The Cloning Process

by Food and Drug Administration (FDA)

Full Flush is a celebrity. No one asks for his autograph, but they do ask for his progeny. Named for a winning poker hand, the aging grand champion bull can't meet the demand of all the cattle ranchers who want more like him. But the bull's clones may keep his legacy alive. Full Flush's five clones "were as normal and healthy as any calves I've ever raised," says rancher and veterinarian Donald Coover of Galesburg, Kan., who bottle-fed the young calves and raised them for the first six months of their lives. The calves, born in 2001, will soon be ready to propagate herds of high-quality beef cattle.

To the uninitiated, animal cloning may conjure up visions of strange, robot-like creatures, but real clones are far from this science-fiction fallacy. "This is just an assisted reproductive technology," says Mark Westhusin, Ph.D., director of the Reproductive Sciences Laboratory at Texas A&M University's College of Veterinary Medicine. "We're not trying to resurrect animals or get animals back."

"Clones are biological copies of normal animals," says Larisa Rudenko, Ph.D., a molecular biologist and risk assessor in the Food and Drug Administration's Center for Veterinary Medicine (CVM). "In theory, they're pretty close to identical twins of an adult animal."

Although the technology to clone farm animals was developed more than 20 years ago, today's method of cloning, somatic cell nuclear transfer (SCNT), has been around only since 1996. Coover estimates that only a couple hundred of the 100 million cattle in the United States are SCNT clones. And you won't find meat or milk from SCNT cloned animals in your supermarket yet--the FDA has asked companies that clone animals not to introduce any of them, their offspring, or their food products into human or animal food until the agency has evaluated the safety of these products. The companies are cooperating, says Stephen Sundlof, D.V.M., Ph.D., director of the FDA's CVM. "And we're being very diligent to make sure if this new technology makes it to the marketplace, that it's safe for people to eat."

It's unlikely that you will eat a cloned animal anytime soon. At a cost of about $20,000 each to produce, clones are used for breeding--not for food. But some scientists and farmers are looking at the descendants of cloned cattle, pigs, goats and sheep as potential sources for food and clothing, if the FDA gives the OK.

Mandated with protecting the nation's food supply and animal health, the FDA is working to set a policy on cloned animals, based on the best available science. "We do not want these products on the market until there has been a thoughtful, thorough and deliberate evaluation of the issues," says Sundlof. "We want to make sure that the public is clearly informed and that they have had a chance to participate in the process."

The Cloning Process

Early methods of cloning in the 1970s involved a technology called embryo splitting, or blastomere separation. Embryos were split into several cells and then implanted into a surrogate mother for growth and development. But there were a limited number of splits that could be made, and only a few clones could be produced from one egg. The characteristics of the clone were also unpredictable because scientists were cloning from an embryo whose traits could not be predicted.

The practice of cloning took on new meaning in 1996 with the birth of Dolly the sheep, the world's first mammal cloned from an adult cell. Dolly was produced using SCNT technology. Since the cloning of Dolly, this technology has been used to clone cattle, mice, goats, pigs, rabbits, and even a cat. Unlike the embryo splitting method, in theory, SCNT can be used to make an unlimited number of copies of one animal.

The SCNT process starts with an unfertilized egg, or oocyte. Scientists remove the oocyte's nucleus, which contains the egg's genes, or hereditary "instructions." What remains after removal of the nucleus is a cell that contains nutrients essential for embryo development and other cellular machinery waiting for a new set of instructions.

A somatic cell from the animal to be cloned--or in some cases, just the cell's nucleus--is cultured in an incubator and then injected under the coating of the unfertilized oocyte. (Somatic cells are any cells of the body except sperm and eggs.) Stimulated by a mild electrical pulse, the oocyte cytoplasm (everything in the cell but the nucleus) and the genetic material from the donated somatic cell combine. If fusion is successful, the resulting fused cell divides just as if it were a fertilized egg and produces an embryo. The embryo is placed in the uterus of a surrogate mother and, if development proceeds normally, an animal clone is born.

But there's a tricky part to this process, says Rudenko. The nucleus of the adult cell is specialized, or differentiated, for a particular function. "The nucleus has matured to a point where its instructions are 'locked away' in a configuration specific to the job that the cell is intended to perform," says Rudenko. "For example, a muscle cell has a different job from a liver cell, and it has a different set of instructions available to it. The complicated part of cloning that we don't fully understand is how those instructions get reset."

The unlocking and resetting of instructions without making changes to the genetic code is called epigenetic reprogramming. This process allows the cell to develop into a new organism instead of continuing to do its old specified cellular functions. And it's the epigenetic reprogramming that scientists haven't yet mastered and that accounts for frequent cloning failures.

Steven Stice, Ph.D., explains epigenetics as the propensity for different outcomes from identical DNA sequences. An example of an epigenetic effect in normal human birth is the different fingerprint patterns of identical twins, says Stice, a professor in the Animal and Dairy Science Department at the University of Georgia and chief scientific officer for ProLinia Inc., a livestock cloning company in Athens, Ga. Epigenetic changes are not unique to cloning but are more noticeable in clones, Stice adds. "Everything from in vitro fertilization to artificial insemination can have epigenetic effects."

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