Ten deaths that may tell a shocking tale

 作者:年韭嫔     |      日期:2019-02-28 01:15:00
By Stephanie Pain DEEP in the Berkshire countryside, sealed off from the outside world, is a prion factory. Unable to get enough prions from natural sources, researchers at the Institute of Animal Health in Compton are making their own, using genetically engineered bacteria. They hope that their studies of the structure of these lethal proteins will provide the key to how they cause such devastating diseases as BSE and Creutzfeldt-Jakob disease. In the early 1980s, the manufacturers of high-protein animal feeds had prion factories of their own, in the form of rendering plants used to turn sheep carcasses into cattle-cake. Unfortunately, some of those sheep suffered from the prion disease scrapie, and the rendering plants turned out enough prions to start a BSE epidemic that has killed 158 000 British cattle. Now it seems that BSE may have killed 10 young people, who probably acquired the disease after eating beef in the middle to late 1980s. The 10 victims ostensibly died from CJD. But the strangeness of their symptoms and the pattern of damage to their brains has convinced the government’s scientific advisers that they may be the first human victims of BSE. CJD afflicts one in a million people each year. Its incubation period is normally decades, so almost everyone affected is elderly: the average age of victims is around 63. The 10 young victims, aged from 18 to 41, have an average Unlike older sufferers, whose first symptoms tend to be forgetfulness and odd behaviour, the younger victims suffered from depression and anxiety. Also, the disease progressed unusually slowly, taking on average 13 months rather than the usual six to kill. But the clincher, which convinced Rob Will and his colleagues at the CJD Surveillance Unit in Edinburgh that these might be the first human cases of BSE, was the damage in the victims’ brains. In all the spongiform diseases, protein fibrils accumulate in the brain. Here there were many more of them, forming larger very distinctive masses of protein. The victims share no common genetic predisposition to CJD, nor had any undergone brain surgery or treatment with contaminated growth hormone, which might have put them at risk. Having eliminated other likely causes, Will and his colleagues decided it was possible that these were the first cases of BSE in humans. They immediately reported their fears to the government’s Spongiform Encephalopathy Advisory Committee. “There was no proof. But something was going on that was common to them. The simplest hypothesis was that they had all been exposed to BSE,” says one member of SEAC. It should be possible to show whether the new “strain” of CJD is human BSE. Scrapie exists in many strains, each of which probably originated in a different breed of sheep. They are thought to be caused by variants of the prion protein with subtly different three-dimensional structures. Each strain has recognisable characteristics in the time it takes to cause disease and the pattern of damage Researchers at the Neuropathogenesis Unit in Edinburgh, part of the Institute of Animal Health, can tell which strain of scrapie is at work by infecting a panel of five breeds of mice. The animals’ responses to infection and the pattern of holes and tangled proteins in the brain give a “fingerprint” for the Unlike scrapie, BSE is remarkably consistent. No matter which herd of cows the sample comes from, the end result is almost identical. So too is the picture that emerges when other species: sheep, goats and pigs, are infected experimentally. Chris Bostock, head of molecular biology at the IAH in Compton, speculates that the reason why BSE has such an unvarying fingerprint is that it originated from just one highly resilient scrapie strain that survived the “This suggests that instead of looking to see if BSE can transmit to man, you can ask has BSE transmitted to man?” says Bostock. By taking samples from the brain tissue of victims of CJD who might have been exposed to BSE, the Edinburgh scientists can test it on their panel of mice and say whether the disease is The Edinburgh team has begun experiments to compare the strain fingerprints of two farmers who died from CJD with those of two victims who had never been exposed to BSE in their jobs and two CJD sufferers who died before the BSE epidemic began. This will be extended to include tissue from some of the young victims. The first results are not expected for another nine months. But even this information will not help to predict whether Britain faces a large epidemic of human BSE. No one knows how many people may have been exposed to the prions, nor how big a dose is needed to cause the disease. Speculation on the scale of the coming epidemic ranges from a few score to half the “Maybe we are seeing the beginning of an epidemic,” says one member of SEAC. “If it is BSE in origin,