News Focus

Down on the Animal Pharm

See allHide authors and affiliations

Science  18 Dec 1998:
Vol. 282, Issue 5397, pp. 2177
DOI: 10.1126/science.282.5397.2177

Although cloned sheep and cattle have just recently caught the public and scientific imagination, agricultural researchers have in fact been tinkering with the genes of livestock for at least a decade. Unlike much of the genetic engineering done on plants, which is aimed at making them more productive or more nourishing (see main text), the goal is to turn sheep, cattle, goats, or other livestock into pharmaceutical factories on the hoof for valuable human proteins.

Getting the necessary genes into the animals is a painstaking and inefficient process, however, which explains part of the appeal of cloning: It should make it easier to duplicate the rare animals in which the gene transfer has succeeded. But even without cloning, researchers have developed herds of sheep and other animals making human proteins, some of which are in advanced clinical trials. “Recombinant protein therapeutics from animals will reach the marketplace soon,” says molecular biologist Jeffrey Turner of Nexia Biotechnologies in Quebec, Canada. And, he adds, “they will offer significant cost savings.”

One protein already being harvested is alpha-1-antitrypsin, which inhibits elastase, an enzyme that helps break down connective tissue and is found in excess amounts in the surface fluid of the lungs of cystic fibrosis patients. Alpha-1-antitrypsin is being tested as a potential treatment for this disease, but it is very expensive to obtain from its current source, human serum. To develop a cheaper supply, researchers including Ian Wilmut at the Roslin Institute, Edinburgh (the same group that cloned the sheep “Dolly”) introduced the human alpha-1-antitrypsin gene into a sheep about 10 years ago. The goal was to develop a herd of animals that would secrete the protein into their milk so that it could be easily obtained.

Early on, skeptics wondered whether the transferred gene would be transmitted to successive generations and, if so, whether the animals would produce the protein in biologically active form and secrete it in sufficient quantities to make recovery practical. But all these hurdles have been cleared. Indeed, “Tracy,” the first sheep transformed with the alpha-1-antitrypsin gene, now has 800 granddaughters, and some are producing enough of the protein—from 13 to 17 grams per liter of milk—for it to be undergoing clinical trials in cystic fibrosis patients in the United Kingdom.

Other human proteins made in animals are also undergoing clinical testing. After proving that the anticlotting agent human antithrombin III produced in goat's milk is safe when administered to humans, Genzyme Transgenics Corporation of Boston, which produces the protein, has begun clinical trials in the United States and Europe to test its efficacy as an anticlotting therapeutic in coronary bypass patients. Also in the pipeline, although at an earlier stage of development, are various vaccine proteins and monoclonal antibodies that might be used for treating diseases such as cancer.

What's more, getting genes into livestock may be much easier in the future, thanks to a new technique reported just last month by Robert Bremel, formerly of the University of Wisconsin, Madison, and now managing director of the biotech firm Gala Design in Sauk City, Wisconsin, and his colleagues (Science, 27 November, p. 1619). By introducing the foreign genes into cow oocytes still undergoing meiosis and fertilizing them later, the researchers were able to increase the gene transfer efficiency from the current 10% or less to nearly 100%. A new field of agriculture, livestock “pharming” may turn into a lucrative business for 21st-century farmers.

Navigate This Article