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Kohler and Milstein's hybridoma technology (1975)

Hybridoma technology

Our B cells, a type of white blood cell, can produce millions of different antibodies. However, each cell on its own can only produce antibodies of a certain, predetermined specificity, which means that many, many different B cells are needed to generate the multitude of antibodies needed by a healthy immune system. When the body is exposed to a given foreign antigen, it can cause the stimulation of a B cell that has fortuitously been endowed with the capacity to identify this particular antigen. The result is that this B cell then starts to divide to form a clone of cells which produce identical antibodies, or “monoclonal” antibodies.

This is how nature works. But in 1975 George Kohler and Cesar Milstein, working at the MRC Laboratory of Molecular Biology in Cambridge, found a way of mimicking the effect to produce monoclonal antibodies “to order”. They did it by merging myeloma cells – cancerous cells resulting from the uncontrolled cells division resulting from a lymphocyte dividing to form a clone of identical cells – with antibody-producing B cells. By fusing the B cell with the myeloma cell, it acquires the ability to divide rapidly, allowing large numbers of identical antibody producing cells to be grown in cell culture.

The system is known as hybridoma technology because it involves cell hybrids to produce sets of identical monoclonal antibodies directed against specific antigens. Kohler and Milstein started out working independently. Milstein had developed cancerous forms of antibody-producing cells that grew and multiplied forever but which churned out antibodies of unknown specificity, while Kohler managed to get antibody-producing cells to make specific antibodies, but these cells didn’t survive for very long. By combining their discoveries, they came up with a way of making monoclonal antibodies of exquisite precision from cells that divided and divided and effectively lived forever.

Monoclonal antibodies, or “MAbs”, have revolutionised immunology in terms of analytic tests and diagnostics, and are now a standard treatment for certain forms of cancer with drugs such as Herceptin (trastuzumab), Avastin (bevacizumab) and Campath (alemtuzumab).

Kohler and Milstein were awarded a share of the 1984 Nobel prize in physiology or medicine for their breakthrough.