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.

Book Review: David and Goliath by Malcolm Gladwell

In my blog post of May 12, Are Scientists More Objective and Rational than the Rest of Us?, I related the stories of some scientists who somehow were able to “think outside the box,” to use the annoyingly well-worn cliché. They broke through the conventional wisdom, academic politics, and scientist groupthink and made radical changes to accepted scientific concepts and explanations for various phenomenon. 

I discussed Clare Patterson, who successfully took on a respected scientist who had became an oil industry lackey and who had pushed the idea that lead in gasoline was not dangerously polluting the environment. 

Then there was Elizabeth Gould, who took on neuroscience guru Pasko Rakic, who had set the field of neurobiology back a full decade by refusing to believe a lot of data coming out that disproved the prevailing notion that sophisticated animals are born with essentially every brain cell they would ever have, and that no new neurons develop during adulthood.

Another good example was German meteorologist Alfred Wegener, who first proposed – way back in 1915 - that South America and Africa had one time been joined. He was almost laughed out of academia. He even had fossil evidence for his proposition, but the geologists of his day not only mocked him but counter-proposed that there are (now sunken) land bridges to account for the fossils - without any evidence that this was in fact the case. Now all geologists accept the theory of plate tectonics.

So what makes some people able to do this? This is actually two questions, not one: First, why can some people think in novel ways while others seem stuck with the groupthink no matter how preposterous it starts to become? Second, why do some of these people succeed in creating – again pardon the second annoyingly well worn cliché – a paradigm shift in the scientific community, while others fail?

I was discussing these questions with a friend, and in response he gave me an interesting book called David and Goliath, Underdogs, Misfits, and the Art of Battling Giants by New Yorker journalist Malcolm Gladwell.

Malcolm Gladwell

It’s mostly about the individual and group factors that lead some people to think apart from prevailing wisdom, rather than about which of these people succeed in making a mark and which do not, but I thought it was a very interesting read.

Now of course Mr. Gladwell is a journalist and not a neuroscientist or psychologist, and his work has garnered a lot of public criticism from professionals in those fields, particularly Steven Pinker and Chris Chabris. Gladwell is above all a storyteller, but he goes on to make some interesting hypotheses about the psychology – and to a lesser extent the sociology – of the people at the center of his stories. He then speculates further about what these hypotheses could mean more generally.

Chabris accused him of “telling just-so stories and cherry-picking science to back them up,” and “presenting as proven laws what are just intriguing possibilities and musings about human behaviour.”

Fair enough, although I'm not sure I would agree that Gladwell is saying his ideas are proven. On the other hand, the belief of some psychologists in the sanctity of statistics and so-called empirical studies in the social sciences is also grossly overestimated. There are some inherent limitations in our current ability to explain and predict things, particularly in psychology. In the words of the neurobiologist Steve Rose, "It is in the nature of living things to be radically indeterminate."

I discussed the issue of “anecdotal” evidence versus inductive conclusions in a prior post. But an even bigger problem is the obvious difficulty in precisely mapping out the interactions between genes and environment, when there are literally thousands of environmental variables and a trillion constantly changing synaptic connections between brain cells, all of which interact at constantly changing frequencies over decades. No one can even come close to controlling for all of these variables in a lab experiment. This is the definition of chaos.

Sometimes the best way to eventually understand a psychological question of this sort – and one can only talk about increased or decreased probabilities of certain results given certain pre-conditions, never about anything approaching absolute certainty – is by looking at all the details in the stories of a variety of individuals. With all of the variables at work, only individual stories can provide some of these necessary details. With psychology, details matter. 

And sometimes it is the exceptions to the conventional wisdom that prove or disprove a perceived “rule.”

So with this in mind, reading Gladwell’s stories does bring up some intriguing possibilities. His major premise is that the experience of certain types of adversities can make someone stronger and far more resolute than he or she might be otherwise. Gladwell brings up, for example, the strength of the population of London during the rocket and bombing attacks by the Germans in World War II. The fact that so many people experienced what he calls a “near miss” – surviving a bombing in which your neighbors did not - can strengthen people's resolve to carry on.

He also discusses how some people with dyslexia had to ingeniously develop alternate ways of accomplishing certain tasks in order to overcome their limitations, which later helped them to be wildly successful. Again, I do not think the author is arguing that dyslexia is a good thing, or that for most people it does not impair or even destroy their attempts at success. So other variables are obviously involved.  

But that doesn’t necessarily negate the premise that sometimes weaknesses can be turned into strengths – as David did in the story of David and Goliath. Goliath was only prepared to fight someone who fought just like him, which left him vulnerable to a projectile from a slingshot.

Then there was the story of Emil “Jay” Freireich, a doctor who was a major player in the vast improvement in the treatment of childhood leukemia. The good doctor lost his father when he was quite young to a probable suicide after the stock market crash of 1929. The family was left destitute, and the mother was frequently absent in order to work, leaving him to fend for himself.

To oversimplify just a bit, Freireich realized that children were dying because individual drugs, which were causing horrific side effects, did not work fast enough. The leukemia killed the children before the drugs really had time to work. The drugs were just not killing enough cancer cells quickly enough. He knew that this meant that the children needed more aggressive treatment, and that drug “cocktails” were probably called for. But this meant that the children would suffer even more horrible side effects as the cocktails were given to them, and the medical establishment recoiled in horror at such a thought.

But Freireich had learned to persist in the face of adversity, and would not be deterred. Of course, the places in which he worked could have easily fired him for his activities, so a lot of luck was also involved. He had to be surrounded by at least some people who recognized the possibility that he might just be right. Fortunately, that was the case. Today’s cure rate for the type of cancer he fought stands at about 90%.

As Gladwell points out, “Does this mean that Freireich should be glad he had the kind of childhood he had? The answer is plainly no. What he went through as a child was something no child should have to endure…the right question is whether we as a society need people who have emerged from some kind of trauma – and the answer is that we plainly do.”

As an aside, Gladwell also brings up sort of in passing something that I wanted to mention because it puts an additional, very interesting new spin on the problem of some African Americans internalizing the racist, negative attitudes of Whites toward Blacks, so that they end up treating each other just like Whites used to treat them. I discussed this in my post of 8/14/2010 called The N-word. 

In some cases, apparently African slaves actually pretended to act out White stereotypes - in order to passive-aggressively harm their slaveholders! Gladwell quotes historian Lawrence Lavine about the phenomenon of the "trickster hero": 

"...a significant number of slaves lied, cheated, stole, feigned illness, loafed, pretended to misunderstand the orders they were given, put rocks in the bottom of their cotton baskets in order to meet their quota, broke their tools, burned their master's property, mutilated themselves in order to escape work, took indifferent care of the crops they were cultivating, and mistreated the livestock placed in their care to the extent that masters often felt it necessary to use the less efficient mules rather than horses since the former could better withstand the brutal treatment of the slaves."

So, when African Americans makes themselves look like a parody of a White stereotype, are they doing this on purpose to be a trickster, or subconsciously out of fears - originally concerning retribution - passed down unknowingly from one generation to the next? Actually, any given case could be either one - or even both. That the behavior can be this ambiguous shows the power of what I call the actor's paradox.

Are Scientists More Objective and Rational than the Rest of Us?

No.  Not particularly.

 

In watching the new version of Carl Sagan’s Cosmos on TV, it was interesting to hear host and astrophysicist Neil deGrasse Tyson wax eloquently how science is based almost entirely on empirical evidence – seemingly unbiased observation and clear experiments – as opposed to the ideas of the majority of the people who are under the sway of religious dogma and mythology as well as other forms of groupthink. 

But then the show began to give hints that scientists could be every bit as biased as anyone else. There was the bit about Robert Hooke trying to take credit for some of Isaac Newton's work. And then there was the story about Robert Kehoe, a respected scientist who became an oil industry lackey who pushed the idea that lead in gasoline was not dangerously polluting the environment and was not being found in increasing concentrations everywhere. It took the stubborn persistence of another scientist, Clare Patterson, to get the truth out.

When I was a kid, I wanted to be a scientist, and I idealized scientists as having the very qualities Dr. Tyson seemed to first imply that they had. Of course, that was long before I entered academia.

I had heard about how cutthroat and vicious academic politics could be. I should have asked myself why that was. 

I didn’t think of scientists in terms of outsized egos, outsized greed, biased experimental designs that were being used to guarantee the results of an experiment before it was even done, the shunning of those with data that seemed to contradict conventional wisdom - with scientists finding ways to prevent such folks from getting their data published in “respectable” journals through the misuse of the peer review process, or by preventing them from getting funding for further research - the use of propaganda and marketing techniques to disseminate pseudo-scientific “facts,” and the powerful effects of political correctness gone amok on what scientists can and cannot say or propose to study.

 

How stupid could I have been to idealize these folks as somehow above all that? When I finally made it to academia, I got to witness all that up close and personal. But it was even worse that I thought. When I started doing research for my last book, How Dysfunctional Families Spur Mental Disorders, I was totally shocked by how far all this went. Many of the issues involved have been the subjects of previous posts on this blog.

 

I came across an article by Michael Specter in the New Yorker about how one prominent scientist, Pasko Rakic, had set the field of neurobiology back a full decade by refusing to believe a lot of data coming out that disproved the prevailing idea that sophisticated animals – and certainly humans – are born with essentially every brain cell they will ever have, and that no new neurons develop during adulthood.  

Pasko Rakic

Scientists who found this data were ignored, and some had to leave the field in frustration. It took the persistence of a willful female scientist named Elizabeth Gould to break through this scientific version of stonewalling.

Elizabeth Gould

The whole subject of scientific groupthink and misbehavior will be covered in a book I recently became involved with as a co-editor – the sequel to the book Pathological Altruism. (It probably will not be out for a couple of years).

One of the most egregious examples of political correctness stymieing science is at the heart of my understanding of self sacrifice in dysfunctional families: the work of E.O. Wilson on sociobiology and kin selection. I had once had a conversation with an evolutionary biologist who told me that only about 20% of evolutionary biologists believed in kin selection, but he strongly implied (without actually saying so) that this was due more to politics that to the science.

E.O. Wilson

As I later learned, I had guessed exactly what was going on in the field, but I had no idea it stemmed from an official published opinion piece from 1975! In reading my colleague Gregg Henrique’s book, A New Unified Theory of Psychology, I learned the following on page 166:

“…on November 13, 1975, a group of fifteen or so scholars, teachers, and students from the Boston, area (most notably among them were Wilson's Harvard colleagues, Stephen J. Gould and Richard Lewontin) formed a group called Science for the People and published a let­ter in the New York Review of Books that said that any applications of sociobiology to humans were to be condemned because they were too politically, dangerous. The letter linked examining biological bases of human behavior to Social Darwinism and Nazi Germany. Even hypotheses stemming from such ideas...

‘consistently tend to provide a genetic justification of the status quo and of existing privileges for certain groups according to class, race or sex. Historically, powerful countries or ruling groups within them have drawn support for the maintenance or extension of their power from these products of the scientific community. . .These theories provided an important basis for the enactment of sterilization laws.. .and also the eugenics policies which led to the establishment of the gas chambers in Nazi Germany.’”

Stephen J. Gould

OK. So because a scientific idea might conceivably be misused in the service of some fascist’s political agenda, we cannot talk about it?!? And one of my previous heroes, Stephen J. Gould, signed on to this? 

How ironic that ideological groupthink, which is itself a manifestation of the biological force of kin selection, is being used to intimidate those who would study kin selection.

Such objectivity. Such empiricism. Rational scientists who deal with nothing but actual evidence?  I’m sure glad that there are at least a few of them still out there.