Fighting Aging as an Effective Altruism Cause: A Model of the Impact of the Clinical Trials of Simple Interventions
Abstract: The effective altruism movement aims to save lives in the most cost-effective ways. In the future, technology will allow radical life extension, and anyone who survives until that time will gain potentially indefinite life extension. Fighting aging now increases the number of people who will survive until radical life extension becomes possible. We suggest a simple model, where radical life extension is achieved in 2100, the human population is 10 billion, and life expectancy is increased by simple geroprotectors like metformin by three more years on average, so an additional 250 million people survive until “immortality”. The cost of clinical trials to prove that metformin is a real geroprotector is $60 million. In this simplified case, the price of a life saved is around 24 cents, 10 000 times cheaper than saving a life from malaria by providing bed nets. However, fighting aging should not be done in place of fighting existential risks, as they are complementary causes.
● Aging and death are the main causes of human suffering now.
● Simple interventions could extend human lives until aging is defeated.
● These interventions need to be clinically tested before FDA approval.
● A trial of the life extension drug metformin is delayed by lack of funds.
● Starting trials now will save 250 million people from death, at a cost of $0.24 for each life saved.
Please comment on the preprint of the article here: https://goo.gl/WaEYt5
Reading through this I have some pretty significant concerns.
First the model behind the "$0.24 for each life saved" figure seems very suspect:
I am also unconvinced by the quality of argument elsewhere in the paper. For instance in the section "False arguments against badness of death" they list common arguments against the badness of death and then claim to refute them. However the responses are often extremely shallow and do not engage at all with the core of the argument. Here are some examples:
The paper contains many other arguments of a similar level of quality, and so although I largely agree with many of its conclusions, I find it generally very uncompelling.
Finally, as the most minor point there are quite a high number of grammatical issues.
Thank you for review.
Taking median date of the AI arrival like 2062 is not informative as in half cases it will not be here at 2062. The date of 2100 is taken as the date when it (or other powerful life-extending technology) almost sure will appear as a very conservative estimate. Maybe it should be justified more in the text.
Yes, it is assumed by Barzilai and gwern that metformin will extend human life 1 year, based on many human cohorts studies, but to actually prove it we need TAME study, and until this study is finished, metformin can't be used as a life-extending drug. So any year of delay of the experiment means a year in the delay in global implementation. For now, it is already delayed for 2 years by luck of funds.
Given all uncertainty, the simplified model provides only an order of magnitude of the effect, but a more detailed model which take into account actual age distribution is coming.
As the paper is already too long, we tried to outline the main arguments or provide links to the articles where detailed refutation is presented, as in case of Gavrilov, 2010, where the problem of overpopulation is analysed in detail. But it is obvious now that this points should be clarified.
The next round of professional grammar editing is scheduled.
Thanks for the reply. Despite my very negative tone I do think this is an important work, and doing good cost benefit analysis like these is very difficult.
I don't share the intuition that human level AI will rapidly cause the creation of powerful life-extending technology. This seems to be relying on a rapid takeoff scenario, which while plausible I don't think can be taken as anything like certain. I think if this is the argument it should be spelled out clearly.
With regards to the effectiveness of metformin, my argument is that you should include a discount factor of a half or so to include the probably that it does not pass the human level trial.
My issue is that I don't see any arguments that the model is even likely to be accurate to within an order of magnitude.
I'm glad to here a more detailed model is in the works, as I said I think this is important work, but that makes getting it right all the more pivotal.
I think if the intention is just to link to other articles with detailed refutations you should just do that and not attempt to summerise (or make it clear this is at most a very rough outline). However for two of the examples I listed no other article is linked.
May I share with you the next version when all that changes will be done? I expect that the next revision will appear in 2 months.
Sure, although I'm not sure how much time I will have to look it over. My email is firstname.lastname@example.org.
The argument that aging is the world's greatest cause of suffering relies heavily on prax. Do older people report lower levels of day-to-day happiness or overall life satisfaction? I recall reading that they do not. If we are to believe that they are wrong, then a direct explanation for it is in order.
The death of investor paradox doesn't work under basic utilitarian math, since it neglects the opportunity costs of fewer new people being born and having utility of their own.
Death is the end of everything, but again this neglects the opportunity cost of allowing new people to be raised with the same resources.
Baillie 2013 doesn't seem to indicate that there is a loss of well-being from knowledge of death. It's an analytic philosophy paper divorced from human experience.
Not certain or substantiated, but highly plausible. Ok.
Again, opportunity costs. Though this response is substantially mitigated by the time required to train a new person to be productive (20-25 years).
I don't believe there is any direct moral reason to value the information in a human mind. Sure there is some pragmatic value, but again there is the problem of opportunity cost, since new minds will have unique memories and information of their own.
That's a good point. But you really should be integrating these straightforward considerations into a single quantitative model that aggregates the costs and benefits.
Only if we care little for the utility of yet-to-be-born people.
Yes, though this is a counterargument to arguments which I wouldn't make. Actually there is a good Pascallian Wager argument to be made here about minimizing the number of potential bad afterlives.
Regarding opportunity costs, you write "The idea of an infinite universe where everything is possible kills the objection." What? I just have no idea what this argument is. Like, it makes no sense. Do all possible universes exist, so that it doesn't matter what we do entirely? Then why talk about fighting aging? I don't get it.
For the $0.24 figure, your calculation for 250 million people being saved doesn't make sense to me. As someone without prior background on the Gomopertz-Makeham law, it just isn't clear. Also, it's not clear what part of gwern's post supports the claim that life expectancy would be extended by one year. And there are explicit quantitative problems.
First, 90% of drugs that reach Phase I trials are not approved (https://www.bio.org/sites/default/files/Clinical%20Development%20Success%20Rates%202006-2015%20-%20BIO,%20Biomedtracker,%20Amplion%202016.pdf), so you should increase the expected cost by a factor of ten.
Second, the drug may not be approved for Phase I trials even if we fund the study.
(The possibility that it is nonetheless approved outside of the US is counterbalanced by the possibility that it is approved within the US but not elsewhere.)
Third, just because a drug is approved does not mean everyone will be able to afford it. This is especially true in poorer countries outside the West, where most of the world population is located. 84% of the world lives on under $20 a day, and gwern says that this drug costs $8 a day in the US. So it looks like most people in the world won't be able to afford it anytime soon.
Fourth, just because someone can afford it does not mean they are open to the concept. Western medicine is not embraced by everyone in the West, and it is often rejected in many other parts of the world. This study found that 27% of Chinese did not consult a Western doctor for their most recent illness.
Fifth, even if someone is okay with Western medicine, they may not want to take an anti-aging pill. 40% of Americans drink practically nothing despite the purported anti-aging benefits of red wine, the remaining 60% don't all drink red wine, and the ones who do presumably don't all do so for anti-aging reasons. Very few people, a tiny minority, take resveratrol. Only a small minority takes Vitamin D, despite its anti-aging benefits. Only a small minority are vegetarian, despite evidence of vegetarian longevity. Anti-aging blood transfer and cryonics are both commonly regarded as creepy jokes in popular culture. And no one seems to be attempting to illegally take metformin. Given all these examples, only a minority can be expected to take metformin prior to the longevity horizon.
Sixth, just because someone is willing and able to take it doesn't mean it's the most effective way to increase their lifespan with their limited excess money. If you are very poor, spending the same money on meat, vitamin fortification, or conventional healthcare may have a greater impact on your longevity. Gwern's calculations on metformin seem to support this.
Seventh, even if metformin is optimal for a poor person, it will still have a nontrivial opportunity cost in the form of foregone health and nutritional expenses.
Eighth, this is still a rough and simple argument which must be adjusted for the Optimizer's Curse when compared against something like anti-malarial bed nets.
Estimating these numbers in my head, it seems like you are overestimating the cost-effectiveness by an order of perhaps several thousand. That is a massive error. Imagine if Givewell had started out by saying that bed nets save lives for $1 each and then revised it up to the current $2,000.
Metformin is not 8 dollars a day, but 2 cents a day in Indian pharmacies. As TAME study and adoption will take at least a decade, people will be in general even reacher and can take the drug.
Metformin has already passed Phaze 1,2 and 3 for many other conditions so its safety profile is well known. It is even known to extend the life of diabetics so they live longer than healthy people.
I explored the problem that not everybody will take it in the article. First, I assume that only half people will take it for whatever reason. Secondary, I explore the ways solving administration problem via food fortification or insurance pressure. Thirdly, metformin is just an example of simple intervention, there are some which are even easier to administrate via food fortification, first of all, vitamin D.
Citation needed. Also, the poverty figure I cited is already adjusted for PPP.
Not by much. Also you assumed that universal drug use would start in 2020, only two years away.
By the way, I'm very confused by the assumption that 5 billion people will be born in 2020. It's obviously wrong, and I don't see what predictive value it has.
Moreover, I don't see how there will be 2.5 billion other people alive in 2100. The claim just isn't supported.
I don't know anything about this. It needs to be cited so that it can be verified and contextualized, and included in the original article so as to prevent people from wasting their time. The prospects for Metformin approval are crucial to your argument about its cost-effectiveness. You can't merely add it as a forum comment to whoever happens to reply.
That's more than perhaps any medication in history.
No, it is known to correlate with living longer. But some or all of that correlation seems to be due to the sickest diabetics being switched from metformin to other drugs.
How could it explain that diabetics lived longer than healthy people?
Anyway, we need a direct test on healthy people to know if it works or not.
If all of the sickest diabetics are switched to other drugs, then the only people taking metformin are the 'healthy diabetics', and it is possible that the average healthy diabetic lives longer than the average person (who may be healthy or unhealthy).
This would give the observed effective without metformin having any effect on longevity.
For example, here https://www.medindia.net/drug-price/metformin/diamet.htm one table of 500mg costs 1 rupee, which is 0.0015 USD.
The model was deliberately oversimplified, as actually these 5 billions will be born the whole duration of the 21 century and will start to take the drug in different ages.
I will add more links on previous studies of metformin, as it probably seems unclear from the article that it is already tested drug for other conditions.
If we speak about fortification of food with useful microelements like iodine, fluoride, and some vitamines it probably has very high reach in developed countries. For some life extending drugs was shown that they could be taken in courses and could have effect on life expectancy.
The problem of constant taking a medical drug is not related to metformin, but to any drug which a person has to take constantly, like hypertension drugs, antidepressant, vitamins etc. This is a different important problem which should be solved to improve public health. There is one possible solution in the form of app (already exist) which records what one has taken and remind to take the drug.
Even if the cost of Metformin is only 2 cents a day, giving to to 5 billion people every day for 80 years would cost about $3 trillion (0.02*365*80*5*10^9). Whilst the cost would (at least potentially) be distributed across the population, it also seems like something that should be mentioned as a cost of the policy.
It was in fact discussed in section 7.1 there we wrote:
The price of a lifetime supply of metformin, 500 USD, will pay for an additional 1-3 years of life expectancy and a proportional delay of age-related diseases.
However, the actual price of the therapy for a person could be negative, because medical insurance companies will be interested that people will start taking age-slowing drugs, as it will delay payments on medical bills. Insurance companies could gain interest on this money. For example, if 100K of medical bills is delayed by three years, and the interest rate is two percent, the insurance company will earn 6 000 USD on later billing. Thus, insurance companies could provide incentives such as discounts or free aging treatments to those who use antiaging therapies.
Medical expenses are wayyy lower in the developing world.
At the time when metformin will reach these markets as a life-extending drug, may be somewhere in 2040, these market will develop.
I more meant it should be mentioned by the $0.24 figure e.g. something like:
"Under our model the direct cost effectiveness is $0.24 per life saved, but there is also an indirect cost of ~$12,000 per life saved from the cost of the metformin (as we will need to supply everyone with it for $3 trillion, but it will only save 250 million lives)."
Noticeably the indirect figure is actually more expensive than current global poverty charities, so under your model buying people metformin would not be an attractive intervention for EAs. This does not mean it would necessarily not be cost effective to fund the trial to 'unlock' the ability for others to buy the drugs, since it might be more efficient than e.g. other developed government use of money, but it does hammer home that the costs of the drugs is very non-negligible.
Also, Alibaba suggests metformin for 5 USD for kg, which implies lifelong supply could be bought for something like 50 USD.
Yes, but 10kg of pure Metformin powder is not much good since it needs to be packaged into pills for easy consumption (since its needs to be taken in sub gram doses). Since you are not able to find pills for less than 2 cents (and even those only in India) I think you should not assume a lower price than that without good reason.
Presumably we run into some fundamental price to form, package and ship all the pills? I would be surprised if that could be gotten much below 1p per pill in developed countries. (although around 1p per pill is clearly possible since some painkillers are sold around that level)
Also, the global market for snake-oil life extension is 300 bn a year, so spending 10 times less would provide everybody with actually working drug.
It probably should be analysed how the bulk price of metformin could be lowered. For example, global supply of vitamin C costs around 1 billion USD a year with 150 kt of bulk powder.
I also not suggesting buying metformin for people. In case of food fortification, the price is probably included into the total price of food and the manufacturers pay lowerest bulk price.
Yes but as I discuss above it needs to be turned into pills and distributed to people, for which a 2 cents per pill cost seems pretty low. If you are arguing for fortification of foods with metformin then presumably we would need to show extraordinary levels of safety, since we would be dosing the entire population at very variable levels.
In general I would find it helpful if you could try and keep your replies in the same comment - this basically seems to be an extension of your other comment about buying metformin in bulk and having it split in two makes it harder to keep track.
Ok. I just have two ideas in different moments of time, that is why there are two comments.
I think that again the problem of expensive pills is not a problem of antiaging therapies, but a more general problem of expensive medicine and poverty. I should not try to solve all possible problems in one article as it will immediately grow to the size of the book.
Most drugs we now consume are overpriced compared with bulk prices; also food is much more expensive in retail. I think it is important problem, but it is another problem.
I'm not saying you need to solve the problem, I'm saying you should take the problem into account in your cost calculations, instead of assuming it will be solved.
In the next version of the article, I will present general equation in which will try to answer all these concerns. It will be (price of the experiment)(probability of success) + indirect benefits of experiment - (fixed price of metformin pills for life)(number of people)(share of adopters)(probability of success of the experiment) - unexpected side effects - growth of food consumption because of higher population. Anything lost?
I'm not quite sure what this equation is meant to be calculating. If it is meant to be $ per life saved it should be something like:
Direct effects: (price of the experiment)/((probability of success)*(lives saved assuming e.g. 10% adoption))
(Note the division is very important here! You missed it in your comment, but it is not clear at all what you would be estimating without it.)
Your estimate of the indirect costs seems right to me, although in the case of:
I would probably not include this level of secondary effect, since these people are also economically productive etc. so it being very hard to estimate.
1 rupee is $0.015 not $0.0015 by nominal exchange rates. Sales tax must be included, as well as comparison with the lower nominal incomes in India rather than the global PPP standard that I gave. Other metformin manufacturers seem to generally charge more (https://www.medindia.net/drug-price/list.asp). Presumably they are not available in all locations; presumably there are areas where people simply don't have easy access to buying these drugs at all. And we are just talking about India, the king of drug IP abuse. I bet if you look at Pakistan or Nigeria then it won't be so easy to buy these drugs there.
I just don't understand how it is possible to assume that even half of the people in the world will purchase and use the most effective product regardless of where they live. Have you tried to convince someone in this position to take any kind of supplements? Like, gone to someone who has very low income, and relies on bicycle or public transport, and explained to them why they should add this or that vitamin or OTC drug to their daily routine? If you had, I don't think you would be making this assumption.
Well yeah, but if you want to calculate the expected value then you must go by what is likely to happen, not what you wish to happen.
Apps exist on smart phones, which lots of people don't have, and most of the remainder won't bother to install or pay attention to it. Moreover, apps don't exist in every language.
Yes, my typo but 0.015 is still around 2 cents as is said in the article.
About persuasion: it is a problem of marketing, which was successfully solved about vitamins.
The global market of vitamin C is around 1 bln USD, btw. https://globenewswire.com/news-release/2016/08/24/866422/0/en/Global-Ascorbic-Acid-Market-Poised-to-Surge-from-USD-820-4-Million-in-2015-to-USD-1083-8-Million-by-2021-MarketResearchStore-Com.html
Speaking more generally, the ethical theory should be based on some kind of axioms. If we take an axiom that "human life is most important value", we easily come to the conclusion that death and aging are bad.
If we take the utilitarian axiom "sufferings are bad", we could come to the same conclusions again, but after more complex constructions, which includes attempts to correctly define sufferings.
I know this surprising fact that older people report better life satisfaction despite having more chronics pain, fewer opportunities, more deceases. I addressed this in the article in the following paragraph:
"This relationship is not obvious, as we are culturally adapted to see age-related changes as normal, and economically based surveys show a u-shaped relation between satisfaction and age (T. C. Cheng, Powdthavee, & Oswald, 2017). However, if all objective and subjective data are taken into account, a plot of this relationship produces a convex form with peak of quality of life at 18, followed by decline (Easterlin, 2006)."
The opportunity cost of life extension is that another person will be never born. But if we take into account the infinite size of the universe, he will be born somewhere else. These infinities are known to cause ethical difficulties as was explored by Bostrom here https://nickbostrom.com/ethics/infinite.pdf
My position is that we first take care about actually exiting people in our space neighbourhood, and later we will take care of all non-existent possible people and of all animals. Maybe we will do it via resurrection of all possible beings near the Omega point, as was suggested by Tipler. The reason to do good level by level is that it helps us to escape "utility monsters" which we can't solve on our level of recourses.
I will try to incorporate replies to your comments in the article
What? Since when? This looks like something you just came up with. Whatever your reasons for believing this, it is a radical and controversial thesis which must be backed up with a serious philosophical argument. Bostrom's paper on infinite ethics does not do the trick here.
Tipler's theory is regarded as implausible by Bostrom as well as others. I can't tell what you mean by the first and third sentences. It seems like your view is that opportunity costs of future people don't matter because you don't care about them. But that was apparent from the original text anyway. What you need to do is support your position against people who disagree.
Ok, I will try without the infinite universe. If we assume that there will be no existential risks and there will be space exploration, there will be a lot of new people (trillions?), much more than actually living people now, so extending life of currently living people is not taking the opportunity from future people to be born.
Moreover, if future people will be born in the world there is no death, suffering and ageing, they could enjoy much better life, as long as they want, so there is no negative opportunity cost for such people - but there is positive opportunity to be born in the better world.
Sure it will take away from the opportunity: the currently living people will have demand for important resources, this extra demand will increase the equilibrium prices of important resources, and these higher prices will cause people to be unable to afford having as many new kids (or the kids who do exist will have a lower standard of living due to higher prices for important resources).
Sure, but there is a negative opportunity cost for the people that could have been born.
The first is an argument against fertility in general, not only about life extension. Higher fertility will increase the population and food prices.
The second is an argument is pro-fertility: by having fewer children I refuse the opportunity to be alive to my unborn children.
So what? It still refutes your claim.
This doesn't even make sense.
Yes, I just suggested it as an example of absurd consequences of the idea that one has value unborn people as much as already existing.
Anyway, If humanity survives and start space exploration, an enormous amount of new people will be born, and they will be born in the much better conditions, where there is no aging and involuntary death. Thus, postponing new lives until creation a better world may be morally good.
I also added the following section to the article where tried to answer yours and other commenters concerns:
4.6. Analysis of the opportunity costs and possible negative consequences of the life extension
Proper cost-benefit analysis of the effective altruistic intervention requires looking into possible opportunity costs of the suggested intervention. Here we list some considerations:
Life extension will increase global population which will increase food and other prices and lower quality of life of the poorest people. The main driver of the population growth is fertility, and if it becomes lower, we move to the next point about the value of unborn people. The main model of the future on which we rely is based on the idea of indefinite technological progress, and if the progress will outperform growth of the population, there will no negative consequences. So, overpopulation will be a problem in the situation of low fertility, low technological progress and very large life extension. This outcome is unlikely as the same biotech which will help extend human life could be also used to produce more food recourses. Also, in our model of the effect of simple interventions, the total effect on the population is rather insignificant, in order of magnitude of several percent, which is smaller than expected error in the population projection.
Life extension will take resources and fewer new people will be born, thus unborn people will lose the opportunity to be alive. As we discussed above, fewer newborn people now could be compensated but much more people which will be born in the future in the much better world.
The older population will be less innovative and diverse. The population is aging anyway, and slowing aging process will make people behave as if they are younger in the same calendar age.
Effects on pension system and employment. Life extension may put pressure on labor market and pension funds, but the general principle is that we can’t kill people to make the economy better. In reality, if powerful life extension technologies will be available, the same technological level will revolutionize other spheres of society.
Optimizer curse could affect our judgment. Optimizer curse is mathematical proof that in case of choice between several uncertain variables, the median error tends to accumulate, and the best solution likely has the biggest error (Smith & Winkler, 2006). This means that our estimation of the metformin efficiency in saving lives is likely to be an overestimation. However, we have around 4 orders of magnitude margin to be the best possible solution to save lives.
We also will explore relations between life extension and existential risks prioritization in the section 8.
These claims about life extension's impact on the economy, finances and resource shortages are controversial and uncited. You also aren't applying sound counterfactual reasoning, instead you are appealing to a generic sense of "well, lots of people will live wonderful lives ANYWAY, so there is no opportunity cost!!" which clearly doesn't address my concerns. Moreover, no one is talking about killing people, we are talking about being more accurate about the value of saving people's lives.
My point is not to keep arguing about this here, but to say that these things should be properly addressed in the paper. With these points and the optimizer's curse especially, you're still not doing real work to improve the argument. You're just taking comments from yourself and other users, and including them in the paper. A paper for cause prioritization cannot be a list of comments, it must be a structured argument.
I updated the section about unborn people and I am going to read and add more links on the topic. Currently it is:
2) Life extension will take resources and fewer new people will be born, thus unborn people will lose the opportunity to be alive. It is not easy to measure value of unborn people without some ethical axioms. If this value is very high, we may try to increase population as much as possible, which seems absurd as in would decrease the quality of life.
While life extension seems to mean fewer new people born each century, the total number of new people is still infinitely large in the situation of constant space exploration (Bostrom, 2003b). Also, fewer newborn people in the 21 cnetury could be compensated by much more people which will be born in the next centuries in the much better world with higher quality of medicine.
If the explorable universe is infinite, the total number of newborn people will not change, but these people will move to later epochs, where they will live even better lives. Tipler (Tipler, 1997) suggested that at the end all possible people will be created by enormous superintelligence in Omega point, and thus all possible people will get chance to be alive. However, we can’t count on such remote events.
But we could compare potential 21th and 22th centuries from our model. In 21th century, fewer people will be born because of life extension, but after superintelligent AI or other power technology will appear, supposedly at 2100, much more new people could live on Earth on much better conditions.
Also, it is not obvious that life extension will affect reproduction negatively because of the “grandmother effect”: the decision about reproduction people typically take in early life, but if they have available grandparents which could help them with babysitting this would increase the willingness to have children as also less strain economy outside the family
There's significant doubt about the effectiveness of Metformin or caloric restriction among humans. NAD+ is being claimed by George Church and others to be more effective, though they might have vested interests since they produce and sell them.
Also, let's not privilege the hypothesis. If you had $60m to invest in gerontological research, would you spend it on Metformin trials?