Cows engineered to lack mad cow disease

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SAN FRANCISCO - Scientists have genetically engineered a dozen cows to be free from the proteins that cause mad cow disease, a breakthrough that may make the animals immune to the brain-wasting disease. An international team of researchers from the U.S. and Japan reported Sunday that they had "knocked out" the gene responsible for making the proteins, called prions. The disease didn't take hold when brain tissue from two of the genetically engineered cows was exposed to bad prions in the laboratory, they said. Experts said the work may offer another layer of security to people concerned about eating infected beef, although though any food derived from genetically engineered animals must first be approved by the Food and Drug Administration."This research is a huge step forward for the use of animal biotechnology that benefits consumers," said Barbara Glenn of the Biotechnology Industry Organization, a Washington industry group that includes the company that sponsored the research as a member. "This a plus for consumers worldwide."The surviving cows are now being injected directly with mad cow disease, known as bovine spongiform encephalopathy, or BSE, to make certain the cattle are immune to it. Those key results won't be known until later this year, at the earliest, according to the Sioux Falls, S.D. based biotechnology company Hematech Inc. that sponsored the research. It can take as long as two years for mad cow disease to be detected in infected animals. The research published in the online journal Nature Biotechnology could be used as a tool that would help researchers better understand similar brain-wasting diseases in humans, Glenn and others said. Scientists are still mystified by the biological purposes of normal prions, which humans also produce. But they believe that even one prion going bad can set off the always fatal and painful brain disease — known as variant Creutzfeldt-Jakob disease in humans. Similar prion-based diseases also are found in sheep, deer and elk. Glenn and others stressed that the mad cow threat to the United States is extremely low due in large part to government regulations enacted after outbreaks in Europe."At the moment we don't have a high threat of BSE," said Val Giddings, a scientist who consults with biotechnology companies. "But if BSE were ever to become a problem, this could turn out to be a good technological fix to it."Also, Hematech's chief scientist, James Robl, said companies still are spending millions of dollars annually to protect their cows from the disease. In the lab, Robl and his colleagues, who included a scientist from the U.S. Department of Agriculture, scraped skin cells from cows and "turned off" the gene that makes prions. Then, using those cells as a "starter kit," they produced 12 calves through cloning processes — the fusing of the cells into the eggs of cows. Three were slaughtered so their brains could be studied and nine are still living."The cloning process itself is very large scale," said Robl, who estimated that Hematech implants about 15,000 cloned embryos into 4,000 cows annually. Most of the pregnancies are terminated before birth to collect cells for the company's research in developing human medicines, he said. Robl said a more immediate use of the technology could be to produce prion-free cows to produce cow serum, a popular laboratory tool used for myriad biological experiments. Since three cows in the United States were diagnosed with BSE beginning in December 2003, most labs order their cow serum from New Zealand. But Hematech isn't much interested in producing serum for scientists and has no plans to become a beef producer. Instead, the company is genetically engineering cows to produce antibiotics and other medicines for people. The company embarked on the mad cow disease project five years ago to ensure it could produce medicines that were free from the brain-wasting disease. BSE is caused when one misshapen prion prompts normal prions to turn bad, slowly boring lesions in the brain and making infected animals go mad. It's thought that people eating infected beef can contract the human variant of the disease, which also occurs spontaneously. At least 180 people worldwide have died after eating meat infected with mad cow disease in the last two decades. Symptoms can take years to develop. But scientists are certain the brain-wasting diseases are caused by the misshapen prions, one of the most mystifying particles in biology. No one knows the function of normal prions and the research published Sunday suggests the proteins have little value. All the prion-free cows the research team created were born healthy, although Robl noted that since they are only two years old they will have to be watched to see if the lack of prions has any future health effects."It furthers the mystery of prions, for sure," Robl said.