A cutting-edge brain research center at UC Irvine quietly ceased human experiments in 2012 when government inspectors uncovered multiple quality problems, including poor sanitation practices and tainted drugs, according to officials and records.
The Brain Imaging Center on the Irvine campus made and used radioactively tagged compounds that substantially exceeded allowable impurity levels in at least 168 patients, asserts a report by the U.S. Food and Drug Administration.
The FDA report, as well a separate state report and a lawsuit, raise questions about how the university conducts experiments on patients, who typically are volunteers or recruited for drug trials.
Questioned doses for experiments on brain activity “were manufactured and released for use in patients” between Jan. 20, 2009, and Jan. 19, 2012, according to the FDA report, which was based on four inspections completed during the spring of 2012.
All told, the report, issued on May 3, 2012, cited 19 areas of concern, including improper testing to prevent bacteria contamination of drugs, faulty sterilization practices and inadequate documentation.
“The inspection team observed some violations of current good manufacturing practice,” an FDA spokesman said recently.
The FDA spokesman added that the agency had prohibited reopening the lab to restart the program for making radioactive drugs until it was notified and could conduct an inspection “to verify the adequacy of the facility.”
Meanwhile, a state Department of Public Health report issued in May of this year cited the Brain Imaging Center for failing to properly monitor radioactive releases to either staff or the public from 2009 through 2011.
The state report by the Radiologic Health Branch also found that “licensed radioactive materials” were stored unsecured for five years until early 2012. The door to the lab with radioactive isotopes wasn’t lockable, reports state.
This was in violation of government policies, increased in the aftermath of 9/11 terrorist attack, to prevent radioactive material from being mishandled or abused, such as employing it for so-called “dirty bombs.”
“These issues are of concern. … It doesn’t meet medical standards," said Chester A. Mathis, director of the University of Pittsburgh PET Center and a national authority on the handling of radioactive materials in medical environments.
A UC Irvine spokesman said the Brain Imaging Center’s “radio-chemistry lab was shut down in February 2012” because of “irregularities.” An investigation occurred, and the program has remained closed since. He added that some equipment is available for regular clinical testing of patients.
The diseases studied at the Brain Imaging Center included Parkinson’s, Alzheimer’s, epilepsy and psychiatric disorders such as schizophrenia. Substance abuse, mood disorders and responses to nicotine were also probed.
Dr. Steven G. Potkin, longtime head of the Brain Imaging Center, quietly left his position in April 2012, and Dr. Steven L. Small was then named director, officials said.
Neither Potkin, who remains at UC Irvine, nor Small would consent to be interviewed by Voice of OC. The UC Irvine spokesman said university leaders would answer questions, but after nearly a week of delays the interview was cancelled.
'Lack of Radioactive Release Information'
The government reports of violations have surfaced as part of a lawsuit filed in July in Superior Court in Santa Ana by a former UC Irvine physician-researcher, who alleges he was fired in retaliation after being hired to address center deficiencies.
In a Brain Imaging Center test, researchers take low-level radioactive isotopes (carbon-11) from a radioactive source, link it to a drug, inject the experimental compound, then use positron emission tomography or PET to scan to create a three-dimensional picture of brain activity.
An isotope like carbon-11 has a short radioactive half-life of about 20 minutes, so the material must be injected quickly after creating the compound. Other isotopes have longer radioactive periods, some hours long.
The FDA grants research facilities special permission to create the drugs, but they must follow stringent rules and regulations.
Properly maintaining the radioactive source in lead-shielded containers and conducting lab work safely requires extensive monitoring and testing, because even though the isotopes emit low radioactivity, repeated exposures over time can cause illnesses or worse.
While the materials’ radioactivity is low, the state specifies dose limits for the public around such a facility.
A state report of an inspection in February 2012 states the university didn’t have monitors or methods to quantify the dose disseminated to the public from the Irvine Hall labs. The “lack of adequate quantitative radioactive release information” prevented inspectors from determining public dosage, the report says.
“It appears … likely the public dose limit was not exceeded,” the report states. UC Irvine officials told the state in a June 2013 letter that they would install appropriate monitors in this or any other radiation facility before operations resume.
Over the years, UC Irvine received millions of dollars in federal research grants associated with the Brain Imaging Center, including a $24-million award from the U.S. National Institutes of Health for five years through about 2010.
Orange County philanthropists also provided substantial donations and support, highlighted at social functions featuring Hollywood celebrities such as actor Patty Duke or the news media figures such as Jane Pauley.
But behind the scenes, records indicate, UC Irvine was struggling to deal with issues threatening patient and staff safety, which were reflected in state inspection reports as early as 2010.
Whistleblower Lawsuit Filed
In January 2012, records show, UC Irvine hired Dr. Carl Taswell to work one day a week at the center.
By April 2012, however, Taswell — a Harvard-educated psychiatrist who also has a research doctorate in imaging from Stanford University — was placed on leave and terminated.
In his 24-page lawsuit, Taswell describes how he and another researcher allegedly were blocked from trying to correct problems.
Along with UC Irvine and regents, those named in the lawsuit include Potkin; Jogeshwar Mukherjee, a researcher directing pharmaceutical preparation; Dr. Scott C. Goodwin, radiology department chairman; and Michael Arias, head of the whistleblower office.
Taswell declined comment, but his Agoura Hills attorney, Louis J. Cohen, issued a statement:
Dr. Taswell had the integrity to take action and did not ignore his duties as a physician. He promptly reported these patient, worker and community safety issues to his supervisors, and when they failed to act, to appropriate government agencies. Within a few weeks, he was fired.
A UC Irvine spokesman said the university had no comment on the lawsuit or its allegations.
The lawsuit also describes how the program came to a halt after UC Irvine’s hiring in January 2012 of a radiopharmaceutical specialist, Farhad Karimi, who has a research doctorate.
Shortly after coming aboard, the lawsuit says, Karimi declined to make the radioactive drugs under conditions described in Taswell’s lawsuit as “deplorable.”
With photographs, Karimi documented the purported unsanitary lab conditions, records say, reporting them to the FDA.
Karimi was discharged by UC Irvine within weeks, lost his U.S. visa, which was dependent on working at UC Irvine, and was forced to leave the country with his family.
Now somewhere in Europe, Karimi was unavailable for comment.
The lawsuit’s disturbing picture of the UC Irvine Brain Imaging Center follows similar problems at Columbia University in New York City, which shocked researchers nationwide.
In that case, human experiments were suspended at the highly touted Kreitchman PET Center for about nine months after a four-year FDA investigation found that researchers administered injections of radiopharmaceuticals with potentially dangerous levels of impurities.
Chester A. Matthis, whom Columbia engaged to write a report on its PET center problems, noted that the New York experience put staff at the approximately 50 PET facilities nationally on notice.
“Everyone knows the rules and knows they should abide by them,” Matthis said.
Yet at UC Irvine, state public health inspectors in 2010 also found safety problems similar to what was again uncovered in 2012.
In July 2010, only 10 days after the New York Times broke the story about the Columbia PET Center, California health department records show state officials conducted their first of three inspections of UC Irvine. State officials claimed the inspections then were routine.
On Aug. 25, 2010, the state health department issued UC Irvine two notices of violations for failure to document tests — one set to chart radiation exposure to research staff at the Brain Imaging Center and another set for public exposures on the Irvine campus.
For both violations, state records state, there was no evidence that UC Irvine’s Radiation Safety Committee — a required panel to monitor experiments involving radiation — had evaluated and approved the necessary exposure tests.
In an Oct. 1, 2010, letter, UC Irvine’s radiation safety officer, Rick Mannix, wrote the state a nine-page letter describing planned corrective actions.
These included monitoring air ducts to check radiation releases from Irvine Hall where the Brain Imaging Center is located; adding lead shielding for experimental drug manufacturing; and better charting of radiation exposure of research staff.
Reflecting earlier issues, Mannix’s letter noted that Radiation Safety Committee meeting records for November 2008 showed a Brain Imagine Center researcher, Min-Liang Pan, had received “very high radiation doses.”
But when the committee attempted to address the problem, Mukherjee, who was Pan's superior, delayed responses until February 2009, the letter states. This prompted the committee to order a suspension of Mukherjee’s experiments if an inspection of the Brain Imaging Center's lab wasn’t conducted promptly.
That inspection finally was held in April 2009, records say, with the committee working on corrections until August 2009.
Now with the UC Irvine human experiments halted, interviews and observations indicate that Mukherjee has started seeking a position at UC San Diego’s PET center.
On Oct. 24, Mukherjee gave a “special” lecture at UC San Diego’s La Jolla campus, which was attended by a Voice of OC reporter. After the lecture, Mukherjee met for dinner with three department heads for “a potential recruitment,” said Dr. William C. Bradley, chairman of UC San Diego's radiology department, who was at the dinner.
Bradley said in an interview he was unaware of the UC Irvine Brain Imaging Center issues involving Mukherjee. “We didn’t realize there was a problem up there,” said Bradley. “But I had a sense something wasn’t right.”
Mukherjee did not respond to repeated calls and emails from Voice of OC.
Taswell’s lawsuit goes into great detail regarding the conflicts over managing and controlling UC Irvine’s Brain Imaging Center experiments.
When UC Irvine hired Taswell, he was given the official title of “radioactive materials authorized user” -- making him responsible for quality and medical control of all aspects of all imaging procedures, the lawsuit states.
The lawsuit alleges that radiology chairman Goodwin told Taswell he was not to be “a rubber stamp” for research projects and “promised” to protect him from retaliation. Goodwin also said a full-time faculty position would be offered in the future, according to the lawsuit.
Media reports and public records show that center director Potkin was investigated repeatedly in the past.
For instance, in 2006 the Los Angeles Times wrote a long article describing how UC Irvine investigated Potkin three times dating to 1989 for alleged ethical and financial irregularities involving research projects and NIH grants. In the article, Potkin denied any impropriety.
No record of a public sanction against him could be found.
Five months before the LA Times article, the NIH had selected UC Irvine and Potkin as leaders of a $24-million NIH grant to develop computer tools to organize and analyze patient and research data from brain imaging centers nationally.
Once Taswell joined UC Irvine in 2012, the lawsuit alleges, he clashed quickly with Potkin over a new research project protocol, which Potkin wanted approved virtually overnight.
Then in late March 2012, Taswell participated in an inspection of the Brain Imaging Center labs along with top UC Irvine officials, such as the chairman of the radiation safety committee, the lawsuit says.
During the inspection, the lawsuit asserts, Mukherjee complained that team members “weren’t authorized to conduct said inspection.”
Afterwards, according to the lawsuit, top UC Irvine officials turned on Taswell, accusing him of “unauthorized entry” into the labs while with the inspection team.
Subsequently, Taswell was put on leave, then terminated in April 2012 after a grievance process that the lawsuit asserts was “shamelessly rigged against him.”
Taswell's attorney, Cohen, noted in his statement that “UCI has a well-documented history of retaliating against physicians and other health-care workers who have the courage and integrity to report serious patient safety concerns.”
For instance, last March UC Irvine paid $1.2 million to the federal government to settle a federal whistleblower lawsuit over alleged forging of anesthesia billing records.
Voice of OC correspondent Thy Vo contributed to this report.
Rex Dalton is a San Diego-based journalist who has worked for the San Diego Union-Tribune and the journal Nature. You can reach him directly at email@example.com.