Friday, Dec. 01, 1961

Heredity & Cancer

The title of the address at the University of Virginia had a ring of scientific heresy: "Heritance of Acquired Characteristics." Yet the speaker was an eminent researcher. Dr. Frank L. Horsfall Jr., director of Manhattan's Sloan-Kettering Institute. What he did, pulling together recent research from a number of laboratories, was to show that:

> Heredity can, at least in the somewhat limited field of bacteria, be changed and even directed.

> Control of heredity in cells could be a key tool in preventing cancer.

Charles Darwin propounded the doctrine that evolution occurs by natural selection, in which some individuals happen, by chance combination of inherited characteristics, to be better adapted to their environment than others--"survival of the fittest." Geneticists later concluded that inheritance was locked in a set of genes that usually bred true, but once in a while spontaneously "mutated" to produce a new characteristic that thereafter bred true and thus produced evolution's changes. This knowledge undercut the Lamarckian concept--named for Jean Baptiste Pierre Antoine de Monet, Chevalier de Lamarck (1744-1829)--that characteristics could be acquired in response to environment and become hereditary.* The cause of mutations remained a mystery.

"Infective Heredity." Recent research, said Dr. Horsfall, has shown that gene mutations can be produced by changes in the environment, and the mutant strains will breed true. It began, he recalled, with the little-recognized achievement of three Rockefeller Institute scientists, Drs. Oswald Avery, Colin MacLeod and Maclyn McCarty in 1944. They showed that if nucleic acid from the genetic material of one strain of pneumococcus germs was stirred in with a batch of pneumococci of another strain, the second strain picked up the inherited traits of the first, and then, "in enduring continuity," bred true from cell to daughter cell. "The heritance of an acquired characteristic was no longer an unsupported theory," he said. "It had become a reality."

Since then, "guided and directed mutation with precisely predictable features" has produced bacteria that mutate after infection with viruses. Formerly harmless strains of diphtheria bacilli will, after viral infection, secrete the poison of virulent diphtheria. Because the bacterial lines breed true, said Dr. Horsfall, both these are cases of "infective heredity" induced by environmental factors.

"In essence," he contended, "the only real difference between induced alterations of this kind and so-called spontaneous mutations, which by definition are heritable, is that in the case of induced alterations the stimulus is known, whereas it is not known when spontaneous mutations occur."

Disappearing Trigger. Cancerous mutations, which are hereditary within cell lines, can be produced by X rays, ultraviolet light, some chemicals, and viruses. Different as these factors seem, said Dr. Horsfall, they are probably identical in that they operate only to produce the first mutation. After that, the cells go on multiplying abnormally, true to their mutant genes, even though the agent that caused the mutation is no longer present. This would explain why viruses that may have triggered human cancers cannot be found after the disease appears.

From recent research work with viruses known to cause animal cancers, Dr. Horsfall reasoned that viruses probably will be shown to cause many cancers in man. Then, hopefully, it may be possible to devise tests to detect such cancer-causing viruses before disease develops, and even to work out immunization procedures to keep the viruses from getting into the cells. The heritance of acquired malignant characteristics would thus be defeated before it could begin.

* Still echoed by Trofim Denisovich Lysenko, who was Stalin's favorite scientist, then was deposed, but is now back in favor as president of the Soviet Academy of Agricultural Sciences.

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