Star USC neuroscientist faces scrutiny following allegations of data manipulation
LOS ANGELES — A star neuroscientist at
USC is facing allegations of misconduct after whistleblowers submitted a report to the National Institutes of Health that accused the professor of manipulating data in dozens of research papers and sounded alarms about an experimental stroke medication his company is developing.
The accusations against Berislav V. Zlokovic, professor and chair of the department of physiology and neuroscience at the Keck School of Medicine of USC, were made by a small group of independent researchers and reported in the journal Science.
The report identifies allegedly doctored images and data in 35 research papers in which Zlokovic is the sole common author. It also raised questions about findings in Phase II clinical trials of a drug called 3K3A-APC, an experimental stroke treatment sponsored by ZZ Biotech, the Houstonbased company Zlokovic co-founded.
Preclinical data appeared to have been manipulated, the report authors allege. In addition, the Phase II results appear to contain errors that would skew interpretation of the data in favor of the drug.
An attorney for Zlokovic said the neuroscientist takes the accusations “extremely seriously” and was “committed to fully cooperating” with a USC inquiry into the matter. However, he said his client could not comment on the allegations while the review was pending.
“Professor Zlokovic would normally welcome addressing every question raised, insofar as allegations are based on information and premises Professor Zlokovic knows to be completely incorrect,” attorney Alfredo X. Jarrin wrote in an email. “And other questions address work not performed at his lab or papers where he was not the senior author or contact author and his role was limited.”
The university also issued a statement saying it takes allegations of research integrity seriously. “Consistent with federal regulations and USC policies, the university forwards any such allegations to its Office of Research Integrity for careful review,” the university said in a statement. “Under USC policy, this review is required to be confidential. As a result, we are unable to provide any further information.”
Last year, USC’S Keck School of Medicine received from NIH the first $4 million of a planned $30-million grant to conduct Phase III trials of the experimental stroke treatment on 1,400 people.
Given the serious issues outlined in their report, the whistleblowers say those trials should be stopped immediately.
“It should certainly be paused in my opinion,” said Matthew Schrag, an assistant professor of neurology at Vanderbilt and co-author of the whistleblower report. “There are red flags about the safety of that treatment.”
He said that evidence from the Usc-led phase II trial of the drug, which was published in 2018 and called RHAPSODY, raised questions of patient safety. Patients in that trial were more likely to die in the week after treatment, and more likely to be disabled 90 days later than those who were given a placebo.
In addition, Schrag said, some patients given the placebo had to wait longer for the standard stroke treatment of the drug TPA or surgery to dissolve the blood clot.
“The faster you’re able to intervene to either restore blood flow with the drug or restore blood flow by removing the clot, the more brain cells survive,” he said.
He added that he did not believe the delay was intentional but that it had the effect of “skewing the results in favor of the drug.”
Schrag previously raised questions about the integrity of other neurological research, work he said was separate from his employment at Vanderbilt.
Scientists have questioned Zlokovic’s research anonymously for years, Schrag said. Many of these concerns were published on Pubpeer, a website on which anonymous contributors can examine scientific papers and highlight potential flaws.
Yet scientists working with Zlokovic did not complain publicly, he said, allowing the studies to continue for years and succeed at attracting tens of millions of dollars in taxpayer funding.
“I think people are concerned about the potential for backlash for harm to their own careers,” Schrag said. “And so I think that motivates people to just go along.”
In its report, the journal Science interviewed four former employees of Zlokovic’s lab who said that Zlokovic routinely pressured them to manipulate data. Two said they were told to discard notebooks with results that didn’t fit preferred conclusions he hoped to reach.
“There were clear examples of him instructing people to manipulate data to fit the hypothesis,” one former employee told the journal.
The severity of the data manipulation charges merits a thorough investigation of Zlokovic’s data, said Elisabeth
Bik, a microbiologist and scientific integrity consultant who co-wrote the whistleblower report.
“Appropriate steps would be for USC to ask Zlokovic to give them the lab’s notebooks and data,” Bik said. “For example, for images where it appears that certain parts might have been duplicated or erased, the original images as they came off a scanner or microscope need to be compared to the published figure panels.”
Bik is among a subset of the report’s authors who are considering filing a federal whistleblower lawsuit. Should the NIH deem that any federal grant money was used improperly, a successful suit would entitle the plaintiffs to a portion of the money the government can claw back.
Zlokovic has received roughly $93 million in
NIH funding, according to Science. A spokesperson for NIH’S Office of Extramural Research would not comment on the specifics of the case.
“We take concerns related to research integrity very seriously, and this may include allegations of research misconduct,” the office said in a statement.