Richard T. Johnson

Although transmissible spongiform encephalopathies (TSEs), which include mad cow disease, have been under investigation since the 1960s, there are still many important unanswered questions. The incubation period for variant Creutzfeldt-Jakob disease (vCJD)—the human form of mad cow disease—is unknown; the minimum dose of misfolded prion proteins needed to cause vCJD is unknown; and the likelihood that new, more easily transmitted prion strains will arise is unknown. Also, researchers still have not been able to determine whether consumption of deer or elk with chronic wasting disease (CWD)—prion disease in cervids—causes illness in humans.

Achieving breakthroughs on these questions will probably require increased funding and major structural changes in the U.S. research program, says Richard T. Johnson, professor of neurology, microbiology, and neuroscience at Johns Hopkins University School of Medicine. Johnson chaired the Institute of Medicine committee that wrote the report published in May on research needs for understanding TSEs (C&EN, May 31, 2004, page 21).

Although Johnson has done no laboratory work on TSEs, he has been tangentially involved with such research throughout most of his career and has written many review articles about prion diseases. In the late 1950s, when he worked at Walter Reed Army Institute of Research in Washington, D.C., he met D. Carleton Gajdusek, who later won the 1976 Nobel Prize in Physiology or Medicine for his work on kuru, a prion disease among the Fore tribespeople of the New Guinea highlands. “I first got involved in TSEs when I was in Papua New Guinea in 1964 and saw kuru,” Johnson says. At that time, scientists believed that kuru was caused by an unconventional virus. After Johnson went to Hopkins in 1969, there were joint meetings involving his lab and Gajdusek’s lab in Patuxent, Md. Johnson examined the first chimp that came down with kuru after Gajdusek had inoculated it with brain tissue from a kuru victim.

Because of his long-term interest in TSEs, Johnson has many ideas on how to improve the U.S. research program. Currently, the National Institutes of Health spends only about $25 million a year on prion disease research, in contrast to the $250 million that Europe spends. Three-quarters of U.S. funds go to just two labs, Nobel Laureate Stanley B. Prusiner’s lab at the University of California, San Francisco, and Rocky Mountain Laboratories in Hamilton, Mont., which is run by the National Institute of Allergy & Infectious Diseases. Both facilities do excellent work, Johnson says, but many more researchers need to be involved in the field.

In 2002, Congress gave the Department of Defense $42 million to study TSEs in hopes that the new money would attract more researchers to the field. But those funds did little to stimulate research. “It is very difficult to encourage workers to enter the field or to train people in the field because the facilities required and the type of work it is don’t fit well with the model for research funding we have in the U.S.,” Johnson notes.

To obtain a grant for research on TSEs, a scientist needs access to a lab where the work can be done. Most prion research requires expensive biological safety level II or level III facilities that can house large animals, Johnson says. Few universities have such facilities. University officials would expect the money for the facilities to come from grants. Another problem is that most prion work on animals requires many years before results can be obtained, he says.

Johnson stresses that it is especially important to do more research on CWD, which is rapidly spreading among deer and elk populations. “Colleagues in Europe say, ‘You are potentially sitting on a [CWD] time bomb and doing nothing about it,’” he says. He notes several reasons why the disease is worrisome: It is more infectious in the field than any of the other TSEs; deer can contract the disease merely from living in a paddock where a CWD-infected deer lived previously. Also, CWD can move across species barriers. When lab monkeys and mice are inoculated with brain tissue from CWD-infected deer, they become infected and die, Johnson says. Furthermore, hunters eat deer and elk, upscale restaurants serve their meat, and cattle share fields with them, he says.

Researchers at the Centers for Disease Control & Prevention assume that if CWD is transmissible to humans, it would cause vCJD. But Johnson says, “Actually, nobody has any idea what symptoms CWD might cause in humans. It might be burning sensations in elderly ladies’ feet. The only way we are going to find out is to increase autopsy rates in this country.” Autopsies, which are disappearing, should be done on all people with chronic neurological diseases, he says.

It would be really useful to do strain typing on the prions from any new cases of mad cow disease that show up in the U.S., Johnson says. Scientists need to know whether the U.S. prion strain is the same virulent strain that arose in England or if it is perhaps a milder form that arose spontaneously in the U.S., he says. It could be a strain that occurs intermittently and causes no disease in humans, he notes. That would be reassuring and help to restore confidence in American beef.