UMass Researchers Announce Birth Of Genetically Modified Cloned Calves

First calves cloned from genetically modified somatic (body) Cells; technology has significant ramifications in medicine and agriculture

AMHERST, Mass. -- Researchers at the University of Massachusetts have announced the birth of two healthy calves created by combining cloning techniques with genetic engineering. The animals, named Charlie and George, were born last week at a ranch in Texas following four years of research by James Robl, professor of veterinary and animal sciences at UMass, and Steven Stice, of Advanced Cell Technology (ACT) Inc., who is also an adjunct faculty member at the University. The male calves are the first to be produced from genetically altered somatic (body) cells. The announcement was made today at the meeting of the International Embryo Transfer Society in Boston.The animals are genetically identical to one another, and were created through a combination of cloning and genetic engineering (also called transgenics) developed by Robl and Stice, who conduct this research under the auspices of ACT, a biotechnology company with close ties to the University. The scientists have developed a reliable way to introduce new traits into livestock cells and produce an unlimited number of exact copies -- clones.

The newborn cloned transgenic calves have a specific gene which serves as a "marker" to confirm that they are the products of genetic engineering. The calves are notable because they lead the way to the production of similar animals that produce very large quantities of therapeutic human proteins, essentially, medications for people in their milk. These proteins can either be extracted and purified, then taken in the form of a pill or injection, or drunk like a conventional glass of milk. This new field, a combination of pharmaceuticals and farming, is called "pharming."

Under an agreement announced last year between ACT and Genzyme Transgenics Corp., the first product to be produced will be human serum albumin, a protein currently derived from pooled human plasma that is used therapeutically to maintain volume in blood vessels. Approximately 440 metric tons of plasma-derived albumin are used annually worldwide. Combining cloning and transgenics to produce recombinant human albumin may provide a safe and more cost-effective substitute for the plasma-derived product. An individual cloned transgenic dairy cow is expected to produce approximately 80 kilograms of recombinant human albumin annually.

Also, scientists’ newfound ability to endow cattle offspring with desirable genetic characteristics is being pursued as a method of producing modified cells for transplantation into human patients, according to Stice. Genetic modification may be used to reduce the chance of rejection of foreign organs, tissues, and bone marrow transplants, and produce therapeutic proteins and improve survival in cell transplants. These cells are currently being tested in animals for treating such disorders as Parkinson’s disease. Many other disorders, such as Alzheimer’s disease, Huntington’s disease, and diabetes, could be treated in the future using this type of cell-based therapy, Stice said.

Robl and Stice make the desired changes in the genetic code, or DNA, of scores of somatic cells that are candidates to become the clones’ genetic donor. This process is more labor-intensive than it sounds: only one in a million cells have the gene alteration that the scientists hope to produce. These select cells are then grown in a petri dish and fused to cow eggs in which the original genetic material has been removed. The resulting embryos are implanted in surrogate mothers. The resulting offspring, all of one sex, will be identical to one another and carry the same genetic information.

The first cloned animals were born in the mid-1980s, and included rabbits cloned by Robl and Stice at the University in 1987. Although cattle were also cloned in the mid-1980s, recently cattle have been reported to be cloned from cultured fetal germ cells. The animals were not genetically modified and required a second cloning procedure for successful development. Moreover, the cloning method used to produce Charlie and George differed significantly from those used in Scotland to produce the cloned sheep Dolly, Molly, and Polly. The major difference is that the cattle cells were not in a quiescent state when fused with the cow eggs.

Robl has been a member of the University faculty since 1985 and is a co-founder and consultant with ACT. Stice joined the University faculty in 1994. He is a co-founder and chief scientific officer of ACT. He received a doctoral degree in veterinary and animal sciences at UMass in 1989. ACT is a wholly-owned subsidiary of Avian Farms, Inc., of Waterville, Maine, a poultry genetics company.