Dr. Fishbein didn’t last long in his official capacity as the DAIDS official in charge of enforcing compliance with clinical research and ethical policy. His lethal misstep was his decision to follow a trail of irregularities affecting a NIAID drug trial called ESPRIT, which tested interleukin-2 (IL-2), a cancer chemotherapy and AIDS drug, known by its brand name, Proleukin. The ESPRIT study was investigating IL-2 clinical outcomes in individuals with asymptomatic HIV+.48 In December 2003, the ESPRIT Medical Officer alerted Dr. Fishbein to troubling side effects in the Proleukin trial, namely, capillary leak and an unusual psychiatric side effect: suicidal ideation. The Medical Officer, Larry Fox, worried that NIAID was putting volunteers in danger by withholding the information about those hazards from the Investigator Brochure, as the law required.49 This brochure is an FDA-mandated document containing updated information detailing, among other things, the side effects and risks of an investigational drug. It provides clinical trial investigators with safety information compiled across study sites to keep study subjects informed about emerging hazards. Furthermore, without an up-to-date document (NIAID had issued the last one in 2000), NIAID was not adequately warning potential clinical trial enrollees about these serious dangers. Recalls Dr. Fishbein, “The drug had grave risks for suicidal ideation, and capillary leaks. The study leadership was ignoring their legal duty to inform the study recruits and participants about these troubling signals.”
By this time, NIAID had invested some $36 million dollars in ESPRIT and had thousands of subjects enrolled at two hundred international locations over nearly four years.50 If these asymptomatic participants were to learn about the emerging risks, NIAID feared they would drop out. It would also be difficult to attract new volunteers. The failure to retain subjects or recruit additional volunteers would nullify the study, one of NIAID’s most costly ever. (Ironically, after eight years and 4,150 subjects, ESPRIT concluded Proleukin offered “no benefits” to clinical outcome in HIV+ patients.)
It was now evident to key NIAID officials that Dr. Fishbein was becoming an all-around nuisance. He was professional, curious, incorruptible, and far too serious about performing his duties. “His big problem,” says Farber, “is that he thought his job was legit. Dr. Fishbein’s personal virtues were all fatal character flaws within the NIAID institutional culture.” Dr. Fishbein’s refusal to toe the line sent him stumbling into the terminal career cul-de-sac at NIAID.
Dr. Fishbein explained further about the Proleukin trial: “It was a serious violation of protocols and the researchers were ignoring their legal duty to report the signal. They omitted and whitewashed all these safety problems. You can’t just focus on efficacy and ignore safety.” Dr. Fishbein told AP reporter John Solomon, “The ones that were in the study, and those that wanted to get in the study, neither were being informed. NIAID feared that if they understood the risks, they would drop out.”
Dr. Fishbein had entered a dangerous realm at NIAID. He was interfering with ongoing drug approvals. Tramont was angry that Dr. Fishbein was allowing concerns about patient safety to become an obstacle to the agency’s central mission of getting new drugs through the approval process with positive reviews. Tramont warned Dr. Fishbein to slow down. “You are moving too fast. You need to get to know how this place works,” Tramont told him. “We need to act more like a pharmaceutical company; we need to get patients, and get studies done.”
In the course of his IL-2 investigation, Dr. Fishbein stumbled on another awkward fact: Anthony Fauci personally owned patents to IL-2 and stood to make millions in royalties if the treatment won FDA approval. Dr. Fishbein was shocked: “Dr. Fauci had a personal financial interest in the drug being tested! He was listed as a co-owner on the patent for Proleukin, and stood to earn royalties from it!” According to little-known HHS rules at that time, NIH employees could collect unlimited royalty payments from drugs they worked on during their agency tenures.51 Dr. Fishbein found it stunning that Dr. Fauci stood to personally gain significant revenues, providing HHS green-lighted Proleukin.
Contemporaneous records obtained by the AP found that some fifty-one NIH scientists were then involved in testing products for which they secretly receive royalties; Dr. Fauci and his trusty longtime sidekick, Dr. H. Clifford Lane, “have received tens of thousands of dollars in royalties for an experimental AIDS treatment they invented [interleukin-2]. At the same time, their office has spent millions in tax dollars to test the treatment on patients across the globe.”52
The AP story expressed understandable indignation about the circumstances under which the government has licensed the commercial rights to IL-2 to Chiron Corp: “Fauci’s division subsequently has spent $36 million in taxpayer money testing the treatment on patients in one experiment alone. Known as the ESPRIT experiment, it is one of the largest AIDS research projects in NIH history, testing IL-2 on patients at more than two hundred sites in eighteen countries over the last five years.”
On February 6, 2004, Dr. Fishbein wrote the Study Executive Committee, requesting issuance of the long-overdue updated version of the Investigator Brochure within sixty days, to include warnings of the newly discovered risks. Within days, Dr. Fishbein recalled, “I wrote a letter to the executive committee telling them to update the brochure. From that point on, the floor came out below me.”
Even though his mandate was to enforce research policy, Dr. Fishbein had crossed the red line at NIAID. He was not just interfering with the drug-approval process: he was meddling with research in which Fauci had a peculiar interest.53
Dr. Fishbein’s questioning about Dr. Fauci’s patents tripped NIH into DEFCON 1. “All sorts of alarms went off,” recalls Dr. Fishbein. “I came into government very naive. At the very least, I assumed that since Dr. Fauci wanted me to make sure studies were properly done, safety came first and that the participants were protected,” he laughed. “I was wrong.” He recounts that he had met Dr. Fauci only once—at the interview when Dr. Fauci hired him as NIAID’s chief ethical and regulatory compliance officer. Dr. Fishbein recalls Dr. Fauci’s earnestness: “This is an important job. If you come across any problems in the agency, I want to hear about them personally. I want you to come directly to me.”54 Dr. Fauci told Dr. Fishbein that his “door would always be open.” But when Dr. Fishbein asked to meet with him about the IL-2 trials, Dr. Fauci went dark, and Dr. Fishbein felt the institution turning against him. “His guardians said he’d get back to me,” recalls Fishbein. “He didn’t.” He adds, “He basically ran away.”
In the course of his subsequent grievance procedures and litigation over his firing, Dr. Fishbein obtained emails and other documents that chronicled what happened behind the scenes. Dr. Fauci’s principal strategy in discussions with his upper-level management was how to sack Dr. Fishbein while keeping NIAID’s Director out of the splatter zone when things exploded. On February 24, 2004, Dr. Fauci met with Kagan and Tramont to plan strategies for ridding himself of Dr. Fishbein. The men hatched a plan by which Kagan and Tramont would orchestrate Dr. Fishbein’s dismissal while making Dr. Fauci’s fingerprints undetectable.