Two years after he was found guilty of misconduct for using another laboratory's research, a leading scientist at Children's Hospital of Pittsburgh of UPMC is being investigated again by a high-level faculty committee.
The committee was appointed after Karen Norris, a longtime University of Pittsburgh immunology professor, complained that scientist Jay Kolls had failed to fully comply with the sanctions imposed on him in 2011 for misusing research from her lab to get federal grants and seek a patent for a vaccine against a dangerous lung infection known as pneumocystis.
The key work he was accused of misusing was done by a doctoral student, Heather Kling, who worked in Dr. Norris' lab. Dr. Kolls, a lung disease specialist, knew about her findings because he served on Dr. Kling's dissertation committee. He cited her monkey research in his original federal grant applications, and appears to have used it in the pending patent application.
The original case came to a head in September 2011, when Dr. Norris made her initial complaints at the same time Pitt officials were negotiating with Dr. Kolls to come back to Pittsburgh from Louisiana State University Health Sciences Center, where he had spent most of his career.
Dr. Kolls was being recruited to become director of the Richard King Mellon Foundation Institute for Pediatric Research at Children's, which was being funded with $23 million from the family charity.
Correspondences related to the investigation
- Sept. 2011: Letter from Karen Norris to Jerome Rosenberg
- Nov. 2011: Letter from Jerome Rosenberg to Karen Norris
- Nov. 2012: Letter from Karen Norris to University Senate Tenure and Academic Freedom Committee
- March 2013: Letter from TAFC to Karen Norris
- April 2013: Letter from Karen Norris to Provost Beeson
Instead of convening a full, independent inquiry at the time, Pitt officials quickly found him guilty of misconduct and ordered him to remove himself from two federal grants worth hundreds of thousands of dollars and to try to make Dr. Norris a co-inventor on his patent application.
Last year, Dr. Norris alleged that he had not complied with the penalties imposed on him by Arthur Levine, the Pitt medical school dean. Dr. Levine conceded that it was time for a full inquiry by a panel of professors with expertise in biological research, according to people familiar with the case. Panel members would not say last week how close they are to being finished, or what they would recommend.
Heather Kling's reaction
Dr. Kolls began serving on Dr. Kling's doctoral committee in 2006, when he was working at Pitt, and he continued to help oversee her work after he returned to Louisiana in 2008.
While working at LSU, he filed the research grants and patent application citing her work.
Dr. Kling, now a postdoctoral student in Dr. Norris' lab, said she feels "saddened by the blatant violation of trust that, as a graduate student, I placed in my thesis committee member and in the University of Pittsburgh."
"I continue to be exceedingly disappointed by the university's handling of this situation and the apparent lack of interest they have demonstrated in resolving this matter," she said, "and I feel betrayed by the lack of protection provided for research being conducted by graduate students at the university."
In an April 8 letter to Pitt Provost Patricia Beeson, obtained by the Post-Gazette, Dr. Norris voiced her own displeasure over Dr. Kling's treatment.
"Most importantly," she wrote, "I am requesting that your office acknowledge to the student involved that the university recognizes the gravity of this kind of scientific and academic misconduct ... The student has never received acknowledgement from Dr. Kolls that he has admitted to his misconduct or that the university has pursued corrective action."
Repeated attempts to reach Dr. Kolls for comment last week were unsuccessful.
In his original federal research grant application, Dr. Kolls cited results from Dr. Kling's monkey research that had not yet been published, and claimed that he was collaborating with the Norris lab on that work.
While the Norris lab had shared some biological material with the Kolls lab, there was no actual collaborative project between the two, according to sources familiar with the case.
The same monkey research is cited in the patent application -- and in that case, there is no indication it came from another lab.
Dr. Kolls and a fellow Children's researcher, Mingquan Zheng, are listed as co-inventors on the patent, which has been filed by LSU.
The two doctors wrote in the patent document that they had examined monkeys infected with the simian version of HIV, and had measured the animals' immune reactions to pneumocystis infections.
But those two researchers do not do monkey lab work on pneumocystis, people familiar with the case said, and the findings cited in the patent seem to be based on work by Dr. Kling.
The patent is crucial to the fate of a vaccine company started with one of the federal grants. MiniVax, based in New Orleans, is raising money to conduct animal experiments on a pneumocystis vaccine and has claimed to investors that its products have a potential market value of $1.4 billion.
The sanctions against Dr. Kolls were imposed in November 2011 by Dr. Levine, who is also Pitt's senior vice chancellor for the health sciences, according to a letter sent to Dr. Norris by Pitt's research integrity officer, Jerome Rosenberg.
The vice chancellor's actions comprised some of the milder sanctions available in such misconduct cases. Scientists found guilty of research misconduct under NIH rules can receive punishments ranging from letters of reprimand, all the way up to being banned from receiving federal grant money.
Dr. Kolls did step away from the basic research grant on pneumocystis, but it was not until last year that he started to separate himself from an official role at MiniVax.
While the company's website still lists him as an adviser, company board member Sandra Coufal said in an email that he had "recused himself" from that role last November. The firm's CEO, A. Ray Chaudhuri, said by email that he had removed Dr. Kolls' name from a recent grant renewal application after it inadvertently had been added.
Dr. Levine, Mr. Rosenberg and other Pitt officials said they could not talk about the case while an investigation was under way.
"Because even an allegation of research misconduct can damage the reputation of an investigator," said an official response emailed to the Post-Gazette, "and because not every dispute over data actually constitutes research misconduct within the federal definitions, the university does not comment on matters in progress."
LSU health sciences officials also declined to comment, and the National Institutes of Health would only say that it had removed Dr. Kolls from the federal grants and added Dr. Norris as an investigator on the research project.
Judd Shellito, the vice chairman of research at LSU Health Sciences Center and one of Dr. Kolls' mentors, who is now serving as a principal investigator on both federal grants, also declined comment. "No thank you," he wrote. "I do not want to speak with you about this."
Dr. Norris said she would only talk about her motivations for bringing charges. "I'm disappointed the University of Pittsburgh appears to have neglected its core academic mission by not holding some of its faculty to even the most basic standards of academic and scientific integrity and by failing to protect students from this kind of exploitation. This is a sad and unfortunate situation for the university and its students."
A tense time
Dr. Norris said that when she first raised questions about Dr. Kolls' research grants in August 2011, David Perlmutter, scientific director of Children's, met with her and asked her not to pursue the allegations because it would damage Dr. Kolls' career and endanger the Mellon research grant. She said she insisted on proceeding, and he eventually concurred.
Asked for comment on Dr. Norris' account of the conversation, Dr. Perlmutter declined. "I have been instructed by the university that I cannot say anything," he said. "I'm not making any comments. I've been told by the university that they are in the midst of investigating her issues."
Last year, Dr. Norris raised new complaints after discovering that Dr. Kolls' patent application materials had used some of the same research from her lab that he had cited in the previous research grants.
Michelle Booden, then a senior patenting and licensing manager at Pitt, began an analysis of the patent application that eventually involved a Baton Rouge patent attorney, John Runnels, who represented LSU.
In interviews conducted by Ms. Booden and Mr. Runnels, Dr. Norris and Dr. Kling repeated their contention that their research had been used without their consent, while Dr. Kolls said he had not used any of the Pittsburgh lab's work as the basis of his patent filing.
Dr. Norris then asked Mr. Rosenberg, the research integrity officer, to reopen the case in July 2012, saying that Dr. Kolls and Dr. Zheng made "a concerted effort to deceive the patent ... investigators and made several false and conflicting statements regarding their work on the development of the pneumocystis ... vaccine and the record of my contributions to this invention," according to a letter obtained by the Post-Gazette.
She also pushed for a separate academic inquiry into how Pitt had handled the initial investigation.
A University Senate committee looked into her allegations and, in March, said it had found several problems with the integrity office's conduct.
Among other things, the Tenure and Academic Freedom Committee questioned the apparent lack of any mechanism at Pitt to monitor Dr. Kolls' compliance with sanctions imposed on him. The panel also noted that Mr. Rosenberg did not report the accusations of misconduct to LSU "when fraud and plagiarism were implicated in both the NIH grant proposals and the patent applications initiated" at LSU.
It's also unclear whether Pitt notified federal officials of the misconduct finding against Dr. Kolls.
Fight over 100 amino acids
A Maryland native, Dr. Kolls, 54, got his M.D. at the University of Maryland in 1985 and has divided his career between New Orleans and Pittsburgh. A specialist in lung diseases, he has done research on pneumonia and cystic fibrosis, along with pneumocystis.
Dr. Norris got her Ph.D. in microbiology and immunology at Wright State University in Dayton, Ohio, in 1985, and has spent her entire research career at Pitt. A tenured professor in the Department of Immunology, she also has concentrated on lung diseases, with a special emphasis on pneumocystis.
At the heart of the scientific dispute is a 100 amino-acid stretch of a protein known as kexin.
Kexin sits on the outer coat of pneumocystis, and research has shown it evokes a strong immune response in the lungs. Because each species of mammals is infected by slightly different forms of pneumocystis, scientists have been eager to find a part of the fungus that is common to most species and would also be present in humans.
Dr. Kling, working with Dr. Norris, identified the 100-amino acid stretch of kexin, which was dubbed Kex1, and they showed that monkeys that had naturally strong antibody responses to that fragment were protected from pneumocystis infection, making it an exciting candidate for a vaccine.
In a paper published this year, she and Dr. Norris showed that a vaccine they made out of Kex1 strongly boosted antibody responses to pneumocystis in rhesus monkeys.
In 2007, Dr. Kling shared some of the Kex1 protein and genes with the Kolls lab. It is not known whether the Kolls lab researchers used that to help develop their own version of a kexin vaccine.
But in the 2010 patent application, Drs. Kolls and Zheng described how they had immunized mice using the whole version of kexin, but then looked for a smaller fragment that could do the job.
Immunology tests they carried out "showed that over 70 percent of the antibody response was directed against a region of [pneumocystis] kexin that is a highly conserved region across mouse, rat, monkey, and human pneumocystis. We call this 100-amino acid region 'mini-kexin,' " the scientists wrote.
In the 2012 patent analysis, Dr. Kolls reportedly told investigators that he and Dr. Zheng had come up with the idea of using the 100 amino-acid portion of kexin, and said they developed a vaccine "based on data in the public domain back in 2005."
MiniVax company documents say researchers there will first work with a mouse model of pneumocystis infection, but hope to contract with Tulane University to do monkey studies, which would provide stronger odds that any treatment would work in humans.
Dr. Coufal, the MiniVax treasurer, said the company had not done primate studies yet, because "we have not raised enough investor capital to conduct such trials currently."
The company has said it not only wants to develop a vaccine based on its mini-kexin, but to create an antibody treatment against pneumocystis aimed at the same target. Company documents prepared for investors estimate that there may be 125,000 Americans who could use such a treatment, for a potential market of $1 billion, and 720,000 people who would benefit from a vaccine, for a market of $400 million.
As the investigation continues, Dr. Kling said she hopes it leads to reforms.
"These events indicate that the School of Medicine has failed in its own stated mission of commitment to the 'highest professional and ethical standards' and underscore the need for a change in policy that will prevent further exploitation of students and restore confidence in the integrity of the academic system."
"Our whole research system is based on honesty and integrity," Dr. Norris added, "and that's what was lacking here."
Mark Roth: email@example.com, 412-263-1130 and on Twitter: @markomar. Bill Schackner: firstname.lastname@example.org, 412-263-1977 and on Twitter: @BschacknerPG. First Published May 26, 2013 4:00 AM