Glowing monkey genes raise ethics issues

WASHINGTON — Scientists have created the first genetically modified monkeys that can pass their new genetic attributes to their offspring, an advance designed to give researchers new tools for studying human disease but one that raises a variety of thorny ethical questions.

In this case, the Japanese researchers added genes that caused the animals to glow green under a fluorescent light and beget offspring with the same ability to test a technique they hope to use to produce animals with Parkinson's, Huntington's and other diseases.

The work, described in the new issue of the journal Nature, was hailed by some medical researchers as a long-sought milestone that could lead to crucial insights into a variety of ailments and provide invaluable ways to test treatments.

But the research was condemned by animal-rights proponents, who said it paves the way for producing colonies of primates conceived expressly to experience a plethora of illnesses and undergo potentially painful and dangerous medical experiments.

Because the work marks the first time a species so closely related to humans has been genetically altered in this way, some also worried the same techniques would be used on chimps or other primates even closer to humans or to try to endow people with desirable genetic traits.

"It's hard to put your finger on what is it about this research that is likely to stimulate ethical debate besides the sort of gut feeling that this is not the right thing to do," said Mark Rothstein, a bioethicist at the University of Louisville. "But I think we'd better contemplate where this research is going and develop policies to deal with it before it slaps us in the face."

Used as research tools

Scientists have genetically engineered many other species to be used as research tools. Animals that get added genetic material are called transgenic. Mice in particular have been created with a wide assortment of characteristics and diseases that mimic human ailments. But because mice are so genetically different from humans, scientists have long sought to breed primates to provide better disease "models."

Although scientists have genetically modified individual monkeys, they had never before succeeded in getting the new traits to pass down through generations, a crucial step for creating large enough numbers for research.

In the new work, Erika Sasakim, of the Central Institute for Experimental Animals in Kawasaki, and her colleagues conducted a series of experiments using marmosets, a small monkey common in South America.

The researchers modified a virus called a lentivirus to carry a jellyfish gene known as GFP — for green fluorescent protein — into the genetic material of the marmosets' cells. The gene is used commonly in research because it is easy to track; cells where the gene is active glow green when exposed to fluorescent light.

The researchers used the genetically engineered virus to insert the jellyfish gene into 80 marmoset embryos, which they then transferred into the wombs of 50 females.

Seven pregnancies resulted in five offspring, four of which showed signs of the jellyfish gene in their hair roots, skin, blood cells and other tissues. Under fluorescent light, the skin on the soles of their feet glowed bright green.

Most important, eggs from one female and sperm from one male had the gene, and the researchers reported that the sperm was used to produce at least one second-generation offspring with the gene, a male whose skin glowed green under the light.

Some other researchers said the work marked a crucial landmark. "The birth of this transgenic marmoset baby is undoubtedly a milestone," wrote Gerald Schatten, of the University of Pittsburgh, and Shoukrat Mitalipov, of the Oregon Health & Science University in an article published with the Japanese paper.

The other side

Others criticized the work.

"These nonhuman primates already suffer in laboratories when we infect them with diseases and when we use them in toxicology tests," said Eric Kleiman, of In Defense of Animals, an international animal-protection organization based on San Rafael, Calif.

"Instead of manipulating the genes of marmosets or other nonhuman primates, why aren't scientists harnessing the power of the human genome or any of the other technology that has exploded over the last 10 years?"

Even some who do not necessarily oppose the use of animals in research said the work raised concerns, including whether the technique could blur the lines between species.

"At some point, how many human genes in a marmoset or rhesus monkey or macaque or whatever does it take to form a new species, a species that is part human at its basis?" Rothstein said.

Even though there has long been a taboo against making genetic changes in people that could be passed down through generations, the new work makes that prospect more likely, others said.

"This is proof-of-concept in a closely related species," said Lori Andrews, who studies reproductive technologies at the Chicago-Kent College of Law of the Illinois Institute of Technology. "It would be easy enough for someone to make the leap to trying this on humans."

"There are always people who want to improve the human race. It's called eugenics and it has a bad history," said Stuart Newman, a professor of cell biology and anatomy at New York Medical College.

Other researchers said it is impossible to answer many key questions without animal research. Creating better animal models could end up reducing the overall number of animals needed for research, they said.

"In the end, if we have good models, we may end up using less animals and we may end up having better answers," said Anthony Chan, a geneticist at the Yerkes National Primate Research Center of Emory University.