Scrambled drugs: transgenic chickens could lay golden eggs. (This Week).

Medications of the future may be made to order--short order from the griddle, that is. Scientists have genetically engineered chickens so that they produce foreign proteins in eggs. This is an important step toward the goal of routinely breeding hens that lay packages of pharmaceuticals.

Starting in the 1980s, scientists have created a variety of ready-made animal drug factories. Genetically altered cows, pigs, sheep, goats, rabbits, and mice and have manufactured foreign proteins in mammary tissue. The researchers harvest the milk of these animals and extract therapeutic substances such as blood-clotting agents and insulin.

Researchers have also developed mice that secrete useful proteins in urine (SN: 1/10/98, p. 21), and in January, scientists described bovine mammary cells that secrete spider silk (SN: 1/19/02, p. 38).

Producing drugs in egg white offers many benefits. "The main thing is that chickens can produce many, many progeny in a short period of time," says Alex J. Harvey of AviGenics, a biotechnology firm in Athens, Ga. A chicken's generation time is around 6 months. That's far shorter than the generation time of a large mammal, such as a goat, which requires 18 months to grow from engineered embryo to milk-yielding adult, adds Harvey.

Chickens also produce lots of protein. Each of the approximately 330 eggs a hen lays annually contains 6.5 grams of various proteins.

Using engineered viruses as gene carriers, Harvey and his colleagues at the University of Georgia in Athens inserted the DNA blueprint for a bacterial enzyme called beta-lactamase into embryos of white leghorn chickens. About 2 percent of these embryos grew into adults that expressed the enzyme in some of their cells.

Next, the researchers bred ordinary fowl with those hens and roosters that expressed beta-lactamase in their sperm or ovules. Progeny of these chickens were found to have copies of the gene in all their cells, and the females laid eggs containing detectable, albeit small, quantities of beta-lactamase.

As the researchers report in the April Nature Biotechnology, the transferred gene remained stable in the chickens. Each hen continued to produce eggs containing the enzyme for at least 16 months, and the inserted gene was functional over at least four generations of hens.

"The good news is that the protein is there [in the eggs]," comments Robert J. Etches, an avian geneticist at Origen Therapeutics in Burlingame, Calif. "The bad news is that it's not there in very high quantities." The next generation of technology should be focused on getting higher concentrations of the foreign proteins in egg whites, he says.

An additional advantage of producing pharmaceuticals in eggs, notes Etches, is that egg white is far less complex biochemically than milk is, and there are established methods for easily extracting various proteins from eggs.

However, Etches adds, the type of virus currently used can only carry small genes into the chicken's DNA. That's a significant problem because many useful genes are 10 or more times as large as the beta-lactamase gene.

Though beta-lactamase itself has no pharmaceutical application and was only found in minute quantities, the research "demonstrates proof of concept" and paves the way for future work, says Anthony P. Cruz, a spokesperson for AviGenics.

The scientists say that they intend to focus next on two efforts: introducing genes for therapeutically useful proteins and developing methods that will produce more of the foreign protein solely in specific tissues, such as the oviduct.