Last month a special committee set up by the Food and Drug Administration (FDA) recommended that the Red Cross and other agencies refuse to accept blood donated by people who have visited England since 1980. This alarming recommendation was made because of fear that such blood might introduce a disorder known as “mad cow disease” into the US blood supply. What is going on here? Just what is the danger that is making the FDA sweat?
“Mad cow disease” is one of a peculiar group of fatal brain diseases that have fascinated scientists for decades. These diseases, transmissible from one individual to another, have the unusual property that it is years and often decades before the disease is detected in infected individuals. The brains of infected individuals develop numerous small cavities as nerve cells die, producing a marked spongy appearance. Central nervous system function is progressively degraded, until death eventually occurs. There is no cure. Given the jaw-breaking name “transmissible spongiform encephalopathies” (TSEs) by doctors, these diseases include scrapie in sheep, “mad cow” disease in cattle, and kuru and Creutzfeldt-Jacob disease in humans.
The search for the cause of TSEs has produced an unexpected and scary result. While most transmissible diseases are caused by viruses, bacteria and other microbes, TSEs are not! In the 1960s British researchers T. Alper and J. Griffith reported that infectious TSE preparations remained infectious even after being exposed to massive doses of radiation, doses that would destroy the DNA or RNA of any virus or microbe. They suggested that the infectious agent was a protein. Perhaps, they speculated, the TSE problem had started when a key brain protein made a mistake and folded itself up incorrectly. Tragically, this protein, when it encountered others of the same sort, was able to induce them to refold into this same mistaken shape. A wave of misfolding would relentlessly expand through the brain like a chain reaction. And, like a spreading rumor, any brain receiving a copy of the misfolded protein would experience the process anew. This heretical suggestion of an infectuous protein was not immediately accepted by the scientific community, as it violates what was thought to be a key tenant of biology, that only DNA or RNA transmit information from one generation to the next.
During the 1980s physician Stanley Prusiner, despite the scorn of much of the scientific community, amassed a body of experimental evidence that Alper and Griffith were right, and that the infectious agent in TSE preparations was a protein, which he named a prion. In 1997, Prusiner was awarded the Nobel prize for his pioneering work on prions. Many scientists are becoming worried that prions may be transmitting TSE diseases to humans. Specifically, they worry that prion-caused bovine spongiform encephalopathy (BSE), the brain disease of cows commonly known as mad cow disease, may infect humans and produce a similar fatal disorder called Creutzfeldt-Jacob disease (CJD). In March 1996, an outbreak of mad cow disease in Britain, with many thousands of cattle apparently affected, created widespread concern. The subsequent death of four dairy farmers from CJD has British scientists worried that prions may be able to pass from cows to people. The case for a connection between eating British beef and CJD is strong: tissue from the brains of the dead farmers and from BSE cows induce the same brain lesions in mice, while classic CJD produces quite different lesions — clearly the CJD that killed the dairy farmers was caused by the same agent that caused BSE. Thus there appears to be legitimate cause for caution. Because the incubation period for CJD can vary from 15 to 45 years, the number of people infected by eating BSE-contaminated meat in England may not become apparent for some time.
According to the Red Cross, the recommendation of the FDA committee to cease accepting blood donors who have visited England since 1980 (when BSE is thought to have started), if adopted, would reduce the pool of American blood donors by more than 10%, putting a real strain on a system already prone to shortages. Only last week, the Missouri Red Cross announced a serious short-fall in donations, down 1% from a year ago. Clearly we need to expand, not reduce, the pool of potential donors. On the other hand, the health cost of introducing prions into the American blood supply would be catastrophic. The FDA is expected to make a decision on its committee’s recommendation in the next few months. It should accept them.