Monkey milestone: Jellyfish gene added

Three-month-old Andi has the wide-eyed look and tireless curiosity of any toddler exploring the world for the first time.

Andi, a rhesus monkey, is unique, however. He is the first primate to carry a gene from another species. Born last October, he is host to multiple copies of a jellyfish gene.

For the scientists who put Andi into the biological record books, the gene transfer could pave new avenues for medical research.

Eventually, they say, primates could be tailor-made for the testing of gene-and cell-based therapies on species that are biologically closer to humans than mice.

Yet, even while it may accelerate progress in medicine, the method used on Andi brings mankind a step closer to the ability to manipulate its own genetic makeup. That raises long-term ethical challenges as thorny as those that surrounded the cloning of a sheep named Dolly in 1996, some bioethicists say.

Biologically, Andi is much closer to humans than a sheep, they say. If desirable genes could reliably be implanted in unfertilized eggs and brought to term with predictable results in a monkey, the prospect of duplicating the feat in humans grows stronger.

"If you refined the technique, should we use this technique on humans? That's a question people should be talking about," says George Annas, a bioethicist who heads the health-law department at Boston University's School of Public Health.

Of mice and monkeys

For its part, Andi's Oregon-based research team is focusing on efforts to move novel therapies from the lab to the bedside.

"Certain diseases could be cured more quickly and safely by having a limited number of special models to perfect the cure of disease," says Gerald Schatten, a researcher at the Oregon Health Sciences University (OHSU) in Portland and a member of the team reporting results in today's issue of the journal Science.

Mice would still carry the load for basic research, he notes. "But there's a huge leap between people and mice."

One way to close that gap, he says, is to enlist monkeys genetically altered to carry gene mutations that researchers associate with certain illnesses in humans.

Until now, no one had successfully used genetic engineering to give a primate novel genes. The researchers, led by OHSU biologist Anthony Chan, selected 224 rhesus-monkey eggs, used viruses to place jellyfish genes in the eggs' genetic lineup, then fertilized the eggs and implanted 40 embryos into surrogate mothers. The genes carry the code for a protein that glows under the right type of lighting.

Five births led to three healthy males, including Andi. Genetic "fingerprint" tests showed that Andi had the gene, although he didn't pass the glow test. Two other twin monkeys, who were stillborn, tested positive for the protein under a black light as well as through other methods. The researchers say the protein still could show up in the two other healthy males.

A first step

Dr. Schatten notes that Andi represents a preliminary step in efforts to provide a reliable, predictable way to insert foreign genes into a monkey's genome. Indeed, he continues, while in principle using genetically modified monkeys for medical research has appeal, as a practical matter "the jury is still out on how primates could contribute."

This leads biotech critics such as Jeremy Rifkin, who heads the Foundation for Economic Trends in Washington, D.C., to join those concerned about the longer-term uses for such techniques.

"The rhesus monkey is a warning," he says. "What we can do to them we can do to ourselves. We can take genetic material from totally unrelated species and shift them across biological boundaries. This is a radical experiment on nature."

Not everyone sees Andi in such stark terms. Alta Charo, a member of the National Bioethics Advisory Commission, notes that the OHSU team's approach is unlikely to be applied to humans, at least in the short run. She notes that there is no need to put nonhuman genes in a human, and that given the team's success rate, the procedure would be deemed too risky to perform on humans.

Yet, she adds, this and other developments point to the need for a tighter set of rules governing biomedical research, particularly as they apply to the use of human subjects. Last month, the commission released a draft report for comment that proposes extending federal research regulations to cover private companies as well as universities or others spending federal money.

"We need to indicate that regulations governing ethical research are more than just a condition of funding," says Ms. Charo, who is a law professor at the University of Wisconsin at Madison. "They are an aspect of basic civil rights."

Schatten says his team does "not support any extension of this technique to humans." But he acknowledges that any technology has the potential for misuse. "We would welcome a deepening of the [ethical] conversation."

(c) Copyright 2001. The Christian Science Publishing Society