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# It’s Groundhog Day! What Can the History of Science Say About the Crisis in Alzheimer’s Disease Research?

#### Abstract

For years now, Alzheimer’s disease (AD) research has been stuck in a Groundhog-Day scenario: an endless time loop with no breakthrough in sight. Disagreement about the validity of the field’s dominant approach, based on the Amyloid Cascade Hypothesis, has led to a seemingly unresolvable trench war between proponents and critics. Our paper evaluates the recent scientific literature on AD from a historical and philosophical perspective. We show that AD research is a classic example of the boundary work at play in a field in crisis: both parties deploy historical and philosophical references to illustrate what counts as good and bad science, as proper scientific method and appropriate scientific conduct. We also show that boundary work has proved unable to point a way out of the deadlock and argue that the science system’s tools for establishing scientific quality, such as peer review and the grant system, are unlikely to resolve the crisis. Rather, they consolidate the dominant model’s position even more. In conclusion, we suggest that some kind of reverse boundary-work is needed that reopens the discussion on the nature of AD, an issue that has never been settled scientifically. Drawing on historical and philosophical work, we make clear that the definition of AD as a biomedical disease for which a cure can be found has consequences, not only for funding opportunities, but also for patients and their lives. A reconsideration of the desirability of these consequences may lead to different choices with respect to research priorities and patient care.

## INTRODUCTION

What do Galileo Galilei, Niels Bohr, and Karl Popper have to do with Alzheimer’s disease (AD) research? And why do colorful historical references, such as this one, interlace the AD literature every so often:

Using that reasoning of Copernicus’s time and a bit later that of the Salem witch hunts, once the ‘heretic’ or ‘witch’ of amyloid-β (Aβ, the putative cause of AD) is removed or deposition prevented, the ‘plague’ of AD would be eliminated, and in addition, who knows, the crops might even be saved [1].

When we, two historians of science, first came across such phrases when conducting a literature review on the recent history of AD research, we were immediately fascinated. What were canonical figures and metaphors from our area of research doing in otherwise highly technical papers predominantly concerned with peptides, plaques, and neurofibrillary tangles?

In this article, we answer this question and diagnose AD research as a classic example of a phenomenon that historians and philosophers have studied for decades: the boundary-work at play in a field embroiled in a scientific crisis. That AD research is in a crisis will not surprise anyone familiar with the literature: many papers in the field today question the scientific quality and even moral integrity of this literature. It is in this context that references to iconic historical figures and debates pop up most frequently. We will show that AD researchers deploy them to illustrate what counts as good and bad science, as proper scientific method, and as appropriate scientific conduct. This is what boundary-work fundamentally is about.

Through a historical survey of our own, we will argue that this rhetorical use of the history and philosophy of science by and large misses the point. Since the early 2000s, the AD field has been stuck in what we call a Groundhog-Day scenario: an endless time loop with no apparent breakthrough in sight. Boundary-work has proved unable to point a way out of the crisis; it rather seems to imprison the field even more in its repetitive cycle.

Our historical work also shows that the deadlock is unlikely to be broken by the science system’s standard tools for establishing scientific quality. In the AD field, peer review and the grant system have worked to consolidate the position of the dominant biomedical model to the extent that it has become extremely difficult to change course.

We suggest that attempts to escape the loop may benefit from some kind of reverse-boundary work that reopens the discussion on the nature of AD, an issue that has never been settled on scientific grounds. Drawing on the work of historians and philosophers of medicine and science, we make clear that the definition of AD as a biomedical disease for which a cure can be found has consequences, not only for funding opportunities, but also for patients and their lives. A reconsideration of the desirability of these consequences may lead to different choices with respect to research priorities and patient care. In conclusion we urge for a collective effort in the AD field—including researchers, funders, clinicians, and patient-representatives—to take a step back and reflect on alternative ways of movingforward.