Laying the Foundation

Immunology, the study of the complex mechanisms by which the body fends off disease and resists transplants, is probably the most promising branch of medical research today. Many experts feel that in this rapidly advancing field, doctors will discover the secrets of cancer control and more successful organ transplantation.

Last week Sweden's Royal Caroline Institute honored the two men whose work has made such hopes plausible. The 1972 Nobel Prize for Physiology or Medicine went to Dr. Gerald Maurice Edelman, 43, a professor of biochemistry at New York's Rockefeller University, and Rodney Porter, 55, a biochemistry professor at the University of Oxford. Working separately, the two researchers discovered the chemical structure of antibodies, the blood proteins that play a crucial role in the body's war against infection.

Edelman, an accomplished violinist who loves poetry "because it is beautiful and useless," was awakened by his wife Maxine after she heard the news on a radio broadcast. "It was 8 o'clock in the morning, a time when I am usually asleep and in some kind of metaphysical state," he said later in the day. "At first I was silent, then glad--delighted, in fact." Porter, who lives on a farm near Oxford, was skeptical when informed that he had won. "Reporters told me that last year and I hadn't," he explained.

Though the American and the Englishman never collaborated directly, their research has, in effect, followed the same paths since 1959. Antibodies form complex, giant molecules. Porter concentrated on those parts of the molecule that give an antibody the capacity to react with a foreign or threatening substance (an antigen) and destroy it. Using a protein-splitting enzyme called papain, Porter broke the antibody molecule into three fragments. He found that the molecule is Y-shaped. The two smaller and similar parts of the structure are the ones that are capable of combining with the antigen; the larger one lacks this ability.

Assuming that antibodies, like most other proteins, are composed of chains of amino acids, Edelman set out to identify the arrangement and composition of the antibody molecules. In 1969, he completed a gamma-globulin model showing the molecule to be made up of 19,996 atoms grouped together in amino-acid building blocks. His findings coincided with those of Porter, showing that the antibody molecule is composed of a double pair of chains, two "light" ones forming the branches of the Y, and two "heavy" ones that make up the trunk. After establishing that antibodies have some flexible amino-acid chains, Edelman was able to demonstrate how the body can form different antibodies to deal with specific diseases. He also demonstrated how parts of the antibody molecule adhere to the antigen molecule, while others attack it.

The impact of the discoveries has been enormous. They have provided scientists with the first clear explanation of how antibodies are built and, according to the Caroline Institute, "laid a firm foundation for truly rational research, something that was previously largely lacking in immunology." Immunologists have already begun to build upon that base in studying rheumatic fever, arthritis and other diseases.

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