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US Scientists Create Antibody-Producing Cows - 2003-10-14

Imagine herds of cattle raised not for their milk or meat, but for medicines. Scientists have long dreamed about changing the genetic makeup of farm animals such as cows and goats to turn them into biological factories for making anything from cancer drugs to human antibodies that could boost a patient's ability to fight disease. Now scientists in the United States and Japan report that they have moved a major step closer to making this vision a reality. They have created a line of cows with the capacity to produce a wide range of antibodies, including those able to fight diseases like smallpox, anthrax and even children's ear infections.

Inside a white barn surrounded by corn and soybean fields, four calves are awaiting their afternoon feeding.

Linda, Heather, Tara and Yoon don't look any different from calves on neighboring farms, but about one-third percent of the genetic material, or DNA, in their cells is human. That may not seem like a lot, but it's about 500 times more foreign DNA than has ever been transferred into a cow.

"Arguably it's the most complex genetic manipulation ever accomplished," said Jim Robl.

Jim Robl is the lead scientist for Hematech, a small Sioux Falls biotechnology company that produced the calves. He explains that each calf carries a set of human genes that, when they're at work in our bodies, enable our immune systems to make antibodies against infections.

To transfer those genes, Dr. Robl and his team had to overcome a major obstacle. Because antibody genes must respond to so many different diseases, they're very big. Most successful genetic modifications of plants and animals to date have involved transferring only small fragments of DNA.

Hematech's scientists together with their collaborators at a Japanese pharmaceutical company had to find a way of inserting these giant genes and they took a lesson from nature. Cells store genetic material in packages called chromosomes. So Dr. Robl's team created an artificial chromosome consisting of the antibody genes and some genetic packaging material.

"So all of those are contained within this small chromosome fragment, all of the essentials to have it carried on through cell division," he said. "And the cell goes on its merry way without interruption or even realizing that this extra chromosome is there."

And it worked. The scientific journal Nature Biotechnology has published the research. Cow cells normally have 60 chromosomes; Hematech's calves have 61. And that 61st is busy churning out human antibodies that are circulating in the calves' blood. In Hematech's cloning laboratory, technicians are preparing to make identical copies of these calves so they don't have to go through the tricky and costly manipulation for each animal. Eventually, the company hopes to produce thousands of such cows.

There are still other scientific hurdles ahead, and the first medical product could be a decade away, but Jim Robl hopes believes the research is finally yielding practical benefits.

"Effectively, I've been working on this project for 20 years," continued Jim Robl. "I've always been interested in seeing something of use come out of all of this effort. So I feel that finally we're getting to something that can actually be put on the market, help people, be injected into patients, treat patients, cure patients of various diseases."

While Hematech plans to use the artificial chromosome to make human medicines, scientists elsewhere are dreaming up other ways to use the technology.

Bob Wall has reviewed the research; he's a genetic engineer for the U.S. Department of Agriculture. He says now scientists can start manipulating biological traits that are influenced by multiple genes, as most are. For instance, he thinks it would take about six genes to give dairy cows resistance to a disease that hinders milk production.

"By being able to use an artificial chromosome as this project did, we'll have a better chance of having it work right the first time we try it," he said. "One gene at a time, which is the technology we had before this publication, wouldn't really get you there."

Meanwhile, Hematech's calves are busy munching away at the feeding trough, unaware that they're paving the way for bigger and more powerful genetic manipulations.