Neb. university delays BU tularemia probe

A federal investigation into how a supposedly harmless batch of tularemia bacteria at Boston University became contaminated with a lethal strain has been delayed by the reluctance of another university to provide samples needed in the probe.

A University of Nebraska scientist acknowledged in interviews last week that he held onto vials of tularemia even after the US Centers for Disease Control and Prevention requested them for its investigation into the tularemia infections of three BU scientists.

Dr. Steven Hinrichs, director of the University of Nebraska Center for Biosecurity in Omaha, said he delayed providing 20 vials of tularemia until he felt confident that the CDC would use what he regards as the premier laboratory method for analyzing the contents.

Hinrichs said a Feb. 11 letter from federal disease investigators sought samples of the dangerous type of tularemia from his lab. He provided the material for testing to the CDC only three weeks ago, according to both Hinrichs and a CDC spokeswoman.

''Obviously, it would be nice to have that all done now so we wouldn't still be waiting," said Dr. Alfred DeMaria, top disease tracker at the Massachusetts Department of Public Health, one of the agencies investigating the tularemia cases. ''Any delay means a delay in getting answers."

The University of Nebraska became a focus of the investigation because researchers from the school's Lincoln campus provided BU scientists with a sample of tularemia so they could begin their work last year on a vaccine against the bacterial illness, commonly known as rabbit fever.

The BU scientists believed they were working with a form of the bacteria genetically engineered to be safe for vaccine studies, and, in fact, scientists on Nebraska's Lincoln campus are permitted to study only that strain. But Hinrichs's lab in Omaha at University of Nebraska Medical Center is permitted to work with the dangerous variety of tularemia, which is covered by strict federal regulations because it is regarded as a potential agent of bioterrorism.

The CDC has declined to provide details of its investigation or to explain why it wants to examine the tularemia from Hinrichs's lab, but Hinrichs said CDC representatives told him ''that there was a link between Lincoln and UNMC."

The nature of that link, Hinrichs said, was not disclosed to him, but he said that samples of tularemia are not transported between the two campuses and that moving the lethal form from Omaha to Lincoln ''would have to invoke almost a nefarious approach."

Hinrichs emphasized that it was not his intent to impede the federal investigation.

''It's important for this study to be done in the right way, and when it's done the right way, we'll be able to find out what happened," Hinrichs said.

''What I'm determined to do is find the truth. If it is a problem that began here, then we will deal with it. Our belief is it is not."

The investigation into how the three BU researchers were exposed to a deadly strain of tularemia began in November, when their exposures were confirmed. Two of the scientists fell ill in May with flu-like symptoms, and the third became sick in September and spent a week in the hospital.

The failure after six months to figure out how the supposedly harmless tularemia became tainted with virulent germs has fueled the frustration at BU, a spokeswoman for the medical school said. And it has spawned concerns among public health authorities. Dr. Anita Barry, director of communicable disease control for the Boston Public Health Commission, said that until the source of the contaminated BU material is identified, tainted tularemia samples could exist in other labs.

''The question always comes up in my mind: Could other sites have a contaminated strain unknowingly?" Barry said. ''If there's some source of contamination out there that hasn't been identified, certainly the possibility is there could be more illness because researchers don't know that they have a contaminated strain."

The CDC is conducting the molecular equivalent of a criminal lineup, trying to determine whether the dangerous form of tularemia found in Boston is a genetic match to the reserves of tularemia in other labs.

A report from the Boston Public Health Commission said BU received a vial of tularemia from the University of Nebraska on April 15, 2004, and another from the University of Iowa on June 3, 2004.

After the tularemia infections were discovered, the CDC performed tests, which showed that the material from Iowa was the harmless form of tularemia. But the vial from Nebraska contained a mixture of the harmless and lethal strains.

The quest for disease investigators then became this: Where did the lethal strain come from?

To answer that, the CDC has analyzed dozens of tularemia samples supplied by BU, the Lincoln campus of the University of Nebraska, and other sources. Now that testing has expanded to include the lethal tularemia from Omaha.

When asked whether the delay in receiving material from Omaha had hindered the CDC investigation, agency spokeswoman Jennifer Morcone responded, ''It's important to remember there's no public health emergency, and we are doing a scientific and systematic analysis."

Both DeMaria and Barry described the CDC process of analyzing tularemia samples as painstaking. The federal disease investigators, DeMaria said, have also had to display diplomacy as they work with an assortment of government and academic entities.

''There are a lot of people involved who have a lot at stake here if they find out the source was questionable or somebody did something they shouldn't have done," he said.

According to the Boston Public Health Commission report, the CDC has been using a test method called pulsed-field gel electrophoresis to compare the DNA fingerprints of different samples.

Nebraska's Hinrichs said he prefers a technique called multilocus variable-number tandem repeat analysis, which provides a more-detailed genetic signature for individual samples of tularemia.

The difference between the two tests can be understood this way: They both start out looking at the forest. The first kind of test provides strong clues about whether the trees have the same number of branches. The second kind is designed to look at the branches and see whether they have the same number and type of leaves.

Hinrichs said he is confident the CDC will use the approach he prefers as well as other techniques.

''I believe they will do an impartial analysis," he said.

The investigation of the tularemia exposures continues as BU proceeds with plans to build a high-security lab on its South End medical campus where scientists would be capable of studying the world's deadliest pathogens, agents such as Ebola, anthrax, and plague.

Critics of the proposal to build that facility, known as a Biosafety Level-4 lab, said that the failure to pinpoint the source of the tularemia contamination further calls into question the wisdom of building the high-security lab amid a densely-populated urban neighborhood.

''Six months into a federal investigation, it's still not clear how these deadly pathogens found their way to BU's lab," said Philip Warburg, president of the Conservation Law Foundation, a leading opponent of the Level-4 lab.

''Should South End residents feel secure going forward with a new lab requiring the utmost in foolproof and tamper-proof safety precautions under these circumstances? We clearly need to proceed with real caution."

Stephen Smith can be reached at stsmith@globe.com.