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Fluttershy comments on Tentative Thoughts on the Cost Effectiveness of the SENS Foundation - Less Wrong Discussion
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Comments (19)
Right, I'm in a similar position here, and I was hoping that someone with some relevant knowledge could make a case for SENS either being a better or a worse funding opportunity than GiveWell. I'm closer to being a risk-neutral expected value maximizer when it comes to charitable donations than most people around here are-- I can think of lots of examples of EA's who are risk-averse regarding their allocation of money they have set aside for charity, at least.
Do you have any predictions for what these might be, or were you generally expressing a belief that, say, large and complex projects like SENS have high failure rates in general?
I have specific ideas about why it will fail: the various interventions to combat the 7 damage types will all meet with complications and unexpected difficulties.
WILT, for example, might kill people or animals for years and years whilst the bugs are ironed out because they won't get the cell replacement therapy right.
MitoSENS will unearth the complexities of mitochondrial DNA and why it's hard to move it into the nucleus.
etc, etc.
But as we do this work, we will learn a lot about the body and there will be some amazing spinoffs. For example LysoSENS and AmyloSENS will probably help with age related diseases. Eventually it might even come together to extend lifespan for another 50 years until the next unforseen problem crops up. But I expect that to take at least till 2090, and a lot will have changed by then. By 2090, cryo, AI and uploading will probably look a lot better than being the next human lab-rat for SENS.
'Ironing out' is an understatement... how the heck do you get fingernail stem cells into the right spots and replenish every hair follicle? Bone marrow is easy, those cells move through the blood and colonize their proper niches when they flow through the bone. But solid tissue, with immobilized cells and extracellular matrix?
Oh hell yes. The animal mitochondrion is a crazy jerry-rigged mess with a genome more overoptimized than many viruses, bizarre specialized ribososomes specifically optimized for making the handful of proteins that the mitochondrial genome codes for while at the same time being obviously slapped together from spare parts, RNA-editing that sometimes is unclear what is important and what is noise, and some of the genes may need to be in the mitochondrion for the purpose of real-time regulation. And the same core set of genes coding for large, hydrophobic, membrane-bound proteins have failed to move into the nuclear genome in all branches of life because that stuff is damn hard to get through two membranes without having it congeal into pellets of inert goo. I've seen interesting work of late involving trying to get RNA-channels embedded in mitochondrial membranes to allow cytosolic RNAs with the proper signal sequences to get into the mitochondrion to be translated there, with some success, but I have little reason to think that such a system would improve upon normal mitochondrial function because poking a complicated system will often just make it worse. This is not to say that mitochondria are perfect, you can imagine in five seconds about twenty ways to make them better than they are - none of which are things you can do by simply going in and making a few simple mods to an existing eukaryotic system.
On another note it is pretty well impossible to get in and modify large fractions of cells in a living organism as opposed to a monolayer of cells in a controlled environment in a laboratory. This being said, I think one of the most fruitful avenues for actual anti-aging research would be looking for ways to chemically boost protein chaperone/recycling activity and improve the regulatory interactions between mitochondria and the cytosol.
"because poking a complicated system will often just make it worse."
yeah that was my view. I have only an amateur interest in biology though.
On the subject of SENS vs givewell, I think givewell have already kind of abandoned the goal of rational philanthropy in the way that they dismissed x-risk and continue to pour money into developing world aid. SENS could at least change the world eventually and affect billions/trillions of lives, whereas givewell's third world aid is always going to be a tiny drop in a gargantuan ocean.
This seems backwards to me. GiveWell's third-world aid probably has big indirect effects, since it's acting to lift these societies from a bad equilibrium of enduring poverty and underdevelopment. SENS is an interesting research program within gerontology, but that's the kind of thing that's going to be pursued anyway if there's any chance of it being useful. We see this quite directly with RepleniSENS, i.e. stem-cell research, which is a thriving field already - there's no reason why this could not apply to other parts of the SENS project. Sustained economic growth in the third world would be a big boon to all sorts of science anyway, due to increased scale if nothing else.
If I agreed with this then I'd be more positive about givewell. I think it's wishful thinking, though. In reality, societies in Africa are not in a bad equilibrium primarily because of malaria or malnutrition, they're in a bad equilibrium because of the backwards values that African people hold, such as loyalty to the tribe/extended family rather than the state, lack of support for western values like accountable government, basic rationality, equality under the law, fair enforcement of contracts, etc. We don't hear much about this because it doesn't fit with the political narrative of the kind of people who spend their time trying to help the third world.
Malnutrition is the visible surface symptom of "these are uncivilised, backwards people caught in a series of petty tribal wars".
EDIT: Just let me disclaim that this is not supposed to be an excuse to not help the developing world. I think we should help them, but not by giving out food or bed nets or medicine. They need better political and value systems, which we could (and should) give them via charter cities.
Countries with bad institutions (including the bad cultural values you list) generally end up in the middle-income range; there are many examples in Latin America. And there's still hope for these to grow further once civil-society institutions get strong enough. Obviously you can find examples where abject poverty is entirely the fault of bad institutions (North Korea), but that's not the case for the countries that are targeted by top GiveWell charities.
So I looked up the poorest countries in the world. Depending on how you measure it, Malawi, the DR of congo and the Central African Republic are at the bottom.
Wikipedia on the Democratic Republic of Congo:
The Central African Republic
Malawi:
I wouldn't say pouring money into the developing world is a tiny drop.
Bill Gates 2014 Annual Letter gives evidence that it's a very good investment.
http://annualletter.gatesfoundation.org/