Just over a year ago, Edinburgh neuroscientists proposed that a new variant form of Creutzfeldt-Jacob disease (CJD) might be caused by the ingestion of beef products, which had been previously infected with bovine spongiform encephalopathy (BSE). An international crisis was followed by a collapse in consumer confidence in meat products. Farming, our major national industry, was threatened with ruin. Scientists in London have shown that there are striking similarities between the infective agent, or prion, that causes the new variant form of CJD and the prion which causes BSE, a piece of evidence which on the surface would appear to strengthen the link between the two conditions.
However, last month at the annual meeting of the American Association of Neuropathologists in Pittsburgh, evidence was presented to show that although the prions in new variant CJD and BSE are similar, they are also similar to the scrapie prion. Scrapie is a devastating neurological illness of sheep which is virtually identical to CJD and BSE and has been present in sheep for hundreds of years. What can one make of this new evidence? Is it simply confirmation of the fact that BSE was introduced into cattle by feeding them bone meal contaminated with scrapie-infected brain tissue? Alternatively, does this evidence imply that we cannot tell whether the new variant form of CJD was caused by eating meat products contaminated by BSE or scrapie? Crucial to this scientific investigation is acceptance of the prion as the sole infective agent responsible for various forms of CJD and its animal equivalents. Briefly, the prion protein, which is normally present in humans, primates and other animal forms, undergoes a change in shape. This altered protein then binds to the normal prion protein and through poorly understood mechanisms causes nerve cell injury and death.
Sceptics of the prion hypothesis refuse to accept that a protein can account for the unique ability of these diseases to transmit across different species. While not dismissing some role for the prion protein, they suggest, without much scientific support, that there must be a virus wrapped up in the prion protein. They also highlight the fact that it is difficult if not impossible to explain the occurrence of many different scrapie strains on the basis of a change in protein shape. The intensity with which this scientific debate is conducted is brilliantly described by Richard Rhodes, winner of the 1988 Pulitzer Prize for his account of the making of the atomic bomb. Deadly Feasts is a gripping and sometimes terrifying account of the history of CJD research. Beginning in Papua, New Guinea, Rhodes details the efforts made by many scientists, but particularly by Carleton Gajdusek and Clarence Gibbs, to show that Kuru, an endemic disease in the Fore tribe similar to CJD, was related to cannibalism.
The descriptions of table-top autopsies on Kuru patients and the injection of Kuru brain tissue into chimpanzees is riveting and borders on the macabre. It is easy to understand the excitement felt by the researchers when Georgette, a five-year-old chimp who had received an injection of Kuru brain extract into her own brain began to show behavioural and other clinical signs similar to the Kuru patients. Five months later Georgette's brain was removed and sent to London where Elizabeth Beck, a neuropathologist, confirmed that the changes in the brain were indistinguishable from Kuru. Following the confirmation of the infective nature of Kuru and later of CJD, the search for the infective agent began.
Early in the course of these experiments it became clear that the causative agent was unconventional and that it did not behave like an ordinary virus. Throughout the late Seventies and early Eighties, the two key players in the chase were Patricia Merz in New York and Stanley Prusiner in San Francisco. I shall never forget the excitement as I watched and listened as Merz demonstrated magnified images of a tiny fibrillary structure which she had found in scrapie brains. These scrapie fibrils were capable of transmitting the disease to other animals.
Later, and despite much hostility to Merz, Prusiner and others showed that the fibrils were composed of protein. A vast amount of work was carried out in the late Eighties and early Nineties to determine the composition and function of the scrapie-associated protein. Prusiner coined the term "prion" and set about convincing the world that the prion protein is the sole agent responsible for CJD as well as the various forms in other animals. The concept of an infective protein is unique in biology, and acceptance of this novel concept poses difficulties for many scientists.
Brooking no opposition to his views, Prusiner has attracted considerable hostility from other investigators in the field. Rhodes portrays the personalities behind the research with startling insights. Having won a Nobel prize for his work on Kuru and CJD, Gajdusek recently spent time in jail following allegations of child abuse. It is ironic that the allegations should have been made by one of the many young people from New Guinea brought to the US by Gajdusek for further education.
Perhaps this amazing story would have been of little interest to the public had it not been for the medical disasters associated with CJD. The accidental inoculation of several children with CJD-contaminated growth hormone and their subsequent death raised the profile of this rare disease in the public mind. Last year's demonstration of a new form of CJD and its possible relationship to ingestion of contaminated beef changed forever our approach to food and its production.
This is a great detective story, superbly written by a master storyteller.
Michael A. Farrell is Consultant Neuropathologist at Beaumont Hospital, Dublin Scrapie sufferers: sheep have carried BSE-like illnesses for hundreds of years