Transgenic Livestock as Drug Factories By introducing key human genes into mammals, biologists can induce dairy animals to produce therapeutic proteins in their milk

Exactly one year after her own birth, Genie, our experimental sow, was serenely nursing seven healthy piglets, her milk providing the many nutrients these offspring needed to survive and grow. But unlike other pigs, Genie’s milk also contained a substance that some seriously ill people desperately need: human protein C. Traditional methods of obtaining such blood proteins for patients involve processing large quantities of donated human blood or culturing vast numbers of cells in giant stainless-steel reactor vessels. Yet Genie was producing copious amounts of protein C without visible assistance. She was the world’s first pig to produce a human protein in her milk. Genie’s ability to manufacture a therapeutic drug in this way was the outcome of a research project conceived almost a decade ago. In collaboration with scientists from the American Red Cross who specialized in providing such blood proteins, we began to consider the possibility of changing the composition of an animal’s milk to include some of these critically needed substances. In theory, this approach could generate any required quantity of the various therapeutic blood proteins that are regularly in short supply. Demand for such drugs comes from many quarters. For instance, hemophiliacs may lack any of several different clotting agents, particularly blood proteins called Factor VIII and Factor IX. Certain people with an inborn deficiency require extra protein C (which acts to control clotting) to supplement their body’s meager stores, and patients undergoing joint replacement surgery can benefit from this protein as well. Another important example of the need for therapeutic blood proteins involves people suffering strokes or heart attacks: these cases often demand quick treatment with a protein called tissue plasminogen activator, a substance that can dissolve blood clots. And some people suffering from a debilitating form of emphysema can breathe more easily with infusions of a protein called alpha1-antitrypsin. All these proteins are present in donated blood only in tiny amounts, and hence they are currently so difficult to produce that their expense precludes or severely limits their use as drugs. For example, treatment with purified Factor VIII (restricted to those times when someone with hemophilia is actually bleeding) typically costs the patient tens of thousands of dollars every year. The cost of continuous replacement of this blood protein for the same period—a desirable but rarely available option— would exceed $100,000. Such enormous sums reflect the many problems involved in extracting these proteins from donated blood or establishing specialized production facilities using cultured cells—an enterprise that can require an investment of $25 million or more to supply even modest amounts of a single type of protein. Developing “transgenic” animals such as Genie (that is, creatures that carry genes from other species) demands only a small fraction of such costs. Yet the new breeds simplify procedures enormously and can produce vast quantities of human blood protein. Replacing conventional bioreactors with transgenic livestock thus offers immense economic benefits. Creating blood proteins in this fashion also stands to better the other cur-