The Quest for a Magic Bullet

A new technique that could help the body to defend itself

When it is invaded by a foreign substance--a virus or bacterium, say, or even the cells from a donated kidney or blood transfusion--the healthy body quickly mobilizes the immune system for a counterattack. Among the forces sent into combat are antibodies, tiny molecular missiles that attach themselves to the intruder's surface and help destroy the invader. They are highly efficient and selective; each antibody is so exquisitely designed that it matches up precisely with only one site on the invader or antigen, almost as if it were a key fitting into a lock.

Because antibodies can seek out even minute amounts of a foreign substance, they are an extremely valuable medical tool. Doctors can use them to match donor and recipients for everything from blood transfusions to kidney and heart transplants; if antibodies from the potential recipient "recognize" anything in the donated tissue as "foreign," the chances are that the transplant will be rejected. In the future, doctors foresee many other uses for antibodies as well, possibly including a cancer therapy.

But such promising applications have encountered a major block: human antibodies, obtained from the blood, can be collected only in tiny quantities. Now that task may become easier. At an immunology conference in Paris, two Stanford University researchers announced that they had produced human antibodies by ingenious alternative means: tiny cells especially bred to act as miniature antibody factories.

The technique builds on pioneering work with mice done five years ago by Cesar Milstein and Georges Koehler in Britain. By injecting foreign substances into the animals, they stimulated the production of antibodies against the invaders. Then they removed the animals' spleens, a major site for antibody production, and mixed the organ's antibody-producing cells with cancer cells. The result: hybrid cells, dubbed hybridomas, that inherited from the spleen the ability to produce antibodies and from the malignant cells the ability to replicate themselves indefinitely. These hybridomas produce identical copies of themselves--clones --and thus serve as minifactories for the manufacture of what researchers call monoclonal antibodies.

Unfortunately, anything produced by mouse cells is foreign to humans and likely to trigger an immune reaction. So Stanford's Drs. Lennart Olsson and Henry Kaplan set out to create human hybridomas. They took spleen cells from victims of Hodgkin's disease, a form of cancer in which the spleen is usually removed during treatment. The cells had already been exposed to the chemical dinitrochlorobenzene and were making antibodies. These cells were then fused with cancerous bone-marrow cells, yielding hybrid cells that could churn out the antibody.

Kaplan acknowledges that this antibody "is of no earthly good to anybody," but the technique employed to create it may open many important avenues of research. Use of monoclonal antibodies could, for instance, help doctors monitor elusive changes on the surfaces of cells and help explain the development of such suspected immunity-related diseases as arthritis, juvenile diabetes, multiple sclerosis and cancer. Finally, if specific surface characteristics of cells are found to be associated with only certain types of cancer, radioactively tagged antibodies could be sent to find the cells in any part of the body. It might even be possible to link cell-killing drugs to them, thus finally creating a magic bullet" that would home in on malignant cells and spare normal ones.

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