-Caveat Lector- From http://www.iht.com/cgi-bin/generic.cgi?template=articleprint.tmplh&ArticleId=3596 }}>Begin Copyright © 2000 The International Herald Tribune | www.iht.com Untangling the Deadly 'Mad Cow' Mystery Barry James International Herald Tribune Thursday, December 7, 2000 PARIS Nobody knows how it started. Nobody knows how it will end. Nobody knows how many people eventually will die from it. Those are among the frightening mysteries scientists are discovering about "mad cow" disease, or BSE, the bovine form of transmissible spongiform encephalopathy. The disease can arise out of nowhere and lie dormant for years, which the official British BSE Inquiry believes is how it started in England. Perhaps only one cow spontaneously developed the disease at first. To become an epidemic it needed an amplifier, which in Britain was the practice of feeding grazing animals the ground- up remains of others of their species. In Europe, 91 people are known to have contracted variant Creutzfeldt Jakob disease, the fatal neurodegenerative affliction that humans can develop when exposed to infected meat. Creutzfeldt Jakob disease, which leads to dementia and eventually leaves the brain pitted with holes and resembling a sponge, was first identified independently by two German doctors in the 1920s, but until recently it was a condition of the elderly. Variant Creutzfeldt-Jakob disease also attacks younger people, some of them in their teens. The human toll might seem small when compared with diseases like malaria, which kills millions of people every year. But the prospect of turning loose a stealthy, deadly and largely unknown pathogen is what most concerns scientists across Europe. The mad cow scare has touched off a panicky reaction against eating beef, but the worrisome fact is that many people already may be infected, perhaps because proteins known as prions that had somehow become aberrant were lurking in their baby food or hamburger many years ago. The danger to humanity, scientists say, is that the general level of potential infection will rise, making it easier for the disease to emerge in future generations. This threat is illustrated by the speed at which bovine spongiform encephalopathy amplified among cattle in Britain in just a few years. There have now been more than 180,000 cases, with many others doubtlessly undiscovered among the 4.8 million cows culled and destroyed sinc e 1996 in an attempt to check the disease. An article in the science journal Nature estimated that 975,000 infected cows entered the food supply. Here is a chilling catalogue, drawn from two dozen interviews with experts and a review of scores of scientific documents, including Britain's recent 16-volume official BSE report, which illustrates why scientists are so concerned about BSE and related spongiform diseases that can affect most species of mammals and birds: •The pathogen that wipes out memory, personality and physical functions is extraordinarily tenacious. It resists heat, alcohol, boiling, ultraviolet light and ionizing radiation. Surgical instruments that come in contact with it can remain contaminated after normal sterilization procedures, and researchers don body protection before handling it. The pathogen can survive years of being buried in the soil, which is worrisome given that cattle remains often end up in landfills. Iceland in the 1950s slaughtered all its sheep to eliminate a related disease called scra pie. When it brought in healthy animals, scrapie soon reappeared. Some scientists believe that scrapie can mask low levels of BSE in sheep. •While they take time to emerge, perhaps over many decades in humans, the spongiform diseases are highly infectious. According to British scientists, a cow can get BSE by eating one gram of infected material - a speck the size of a peppercorn - from another cow. Even a minute trace of the material in meat and bone meal, the protein supplement produced from rendered animal remains, can infect a cow. The European Union's Standing Scientific Committee says that "the minimal infective dose considered to be valid for animals should also be applied for humans." Nobody knows what a minimal dose is, but British scientists d iscovered that a piece of wire that had been in contact with the pathogen for five minutes became as infectious as a solution made from infected brain. •Although the spongiform diseases are most infectious among members of the same species, they can jump the barrier to other species with varying levels of ease. Much has still to be learned about this species barrier, par ticularly so far as humans are concerned. Scrapie, for example, is believed not to infect humans. But in the United States, doctors identified several cases of variant Creutzfeldt Jakob disease among people who had eaten squirrel brains, and scientists warn that a spongiform encephalopathy called chronic wasting disease, found among deer and elk in the United States, is another potential threat to humans. Once the pathogen has adapted to a new species, it can infect other members of that species with a much lower dose. In zoos, the pathogen has caused an outbreak of spongiform diseases among primates, big cats, antelope an d other species, through the feeding of infected material. One study last year identified 82 cases in zoos. Bovine spongiform encephalopathy can be experimentally provoked in sheep, and domestic cats have acquired a simil ar encephalopathy from pet food. A 12-year old lion in the Newquay zoo in England was put down recently and found to be suffering from a form of transmissible encephalopathy. •The spongiform encephalopathies are surreptitious. An animal can harbor a spongiform disease and show no symptoms. Mice infected with hamster prions remain apparently healthy throughout their normal life span, but in fac t become highly infectious. Cattle are believed to be infectious at an early stage of incubation as the disease spreads through the central nervous system toward the brain, the most lethal tissue of all. Because the incub ation period in cows is thought to be longer than three years, the European Union this week decided to destroy cattle for market older than 30 months unless tested after slaughter and found to be free of BSE. The possibility that an animal can be infectious and show no symptoms raises the question whether people can as well. Scientists fear, for example, that a patient with undetected Creutzfeldt-Jakob disease who was undergoi ng surgery treatment for another disease might pass it along through surgical instruments. Since nobody knows the average incubation period in man, blood transfusion services in several countries, including the United Sta tes and Canada, are turning away donors who have lived in Britain although it is not certain that the defective prions can be passed on through blood. When the mad cow epidemic emerged in Britain in the 1980s, Stanley Prusiner, a U.S. neurologist and Nobel laureate, had already published his findings that the spongy condition of victims' brains was caused by "proteinace ous infectious particles," or prions. Proteins are the body's primary component and the basis of all enzyme reactions. As they are produced, they fold or coil three-dimensionally. The agent that causes spongiform disease is a protein that has folded wrongly, and which is able to pass this defect to normal proteins. Because the defective prions resist breakdown by enzymes, they build up within nerve cells and eventually the brain. The Prion Principle It is as though bricks told an architect how to build a house. Kurt Vonnegut described the prion principle in his novel "Cat's Cradle," in which a crystal of Ice-IX "taught the atoms the novel way in which to stack, lock and crystallize" until the oceans turned to ice. Unlike viruses, proteins contain no genetic material and therefore provoke no immune response. This is why it is so difficult to detect prion disease in a living being. A brain or tonsil biopsy might find Creutzfeldt-Jako b disease in a human, for example, but only if doctors examine an infected part. The defective proteins survive the rendering process that turns an animal's carcass into industrial fats and gelatin on the one hand, and meat and bone meal on the other. The meal is an effective and cheap protein that he lps animals grow and produce milk. When it became apparent that turning herbivores into carnivores was the likely cause of BSE, Britain forbade feeding ruminant meat and bone meal to cattle in 1988, but continued to expor t the material, thus spreading the disease to other countries. Scientists consider the inexpensive meat that comes from old dairy cows to be the most dangerous. It is pooled in beef patties, meat pies and pasta fillings; meat from as many as 60 animals may go into a hamburger mix. So me of the cheapest meat is stripped by machines and high-pressure jets from the bone, which is likely to be highly infectious in a sick cow. Each cow provides about seven kilograms (15 pounds) of machine-recovered meat th at is incorporated into five- to seven-ton batches of material. The EU's standing scientific committee estimated that each batch contains meat from about 1,000 animals, any one of which could infect the whole, and expose as many as 400,000 persons to the agent. Even the most dedicated vegetarian cannot avoid cattle products, which enter a vast range of goods from cigarette filters to soap. Tallow made from animal fat is used in everyday objects from carpets to television sets. I n general, only between one-third and a half of the animal is eaten. "The real market is in the by-products," said Paola Colombo, an EU Commission official. Ballanchine Was a Victim "Cosmetics, pharmaceuticals, Gucci handbags - that's animal waste." People daub their faces with anti-aging creams made from lightly processed bovine materials, an undefined danger indeed, but the choreographer George Bal lanchine died of Creutzfeldt-Jakob disease after using a bovine glandular product to preserve his youthful looks. The first French victim of variant Creutzfeldt-Jakob disease was a body-builder who used a muscle-boosting preparation of the kind still sold virtually unregulated in health food stores in the United States. One contains "freeze dried bovine brain, spleen, pituitary glands and eye tissue," said Michael Hansen, a microbiologist with the U.S. Consumers' Union. "It's almost a cow in a pill." Questionable cattle products have gone into baby food, pet chow, beauty preparations and vaccines. Only last month, Britain withdrew supplies of polio vaccine after discovering that they were cultivated from British bovin e serum produced when mad cow disease was at its height. Eleven million children and travelers have received the oral vaccine. Vaccines against measles, mumps, rubella, diphtheria and whooping cough also were made from Br itish-sourced bovine material until at least 1993. The government said the risk of contracting variant Creutzfeldt-Jakob disease from vaccine was "incalculably small," but this is not what was said by the author of the first major British mad cow investigation, Sir Richar d Southwood. He warned in an internal memorandum that the danger of infection from vaccines was "moderately high." He recommended that the removal of bovine material from vaccines should be a priority area for action. If the number of people who have been exposed to and perhaps even infected by prions is unknown and unknowable, the number of people likely to die will become known only with time. The victims will suffer from insomnia, m emory loss, depression, anxiety, withdrawal and fearfulness, and eventually loss of coordination, incontinence and blindness. Estimates of eventual deaths from Creutzfeldt-Jakob disease range from "several dozen" by the French health secretary, Dominique Gillot, to 250,000 in a recent British government study. "We might be seeing an epidemic that involves hundreds of thousands of people," said John Collinge of Britain's advisory committee on spongiform encephalopathies. "Let's hope that is not the case, but it's still possible. We need to guard against false optimism and wishful thinking, which has bedeviled this field for too long." John Kent, a professor of statistics at Leeds University who has tried to quantify the crisis, said that the mathematical models were not to be trusted because scientists do not know how much is an infectious dose and do not know how many people ate infected meat. "Those are two really big variables," he said. "All we can do is to set out a range of possibilities." 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