Analyzing an Antibody

Surely but slowly, scientists are learning the structure of the basic molecules of life. They are gradually discovering how those molecules perform their exquisitely delicate and extraordinarily precise functions in all animals, from the amoeba to man. Despite their submicroscopic size, biologically active molecules are huge and complex--in atomic terms. Each one contains hundreds of thousands of atoms, arranged in submolecular groups--"building blocks" that are in turn arranged in definite numbers and patterns. Finding out how the building blocks are assembled in the major molecules has proved to be a challenging and time-consuming task.

Last week Dr. Gerald Edelman and his colleagues at Rockefeller University demonstrated that they were equal to the challenge. They announced that they have successfully deciphered the chemical structure of an entire gamma globulin or antibody molecule, one of the basic defenders against disease in all the higher forms of life.

Beads of Acid. Because these molecules occur in such enormous variety in the body, scientists can rarely get a large quantity of any single antibody from normal individuals. But one form of cancer of the antibody-forming cells, multiple myeloma, causes proliferation of cells that then mass produce a pure gamma globulin that is unique to each patient. From a cooperative myeloma victim, the Rockefeller researchers obtained samples of blood and processed it to extract the globulin antibody. The remaining blood was returned to the donor. In H years, they got what by molecular standards is a huge amount--2 Ib.

The antibody molecule is a protein, made up of chains of amino acids, of which there are 20 varieties. In 31 years of detailed work, the Edelman team learned by chemical and physical analysis that this particular molecule contains 19,996 atoms (of hydrogen, carbon, nitrogen, oxygen and sulphur) grouped in 1,320 amino-acid units, which in turn are assembled with the aid of chemical bonds into two "light" chains of 214 amino acids apiece and two "heavy" chains of 446 each (see diagram). Schematically, the four chains, in which the acids are strung like beads, look like a letter T. The middle part of the T varies little from antibody to antibody. The chains' ends at the tips of the crossbar constitute the antibody's active regions and can be varied in billions of different ways to fit the structure of the particular foreign molecule that it is equipped to combat.

When any vertebrate animal is "invaded" by foreign proteins--whether bacteria, viruses, or tissues from another animal as in a graft or transplant--the invaders soon meet one of the host's body cells that is armed with the appropriate antibody. This contact is a signal to the cell to divide. Its progeny also divide and soon there is an army of antibodies, each able to seize and hold two invading molecules. Powerful scavenger cells such as phagocytes then can go into action and effectively remove both combatants.

Selective Immunity. Dr. Edelman, 39, a physician and molecular biologist, insists that the chemical description of an antibody molecule is basic science, and he will not speculate on its potential medical uses. But his remarkable accomplishment may well be an important step toward the day when doctors will be able to selectively regulate immune reactions, allowing patients to accept transplants without lowering their resistance to disease.

This file is automatically generated by a robot program, so reader's discretion is required.