Monkey see, monkey glow

SAN FRANCISCO — Altering the genome in such a way that changes could be passed on to future generations is a line that science has not yet crossed for humans — but it now has for monkeys.

An experiment in Japan has bought science closer to genetic engineering's ethical boundary, an area that many countries, including the United States, have yet to demarcate under law.

Researchers at the Central Institute for Experimental Animals in Kawasaki recently imbued a handful of South American monkeys with a gene for florescence, and then showed that the initial cohort could pass on this trait to their offspring — the first inheritable genetic manipulation in the family of primates that includes humans.

The Japanese scientists experimented on marmosets, a species of primates more distant from humans than Rhesus monkeys or chimpanzees. The journal Nature, which reported on the experiment, said the technique had “little immediate bearing” on human genetic alteration because the marmoset is so far removed from man. But a commentary in the journal acknowledged that the experiment raised bioethical concerns — “foremost among them is the prospect of unwarranted and unwise application of transgenic technologies” to human beings.

Scientists have long known how to create colonies of mice and rats with inheritable disease traits for use in drug research. The potential addition of marmosets to that list was sufficient to inflame animal rights activists.

But the proximity of genetic alteration to human inheritance was the novel concern raised by the experiment — a prospect which many nations have yet to consider, according to Marcy Darnovsky with the Center for Genetics and Society in Oakland, Calif.

The center, which has helped survey the legal status of inheritable genetic modification around the world, says 44 nations already have laws that would prohibit such experiments on humans, including Japan, Canada, Australia and the members of the European Union.

Darnovsky said the cloning of Dolly the sheep, announced in 1997, prompted the European Union to consider that scientists might try to make inheritable modifications to humans. Member nations included a prohibition against any such attempts in the 1999 Convention on Biomedicine and Human Rights. The convention allowed “genetic engineering only for preventive, diagnostic or therapeutic reasons and only where it does not aim to change the genetic make-up of a person's descendants,” according to an official summary.

“In Europe this all got considered under a framework of human rights,” Darnovsky said, the concern being that human alteration “would lead to a world of genetic haves and have nots.”

But in the United States, Darnovsky said, the issue got caught up in what she called “the embryo swamp” — the disagreement over how to define human life that has polarized American debate on issues ranging from abortion to stem cell research. As a result, professional guidelines remain the only U.S. bulwark against the genetic engineering of human inheritance, Darnovosky said.

As the Nature commentary suggests, mainstream scientists do not now believe they could ethically attempt such modifications on human beings — even if considered desirable — because current techniques involve so many failures, Darnovsky said. The Japanese researchers, for instance, altered 80 marmoset embryos to include a florescent jellyfish gene, then implanted these embryos into 50 surrogate females to produce seven pregnancies and five offspring, four of which expressed the green glow in the presence of ultraviolet light.

Yet after all that effort, those first-generation results weren't the real breakthrough. Oregon State University scientists had already genetically engineered a florescence gene into a Rhesus monkey in 2001. The novelty in the Japanese experiment was the birth of a second-generation male offspring, fertilized in vitro using the sperm of an altered first-generation male. To go to such lengths, including miscarriages, to produce an inheritable human modification would violate too many ethical norms, Darnovsky said.

But in time, other researchers could improve the technique with the ultimate goal of modifying humans, suggested Lori B. Andrews, with the Illinois Institute of Technology's Chicago-Kent College of Law, in a story in the Washington Post. “This is a proof of concept in a closely related species,” Andrews said.

The editors of Nature hailed the Japanese achievement as an advance in drug research while warning that “scientists everywhere must be ready to discuss ... the possibility of transgenic humans and other controversial topics.” Darnovsky said the same is true for governments, like the United States, which have no laws on the subject. “We're really the outlier here,” she said of the United States.

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