The Significance of a Dark Spot

The moment a female mammal is conceived -- whether mouse, cat or woman -- she has two X chromosomes, one each from father's sperm and mother's ovum. The presence of the pair of Xs, which are reproduced in all of her body's cells, is what makes her female. But each X chromosome packs many other chemically coded instructions for the body; if both a woman's Xs remained active throughout life, she would be flooded with a double quota of some blood-clotting factors, enzymes and other vital proteins. Since she is not, something must happen to deactivate one of those X chromosomes.

Cytologists (cell scientists) had known since the early 1900s that some animal cells studied under the microscope contain a little dark spot that others lack. Yet not until 1949 did Canadian Neuro-Anatomist Murray L. Barr realize that the spots, which he was studying in cats' nerve cells, appear only in cells from females. Later research showed that the spots, now known as "Barr bodies" or sex chromatin, consisted of one X chromosome -- the one that is inactivated after it has done its job of helping to determine femaleness.

Testosterone Treatment. All this seemed to be solely in the province of genetics, and to have nothing to do with cancer, until Dr. H. A. Hienz, at the Pathology Institute in Essen, Germany, brought the two together. He was seeking an explanation of the fact that many women who have had surgery for cancer of the breast get along well for years on regular doses of the male hormone testosterone, while others on the same treatment soon suffer fatal recurrences of their cancer. Current theories to explain this phenomenon did not satisfy Dr. Hienz, or Dr. P. N. Ehlers of Heidelberg.

Could it be, they wondered, that Barr bodies might somehow account for the varying reactions to hormone therapy? First they had to find out whether there was any difference in the Barr bodies of different cancer patients. Dr. Hienz discovered that cancer cells from about two-thirds of the breast-cancer cases he was studying contained a normal quota of Barr bodies. But in cells from the remaining third of the patients he could find few or no dark spots. The absence of Barr bodies in some of the cancer cells suggested that those cells had been, in effect, partly defeminized. The change, the doctors thought, might indeed explain a difference in their reaction to a male hormone.

Wanted: 1,000 Cases. Dr. Ehlers took the next step and traced the histories of 114 patients for any correlation between Barr's dark spots and the effects of testosterone. In general, those whose cancer cells contained Barr bodies did far better on testosterone than similar cases not treated with the hormone. Survival rates were good among Barr-negative patients who did not get testosterone. But the Barr-negative patients who took the hormone survived, on the average, a much shorter time. A Vienna study of 201 patients produced similar results. But the cautious German and Austrian researchers still insist that it will take a thousand or more cases, studied for years in minutest detail, to show whether their Barr-body theory is correct.

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