With Doug still at his house with Jennifer, Gail was living on her own, so Dean moved into his old room in the basement. Karla was relieved that he’d be available to keep an eye on things; despite the occasional forgetfulness that Deb and his children noticed, he was still very much his old self. Every morning, before he drove to work, he left two cigarettes for Gail on the kitchen table. On his days off, he drove four and a half hours home to see his family; with Tyler, he’d go out to the bar for a beer. With McKenna, he cheered her on at her volleyball and basketball games.
Having Dean around offered seventy-six-year-old Gail some security, which she needed for the first time in the fifty or so years she had lived in the town. Apart from her failing health, Tioga suddenly found itself overrun with roughnecks coming to seek their fortune from all corners of the United States, and with them came a startling side effect: From 2005 to 2011, violent crime in the Williston Basin, which includes Tioga, increased 121 percent.
In the old days, Gail never minded when Moe’s buddies wandered down the street from the bars and let themselves in to raid her refrigerator. But those days were long gone; now, when men came begging, Dean chased them off.
• • •
One fall morning, Jamie and Rikki Rice, his best friend, went out for breakfast. It was only 7:30 a.m., and the air was still chilly. As they headed to the café uptown, talking and laughing, they noticed some guy in the street. His hair was wet, as though he’d just stepped out of the shower, and he was holding up his pants and trying to run. In Tioga, strange sights were not so unusual anymore, with the oil boom attracting every misfit west of the Mississippi.
“Look at this goofball,” Rikki said, and they laughed.
And then, just as abruptly, their laughter stopped, because they realized they were looking at Doug.
“Holy fuck,” said Jamie. His eyes filled with tears.
They pulled up and offered Doug a ride; he was trying to make his way to Gail’s. He refused their offer. Not knowing what else to do, they continued on to the café, and pretended the entire episode had never happened.
“That was a rude awakening for me,” Rikki said. In a few months, the weather could easily dip to thirty below, and if Doug attempted the same journey and got lost, he could freeze to death. Even in large cities, Alzheimer’s patients frequently wandered off from their families, sometimes with tragic consequences. The Alzheimer’s Association reports that more than 60 percent of dementia patients wander, and if they are not found within twenty-four hours, up to half of them die or are seriously injured.
Wandering is a hallmark of Alzheimer’s because of the disorientation the disease causes. Unable to recognize their surroundings, patients might believe they have to get home when they’re already home. Adding to the problem is the fact that Alzheimer’s patients sometimes think they are in a different time in their lives, because the disease destroys the most recent memories first, so they could begin looking for a landmark from years past that only they would know.
It would not be the last time Doug was found staggering through the streets. He was becoming another of Tioga’s many odd town fixtures. Complicating the deterioration of his mental state were the respiratory troubles that had plagued him since the industrial pipe smashed his face in 2008. With Jennifer working so much, he was often alone, so he kept trying to get to the only safe haven he knew: his mother’s house.
The following July, Jamie’s girlfriend, Chelsey Determan, was cruising along in her big SUV when she spotted Doug by the side of the road, stumbling, struggling, his face flushed, unable to breathe. It was sweltering, with temperatures topping a hundred degrees.
Shocked, she pulled up beside him.
“Get in,” she said firmly. She was young enough to be his daughter, but Doug obeyed. She recognized how critical the situation was and drove straight to the hospital, calling Gail en route so she could meet them there.
It turned out to be another bout of reactive airway disease. Doug was lucky that Chelsey found him; his condition was bad enough to keep him in the hospital for six days. Worried that the outcome could have been much worse, Karla contacted the nursing home adjacent to the hospital to see if he could simply transition into their care.
At first, the home’s staff demurred. Some of them had been friends with the DeMoe boys and shared their misspent youth; they knew how wild they were, particularly Doug. Everyone had known Brian, of course, and they’d heard how combative he’d been when he was locked up. They weren’t really equipped to handle a working-aged man of Doug’s size and strength; if he fought them, they feared they wouldn’t be able to keep him—or the other residents—safe.
But Karla wouldn’t accept a refusal. Brian’s experiences in the Minot nursing home were still fresh in her mind. She could not, would not, allow that to happen again. She begged, cajoled, pleaded, played on their sympathies. She even persuaded the local Alzheimer’s Association chapter to intervene and offer additional training.
“I don’t know how Mom would deal with it if he wasn’t in town,” Karla said. “It would kill her to not be able to see him.”
Everyone in town knew Gail; she was still the most popular woman in Tioga, a regular churchgoer, the belle of the senior citizens’ center. When Dean took her out to the bar, all the locals stopped to buy her a drink. Nobody wanted to compound her losses.
Finally, the home’s administrators caved. Since Doug was used to going to the hospital so frequently, Karla asked his doctor to tell him he needed to return for more recovery time. The hospital’s beds were full, they lied—a plausible lie, given the frequency of industrial accidents occurring in the oil fields. They explained to Doug that he would be taking up residence in long-term care while he waited for a bed to open up.
Doug was convinced. Meekly, he moved into the home. At first, he thought he was in a hospital; but in time, he began to refer to the facility as “my apartment.” He was, by far, the youngest person in the hallways; but Doug never seemed to notice. Gail or one of his other family members came to visit him and take him on outings nearly every day.
Just as Brian had done in his early years at a care facility, when Doug had had enough of his day trips, he announced that he needed to get back to his apartment, and his family complied; they were just glad he wasn’t fighting with them the way Brian initially had.
Gary Anderson came to visit, and Doug smiled when he saw him, but it pained Gary to see his wild, reckless childhood buddy so changed. He didn’t stop by as often as he felt he should. Among the many invisible side effects of Alzheimer’s is the collateral damage it can do to once-solid friendships. People who are on the outside, looking in, often pull away, having no point of reference to guide their reactions to the disease. They avoid the uncomfortable situation, but in doing so, they are unwittingly isolating both the patient and the patient’s family at a time when they need support the most.
Gary took some comfort in the knowledge that Chelsey frequently brought Savannah to see her uncle Doug. His friend had always been a sucker for little children.
Nineteen
A BIG IF
ERIC REIMAN’S NEW research partner, Pierre Tariot, arrived in Phoenix to an empty building in 2006, charged with a weighty task: to design a clinical trial to test experimental Alzheimer’s drugs in patients who did not yet exhibit symptoms of the disease. Reiman, the brain-imaging expert who now headed the Banner Alzheimer’s Institute, had persuaded Tariot, whose own expertise was in designing trials, to leave his post in upstate New York to tackle the disease as aggressively as possible.
Their conundrum, which had faced them since Reiman first started talking about clinical trials, remained: How could they achieve a result significant enough to win support from the government and capture the attention of the pharmaceutical industry without spending twenty years on the process? And could they work tests on biomarkers—such as telltale proteins in spinal fluid, or a slowdown in the brain’s metabolism of glucose—into the mix, so they’d
know whether a shift in the composition of the biomarkers predicted a drug’s success or failure?
Tariot and Reiman worked so hard designing the study that Tariot began taking off whole days where he didn’t answer the phone or respond to email; he just read, thought, wrote, and talked to the world’s experts.
“That alone probably was a critical element for us to make progress,” he said. “Otherwise, you spend your days reacting to the crisis du jour rather than saying, ‘Now, wait a minute: How are we going to do this?’ ”
The two doctors started by asking the best specialists they could find in other fields. With their help, Tariot and Reiman identified combinations of tests that were sensitive enough to detect and track what cognitive decline looks like in people years before they showed any outward signs of dementia.
But where would they find people on whom they could use the tests? There was one group that could not be ignored: people who carried the autosomal dominant genetic mutation.
Reiman’s and Tariot’s cognitive tests were designed to work on patients as young as thirty. Though these patients functioned and tested normally, the results would tease out subtle shifts in brain function. But this realization brought a cascade of additional questions: When did those changes begin? Did the subjects already have evidence of brain damage that could be seen on an MRI? Did they have amyloid deposits? Were there abnormalities in their spinal fluid? Which would change first, the biomarkers or the clinical measures—and would they have any relationship to each other? What factors influenced the age at which the disease began to show?
“In our field, there are no answers to those questions,” said Tariot. But researchers in other diseases—notably HIV and cancer—had already pioneered ways to find the information the Alzheimer’s field sought. Among them was Don Berry, the lead statistician for the MD Anderson Cancer Center at the University of Texas. Though Berry’s normal consulting fee would have priced him out of their budget, after hearing the Banner Institute’s sales pitch, he spoke to Reiman and Tariot’s team for free.
• • •
By January 2011, the team was ready to present its plan to government regulators. At one of its public meetings, representatives from the FDA and its counterpart, the European Medicines Agency, agreed to attend.
Though the meeting was not formal or legally binding, both agencies indicated that Banner was moving in the right direction, and that regulators would be flexible in their approval because they recognized that the Alzheimer’s problem was reaching critical mass. The first baby boomers turned sixty-five that year, and the Alzheimer’s Association was publicly predicting that one in eight of them would develop the disease—or roughly 10 million people. Of those who lived to eighty-five, nearly half would get it. Time was running out.
Prior to the meeting, Banner already had interest from pharmaceutical companies, which posed an entirely different problem. As Bill Klunk and Chet Mathis had found when they were developing PiB, companies that were investing considerable amounts of money in a treatment wanted some control over its development, even if the scientists who invented the treatment didn’t agree with their decisions.
“If we proposed a study like that, where on earth are we going to find enough people to actually perform a sufficient test of the treatment, if there are only five hundred kindreds [with the mutation] around the world?” Reiman asked.
It was then that a couple of his colleagues reminded him of two names he’d heard before: Ken Kosik, who’d traded Harvard for a corner office overlooking the Pacific Ocean at the University of California, Santa Barbara, and Francisco Lopera, who had been buried for years in South America, mapping the constellation of an unthinkably large Colombian family who carried the PS1 mutation for Alzheimer’s—the same one the DeMoes carried. Three years before the 2011 meeting with regulators, Reiman made the phone call.
• • •
In Colombia, Lopera was in the middle of discussions with Swiss pharmaceutical giant Novartis about a collaboration involving his paisa families. After decades of frustration, it finally seemed as though he was going to be able to deliver some hope to people who had lived for generations with none. But in the midst of those talks, Kosik received the phone call from Reiman.
Kosik persuaded Lopera to meet with Reiman and Tariot at the Banner Institute and hear what they had to say.
Immediately, the two groups recognized in each other a common bond, one that Lopera hadn’t sensed in his discussions with Novartis.
“I saw that for me, it was easier to work with academic people than with pharmaceutical people,” Lopera said. “It was a big responsibility to take the decision about what kind of treatment was best for my families.”
The Colombian team wanted to work in what is known as a pre-competitive atmosphere, which would allow them to remain impartial when they selected a drug treatment. They didn’t want that decision being driven by business factors, only academic goals, avoiding the same kind of conflict of interest for which Trey Sunderland had been rebuked. They wanted to pursue the treatments that made the most scientific sense, not the ones for which they’d been paid. In essence, they wanted the “Camelot” of pure, impartial science that the NIH had purported to be.
• • •
Of course, academia has its own problem: the currency of credit. Scientific research is littered with examples of professorial catfights over who was first on the scene in an important discovery, and with good reason: Being first is tantamount to being best. When Jonas Salk announced that he’d created a polio vaccine, he became an instant demigod, feted and honored for the rest of his life; when a pilot announced Salk’s presence on an airplane, other passengers reportedly burst into spontaneous applause.
But years before him, a virologist named Hilary Koprowski mixed his own vaccine in a kitchen blender and drank it, inoculating himself against polio in 1948, seven years before Salk introduced the injectable killed-virus version that made him a legend. When Koprowski died, the New York Times quoted a historian who labeled him “the forgotten man.”
In Alzheimer’s disease, Dmitry Goldgaber’s success in locating the APP mutation on chromosome 21 bested other teams by the narrowest of margins; working with Family N and other subjects, Peter St. George-Hyslop reached a photo finish in identifying the PS1 mutation. Achievement begets admiration, but it also invites rivalry, and Kosik was wary of setting the Colombian families up to become pawns in an institutional battlefield.
But the Banner doctors were open and generous; immediately, the teams sensed a common purpose, and the bargain was struck. “This is the first time anybody has offered something that could actually help our families,” Lopera said. They began talking in 2008, and they formally established the collaboration in 2010.
The Banner team’s arrival in Colombia would prove to be a seminal experience for both the doctors and the paisa families. Like most people, Reiman was somewhat apprehensive about the visit, as Kosik recalls. He was, after all, planning to launch a clinical trial in a country famous for kidnappings and guerrilla warfare. The team met with some of the families, unannounced, in a little schoolhouse on the outskirts of Angostura.
Tariot was struck by the warmth of the people and the terrible beauty of the landscape. Here, superstition dwelled side by side with traditional medicine; curanderos—traditional Latin American shamans—practiced alongside doctors. In Colombia, these healers also sometimes pull double duty as witches.
“Sometimes the job is to cure the person, and sometimes it’s to curse them,” Kosik explained.
Even to the most sophisticated doctors, it was a novel experience to search for the answers to their medical mystery in the far corners of the world.
Sitting with a group of paisa, Tariot told a fifty-four-year-old man that his sons were participating in research that they hoped would work toward a better treatment: “We think your sons are heroes,” he said.
Tariot and Reiman would never cease to be in awe of people who, even in the lowes
t point of their lives, chose to offer what little time they had left on earth to a field that had largely ignored them, knowing their contributions might only benefit people they would never meet.
“You cannot meet these families and not be transformed,” said Reiman. “Cannot happen. Pierre and I have met close to a thousand family members in Medellín. And you go into their home, and you see several family members affected at the same time.”
His voice rose as he described what he saw: “Struck in the prime of their life, not able to work, and their children gave up work to care for them. And they’ve been living with it one generation after another. It’s almost treated like a curse. To go in there and to talk, it’s both a privilege and a keener sense of responsibility.”
Many of them were shamed or frightened by Alzheimer’s. It was difficult to parse out the medical knowledge these doctors brought from the superstitions of the curanderos. But still, they agreed to participate.
Reiman polled the family members, asking: “If we could provide one service, what would it be?”
The answer told him everything he needed to know about the circumstances in which they were living: adult diapers.
The thought that his team could help empower people who had lived for generations with a nameless, hated disease was exhilarating. It was science at its best. At the same time, he had to remind these people that what they were agreeing to do was experimental. There were no guarantees that whatever drug they chose would work, or even be safe or tolerable.
“We’re going to learn a tremendous amount from this single mutation,” Reiman said. “But those are all big ifs: A big if whether the treatment will work; all sorts of things can go wrong in clinical trials. And a big if [whether] one or more of these clinical biomarkers predict a clinical outcome.” In other words, if a drug successfully reduced amyloid or tau in spinal fluid, for example, it might predict that years down the road, Alzheimer’s symptoms such as forgetfulness or aggression would be delayed or prevented.
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