Countering The Cabal

One of the admirable things about modern science is its inherent skepticism.  Scientists are supposed to be constantly challenging accepted ideas, developing hypotheses, and designing experiments to try to disprove the hypotheses — all in the name of gathering data, advancing our knowledge and developing new ways to analyze or address problems.  Whether it is physics, or biology, or the treatment of disease, the “scientific method” has reliably produced enormous gains in our understanding and huge advances in numerous fields.

investigacic3b3n-cientc3adfica-pac38ds-vasco-1024x683-1But what if scientists stopped behaving as skeptical scientists?  What if, instead, scientists came to believe so deeply in a particular theory that they became zealous advocates for that theory — almost as if they were adherents to a religious belief, rather dispassionate, objective scientists?

That’s the sad story that this article tells about research into Alzheimer’s disease, which affects nearly 6 million Americans and one in 10 people 65 and older.  Unlike other areas of medical research where great strides have been made — think of the rapid developments in the treatment for HIV and AIDS, for example — research into Alzheimer’s disease has not produced much progress.  Some of that may be attributable to the fact that the human brain is complicated, but many observers now are saying the absence of significant gains is attributable, at least in part, to what they call “the cabal”:  a group of influential researchers and related individuals who believed so fervently in a particular theory about Alzheimer’s that they thwarted research into other approaches to the disease.

The particular theory is that a substance called beta-amyloid accumulates in the brain, creating neuron-killing clumps that cause Alzheimer’s.  It quickly became so accepted in the Alzheimer’s world that scientists, venture capitalists, scientific journals, and research funding entities wouldn’t support or publish work on alternative theories — even if that’s what the scientific method teaches.  One observer quoted in the article linked above said:  “Things shifted from a scientific inquiry into an almost religious belief system, where people stopped being skeptical or even questioning.”  That’s a pretty chilling indictment, because it’s directly contrary to what is actually supposed to happen.

Notwithstanding the impact of the claimed “cabal,” some alternatives hypotheses that appear to be promising have been developed, and some small trials of potential treatments have occurred.  Still, it’s clear that not much progress has been made in treating dementia over the past few decades, and many people now believe that the near-universal acceptance of the beta-amyloid theory is at least partly to blame.  It’s a disturbing, cautionary tale about the bad things that can happen when scientists stop acting like scientists.

Rethinking Alzheimer’s

Alzheimer’s disease has been a known condition since it was discovered, in 1906, by a German doctor, and it has been the focus of lots of attention and research for decades.  It ranks as one of the top causes of death in the United States and is the third leading cause of death among people 60 and older, just behind heart disease and cancer.

So, after more than a hundred years, why haven’t we figured out how to treat this dread and deadly disease that robs people of their minds and personalities and leaves them empty shelves of their former selves?  Why, for example, have doctors and drug companies been able to develop effective treatments for HIV and AIDS, but not Alzheimer’s?

alzheimer_brainIt’s not that the scientific and medical community isn’t trying — but identifying the real cause of Alzheimer’s, and then devising a meaningful treatment, is proving to be an incredibly elusive challenge.  A brain with Alzheimer’s is like a car crash with no witnesses, where the accident reconstruction expert tries to find clues from the physical evidence.  Do those skid marks indicate that the driver was going too fast, or do they suggest that the driver was distracted, or was the driver paying attention when something like a deer unexpectedly came onto the road?  In the case of Alzheimer’s the brain is mangled and distorted and physically changed, both chemically and structurally.  Are those changes what caused the disease, or are they mere byproducts of the active agent that does the real harm?

For more than a quarter century, Alzheimer’s researchers and drug companies have been focusing on the “amyloid hypothesis,” which posits that an increase in amyloid deposits causes the disease, and have worked to develop drugs to target amyloid.  The hypothesis was devised because Alzheimer’s patients have an unusual buildup of amyloid in their brains, amyloid buildups have been found to be harmful in other bodily organs, and people with a genetic history of Alzheimer’s in their families also have been found to have mutations in the genes responsible for amyloid production.  With this kind of evidence, it’s not surprising that amyloid production has been the focus of treatment efforts.

Unfortunately, though, the trials of drugs that address amyloid production haven’t been successful — and after repeated failures, some scientists are wondering whether the amyloid hypothesis should be scrapped, and the disease should be examined afresh.  The amyloid hypothesis remains the prevailing view, but a minority of researchers think that the focus on amyloid buildup is like trying to close the barn door after the livestock have already escaped.  And they wonder whether the amyloid hypothesis has become entrenched with so many people, who invested so much time and money in developing amyloid-based treatments, that work on alternative approaches is being undercut.

It’s a classic test for the scientific method.  Over the years, there are countless examples of instances where prevailing views on medical, or physical, problems were overturned in favor of new approaches that turned out to accurately identify cause and effect.  The scientific method is supposed to objectively find the right answers.  For Alzheimer’s disease, maybe it is just a matter of tweaking how to develop the right treatment for the amyloid build-up — or maybe it’s something else entirely.

Those of us who have dealt with Alzheimer’s in our families hope the scientific and medical community put aside preconceived notions, dispassionately assess the evidence, and explore every avenue for developing a successful treatment.  This disease is just too devastating to go unaddressed.