A University of Wisconsin-Madison School of Veterinary Medicine professor was sanctioned after officials determined unauthorized recombinant DNA research with select agents had been conducted in the laboratory he oversaw.
Following a series of investigations spanning more than a year and a half, the university concluded Dr. Gary A. Splitter either knew of, or participated in, restricted research encoding antibiotic-resistant genes into Brucella melitensis, a bacterium the government considers a serious threat to human and animal health.
University Provost Paul M. DeLuca Jr. wrote Dr. Splitter on Jan. 29, informing the professor of animal health and biomedical sciences that his laboratory and research privileges had been revoked for five years. The suspension was effective retroactive to Dec. 12, 2008, when Dr. Splitter's access to his biosafety level 3 laboratory was restricted.
Dr. Splitter's misconduct resulted in the University of Wisconsin-Madison paying a $40,000 fine to the Department of Health and Human Services to settle alleged violations of select agents regulations.
A member of the UW faculty for nearly 32 years, Dr. Splitter can continue teaching and participating in research but in limited ways, such as analyzing data and reviewing and writing papers.
The existence of the modified bacterial strains came to light during a routine inspection of UW's select agents program by the Centers for Disease Control and Prevention in August 2007.
William S. Mellon, PhD, associate dean for research policy, said Dr. Splitter's laboratory had produced, without university or government approval, strains of Brucella encoded with antibiotic-resistant markers for spectinomycin and trimethoprim.
By January 2008 the university had closed the laboratory, an investigation of Dr. Splitter had commenced, and the bacteria were destroyed.
"The concern is not a biosecurity issue but a biosafety issue," Dr. Mellon explained. "If someone acquires a laboratory infection, if that happens with a recombinant agent with an antibiotic resistance, you compromise treatment options. For us, that's pretty serious, especially with select agents."
"It's imperative that we play by all the rules and regulations; otherwise, your entire program is at risk," he added.
Human cases of brucellosis may involve symptoms similar to those of severe flu that can persist for several weeks or months. Brucellosis is rarely fatal in people, yet the government considers it a serious disease. No one at the UW laboratory was infected with the altered strains.
Throughout his career, Dr. Splitter has extensively researched Brucella, and his articles have appeared in such publications as the Journal of Bacteriology, Science, and the Journal of Biological Chemistry.
Dr. Splitter said he knew a graduate student had introduced a spectinomycin-resistant gene to the bacteria, and another graduate student and a postdoctoral researcher were working with the strain. But because the antimicrobial isn't used in the treatment of brucellosis, the research is not restricted research, according to Dr. Splitter.
It wasn't until the CDC inspection that he learned the gene used to create the spectinomycin resistance also confers cross-resistance to streptomycin, which is used to treat brucellosis. "Once we did find out, I reported it to university officials, and I fully cooperated with every investigation, and I destroyed (the bacteria). I felt like I was doing the right thing," he said.
Dr. Splitter faulted the university's Institutional Biosafety Committee protocol policy for not requiring details about every recombinant DNA construct. "The university wasn't asking for that (information). They should have been," he said.
As for the trimethoprim-resistant Brucella, Dr. Splitter says a postdoctoral researcher who is no longer at the university created the strain, which has been destroyed.
In his letter, the provost said Dr. Splitter's explanation "lacked credibility." Even if it were a case of freelancing students, the university maintains it was Dr. Splitter's responsibility to know what was happening in his laboratory, especially with research involving select agents.
"If you were to ask me do I know every experiment that every graduate student, postdoctorate, and technician who works with me is doing, probably not. But I can tell you if we're doing select agent work I would. That's the difference," Dr. Mellon said.
The grad students and postdoctoral researcher were interviewed, but university officials found them not to be at fault, according to Dr. Mellon.
The university has since required principal investigators participating in UW's select agents program to attend meetings reviewing biosafety protocols. "We certainly did a fair bit of education," Dr. Mellon said.
Dr. Splitter chose not to appeal the provost's decision, citing the expenses associated with such an effort.