’Collective reflection needed for way out of crisis Alzheimer’s research’

Illustration: Niels KerstesIllustration: Niels Kerstes

A vast amount of money is involved in Alzheimer’s disease research. However, scientists have been unable to achieve substantial clinical results in recent decades. In a recent analysis of the situation, Utrecht University historian of science Bert Theunissen and his colleague from Erasmus University Rotterdam Noortje Jacobs now argue that a deadlock has developed that makes progression unlikely. Their publication will appear in the Journal of Alzheimer’s Disease on 6 December.

Total standstill

It all started when Theunissen received a visit from a colleague. This pharmaceutical scientist was losing hope in the future of Alzheimer’s research. The field was at a total standstill, and the scientist found it unbelievable that there had been hardly any breakthroughs in the past 30 years. She wondered if Theunissen could take a look at the situation from a history of science perspective. Together with medical historian Jacobs, he decided to delve into the history of the research field and put their combined knowledge to work.

Groundhog Day

In their analysis, the two soon encountered a peculiar dynamic: Alzheimer’s research appears to take place within several camps that are on bad terms with each other. The camps’ opinions about the cause of the disease differ fundamentally. Indeed, there remains debate about what kind of disease Alzheimer’s actually is, and about possible treatments. "The camps repeatedly make harsh accusations against each other, such as doing bad science and monopolizing funds", says Theunissen. "Meanwhile, research stagnates in a sheer repetition of arguments." Jacobs and Theunissen describe the state of the research field as ’Groundhog Day’, after the movie in which the main character experiences the same day over and over again.

Mafia

The camp that has raised the most funds for the past 30 years takes a biomedical approach to Alzheimer’s disease. The group adheres to the 1992 Amyloid Cascade Hypothesis that Alzheimer’s is caused by accumulation of the protein amyloid-beta in the brain. Theunissen: "Clinical and genetic data seem to support the hypothesis. And the hypothesis also suggests a treatment: target the accumulation of amyloid-beta. Trials with various pharmaceuticals show that it works, but treated patients scarcely improve." According to Jacobs and Theunissen, opponents consider this a clear case of falsification of the research hypothesis, but proponents insist they are on the right track. "And this is how it has been going for years, while the Amyloid Cascade Hypothesis continues to dominate research, like a ’mafia’, some opponents say", Theunissen adds. "In any case, it is clear that science’s self-correcting procedures - for example through peer review - do not seem to be working in this case."

Today, one can draw the comparison to an ocean liner that has difficulty changing direction. According to critics, Alzheimer’s research is ’too big to fail’

Lobby

How can this be explained? According to Jacobs and Theunissen, historical research shows that political considerations played a role. Until the 1950s, many physicians viewed Alzheimer’s as an untreatable phenomenon of old age. To make research a viable venture, biomedical researchers, according to Jacobs and Theunissen, had to convince funders that it was a disease, with one clear cause. "They presented politicians with the prospective of a future disaster of an aging, Alzheimer’s’infested population, resulting in unmanageable healthcare costs", Theunissen explains. "The government therefore had to invest money in research into its cause and cure." Their lobbying effort was successful: Alzheimer’s research received billions in government funding, and the pharmaceutical industry also bet high on finding a cure, they conclude. "Today, one can draw the comparison to an ocean liner that has difficulty changing direction. According to critics, Alzheimer’s research is ’too big to fail’."

Step back

The historians do not offer a solution to the problem in which Alzheimer’s research finds itself. "It is a very complex issue that has been going on for 30 years, and we have only mapped the situation", Jacobs says. They do, however, offer advice to all involved. "There is still debate about what kind of a disease Alzheimer’s really is, and that makes one think about the allocation of funds between prevention, patient care, and research into the cause. So, step back and look at alternative ways forward. Stop harping on one’s own rightness and thinking in camps. Start listening to the perspective of others and try to find opportunities to work together." After all, that’s also how weatherman Phil from the movie Groundhog Day managed to break out of his own repetitive cycle.