I was asked why many leads in ME research have not been followed up. This is closely tied to the dire lack of research.
I think we can sum this up in one line, but the details are so very complex. We probably know all the reasons, they are just scattered over patient comments from many years. If someone has an hypothesis its probably right and probably only a small part of the big picture. So here it is - progress occurs when enough people make enough effort with enough resources, and we have never had enough.
That sentence hides enormous complexity. I have found it useful to think of accelerators and brakes, and our destinations are tests, treatments and cures.
I used to think we just have to push research. Then I realized the factors acting against us are powerful, and we need to oppose them too. What follows is a list of just some of the factors, and its probably not a complete list.
ME is about as complex a disease as there is. Its also different from other diseases we understand. Nobody had a clue as to where to do definitive research. There is a long line of failure or results that cannot be replicated. This will continue until we have answers. We will only be sure we have answers some years after the research shows potential answers. I am hoping that is now, but I need hindsight to be sure. The current leads are at least promising.
Many early researchers failed to prove ME or CFS was caused by, for example, EBV. Failed experiments can turn some researchers off. Many researchers need successes, not failures.
McEvedy and Beard published that ME was hysteria in about 1970. They had no solid evidence, the case for hysteria even existing (as opposed to being created by definition) is extremely weak, and if I recall correctly they didn't even see a single patient. This was a paper from a PhD thesis.
Also around 1977 we had the initial creation of the BPS movement as we know it, based on a paper by Engels, which I blogged about here:
I think ME became tainted in the 70s, not the 80s, and not because of the label CFS. CFS just made it worse. Switching back to ME from CFS will not really fix things, though not much is worse than a diagnosis of chronic fatigue, which could be almost anything. We should start calling loose CFS diagnoses "Idiopathic Chronic Fatigue", and perhaps refer to the Oxford definition using that label.
AIDS came along and many researchers moved to AIDS and later HIV research. In the 80s there were researchers who did both CFS or ME and AIDS research. HIV got the money, public attention, research grants etc.
Not enough people visibly die from ME. HIV got attention because it was lethal and communicable. It got attention because many with HIV, and their friends, family and allies, are well enough to effectively advocate for themselves.
As a nebulous disease or disorder, hard to diagnose, its easy for CFS and even ME to be treated as political footballs. I would like to start calling us the abandoned sick, though that is about many more diseases than just CFS or ME.
Its human nature to pigeonhole things. So long as we are considered just fatigued we can be ignored. So long as its considered mental, we can be ignored. The big issue we face is called a category mistake, categorizing something as though it were something else. Its not unique to ME in medicine, I think depression is a huge kludge of category mistakes all mashed together.
Research only advances if there is money, and a researcher has to convince grant reviewers that there is not only merit in the research, but sufficient merit to fund it ahead of other proposed studies. This can be hard to do in a climate of general bias against the area. There will never be enough funding to pursue every potential lead.
Research requires funding. Grants are reviewed by a small group. Often its just three people who review the application, and make a recommendation. We have the absurd situation where a world leading researcher, Ian Lipkin, had a proposal knocked back not because it was flawed, or lacked merit, but because "CFS is psychological" or something similar. If we applied those standards to psychogenic research then nearly all of it would not get funding, as the history is that all of these disorders that have been proven have been physiological, not psychogenic. Their failure rate, where we have definitive answers, is 100%. The most famous example is of course peptic ulcers, in which the advancement of knowledge was provably manipulated, which I have blogged about here:
Drug companies have not got involved much, but that is to be expected. Unless there have a clear target there is no reason to get involved. Drug research is expensive, and they cannot be expected to research something for which they have no clear drug or drug target. I cannot say the same about diagnostic limitations because there is not much in the way of objective diagnostic criteria for most of the psychiatric disorders they do drug research into. I know we like to blame the drug companies for many things, some of which is a fair assessment, but when the basic research is unsound or flawed then their research will be flawed too.
Due to biases in academia many researchers are told not to get into researching CFS or ME. In at least one case there is some evidence of action being taken against a researcher by their academic institution.
Crowd-sourcing now gives us opportunities to fund research - there is no reason for patients to not fund pilot projects if there is enough interest. The issue is lack of interest being generated. Of course you still need researchers who are interested in doing the research.
We still have poor epidemiology. The CDC's epidemiological studies were not very good. We have no definitive knowledge of longitudinal changes in patients. It was only recently we found indications that the biochemistry might change at about the three year mark. We need not just better knowledge of the biochemistry, but better knowledge of how it changes over time.
Some of the BPS research advocates are also painting a picture, albeit based largely on fancy and without any substantive evidence, that demonizes patients. This can create a biased image in the media and bureaucracy. There is a lot of evidence for this, its not worth discussing further here. This is part of that political game I alluded to earlier.
The BPS issues also appear to be a political struggle, and we see this from the early 80s. They want to change the public agenda. What distinguishes politics from science, in my probably naive view, is politics advances by rhetoric and persuasion, and science (at least ideally) advances by evidence and sound reasoning.
There are financial implications here too. Many CFS and ME cases are misdiagnoses, and it costs a lot to do the testing to find out what is actually wrong. Insurance or government usually have to pay, depending on the local system and what services are used. Denial of testing is hugely rewarding. Denial of insurance payouts is even more rewarding. There are economic pressures to do this, and some of the people promoting the BPS view have conflict of interest due to insurance ties etc.
One thing that is being ignored, which makes no financial sense, is that failing to advance the science on complex chronic diseases mean more people stay sick for longer, with greater economic impact. My estimate is that ME alone costs the world on the order of a trillion dollars a decade. Research funding commensurate with this problem needs to be at least one to two orders of magnitude higher.
Now the investigative media, or even basic journalism, should see the flaws inherent in many published claims, particularly about CBT or GET. They typically miss it. Sometimes this is due to the wrong person being given the story, such as a restaurant reviewer, or maybe the wrong editor, but its not easy for journalists to write in medical science areas. Most are not qualified. Fortunately we had David Tuller become interested, and there are a handful of others, but largely the media have failed us.
Advocacy has also been inadequate. It has been said that we lack critical mass. Until about seven years ago there were on the order of 2000 advocates globally, trying to advocate for seventeen to thirty million patients. Most of us are sick to very sick. Its hard to do much when bound to your house or bed, and with cognitive impediments. Things are changing now, as more patients are taking to advocacy, even if its just simple things like signing a petition. This is going to improve.
There is no central conspiracy behind this according to current evidence. That does not mean some of the conspiracy ideas are unfounded, just that they have been over-emphasized or exaggerated. Its not a single factor driving this, but a confluence of events. I do keep in mind however that it takes just two people to create a conspiracy.
What have I missed? That is probably a long list too. This is a deep social and cultural problem, and a failure in science, politics, economics, ethics and morality. Its not simple. Yet it all boils down to not enough people doing enough. At some point we will look back and see that things changed a few years back. That turning point might be now, or even the last year or two. I hope so.