This spring, news of a biological breakthrough arrived in the form of baby marmosets whose feet glowed green under ultraviolet light. Researchers at the Central Institute for Experimental Animals in Kawasaki, Japan, had genetically engineered the monkeys to incorporate a gene, derived from jellyfish, that produces green fluorescent protein. It was the first time scientists had added a gene to a primate in such a way that a new trait could be passed to a second generation.
The feat heralds an exciting possibility: if the genes associated with some cases of human illnesses such as Huntington’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease were introduced into primates, colonies of the genetically altered animals could be used to test therapies for these disorders. This would probably be far more effective than studying the effects of the genes in, say, mice or rats, because primates’ brains are much closer to humans’ in terms of complex motor functions and cognition. “We’ve been waiting a long time for [disease] models like these,” says John Morrison, a professor of neuroscience at Mount Sinai School of Medicine in New York.
For years, researchers have created animal models for the study of disease by transferring new genes into less advanced animals such as mice. In 2001, scientists at Oregon Health and Science University reported the first transgenic primate, a rhesus monkey that produced green fluorescent protein. But the Japanese researchers broke new ground. Erika Sasaki and her colleagues introduced the jellyfish gene into early-stage marmoset embryos. Then they transplanted the embryos into adult female monkeys, resulting in several pregnancies and a few offspring that carried the gene. Sperm and egg cells from monkeys with the gene were then used to produce additional offspring in vitro, some of which also carried the gene and produced the fluorescent protein.
Of course, creating a few transgenic marmosets is a long way from creating colonies available for testing disease-specific treatments. For one thing, Sasaki and her colleagues used a virus to introduce the new gene, which means that they could not control how many copies would be inserted into the monkeys’ genome or exactly where they would be incorporated. Researchers will probably need to develop a more precise, consistent way to introduce new genes, especially if they want to simulate diseases.
Besides, marmosets may not be an ideal research model. They were a good choice for the Japanese team because they reach sexual maturity relatively quickly, and females may produce 40 to 80 offspring in a lifetime. They’re also less expensive and more efficient to work with at the colony level than larger primates that reproduce less copiously. Still, they have yet to prove themselves as models for neurodegenerative diseases. That’s because their brains differ more from humans’ than the brains of Old World monkeys like rhesus macaques do. And less is known about their normal cognitive function, because it has not been studied as actively. So for studying disruptions of higher-order processes like memory, which can be central to neurodegenerative diseases such as Alzheimer’s, they may not be good enough.
Still, the possibility of transgenic primate models could revolutionize medical research. Such primates could offer a proving ground for new therapies that look promising in mice but seem too risky to try in humans. This is especially true for disorders that involve the brain and nervous system. Morrison says the lack of good primate models has been a “major obstacle” in developing and testing new treatments for several neurodegenerative diseases.