Looking for Madam Tetrachromat


By Glenn Zorpette


November 1, 2000


"Oh, everyone knows my color vision is different," chuckles Mrs. M, a

57-year-old English social worker. "People will think things match, but I can

see they don't." What you wouldn't give to see the world through her deep

blue-gray eyes, if only for five minutes.


Preliminary evidence gathered at Cambridge University in 1993 suggests that this

woman is a tetrachromat, perhaps the most remarkable human mutant ever

identified. Most of us have color vision based on three channels; a tetrachromat

has four.


The theoretical possibility of this secret sorority -- genetics dictates that

tetrachromats would all be female -- has intrigued scientists since it was

broached in 1948. Now two scientists, working separately, plan to search

systematically for tetrachromats to determine once and for all whether they

exist and whether they see more colors than the rest of us do. The scientists

are building on a raft of recent findings about the biology of color vision.


The breakthroughs come just in time. "Computers, color monitors, and the World

Wide Web have made having color blindness a much bigger deal than it ever was

before," says Jay Neitz, a molecular biologist who studies color vision at the

Medical College of Wisconsin in Milwaukee. Color-blind individuals, he explains,

often lose their way while navigating the Web's thicket of color cues and codes.

"Color-blind people complain miserably about the Web because they can't get the

color code," Dr. Neitz says. (Just try surfing on a monochrome monitor.)


Most people are trichromats, with retinas having three kinds of color sensors,

called cone photopigments -- those for red, green, and blue. The 8 percent of

men who are color-blind typically have the cone photopigment for blue but are

either missing one of the other colors, or the men have them, in effect, for two

very slightly different reds or greens. A tetrachromat would have a fourth cone

photopigment, for a color between red and green.


Besides the philosophical interest in learning something new about perception,

the brain, and the evolution of our species, finding a tetrachromat would also

offer a practical reward. It would prove that the human nervous system can adapt

to new capabilities. Flexibility matters greatly in a number of scenarios

envisaged for gene therapy. For example, if someone with four kinds of color

photopigments cannot see more colors than others, it would imply that the human

nervous system cannot easily take advantage of genetic interventions.


For years now, scientists have known that some fraction of women have four

different cone photopigments in their retinas. The question still remains,

however, whether any of these females have the neural circuitry that enables

them to enjoy a different -- surely richer -- visual experience than the common

run of humanity sees. "If we could identify these tetrachromats, it would speak

directly to the ability of the brain to organize itself to take advantage of

novel stimuli," says Dr. Neitz. "It would make us a lot more optimistic about

doing a gene therapy for color blindness."


There have been very few attempts to find Madam Tetrachromat. The one that

turned up Mrs. M in England, in 1993, was led by Gabriele Jordan, then at

Cambridge University and now at the University of Newcastle. She tested the

color perception of 14 women who each had at least one son with a specific type

of color blindness. She looked at those women because genetics implies that the

mothers of color-blind boys may have genetic peculiarities of their own. Among

that somewhat peculiar group of women, one could expect to find the odd



It's almost as if the supersense these women enjoy comes at the expense of the

men in their families. "I'm just sorry I've robbed my son of one of his color

waves," Mrs. M says.


Dr. Jordan reports that of the fourteen test subjects in her study, two showed

"exactly" the behavior that would be expected of tetrachromats. "It was very

strong evidence for tetrachromacy," she adds. The apparent tetrachromats were

Mrs. M, who was identified in the study as cDA1, and another candidate, cDA7.


Dr. Jordan set up an experiment in which subjects tried to determine whether a

pair of colored lights matched. They used joysticks to blend two different

wavelengths as they pleased. The resulting hues lay outside the spectrum of the

blue photoreceptor, rendering it nearly useless, so that normal trichromats

would have the use of only their red and green photoreceptors. Having hit upon a

color, the subjects would then try to reproduce it by mixing two other

wavelengths. Because the trichromats had the use of only two receptors, they

found a whole slew of mixes that produced a matching color.


However, any tetrachromat should have been able to use three receptors in this

color space, and therefore make a single, precise match. In the experiment, cDA1

and cDA7 performed pretty much as a tetrachromat would be expected to.


Nevertheless, Dr. Jordan declines to say that she has finally found a

tetrachromat, partly because her testing is still a work in progress. The vast

majority of us have no idea what tetrachromacy would be like. Anyone who had the

supersense wouldn't know she did, let alone be able to describe it. After all,

it is an exercise in futility for trichromats to try to explain their visual

experience to color-blind people.


Dr. Neitz and Dr. Jordan each plan a more definitive search for tetrachromats.

Dr. Neitz plans to take advantage of the fuller understanding of the underlying

genetics of color vision. His will be the first experiment that will use genetic

techniques to identify women with four different color photopigments.


What will he be looking for? Let's start with the basics. The genes for the red

and green photopigments are adjacent to each other on the X chromosome;

strangely, blue is way off by itself on another chromosome. Women, of course,

have two X chromosomes and therefore two sets of red and green photopigment

genes. Men have only one X, so they have just one shot at getting the red and

green photopigment genes right.


Unfortunately for men, it turns out that those genes are prone to a kind of

mutation that occurs when eggs are formed in a female embryo. When the eggs are

created, the X chromosomes from the maternal grandmother and grandfather mix

with each other in random places to make the egg's brand-new X chromosome.

Because the genes for the red and green photopigments are right next to each

other, those genes sometimes mix. That's perfectly normal. But every once in a

while, the mixing occurs in a lopsided way, and the result, 30 years later,

could very well be a man who has to check with his wife every time he dresses.


A lopsided mix can have three outcomes: (1) the egg in the embryo has an X

chromosome that's missing either a red or a green photopigment gene, (2) the X

chromosome has two slightly different red photopigment genes, or (3) the X

chromosome has two slightly different green photopigment genes. In any of these

cases, if that egg gets fertilized and becomes a male, the man will get that X

chromosome and be color-blind.


Here it gets interesting. Suppose a woman inherits one X chromosome with two

slightly different green photopigment genes. And let's say her other X

chromosome has the normal complement of red and green photopigment genes.

Because of a well-known biological phenomenon called X inactivation -- which

causes some cells to rely on one X chromosome and others to rely on the other --

that woman's retinas would have four different types of photopigments: blue,

red, green, and the slightly shifted green. (It would also be possible, through

a different genetic sequence, to produce blue, green, red, and a shifted red.) X

inactivation is only possible in women, so there has never been, and probably

never will be, a male tetrachromat.


True tetrachromacy would require a few other characteristics in addition to

retinas with four different photopigment receptors. For instance, there would

have to be four neural channels to convey to the brain the sensory inputs from

the four receptors, and the brain's visual cortex would have to be able to

handle this four-channel system. If a woman were born with four types of

photopigments, would her brain wire itself to take advantage of them? No one

knows for sure, but some experts strongly suspect it would. "Yes, definitely,"

says Jeremy Nathans, a pioneer in color-vision research at Johns Hopkins

University School of Medicine. One reason to think so is the brain's great

plasticity in other respects. People with special skills -- musicians,

bilinguals, deaf people who learn sign language -- often show characteristic

brain patterns.


Dr. Nathans also believes, however, that for full-blown tetrachromacy, the

fourth photopigment must not have a peak in sensitivity that is too close to the

peaks of either the red or the green photopigments. That's the rub, as far as

he's concerned -- he suspects that most female tetrachromats would have only

mildly superior color vision, because the genetics indicates that the fourth

photopigment would almost always be very close to either the red or the green.

Every now and then, however, an oddball photopigment might appear, well

separated from both red and green. "The genetics do not rule it out," Dr.

Nathans explains. "It would be a rare event. But who's to say it hasn't

happened? There are a lot of people out there."


That idea finds support in the recent discoveries about the genetics of color

vision, many made by Dr. Neitz's group. Those findings have shown that the

genetics underlying color vision are surprisingly variable, even within the

narrow range regarded as normal. "The variety in photopigment genes in people

with normal color vision is enormous," Dr. Neitz reports. "It's enormous."


Would there be any practical advantages to tetrachromacy? Dr. Jordan notes that

a mother could more easily spot when her children were pale or flushed, and

therefore ill. Mrs. M reports that she has always been able to match even subtle

colors from memory -- buying a bag, for example, to match shoes she hasn't laid

eyes on for months. And computers, color monitors, and the Internet raise a

whole raft of possibilities. Just as someone with normal three-color vision

surfs rings around a dichromat on the Internet, a tetrachromat, looking at a

special computer screen based on four primary colors rather than the standard

three, could theoretically dump data into her head faster than the rest of us.


If Dr. Neitz or Dr. Jordan finally finds Madam Tetrachromat, the discovery will

confirm that the human nervous system can handle four-channel color vision. And

that confirmation would raise the possibility that, within a couple of decades,

gene therapy will make tetrachromacy just another option that wealthy parents

could check off on the list when they are designing their daughters.


It won't be possible with male children -- not for quite some time, anyway. So

as long as we're on this flight of fancy, let's take one more short hop: a few

decades from now, men and women will still be seeing the world differently. But

the expression might not be merely figurative any more.




Free book chapter on color vision.



Q & A on the biology of human color vision.



Web site for Jay Neitz's laboratory on color vision at the Medical College of

Wisconsin. Includes images showing how the color blind would see certain scenes

and objects.



Explanation of the genetics behind color-vision deficiencies.




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