Three Men & a Messenger

Stockholm's Caroline Institute last week awarded the 1965 Nobel Prize in physiology and medicine to three French investigators for brilliantly imaginative research into the mechanisms by which genes regulate vital biochemical processes. Though the work has no present practical application, it has inspired hundreds of other researchers, and hopefully, within a generation or so, it may lead to means of controlling genetic processes in humans. The three Pasteur Institute scientists who will share the $56,400 prize:

> Andre Lwoff, 63, French-born but of Russian-Polish extraction, has spent all his life at the Pasteur, since 1959 has also been professor of microbiology at the Sorbonne.

> Franc,ois Jacob, 45, with the Free French forces in 1940-45, at Pasteur since 1950; now professor of cellular genetics at the College de France.

> Jacques Monod, 55, Paris-born, trained in the U.S. in 1936, awarded U.S. Bronze Star; at Pasteur since 1945; professor of cellular biochemistry at Paris' Faculte des Sciences.

Twentieth century geneticists gradually evolved the theory that whether an organism is to be microbe, mouse or man, its biochemical functions are determined by genes strung together to form chromosomes. Each gene is believed to be a submicroscopic but still "giant" molecule of a nucleic acid, usu ally deoxyribonucleic acid (DNAJ, but in some viruses ribonucleic acid (RNA) Each gene, the theory held, directly controls the cells' production of some one specific chemical--in most cases an enzyme, one of the body's countless catalysts that are essential to nearly all its functions.

With Stand-ins. To check and expand on these hypotheses, Lwoff chose to work with single-celled organisms, such as bacteria, because they have a single chromosome (whereas man has 46). As stand-ins for genes he chose viruses that infect bacteria (bacterio-phages), because their cores consist of nucleic acid. What actually happens Lwoff found, is not as simple as had been thought. The viral nucleic acid, in effect masquerading as a gene, might do one of two things after invading a bacterium: 1) stimulate the bacterial cell to produce hundreds of copies of the virus particle, and destroy itself in the process, as happens in many ordinary human viral infections, or 2) attach itself to the host cell's genetic material and then lie dormant, only to reappear consistently in successive generations of host-cell bacteria. After this dormant phase, chemicals or radiation can still trigger the intruder gene into becoming infective and destructive.

Jacob and Monod carried this line of experimentation further, discovered that a macromolecule of DNA itself does not tell the cell what substances to manufacture. Instead, it makes a partial copy of itself, called "messenger RNA," to execute its orders. The Jacob-Monod hypothesis goes on to suggest that a second or "operator" gene, also present in the DNA, may work with the basic gene in a complex feed-back mechanism. And there may even be a third type of gene.

Reaching Forward. So far, these hypotheses have been substantially proved for bacteria, and there is convincing evidence of the existence of "messenger RNA" in mammalian cells. As a result, there is a great temptation to extrapolate all the way from microbe to man and assume that long-dormant viruses may belatedly trigger cancerous changes in human cells. The evidence for this, so far, is extremely tenuous. But the Nobel Prize committee, which has sometimes been as much as 30 years late in recognizing achievement, has now reached toward the future in making its 1965 award.

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