Thanks to a genetic manipulation, three color-blind mice recently gained the ability to see the world in the same hues as humans do.

Mice and nonprimate mammals—much like color-blind people—see relatively few hues, because their retinas contain photoreceptors (cells with a light-sensing protein pigment) that only absorb blue (short) and green (medium) wavelengths of light. Scientists say that most primates, including humans, have a third receptor that also absorbs red, or long wavelengths, thanks to a primate ancestor who passed along a gene mutation for it an estimated 40 million years ago.

According to Gerald Jacobs, a psychologist at the University of California, Santa Barbara, the research that allowed these mice to see in full color was an attempt "to replicate what must have been the first stage in the evolution of primate color vision." The ability to see the world as humans do, he says, "requires an additional sensor—or photopigment—and the nervous system being able to compare the signals."

Would merely adding the new photoreceptor be enough to enable an animal to process new hues or is some brain rewiring—which would take several successive generations to develop—also be needed? The finding, published in this week's Science: new sensory input is all it takes to enhance vision from, say, a box of 16 to a box of 128 colors of crayons.

Jacobs, along with Jeremy Nathans, a professor of molecular biology and genetics at the Johns Hopkins School of Medicine, trained mice, which had been genetically altered to have a full complement of photoreceptors, to distinguish differences in shades of color that normal mice would not notice.

Only female mice were used for the experiment, Jacobs says, because the genes that code for pigment proteins are located on the female, or X chromosome. Nathans' group engineered mice to have a human long-wavelength receptor gene in place of their medium-wavelength receptor. After they were bred with normal mice, the male offspring (which carry only one X chromosome, as opposed to two in females) ended up with either all medium- or all long-wavelength photoreceptor cells, but never a mix of both, in their retinas.

Some of the female mice, however, ended up with genes for both photoreceptors: a medium wavelength gene on one X chromosome and a long wavelength one on the other. In each cell in the female body, one of the X chromosomes is randomly inactivated to eliminate redundancy. Some of the cells in the retina will inactivate the chromosome coding for long-wavelength receptors, whereas others will silence the medium-wavelength receptor gene. Thus, some retina cells will have medium-wavelength photopigment and others will produce the long-wavelength variety.

Researchers then exposed the mutant, female mice to a light-discrimination test involving three colored panels—two of similar hues and the other differing in brightness or shading. After a significant training period—the researchers conducted well over 10,000 trials, rewarding mice who singled out the odd panel with a drop of soy-milk—three mice with the full complement of photo receptors were able to correctly finger the different panel 80 percent of the time. Normal mice, on the other hand, were only successful about one third of the time, a percentage equivalent to just randomly guessing.

Jacobs points out that not all of the mutant mice were able to successfully complete the color discrimination test, which he says could indicate how species deal with newly introduced abilities during evolution. He adds that the next step will be to determine how the brain incorporates the new color signals and makes the comparisons necessary to distinguish between different shades. "What this shows is that not only can you expand the range in which animals can sense stimuli," he asserts," but they can derive a new dimension of sensory experience."