Timelines: 1975

César Milstein and Georges Köhler

A wonderfully useful invention

German cell biologist Georges Köhler and Argentine biochemist César Milstein invent hybridoma technology in Milstein’s British Medical Research Council lab at Cambridge.

Hybridomas are cells produced by the fusion of mammalian B-lymphocytes (antibody-producing cells) and myelomas (malignant bone marrow cells). Because they are cancerous, hybridoma cells can be maintained indefinitely in culture, all the while secreting antibody proteins according to the specific genetic instructions donated by the original B-lymphocyte parent. The proliferation of hybridomas is, in effect, a method of cloning antibody genes and, simultaneously, manufacturing homogenous (monoclonal) antibodies in large quantities.

The discovery was accidental. Köhler and Milstein had been studying in cellular genetics. Their first interest in the protein products of fused myelomas was the utility of these molecules in the analysis of rates of cellular mutation and the generation of antibody diversity. They recognized, however, that due to their particularized genetic codes and ‘immortality,’ the new hybrid cells were not just objects of scientific inquiry, but a novel kind of technological instrument. The understated conclusion of Köhler and Milstein’s landmark paper in the journal Nature reads: “Such cultures could be valuable for medical and industrial use. ”

In fact, the invention has been worth billions. Because they can hone in on specific biological targets with unerring precision, monoclonal antibodies have been used to monitor biological and chemical processes of all sorts, and to diagnose and combat a wide range human diseases. Researchers are just beginning to tap their potential in medical and industrial applications.

Monoclonal antibodies are produced by B cells harvested from the spleens of animals immunized with the target antigen.  The B cells are fused with myeloma tumor cells to form 'immortal' monoclonal-generating hybridomas.