Monday, Jan. 20, 1947

Tempest in the Cells

The most sacrosanct doctrine in biology had been called in question. The two biological revolutionists who did it--Drs. Sol Spiegelman and Martin D. Kamen of Washington University, St. Louis--fled home from Manhattan this week, hotly pursued by biological tories. They had attacked the Divine Right of Genes.

The doctors' subversive opinions were part of a general attack by radical biologists on conventional conceptions of growth: the basic life process. If the new theories hold, they will affect all biology, from animal breeding to the understanding of cancer.

"What we started to do," said Dr. Spiegelman, "was to find out how genes operate." Genes are infinitesimal bodies (perhaps single protein molecules) in the nucleus of every living cell, from bacteria to man. According to orthodox, "Mendelian" biology, they are the sole arbiters of heredity. When a cell divides, each gene divides too, and transmits a definite characteristic to the "daughter" cells.

Genes Not All. This classical explanation of heredity, taught in every biology textbook, is not wholly satisfactory. Some cells, notably certain cancer cells in mice, seem to develop oddly, defying their hereditary genes. At Indiana University, Dr. Tracy M. Sonneborn found that the one-celled animal paramecium sometimes did this too.

Drs. Spiegelman and Kamen worked with yeast cells, proved that their chemical behavior could be changed, while the genes remained unchanged. This suggested strongly that something besides the genes affected cell characteristics.

To spot this "something," they used the ultramodern technique of radioactive tracers. First they grew yeast cells in a solution containing radioactive phosphorus-32, whose uneasy atoms the cells built into certain of their proteins. With a Geiger counter, the scientists could follow these radioactive protein molecules.

"Self-Duplicating Bodies." When the cells were allowed to multiply freely, some of the protein molecules characteristic of the nucleus (where the genes are) tended to flow into the "cytoplasm," the part of the cell outside the nucleus. This indicated (along with related biochemical data) that the genes were sending out "partial replicas" of themselves, which entered the cytoplasm and multiplied there independently.

These busy "self-duplicating" bodies the scientists called "plasmagenes." There are probably thousands of them, competing actively for nourishment in the cell's body like cattle, prairie dogs and rabbits on an overstocked range. Anything which affects this competition may favor certain plasmagenes above the others, allowing the favored ones to multiply abnormally, as rabbits once did in Australia. A change in the balance of plasmagenes affects the cell's chemical behavior, as rabbits affected Australia by eating much of its rangeland bare of grass. The cell's genes take no part in the transformation.

New Control. What good was the discovery? The biological revolutionists were reluctant to say. But they admitted (with a gleam in their eyes) that it gave a new, promising method of controlling cell life and growth. They had already con trolled yeast cells by regulating competition among plasmagenes. Future biologists might do the same with bacteria cells or man cells.

One vital problem might be cleared up.

Cancer is caused when a cell of the human body loses its normal function and starts multiplying lawlessly. This perversion can not be blamed on true "mutation," which involves the genes themselves. It happens too often for that.

But plasmagenes are much more numerous than genes. If something goes wrong with the division of one of them, a law less plasmagene may be produced. It multiplies wildly at the expense of others.

The corrupted cell turns into a deadly cancer.

Drs. Spiegelman and Kamen emphasized that they had no cure for cancer.

But they may have charted a course for future cancer physiologists.

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