[wordup] Human Mutants? Madam Tetrachromat ...

[Adam Shand]

From: Morgan Likely <mrorange at homernet.net>
URL: http://www.redherring.com/index.asp?layout=story&channel=70000007&doc_id=1910013991

Looking for Madam Tetrachromat
November 1

"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 tetrachromat.

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.