Genetically modified monkeys pass new genetic profile to offspring
Washington Post | May 27, 2009
By Rob Stein
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 host of thorny ethical questions.
In this case, the Japanese researchers simply added genes that caused the animals to glow green under a fluorescent light and beget offspring with the same spooky ability in order to test a technique they hope to use to produce animals with Parkinson’s, Huntington’s and other diseases.
The work, described in Thursday’s issue of the journal Nature, was hailed by some medical researchers as a long-sought milestone that could lead to crucial insights into a host of ailments and provide invaluable ways to test new treatments.
But the research was condemned by animal rights proponents, who said it paves the way for the producing colonies of primates conceived expressly to suffer a plethora of cruel 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.”
Scientists have genetically engineered many other species to be as research tools. 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 been able to genetically modify 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 that matures and reproduces quickly.
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 importantly, eggs from one of the females and sperm from one of the males had the gene, and the researchers reported in the scientific paper that male’s sperm was used to produce at least one second-generation offspring with the gene — a male named Kouichi whose skin glowed green under the light.
In a telephone briefing for reporters, the researchers said they had since produced four offspring — two from the male and two from the female — three of which glowed green.
“We believe this is the first case that is ever established in the world that has an introduced gene that is successfully translated to the next generation in a primate,” said Hideyuki Okano of Keio University School of Medicine.
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 and Sciences University in an article published with the Japanese paper.
But others criticized the work.
“These non-human 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 non human 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. This is a step backward, not a step forward.”
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’s clearly the potential to try to use this to try to upgrade people,” Andrews said. “Some in the future might want to put a gene into humans to give them the running speed of a cheetah, for example, or maybe create the potential for night vision. There is a huge market — bigger than Prozac or Viagra.”
Andrews noted that reproductive technologies are largely unregulated in the United States.
“This is just another reason why we need to go behind the doors of the IVF clinics and create an oversight mechanism that works,” Andrews said.
“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 “Every time I see a piece of technology that facilitates possibly genetically engineering humans I’m concerned about it.”
Other researchers agreed that animal research should be kept to a minimum but argued that it is impossible to get answer many key questions any other way. 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 to for what we are looking for,” said Anthony Chan, a geneticist at the Yerkes National Primate Research Center of Emory University who helped create a rhesus monkey with Huntington’s disease.
But Chan agreed that steps should be taken to make sure the technology is not used on people.
“We should never do it in humans,” Chan said. “We don’t want to change our evolutionary path. That would have a profound impact on the next generation.”
