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Animal: Gene-engineered cattle resist mad cow disease: study
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- Date: 3 Jan 2007 14:17:01 +0100
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PART 1
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TITLE: GENE-ENGINEERED CATTLE RESIST MAD COW DISEASE: STUDY
SOURCE: Reuters
URL: http://today.reuters.com/news/articlenews.aspx?type=healthNews&storyID=2007-01-01T091910Z_01_N31264936_RTRUKOC_0_US-MADCOW-BREED.xml&WTmodLoc=HealthNewsHome_C2_healthNews-3
DATE: 01.01.2007
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GENE-ENGINEERED CATTLE RESIST MAD COW DISEASE: STUDY
WASHINGTON (Reuters) - U.S. and Japanese scientists reported on Sunday that they had used genetic engineering to produce cattle that resist mad cow disease.
They hope the cattle can be the source of herds that can provide dairy products, gelatin and other products free of the brain-destroying disease, also known as bovine spongiform encephalopathy or BSE.
Writing in the journal Nature Biotechnology, the researchers said their cattle were healthy at the age of 20 months, and sperm from the males made normal embryos that were used to impregnate cows, although it is not certain yet that they could breed normally.
The cattle lack the nervous system prions, a type of protein, that cause BSE and other related diseases such as scrapie in sheep and Creutzfeldt-Jakob disease, known as CJD, in humans, the researchers said.
"(Prion-protein-negative) cattle could be a preferred source of a wide variety of bovine-derived products that have been extensively used in biotechnology, such as milk, gelatin, collagen, serum and plasma," they wrote in their report.
Yoshimi Kuroiwa of Kirin Brewery Co. in Tokyo, Japan and colleagues made the cattle, known as knockouts because a specific gene has been "knocked" out of them, using a method they call gene targeting.
"By knocking out the prion protein gene and producing healthy calves, our team has successfully demonstrated that normal cellular prion protein is not necessary for the normal development and survival of cattle. The cows are now nearly 2 years old and are completely healthy," said James Robl of Hematech, a South Dakota subsidiary of Kirin.
"We anticipate that prion protein-free cows will be useful models to study prion disease processes in both animals and humans," Robl, an expert in cloning technology, said in a statement.
Misfolded prion proteins are blamed for BSE and other, similar brain diseases. It is known that certain genetic variations make animals more susceptible to the diseases.
BSE swept through British herds in the 1980s and people began developing an odd, early-onset form of CJD called variant CJD or vCJD a few years later. CJD normally affects one in a million people globally, usually the elderly, as it has a long incubation period.
There is no cure and it is always fatal.
As of November 2006, 200 vCJD patients were reported worldwide, including 164 patients in Britain, 21 in France, 4 in the Republic of Ireland, 3 in the United States, 2 in the Netherlands and 1 each in Canada, Italy, Japan, Portugal, Saudi Arabia and Spain.
The disease may have first started to infect cattle when they were fed improperly processed remains of sheep, possibly sheep infected with scrapie. Although people are not known to have ever caught scrapie from eating sheep, BSE can be transmitted to humans.
BSE occasionally occurs in cattle outside Britain although it is now rare.
PART 2
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TITLE: SIOUX FALLS FIRM OPENS DOOR TO ELIMINATING MAD COW
SOURCE: Argus Leader, USA
URL: http://www.argusleader.com/apps/pbcs.dll/article?AID=/20070102/BUSINESS/701020305/1003
DATE: 02.01.2007
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SIOUX FALLS FIRM OPENS DOOR TO ELIMINATING MAD COW
A Sioux Falls-based biotechnology firm is receiving international recognition for its research in developing cattle that don't appear to be able to contract mad cow disease.
Scientists at Hematech say they've raised 12 healthy Holstein bull calves that don't have the naturally occurring prion proteins that can misfold and cause bovine spongiform encephalopathy, otherwise known as BSE or "mad cow disease."
While the occurrence of BSE in the United States has dropped in recent years, thanks in part to changed feeding practices and better government surveillance, Hematech's findings are creating a buzz in the biotechnology world. The study is published in the most recent edition of the Nature Biotechnology journal.
"It does give us some insurance for our research in our future," said Hematech President Jim Robl.
Biotechnology experts say Hematech's advancements will be useful in future studies of BSE and related prion diseases, as well as in other research applications and perhaps the development of BSE-free beef.
"The value of this paper in its implications for producing human antibodies, polyclonal antibodies, and other bovine derived compounds from cattle that can be certified as being absolutely BSE-free is potentially very high indeed," said L. Val Giddings, vice president for food and agriculture of the Washington, D.C.-based Biotechnology Industry Organization. The group represents biotechnology organizations and firms nationwide.
Investment in research
Hematech - which uses genetically altered cattle to produce human antibodies used to create treatments for human diseases - began developing the prion-free cattle as a side project, Robl said. The company's main work focuses on harvesting human antibodies from its genetically modified cattle in the hopes of developing treatments for chronic human diseases.
Hematech and its parent company, the pharmaceutical division of Japan's Kirin Brewing Ltd., have spent millions of dollars and thousands of hours of research to perfect bovine-human antibody genes in cattle. Robl estimated the company spends $15 million to $18 million annually on research.
"We are the largest cloning operation in the world, and I think that we have some of the most sophisticated gene-manipulation technology here," Robl said.
How it works
The Nature Biotechnology paper is a continuation of findings Hematech had published in 2004, when it announced its gene-targeting system had produced the prion-free embryos reported in the latest study.
"It is a second chapter in that story," Robl said. "At that point, we had not successfully produced live animals.
"We went on from that study to produce the calves."
The cattle developed by Hematech have no prions, the misshapen proteins behind contracting mad cow disease. The cattle are created by transplanting the nuclei of cells into unfertilized eggs after destroying their cattle antibody and prion genes.
The breakthrough arose through successful production of calves that carry only the human antibody genes, instead of half-human, half-bovine antibodies. The technique "knocks out" the bovine-chain antibody genes.
Robl said the cattle now are virtually indistinguishable from other Holsteins, except they don't have prions. Hematech has tested the cattle's organs and brain and bodily functions and has also fertilized bovine eggs with the bulls' sperm to create embryos, he said.
"Our team has successfully demonstrated that normal cellular prion protein is not necessary for the normal development and survival of cattle," he said. "The cows are now nearly 2 years old and are completely healthy."
The next steps will involve further tests as the cattle age to "definitively prove" they can't contract BSE and to produce offspring from them.
Not for ag production
The Biotechnology Industry Organization is looking long-term at the potential for on-farm production of BSE-free beef.
The Hematech study and others also might provide momentum for the U.S. government on regulations on so-called transgenic animals, said Barb Glenn, the group's managing director for animal biotechnology, food and agriculture.
"The implications for this technology for beef production and trade are significant," Glenn said.
Hematech said it is not planning to use the technology to create herds of BSE-resistant beef cattle; the cost of the research is too high. Rather, the cattle produced will further research into prions and help Hematech ensure they can produce human antibodies from cattle without fear of BSE transmission to a human patient.
"Our objective is not to produce these for agricultural production," Robl said.
Sam Holland, South Dakota's state veterinarian, said he's encouraged by Hematech's research. Prion diseases don't just affect cattle; similar diseases include scrapie in sheep, chronic wasting disease in deer and Creutzfeldt-Jakob disease in humans.
"It's the type of research that could have potential on diseases in other species," Holland said. "You never know what kind of impact that could have."
PART 3
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TITLE: SCIENTISTS DEVELOP COWS FREE OF PROTEINS CAUSING MAD COW DISEASE
SOURCE: The Columbian, USA
URL: http://www.columbian.com/news/APStories/AP01022007news88915.cfm
DATE: 01.01.2007
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SCIENTISTS DEVELOP COWS FREE OF PROTEINS CAUSING MAD COW DISEASE
SAN FRANCISCO (AP) -- 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, D.C., 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.
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