do much. NMN is safe but upside may be overblow, at least for younger folks. There is only one study that shows lifespan benefits with NR. Some people report feeling anecdotally better on NMN, but it's mostly older folks and could be placebo. You can get a good number of NAD benefits by exercising & fasting instead of taking NMN. It's expensive. That being said, if you wish to experiment with it, it's safe!

Expand full comment

Oh and metformin is the other drug that is safe and has healthspan benefits. However, it can blunt increases in muscle mass, not muscle strength, if taking it with exercise.

Expand full comment

Isn't it mainly effective for people with metabolic problems? Apart from it being a diabetes drug originally, I've read that the published effects mix a big effect for unhealthy people with minimal effect for the metabolically healthy.

Expand full comment

This is based on an n=1 sample, but I take high-dose metformin (2000mg/day) for its alleged lifespan benefits and although I can't make any claims about its effectiveness in that regard, it definitely has some dramatic effects. I've gone down a belt notch without any intentional change in diet and my blood sugar is near the bottom of the normal range, which I think is where you want it to be.

I don't do intermittent fasting but I think if you wanted to, metformin would also make it a lot easier, since you'd get fewer hunger cravings.

Expand full comment

It's most commonly used as a Type 2 diabetes drug! The studies that have been done are people above 65 and they showed that those who took metformin had 17% less mortality than healthy people not taking metformin. That being said, it's possible that the healthy 65 year olds could have benefited from it maybe because they weren't as metabolically healthy as a younger person (even though they were "healthy" for their age).

It is an open question whether metformin will be beneficial for people in their 20s, 30s, or 40s specially if they are exercising & metabolically healthy. That being said, I don't think it has side effects, except for blunted gains in muscle mass, not muscle strength!

My next podcast will be with Nir Barzilai who researches on metformin if you're interested in learning more :)

Expand full comment

It doesn't seem to be safe for everyone. Digestive problems, I think.

Expand full comment

I read Sinclair's book last year, did a bit of research, and started taking NMN daily in sublingual powder form - it's quite cheap and at least harmless. I'm 54, pretty healthy and active, and can report feeling anecdotally better, though that could be a placebo and obviously it will be another few decades before any major positive effects on my mitochondria kick in.

Expand full comment

Good to know, Patrick! Yes sounds like a lot of people above 50 seem to anecdotally report more energy on taking NMN. I'm in my 20s and I was taking it, but didn't notice a difference, but who knows! Agreed with you that it's harmless and placebo effect is still strong, so if it's having a benefit that way, so be it :)

I'd be curious to see more studies being done though because so far there is very little data except one study that shows minor lifespan benefits with NR in mice

Expand full comment

How much do you take?

Expand full comment

> And finally, what’s the worst that could happen? An overly literal friend has a habit of always answering that question with “everyone in the world dies horribly”. But in this case, that’s what happens if we don’t do it. Seems like we have nowhere to go but up!

I am always surprised that there isn't much, much more support for anti-aging research. I'd figure that everyone expects to age and no one wants to. So the government/billionaires/whatever should be showering the research with money. Yet that doesn't seem to be the case.

Expand full comment

>billionaires/whatever should be showering the research with money. Yet that doesn't seem to be the case.

It is. https://www.technologyreview.com/2021/09/04/1034364/altos-labs-silicon-valleys-jeff-bezos-milner-bet-living-forever/

Expand full comment

I suppose that depends on what you define as 'shower'... For perspective, Jeff Bezos alone is probably spending ~3.7x more per year (~$1b) on 'make rocket go boom' than Altos has raised total ($270m). Or to put it another way, Altos's capital of $0.27b is 0.01% of Jeff Bezos's net worth ($205b?).

Expand full comment

That's 0.1%, not 0.01%, though still small!

Expand full comment

I think the key issue is that we know how to make rockets go to space, but so far are pretty iffy on anti-aging (and cancer, for that matter.) One could reasonably assume that we are not close to the "shower money on it and it will happen faster" state for those things yet. Medicine, at least, seems to be one of those fields where you can't spent 9x as much and get results 9x faster.

Expand full comment

Perhaps it doesn't look like it as much from the outside, but as a cancer researcher, I would say that not only do we know a lot about cancer, but we've used that information to dramatically improve treatment (and in many cases cures) for cancer over the past half-century. Despite a public perception that there's nothing happening in cancer, we've been making steady progress.

I agree that 9x more spending is probably not going to result in 9x more results, but we are seeing some progress for all the effort we've been putting into the problem. From where I sit, I fully expect that my children will not understand why the idea of cancer was such a scary thing for previous generations.

Expand full comment

I don't doubt that you are right. I wonder though how much advancement is a question of more money and more researchers and how much it is just a question of time. The diminishing returns for adding additional researchers (what I assume is happening with more money) seems to have gotten steep, such that adding another researcher is nearly zero value add when it comes to speeding along research. That seems to be the case in just about all fields at the moment, at least on average, but of course that leaves a lot of room for specific fields having a lot better return.

I am just pessimistic on where we are on the "spend money -> get results faster" curve in general when it comes to science, or at least the science that gets funded by NHS, NIH, etc. The quality of research in general is so low that I think money spent realigning incentives is more useful, but then again fixing the incentives in science is probably well beyond what a few really rich people can do.

Expand full comment

I agree that basic research needs a complete overhaul. The dilemma you face as a researcher is:

1. Work in an obscure field nobody cares about until you win a Nobel or get kicked out for never doing anything 'important'.

2. Work on the new 'hot topic' and rush to publish.

With strategy (1) you can take your time and do the research right, but you'll never have the money to do so. With strategy (2) taking your time to do the research right will never pay off, because someone will scoop you and get their work published first, or if it was wrong all you'll be able to do is publish a controversial 'corrective' paper that people will be annoyed at you with until they finally accept your careful work demonstrating that people were rushing to judgement. Meanwhile, the person who was willing to rush publication will get accolades and advancement whichever direction the research went. And since the 'careful research' direction isn't viable anyway, they can keep rushing publications for a whole career so that the errors that would have been corrected with careful research just get subsumed into the general morass of the 'replication crisis'.

Not sure what the solution is, but throwing more money at the system isn't likely to fix it. It'll probably just make it worse.

As someone who works on the clinical development side (from a small pharma perspective) I have to say that a lot of the research we might otherwise want to rely on is sloppy at best. Still, there's a lot of careful research being done downstream in the clinic. But clinical development takes years before you get data on each expensive trial. While benchwork gets results much faster at a fraction of the price. If we wanted to accelerate clinical development across the board, we would set high standards for academic research so less bad science got into the clinic before it was corrected.

Expand full comment

For $XXX you can make a rocket go to space, and know that it will happen. How much does anti-aging cost? We don't know, because we haven't got anti-aging and the "best" stuff we have is highly speculative and often falls into hype like the author here. If you were 60 years old and had infinite money, how would you spend it on anti-aging? Lots and lots of baseline research projects, I would suppose, but they aren't likely to pan out for many years, if ever. Bezos will likely be dead or too far gone by the time this research (realistically) gets anywhere. If he wants to throw some money into pet projects, which he is, on the off chance that we get a sudden breakthrough, then he's already covered on that. Throwing more money into it at this stage of research is probably just throwing money away.

The rocket analogy to anti-aging would probably be something more like this - For a billion dollars you can take away one year of aging, so a 60 year old can become 20 again by spending $40 billion up front and then $1 billion per year after that (or alternately, remain at a stable age for $1 billion a year but not reverse aging). If such a technology existed, I would bet Bezos would be using it.

Expand full comment

Maybe they are, in secret...

Expand full comment

I think most Americans oppose anti-aging research. Western religions are based on the fear of death, and we've spent over 2000 years convincing each other that death is good and life is bad, and that society would be ungovernable if people didn't have a life after death to be both hopeful and fearful about. Many important Western philosophers, for instance Plato's Socrates, Jesus, Schopenhauer, Freud, Baudrillard, and Foucault, thought that death is good or desirable. A larger number, plus Buddhism, claim that death is better than life (because life is nothing but suffering).

(Oddly, most Americans also oppose the right to die.)

The NIH and FDA both explicitly oppose anti-aging work. The FDA says aging is not a disease and hence drugs against it can't be approved. The NIH refuses to fund research that targets aging rather than one particular disease of aging (although the National Institute of Aging recently floated these general aging research topics: https://www.nia.nih.gov/research/blog/2021/09/check-out-nias-new-cleared-concepts-aging-research ).

Expand full comment

The FDA has approved treatment for Progeria. They don't have any problem with treating aging diseases, you just need to actually be able to define what you're treating.

To define something as a disease, you'd have to actually define what that thing actually is. Aging is ill-defined and may not be one thing; in fact, a lot of theories of aging suggest it is actually many things. This would also explain why trying to fix one thing doesn't result in immortal mice; even if you fix one thing that kills mice, the other thing will kill them instead. You'd have to fix all the things to get an immortal mouse.

I suspect that aging is DNA damage AND epigenetic damage AND fault accumulation AND probably numerous other things added together.

It's not one thing, it's all the things, so you're not going to be able to make a single "anti-aging" treatment, you have to treat each of the parts of it.

If someone developed a drug that, say, greatly reduced harmful mutations, thus acting as preventative for cancer and various other aging-related genetic diseases, I don't think that the FDA would have any problem with approving that; it's no different than a vaccine, in the end.

I am also skeptical of the idea that most Americans would oppose anti-aging research, given how successful various types of fake anti-aging products are financially, and how most Americans are in favor of living longer, healthier lives.

Assuming it doesn't involve eating less french fries, anyway, because really, if it does, what is the point? :V

Expand full comment

I'd agree with this. I'm actually moderately optimistic that effective anti-ageing therapies will be developed over the next couple of decades, given that the incentives are so enormous.

Expand full comment

The FDA considers progeria a disease, but not aging. It seems likely that a drug which reduced aging would also delay progeria, and thus the drug could be approved for progeria, and legally prescribed for anyone. But it also seems that the chance of your doctor writing you a prescription for that drug to reduce your normal aging would be similar to the chance of your doctor writing you a prescription for a muscular dystrophy drug to help with your bodybuilding, i.e., none.

Expand full comment

Well, at that point it depends on your doctor - it's perfectly legal to script a drug off-label.

Expand full comment

Re. "I am also skeptical of the idea that most Americans would oppose anti-aging research, given how successful various types of fake anti-aging products are financially, and how most Americans are in favor of living longer, healthier lives."

Well, I'm more confident that most philosophers and bioethicists oppose anti-aging research, and that most people who would be politically activated by a potential cure for aging would be against it.

Recall the book that President Bush 2's "President's Council for Bioethics" published, which mostly warned against trying to improve humans, as being an affront to "human dignity". A country that elected a president that selected a council so firmly opposed to life-enhancement tech can't be very enthusiastic about extending lifespan.

Expand full comment

What's amusing to me is the never-addressed glaring contradiction between thinking that life is bad, and having children is one of the loftiest acts of virtue. The one in which you condemn the person you're supposed to care about the most to a lifetime of suffering.

Expand full comment

It's not a glaring contradiction at all. Most people who have children (me among them) think life is worth living on net, or at least lives similar to our own, but only *conditional on it having an end*.

There's no more contradiction in this than "I like movies, which tell a coherent story that ends, more than Spider-Man comics, which have decades long incoherent serial nonsense".

You may not agree, and that's fine, but it's not a hard position to understand, or contradictory or even obviously wrong. It is a *preference* for a certain kind of life story.

Expand full comment

I don't disagree in the sense that involuntary immortality would be much worse than inevitability of death. However, being able to determine its time and the manner without the certainty of eventual decrepitude would be much preferable to me (and to the vast majority of people I'm pretty sure). Of course, all evidence points to the universe not caring about our preferences whatsoever, and the prospects of this changing remain dim.

Expand full comment

Your summary of the religious position is too simplistic, so you're missing why the nuance can exist and the contradictions aren't contradictions.

Life includes suffering, and inevitably will. If you stopped aging, you would still die in car crashes and have heart attacks from high cholesterol. Living forever (and still enjoying life, rather than living in a bubble for safety) is a worthless pipe dream and always will be. Hedonism offers no worthwhile benefit, only the appearance of worth on a short timeframe. People will get tired of hedonism the same way they get tired of anything else. By attempting to fulfill temporary and ultimately meaningless objectives, you only end up with false hope and growing frustration as you continue to seek out new and more exciting alternatives.

The only things that really matter and provide real value are our relationships with other people, and even more so with the eternal God. Death, and aging itself, are benefits because they encourage us to build those relationships and value the relationships over the material. Having children is a matter of creating social bonds and exemplifying the ideal of relationships. Never existing isn't a help, because there are real things that exist and that are good - those relationships. Material accumulation or hedonistic pleasure, on the other hand, are not ultimately beneficial. Growing older and dying are catalysts for us to pass along our knowledge, positions, and wealth to the new generations, building relationships with the new as we transition out of life. Take those things away, and there's no reason to interact with young people and create relationships (or have children), leading to an inevitable stagnation and endless hedonistic pursuits that will never actually solve our problems or bring us peace. We'll become more and more frustrated by the pains we still experience, losing the calmness and peace that comes from accepting our inevitable death and living a life that promotes others instead of running that hedonistic treadmill.

Expand full comment

I wasn't summarizing "the religious position". I listed specific philosophers and one specific religion, which all specifically said death is better than life, or death is desirable. As in repeatedly writing "All life is suffering", and telling people the greatest thing they could possibly hope for is real death, as Buddhism does, and as many Western philosophers have done. I think I could have listed all the existentialists as well, but I didn't because I haven't recorded specific quotes by them on the topic.

Expand full comment

(In the case of Jesus, death is better than life only for /some/ people. Although actually it's difficult to know now when he was talking about an afterlife, and when he was talking about a kingdom on Earth. He, or his followers, weren't interested in differentiating the two.)

Expand full comment

> Life includes suffering, and inevitably will.

Sure, but there can be more suffering or less suffering, and less suffering is better. Without this assumption, many things we do would not make sense, for example medicine in general.

> People will get tired of hedonism the same way they get tired of anything else.

Then I'd leave it for them to find a hobby, or perhaps kill themselves.

> our relationships with other people

Which are sometimes interrupted by those people dying.

If death is so good, why don't we make a law to kill everyone when they get 30? (Enough time to have kids and keep the humanity existing. Unless perhaps extinction is also good.) This would be even more awesome than what we have now, wouldn't it?

Those 20 something people could then tell each other wisely sounding scary stories about the horrors of their ancestors living to their 50s or 80s leading utterly meaningless lives full of material accumulation and hedonism.

Expand full comment

Logan's Run would be the most famous fictional example of that society, it's an idea that has certainly been explored before. Good point that it's a useful analogy here, much as reading Flatworld helps understand the implications of a 4th dimension

Expand full comment

This may be a stupid question: If the FDA doesn't consider aging a disease, couldn't a "dietary supplement" claim to "cure/prevent/slow aging" without needing to be regulated as a drug? That seems better, at least for availability-after-development, although maybe not for getting research funding or profits.

Expand full comment

It's a good question. I don't know what chemicals qualify as "dietary supplements", but they do all seem to be natural products. I don't think a chemical not occurring in nature could be sold as a dietary supplement, but I don't know. I do recall a case about 25 years ago, when a wrinkle-removing cosmetic was taken off the market by the FDA with the argument that it must be a drug, not a cosmetic, because it actually removed wrinkles, and therefore was a drug, and therefore had to formally prove to the FDA that it removed wrinkles. I wish I remembered more specifics, but I don't.

Expand full comment

Here is a vague FDA policy and a list of dozens of actions against cosmetics:

"if a product is intended to make lines and wrinkles less noticeable, simply by moisturizing the skin, it’s a cosmetic...if a product is intended, for example, to remove wrinkles or increase the skin’s production of collagen, it’s a drug or a medical device."

https://www.fda.gov/cosmetics/cosmetic-products/wrinkle-treatments-and-other-anti-aging-products

https://www.fda.gov/cosmetics/warning-letters-related-cosmetics/warning-letters-address-drug-claims-made-products-marketed-cosmetics

Expand full comment

Thanks!

So the FDA guarantees that any wrinkle-removing product we can buy, won't work.

Expand full comment

Judaism is clearly in favor of living in a way that Christianity isn't, though Christianity isn't simply pro-death. It's complicated and I don't have all the details.

I read an account of a bio-ethics and longevity conference (probably can't find the link), and the only person in favor was a rabbi.

Expand full comment

Christianity thinks of itself as not-anti-life because it's contrasting itself with Manichaeism, purer Platonism, Gnosticism, and other popular philosophies of the 3rd century which said that all physical reality is inherently evil. St. Augustine concluded that physical reality must be *capable* of perfection, because God was incarnated physically. Christian theologians make a big deal of this, but really, the difference between "matter is corrupt 100% of the time" and "there was this one bit of matter 2000 years ago that wasn't corrupt" is not that big.

Expand full comment

There's also the "people are fundamentally bad because they want sex" part. This makes the vast majority fundamentally bad.

Expand full comment

I really think the primary thing is expectations management. I think people get really upset (or think they will get really upset) if they get their hopes up and end up being disappointed. And so people learn this psychological defense mechanisms to avoid letting their hopes get up in the first place. And this is a problem because if we believe we can't do this thing, we'll never try and so we never will.

Expand full comment

The medium matters for the message. A lot of the anti-aging people are social misfits who have blown all their weirdness points already and keep going on about how bad the people who don't support them are.

And normies see them and think "the first people to be immortal are going to be *those* people??"

Some good PR firms would really help with messaging. The major problem is that it involves a lot of the current crew sitting down and being quiet.

Expand full comment

Your perspective deeply confuses me.

>A lot of the anti-aging people are social misfits who have blown all their weirdness points already and keep going on about how bad the people who don't support them are.

I don't know anyone like this. Certainly Sinclair isn't like this, he seems extremely normal and I haven't observed an ounce of victim complex from him. The other big name is Aubrey de Gray, who is certainly eccentric and weird but I also haven't observed a victim complex from him.

What I could understand your "going on about how bad the people who don't support them are" could be about, is the criticism that they have for people who don't support anti-aging research at modest levels compared to research into other diseases which have broad support.

>The major problem is that it involves a lot of the current crew sitting down and being quiet.

Again I'm not sure who you are referring to as the "current crew" but again I emphatically don't believe this is the problem. I think the main problem is that most people do not conceive of life extension to be remotely within the realm of realistic scientific progress within our lifetime.

Expand full comment

Most anti-aging stuff is a scam. People are rightfully leery of it. Doubly so because we don't actually know what aging is, and my guess is that aging is probably many things.

Expand full comment

Billionaires don't have *that* much money to spend. The real money is in the middle class, which has far less money individually, but who number in the hundreds of millions, as opposed to ten to twenty or so.

As it happens, people have a fairly short time horizon on death. When they are actually suffering from a fatal disease -- after the first heart attack, say, or when cancer is diagnosed -- then they will indeed spend a large fraction of their income on trying not to die. So the money available to treat active disease that will predictably lead to death shortly is substantial.

On the other hand, ask your generic 25-year-old whether he would donate 25% of his before tax-income to longevity research -- or have his taxes rise by 50-75% to pay for it -- which is what it would take, not milions but billions of dollars -- and he would laugh. Maybe 0.5-1%, sure. But that won't cut it.

You could certain siphon off a few billions from free daycare or community college, "infrastructure" or refundable tax credits, or any of the other massive wealth-transfer programs the Federal government runs that add up to a trillion or so per year, but I rather suspect the political pushback would be fatal.

Expand full comment

>25% of his before tax-income to longevity research -- or have his taxes rise by 50-75% to pay for it -- which is what it would take, not milions but billions of dollars -- and he would laugh. Maybe 0.5-1%, sure. But that won't cut it.

Where does your intuition on these numbers come from? https://www.statista.com/statistics/216928/us-government-revenues-by-category/ says that the US gov collects 1.6T in personal income taxes a year. This https://taxfoundation.org/publications/latest-federal-income-tax-data/ claims that the average tax rate per person is 13.3% of their income. This is shoddy math but hopefully within an order of magnitude correct: 1% additional tax on the average person's income should raise total take by 1/13th, or 7.5%, or $120B.

Let's halve that as a conservative estimate for my lazy math, you don't think $60B a year wouldn't dramatically increase our odds of making good advancement in longevity research (specifically, something like a 25% increase in life expectancy for people with access to such healthcare)?

Expand full comment

My impression is that 1% of 13% is 0.13%, so if you raise the average tax bill by 1% you get an extra 0.13% in revenue.

Anyway, if you want 7.5% more revenue, it follows the average tax bill has to rise by 7.5% and yes I rather suspect a lot of people would get crabby about that. Supposedly the average Federal tax bill was around $15,000,so you're talking an extra $1100 a year. I would guess if you went on the hustings and said we're going to raise your taxes by $1000 a year to fund longevity research you might very well get a fair amount of pushback.

Expand full comment

"as opposed to ten to twenty or so."

https://www.forbes.com/billionaires/ lists over 2600 billionaires.

Expand full comment

This. I'm constantly surprised by how chilled almost everyone is about they fact that they and literally everybody they ever loved are going to die, most likely in pain.

Expand full comment
founding

The simplest answer to "Why doesn't the body already do this?" is anti-aging isn't free: it costs resources the body can use on other things, like manufacturing sperm or cogitation or even burning for warmth. Animal lifespan varies based on a lot of things but it tends to be shorter in animals that can expect to die by accident or predators because in those animals there is no evolutionary benefit to adaptations for increased lifespan beyond a certain point. Meanwhile, birds that are the same size as mammals that can be expected to live 3-5 years will live 80 years, because flight and their relative intelligence means birds are much less vulnerable to predators and accidents and local food shortages.

Personally I think Algernon's law is absurd and betrays a lack of attention to the natural world and the constraints of evolution.

Expand full comment

I mean, this is just exactly one of the exceptions described here, right? https://www.gwern.net/Drug-heuristics#loopholes It falls under Gwern's exception 3, or Bostrom's exception 1 or 2.

Expand full comment

Isn't there a big evolutionary advantage to shorter lifespans, at a point? Natural selection of best fitness works faster when people have a few kids and die, and then their kids select for suitability and have more kids, rather than the same people just popping out effectively the same evolutionary generation forever

Expand full comment

There's an evolutionary advantage to having a short time to produce the next generation. There's no advantage to dying early.

Expand full comment

Wouldn't having a short time to produce the next generation without dying early result in overpopulation

Expand full comment

Overpopulation is a problem for species, not individual genes. Remember: group selection is bunk, scarce resources only makes individuals compete more desperately.

Expand full comment

Chiding that we "remember" a progressive dogma? What an odd way to reason through a problem. The above-mentioned flaw in Algernon's Law is near trivially correct, but it will probably take Paige Harden-type gentle coaxing for the larger part of the polite establishment to recover its sense.

Expand full comment

...what?

I have literally never heard of anyone say that group selection being bunk is 'progressive dogma'

What are you even referring to?

Expand full comment

That's a group selection argument. When someone tried to select for animals that attempt to avoid overpopulation, the result was cannibalizing the children of others. https://www.overcomingbias.com/2007/11/group-selection.html

Expand full comment

There's an advantage to not consuming resources past the point of being able to acquire them for your offspring.

Expand full comment

People do consume less as they age and become less productive. https://www.econlib.org/archives/2009/10/was_having_kids.html

Expand full comment

Evolution doesn't actually favor kids, it favors the more "you" there is around. Living longer effectively generates more "you" as well.

Expand full comment

"Evolution doesn't favor kids" is true of individual evolution. It is not true of species evolution(competition among species). Species evolution favors kids in several conflicting ways.

Consider sexual vs. asexual reproduction. With asexual reproduction, the population doubles rapidly but you get less evolution (only from mutations) and less variation of the gene pool. Given two populations 1 reproducing sexually and the other asexually, the asexual one virtually always wins due to reproduction rate and finite resources.

Sexual reproduction is half as fast (2 gametes are needed to create 1), however there is far more genetic variation. This leaves the species more adaptable to changing conditions. Since both of these two reproduction methods coexist(millions of years later), it follows that each has benefits in different scenarios.

Expand full comment
Comment deleted
Expand full comment

Yes, I made that up. I guess I should have realized that it had to have an agreed-upon name.

Expand full comment

Algernon's law is like the efficient markets hypothesis, where the real world answer is "yes, that's true, except when it's not."

Expand full comment

Yes, both of them underestimate the difficulties of finding and trying something new.

Expand full comment

It seems like the other relevant dimension here is that we're talking about aging. Evolutionary selection for slowing down aging seems… complicated.

Perhaps slowing down aging increases lifespan, but doesn't affect your younger years. In this case, you've already passed on your genes (or not) before having a longer lifespan matters.

Expand full comment

Creatures that die early have little selective advantage in living longer - they're mostly going to die by age one anyway, so what's the point of a gene that helps you live from age 2 to 3?

Living longer is upside, but most creatures can't achieve that. Those that can often do.

Expand full comment

Algernon's law is indeed as absurd as the novella that spawned it - a sentimental sci-fi about a dying mouse as I recall... plus Algernon is just a silly name (apologies to any actual Algernons here) hence Wilde

Expand full comment

It's a short story, later developed into a novel, called "Flowers for Algernon". There is a mouse in it, but it is notable as the subject of a revolutionary surgical procedure to increase intelligence. The researchers need a human subject, and they find one in Charlie Gordon, a mentally retarded man. The operation works and vastly increases his intelligence, but things don't go well.

As the mouse begins to behave erratically and regress then dies, so Charlie realises the same will happen to him and he loses all his intelligence and ends up as he began.

https://en.wikipedia.org/wiki/Flowers_for_Algernon

Expand full comment

Oh yes, it's coming back to me... so would you rather get vastly increased intelligence, but knowing you'll regress to a vegetable after a while, and a mouse will die for you, or continue in your current state of blissful ignorance?

Expand full comment

As I recall, he didn't regress to a vegetable, he regressed to his early state of fairly severe retardation.

Expand full comment

Precisely. No such thing as a free lunch, but calories are a hell of a lot cheaper than they used to be so there ought to be a lot of very nice lunches out there indeed that modern humans can now afford where once we couldn't.

Expand full comment

Only ~1/2 way through. But you haven't mentioned my fav. aging idea. Aging is the response of a multi-cellular organism to cancer. (One cell going crazy and dividing forever.) There is a limit on the number of cell divisions for non-reproductive cells. (most of your body.) When you reach the limit, cells stop dividing and repairing and you get older. The limit stops cancer at least to first order...

Expand full comment