“Which medical research should be receive more funding” is a hugely important question, with hundreds of *billions* of dollars spent on medical research yearly. It’s also one that is not always approached in a rational and evidence-based way, which is understandable, as most people think about this question when they or their loved ones ends up suffering from a particular disease.

As an EA, it’s somewhat ironic that I started thinking about medical research because someone close to me became disabled from a horrible illness, but researching this illness gave me lots of ideas that could be more widely applicable to cause prioritisation within medical research. I’ll use this illness as a case study, using the ITN framework.

Neglectedness

I’ve deliberately not named the illness yet, as there is significant controversy about its name. In fact, there are various controversies around this illness, which we’ll look at in more detail. The controversies both contribute to and are a symptom of its neglectedness, which makes it quite interesting for researchers and EAs to objectively investigate.

Here I’ll use the name myalgic encephalomyelitis, or ME. It’s an illness characterised by extreme fatigue, which in the most severe cases can lead to not being able to move the body at all, beyond basic functions like breating. It is commonly accompanied by pain. There is no cure, very few medicine to manage symptoms, and the cause is not understood at all. Researchers have observed immunological and neurological abnormalities, but that’s about it. Tens of millions of people worldwide fit the diagnosis, with about a quarter of them being homebound or even unable to leave their bed.

The history of controversy is a nasty one. It is now known that it’s a disease that affects the immune system, and diseases like that disproportionally affect women, for reasons still unknown. This is a well-established, empirical fact. But in the past, the condescending, patriarchal society would label this “mass hysteria”. The revised name became “Chronic Fatigue Syndrome”, which is a bit better, but still trivialises this crippling disease (“I’m always tired too”). This history continues in different forms, with some insurance companies and governmental bodies still labelling the disease as a “psycho-social disorder”. This is an obvious cop-out for a disease that has virtually no objective lab tests to confirm it, but which is very real nonetheless.

Diseases can be real — causing symptoms and suffering — and yet have no objective tests, simply because science has not advanced enough. This then causes a downward spiral: victims are shamed and blamed (“just get off your ass”), insurance companies see a way to improve their bottom line (“we don’t cover psychological conditions”), doctors are powerless at best and harmful at worst (“do some exercise, that’s good for everyone”), patients get desperate and turn to alternative medicine and conspiracy theories, people see that and decide that this disease really must be a sham, and finally researchers stay away in fear of their funding drying up or even losing their jobs.

This is very interesting to EAs. It’s like mis-pricing of stocks, where investors act emotionally instead of rationally. If we can identify diseases for which this happens, and “correct the valuation”, we could not only correct the amount of funding a cause receives, but potentially even break this downward spiral. We could attract funding from traditional sources which have eschewed these causes because of stigma. I don’t know of where to allocate funds to most effectively make that happen, be it in basic research, or public campaigns, or lobbying, or something else, but it seems a huge opportunity to me.

Importance

A standard measure of disease burden is DALY, Disability-Adjusted Life Years, where you count the number of premature deaths because of an illness, plus the number of “equivalent” years lost due to disability. What equivalent means here is tricky, and there are various ways of measuring it, based on quality of life, or loss of function, or how many years with a disability people are willing to trade in for one year of premature death, and so on. In the end a disease gets a “disability weight” (DW) to indicate how much suffering it causes, between 0 (perfect health) and 1 (death).

Because ME gets neglected by researchers, good data for determining the disease burden of ME is scarce. For example, ME was not included in the 2016 Global Burden of Disease (GBD) study. A recent study looked at two methods of estimating disability weights to come up with a weight of 0.46 (and for the one quarter of patients with severe ME, 0.76). It’s fascinating how this is estimated, and I highly recommend reading the underlying studies!

For comparison, here are the ME disability weights put in context (based on the 2016 GBD study). There are a ton of caveats in comparing these, but this should give you a rough idea.

Condition Disability weight (DW) ME (weighted average) 0.46 ME (severe) 0.76 Multiple sclerosis (moderate) 0.463 Multiple sclerosis (severe) 0.719 Dementia (severe) 0.449 AIDS (without treatment) 0.582 HIV/AIDS (with treatment) 0.078 Anxiety disorder (severe) 0.523 Autism 0.262 Loss of one leg (without treatment) 0.173 Asthma (controlled) 0.015

The other part is premature deaths. Suicide is at a ridiculously high rate for ME patients, about 17 times the national US average (compared with 2 times the average for cancer and MS patients and 6 times the average for patients with depression). There also seems to be a link with heart disease and cancer. Taking all that into account, plus the disability weights, plus a conservative estimate of about 1 million patients in the United States with ME, the estimated disease burden in the US is 714,000 DALY.

To get a sense of context here, compare this with 2015 US DALYs and NIH spending:

DALY NIH spending spending per DALY ME: 0.71M $7M $9.8 Multiple sclerosis: 0.28M $94M $331 Cancer: 13.5M $5389M $399 Mental illness: 7.7M $2263M $292 Heart disease: 7.8M $426M $55

Looking at the raw data, there is quite a bit of variation in funding, but estimated funding for ME per DALY is just insanely low. Using the previous analogy, this is almost literally mispricing in the market!

All of this is still too limited for well-weighted decision for EA standards. For example, how does this extrapolate to *global* disease burdens instead of just the US? How robust are the analyses and the underlying studies? What kind of error bars are we talking about when comparing numbers here? I couldn’t find answers to those questions, so this is fairly speculative, but the several-orders-of-magnitudes underfunding based on DALYs by the NIH does suggest that there might be something interesting here.

Tractability

Now, underfunding doesn’t mean that it’s a good use of your dollars. Is there “room for more funding”?

I have two conflicting intuitions about this: first of all, since ME is so dramatically underfunded, any kind of research into the fundamental causes of the disease should find at least something, because there are such severe symptoms that basically no-one has looked into yet using modern methods. On the other hand, it could be hard to find someone competent because of the stigma and misunderstanding.

In the case of ME though, there seems to be some momentum. A few years ago, the director of the Stanford Genome Technology Center, Ron Davis, saw his son fell severely ill with ME, after which he started a research group to look into the disease. He also started a foundation and got endorsements for ME research from his extensive network, including several Nobel prize winners and NAS members. When you start looking, you find similar stories, such as the Cornell ME/CFS center, which was founded by someone whose family member has ME.

These people are highly skilled, and might never have gotten into ME research if it weren’t for family members getting it. But now they are highly motivated, and in the position to break out of the downward spiral of stigma. If they can even find a *hint* of a physical cause (“biomarker”), the names of institutions like Stanford or Cornell would be behind a legitimisation of the disease. This could lead to more funding, more decent research, and even better outcomes for patients in the short term, through increased awareness and education among doctors.

Timing is crucial here. You want to have a good team with a research proposal that has some chance of finding something, so you want to wait for that. But you also don’t want to wait too long, or the effort might lose momentum — researchers might give up or retire, a group of well-intentioned Nobel Prize winners may fall apart, and so on.

In the Stanford case, it might be the perfect time for an intervention by EAs. They have a plan of doing a wide range of state-of-the-art tests on a small number of very severe patients, like the son of the director. This both saves money and increases the likelihood of finding something, as any biological effects will probably be more pronounced in such sick patients. They can do these tests cheaply because their lab has (co-)invented some of the technology that they’re testing with. They raised enough funding from grants and private funds to collect the samples and get preliminary results, but need more money to continue doing tests and analysis. Money is actually the blocker, so each additional dollar would immediately be put to use.

Conclusion

For an underfunded, misunderstood, and important disease like ME, and others like it, it’s hard to say where exactly to spend your money to make a difference. There are a number of different things to target, and they all reinforce each other: more funding for research, more public awareness, better education of doctors, and so on. For ME, a lot of groups focus on public awareness, with online campaigns, protests, and a recent award-winning documentary by a Harvard student with ME. It looks like those efforts are helping, with recent results including revised government guidelines and a surprisingly huge anonymous cryptocurrency donation. That said, I suspect that additional dollars would be best spent on medical research.

When learning about ME, I had a lot of ideas relevant for EA. Some might be already known, or perhaps even debunked, but maybe there are some new ones in here, too:

Stigma could be an indicator of neglected diseases.

Association with alternative medicine and questionable practices could be such an indicator too. There could be more to it when you dig deeper, as people can get desperate for a solution.

Stigma and association with questionable practices can amplify the neglectedness of a disease.

Basic research could have an outsized impact on such diseases, by breaking through stigma.

When removing stigma from a field of research, that could attract funding and scientists, thus amplifying our dollars.

This effect might be bigger than that of activist campaigns, per dollar contributed.

In the long term there could be a lot of room for funding in diseases with low funding per DALY.

In the short term however, it might be hard to find good research worth contributing to.

It might be worth finding top researchers who have a family member suffering from a disease, as they will be motivated.

This will be easier the more widespread a disease is, thus correlating with its importance.

I think proper timing in selecting good research is key, in order to accelerate something that has some momentum.

I’m still an EA noob, but I suspect that a small amount of funding towards top research into diseases like this could be quite competitive, especially compared to other interventions in the developed world. What do you think?