Читать книгу The Forgetting: Understanding Alzheimer’s: A Biography of a Disease - David Shenk - Страница 12

Taos

“Ten years to a cure,” a Japanese scientist whispered to me in our hotel lobby as we waited for the shuttle bus to the Taos Civic Plaza.

The whisper was as telling as the words. He couldn’t contain his optimism, and yet he also couldn’t afford to put it on display.

Other Alzheimer’s researchers had lately been adopting a similar posture. As scientists, they were reserved by nature. But the recent acceleration of discovery had made them a little giddy. Hundreds of important discoveries had come in recent years, and funding for research was way up. The study of Alzheimer’s was now in the top scientific tier, alongside heart disease, cancer, and stroke research. This seemed fitting, since the disease was emerging as one of the largest causes of death in the U.S., not far behind those other three.

There was now even an Alzheimer’s drug on the market. Aricept, introduced in 1997, which boosted the brain’s supply of the neurotransmitter acetylcholine. Some of the functional loss in early Alzheimer’s involves a deficiency of acetylcholine; replenishing it with this drug seemed to help about half of early and middle-stage patients to slow or even arrest the progression of symptoms for a year or more.

On the one hand, this was a giant advance: a real treatment that often made a tangible difference. But it was also a frustrating baby-step: Aricept did not slow the advance of the actual disease by a single day. It only worked on the symptoms. Scientists couldn’t stop Alzheimer’s yet—only put a thick curtain in front of it for a while.

More ambitious advances were brewing. An electronic update service named Alzheimer’s Weekly had been launched in 1998. Neurologists in the 1960s would have considered this phrase a sarcastic reference to the drudging nature of discovery: Understanding of the disease was practically frozen for more than half a century. But after a thaw in the 1970s and a renewed effort in the ’80s, genetic and molecular discoveries started to cascade so quickly by the mid-1990s that the excavation of Alzheimer’s seemed to be moving at the same clip as sporting events and financial markets.

Now a weekly update was not only useful but essential. In fact, updates on other Web sites came almost daily:

News from the Research Front

3 September 1998. H. J. Song et al. report that they are able to manipulate growth cones …

5 September 1998. Puny polymer pellets show promise as a vehicle for delivering nerve-growth factor to the basal forebrain …

6 September 1998. A novel brain-imaging agent promises to open up a window on the functioning of the brain’s dopamine system …

10 September 1998. Findings published in Nature Neuroscience indicate that the accumulation of calcium in the mitochondria triggers neuronal death …

10 September 1998. C. Y. Wang et al. report they have identified four genes that are targets of NF-kB activity …

11 September 1998. E. Nedivi et al. describe CPG15, a molecule that enhances dendritic arbor growth in projection neurons …

—from the Alzheimer Research Forum (at www.alzforum.org)

The research was so intensely specialized that few individual scientists appeared to even be working on the problem of Alzheimer’s disease per se. It was more like each was unearthing a single two-inch tile in a giant mosaic. By themselves, these individual experiments were so narrowly focused that they were far removed from a comprehensive understanding of the disease. But the minutiae had a purpose. If the great challenge of Alois Alzheimer had been to distinguish a general pathology of dementia from the normal cells of the brain, the task of contemporary scientists—employing exotic techniques with names like fluorescent protein tagging, immuno-lesioning, and western blot analysis—was to try to see what the process looked like in flux. Alzheimer glimpsed a mono-colored, silver-stained microscopic snapshot. Contemporary scientists, crunching and exchanging data with parallel processors and fiber optics, were trying to patch together more of a motion picture. Once they understood the actual disease process, particularly the early molecular events, they hoped they would be able to proceed toward genuine therapies.

The research had expanded in every direction, and had also gone global. Thousands of scientists from every continent now worked on the problem, as time became critical. In a little over a decade, the much-anticipated “senior boom” would begin, eventually quadrupling the number of Alzheimer’s cases and making it the fastest-growing disease in developed countries. In addition to the sheer misery, the social costs of such a slow, progressive disease would be staggering. In the U.S., the costs of doctor’s visits, lab tests, medicine, nursing, day care, and home care was already estimated to be $114.4 billion annually. That was more than the combined budgets for the U.S. Departments of Commerce, Education, Energy, Justice, Labor, and Interior.

“We have to solve this problem, or it’s going to overwhelm us,” Zaven Khachaturian said. “The numbers are going to double every twenty years. Not only that: The duration of illness is going to get much longer. That’s the really devastating part. The folks who have the disease now are mostly people who came through the Depression. Some had college education, but most did not. The ones who are going to develop Alzheimer’s in the next century will be baby boomers who are primarily much better educated and better fed. The duration of their disability is going to be much longer than the current crop. That’s going to be a major factor.

“See, in considering the social impact of the disease, it’s not so much the pain and suffering that matters. From the point of view of the individual, that is of course the important factor. But from the point of view of society, what’s important is how long I am disabled and how much of a burden I am to society. With cancer and heart disease, the period where I cannot function independently is fairly short—three to five years. With Alzheimer’s, it’s going to be extremely long—like twenty years, where you are physically there, you don’t have any pain, you appear normal, and yet you have Alzheimer’s. You cannot function independently.”

If Khachaturian was correct, and the average duration of the disease was set to more than double, then the problem would be even worse than epidemiologists were predicting. Either way, it was clear that if Alzheimer’s disease was not conquered reasonably soon, it would become one of the most prominent features of our future. Nationally, the number of nursing home beds would at least quadruple. (The stay of Alzheimer’s sufferers in a nursing home is, on average, twice as long as that of other patients.) We would need vastly more home health care workers, elder-care nurses and physicians, assisted living facilities, day-care programs and support groups. (There was already a grave shortage of qualified professional caregivers—and, due to the low pay, a shocking annual turnover rate of 94 percent.) Family leave would also have to be redefined. Progressive nations would likely adopt a system of employee flexibility for senior care (extended leave, flexible work hours, and so on) similar to the one recently implemented for new parents in the U.S.—with the added caveat that revene parenthood lasts significantly longer and is more draining than conventional parenthood.

All this would cost money, and would require a painful shift in resources away from other public needs. Public officials would be forced into difficult decisions. Would the U.S. government, for example, continue to allow an Alzheimer’s patient to give away all assets to his children in order to qualify for government-sponsored care? Would governments require citizens to have some sort of dementia or frailty insurance?

And what about public safety issues? With as many as fifteen million people suffering from insidious (and largely invisible) cognitive decline, how would we insure street and highway safety without automatically invalidating all driver’s licenses of senior citizens?

There was a dual race on, then. Researchers were racing against one another, and against time. The prize for the winner of this race—if there was to be a winner—would be worldwide fame, nearly unparalleled professional esteem, enormous wealth, and the pride of knowing that you were personally responsible for preventing an ocean of future human suffering.

One glimpse into the magnitude of an Alzheimer’s cure: In the nearly fifty years since Jonas Salk and Albert Sabin introduced their vaccines against polio, somewhere between 1 and 2 million lives have been saved. Curing Alzheimer’s disease sometime in the first decade of the twenty-first century would save as many as 100 million lives worldwide in the same length of time.

The far-flung researchers kept in touch by E-mail, phone, and fax, and accomplished much in their labs spread out all over the world. Still, every so often, they needed to come together physically, to be in the same room to check their progress, to goad each other, critique and criticize each other, to energize.

In 1999, the gathering place was Taos. They came from everywhere, a global convergence of neuromolecular intelligentsia sitting on fold-out chairs in Bataan Hall to share knowledge and probe their ignorance. There was still so much they didn’t know: Why are women more susceptible to Alzheimer’s than men? Why are Cree and Cherokee Indians less susceptible than the rest of us? What is it about the environment in Hawaii, as contrasted with Japan, that apparently doubles one’s chances of getting Alzheimer’s? Why do a third of Alzheimer’s victims develop Parkinson’s disease but not the other two-thirds? Why do some cigarette smokers seem to be less likely to develop Alzheimer’s than nonsmokers?

After ninety-plus years, the field was littered with half-answers to these questions—and far more basic ones: Does Alzheimer’s have one cause or many? Is it really one disease or a collection of very similar diseases? Which come first—plaques or tangles? Why do they always originate in the same part of the brain? How long do they proliferate before they begin to affect brain performance? Why do some people accrue a brain full of plaques and tangles but never display any symptoms of the disease? Is anyone naturally immune to Alzheimer’s?

So, humbly, they gathered. With respect for the vexing nature of this disease, the molecular biologists and geneticists spent thirty hours listening to theories of plaque and tangle formation, and intervention strategies. After each short talk, they quickly lined up behind a microphone in the aisle to poke the presenter with questions, looking for holes in the research and analysis. The tone was alternately respectful and suspicious, and occasionally hostile.

Hostile because of the billions of dollars at stake, and also because of a fracturing debate within the community about which aspect of research mattered most. A nearly one-hundred-year-old question still had not been answered: Which are closer to the root of the problem—the plaques or the tangles?

Alois Alzheimer thought it was the tangles. “We have to conelude,” he wrote in 1911, “that the plaques are not the cause of senile dementia but only an accompanying feature.”

Most, however, now said the plaques. In a field where there were so many open questions and possible approaches, the vast majority of researchers in this room and elsewhere were focused tightly on the issue of plaque formation, while relatively few were concerned with tangles and only a handful of others busied themselves with important issues like inflammation, viruses, and possible environmental factors.

The disparity bothered many. “When I was a little girl, I wanted to go into science because I thought it was a very open community,” Ruth Itzhaki, a biologist from the University of Manchester, told me one morning in Taos. “I learned better. It is, in fact, a very cynical community layered with politics and filled with people who just want to follow the herd.” Itzhaki was herself embittered by her struggle to fund research linking the herpes simplex virus 1 (HSV1) with Alzheimer’s.

Could Alzheimer’s be herpes of the brain? It was not the most prominent theory of the day, but no one could rule it out. Nearly all humans are infected by HSV1 by the time they reach middle age. The virus mostly seems to lie dormant but can become active and create cold sores and other hazards in times of stress. Whether or not HSV1 does any damage depends largely on individual levels of immune response and on genetic makeup.

In her presentation, Itzhaki said she had found evidence of HSV1 presence in the temporal and frontal cortex of the brain, as well as in the hippocampus—three areas closely associated with Alzheimer’s. She posited that the virus might be interacting with a particular gene to set the disease process in motion. If proven true, a massive new global infant immunization project would be in order.

But the crowd in Taos did not seem very interested. Her talk drew little in the way of response. The focus quickly shifted back to plaques.

One evening I got a telephone call from a friend. He was telling me what a tough day he’d had on the job; he’d made several mistakes. “If you have Alzheimer’s, I must have a double dose of it,” he said.

I could feel myself entering a state of rage. “Do you forget simple words, or substitute inappropriate words, making your sentences incomprehensible? Do you cook a meal and not only forget you cooked it, but forget to eat it? Do you put your frying pan in the freezer, or your wallet in the sugar howl, only to find them later and wonder what in the world is happening to you? Do you become lost on your own street? Do you mow your lawn three or four times a day? When you balance your checkbook, do you completely forget what the numbers are and what needs to be done with them? Do you become confused or fearful ten times a day, for no reason? And most of all, do you become irate when someone makes a dumb statement like you just made?”