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IN LIVING COLOR: A squirrel monkey named Dalton feasts on food that he can see in full color thanks to gene therapy that fixed his color-blindness in about five months.
NEITZ LABORATORY

Two naturally color-blind squirrel monkeys, Dalton and Sam, can now see their food—and the world—in full color, after a decade of study by a husband and wife research team who treated them with gene therapy.

The findings are the latest to blindside the traditional wisdom that adults cannot acquire vision they never had. It also sheds light on new leads in the quest to understand how color vision evolved in the first place.

Just like humans, monkeys are occasionally born with a defective gene that is responsible for some of the color receptors in their retinas, leaving them red–green color-blind. With this condition, even the brightest version of these colors is indistinguishable from gray. "Everything else is normal about them," Jay Neitz, a professor of ophthalmology at the University of Washington (U.W.) School of Medicine in Seattle and senior study author, says of the monkeys.

Although some vision experiments can be tricky to adapt to animals that can't respond to verbal instructions, the tests for color-blindness, called the Cambridge Color Test, were nearly identical to those given to young children. "We can test the vision of these monkeys every bit as accurately as we can test vision in humans," Neitz says. Researchers displayed a color figure among dots of a contrasting background color, slowly changing the contrasts and the colors to determine the monkeys precise point of color-blindness—specifically, where the figure was suddenly visible or invisible. The monkeys traced the shapes, when they saw them, on a touch screen monitor and received grape juice as a reward.

Unlike some other common vision disorders, such as age-related macular degneration, color blindness is a heritable disorder caused by a single gene that is defective or absent. Neitz and his wife, Maureen Neitz, also in the U.W. ophthalmology department, and the rest of their team have pinpointed that gene and developed a working virus vector to carry a functional copy of it.

The researchers injected the gene-carrying virus into the monkeys' eyes. In about 20 weeks they attained full color vision and have shown no harmful side effects. Although their vision didn't quite reach that of monkeys born with normal genes, Neitz notes that the weakness might be attributable to the need for improvement on the human end in perfecting the treatment.

The results were published online today in Nature (Scientific American is part of the Nature Publishing Group).

That the monkeys' minds were still able to perceive color that they had never previously encountered supports the idea that even into adulthood the brain can perceive a range of new colors, highlighting its persisting plasticity. It also suggests that the primate brain might have been capable of seeing color before the eyes were able to deliver it. If a new kind of photoreceptor appeared in the retina but the brain didn't process anything differently, "how could that new mutation get propagated through the population?" Neitz asks. "You almost have to have it happen right away because if you have to wait for all the parts and circuitry to come in, it would never evolve."

On a more pragmatic level, the researchers hope to soon be able to translate the findings into clinical trials to test safety and efficacy in people. The group used human genetic material in the monkeys in the interest of expediting future research. Will their success, then, translate easily to humans? "You really can't know until you do it," says ophthalmologist Tim Stout of Oregon Health & Science University in Portland, who wasn't involved in the research. "We are remarkably similar to nonhuman primates."

Red–green blindness affects about 7 percent of U.S. men and 0.4 percent of women, and is one of the most common genetic disorders. So curing it would bring relief to many. "If you talk to the 19-year-old color-blind kid who wants to be a jet pilot, he would talk about it as if he were blind," Neitz says. "If this could be made safe for humans, would there be people who would line up for it?" Neitz asks. "Absolutely."