Surely, there are lager effect sizes there, but they need much more testing to prove the safety and such testing is the most expensive part of any trials. There is a few already safe intervention which could help to extend life, that is, besides metformin, green tee and vitamin D.
Even as a trillion dollar project, fighting aging could be still cost-effective, after we divide the benefit for 10 billion people.
If we speaking on de novo therapies, current price of just one drug development is close to 10 billions, and comprehensive aging therapy like SENS should include many new interventions, so it may be reasonable to estimate that it will be equal to 100 new interventions, and thus trillion dollar price is real. The sum is large but affordable for humanity as whole: total space funding for all history is around this price.
However, it is impossible to get such trillion dollar funding via donations. But EA efforts could be used to attract larger funders, like pension funds, farma, governments, billionaires and insurance companies for funding such projects as they will eventually benefit from the cure for aging.
The main question as I see: is current spending of 1 billion-a-year on aging enough to delay aging for 10 years? Aging is a problem of (hyper)exponentially increasing complexity with time. There are probably a few interventions which could give 1-3 years of expected life extension (and aging delay): metformin, vitamin D and green tea, and proper testing of them could cost as few as tens millions of dollars as in proposed TAME study of metformin. This (+chance to survive for other life extending technologies) means much higher cost-effectiveness of such small experiments, as I described in the post. There are several other ways to donate more cost-effectively than directly funding aging research, like lobbying WHO that aging is a disease.
On the other hand, as aging is so quickly grows in time, adding up with small interventions will not give us 10 years delay of aging. So when we speak about 10 years aging delay, costs become much higher, as there is no more low-hanging fruits.
I read an opinion that current aging research may benefit of 10 times increase in spending. But it is still not clear, how much should be spent in this mode to find “a cure for aging”. I guestimate that at least a trillion dollars for 10 ten years delay of aging - above the level which we could get via simple (but undertested) interventions, which is 3-5 years.
Now, spending a trillion dollars will give 10 billion people 10 years QALY each, which is only 10 dollars for QALY (assuming that we should not count the price of therapy, as people will pay themselves, and they only need an opportunity for life extension, but not constrained in health spendings).
In fact, I tried also to explore this idea—which I find crucial—in my Russian book “Structure of global catastrophe”, but my attempts to translate into English didn’t work well, so I now slowly convert its content in the articles.
I would add an important link on the A Singular Chain of Events by Tonn and MacGregor, as well as work of Seth Baum on double catastrophes. The idea of “Peak everything” about simultaneous depletion of all natural resources also belong here, but should be combined with idea of Singularity as idea of acceleration of everything, which combined create very unstable situation.
Theoretical reasons for Doomsday weapon was laid by Herman Khan in “On Thermonuclear war”. I scanned related chapter here: https://www.scribd.com/document/16563514/Herman-Khan-On-Doomsday-machine
The main idea is that it is ideal defence weapon, as no body will ever attack a country owning such a device.
The idea of attacking the Yellowstone is discussed very often in Russian blogosphere (like here https://izborskiy-club.livejournal.com/310579.html), and interest to the geophysical weapons was strong in the Soviet Union (details here: http://nvo.ng.ru/armament/2006-04-21/6_weapontheyfear.html) - this interest ended up in creating Poseidon artificial tsunami system which is now under testing.
I’ve read that US has an instrument to attack hardened underground facilities by multiple heavy nuclear strike in one place, which allows creating much deeper crate than a single nuclear explosion and destroy targets around 1 km deep. The same way an volcanic caldera cover could be attacked, and such multiple strikes could weaken its strength until it blow up by internal pressure—so you don’t need to go through the whole caldera’s cover. no new weapons for it is needed—just special targeting of already exiting.
Russian Poseidon system has 100-200 Mt bombs delivered by a very large torpedo and is in final stages of construction. https://en.wikipedia.org/wiki/Status-6_Oceanic_Multipurpose_System
“Normal” nuclear war could be only only a first stage of multistage collapse. However, there are some ideas, how to use exiting nuclear stockpiles to cause more damage and trigger a larger global catastrophe—one is most discussed is nuking a supervolcano, but there are others. In Russian sources is a common place that retaliation attack on US may include attack on the Yellowstone, but I don’t know if it is a part of the official doctrine.
Future nuclear war could be using even more destructive weapons (which may exist secretly now). Teller has been working on 10 gigaton bomb. Russians now making Poseidon large torpedo system which will be probably equipped with 100 Mt cobalt bombs.
“Normal” global warming is not x-risk, but possible heavy tail connected with something unknown could be. For example, the observed stability of our climate may be just an “anthropic shadow”, and, in fact, climate transition to the next hotter meta-stable condition is long overdue, and could be triggered by small human actions.
The next meta-stable state may be with median temperature 57C according to the article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748134/ (“The climate instability is caused by a positive cloud feedback and leads to a new steady state with global-mean sea-surface temperatures above 330 K”)
Because of rising solar luminosity the extinction level global warming is a question of “when”, not “if”, but typically it is estimated to happen hundreds millions years from now.
I also once tried to create a map of s-risks here
I would add to your typology the s-risks of quantum immortality—an infinitely log timeline where a person is not dying from aging. Actually, I concluded now that such timeline will eventually end up in some form of AI resurrection, but such AI may be hostile.
Another type which should be mentioned is “hostile human augmentation”, where neurons are rewired by hostile AI to make the victim feel even stronger and stronger pain. Which end up in tiling universe with anti-orgasmatronium.
Another distinction which should be mentioned is between a pure “pain s-risks” and s-risks where a person also have moral sufferings via understanding of her bad—and probably eternally worsening—situation (as in the story “I have no mouth but I must scream”).
Smaller organisation also probably have to pay larger relative cost for failed grants’ attempts. Their main talents have to spend significant amount of time on writing grant proposals (or write shorter proposals of lower quality).
One point is that in our time life extension is more important than QALY, because life extension increases the chances of a person to survive until potential indefinite life extension (or some other important scientific breakthroughs with significant value).
One more way to treat burnout is to completely change the profession or main type of activity. I did it a few times. I find that after around 10 years I have enough interest to return to abounded field.
Such decisions are costly and may not help to have great success in life, as some most successful people were able to concentrate on one-two projects for much longer than others. But also some people are successful exactly because they are working in different projects (e.g. Musk).