Medicine: Those Amazing Chemical Scissors

Three win Nobel Prize for work with versatile enzymes

Because the basic blueprint of human life is encoded in hundreds of thousands of genes contained in unwieldy strands of DNA in each living cell, researchers have had a hard time deciphering it. But in recent years they have been greatly aided in their work by a group of remarkable tools: enzymes that act as chemical scissors, cutting strips of DNA into precise and manageable fragments.

The discovery of these so-called restriction enzymes promises to help un ravel the mysteries of cell development, hereditary disease and cancer. It has al ready allowed scientists to analyze the chemical structure of genes and to map their sequence along DNA strands. It has ushered in a new age of genetic engineer ing by making possible the combining of genetic material from different species by the controversial recombinant ” DNA technique.

Last week Sweden’s Karolinska Institute underlined the importance of restriction enzymes by awarding the Nobel Prize for Medicine, this year worth $165,000, to a trio of pioneers in the field. The three, all microbiologists: Werner Arber, of the University of Basel in Switzerland, and Drs. Hamilton O. Smith and Daniel Nathans, Americans, both of Johns Hopkins University.

Arber, 49, first postulated the existence of restriction enzymes in the early 1960s while studying viruses that invade bacteria. After labeling a virus with a radioactive isotope that acted as a tracer, Arber found that when the virus entered a bacterium, most of the viral DNA was destroyed. But how?

Arber theorized that the bacterium produced a “restriction” enzyme that cut the viral DNA into smaller pieces (the host bacterium’s DNA is protected from its own chemical scissors by other enzymes). Arber further proposed that the enzymes recognized and acted upon specific sites along the DNA strand.

Arber’s theories were verified by Smith, 47, a former naval medical officer and member of the U.S. Public Health Service who turned to genetic research. In 1970 Smith published two classic papers that described his discovery of a restriction enzyme produced by the bacterium Hemophilus influenzae and the way it worked.

The enzyme did indeed break the DNA of invading organisms into fragments. Most important, Smith was able to show that everytime the enzyme found a particular sequence of the chemicals that make up

DNA, it severed the strand at that point.

Scientists have since found about 100 restriction enzymes that act at particular sites on the strands.

Using the enzyme discovered by his colleague, Nathans, 49, applied it to his work with a monkey virus, SV40, known to cause cancer in animals but not man.

In 1971 Nathans showed that the enzyme broke SV40 DNA into eleven well-defined fragments. Two years later he described the way SV40 was split when two other en zymes were used. By analyzing the frag ments produced by all three enzymes, Nathans was able to map the SV40 genes.

The general approach designed by Nathans has since been used by other scientists to map the DNA of organisms that are far more complex. The institute also cited Nathans for his bril liant discussion of other possible applications of the enzymes to genetics.

One of those applications — the recombinant DNA technique — has begun to fulfill its widely her alded promise. By inserting genes into the DNA of a laboratory strain of the common intestinal bacterium E. coli, re searchers have induced the little bug to produce somatostatin, a mammalian brain hormone. Last month the bacterium manufactured synthetic human insulin, raising hopes that the hormone vital to the well-being of the world’s diabetics may some day soon be available in virtually unlimited supply.