Begin forwarded message: Date: February 16, 2007 3:47:38 AM PST Subject: [ctrl] Pharm Animals Crank Out Drugs
With its tranquil ponds and rolling fields, the GTC Biotherapeutics farm in Charlton, Massachusetts, looks like a typical pastoral retreat. But its 1,400 goats don't produce any butter or cheese. Instead, the animals are sophisticated drug incubators, with millions of dollars of potential profit accumulating in their udders each day.
GTC Biotherapeutics is among several companies worldwide perfecting the art of "pharming" -- genetically modifying animals to churn out drugs for disorders like hemophilia and cancer. The first government-approved drug from transgenic animals, GTC's anti-clotting agent ATryn, was approved in Europe late last year, vindicating biotech's years-long quest to steer animal husbandry in entirely new directions.
With the approval of the anti-clotting agent, the drug industry will now likely increase the use of transgenic animals, says Robert Kay, CEO of Origen Therapeutics. Kay predicted drug makers will try to develop several transgenic animal "systems," including mice, rats, goats, cows, pigs, sheep and chickens.
"We should begin to see the approach make an impact," he says. "We can reasonably expect that new advances will be made."
The technique offers a way to produce large quantities of drugs that are otherwise difficult to develop. It involves genetic modification of an animal embryo's genetic makeup, or genome. Just after fertilization, "pharmers" insert into the embryo a human gene that codes for a particular protein -- usually one that's produced naturally in humans, but that's lacking in people who have certain diseases. They attach that DNA code with a gene that codes for a sugar found in mammalian milk, insuring that the therapeutic protein will be expressed only in the animals' milk or eggs.
GTC's ATryn contains the human protein antithrombin, which helps prevent blood clots that could lead to a stroke or heart attack. About one in every 5,000 people has a genetic deficiency of this protein. The drug is also administered during surgery because excessive bleeding can lower blood levels of the protein, leading to clots.
"It doesn't appear you can have too much of it," says Geoffrey Cox, GTC's chief executive officer. "But if you have too little, there's a severe risk of thrombosis." Thrombosis is the formation of a clot inside a blood vessel.
Antithrombin is typically extracted from human blood plasma donations, but it's present only in very small quantities. That makes soliciting donors and extracting proteins from the plasma expensive and labor-intensive.
But now that GTC's goat herd has reached critical mass, the protein can be harvested in massive quantities. "Each of our goats can produce a kilogram of antithrombin each year," Cox says. "It takes 50,000 people to donate that same amount."
GTC is developing a similar protocol using rabbits to produce another clotting protein, called rhFVIIa, which some hemophiliacs lack.
At Scotland's Roslin Institute, birthplace of Dolly the cloned sheep, biologist Helen Sang is turning another farmyard inhabitant, the chicken, into a similar drug-production machine. Sang is pioneering a new, more efficient way to engineer chickens that produce human proteins in the albumen of their eggs.
"We're taking up where people left off (with chickens) quite a few years ago, but we're using a more sophisticated viral vector," she says.
Her findings were published in January in Proceedings of the National Academy of Sciences of the United States of America.
Chickens reproduce very quickly and generate high concentrations of proteins in their egg whites. So Sang thinks transgenic chickens could emerge as drug factories that are at least as efficient as goats.
"We're not talking about one method being the absolute best," she says. "Chickens may be best for producing one protein, and goats may be best for producing another." The Roslin Institute has formed a partnership with gene-therapy company Oxford BioMedica and anticipates its poultry-based strategy will enable it to manufacture protein-based drugs in the coming decade, though it has not disclosed which ones.
Burlingame, California-based Origen Therapeutics is also developing transgenic chickens that express human proteins in egg albumen. The company's scientists plan to develop human cancer-fighting antibodies. They also hope to breed a chicken that will produce the entire range of human antibodies in its eggs. If the company succeeds, harvesting compounds for drug therapies will be a little like choosing a flavor from a soda fountain.
Some consumers, scientists acknowledge, have misgivings about creating animal-human hybrid genomes.
"It's a whole new ballgame, and we need to proceed with caution," said Margaret Mellon, director of the Union of Concerned Scientists' Food and Environment Program.
Mellon said drug-production processes would need to be standardized, which might be difficult when dealing with several disparate species. In addition, there are concerns that viruses could be hidden in animal DNA and passed on to humans, or that drugs produced in milk might be contaminated with prions. There's also the welfare of the animals themselves: The drugs they produce might be harmful to them.
Catherine Willett, a science policy advisor for People for the Ethical Treatment of Animals, stressed the welfare issues.
"Genetic engineering is responsible for a skyrocketing increase in the numbers of animals being used in laboratory experiments," she said. "(and) is likely to have drastic long term ill-effects in the animals themselves."
But Origen scientist Marie Cecile Van de Lavoir said the potential human health benefits justify tinkering with nature's plan.
"If a transgenic animal produces a great cancer therapy," she says, "I won't hear anyone saying, 'You shouldn't do that.'"
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