Wednesday, Oct. 05, 1983

SCIENCE

The Promise of the New Genetics

WILDLY excited, two men dashed out of a side door of Cambridge University's Cavendish Laboratory, cut across Free School Lane and ducked into the Eagle, a pub where generations of Cambridge scientists have met to gossip about experiments and celebrate triumphs. Over drinks, James D. Watson, then 24, and Francis Crick, 36, talked excitedly, Crick's booming voice damping out conversations among other Eagle patrons. When friends stopped to ask what the commotion was all about, Crick did not mince words. "We," he announced exultantly, "have discovered the secret of life!"

Brave words--and in a sense, incredibly true. On that late winter day in 1953, the two unknown scientists had finally worked out the double-helical shape of deoxyribonucleic acid, or DNA. In DNA's famed spiral-staircase structure are hidden the mysteries of heredity, of growth, of disease and aging--and in higher creatures like man, perhaps intelligence and memory. As the basic ingredient of the genes in the cells of all living organisms, DNA is truly the master molecule of life.

The unraveling of the DNA double helix was one of the great events in science, comparable to the splitting of the atom or the publication of Darwin's Origin of Species. It also marked the maturation of a bold new science: molecular biology. Under this probing discipline, man could at last explore--and understand--living things at their most fundamental level: that of their atoms and molecules.

Using laboratory skills that were unheard of a generation ago, scientists have isolated, put together and manipulated genes, and have come close to creating life itself. In 1967 Stanford University's Arthur Kornberg synthesized in a test tube a single strand of DNA that was actually able to make a duplicate of itself. Kornberg's "creation" was only a copy of a virus, a coated bit of genetic material that occupies a twilight zone between the living and inanimate. But many scientists have become convinced that they may eventually be able to create functioning, living cells.

Molecular biology, in part, is rooted in the science of genetics. Ever since Cro-Magnon man, parents have probably wondered why their children resemble them. But not until an obscure Austrian monk named Gregor Mendel began planting peas in his monastery's garden in the mid-19th century were the universal laws of heredity worked out. By tallying up the variations in the offspring peas, Mendel determined that traits are passed from generation to generation with mathematical precision in small, separate packets, which became known as genes (from the Greek word for race).

Mendel's ideas were so unorthodox that they were ignored for 35 years. But by the time the Mendelian concept was rediscovered at the turn of the century, scientists were better prepared for it. They already suspected that genetic information was hidden inside pairs of tiny, threadlike strands in cell nuclei called chromosomes, or colored bodies (for their ability to pick up dyes). During cell division they always split lengthwise, giving each daughter cell a full share of what was presumed to be hereditary material.

By the 1940s, the molecular biologists had come on the scene, and they insisted that fundamental life processes could be fully understood only on the molecular level. In their investigations, some used the electron microscope, which revealed details of structure invisible to ordinary optical instruments. Others specialized in X-ray crystallography, a technique for deducing a crystallized molecule's structure by taking X-ray photographs of it from different angles.

Inspired by these experiments, Watson, then a young Ph.D. in biology from Indiana University, decided to take a crack at the complex structure of DNA itself. The same thought struck Crick, a physicist turned biologist who was preparing for his doctorate at Cambridge. Neither man was particularly well equipped to undertake so formidable a task. Watson was deficient in chemistry, crystallography and mathematics. Crick, on the other hand, was almost totally ignorant of genetics. But together, in less than two years of work at Cambridge, these two spirited young scientists showed how it is possible to win a Nobel Prize without really trying.

In 1968 Watson himself produced a highly irreverent, gossipy bestseller, The Double Helix, which revealed the human story behind the discovery of DNA'S structure: the bickering, the academic rivalries, even the deceits that were practiced to win the great prize. From the X-ray crystallography laboratory at King's College in London, where Biochemist Maurice Wilkins was also investigating the molecule's structure, they quietly obtained unpublished X-ray data on DNA. Relying as much on luck as logic, they constructed Tinkertoy-like molecular models out of wire and other metal parts. To everyone's astonishment, they suddenly produced a DNA model that not only satisfied the crystallographic evidence but also conformed to the chemical rules for fitting its many atoms together. This file is automatically generated by a robot program, so viewer discretion is required.