Synthesis of an Enzyme

Man prides himself upon his growing mastery over nature, but in the ultimate biochemical analysis nature remains the master of man. With their most sophisticated laboratory glassware and corrosive reagents, scientists can set off any one of a few thousand bio chemical reactions in an hour or two, but they need to generate unnaturally high temperatures to do the job. Nature can instantly produce millions, or possibly billions, of such reactions at normal body temperature. The agents that effect such biological miracles are enzymes, commonly referred to as "nature's catalysts." They provide no nourishment to animal or man, yet they are essential to the metabolism of all creatures. They are the honest brokers or middlemen of life, mediating countless actions between living creatures and their environment and within the creatures themselves.

Last week, two groups of scientific researchers jointly announced that they had succeeded for the first time in synthesizing an important enzyme in the laboratory. The triumphant research teams came from Manhattan's Rockefeller University and the Merck Sharp & Dohme Research Laboratories at Rahway, N.J. Working independently from different starting points and along different routes, both of the research groups reached the same end point: synthesis of ribonuclease, an enzyme found in the pancreas (sweetbreads) of cattle that helps to break down ribonucleic acid.

How They Did It. The Rockefeller researchers, Drs. Robert B. Merrifield and Bernd Gutte, began their experiment with a tiny bead of plastic, onto which they hooked a 124-link chain of amino acids. There are 20 different amino acids, and, because all proteins, including enzymes, are made of amino-acid chains, the acids have been recognized for many years as the "building blocks of life." The exact sequence and identity of successive acids in the ribonuclease chain were recently established, and the Rockefeller team's job was to link them, one at a time. The painstaking process involved 369 chemical reactions and no fewer than 11,931 different laboratory steps, taking three weeks in all to complete.

The Merck researchers, Drs. Robert G. Denkewalter and Ralph F. Hirschmann, went at it differently. They prepared groups of six to 17 amino acids in linked series. They then put these groups together to form the ultimate 124-link chain. Their product turned out to be the same as the Rockefeller synthetic enzyme; its identity was proved by the way in which it broke down ribonucleic acid.

Dependent Generals. Ribonucleic and deoxyribonucleic acid are the fundamental chemicals that determine the nature of living things--whether they will grow normally or abnormally, whether they will reproduce their kind or perish. The two nucleic acids are as dependent on their loyal enzymes as a general on his junior officers. The bovine ribonuclease that has been synthesized will have no immediate value as a treatment for any of the ills of animals or man. But its synthesis shows that man is coming closer to his goal of emulating nature at the most basic, biochemical level.

The first synthesis of an enzyme, said Merck's Dr. Max Tishler last week, should provide much of the knowledge needed for researchers to devise and produce "the next generation" of healing agents.

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