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What
is astonishing about vom Saal's wombmate
studies is how little it takes to dramatically change the tune. Hormones
are exceptionally potent chemicals that operate at concentrations
so low that they can be measured only by the most sensitive analytical
methods. When considering hormones, such as one of the estradiols,
the most potent estrogen, forget parts per million or parts per billion.
The concentrations are typically parts per trillion, one thousand
times lower than parts per billion. One can begin to imagine a quantity
so infinitesimally small by thinking of a gin and tonic made with
a drop of gin in a train of tank cars full of tonic. That one drop
in a train 6 miles long would be one part in a trillion.
The
striking lifelong differences between a pretty sister and ugly sister
stem from no more than a 35 parts-per-trillion difference in their
exposure to estradiol and a one part-per-billion difference in testosterone.
Using the gin and tonic analogy, the pretty sister's cocktail had
135 drops of gin in 1000 tank cars of tonic and the ugly sister's
100 drops-a difference that might not be detectable in a glass much
less in a tank car flotilla.
This
is a degree of sensitivity that approaches the unfathomable, a sensitivity,
vom Saal says, "beyond people's wildest imaginations."
If such exquisite sensitivity provides rich opportunities for varied
offspring from the same genetic stock, this same characteristic
also makes the system vulnerable to serious disruption if something
interferes with normal hormone levels -a frightening possibility
that first dawned on vom Saal when Theo Colborn called him to talk
about synthetic chemicals that could act like hormones.
To
appreciate vom Saal's concern, one must understand more about the
intricate choreography of events before birth known as sexual differentiation
and the key role played by hormones in this developmental ballet.
In mice, elephants, whales, humans, and all other mammals as well
as in birds, reptiles, amphibians, and fish, the process that creates
two sexes from initially unisex embryos is guided by these chemical
messengers. They are the conductors that give the cues at the right
moment as tissues and organs make now or never choices about the
direction of development. In this central drama in which boys become
boys and girls become girls, hormones have the starring role.
Our
understanding of what determines whether a fertilized egg becomes
a male or female is very recent. Before the 20th century, it was
widely assumed that the sex of the baby was determined by environmental
factors such as temperature.
It
was only in 1906 that two scientists -Nettie Marie Stevens and Edmund
Beecher Wilson-independently noted that each cell in women had two
X chromosomes while men always had an X and a Y, an observation
that led to the theory that the number of X chromosomes determined
sex. In the past decade, researchers have finally established that
it is a gene on the Y chromosome rather than the number of X chromosomes
that determine sex.
As
most of us learned in high school biology, the eggs produced by
the mother all carry one X chromosome, and that the sperm from the
father carry either an X or a Y chromosome. The sex of the baby
hangs in the balance as the sperm burst out of the starting gate
and race against each other in the reproductive marathon. If this
most primordial of athletic events were broadcast like the Boston
Marathon, we might hear that three Ys are neck and neck at the entrance
to the cervix, but an X is making a move on the outside in the push
into the uterus. A field of 75 million sperm have been pushing hard-sweeping
their tails back and forth in steady swimming motions, but in the
biological equivalent of Heartbreak Hill, many are beginning to
flag as they enter the fallopian tube leading from the top of the
uterus. It's a tight race right to the finish line, but in the final
seconds one racer thrusts ahead of the others. At the finish line
of this race, an egg awaits the victor, rather than a crown of laurel,
as it crashes through. If the Y-carrying sperm gets to the egg first,
the baby, who has XY chromosomes, will be a boy. If the first sperm
to the egg carries an X, the XX chromosome will produce a girl.
Such
stories about the race between the Xs and the Ys for the egg left
many of us with the impression that the outcome was all in the genetic
instructions carried by the sperm. If the sperm delivered a Y, bingo,
it was a boy-what unfolded between conception and birth was all
more or less automatic and dictated by that genetic blueprint. In
fact, the process is much more complex. The sex-determining gene
in that Y chromosome has only a quick walk-on part in the elegant
and wondrous process through which boys become boys.
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