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New old-fashioned drug makers: goats

A herd has been genetically engineered to make a human protein in their milk that can prevent dangerous blood clots. If the drug is approved by the FDA, the barn door could swing open.

January 10, 2009|Karen Kaplan

They have four legs, fuzzy faces and udders full of milk.

To the uninitiated, they look like dairy goats. To GTC Biotherapeutics Inc., they're cutting-edge drug-making machines.

The goats being raised on a farm in central Massachusetts are genetically engineered to make a human protein in their milk that prevents dangerous blood clots from forming. The company extracts the protein and turns it into a medicine that fights strokes, pulmonary embolisms and other life-threatening conditions.

GTC has asked the Food and Drug Administration to OK the drug, called ATryn. An expert panel voted overwhelmingly Friday that it is safe and effective, putting it on the verge of becoming the first drug from a genetically engineered animal to be approved in the U.S. The agency is expected to make a final decision in early February.

If approved, the drug would be followed by perhaps hundreds of others made from milk produced by genetically engineered goats, cows, rabbits and other animals. Other products in the pipeline are designed to treat people with hemophilia, severe respiratory disease and debilitating swollen tissues.

"As soon as we were able to make genetically engineered animals, this was an obvious thing to do," said James Murray, a geneticist and professor of animal science at UC Davis. "It's totally cut-and-paste. This is kindergarten stuff with molecular scissors."

The biotechnology industry is rooting for ATryn. The FDA's endorsement would signal to Americans that they have nothing to fear from the futuristic technology -- and suggest that the millions of dollars they've invested in the technology could soon begin to pay off.

If the drug is approved, "it takes a big question mark off the table in terms of products that are developed from this technology," said Samir Singh, president of U.S. operations for Pharming Group, which is developing medicines using milk from genetically engineered cows and rabbits.

The public has had misgivings about eating food from genetically modified animals, and some vocal critics of such technology say the wariness could extend to medicines.

"I think many people are going to have the same revulsion," said Jaydee Hanson, a policy analyst at the Center for Food Safety, a Washington advocacy group that opposes genetic manipulation of food and animals.

For scientists, the appeal is obvious. Many drugs are now synthesized in bioreactors by bacteria or Chinese hamster ovary cells, and they require extensive processing to be suitable for human use. Genetically engineering animals is a more straightforward alternative for producing proteins, which form the basis of all biological drugs.

"We're taking advantage of the fact that the mammary gland was designed by nature to make proteins," said Tom Newberry, GTC's vice president for government relations.

The process of designing animal milk with human proteins starts by identifying the human gene containing instructions for making a medically useful protein. That human DNA sequence is combined with pieces of animal DNA that regulate when and where the protein is produced. Those regulatory controls ensure that the human gene is only switched on in the mammary gland during lactation and doesn't interfere with any other part of the animal's body.

The DNA package can be injected into a single-cell animal embryo with a microscopic needle, though it's a hit-or-miss proposition. When the embryo divides, it may or may not incorporate the foreign DNA into its own genome. The embryo is then transferred to the uterus of a surrogate mother, with a 1% to 3% chance that it will result in a healthy animal containing the human gene.

A more advanced alternative is to start with a normal animal cell and splice the DNA package directly into the cell nucleus. The modified cell can be cloned to create a new animal that expresses a human gene. With three to five founder animals, a company could use traditional breeding methods to create an entire herd of genetically engineered cows, sheep or goats.

"Something like five or six cows can produce the world's requirement for some drugs," said Murray of UC Davis. Demand for most drugs could be met with herds no bigger than 50 cows or 100 goats, he said.

Companies separate the components of engineered animals' milk based on their size, shape, electrical charge and other chemical characteristics. The process ultimately leads to vials of pure protein that carry out specific functions in the human body.

The species of animal depends in part on the volume of protein needed or how quickly it needs to be produced.

The companies say it's cheaper to create the animals than to build and maintain expensive bioreactors. The technique could make it cost-effective for companies to develop drugs to treat diseases that affect relatively few patients.

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