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SECOND GLANCE

Sam and Dalton
Pioneering Monkeys

A three year old boy fell eighteen feet into a zoo enclosure containing seven gorillas. He was immediately rescued not by zookeepers, but by one of the animals. A large female gorilla picked up the unconscious form of the boy and laid it at a door to be easily retrieved by zookeepers. This cross species contact has resulted in thousands of dollars in donations to the zoo. It is perhaps because of these donations that zookeepers have kept quiet about one vital detail: a hastily scrawled note tucked in the boy's collar. It said, “Thanks, but we prefer fruit."

Dalton and Sam are two small monkeys of the Squirrel variety. Their species originally lived in Central and South America under the natural protection of a forest canopy. They subsisted on fruit and insects and did their best to avoid natural enemies such as falcons. However, now they are living off the fat of the land under human protection. Dalton and Sam are the guests of Jay and Maureen Neitz of the Univ. of Washington, Seattle, Wash. Laboratory reports of color vision research there has broken a few of the boundaries that were heretofore impregnable. 

Unlike humans, who have three color pigments known as opsins, male squirrel monkeys have but two. The Neitzes, together with other researchers, provided the missing red pigment which, via gene therapy, was provided to the retinal cones of the monkeys. After a few months it was reported that the monkeys were able to see a world which included the added red hues. 

You might ask how in the world could the researchers tell what colors the monkeys could see or couldn't see. Their color skills were judged by their reaction with a specially designed color vision test and were rewarded with fruit juice. Researchers were astonished to discover that the monkeys' brains could utilize the new third opsin. It's really not that complicated. The new opsin provided for Dalton and Sam is a colorless protein which changes the signal from affected cones and it is relayed from the retina to the visual cortex. The red opsin gene was carried by a virus particularized for gene therapy experiments. The virus was injected into the monkey's eyes and fastened to the cones in the retina together with a piece of DNA. The cones were triggered to make the new red opsin preferable to their own green opsin. The virus carrier affected some cones, but some were not. 

Therefore, the monkeys had both red and green working in addition to their unaffected blue cones. It was thought that adding new visual receptors required to achieve perfect color vision should be added in the earliest years of life while the brain is still impressionable by new stimuli.

Dr. Jeremy Nathans is a molecular biologist at Johns Hopkins Univ. He has produced a laboratory mouse with full color vision. Scientists feel that the monkey experiments will assist other researchers in understanding the neurological components used by the human and other primates to analyze color. Further work is required to test how the cells in the visual cortex react to the new signals from the retina. 

Male monkeys, like Dalton and Sam inherited their color skills because their forebears developed differently from other primates before full color vision resulted. Before the change they perceived only two colors. One pigment was blue and another that reacted best to either green or red, depending on which gene was dominant. About 150 million years ago, give or take a million, the early primates experienced a genetic change. It seems that the gene for the red/green pigment was duplicated. This permitted subjects to see red and green instead of just either one or the other. 

It has been noted that monkeys, currently, have never developed the duplicated gene. Nevertheless, many female monkeys possess full color vision skills. It's simple: the red/green opsin is sustained by the X chromosome. Females inherit a different combination from each parent embodying both red and green opsins along with the blue opsin present in another chromosome. However, the males, having only one X chromosome inherit just one variant of the red/green opsin. In the case of Dalton and Sam, it's the green. This discovery has led researchers to believe that a treatment can be developed for color blind humans. 

Scientists, until now, did not feel that an adult brain could be manipulated in this manner. But Dr. Neitz introduced therapeutic genes into retinal tissue of our monkeys and changed all previous ideas regarding color vision and how it can be altered. The success of the gene therapy was revealed by tests which proved that the monkeys possessed the needed pigments to see all the colors. They correctly distinguished between red from green on computer image tests. The monkeys used this method to trace the color patterns. When the animals chose correctly they were rewarded with grape juice. The tests were similar to those given to elementary school children the world over. It is called the Cambridge color dot test. The monkeys were treated over two years ago and the results have remained stable. After only five weeks of treatment the monkeys began to acquire color vision. After twenty weeks, the researchers said, "It was as if they awoke and saw these new colors that were previously invisible to them." 

The monkeys, after a year and a half of testing, were able to discern 16 hues, with some of the colors varied in intensity by eleven fold. The animals will continue to be monitored so that any long term effects can be discovered. 

Still, the monkey's actual sensation of color and what it looks like to them remains a mystery. Melissa Saenz, a neuroscientist at Caltech in Pasadena, Calif. claims that even though the monkeys can discriminate some new colors there is no evidence that the monkeys perceive a new dimension of color. For example, the monkeys may now perceive red and green as different shades of yellow and blue, colors that the animals already knew. She adds, "If it doesn't involve experiencing new sensations of color, it would not dramatically change the experience of color blind people if the treatment were applicable to humans."

Winifried Arnoaku, an ophthalmologist of the Univ. of Nottingham, U.K. suggests that this research could eventually benefit approximately 7% of males and 1% of females born with genetic color deficiencies. Other areas of advantage exist in those cases wherein color vision is affected by macular degeneration, diabetic retinopathy or side effects due to medications. Human DNAs were used so that the switch to human genes will be made easier through clinical research. Another area of help will be afforded to victims of Leber congenital amaurosis, a form of blindness that strikes children. About 1 in 30,000 Americans have a hereditary form of blindness called achromatopsia, which causes nearly complete color blindness and extremely poor central vision. These patients could benefit by this same treatment. The color blind population in the U.S. is about 3.5 million, more than 13 million in India and more than 16 million in China. 

Dr. Neitz states, "We've had Dalton and Sam for 10 years. They are like our children. They are friendly, docile monkeys that we just love. We continue to check their vision and allowing them to play with the computer is part of their enrichment." Dalton is named for John Dalton, an English chemist, who realized he was color blind and published the first paper about the condition in 1798. Much has been learned since those early days. It is hoped that in the not too distant future, all mysteries will be solved.

Elmer Friedman, O.D.
elmerf@verizon.net

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