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News Gram™ May 2004

May 2004 ~ Vol. 10, No. 10

That science may not be the pristine enterprise many people imagine it to be comes as no surprise to most philosophers, sociologists and scientists who have studied how science operates. The fact is that there are all sorts of influences on the acceptance of and support for various scientific theories that have nothing to do with science.

Even mathematics is not immune to such forces. Isaac Newton, who invented the calculus (at around the same time as Gottfried Wilhelm Leibniz) delighted the English aristocracy with his theory of infinitesimal intervals and that delight contributed to the acceptance of the new mathematics of the 17th century.

In medicine, where egos, dollars, awards and academic status all seem to hinge on the results of laboratory work, it becomes all to clear that the war on disease sometimes takes a back seat to benighted considerations. Take Jie Shen, a researcher at Harvard who is working on Alzheimer's disease. Sharon Begley, a reporter for the Wall Street Journal, recently recounted Dr. Shen's troubling story.

According to Ms. Begley's account, Dr. Shen has been challenging the reigning model of the disease known as the amyloid theory. The theory states that the disease process involves the formation of plaques made out of beta-amyloid that interfere with nerve transmission and destroy the nerve cells themselves. Over a period of time, these lesions cause a broad array of difficulties that render a person helpless - according to the theory - but not according to Dr. Shen. She asserts that the brain needs amyloid in order to function normally. Rather than viewing the protein as a culprit in the disease process, she sees it as a substance necessary for thinking and carrying out various mental functions.

One would think that science is well equipped to handle such a difference of opinion. All one has to do is to present both points of view to other people in the field, run some additional experiments and studies, then wait for the results to roll in. It is this way of doing things that makes science strike us as rational.

Well, here's a wakeup call. That's not the way it's done - not by a long shot. Just ask Jie Shen. When she submitted her group's findings to two different journals, she went from a sprint around the track to molasses on her heals. The reviewers were merciless in requesting more detail and more theoretical explanation, the kind of thing one rarely encounters, if ever, in this sort of article. Dr. Shen submitted her paper in 2002 and it was only a month ago that it appeared in print. As a result, the public deliberation of this opposing theory was delayed for years.

Were we to debate the pros and cons of the amyloid theory we would run out of space and readers before we even got started. There is one fact, though, that might be interesting in this dispute, namely, that amyloid plaques and neurofibrillary tangles, the two pathognomonic lesions of Alzheimer's disease are present in most normal people as they age. Many patients appear to have a great deal of neuron loss, presumably as a result of amyloid buildup, yet show very few, if any, signs of cognitive decline.

The deeper message in this unhappy story is that science is not an orderly, rational, continually progressive process toward the truth. It is more akin to a series of human conflicts about whose ideas are best, whose ego strength is most durable, whose strategies are most effective. We tend to expect duplicity, narrow-mindedness, selfishness and all the other vices we usually attribute to people outside the ken of science. Yet, we find them all among the most august researchers. Universities that pride themselves on their open-mindedness, their cultivation of new ideas and, above all, their fairness, turn out to be no kinder or gentler than those mega-corporations whose executives may be spending their retirements in prison.

None of this is to say that science doesn't pursue the truth. It certainly does - with a vengeance. But it is not immune from human self-interest or institutional bias. Sharon Begley's article and a second piece a week later on the same subject are eye openers for those who, like most people, confuse narrow expertise with moral rectitude.

Of course, without the powerful incentive of self-interest - or just plain selfishness - we might not find as many people engaged in such difficult, frustrating and time-consuming research. The possibility of a Nobel Prize, an endowed chair or a multi-million dollar grant can incline one to ignore the issue of right or wrong. But it can also drive a person to spend the night poring over lab results, reviewing past studies or trying to isolate a protein just one more time. Science works not only because it is rational but also because it is human.

Do you want to know my own guess? I think the amyloid theory is wrong. The reason is that most theories and hypotheses are wrong. Most of the time, science moves ahead by proving that the path it was on was going in the wrong direction. The philosopher Karl Popper made this idea the cornerstone of his entire conception of science. In this respect, I'm on Popper's side. We learn from our mistakes. That's a maxim that's all too true in scientific research. In this wager, I side with the new guys, the ones who can't get into the big-time journals and prestigious meetings. In the end, they will be on top, maybe even posthumously. And we will be the beneficiaries of their stubborn insistence that those in power were wrong-headed, human and fallible.

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