(4 of 6)
The controversy over A2M continues to smolder. Roses, now worldwide director of genetics at Glaxo Wellcome, says he and his colleagues looked at that gene. "I even filed a patent on it," he says with a grin. But he's now convinced that it's not the right gene. Tanzi, however, refuses to acknowledge defeat. "There's a ton of biology that suggests it's a good candidate," he says. Among other things, A2M appears to mediate the rate at which neurons produce beta amyloid.
In his eloquent memoir about his father's struggle with Alzheimer's--Hard to Forget (Random House, $25)--writer Charles Pierce describes his dismay at the often savage sparring among scientists that he witnessed firsthand. It made him "want to throw things," he writes, "to scream at all these brilliant people that I didn't care a damn about which one of them got to be first as long as someone was." And yet, as Tanzi observes in his soon to be published account of the Alzheimer's wars--Decoding Darkness (Perseus, $26)--there is another way to look at the extreme contentiousness that has for so long characterized the field. He believes "that the hot sparks of conflict, singeing so many of our butts, were making us charge forward as fast as we could go."
If the level of competition in the Alzheimer's field seems exceptionally intense, it's because the stakes are so high. Any drug that can stem or stop or prevent this disease, it is estimated, would easily generate revenue of several billion dollars a year.
BAPTISTS VS. TAUISTS
By the mid-1990s, the debate between the Baptists (the first three letters stand for beta-amyloid protein) and the Tauists had intensified--and for a while the Tauists appeared to be gaining ground. For one thing, the normal function of beta amyloid (if it had one) remained mysterious. All that scientists knew was that it was secreted by virtually every cell in the body, that it came primarily in two lengths, and that, in the brain, the slightly longer version was more likely to aggregate into plaques.
Tau, by contrast, clearly played a critical role in the brain. In its normal form it helps support the axons--long projections that carry signals from one nerve cell to another--holding them together like ties on a railroad track. When tau goes bad and clumps into tangles, the axons shrivel up and die. The case for tau further solidified in 1998, when researchers discovered a form of dementia associated with mutations of the tau gene. People with these mutations did not develop the plaques associated with Alzheimer's disease, but at death, their brains were riddled with tangles.
Then, last year, the Amyloid People staged a surprise attack. First, researchers at Elan Pharmaceuticals of South San Francisco stunned their colleagues by reporting that they had taken mice genetically engineered to develop plaques and vaccinated them with a fragment of beta amyloid. Twelve months later, seven out of nine mice remained plaque free. Then the Elan team vaccinated year-old mice whose brains were riddled with plaques. Result: the plaques started to melt away. Elan quickly drew up plans to test the vaccine in humans.