SAG HARBOR
Fall 2014
Within two days, B. and I were interviewing more home-care prospects. I could sense B. still holding back on hiring anyone to come into our home. She tells other people she knows she needs help, but when the doors close and it’s just us again, I get, “No, no, no, I don’t want some kindergarten student getting in my way.”
How do you force your wife to accept home-care help when she doesn’t want it? I’m telling you: it’s not as easy as just hiring the person and bringing her into your home. I knew that unless B. accepted her, we’d all go through hell. With B., the best way was to coax her, bit by bit, until she came around. As awful as the last week was, I still thought we had time to ease B. into the home-care idea.
This wouldn’t be easy, not in any sense. Even on a limited basis, Colleen or whomever else we hired would cost at least $1,000 a week. So $52,000 a year—just for starters. A lot more for round-the-clock help—which was in our future, I knew. In all, maybe $100,000 a year before long. We had resources. But I could see how easily Alzheimer’s drains an average American family’s savings.
As the horror of that night began to recede, I started thinking about how to plan financially for this future, while also doing good and making a difference. Two ideas popped into my mind. I wanted to keep B.’s successful line of home products on the shelves and selling, as they had for fifteen years now. But I also wanted to introduce a new line of all-natural white goods—sheets and towels and such—that we would call B. Smith Basics. These would have no chemicals—100 percent natural. This tied in with our whole campaign of a healthier diet, and healthier living through keeping it simple. Keeping healthy was, so far, the best advice that doctors had for keeping Alzheimer’s at bay. I hadn’t decided whether those products would include messaging about Alzheimer’s, but they might. Maybe part of their proceeds would be donated to research. I wanted Bed Bath & Beyond to help us raise global awareness and money for Alzheimer’s. Maybe this could do it. I had another idea about how to do that: with a stamp.
A stamp for Alzheimer’s awareness, with B. Smith as the face on the stamp.
This wasn’t so crazy as it seemed. Not long before, a breast cancer awareness stamp had raised $80 million for breast cancer research. A surtax was added to the price of a forty-nine-cent stamp—five cents, I think it was. The forty-nine cents went to the federal government as usual; the surtax went to the good cause. The catchphrase just came to me: “If you want to make a difference, put a stamp on it.” And why not bring Bed Bath & Beyond into the picture? They had a mailing list with 37 million customers. If I could get them to use B. Smith stamps on their mailers, that could be serious money for Alzheimer’s research. I started making calls to educate myself on what all this might involve.
Already I knew one very deserving recipient: the Alzheimer’s Drug Discovery Foundation (ADDF), founded and run by our new doctor, Howard Fillit.
Howard was the one I wanted to see now. He was the key. I wanted all his advice on dealing with B., from ID bracelets to home care. But I wanted to talk to him, too, in his other capacity, as a leader in the fight against Alzheimer’s. I wanted to know what was happening on the front lines of drug research—and I wanted to raise buckets of money with B. Smith Alzheimer’s stamps to help him find the right drugs that much sooner.
Howard’s ADDF offices are on West Fifty-Seventh Street. He has a staff but really, the ADDF is Howard. He’s the one who was persuaded by Ronald and Leonard Lauder, sons of Estée, to start a major philanthropic effort back in the late l990s to accelerate the discovery of new drugs for Alzheimer’s.
Up until that point, as Howard explained, scientists were scattered around the country studying the genes that might or might not cause the disease. We had doctors holding clinical trials for drugs that might or might not make a difference. We had big drug companies paying for some of those studies, and the federal government paying for others. And still we had no drug that actually treated or cured the disease—partly because more research was needed, and more money to fund it, partly because all those efforts were separate and apart from one another: silos on the Alzheimer’s landscape. A private foundation could cut through some of the red tape. It could choose the most promising drugs and pay for Phase I and Phase II trials. It could finance new biotechs and spin them off to big drug companies if the data looked good. The Lauders knew that Alzheimer’s research was one long trail of failures. But something had to be out there, and private philanthropy was maybe the best hope of finding success.
In his ADDF office, Howard gave me a short history of Alzheimer’s.
In 1906, a German psychiatrist named Alois Alzheimer told colleagues of a curious case of dementia in one of his female patients, aged fifty-two. The patient had had memory loss, hallucinations, and fits of jealous rage at her husband. After her death, Alzheimer put her brain tissue under a microscope. Utilizing some dyes to stain the tissue, he noted abnormal deposits in the brain that he called “senile plaques.” Dr. Alzheimer also saw “dense bundles of fibrils” that he called neurofibrillary tangles. The tangles appeared to be in dying neurons. Later, scientists would determine that the tangles were primarily made of a protein they called tau. Dr. Alzheimer’s role in making that link between amyloid and the tau-related dementia it seemed to cause in a relatively young woman—a form of presenile dementia—led colleagues to name it in his honor. There it remained, all but ignored, for the next sixty or seventy years.
The problem was that most people, including neurologists, saw senility in older people as part of the normal aging process. You got to your seventies or eighties, things happened. Maybe your memory loss was a lot worse than the next guy’s, but so what? Your time was about up.
In the late 1960s, some pathologists in London did autopsies on people who died with “senility” and found the same pathology that Alzheimer had described in 1906. It was then that senility went from being thought of as a normal part of aging to being recognized as a disease of old age. In the early 1980s, a researcher named George Glenner took the next step, isolating the senile plaques from human brain autopsy tissue and determining that a major component was a protein called beta-amyloid. Scientists thought they had found the “cause” of Alzheimer’s disease.
This was also the time that the whole science of genomics emerged. Suddenly scientists were sequencing the DNA of animals and, eventually, humans, seeing a whole new world of genes and the proteins they coded—proteins that gave you curly hair or blue eyes or a prominent nose. Some of those proteins appeared to have flaws or mutations; those flaws seemed to cause diseases. The DNA for beta-amyloid was sequenced. Mutations in the DNA coding for beta-amyloid were found in people with “early onset” or presenile Alzheimer’s, like the first patient described by Dr. Alzheimer. For a while the whole scientific community thought for sure that a breakthrough was around the bend. All they needed was a molecule that blocked the flaw from causing the disease. But the next two decades passed, and no easy answer appeared.
Maybe Alzheimer’s was caused by a more complex process. Maybe nothing the scientists had assumed was what they thought. Maybe not even amyloid plaques were involved. True, they appeared in Alzheimer’s patients. But maybe they didn’t cause the disease. Maybe they were just a result of it. The plaques, after all, can be present in individuals who never develop symptoms of Alzheimer’s. Howard, for one, remains a skeptic about amyloid. There are many forms of amyloid, he says, found in various parts of the body, and often they are not the cause of a disease but the product of it. He thinks amyloid was just the obvious culprit—the low-lying fruit, as he puts it. In the end, he feels amyloid plaques could prove a neurological decoy. Despite many billions of dollars spent on clinical trials attempting to prevent or remove the beta-amyloid, none of these drugs have worked in humans until very recently, and far larger trials—both for safety and efficacy—are needed. Meanwhile, he calls for funding other strategies and trying other targets.
To Howard, and others, the likelier suspects are the so-called tau tangles, the actual dying neurons. Maybe amyloid plaques simply enable the tangles to form, and the tangles are what kill the cells. Or maybe the plaques and tangles have nothing to do with each other; maybe the tangles form on their own in order to do their killing work. Maybe protecting the neurons is the best way to prevent Alzheimer’s.
Back in the mid-1980s, both sides—those scientists arguing that amyloid plaques caused Alzheimer’s, and those pushing the tau tangle theory—expected genomics to settle the debate in a year, maybe two. But the standoff persisted, as some of the early excitement over genomics subsided. With its amazing DNA sequencers, genomics could zero in on genetic flaws associated with a disease, but it couldn’t say whether those flaws actually cause the disease—only that they’re associated with it. Big difference. The cascade of new drugs expected to come of genomics has proved to be more of a trickle, as trials reveal adverse effects, or the drugs simply fail to work.
“The challenge of finding a drug is more daunting than ever,” Howard told me. “It’s harder than putting a man on the moon.” The universe of molecules that could be drugs is almost infinite. Yet so far, we have just ten thousand on the market for the whole kit and caboodle of human disease. That sounds like a lot—but it’s a lot smaller than infinity. And only about five hundred of those are unique drugs; the rest are combinations of the original five hundred, and new ways to administer them.
Finding that next drug is so hard that 90 percent of researchers at pharmaceutical companies spend their whole careers working on drugs that never get to market. Either the drug doesn’t perform as hoped or it has some harmful effect. Getting a molecule to do what you want it to do—every time—and not cause any harm in the process, is really, really hard. And maybe with Alzheimer’s, as Howard explained, no single drug will do the trick. “Look at AIDS,” he said. “It turned out we needed a whole cocktail of drugs for that.”
Meanwhile, costs continue to climb. A recent study out of Tufts University has shown that getting a new drug through all three phases of FDA government-monitored trials and out to market now costs $2 billion. Baked into that figure, as Howard had pointed out at the ADDF luncheon, is the cost of failure: the cost of the last drug or two that a company invested in to no avail and hopes to get its money back on. It adds those losses to the cost of the new drug, hoping to recoup them in the end.
Facing those odds, the drug companies have become risk-averse, to say the least. Howard sympathizes with them; he thinks drug companies, despite their bad rap, are almost heroic for taking the risk with billions of dollars to test new drugs again and again. But he also feels the breakthrough drugs for Alzheimer’s will come from cutting-edge biotechs and university labs doing clinical, early-stage research. They’re the kind of efforts the ADDF is backing. They’re where innovation will happen. Now it’s only a question of backing the right one.