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ial he iu, i . days aacte- iT was k jail, about sorting try. At in my Bae Sone ARR overn- > addi- led the rim of al fees osecu- e who xim to it new ed the ag that lefense curity. Butler sars in arty to ‘eveals f what € pen- ruined some- sends CREDIT: KM WATKINS LUBBOCK AVALANCHE-JOURNALIAP: CREDIT: GARY GAUGLER/PHOTO RESEARCHERS INC. To reconstruct Butler’s path, Science sent two reporters to Lubbock to attend his trial, review court documents, and conduct interviews. Unless otherwise noted, all di- rect quotes in this story come from trial tes- timony or documents entered into evidence. Many of those most knowledgeable about the case, including Butler himself, have been silenced by a court-imposed gag order. But their testimony provides a detailed, if sometimes disputed, record of an extra- ordinary career and its controversial demise. A calming hand Lubbock, Texas, has two industries: cotton and, college students. And although the seemingly endless, pancake-flat farm fields that surround the drab town are stil] its soul, it is the sprawling campus of Texas Tech University that is its heart. The school’s 30,000 students and staff pump more than $1 billion a year into the-local economy, and thousands of fans avidly follow the for- tunes of its sports teams. Texas Tech gradu- ates and faculty also figure prominently in the community: The judge in Butler’s case, “Maximum Sam” Cummings, is an alum, for example, and the lead prosecutor, US. Attorney Richard Baker, teaches at Texas Tech’s law school. Butler became part of that cozy com- ‘ munity in 1987, when the Tennessee-born physician and his Swedish wife, Elisabeth, arrived from Case Western Reserve Uni- versity in Cleveland, Ohio. As head of the health center’s infectious-disease division, Butler quickly became known as an excel- lent doctor and teacher. A former assistant, Kimberly Bethune, testified that the tall, snowy-haired physician could put patients at ease simply by placing a hand on their shoulder. And although other doctors might resent having residents bug them on weekends, Butler graciously answered calls at all hours. He was also adept at en- rolling patients in clinical trials for drug companies—a significant source of cash for the health center. But 3 years ago, one of those trials placed Butler on a collision course with Bar- bara Pence, the health center’s associate vice president for research. The confrontation would ultimately cause a university panel to withdraw its approval for him to perform buman research, and it would trigger finan- cial investigations that prosecutors claim caused him to instigate a bioterror scare. Pence, a slight, middle-aged pathologist, is a Texas Tech graduate who has spent her entire career at the university. She holds one of the health center’s most sensitive jobs, overseeing its burgeoning research budget and its Institutional Review Board (IRB). The government-mandated IRB—composed www.sciencemag.org SCIENCE VOL302 19 DECEMBER 2003 of a shifting cast of researchers, nurses, cler- gy members, town folk, and sometimes even ex-convicts (prisoners are often study subjects}—is responsible for protecting pa- tients who participate in clinical studies, No trial can start without its blessing. Pence testified that in late March 2001, the IRB expressed serious concerns about one of Butler’s trials. Together with more than 150 other doctors across the nation, Butler was testing the efficacy of a drug de- veloped by Chiron Corp. of Emeryville, California, to treat sepsis, a massive blood infection that often results in death. Butler had told the IRB that he expected up to 50% of the severely ill patients enrolled in the study to die. But during a routine review, IRB members noted that about 70% of But- ler’s first small group of patients had died and that some paperwork appeared to be missing. The panel decided to suspend the trial and ask for more information. A month Jater, after Butler com- plied, it allowed the study to resume. Still, Butler was upset. In particular, he was angry at Pence, believing that she was at least partly respon- sible for the “very abrupt and disrespect- ful” suspension of the trial—the first of his career. The “terrible experience,” he testi- fied, damaged his rep- utation and “essential- ly ruined” his rela- tionship with Chiron. It also triggered a time-consuming re- view by the FDA; the agency ultimately cleared him. In mid-2001, Butler filed a grievance against Pence, who tried unsuccessfully to convince university officials that his beef was with the IRB, not her. The opponents picked two faculty mediators to examine the issue, and in February 2002 they issued a re- port that criticized both Pence and Butler for missteps. And although Pence disagreed with some of the findings, she and Butler eventually signed a settlement statement. The matter didn’t end there, however. Pence, who said she was ynaware that FDA had given Butler’s sepsis trial a clean bill of health, was still worried about the study, which had ended some months earlier. Four days after receiving the mediators’ report, she asked health center auditors to investi- gate whether Butler had improperly billed some medical tests to the government or pa- tients. Then, 9 days later, she asked Stacey Pugh, clinical trials administrator, to re- view Butler’s reporting of trial deaths and his adherence to the study’s scientific proto- col, according to court records. Butler con- sidered the studies “retaliation” for his grievance, he testified. But Pence insisted that she was “just doing my job. ... There were dead people we couldn’t account for” Butler was decidedly uncooperative with both investigations, Pence and other health center officials testified. And Pugh’s report, delivered in late summer of 2002, was highly critical of Butler. “I found a number of-problems, some of which I] thought were quite serious,” Pugh testified. For instance, she alleged that Butler had improperly filed patients’ con- sent forms, ordered tests before obtaining their consent, and then billed the patients instead of the study’s sponsors. In Sep- tember, acting on Pugh’s report, the IRB wrote Butler that he had apparently vio- Destructive force. Yersinia pestis bacteria, the cause of Black Death. lated federal regulations and Texas Tech policies in the sepsis study. It asked for an explanation—and fast. In the meantime, Pence’s office stumbled onto another serious matter. In late July 2002, during a routine telephone conver- sation about a paperwork problem, an employee of the Pharmacia-Upjohn (now Pfizer) pharmaceutical company in Kalama- zoo, Michigan, mentioned to one of Pugh’s staffers that the company had an unusual way of paying Butler for his clinical trial work. Typically, a Pharmacia official testi- fied, the firm completed a single contract with each of its trial investigators, spelling out the payment for each enrolled patient. The money was generally sent to a special account at the investigator's university. In Butler’s case, however, Pharmacia had twin contracts with the scientist for several trials involving a diabetes drug. One of the HOMAS BUTLER“ 2055 fort