The cost of fraud

My Aunt Florence, my mother's older sister, died of Alzheimer's disease.

Her children, especially my cousin Linda, took care of her as she slowly declined during the last fifteen years of her life.  She finally died in 2008 at the age of ninety, and by that time there was little left of her but a physical shell.  She was unresponsive, the higher parts of her brain destroyed by the agonizing progression of this horrible illness.  She went from being a bright, inquisitive, vital woman, an avid reader who did crossword puzzles in ink and could beat the hell out of me in Scrabble, to being... gone.

My Aunt and Uncle in better times

During this ordeal I lived fifteen hundred miles away, so I wasn't confronted every day by the terrible reality of what Alzheimer's does, both to the people suffering it and to their families.  Even so, it was my aunt's face I kept picturing while I was reading an article in Neoscope sent to me by a friend -- all the while getting angrier and angrier.

If you've kept up at all with the research on Alzheimer's you probably are familiar with the words beta amyloid.  It's a short-chain protein, whose function is unknown, which allegedly is directly toxic to nerve cells (and can cause other proteins to misfold, suggesting an etiology similar to Creutzfeld-Jakob syndrome, better known as "mad cow disease").  A great deal of money and time has been spent investigating the role of beta amyloid in Alzheimer's, and in developing drugs that interfere with its production -- significantly, not a single one of which has been shown to slow down the progression of the disease, much less reverse it.

It turns out this is no coincidence.  There is good evidence that the often-cited papers on the topic by Sylvain Lesné -- who wrote convincingly that a specific beta amyloid species, Aß*56, was the culprit in the devastating destruction you see in Alzheimer's sufferers -- were based on faked data.

Not even well-faked, either.  The images Lesné included from "Western blot" experiments, a commonly-used separation technique used to detect specific proteins in mixtures, were cut-and-pasted, something that can be seen not only in faint cut lines in the images but in the fact that the bands in the photographs have clearly been duplicated and moved (i.e., if you look at the edges of the bands, several of them have identically-shaped edges -- something that would be next to impossible in an actual Western blot).

It's a devastating finding.  About how the hell fraud like this got past peer review, biochemist Derek Lowe writes in Science:

The Lesné stuff should have been caught at the publication stage, but you can say that about every faked paper and every jiggered Western blot.  When I review a paper, I freely admit that I am generally not thinking “What if all of this is based on lies and fakery?”  It’s not the way that we tend to approach scientific manuscripts.  Rather, you ask whether the hypothesis is a sound one and if it was tested in a useful way: were the procedures used sufficient to trust the results and were these results good enough to draw conclusions that can in turn be built upon by further research?  Are there other experiments that would make things stronger?  Other explanations that the authors didn’t consider and should address?  Are there any parts where the story doesn’t hang together?  If so, how would these best be fixed?

There is a good-faith assumption behind all these questions: you are starting by accepting the results as shown.  But if someone comes in with data that have in fact been outright faked, and what’s more, faked in such a way as to answer or forestall just those sorts of reviewing tasks, there’s a good chance that these things will go through, unfortunately.

Lesné's apparently fraudulent research doesn't invalidate the whole beta amyloid hypothesis; other, independent studies support the toxic effects of beta amyloid on nerve cells, and have shown there's beta amyloid present in damaged cells.  But Lesné's contention that Aß*56 was causative of Alzheimer's was apparently a blind alley -- and the presence of the protein in the neurons of Alzheimer's sufferers could as well be a result of the disease as a cause.

What concerns me about this kind of thing, though, is the damage it does to the scientific enterprise as a whole.  Here in the United States, in the last twenty years, we've been dealing with the effects of a surge of anti-science propaganda on a number of fronts, most notably anthropogenic climate change and the efficacy of vaccines.  When highly cited, widely publicized work like Lesné's is shown to be based on fraudulent data, it gives more ammunition to the crowd who is already shrieking about how the scientists are making it all up to get grant money and are fundamentally untrustworthy.

And as my friend who sent me the link pointed out, there is a profit motive involved in science.  The publish-or-perish model of scientific research means that the competition for grant money is intense and often cutthroat.  Producing publishable results doesn't just get you funded, it is also the key to tenure-track research positions and the stability and prestige that come with them.  Don't get me wrong, I still strongly believe that 99% of scientists are rigorously ethical, and the vast majority of research is reliable; but when you set the system up to punish negative results, it gives the unscrupulous a hell of an incentive to cheat, and the naysayers yet another opportunity to tar all scientists with one brush.

But what haunts me most in this case is the human cost.  This disease destroys lives, and does it in a slow, agonizing, dehumanizing way.  The idea that falsified data may have led researchers down a fruitless rabbit hole, wasting huge amounts of time and money while people suffered and died, is horrifying.  I keep picturing my Aunt Florence's face, as she languished for years, her brain decaying while her body lived on, and wonder how the people who perpetrate such fraud can sleep at night.

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Music and dementia

My mother's elder sister died ten years ago, at the age of 90, after a long, slow, tragic decline from Alzheimer's disease.  I remember my Aunt Florence as a bright, intelligent woman, who loved to read, had a whipcrack sense of humor, and could beat just about anyone around at Scrabble.  The first symptoms were a gradual descent into what my mom called "fogginess," but it was accompanied by worry, anxiety, and paranoia.  She lost more and more of herself to this horrible disease, and during the last few years of her life she was immobile, unresponsive, with no apparent awareness of her surroundings.

My cousin, her eldest daughter, and her family cared for Aunt Florence with a diligence and selflessness that borders on heroism.  Even after she no longer knew where she was or who was in the room with her, they talked to her, made sure she was kept warm and safe, and was hugged and shown affection every single day.

To me, dementia is one of the scariest things out there.  I can't imagine anything more fundamentally terrifying than to lose one's memory and sense of self, to have a damaged mind trapped in a withering body, to be totally dependent on others for my care.  No one should have to endure that.  I'm hopeful that research in Alzheimer's will one day find a therapy or medication that slows down the progress of the disease, or perhaps cures it entirely.

In the meantime, there's been some interesting research into palliative care.  Just last week, the American Association for the Advancement of Science announced some research that will be published this month in the Journal of Prevention of Alzheimer's Disease, done at the University of Utah, that considers using music as a way to alleviate the horrible anxiety that comes along with the early and middle stages of the disease.

Researchers found that the part of the brain that mediates our emotional response to music is relatively undamaged by Alzheimer's (for reasons as yet unknown).  They investigated the possibility that even people whose memories were largely gone might remember, and be comforted by, hearing familiar music.  And their results were striking.

Jace King, lead author of the study, said the response was obvious.  "When you put headphones on dementia patients and play familiar music, they come alive.  Music is like an anchor, grounding the patient back in reality."

[Image licensed under the Creative Commons Evdokiya, EscportalW Music transparent, CC BY-SA 3.0]

The researchers placed the test subjects in an fMRI machine, and monitored brain activity while playing one of three things through headphones -- a selection from the patient's music collection, the same music played backwards, and silence.  The familiar music triggered dramatically increased activity in the cerebrum, and a spike in functional connectivity.

The previously quiet parts of the brain were once again talking to each other.

Norman Foster, senior author of the paper, was encouraged by these results.  "This is objective evidence from brain imaging that shows personally meaningful music is an alternative route for communicating with patients who have Alzheimer's disease," Foster said.  "Language and visual memory pathways are damaged early as the disease progresses, but personalized music programs can activate the brain, especially for patients who are losing contact with their environment."

It's not a cure, or even a treatment, for the disease, but anything that can alleviate the horrific anxiety that comes along with it is a blessing.  "In our society, the diagnoses of dementia are snowballing and are taxing resources to the max," study co-author Jeff Anderson said.  "No one says playing music will be a cure for Alzheimer's disease, but it might make the symptoms more manageable, decrease the cost of care and improve a patient's quality of life."

Which is tremendous in and of itself.  Considering how much music affects me emotionally -- I'm the guy who wept the first time I heard Ralph Vaughan Williams's Fantasia on a Theme by Thomas Tallis -- it's fantastic that there is a way to bring some of that emotional depth back to people who are becoming progressively disconnected from their world.

So if, heaven forfend, I ever descend into that deep, dark pit that is Alzheimer's, please give me a temporary reprieve by playing some of my favorite music.  You could start with Stravinsky's Firebird.

After that, use your imagination.  I'll be thankful, even if at that point I may not be able to say so.

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This week's featured book is a wonderful analysis of all that's wrong with media -- Jamie Whyte's Crimes Against Logic: Exposing the Bogus Arguments of Politicians, Priests, Journalists, and Other Serial Offenders.  A quick and easy read, it'll get you looking at the nightly news through a different lens!