They are tiny magic bullets that are quietly shaping the lives of millions of patients around the world. Produced in the lab, invisible to the naked eye, relatively few people are aware of these molecules' existence or where they came from. Yet monoclonal antibodies are contained in six out of ten of the world’s bestselling drugs, helping to treat everything from cancer to heart disease to asthma.
Known as Mabs for short, these molecules are derived from the millions of antibodies the immune system continually makes to fight foreign invaders such as bacteria and viruses. The technique for producing them was first published 40 years ago. It was developed by César Milstein, an Argentinian émigré, and Georges Köhler, a German post-doctoral researcher. They were based at the UK Medical Research Council’s Laboratory of Molecular Biology in Cambridge.
Harnessing the power of the immune system
Milstein and Köhler wanted to investigate how the immune system can produce so many different types of antibodies, each capable of specifically targeting one of a near-infinite number of foreign substances that invade the body. This had puzzled scientists ever since the late 19th century, but an answer had proved elusive. Isolating and purifying single antibodies with known targets, out of the billions made by the body, was a challenge.
The two scientists finally solved this problem by immunising a mouse against a particular foreign substance and then fusing antibodies taken from its spleen with a cell associated with myeloma, a cancer that develops in the bone marrow. Their method created a hybrid cell that secreted Mabs. Such cells could be grown indefinitely, in the abdominal cavity of mice or in tissue culture, producing endless quantities of identical antibodies specific to a chosen target. Mabs can be tailored to combat a wide range of conditions.
When Milstein and Köhler first publicised their technique, relatively few people understood its significance. Editors of Nature missed its importance, asking the two scientists to cut short their article outlining the new technique; as did staff at the British National Research Development Corporation, who declined to patent the work after Milstein submitted it for consideration. Within a short period, however, the technique was being adopted by scientists around the world, and less than ten years later Milstein and Köhler were Nobel laureates.
Image:Monoclonal antibodies
Credit: Linda Bartlett
Reproduced courtesy of the University of Cambridge
__________________________________________