Golden eggs: engineered hens lay drugs.

Scottish scientists have genetically engineered hens that can not only produce useful drugs in their eggs but also reliably pass on this characteristic to new generations of chickens. Successfully combining these two traits represents a first for researchers aiming to transform animals into living drug factories, the scientists say.

Certain proteins can counteract a variety of medical conditions, from anemia to diabetes to cancer. While some of these protein drugs are relatively simple to make in the lab, others are difficult, time-consuming, or expensive to produce.

Since animals naturally make thousands of proteins, researchers have sought to harness this innate capability. Over the past several years, scientists have engineered cows, sheep, and other mammals to produce protein drugs.

However, these animals have several drawbacks, says Simon Lillico of the Roslin Institute outside Edinburgh. Most of the engineered animals are large, expensive to house and feed, and take years to mature enough to produce the desired proteins. Furthermore, these animals can't stay healthy while making compounds toxic to mammalian cells--a trait many medicines require.

Some researchers have suggested that chickens--with their small sizes, low maintenance needs, and quick generation times--could produce protein drugs in their eggs. But Lillico notes that previous attempts to engineer drug-producing chickens have run into problems. For example, in some engineered hens, drugmaking capability fades with each generation.

Lillico and his colleagues, led by the Roslin Institute's Helen Sang, took a new approach. They constructed drug-coding genes that would insert themselves into the gene that all chickens carry for making the egg-white component ovalbumin.

The team worked with two synthetic genes that code for different protein drugs: an antibody called miR24, which has shown promise against melanoma, and a protein called human interferon-beta-la, which is already used to treat multiple sclerosis. The researchers employed viruses to ferry both genes into cells in young chick embryos inside unhatched eggs.

When the eggs hatched, the researchers selected the male chicks that carried the altered gene. When the team later bred these roosters with normal hens, half the female offspring laid eggs containing both protein drugs in their whites, the researchers report in an upcoming Proceedings of the National Academy of Sciences. The researchers continue to screen for male offspring carrying the genes and to breed them with normal hens. They now have five generations of drug-producing birds, Lillico says.

The newly engineered chickens "could pave the way to something very interesting," says animal sciences professor Frangois Pothier of Laval University in Quebec City, who has engineered pigs to produce useful proteins in their semen. Pothier points out that before chickens roost in pharmaceutical factories, the researchers in Scotland have many hurdles to overcome, such as increasing the small amounts of the two drugs present in the hens' egg whites.

However, Pothier notes that once the scientists perfect their technique, it might be possible to introduce a variety of useful proteins that would improve eggs' food value.

"You can imagine that eventually, not only could you modify the content of an egg for therapeutics, but you could perhaps change the flavor or add something interesting for health," such as vitamins or heart-healthy fatty acids, Pothier says.