Too Good to Be True

A professor who knows he might be dying flouts research protocols and teams up with a Hollywood producer to test a highly experimental herpes vaccine on human subjects. The patients -- some of whom traveled to a house in the Caribbean for injections -- start reporting adverse side effects. The professor largely dismisses the patients’ concerns and later dies, leaving his apparently unwitting institution to answer for him.

It sounds like the stuff of fiction, but it’s Southern Illinois University’s reality.

Between 2013 and 2016, William Halford, a late professor of medical microbiology, immunology and cell biology there, injected patients with a herpes vaccine, both preventative and therapeutic, in hotel rooms near campus and in St. Kitts -- all without approval from an institutional review board overseeing research on human subjects.

Many details about the research and the vaccine itself remain unclear. Southern Illinois is nevertheless facing questions from patients, the public and even Congress about how a professor using its facilities was able to go rogue.

“This came upon us really unexpectedly,” said Jerry Kruse, dean and provost of Southern Illinois’s School of Medicine. “There’s been a lot of publicity about it, and I can’t quantify the effect that that has had on public confidence in us. But I regret that this has happened.”

Promising Findings

Kruse, who became dean in early 2016, met Halford in October of that year at a university innovation conference in Chicago. Halford, a presenter, introduced himself as a professor but quickly clarified that he was speaking for his independent company, Rational Vaccines. Then he shared what Kruse recalls as promising findings about a potential cure for genital herpes, from the St. Kitts trial.

“That obviously stirred a lot of enthusiasm,” Kruse said. “There was nothing for me to do but shake his hand.”

Less than year later, in July 2017, Halford died, after a long battle with nasal cancer. Weeks after that, Kruse said, both he and the university’s IRB first learned of serious research “irregularities and improprieties” during a meeting with Rational Vaccine’s CEO, a movie producer named Augustin Fernandez.

Prior to the St. Kitts trial, and before the formation of Rational Vaccines, Halford had given a series of shots to at least eight patients at hotels near campus, including the Holiday Inn Express. Halford apparently believed in the vaccine so much that he’d been injecting himself, too, even though he did not have herpes.

But such activity -- by university policies and the basic dictates of medical science -- would have required the oversight of the institutional IRB, which Halford did not seek.

Around the same time, there were rumblings that the St. Kitts trial also lacked oversight, which would have been required even though Halford ran it in his capacity as a private researcher. The Food and Drug Administration says that human trials of drugs intended for the U.S. market must be approved by an institutional review board. St. Kitts has said should have been asked to vet a plan for a trial involving a live virus, but was not. Southern Illinois also shares the patent to the vaccine and its related agreement with Halford says that proper research oversight will be obtained.

Kruse said the institution soon launched an internal investigation to see what had gone wrong, and how. Southern Illinois also shared information on the matter with the federal Office for Human Research Protections, at the office’s request, in October 2017. An initial report by the campus IRB found serious noncompliance, prompting a more in-depth internal investigation. Both that inquiry and the federal investigation are ongoing.

Southern Illinois, for its part, is reviewing the particulars of the Halford case -- including the extent to which university resources were involved and if Halford accurately represented the efficacy of his vaccine -- along with existing policies and procedures for research involving human subjects.

Kruse said such policies have worked well in the past, and that by all accounts Halford was a great teacher who worked “by the book” in his research with animal subjects. Yet one clear outcome of the investigation will be that the university works harder to raise awareness of compliance requirements for research involving human subjects, he said.

“How do we identify people who go off the beaten path and intentionally and willfully hide activities like this from the university? How can we better get to that earlier?”

Held to Account

Kruse said that if Halford were alive, he would certainly be suspended from research activities during the university’s investigation. He didn’t rule out termination. But all of that is, of course, moot. The problem is largely Southern Illinois’s now.

Much of the story has played out in the public eye, through a series of investigative reports from Kaiser Health News. Several patients, who have thus far remained anonymous, told the news service that they complained about painful new herpes outbreaks or severe discomfort after the injections, and Halford brushed them off as minor or unrelated to the trial.

Kaiser also has raised questions about exactly when the university was made aware of Halford’s misconduct. Kruse insisted this week that neither he nor the IRB knew that anything had happened outside St. Kitts -- let alone just off campus -- until the summer meeting with Fernandez. A spokesperson for Rational Vaccines said in a statement Monday that Fernandez did not meet Halford until 2014 and that neither he nor the company had anything to do with research prior to that.

Earlier this month, the university responded in writing to a series of questions from Senator Charles Grassley of Iowa, chairman of the Committee on the Judiciary. Among other questions about the case, Grassley wanted to know what corrective action has been taken to ensure IRB compliance going forward.

Given that Halford is dead, Southern Illinois president Randy J. Dunn wrote to Grassley, disciplinary options are few. But he said the university will act on recommendations from its Misconduct in Science Committee, which continues an in-depth review of the case.

In general, Dunn said, reports of potential misconduct trigger investigations by the IRB, and the board notifies relevant federal agencies of any serious findings of misconduct.

Southern Illinois’s IRB has received three reports of potential unapproved research within the last five years, Dunn said. All those reports resulted in review, he said, with findings of misconduct in two cases, including Halford’s.

In the other instance of misconduct, the researcher’s privileges and protocols were suspended, and the OHRP approved of the university’s unspecified corrective action. Of all three cases, only Halford’s involved an unapproved protocol -- meaning that wholly unvetted research projects remain rare, at least at Southern Illinois.

Kruse oversees about 350 faculty members as dean, and professors are trained annually about appropriate research conduct. Administrators at Southern Illinois and elsewhere generally trust that professors will do the right thing when it comes to human subjects research. Still, some critics have suggested that Halford's institution ought to have known more about what he was doing for years.

Interestingly, Halford's attempt to publish his trial St. Kitts findings in 2017 failed, with an anonymous reviewer for Future Virology calling the paper "partly a vision, partly science, and partly wishful thinking." Halford "believes, based on little data, that this vaccine will provide both a therapeutic and a prophylactic benefit," the reviewer wrote. 

Robert Klitzman, a professor of clinical psychiatry at Columbia University who studies medical ethics, said Monday that all institutions “have responsibilities to ensure that their faculty, students, administrators and staff know about needs for protections of human subjects in research.”

Given that Southern Illinois shared the vaccine patent with Halford, doing “due diligence” would have meant making sure that proper oversight had been obtained, he said. Klitzman noted that the research was sufficiently high-profile for the university to announce when tech billionaire Peter Thiel funded it. 

Klitzman also said that vaccine research is “high risk and invasive, and many human study participants have, historically, died in such studies.” 

Kruse said the university has engaged with Halford's patients who contacted it directly. Outreach to the others is planned, he said.