MILWAUKEE – In a California laboratory, “humanized” brains of more than 100 mice that were injected with chronic wasting disease lie frozen, waiting for the second part of an experiment that could help answer a burning question.
Can people get sick by eating deer infected with chronic wasting disease?
With the start of the second deer-hunting season since chronic wasting disease was discovered in Wisconsin, the jury is still out.
“We probably are exactly in the same position we were a year ago,” said Richard Olds, professor and chairman of medicine at the Medical College of Wisconsin.
A series of obstacles could cause that quest to go on for years, or even decades, researchers said.
“This will be an open issue for at least a decade,” said Olds, an infectious disease expert. “In fact, if it is less than that, it will be really bad news.”
As the result of an extensive testing program based on last year’s hunt, hunters at least know that the disease appears to be restricted to the so-called eradication zone centered near Mount Horeb in the southwestern part of Wisconsin, and a smaller area in southern Rock County, as well as a few game farms.
At the moment, scientists don’t know how deer get the disease, let alone whether people can.
For years, the study of so-called transmissible spongiform encephalopathies, or TSEs, had been a somewhat obscure branch of science that straddled the fields of veterinary and human medicine.
TSE diseases include chronic wasting disease in deer and Creutzfeldt-Jakob disease, a rare, incurable neurological disorder, in people.
Both diseases, as well as all other TSEs, are believed to be caused by an unusual infectious agent known as a prion, a type of rogue protein that has no genetic material and is very difficult to destroy. The rogue prions attack normal prion proteins in the human brain.
Research into TSEs accelerated after the mad cow outbreak in Great Britain in the 1980s. Initially, British government officials offered assurances that people were not susceptible to the disease, only to discover later that humans could get a version of mad cow disease, called variant Creutzfeldt-Jakob disease.
At last count, 143 people have died of variant Creutzfeldt-Jakob in Great Britain and an additional 10 outside the country.
In the United States, a new sense of urgency was brought to TSE research after chronic wasting disease was found in Wisconsin, the first time it was seen in wild deer east of the Mississippi River.
Since that discovery in February 2002, there has been little new scientific research on the risk facing people.
Researchers and public health officials have only a couple of tools for unraveling that issue, and both could take years to provide real answers.
Since experiments can’t be done on people, researchers have turned to genetically engineered mice.
These mice have been engineered so their brain cells produce the same prion protein that people do. This protein is a complex chain of amino acids that is found in nearly all mammals.
It is believed that prions cause normal prion proteins to become misshapen, resulting in clumps of protein forming in the brain and the death of brain cells.
There are no cures for prion diseases.
Scientists can inject brain tissue from infected deer into the brains of humanized mice and watch for neurological symptoms. Since laboratory mice live about two years, such experiments can be time-consuming.
But even if the mice don’t develop symptoms, it still would not answer the question of whether humans are at risk, because prion infections can incubate in people for years or decades before producing symptoms.
At least a couple of research groups, including scientists at the University of Wisconsin-Madison, say they are planning to do such experiments.
Test tube research by scientists at the National Institutes of Health in 2000 showed that while there is a so-called species barrier between deer and people, chronic wasting disease prions were able to convert normal human prion protein to the abnormal, diseased form. And they did so at about the same rate as mad cow disease.
Patrick Bosque, an assistant professor of neurology at the University of Colorado Denver Health Hospital, said it could take years to prove whether people are at risk.
Until then, he said, it’s reasonable to assume that if enough people are exposed to the disease that, over time, at least a small number will get sick.
“It is clear more needs to be known about the risk of transmission of CWD to humans,” Bosque said. “Statements to the effect, ‘There is no evidence that CWD can be transmitted to humans,’ are deceptive.”
At the same time lab experiments are being planned in humanized mice, public health officials are increasing their surveillance of unusual neurological disease in people to look for any clusters or individual deaths in deer hunters or people who ate venison.
“You still need to find that human case,” said Ermias Belay, a medical epidemiologist in the Creutzfeldt-Jakob surveillance program at the U.S. Centers for Disease Control and Prevention in Atlanta.
But that could take many years, he said. Such cases might show up as Creutzfeldt-Jakob disease, a disorder that is believed to occur in one in 1 million people per year.
“You will need millions and millions of people to be exposed before you see the human cases,” he said.
The Wisconsin Division of Public Health began such a tracking program earlier this year.
Neurologists and other hospital personnel around the state have been asked to voluntarily report unusual dementia cases, said Jim Kazmierczak, state public health veterinarian.
Such cases include dementias in people younger than 55 or rapidly progressing dementias accompanied by other symptoms.
When those patients die, an autopsy will be requested of the family. They also will be asked about various risk factors such as wild game consumption, a family history of Creutzfeldt-Jakob disease and whether the person ever lived in Great Britain.