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Primate studies to focus on CWD

Researchers trying to find out if humans can catch disease plaguing deer, elk populations

By Lou Kilzer, News Staff Writer
June 29, 2002

The race is on to find out whether a fatal brain disease in deer and elk poses a risk to human venison eaters.

"That's what everybody is trying to find out," said Dr. Pierluigi Gambetti, head of a national team studying the occurrence of the deadly protein disease.

Perhaps most significantly, a National Institutes of Health laboratory in Montana is planning to experiment with primates to try to determine human susceptibility to chronic wasting disease.

"Primate research is the most direct way to find out if people are susceptible," said NIH research scientist Richard Race. "It's the species that's most closely related from an evolutionary point of view to people. You cannot inoculate humans on purpose, so the next best thing is some kind of a non-human primate."

But even with the groundbreaking research, Race said, answers are unlikely to come anytime soon. The process could take years, he said.

Meanwhile, Gambetti's group and others are gearing up for studies of genetically manipulated mice to see if they can be infected with chronic wasting disease.

"We don't know whether it can be transmitted to humans and if it is transmitted, what it's going to look like," said Gambetti.

There are no proven cases of CWD infecting humans, but concern has intensified as the disease has spread from its endemic areas in Colorado and Wyoming to several other states and two Canadian provinces.

There have been several cases reported in which human venison eaters have contracted Creutzfeldt-Jakob disease (CJD), which, like CWD, is a transmissible spongiform encephalopathy (TSE), but one that occurs naturally in humans.

Gambetti said that these cases seem to fit into known subtypes of CJD, but he added that the assumption that human cases from deer or elk would look different upon microscopic examination than ordinary CJD is just that -- an assumption.

Most scientists believe all TSEs -- CWD, CJD and mad cow disease in cattle -- are all caused by a mutant protein called a prion.

Most scientists believe there is a strong barrier preventing prions from one species from infecting another. But 131 European human eaters of beef have contracted a variant of CJD caused by eating cattle suffering from mad cow disease, or bovine spongiform encephalopathy (BSE).

That has sparked concern that other spongiform encephalopathies, including CWD, could jump to humans or livestock.

Some mice experiments already under way have not detected human susceptibility, said Patrick Bosque, a Denver neurologist who conducted some of the research in the San Francisco laboratory of Nobel laureate Stanley Prusiner.

Bosque said those mice have been manipulated to contain a human gene that produces human protein. After inoculation with CWD, the protein has not changed to the deadly mutant prion form after more than 600 days.

However, Bosque said the mice model in the experiment might be flawed. A control group of mice was simultaneously injected with mad cow prions directly into their brains. Those mice also did not show susceptibility, even though it is known that humans are in fact vulnerable to mad cow.

That raises red flags about the findings, Bosque said.

More studies with more mice are necessary, most agree.

"Not many people have done much study on a molecular basis in terms of what the migration pattern would be," if CWD crossed to humans, said Dr. Shu Chen, the protein expert at Gambetti's lab, the National Prion Disease Pathology Surveillance Center.

Of human susceptibility, Chen echoed a familiar refrain in prion research: "The problem is that nobody knows."

Using primates to search for answers is a costly and potentially controversial step, acknowledged Bruce Chesebro, head of the laboratory of persistent viral diseases at the NIH facility that will conduct the research.

Race, the chief scientist involved, knows the pitfalls.

"No matter what the outcome, there are going to be people who fault how it was done," he said. "One of the reservations we have is that there are no right answers. Whatever you give the primates some people are going to say you gave them too much. Some people will say you didn't give them enough."

And there's a political aspect, as well, Race acknowledged.

"If word gets out that it's actually being done, you get all the animal protest groups and people like that bugging you all the time," he said. "One thing about it if we do it here (at the lab in Hamilton, Mont.) is that security is really tight."

Race is the lead researcher on a continuing mice experiment that has shaken the prion field.

In it, hamster prions were injected into mice, which then showed no outward or microscopic sign of the disease. However, when brain matter from those mice is injected into another set of mice and hamsters, they become sick from mutant prions and die.

No one knows how these "sleeper carriers" stay healthy, or why subsequent test animals become sick. But it raises the concern that if CWD infected other animals, it is possible that at least the first generation of the infected species might not get sick.

"It used to be thought the hamster (prion disease) didn't go into mice. There was a species barrier," said Anne Raines, a fellow scientist at Rocky Mountain Laboratory. "And now we have some of those mice going down in a short amount of time; 100 days or so."

"It's such a cool study," said Raines. "Most people wouldn't do it, because if you're a post-doc or a young investigator it's really hard to take three or four years to get results," she said, noting that Race is nearing retirement.

"But (Race) is the sort of person that can dork around and do something like this and not be under pressure. We're up to fourth or fifth pass on these guys (mice) now. It's really interesting what we're finding. It (the prion disease) appears to be possibly sorting out into different strains."

Race said that while he might begin the primate research, he would leave it to others to finish it.

"There will be somebody here to see it through," Race said.

Contact Lou Kilzer at (303) 892-2644 or kilzerl@RockyMountainNews.com.