The Inheritance

by Niki Kapsambelis

  The problem was that pharmaceutical companies did sometimes provide funding to NIH studies, and though theoretically there were boundaries to safeguard against any conflict of interest—such as the Institutional Review Board, to which scientists submitted potential conflicts—those lines tended to blur. “The NIH is supposed to be above all that,” as one former employee pointed out. “In taking money from the companies, it really undermines what the NIH is supposed to be about.”

  At the same time, a lot of government scientists were consulting for private companies. Such arrangements, too, were permissible, provided they were fully disclosed to NIH leadership. There were caveats to those deals: They had to be reviewed and approved, and the NIH did not allow its scientists to consult for companies with whom they were also collaborating. Ultimately, though, the NIH leadership would argue that public-private collaborations could offer some advantages: The government could provide wider sample sizes for trials, as well as world-class expertise, whereas drug companies could offer deeper pockets. Ostensibly, the arrangement was a win-win.

  Certainly, the pharmaceutical scene was heating up in those years. The Cognex that NIMH recommended to Jerry DeMoe in 1995 was quickly eclipsed when a newer, sexier drug from the same family arrived on the scene: donepezil, known by the trade name Aricept—which won FDA approval in 1996 and was sold in the United States by the pharmaceutical giant Pfizer.

  Since Aricept’s introduction, it has become one of the most widely prescribed drugs for Alzheimer’s patients, ringing in more than $2 billion in annual sales before its patent protection expired in November 2010. It was what Karla’s cousin Dawn was taking. (Cognex would be discontinued by its then manufacturer, the Japanese pharmaceutical company Shionogi, in 2012, after persistent reports about its damaging effects on the liver.) Perhaps the most poignant evidence of the public’s desperation for an answer to Alzheimer’s is contained in those sales figures, when even a drug that does not cure, and in fact only temporarily and partially staves off symptoms, is worth billions.

  • • •

  Looking to further the progress they’d just made with Aricept and to possibly develop new drugs, in late 1997 David Friedman, a PhD-trained neuroscientist for Pfizer, approached Trey Sunderland with a proposal: He wanted to create a three-way collaboration among NIMH, Pfizer, and the British company Oxford Glycosciences Limited to discover new, unknown biomarkers in Alzheimer’s disease. Friedman had read some of Sunderland’s published work and respected him because he seemed to recognize the importance of biomarkers—whether they signaled different stages of the disease or the potential for seemingly healthy people to develop Alzheimer’s.

  Sunderland cleared the agreement with his supervisor. It was the kind of public-private alliance the NIH encouraged, so long as scientists disclosed any potential conflicts of interest.

  Under the agreement between Sunderland and Friedman, NIMH would provide scientific expertise, staffing, data analysis, and human tissue samples from Alzheimer’s patients or at-risk subjects. The samples, in Friedman’s opinion, were the least important item on that wish list; it was really Sunderland’s expertise Pfizer was after. Pfizer had sought out Sunderland because they needed someone with “the experience, and knowledge, and access to samples that would make this project possible,” Friedman said.

  In total, Sunderland sent thirty-two hundred or so vials of plasma and spinal fluid to Pfizer for both the unknown biomarker study and the study of known biomarkers such as beta-amyloid and tau. The samples were worth approximately $6.4 million and had taken about fifteen years to collect. What made the Alzheimer’s samples so valuable, according to Friedman, was that Sunderland knew the story behind the people who’d supplied them: What their family history was like. What their clinical symptoms were. He was the man who could connect the dots between any possible biomarkers and how the disease manifested itself in the person who carried them.

  Pfizer wanted those vials to help develop drugs that would target the disease in its earliest stages. In April 2003, the storied Journal of the American Medical Association published some of their results in an article authored by Sunderland, members of his NIMH staff, and Pfizer employees. From David Friedman’s point of view, it had been a very successful collaboration. But the company also used Sunderland to promote Aricept as an option to audiences of doctors during a televised NIH presentation in 2003.

  Though he recommended the use of Aricept, Sunderland never told audiences he was being paid by its manufacturer; they only knew he was an NIH expert. In May 1998, he had negotiated his own private arrangement with Pfizer, under which he was paid $25,000 per year as a consultant, with separate payments of $2,500 per day for one-day meetings. All told, he earned roughly $500,000 from his five-year private arrangement, a payment that Pfizer considered “modest at best” compared to other, similar arrangements. Of that amount, Sunderland failed to disclose about $300,000 to his bosses. From 1999 to June 2004, he took the show on the road, speaking at US and international conferences while Pfizer paid him.

  Aricept was a massive success by many standards. But there were some researchers—including one of Sunderland’s own protégés, a young scientist named Susan Molchan—who believed Alzheimer’s patients could possibly get the same benefits—a temporary slowdown in cognitive decline, for example—as these hugely profitable but expensive, privately controlled drugs provided from far more ordinary treatments. Dawn’s daughters shared that skepticism about Aricept’s benefits. And ultimately, it was the tissue samples that Sunderland had given to Pfizer, many of which had been collected by Molchan, that would spell his professional downfall.

  • • •

  Molchan was a graduate of the University of South Florida’s medical school who went to work for Sunderland in 1987. Instead of moving on to a university after a few years at the NIMH, as most ambitious young scientists do, she committed herself to government service and to studying memory issues and ways to help Alzheimer’s patients outside the traditional drug regimens.

  One of Molchan’s early studies examined the effects that stimulants had on memory; she wanted to know whether a drug like Ritalin or even a simple cup of coffee could confer benefits.

  In 1993, Molchan embarked on a study that tested whether lithium—an element sometimes used to treat mania—might help prevent tau proteins from becoming toxic. Toward that end, she collected the spinal fluid of Alzheimer’s patients, as well as healthy volunteers. By NIH standards, the lithium study was small: gathering samples from just twenty-five people. However, Molchan took more fluid than was typical, with the intent of storing some for future research, to which the patients each consented. Although Molchan was devoted to the study, it received little support from the institution at large and faded away without generating any concrete results.

  Molchan began to think that her studies got less support because she was suggesting that caffeine or other mild stimulants could do the same job as Aricept for less money. During her five years at the FDA, she came to believe that clinical trials could be manipulated, allowing drugs to win approval even without proving much clinical benefit. She cited cholinesterase inhibitors such as Aricept as one example.

  When Molchan arrived in 1987, she said Sunderland promised to support her for a tenure-track position. She and her husband had started a family that would grow to include three daughters. However, as it turned out, the atmosphere at NIMH wasn’t welcoming for a young working mother. Very few women had tenure or were on a tenure track. Access to resources depended largely on office politics; Molchan and a colleague were both promised a research assistant, but neither person received one. If the women complained, they were sometimes told they had psychological disorders; according to Molchan, Sunderland informally diagnosed her as paranoid and depressed, while another woman was ordered to see a psychiatrist.

  Perhaps predictably, Molchan’s application for tenure-track positions went nowhere. Frustrated that younger male colleagues with less experience were get
ting professional advantages that she didn’t have, she filed a sex discrimination claim that was dismissed. Finally, in 1996, she decided to move on and took a position with the FDA.

  In 2001, a job opened up at the National Institute on Aging, one that rekindled Molchan’s interest in Alzheimer’s research. Three years later, in the fall of 2004, she was alerted to a lithium study requiring spinal fluid similar to the archive she’d left behind at NIMH. The colleagues who proposed the study suggested that Molchan retrieve the NIMH spinal fluid samples she had previously collected to use in the new project.

  When she contacted Sunderland for access to the archive, however, he responded by sending a tiny amount of spinal fluid from eight Alzheimer’s patients and two unaffected people.

  “Now, I understand we didn’t need a whole lot, but we would have liked a little more than a half of a cc,” Molchan said. But when she asked what happened to the rest, Sunderland appeared to hedge. It had been a long time since she collected those samples, her former boss explained; moreover, some were lost through freezer failures.

  True, at the time, the NIH’s policies for tracking its human tissue samples were erratic. By 2006, the NIH was beginning to discuss ways it could centralize its tracking system through a computerized database and start requiring the transfer of all human samples to involve some form of written recordkeeping. But before then, how well samples were recorded depended on what lab they were in; some kept written records, others didn’t. The only system-wide regulations the NIH had concerned hazardous biological materials. Otherwise, ordinary tissue samples such as Molchan’s spinal fluid were largely untraceable. If a freezer malfunctioned, or samples spoiled some other way, nobody had to account for them. If they were stolen or used for purposes other than those to which the donors had agreed, nobody had any way of knowing.

  However, for Molchan this atmosphere of carelessness didn’t explain away Sunderland’s vagueness about the vials, because Sunderland himself had always been scrupulous with the lab’s samples, documenting how much was on hand and including additional details, such as whether the fluid had been collected at the beginning or end of the spinal tap. Every twenty-four hours, someone measured and recorded the temperature in the freezer. If it broke, or the temperature even fluctuated, alarms went off. Knowing what she knew about her former boss’s habits, it seemed unlikely to Molchan that every backup system might fail, wasting so many people’s sacrifices.

  Ultimately, the fate of the missing samples would become the subject of a prolonged legal battle that would cast Pearson Sunderland III from the comfortable position of NIMH’s chief of geriatric psychiatry to being a disgraced footnote in the history of Alzheimer’s research.

  When Molchan failed to get any answers from Sunderland or other channels at NIMH about the fate of her samples, she contacted the inspector general and the Department of Health and Human Services. Finally, in April 2005, she tried the Committee on Energy and Commerce, whose chairman, a Texas Republican named Joe Barton, had a mother who’d died from Alzheimer’s. Her complaint got the politicians’ attention, and the matter was brought before the House Subcomittee on Oversight and Investigations.

  On June 13, 2006, she testified before the subcommittee about her concerns.

  “As a doctor, my first obligation is to advocate for patients who put their trust in me,” she said. Her testimony echoed the Noonans’ demand that all of their biological samples be widely shared. “Some of these patients had contributed their time and bodies to a number of my research studies and others at the NIMH. These good people are always ready to help and work on Alzheimer’s in any way my colleagues and I asked.”

  Some patients were fine with their tissues being used in any way the researchers saw fit. But not everyone felt that way. Submitting to a spinal tap—or agreeing to donate your brain postmortem—for the greater good of finding a cure was a noble cause, especially given the emotional investment and the fact that it subtracted from what precious time you had left to spend with loved ones while you still recognized them. Not everyone would have agreed to make those same sacrifices if they knew what Sunderland was doing. At the very least, it was a violation of trust. At worst, it could dissuade participants from research that could yield better results. Not everyone had the means or the energy to participate in multiple studies.

  Molchan recounted the tale of the missing samples and her efforts to track them down. Congressman Barton asked her whether Sunderland ever told her to simply mind her own business.

  He hadn’t, Molchan said; but Insel, the NIMH director, pretty much had.

  Paraphrasing what Insel had told her, she said, “Dr. Sunderland is occupied with plenty of other things right now. Please leave him alone.”

  For his part, when testifying in front of the committee, Insel did not hide his admiration for Sunderland, with whom he had once shared an office at NIMH, and admitted that he never asked Sunderland what happened to the missing tubes of spinal fluid.

  • • •

  Despite his place in Insel’s good graces, Sunderland was nonetheless feeling pressure about the irregularities in his Pfizer agreement. On August 19, 2004—about the same time he met the DeMoes—the NIH’s Office of Management Assessment interviewed him about the arrangement. He contended that he was not involved in any conflict of interest; at worst, he said, he had made some honest mistakes in his disclosure paperwork. The investigators were not convinced.

  “Not disclosing over $500,000 [sic] in income was not an oversight or lapse in judgment but appears to be a deliberate decision not to comply with the rules, policies and procedures that are necessary to protect the NIH, its scientists and most importantly, its science,” the Office of Management Assessment concluded.

  The NIH recommended to the Commissioned Corps, which technically employed Sunderland, that he lose his job. In a cover note attached to the recommendation, Insel expressed his regret over the whole affair.

  “I thought of Dr. Sunderland as one of the people who had made tremendous contributions to the agency,” Insel said, but the NIH’s Office of Management Assessment concluded if Sunderland had committed similar infractions as a civil servant, he would have been fired.

  Even so, his golden-boy persona still carried some of its old luster. By the time his case reached the congressional subcommittee seven months later, Sunderland was still on the job—a fact that frustrated Barton, the congressman from Texas, as did the doctor’s lack of cooperation with the congressional subcommittee staff charged with gathering information about his case.

  “What little information that we have gotten, some of it appears to be misleading or intentionally inaccurate,” Barton told Insel. “So we have a person who has, on the surface, suffered no repercussion—none—and you talk about a Camelot.”

  Nonetheless, at the hearing Insel argued that parts of Sunderland’s relationship with Pfizer had been helpful. For example, Pfizer had tested one of the spinal fluid proteins with an antibody that was not widely available, saving the NIH a “tremendous” amount of money in the process.

  Insel pointed out that the ethics case had been referred to the Department of Justice, and that he had done all he could do; he was Sunderland’s supervisor, but he couldn’t fire him. In fact, Insel seemed almost indignant, as if the unfinished state of affairs were somehow unfair to Sunderland.

  “We made a referral. We are now seven months down the road, and this gentleman is still waiting to find out about his fate,” he said. “The true north here has to be the question of separating out public role, official duty, from private [gain]. And if that wasn’t on the table, then we are here to congratulate Dr. Sunderland on having done, I think, a really exciting scientific collaboration which . . . may actually bear some really important discoveries for families with Alzheimer’s disease.”

  Barton was sympathetic, but only to a point. He would have far preferred that the hearing was called to highlight research breakthroughs. Instead, they were dealing with a prodigal son. />
  And for all the NIH’s talk about toughening up its ethics standards, there really did not seem to have been any cultural change within the institution, Barton said; nobody seemed to be condemning Sunderland’s actions. Barton concluded by saying such a lapse was “inexcusable.”

  On December 8, 2006—six months after the subcommittee hearings—Trey Sunderland pleaded guilty to a criminal conflict of interest as part of a plea bargain. Two weeks later, a federal judge in Baltimore spared him from serving any prison time, but ordered him to repay $300,000 to the government and sentenced him to two years of supervised probation. Sunderland said he planned to perform four hundred hours of community service at a retirement home for veterans in Washington, DC.

  In one of the only public comments he would ever make about the case, Sunderland consulted some prepared notes and said that when he thought back on the events that led to his troubles, he could not explain what had happened.

  “This process has humbled me in a way that I have never experienced before,” he said. His voice quavering, he added, “This has been the most difficult thing I’ve ever had to do.”

  Despite her protests against his use of the samples, Molchan remained sympathetic to her former boss on a personal level. They shared several mutual friends. She wrote to the judge asking for clemency and drove up to Baltimore with her husband to witness the sentencing. He had once been Mr. Perfect, and she felt that he’d been a victim of his ambition. The other punishments were adequate.

  Besides, she noted, other NIH researchers had done the same thing: “He’s not as smart as them,” she said. “Some of the guys got away with a lot more drug company money than he did, but they were smarter and didn’t get caught.”

  After he lost his job with the NIH, Sunderland sustained further blows to his professional career. His medical license was revoked in Maryland in 2009 and in New York in 2011. In 2010, Sunderland applied to regain his license to practice in Maryland, but his application was denied. “He has not convinced the Board that he fully understands the deceitful characteristics of his conduct,” said the denial.