Heredity: The Lyon & the Mouse

The 1,500 experts in medical and related sciences who gathered last week in Manhattan’s Americana Hotel spent hours listening intently to highly technical discussions of sex chromosomes, enzyme systems and skeletal development. In the Imperial Ballroom, earphones provided simultaneous translation in three languages. It was the second international conference on congenital malformations sponsored by the National Foundation-March of Dimes. The world’s outstanding researchers were tackling an immense problem: one baby out of every 15 is born with some defect, be it physical, mental or chemical. In the U.S. alone, that means more than 250,000 victims each year.

Making Mosaics. At this deeply scientific confab on one of humanity’s most distressing problems, the unexpected heroine was a quiet Englishwoman who presented no paper and who is, of all things, editor of a semiannual Mouse News Letter. Since the first such conference in London three years ago, the most noteworthy progress in unraveling the mysteries of human heredity has been based on the work of Geneticist Mary F. Lyon, 38. Born in Norwich, daughter of a civil servant, Mary Lyon got a Ph.D. from Cambridge University, specializing in mouse genetics. She now works at the Radiobiological Research Unit at Harwell, 50 miles west of London. Dr. Lyon became intrigued by the fact that some mice—but only females, it seemed—showed up with Joseph’s coats of several colors. This could not happen under classical Mendelian laws of inheritance.

Two years ago, Dr. Lyon proposed a revolutionary hypothesis. Every female mammal, whether mouse or woman, has two X (female) chromosomes, one each from father and mother. A male has one X and one Y. Since the X chromosome carries genes that control the production of many enzymes which in turn govern the body’s chemistry, a female with two Xs should have twice as much of these enzymes as a male with one. But she doesn’t. Dr. Lyon’s proffered explanation: one of the female’s X chromosomes is muted soon after conception and becomes a silent partner. It shows up thereafter only as a dark spot in microscope slides of her cells. But before it is muted, it starts the production of lines of cells that continue to live side by side with lines from the dominant X. So a female mammal is a “genetic mosaic.”

Some Sterile Cats. Building upon Miss Lyon’s theory, other researchers have explained a mystery about calico cats. In theory, such a cat has to be a female because its black and orange patches must result from two different X chromosomes. What seemed to be male calico cats have turned out, on study of their cells, to have two X chromosomes as well as a Y. They are an intersex form, and they are sterile.

Applying the Lyon hypothesis to women, geneticists at California’s City of Hope have shown mosaicism in women who suffer from a form of Mediterranean anemia. But this is only one of at least 58 inborn defects that appear to result from defects in X chromosomes. Among others: some forms of color blindness and of anemia, hemophilia, muscular dystrophy, deafness.

What made the editor of Mouse the Lyoness of the conference is the hope of all geneticists that further exploration of her hypothesis will lead to better understanding of these crippling handicaps, and eventually, perhaps, to their prevention.