Firstly why is it that so few biomedical research applications have been successful? If it's true that (as Steve Brine said) the proposals received have not been good enough, then why on Earth is the MRC not doing more to promote better applications?
I do appreciate people's frustration but I think it is important to realise that the situation is not as puzzling as it might seem.
In simple terms there are three sorts of grant application. The first is like PACE and is easy to fund. It says that we have developed a treatment that in preliminary studies looks as if it might work and we want to do a large definitive study. It is true that PACE had serious design flaws but that might not have been obvious from the original application, which included objective outcome measures. There is also an odd anomaly that drug studies do not get funded by MRC because industry is expected to invest in them. Studies of procedures like CBT or bone marrow transplantation do get funded because nobody else will. To reject the PACE application you would need to argue that the theory behind it must be wrong. But that is not a scientific approach. The scientific approach is to say, well let's test it and see.
The second sort of application is what PWME want - an application to investigate a theory of whatever the mysterious cause of ME is. So the application might say we have suddenly had this brilliant idea of how we can discover that and we want 10M pounds. The reasonable reaction to this from the MRC, and almost all funding bodies is to ask for some preliminary evidence that this is likely to get anywhere. Alternatively they may set up ring-fenced seed funds for small initial projects. They did that in 2012 and presumably none of those projects has led to anything that looks worth further investment. I did not see anything very exciting at the 2014 Bristol meeting.
The third sort of grant says that we all realise that nobody has a strong enough lead to pursue so let's set up a massive fishing trip to see if we can trawl up some clues. That was the basis of MEGA. MEGA was not well thought out but something much more solid is being thought through just now. One can ask why this sort of approach was not set up ten years ago. I think that is a good question but genomics and metabolomics were not as streamlined in those days. In fishing terms the nets were not big enough to be expected to do the job.
I think people may not appreciate that an organisation like MRC cannot magically increase the rate of good applications of type 2. It is a bit like putting out a call saying 'We invite applications for solving of Fermat's Last Theorem. Applicants must demonstrate that they have identified the method for solving the theorem.' This is of course absurd because if you have identified the method you have solved it.
Biomedical research into causes of disease is like that. Someone has to suddenly have a brilliant idea. It is worth remembering that despite vast amounts of money being poured into research in the last twenty years the output of breakthroughs in understanding how disease work has dropped like a stone compared to the 1980s and 1990s. Even the development of novel treatments has petered out for most conditions.
I realise that people may think that there are lot of brilliant leads being developed in the USA on NK cells, viruses, cytokine profiles, metabolic traps, and so on. But the sad reality is that the original data are not very convincing and replication studies have tended to show nothing. Moreover, it is doubtful that the theories that have been put up make much more sense than the psychological ones. Moreover, replication needs to be done by people who are genuinely expert in the technologies involved. Neuroimaging studies need to be replicated by people who understand neuroimaging in great detail. The CureME team in London had an NIH grant to replicate NK findings because they were experts in NK cell biology. Nothing was found.
I don't want to seem pessimistic. I am actually very optimistic that finally the science community is taking ME seriously. The MRC know full well that people think they have let them down. We do not need a Parliamentary Committee to tell Fiona Watt what she knows all about. She has sat round a dinner table with Steven Holgate, Dan Peterson, Maureen Hanson, Don Staines, Charles Shepherd, Luis Nacul and everyone else and listened to the story.
But I think it is worth realising that the situation has been bad not so much because of political interference, although there has been that, but just because human beings are not always quite as bright as we take them to be. Money does not buy bright ideas. In the golden age of biomedical science (1970-1990) ME was too difficult a problem to tackle - nobody could find anything. Now is the time to try, but before you can make sensible use of money you need intelligent dialogue between clinicians and scientists of the highest calibre about where the likely answer lies. I see that happening now but it is going on in quite corners.
