The world is basically [food secure, except Africa](http://blog.givewell.org/2009/03/16/can-the-green-revolution-be-repeated-in-africa).

Things [aren't improving the way people hope](http://www.givewell.org/international/technical/additional/Easterly-paper).

The Gates Foundation [can't spend their way out of this problem the traditional way](http://blog.givewell.org/2009/10/29/gates-foundation-on-agriculture-funding-where-are-the-facts/).

What's to be done?

Reading up on the GiveWell Open Philanthropy Project's investigation of science policy lead me to look up CRISPR which is given as the example of a very high potential basic science research area.

In context, Givewell appears to be interested in the potential for Gene drive. I am not sure if I am using the term in a grammatically correct way.

Austin Burt, an evolutionary geneticist at Imperial College London,^[5] first outlined the possibility of building gene drives based on natural "selfish" homing endonuclease genes.^[4]Researchers had already shown that these “selfish” genes could spread rapidly through successive generations. Burt suggested that gene drives might be used to prevent a mosquito population from transmitting the malaria parasite or crash a mosquito population. Gene drives based on homing endonucleases have been demonstrated in the laboratory in transgenic populations of mosquitoes^[6] and fruit flies.^[7][8] These enzymes could be used to drive alterations through wild populations.^[1]

I would be suprised if I am the first community member to ponder whether we could just go ahead and exterminate mosquito's to control their populations. Google research I conducted ages ago indicated that doing so resulted in no effective improvement in desired outcomes over the long term. I vaguely remember several examples cited, none of which were Gene Driving, which I have only just heard of. I concluded, at the time, that controlling mosquito populations wasn't the way to go, and instead people should proactively protect themselves.

In 2015, study in Panama reported that such mosquitoes were effective in reducing populations of dengue fever-carrying Aedes aegypti. Over a six month period approximately 4.2 million males were released, yielding a 93-percent population reduction. The female is the disease carrier. The population declined because the larvae of GM males and wild females fail to thrive. Two control areas did not experience population declines. The A. aegypti were not replaced by other species such as the aggressive A. albopictus. In 2014, nine people died and 5,026 were infected, and in 2013 eight deaths and 4,481 infected, while in March 2015 a baby became the year's first victim of the disease.^[9]

It's apparent that research is emerging for the efficacy of Gene Driving. In conducting research for this discussion post, I found most webpages in top google results were from groups and individuals concerned about genetically modified mosquitos being released. I am interested in know if that's the case for anyone else, since my results may be biased by google targeting results based on my past proclivity for using google-searching to confirm suspicions about things I already had.

It appears that the company responsible for the mosquitos is called Oxitec. I have no conflict of interest to disclose in relation to them (though I was hoping to find one, but they're not a publicly listed company!). They appear to be supplying trials in the US and Australia. Though, I haven't looked to see if they're involved in any trials in developing countries. It stuns me that I was not aware of them, given multiple lines of interest that could have brought me to them.

My general disposition towards synthetic biology has been overwhelming suspicious and censorial in the recent past. My views were influenced by the caution I've ported from fears of unfriendly AI. I wanted to share this story of Gene Driving because it is heartwarming and has made me feel better about the future of both existential risk and effective giving. 

Edit: Synthetic biology for fun and profit! Any biohackers around? I just discovered the [registry of standard biological parts](http://parts.igem.org/Main_Page?title=Main_Page), the [biobrick assembly kit](https://www.neb.com/products/e0546-biobrick-assembly-kit) and [genome compiler](http://www.genomecompiler.com/?_ga=1.251739919.769837041.1438856618). I'm having the biggest nerdgasms I can recall. Who wants to chlorinate the mosquito gene pool with me?

Synthetic biology for good: So who's gonna do the protocol design for the tsetse fly gene drive? Whose gonna model the disease?

How much would it cost? [Here's an esteimate](http://lesswrong.com/lw/mld/genosets/cnys). Seems like an easy investment decision in public wellbeing.

GiveWell have just announced their latest charity recommendations! What are everyone’s thoughts on them?

A summary: all of the old charities (GiveDirectly, SCI and Deworm the World) remain on the list. They're rejoined by AMF, as the room for more funding issues that led to it being delisted have been resolved to GiveWell's satisfaction. Together these organisations form GiveWell's list of 'top charities', which is now joined by a list of other charities which they see as excellent but not quite in the top tier. The charities on this list are Development Media International, Living Goods, and two salt fortification programs (run by GAIN and ICCIDD).

As normal, GiveWell's site contains extremely detailed writeups on these organisations. Here are some shorter descriptions which I wrote for Charity Science's donations page and my tool for donating tax-efficiently, starting with the new entries:

GiveWell's newly-added charities

Boost health and cognitive development with salt fortification

The charities GAIN and ICCIDD run programs that fortify the salt that millions of poor people eat with iodine. There is strong evidence that this boosts their health and cognitive development; iodine deficiency causes pervasive mental impairment, as well as stillbirth and congenital abnormalities such as severe retardation. It can be done very cheaply on a mass scale, so is highly cost-effective. GAIN is registered in the US and ICCIDD in Canada (although Canadians can give to either via Charity Science, which for complex reasons helps others who donate tax-deductibly to other charities), allowing for especially efficient donations from these countries, and taxpayers from other countries can also often give to them tax-deductibly. For more information, read GiveWell's detailed reviews of GAIN and ICCIDD.

Educate millions in life-saving practices with Development Media International

Development Media International (DMI) produces radio and television broadcasts in developing countries that tell people about improved health practices that can save lives, especially those of young children. Examples of such practices include exclusive breastfeeding. DMI are conducting a randomized controlled trial of their program which has found promising indications of a large decrease in children's deaths. With more funds they would be able to reach millions of people, due to the unparalleled reach of broadcasting. For more information, read GiveWell's detailed review.

Bring badly-needed goods and health services to the poor with Living Goods

Living Goods is a non-profit which runs a network of people selling badly-needed health and household goods door-to-door in their communities in Uganda and Kenya and provide free health advice. A randomized controlled trial suggested that this caused a 25% reduction in under-5 mortality among other benefits. Products sold range from fortified foods and mosquito nets to cookstoves and contraceptives. Giving to Living Goods is an exciting opportunity to bring these badly needed goods and services to some of the poorest families in the world. For more information, read GiveWell's detailed review.

GiveWell's old and returning charities

Treat hundreds of people for parasitic worms

Deworm the World and the Schistosomiasis Control Initiative (SCI) treat parasitic worm infections such as schistosomiasis, which can cause urinary infections, anemia, and other nutritional problems. For more information, read GiveWell's detailed review, or the more accessible Charity Science summary. Deworm the World is registered in the USA and SCI in the UK, allowing for tax-efficient direct donations in those countries, and taxpayers from other countries can also often give to them efficiently.

Make unconditional cash transfers with GiveDirectly

GiveDirectly lets you empower people to purchase whatever they believe will help them most. Eleven randomized controlled trials have supported cash transfers’ impact, and there is strong evidence that recipients know their own situation best and generally invest in things which make them happier in the long term. For more information, read GiveWell's detailed review, or the more accessible Charity Science summary.

Save lives and prevent infections with the Against Malaria Foundation

Malaria causes about a million deaths and two hundred million infections a year. Thankfully a $6 bednet can stop mosquitos from infecting children while they sleep, preventing this deadly disease. This intervention has exceptionally robust evidence behind it, with many randomized controlled trials suggesting that it is one of the most cost-effective ways to save lives. The Against Malaria Foundation (AMF) is an exceptional charity in every respect, and was GiveWell's top recommendation in 2012 and 2013. Not all bednet charities are created equal, and AMF outperforms the rest on every count. They can distribute nets cheaper than most others, for just $6.13 US. They distribute long-lasting nets which don’t need retreating with insecticide. They are extremely transparent and monitor their own impact carefully, requiring photo verification from each net distribution. For more information, read GiveWell's detailed review, or the more accessible Charity Science summary.

How to donate

To find out which charities are tax-deductible in your country and get links to give to them tax-efficiently, you can use this interactive tool that I made. If you give this season, consider sharing the charities you choose on the EA Donation Registry. We can see which charities EAs pick, and which of the new ones prove popular!

Summary: Overhead expenses' (CEO salary, percentage spent on fundraising) are often deemed a poor measure of charity effectiveness by Effective Altruists, and so they disprefer means of charity evaluation which rely on these. However, 'funding cannibalism' suggests that these metrics (and the norms that engender them) have value: if fundraising is broadly a zero-sum game between charities, then there's a commons problem where all charities could spend less money on fundraising and all do more good, but each is locally incentivized to spend more. Donor norms against increasing spending on zero-sum 'overheads' might be a good way of combating this. This valuable collective action of donors may explain the apparent underutilization of fundraising by charities, and perhaps should make us cautious in undermining it.

The EA critique of charity evaluation

Pre-Givewell, the common means of evaluating charities (Guidestar, Charity Navigator) used a mixture of governance checklists 'overhead indicators'. Charities would gain points both for having features associated with good governance (being transparent in the right ways, balancing budgets, the right sorts of corporate structure), but also in spending its money on programs and avoiding 'overhead expenses' like administration and (especially) fundraising. For shorthand, call this 'common sense' evaluation.

The standard EA critique is that common sense evaluation doesn't capture what is really important: outcomes. It is easy to imagine charities that look really good to common sense evaluation yet have negligible (or negative) outcomes.  In the case of overheads, it becomes unclear whether these are even proxy measures of efficacy. Any fundraising that still 'turns a profit' looks like a good deal, whether it comprises five percent of a charity's spending or fifty.

A summary of the EA critique of common sense evaluation that its myopic focus on these metrics gives pathological incentives, as these metrics frequently lie anti-parallel to maximizing efficacy. To score well on these evaluations, charities may be encouraged to raise less money, hire less able staff, and cut corners in their own management, even if doing these things would be false economies.

Funding cannibalism and commons tragedies

In the wake of the ALS 'Ice bucket challenge', Will MacAskill suggested there is considerable of 'funding cannabilism' in the non-profit sector. Instead of the Ice bucket challenge 'raising' money for ALS, it has taken money that would have been donated to other causes instead - cannibalizing other causes. Rather than each charity raising funds independently of one another, they compete for a fairly fixed pie of aggregate charitable giving.

The 'cannabilism' thesis is controversial, but looks plausible to me, especially when looking at 'macro' indicators: proportion of household charitable spending looks pretty fixed whilst fundraising has increased dramatically, for example.

If true, cannibalism is important. As MacAskill points out, the money tens of millions of dollars raised for ALS is no longer an untrammelled good, alloyed as it is with the opportunity cost of whatever other causes it has cannibalized (q.v.). There's also a more general consideration: if there is a fixed pot of charitable giving insensitive to aggregate fundraising, then fundraising becomes a commons problem. If all charities could spend less on their fundraising, none would lose out, so all could spend more of their funds on their programs. However, for any alone to spend less on fundraising allows the others to cannibalize it.

Civilizing Charitable Cannibals, and Metric Meta-Myopia

Coordination among charities to avoid this commons tragedy is far fetched. Yet coordination of  donors on shared norms about 'overhead ratio' can help. By penalizing a charity for spending too much on zero-sum games with other charities like fundraising, donors can stop a race to the bottom fundraising free for all and burning of the charitable commons that implies. The apparently-high marginal return to fundraising might suggest this is already in effect (and effective!)

The contrarian take would be that it is the EA critique of charity evaluation which is myopic, not the charity evaluation itself - by looking at the apparent benefit for a single charity of more overhead, the EA critique ignores the broader picture of the non-profit ecosystem, and their attack undermines a key environmental protection of an important commons - further, one which the right tail of most effective charities benefit from just as much as the crowd of 'great unwashed' other causes. (Fundraising ability and efficacy look like they should be pretty orthogonal. Besides, if they correlate well enough that you'd expect the most efficacious charities would win the zero-sum fundraising game, couldn't you dispense with Givewell and give to the best fundraisers?)

The contrarian view probably goes too far. Although there's a case for communally caring about fundraising overheads, as cannibalism leads us to guess it is zero sum, parallel reasoning is hard to apply to administration overhead: charity X doesn't lose out if charity Y spends more on management, but charity Y is still penalized by common sense evaluation even if its overall efficacy increases. I'd guess that features like executive pay lie somewhere in the middle: non-profit executives could be poached by for-profit industries, so it is not as simple as donors prodding charities to coordinate to lower executive pay; but donors can prod charities not to throw away whatever 'non-profit premium' they do have in competing with one another for top talent (c.f.). If so, we should castigate people less for caring about overhead, even if we still want to encourage them to care about efficacy too.

The invisible hand of charitable pan-handling

If true, it is unclear whether the story that should be told is 'common sense was right all along and the EA movement overconfidently criticised' or 'A stopped clock is right twice a day, and the generally wrong-headed common sense had an unintended feature amongst the bugs'. I'd lean towards the latter, simply the advocates of the common sense approach have not (to my knowledge) articulated these considerations themselves.

However, many of us believe the implicit machinery of the market can turn without many of the actors within it having any explicit understanding of it. Perhaps the same applies here. If so, we should be less confident in claiming the status quo is pathological and we can do better: there may be a rationale eluding both us and its defenders.

I first wrote up the following post, then happened to run into Holden Karnofsky in person and asked him a much-shortened form of the question verbally.  My attempt to recount Holden's verbal reply is also given further below.  I was moderately impressed by Holden's response because I had not thought of it when listing out possible replies, but I don't understand yet why Holden's response should be true.  Since GiveWell has recently posted about objections to GiveDirectly and replies, I decided to go ahead and post this now.

A question for GiveWell:

Your current #2 top-rated charity is GiveDirectly, which gives one-time gifts of $1000 over 9 months, directly to poor recipients in Kenya via M-PESA.

Givewell tries for high standards of evidence of efficacy and cost-effectiveness.  As I understand it, you don't just want the charity to be arguably cost effective, you want a very high probability that the charity is cost-effective.

The main evidence I've seen cited for direct giving is that the recipients who received the $1000 are then substantially better off 9 months later compared to people who aren't.

While I can imagine arguments that could repair the obvious objection to this reasoning, I haven't seen yet how the resulting evidence about cost-effectiveness could rise again to the epistemic standards one would expect of Givewell's #2 evidence-based charity.

The obvious objection is as follows:  Suppose the Kenyan government simply printed new shillings and handed out $1000 of such shillings to the same recipients targeted by GiveDirectly.  Although the recipients would be better off than non-recipients, this might not reflect any improvement in net utility in Kenya because no new resources were created by printing the money.

There are of course obvious replies to this obvious objection:

(1)  Because the shillings handed out by GiveDirectly are purchased on the foreign currency exchange market using U. S. dollars, and would otherwise have been spent in Kenya in other ways, we should not expect any inflation of the shilling, and should expect an increase in Kenyan consumption of foreign goods corresponding to the increased price of shillings implied by GiveDirectly adding their marginal demand to the auction and thereby raising the marginal price of all shillings sold.  The primary mechanism of action by which GiveDirectly benefits Kenya is by raising the price of shillings in the foreign exchange market and making more hard currency available to sellers of shillings.  So far as I can tell, this argument ought to generalize:  Any argument that the Kenyan government could not accomplish most of the same good by printing shillings will mean that the primary mechanism of GiveWell's effectiveness must be the U.S. dollars being exchanged for the shillings on the foreign currency market.  This in turn means that GiveDirectly could accomplish most of its good by buying the same shillings on the foreign currency market and burning them.

(Or to sharpen the total point of this article:  The sum of the good accomplished by GiveDirectly should equal:

• The good accomplished by the Kenyan government printing shillings and distributing them to the same recipients;
• plus the good accomplished by GiveDirectly then purchasing shillings on the foreign exchange market using US dollars, and burning them.

Indeed, since these mechanisms of action seem mostly independent, we ought to be able to state a percentage of good accomplished which is allegedly attributed to each, summing to 1.  E.g. maybe 80% of the good would be achieved by printing shillings and distributing them to the same recipients, and 20% would be achieved by purchasing shillings on the foreign exchange market and burning them.  But then we have mostly the same questions as before about how to generate wealth by printing shillings.)

(2)  Inequality in Kenya is such that redistributing the supply of shillings toward the very poor increases utility in Kenya. Thus the Kenyan government could accomplish as much good as GiveDirectly by printing an equivalent number of shillings and giving them to the same recipients.  This would create inflation that is a loss to other Kenyans, some of them also very poor, but so much of the shilling supply is held by the rich that the net results are favorable.  Printing shillings can create happiness because it shifts resources from making speedboats for the rich to making corrugated iron roofs for the poor.

(It would be nice if the Kenyan government just printed shillings for GiveDirectly to use, but this the Kenyan government will not realistically do.  Effective altruists must live in the real world, and in the real world GiveDirectly will only accomplish its goals with the aid of effective altruists.  One cannot live in the should-universe where Kenya's government is taking up the burden.  Effective altruists should reason as if the Kenya government consists of plastic dolls who cannot be the locus of responsibility instead of them - that's heroic epistemology 101.  Maybe there will eventually be returns on lobbying for Minimum Guaranteed Income in Kenya if the programs work, but that's for tomorrow, not right now.)

(3)  Like the European Union, Kenya is not printing enough shillings under standard economic theory.  (I have no idea if this is plausibly true for Kenya in particular.)  If the government printed shillings and gave them to the same recipients, this would create real wealth in Kenya because the economy was operating below capacity and velocity of trade would pick up.  The shillings purchased by GiveDirectly would otherwise have stayed in bank accounts rather than going to other Kenyans.  Note that this contradicts the argument step in (1) where we said that the purchased shillings would otherwise have been spent elsewhere, so you should have questioned one argument step or the other.

(4)  Village moneylenders and bosses can successfully extract most surplus generated within their villages by raising rents or demanding bribes.  The only way that individuals can escape the grasp of moneylenders and rentiers is with a one-time gift that was not expected and which the moneylenders and bosses could not arrange to capture.  The government could accomplish as much good as GiveDirectly by printing the same number of shillings and giving them to the same people in an unpredictable pattern.  This would create some inflation but village moneylenders or bosses would ease off on people from whom they couldn't extract as much value, whereas the one-time gift recipients can purchase capital goods that will make them permanently better off in ways that don't allow the new value to be extracted by moneylenders or bosses.

If I recall correctly, GiveDirectly uses the example of a family using some of the gift money to purchase a corrugated iron roof.  From my perspective the obvious objection is that they could just be purchasing a corrugated iron roof that would've gone to someone else and raising the prices of roofs.  (1) says that Kenya has more foreign exchange on hands and can import, not one more corrugated iron roof, but a variety of other foreign goods; (2) says that the resources used in the corrugated iron roof would otherwise have been used to make a speedboat; (3) says that a new trade takes place in which somebody makes a corrugated iron roof that wouldn't have been manufactured otherwise; and (4) says that the village moneylenders usually adjust their interest rates so as to prevent anyone from saving up enough money to buy a corrugated iron roof.

The trouble is that all of these mechanisms of action seem much harder to measure and be sure of, than the measurable outcomes for gift recipients vs. non-recipients.

To reiterate, the sum of the good accomplished by GiveDirectly should equal the good accomplished by the Kenyan government printing shillings and distributing them to the same recipients, plus the good accomplished by GiveDirectly purchasing shillings on the foreign exchange market using US dollars and then burning them.  It seems to me to be difficult to arrive at a state of strong evidence about either of the two terms in this sum, with respect to any mechanism of action I've thought of so far.

With respect to the second term in this sum:  GiveDirectly buying shillings on the foreign exchange market and burning them might create wealth, but it's hard to see how you would measure this over the relevant amounts, and no such evidence was cited in the recommendation of GiveDirectly as the #2 charity.

With respect to the first term in this sum:  Under the Bayesian definition of evidence, strong evidence is evidence we are unlikely to see when the theory is false.  Even in the absence of any mechanism whereby printing nominal shillings creates happiness or wealth, we would still expect to find that the wealth and happiness of gift recipients exceeded the wealth of non-recipients.  So measuring that the gift recipients are wealthier and happier is not strong or even medium evidence that printing nominal shillings creates wealth, unless I'm missing something here.  Our posterior that printing shillings and giving them to certain people would create net wealth in any given quantity, should roughly equal our prior, after updating on the stated experimental evidence.

When I posed a shortened form of this question to Holden Karnofsky, he replied (roughly, I am trying to rephrase from memory):

It seems to me that this is a perverse decomposition of the benefit accomplished.  There's no inflation in the shilling because you're buying them, and since this is true, decomposing the benefit into an operation that does inflationary damage as a side effect, and then another operation that makes up for the inflation, is perverse.  It's like criticizing the Against Malaria Foundation based on a hypothetical which involves the mosquito nets being made from the flesh of babies and then adding another effect which saves the lives of other babies.  Since this is a perverse sum involving a strange extra side effect, it's okay that we can't get good estimates involving either of the terms in it.

Please keep in mind that this is Holden's off-the-cuff, non-written in-person response as rephrased by Eliezer Yudkowsky from imperfect memory.

With that said, I've thought about (what I think was) Holden's answer and I feel like I'm still missing something.  I agree that if U.S. dollars were being sent directly to Kenyan recipients and used only to purchase foreign goods, so that foreign goods were being directly sent from the U.S. to Kenyan recipients, then improvement in measured outcome for recipients compared to non-recipients would be an appropriate metric, and that the decomposition would be perverse.  But if the received money, in the form of Kenyan shillings, is being used primarily to purchase Kenyan goods, and causing those goods to be shipped to one villager rather than another while also possibly increasing velocity of trade, remedying inequality, and enabling completely different actors to buy some amount of foreign goods, then I honestly don't understand why this scenario should have the same causal mechanisms as the scenario where foreign goods are being shipped in from outside the country.  And then I honestly don't understand why measured improvements for one Kenyan over another should be a good proxy for aggregate welfare change to the country.

I may be missing something that an economist would find obvious or I may have misunderstood Holden's reply.  But to me, my sum seems like an obvious causal decomposition of the effects in Kenya, neither of whose terms can be estimated well.  I don't understand why I should expect the uncertainty in these two estimates to cancel out when they are added; I don't understand what background causal model yields this conclusion.

To be clear, I personally would guess that the U.S. would be net better off, if the Federal Reserve directly sent everyone in the U.S. with income under $20K/year a one-time $6,000 check with the money phasing out at a 10% rate up to $80K/year.  This is because, in order of importance:

• I buy the analogous market monetarist argument (3) that the U.S. is printing too little money.
• I buy the analogous argument (2) about inequality.
• (However, I also somewhat suspect that some analogous form of (4) is going on with poor people somehow systematically having all but a certain amount of value extracted from them, which is in general how a modern country can have only 2% instead of 95% of the population being farmers, and yet there are still people living hand-to-mouth.  I would worry that a predictable, universal one-time gift of $6K would not defeat this phenomenon, and that the gift money will just be extracted again somehow.  In the case of Minimum Guaranteed Income, I would worry that the labor share of income will drop proportionally to small amounts of MGI as wages are just bid down by people who can live on less.  Or something.  This would be a much longer discussion and the ideas are much less simple than the above two notions, probably also less important.  I'm just mentioning it again because of my long-term puzzlement with the question "Why are there still poor people after agricultural productivity rose by a factor of 100?")

What I wouldn't say is that my belief in the above is as strong as my belief in, say, the intelligence explosion.  I'd guess that the printing operation would do more good than harm, but it's not what I would call a strong evidence-based conclusion.  If we're going to be okay with that standard of argument generally, then the top charity under that standard of reasoning, generally and evenhandedly applied, ought to work out to some charity that does science and technology research.  (X-risk minimization might seem substantially 'weirder' than that, but the best science-funding charities should be only equally weird.)  And I wouldn't measure the excess of happiness of gift-recipients compared to non-recipients in a pilot program, and call this a good estimate of the net good if a Minimum Guaranteed Income were universally adopted.

So to reiterate, my question to Givewell is not "Why do you think GiveDirectly might maybe end up doing some good anyway?" but "Does GiveDirectly rise to the standards required for your #2 evidence-based charity?"

Givewell’s Holden Karnofsky, who has previously posted his thoughts on Givewell supporting SI/MIRI recently discussed the potential for Givewell to begin evaluating biomedical charities, in Givewell’s Yahoo Group.  Someone suggested (as I have through less direct means) that they take a hard look at SENS Research Foundation, and then Aubrey de Grey appeared and began an interesting discussion with Holden.

The thread begins with Holden’s long initial post about Givewell’s stance on investigating and recommending biomedical charities, which is definitely worth the read for greater insight. The rest of the conversation is aggregated below for anyone else who can’t stomach Yahoo Groups’ interface.

Overall, Holden seems to agree with the goal of SENS, and interested in the details, but the conversation seems to have ended in October 2012 with Holden stating that he was waiting for Dario Amodei’s thoughts on SENS.

Holden,

First, I think that this is an excellent document. I checked for a
number of things that I had heard about (Breakout Labs, John
Ioannidis, Cochrane Collaboration) and they're all there in your
document.

The one thing that's not explicitly mentioned: longevity and life
extension research. At least prima facie, this seems like something
that should be more important than individual disease research, and it
seems like a classic "Valley of Death" case (pun unintended, but
noted) -- T1 stage to use your terminology. I think the SENS website
http://www.sens.org would be a good starting point for one of the (to
me promising) approaches to life extension. I recall from past
conversations that you were aware of SENS, so this is not new to you,
but I think that longevity should be included as part of any
discussion of biomedical research and given separate consideration
given that it has a much lower status than research into specific
conditions such as cancer, dementia, etc. You may ultimately conclude
that not enough can be done in this area, but I think it should be
part of your preliminary stuff. [btw, the United States has a National
Institute of Aging, but it's much lower-status than most of the other
grantmakers mentioned here].

Vipul

---

Hi Vipul,

Thanks for the thoughts. I had a followup conversation with Dario about this topic a few days ago. I think the question of "could one fund translational research to treat/prevent aging?" provides an interesting illustration of some of the tricky dynamics here for a funder:

• It's possible that if there were a great deal more attention giving to treating/preventing aging, we would have some promising treatments. So in a broad sense it's possible that aging is underinvested in.
• A lot of the best basic biology research isn't clearly pointing toward one treatment/condition or another; it's about understanding the fundamentals of how organisms operate. So having an interest in treating aging, as opposed to cancer, might not have a major impact on which projects one funds, if one's main goal is to fund outstanding basic biology research.
• Perhaps because of the lack of emphasis on treating aging (or perhaps because it's simply too difficult of a problem), there don't seem to be promising findings in the "Valley of Death" relevant to aging; the few promising leads have been explored.
• So even if, in a broad sense, there is too little attention given to this problem, knowing this doesn't necessarily yield a clear direction for a relatively small-scale funder of biomedical research.

Best,
Holden

---

Hi everyone,

My attention was brought to this thread, by virtue of the fact that it was my work that gave rise to SENS Foundation, and I'm looking forward to getting more involved here; I've held the Effective Altruism movement in high regard for some time. However, given my newbie status here I want to start by apologising in advance for any oversight of previously-discussed issues etc. I'm naturally delighted both at Holden's post and at Vipul's reply (which I should stress that I did not plant! - I do not know Vipul at all, though I look forward to changing that). I would like to mention just a few key points for discussion:

- Holden, I want to compliment you on your appreciation of how academia really works. Everything you say about that is spot on. The aversion to "high risk high gain" work that has arisen and become so endemic in the system is the most important point here, in terms of why parallel funding routes are needed.

- I'm slightly confused that a lot of Holden's remarks are focused on the private sector (i.e. startups), since my understanding was that GiveWell is about philanthropy; but I realise that there is not all that clear a boundary between the two (and I note the mention of Breakout Labs, with which I have close links and which sits astride that divide more than arguably anyone). The "valley of death" in pre-competitive translational research is a rather different one than that encountered by startups, but the principle is the same, and research to postpone aging certainly encounteres it.

- Something that I presume factors highly among GiveWell's criteria is the extent to which a cause may be undervalued by the bulk of major philanthropists, such that an infusion of additional funds would make more of a difference than in an area that is already being well funded. To me this seems to mirror the logic of focusing on the shortcomings (gaps) in NIH's funding (and that of traditional-model foundations). Holden notes that "Anyone we consider for funding ought to be able to explain why they're better at allocating the funds than the NIH" and I agree wholeheartedly, but my inference is that he thinks that some orgs may indeed be able to explain that. I certainly think that SENS Foundation can.

- Coming to aging: research to postpone aging has the unique problem of quite indescribeable irrationality on the part of most of the general public, policy-makers and even biologists with regard to its desirability. Biogerontologists have been talking to brick walls for decades in their effort to get the rest of the world to appreciate that aging is what causes age-related ill-health, and thus that treatments for aging are merely preventative geriatrics. The concept persists, despite biogerontologists' best efforts, that aging is "natural" and should be left alone, whereas the diseases that it brings about are awful and should be fought. This is made even more bizarre by the fact that the status of age-related diseases as aspects of the later stages of aging absolutely, unequivocally implies that efforts to attack those diseases directly are doomed to fail. As such, this is a (unique? certainly very rare) case where a philanthropic contribution can make a particularly big difference simply because most philanthropists don't see the case for it. It underpins why having an interest in treating aging, as opposed to cancer, absolutely has a major impact on which projects one funds. It's also a case for (if I understand the term correctly) meta-research.

- A lot of the chatter about treating aging revolves around longevity, but it shouldn't. I'm all in favour of longevity, don't get me wrong, but it's not what gets me up in the morning: what does is health. I want people to be truly youthful, however long ago they were born: simple as that. The benefits of longevity per se to humanity may also be substantial, in the form of greater wisdom etc, but that would necessarily come about only very gradually (we won't have any 1000-year-old for at least 900 years whatever happens!), so it doesn't figure strongly in my calculations.

- When forced to acknowledge that the idea of aging being a high-priority target for medicine is an inescapeable consequence of things they already believe (notably that health is good and ageism is bad), many people retreat to the standpoint that it's never going to be possible so it's OK to be irrational about whether it's desirable. The feasibility of postponing age-related ill-health by X years with medicine available Y years from now is, of course, a matter of speculation on which experts disagree, just as with any other pioneering technology. I know that Holden and others have expressed caution (at best) concerning the accuracy of any kind of calculation of probabilities of particular outcomes in the distant (or even not-so-distant) future, and I share that view. However, an approach that may appeal more is to estimate how much humanitarian benefit a given amount of progress would deliver, and then to ask how unlikely that scenario needs to be to make it not worth pursuing. My claim is that the benefits of hastening the defeat of aging by even a few years (which is the minimum that I claim SENS Foundation is in a position to do, given adequate funding) would be so astronomical that the required chance of success to make such an effort worthwhile would be tiny - too tiny for it to be reasonable to argue that such funding would be inadvisable. But of course that is precisely what I would want GiveWell to opine on.

- In the event that GiveWell (or anyone else) were to decide and declare that the defeat of aging is indeed a cause that philanthropists should support, there then arises the question of which organisation(s) should be supported in the best interests of that mission. We at SENS Foundation have worked diligently to rise as quickly as possible in the legitimacy stakes by all standard measures, but we are still young and there remains more to do. If I were to offer an argument to fund us rather than any other entity, it would largely come down to the fact that no other organisation has even a serious plan for defeating aging, let alone a track record of implementing such a plan's early stages.

- A significant chunk of what we do is of a kind that I think comes under "meta-research". A prominent example is a project we're funding at Denver University to extend the well-respected forecasting system "International Futures" so that it can analyse scenarios incorporating dramatically postponed aging.

I greatly welcome any feedback.

Cheers, Aubrey

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Hi Aubrey,

Thanks for the thoughts.

The NIH appears to have a division focused on research relevant to this topic: http://www.nia.nih.gov/research/dab . Its budget appears to be ~$175 million (per year). The National Institute on Aging, which houses this division, has a budget of about $1 billion per year, including a separate ~$400 million for neuroscience (which may also be relevant) as well as $115 million for intramural research. Figures are from http://www.nia.nih.gov/about/budget/2012/fiscal-year-2013-budget. The Institute states that its mandate includes translational research (http://www.nia.nih.gov/research/faq/does-nia-support-translational-research). How would you distinguish your work from this work?

(For the moment I'm putting aside the question I raised in my previous response to Vipul on this topic, regarding whether it's best to approach biology funding from the perspective of "trying to treat/cure a particular condition" or "trying to understand  fundamental questions in biology whose applications are difficult to predict.")

Best,
Holden

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Hi Holden - many thanks.

First: yes, there are really three somewhat separate questions for someone trying to evaluate whether to support SENS Foundation:

1) Is the medical control of aging a hugely valuable mission?

2) Assuming "yes" to (1), is it best achieved by basic research or translational research?

3) Assuming translational, is SENS Foundation the organisation that uses money most effectively in pursuit of that mission?

I had rather expected that you would take some convincing on item (1), and much of what I wrote last time was focused on that. Since it isn't the focus of your question to me, I'm now going to assume until further notice that there is no dissent on that.

So, to answer your question: actually you're not putting aside the basic-vs-translational question as much as you may think you are. The word "translational" is flavour of the month in government funding circles these days (not only in the USA), so it's not surprising that the NIA has a public statement of the kind you pointed to. However, notice that the link they give "for more information" is to a page listing ALL "Funding Opportunity Announcements". There is no page specifically for translational ones, and the reason there isn't is that the amount of work that the NIA actually funds that could really be called translational is tiny. In other words, the page you found is actually just blatant spin. The neuroscience slice you mention is an anomaly arising from the way NIA was founded (the natural place for that money is clearly NINDS): the fact that it's NIA money does not, in practice, translate into its being spent on work to prevent neurodegeneration by treating its cause (aging). Instead, just like NINDS money, it's spent on attacking neurodegeneration directly, as if such diseases could be eliminated from the body just like an infection: the same old mistake that afflicts, and dooms, the whole of geriatric medicine.

So, the first answer to your question is that SENS Foundation really DOES focus on translational research, with an explicit goal of postponing age-related ill-health. But there's also another big difference: we can attack this problem relatively free of the other priorities that afflict mainstream funding (whether from NIH or from trasitional foundations). Most importantly, though we do and will continue to publish our interim results in the peer-reviewed literature, we are much less constrained by "publish or perish" tyranny than typical academics are. This allows us to proceed by constructing and implementing a rational "project plan" (namely SENS) to get to the intended goal (the defeat of aging), whereas what little translational work is funded by NIA or others is guided overwhelmingly by the imperative to get some kind of positive result as quickly as possible, even when it's understood that those results are not remotely likely to "scale", i.e. to translate into eventual medical treatments that significantly delay aging. A great example of this is the NIA's Interventions Testing Program (ITP) to test the mouse longevity effects of various small molecules. The ITP only exists at all (and in a far smaller form than originally intended) as a result of several years of persistence by the then head of the NIA's biology division (Huber Warner), and it focuses entirely on delivery of simple drugs starting rather early in life, with the result that no information emerges that's relevant to treating people who are already in middle age or older. (This is despite the fact that by far the most high-profile result that the ITP has delivered so far, the benefits of rapamycin, actually WAS a late-onset study: it wasn't meant to be, but technical issues delayed the experiment.) In a nutshell, there is a huge bias against high-risk high-gain work.

The third thing that distinguishes SENS Foundation's approach is that we can transcend the "balkanisation" (silo mentality) that dominates mainstream academic funding. When one submits a grant application to NIA, it is evaluated by gerontologists, just as when one submits to NCI it is evaluated by oncologists, etc. What's wrong with this is that it biases the system immensely against cross-disciplinary proposals. SENS is a plan that brings together a large body of knowledge from gerontology but also a huge amount of expertise that was developed for other reasons entirely - to treat acute disease/injury, or in some cases for purposes that were not biomedical at all (notably environmental decontamination). It doesn't matter how robust the objective scientific and technological argument is for work of that sort: it will never compete (especially in today's very tight funding environment) with more single-topic proposals all of whose details can be understood by reviewers from a particular single field.

The final thing to mention, and this actually also answers your question to Vipul about basic versus translational research, is that SENS is a plan that has stood the test of time. I've been propounding it since 2000, well before SENS Foundation existed, and it used to come in for a lot of criticism (initially more in the form of off-the-record ridicule, and latterly, at my behest, in print), but in every single case that criticism was found to stem from ignorance on the part of the detractor, either of what I proposed or of published experimental work on which the proposal was based. That's why I'm now regularly asked to organise entire sessions at mainstream gerontology conferences, whereas as little as five years ago I would never even be invited to speak. It's also why the Research Advisory Board of SENS Foundation consists of such prestigious scientists. This is a very strong argument, in my view, for believing that now is the time to sink a proper amount of money into translational gerontology (though certainly not to cease doin basic biogerontology too). It's well known that basic scientists are often not the most far-sighted when it comes to seeing how to apply their discoveries (attitudes in 1900 to the feasibility of powered flight being the canonical example). It is therefore a source of concern that almost all the experts who have the ear of funders in this field are basic scientists, whose instinct is to carry on finding things out and to deprioritise the tedious business of applying that knowledge. SENS has achieved a gratisfying level of legitimacy in gerontology, but it is still foreign to most card-carrying gerontologists, and as such it remains essentially unfundable via mainstream mechanisms. Hence the need to create a philanthropy-driven entity, SENS Foundation, to get this work done.

Let me know if this helps, or if you have further questions.

Cheers, Aubrey

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Hi Aubrey,

Thanks again for engaging so thoughtfully.

I agree that a new technology/treatment that could delay or reverse aging (or aspects of it) would be enormously valuable. Regarding the rest of your argument, this is a good example of the challenges I've been discussing in understanding biomedical research.

You state that you have a high-expected-value plan that the academic world can't recognize the value of because of shortcomings such as "balkanisation" and risk aversion. I believe it may be true that the academic world has such problems to a degree; however, I also believe that there are a lot of extremely talented people in academia and that they often (though not necessarily always) find ways to move forward on promising work. Without more subject-matter expertise (or the advice of someone with such expertise), I can't easily assess the technical merits of your argument or potential counterarguments. Hopefully we'll have a better system for doing so at some point in the future.

I'll be very interested to see Dario's thoughts on the matter if he responds. I'd cite Dario as an example of an academic who ultimately wants to do work of the greatest humanitarian value possible, regardless of whether it is prestigious work. And as my summary of our conversation shows, he acknowledges that the world of biomedical research may have certain suboptimal incentives, but didn't seem to think that these issues are leaving specific, visible outstanding research programs on the table the way that your email implies.

Best,
Holden

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Excellent. I too am keen to see Dario's comments. Dario also has the advantage of being based just a few miles from SENS Foundation's research centre, so we can definitely get together f2f soon if he wants.

Cheers, Aubrey

 

Givewell's blog has recently begun a series of 5 self-evaluation posts (they are on the 4th right now) which discuss where the organization is at and where they're going. They're all worth a read. In particular, they build up to a survey for Givewell followers about how you'd like the organization to direct their research in the future, with options to emphasize existential risk and research even if the evidence is lower quality.

GiveWell recently release notes from their interview with Jaan Tallinn, Skype co-founder and a major SIAI donor, about SIAI (link). Holden Karnofsky says 

[M]y key high-level takeaways are that

1. I appreciated Jaan's thoughtfulness and willingness to engage in depth. It was an interesting exchange.
2. I continue to disagree with the way that SIAI is thinking about the "Friendliness" problem. 
3. It seems to me that all the ways in which Jaan and I disagree on this topic have more to do with philosophy (how to quantify uncertainty; how to deal with conjunctions; how to act in consideration of low probabilities) and with social science-type intuitions (how would people likely use a particular sort of AI) than with computer science or programming (what properties has software usually had historically; which of these properties become incoherent/hard to imagine when applied to AGI)

From the GiveWell blog, which is often interesting & applicable to our interests, comes a post on the quality of their volunteers:

"In our experience, valuable volunteers are rare. The people who email us about volunteer opportunities generally seem enthusiastic about GiveWell’s mission, and motivated by a shared belief in our goals to give up their free time to help us. Yet, the majority of these people never complete useful work for us.

We ask new volunteers to first complete a test assignment that takes about 2-4 hours. The assignment involves fixing the formatting of our list of sources on two practice pages and allows us to get a sense of their attention to detail and commitment to volunteer hours. Of the 34 people who emailed us expressing an interest in volunteering between September 2010 (when we started keeping track) and May 2011, only 7 have completed the test assignment and gone on to complete valuable work for us.

Of the 34, 10 never responded to my email outlining what GiveWell volunteers do and asking them if they’d like me to send the first assignment. 13 responded to this email and I sent them the first assignment, but they didn’t complete it. The final 4 completed the test assignment, but didn’t send back the next (real) assignment I sent.

It seems rather surprising that almost 80% of people who take the initiative to seek us out and ask for unpaid work fail to complete a single assignment. But maybe this shouldn’t be surprising. Writing an email is quick and exciting; spending a few hours fixing punctuation is not."

(The dropout rate is probably not due to the perceived low utility of the work - GiveWell seems to be up-front that the test assignment is a test.)

I draw a few lessons from this:

• there is likely low-hanging fruit for volunteers in charities or communities in the area of sustained tedious tasks; collecting anecdotes, reports, links, that sort of thing come to mind as LW examples
• additional incentives like jsalvatier's contests may be necessary to draw out community volunteer resources
• tricking volunteers into work might be a fruitful approach - perhaps asking for explicit pointers to research or other help might not work, but presenting a half-complete version will elicit useful responses one can mine. (A more productive kind of trolling.)

Holden Karnofsky of GiveWell.org interviewed Jasen Murray of SIAI and published his notes (Edit: PDF, thanks lukeprog!), with updates from later conversations. Lots of stuff to take an interest in there - thanks to jsalvatier for drawing our attention to it. One new bit of information stands out in particular:

• Michael Vassar is working on an idea he calls the "Persistent Problems Group" or PPG. The idea is to assemble a blue-ribbon panel of recognizable experts to make sense of the academic literature on very applicable, popular, but poorly understood topics such as diet/nutrition. This would have obvious benefits for helping people understand what the literature has and hasn't established on important topics; it would also be a demonstration that there is such a thing as "skill at making sense of the world."