Book Review: Madness and Memory by Stanley B. Prusiner, M.D.

I thought I'd take a short break from the main themes of this blog to focus on another subject on which I have been working (getting together an edited volume by multiple contributors): How scientists may block important, transformative ideas from gaining prominence because of group biases and prejudices. I will review the book Madness and Memory, which is an amazing first-person account of the trials and tribulations of one scientist who somehow managed to keep getting his research funded, and who continuously did very careful studies despite mass skepticism about his discoveries from other scientists as well as from the lay press.Strangely enough, the skepticism from infectious disease doctors, particularly those who specialize in viruses, continued even after the scientist, author Stanley Prusiner, was awarded the Nobel Prize in medicine for his work!In this case, I do understand the reasons for the skepticism. Dr. P. discovered an entirely new form of seemingly self-reproducing infectious agent that did not contain either DNA or RNA. These nucleic acids were reasonably thought by almost all biologists to be required for any biological agent to reproduce itself. The new agents are called prions (pree-ons), and consist entirely of proteins. They are the definite cause of some obscure neurological degenerative diseases such as Kuru, Scrapie, and Creutzfeld-Jakob disease. (In medical school I knew it as Jakob-Creutzfeld disease - the name reversal has a rather silly story which the author relates in his book. Despite the ramblings of memory "expert" Elizabeth Lofton, my memory that the name had been different when I was in medical school 45 years ago was entirely accurate). You may also have heard of another important prion-caused entity, dubbed by the press as "mad cow disease." People could get it from eating meat from infected cattle.Most importantly, prions are quite likely the cause of the more common types of neurodegenerative disorders: Parkinson's Disease, Lewy Body Demetia, and Alzheimer's.As best as I can understand prions from the descriptions in the book, they are once-normal proteins that had been encoded, as one might expect, by chromosomal DNA in various organisms, but which somehow later changed shape and became almost more of a toxin than an infectious agent. The altered proteins then somehow lead to a chain reaction in which other normal proteins of the same chemical makeup change shape as well, and therefore seem to multiply. Tissue with the prions can then be transferred to another organism and then start to destroy the nervous systems in the new beast over extended periods of time. The time before animals become symptomatic can be years. (Before it was found that prions contained no DNA or RNA, these diseases were assumed to be caused by a "slow virus"). It is this property, I surmise, that makes them "infectious."The fact that Prusiner did not get discouraged when he was being attacked by all sides is very impressive. His networking skills must have been substantial, as every time someone threw a road block in the way of his research, he was able to find someone else who could provide him with an alternative. He would literally call up the editors of the most prestigious journals like Cell and Science and discuss his research results before even submitting an article for publication. (When I was an academic, I had no idea that you could even do that! And I probably wouldn't have gotten away with it anyway). He was also able to manage to find help from academics in several seemingly unrelated disciplines who would be key in his discoveries. At least he didn't have to worry about the privacy rights of his rats and hamsters. Psychiatrists like me who work with subtle and pretext-laden human interactions have to be concerned about that.The pressures he faced were enormous. In academia, if you don't get enough publications, you don't get tenure, and if you don't get tenure, you no longer have a job. You also live in constant fear that some other scientist somewhere else will beat you to a confirming experiment and publish it before you do, or that someone else will make a discovery that will bring your ideas into question ("A few pages in a reputable journal can render another scientist's years of toil virtually worthless"). You get feedback from "peer reviewers" of your submitted work than can be absolutely vicious. Dr. P. had to suddenly find new places to house his rodents due to concerns about animal rights activists who were more concerned with rats than people. The press, always looking for a sexy story, quoted his critics to publicly attack him.I am envious of anyone like Dr. Pruisner who was so skillful at negotiating academic politics, because I was not. I unfortunately had minimal guidance from those around me. I found it impossible to get funding for researching the phenomena that I was witnessing first hand every day in my practice with my patients with personality disorders and their families, and which only one other author was even writing about. Prusiner quotes someone named Maurice Maeterlinck about this type of problem: "At every crossway on the road that leads to the future, tradition has placed, against each of us, then thousand men to guard the past."He also quotes Hilary Koprowski on the "Four stages of adopting a new idea:"1. "It's impossible, it's nonsense, don't waste my time."2. "Maybe it's possible, but it's week and uninteresting. It's clearly not  important."3. "It's true and I told you so. I always said it was a good idea.4. "I thought of it first." For anyone interested in understanding what doing science is really like, and what scientists can be up against, I recommend this book.


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