This is one of my favorite articles I’ve read on this website in months. Since I’m guessing most people won’t read the whole thing, I’ll just quote a few of the highlights here:
Measles is an unremarkable disease based solely on its clinical progression: fever, malaise, coughing, and a relatively low death rate of 0.2%~. What is astonishing about the disease is its capacity to infect cells of the adaptive immune system (memory B‑ and T-cells). This means that if you do end up surviving measles, you are left with an immune system not dissimilar to one of a just-born infant, entirely naive to polio, diphtheria, pertussis, and every single other infection you received protection against either via vaccines or natural infection. It can take up to 3 years for one’s ‘immune memory’ to return, prior to which you are entirely immunocompromised.
I had literally no idea Measles did this. As if I needed another reason to get vaccinated.
On the highest end, Alzheimer’s received $3538M in funding in 2023, and caused 451 DALYs per 100k people worldwide. So, 3538:451, or 7.8.
Then Crohn’s Disease, which has the ratio 92:20.97 (4.3).
Finally, near the bottom of the list is endometriosis, 29:56.61, or .5.
It’s kind of shocking there is such a big difference between diseases when it comes to funding. Literally a 16x discrepancy between Alzheimer’s funding and endometriosis (and a 52x difference between Alzheimer’s and COPD!) I so wish that DOGE had been functional because it’s exactly situations like this that pose the biggest opportunity for improved government operations.
I think the most interesting part of this disease is how it’s kind of sort of not really a form of cancer. It’s basically cancer that causes a lot of issues but very rarely grows in the aggressive way that other cancers do.
The fact that you literally find endometrial lesions with some of the mutations that are hallmarks of cancer implies that there’s probably a lot of endometriosis cases that are cleared up by the immune system naturally which no one ever finds out about. These mutations show up because they provide a survival advantage to the endometrial cells.
Minor nitpick about heritability
Lastly I have a very minor nitpick. The Nature paper you linked ostensibly showing very high heritability doesn’t actually mention heritability in the abstract. The paper made a genetic predictor for endometriosis which explained 5% of the variance (not particularly high, especially given the sample size they were working with).
It does cite a paper about heritability, but that paper doesn’t showing endometriosis as being unusually heritable; it shows 47% of the variance can be explained by additive genetic factors. That’s pretty middle-of-the-pack as far as heritability goes. Conditions like Alzheimer’s and Schizophrenia are significantly more heritable; roughly 70% and 80% respectively.
Actual heritability of Endometriosis is likely somewhat higher than that because most conditions have some non-additive genetic variance. This paper (somewhat questionably) attributes the entire remainder of the variance to “unique environmental factors”.
The actual genetics of the disease itself are almost shockingly polygenic. The study had 61k cases, yet only identified 42 genome-wide significant hits. I can’t look at the rest of the paper due to a paywall (SciHub has stopped archiving new articles :() but it seems there aren’t any especially common alleles with large effect sizes.
This actually strongly the supports the “multiple causes of endometriosis” narrative you explore in your post: if there are that many genetic variants with small effects, there are probably many different ways the disease can manifest (or at least many influences on when and how it shows up).
This is a bit of an aside, but I hesitate to be too shocked by differences in funding:DALY ratios. After all, what you really want to know is change in DALYs at a given level of funding. It seems pretty plausible that some diseases are 10x (or even 100x) as cost-effective to ameliorate as others.
That said, funding:DALY seems like a fine heuristic for searching for misallocated resources. And to be clear, I expect it’s not actually a difference in cost-effectiveness that’s driving the different spending, but I’d want to check before updating too much.
This is one of my favorite articles I’ve read on this website in months. Since I’m guessing most people won’t read the whole thing, I’ll just quote a few of the highlights here:
I had literally no idea Measles did this. As if I needed another reason to get vaccinated.
It’s kind of shocking there is such a big difference between diseases when it comes to funding. Literally a 16x discrepancy between Alzheimer’s funding and endometriosis (and a 52x difference between Alzheimer’s and COPD!) I so wish that DOGE had been functional because it’s exactly situations like this that pose the biggest opportunity for improved government operations.
I think the most interesting part of this disease is how it’s kind of sort of not really a form of cancer. It’s basically cancer that causes a lot of issues but very rarely grows in the aggressive way that other cancers do.
The fact that you literally find endometrial lesions with some of the mutations that are hallmarks of cancer implies that there’s probably a lot of endometriosis cases that are cleared up by the immune system naturally which no one ever finds out about. These mutations show up because they provide a survival advantage to the endometrial cells.
Minor nitpick about heritability
Lastly I have a very minor nitpick. The Nature paper you linked ostensibly showing very high heritability doesn’t actually mention heritability in the abstract. The paper made a genetic predictor for endometriosis which explained 5% of the variance (not particularly high, especially given the sample size they were working with).
It does cite a paper about heritability, but that paper doesn’t showing endometriosis as being unusually heritable; it shows 47% of the variance can be explained by additive genetic factors. That’s pretty middle-of-the-pack as far as heritability goes. Conditions like Alzheimer’s and Schizophrenia are significantly more heritable; roughly 70% and 80% respectively.
Actual heritability of Endometriosis is likely somewhat higher than that because most conditions have some non-additive genetic variance. This paper (somewhat questionably) attributes the entire remainder of the variance to “unique environmental factors”.
The actual genetics of the disease itself are almost shockingly polygenic. The study had 61k cases, yet only identified 42 genome-wide significant hits. I can’t look at the rest of the paper due to a paywall (SciHub has stopped archiving new articles :() but it seems there aren’t any especially common alleles with large effect sizes.
This actually strongly the supports the “multiple causes of endometriosis” narrative you explore in your post: if there are that many genetic variants with small effects, there are probably many different ways the disease can manifest (or at least many influences on when and how it shows up).
This is a bit of an aside, but I hesitate to be too shocked by differences in funding:DALY ratios. After all, what you really want to know is change in DALYs at a given level of funding. It seems pretty plausible that some diseases are 10x (or even 100x) as cost-effective to ameliorate as others.
That said, funding:DALY seems like a fine heuristic for searching for misallocated resources. And to be clear, I expect it’s not actually a difference in cost-effectiveness that’s driving the different spending, but I’d want to check before updating too much.