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Friday, 14 July, 2000, 02:09 GMT 03:09 UK
Scientists salute 25-year-old discovery
Mono LMB
Specificity: A model of a monoclonal antibody
By BBC News Online's John Newell

Scientists have gathered in London to celebrate one of the great discoveries in modern medicine - monoclonal antibodies.

It is 25 years ago this summer that Cambridge researchers Drs Cesar Milstein and George Kohler found a way to make any required antibody in pure form, in the test tube.

It was a breakthrough that has brought science within touching distance of a "magic bullet" - a tailored weapon that can home in and destroy the causes of disease.

Monoclonal antibodies still have some way to go to fulfil this dream but their obvious potential was sufficient to earn Milstein and Kohler a Nobel Prize in 1984.

The UK's Medical Research Council, which funds the lab where the men did their pioneering work, paid its own tribute on Thursday by honouring Dr Milstein with its first Millennium Medal for outstanding scientific achievement.

Sadly, Dr Kohler could not share the award - he died in 1995 aged just 49.

First line of defence

Antibodies, the complex protein molecules produced by the immune system, are the first line of defence of humans and animals against disease.

Cesar Milstein LMB
Cesar Milstein: His was one of the great breakthroughs
The human immune system can make more than two million different antibodies, each of which recognises, binds itself to and begins the process of destroying just one target, a protein antigen on a bacterium or virus.

Before Milstein's and Kohler's achievement it was only possible to make antibodies in tiny quantities and messy mixtures. But they found a way to stimulate cells to produce any required antibody, and then to make those cells into "immortal" cell cultures, that could be grown to any required size that would go on producing just the one wanted antibody for as long as it was required.

Monoclonal antibodies made in this way had vast potential for speeding up research and for diagnosing and treating many different diseases.

Because a pure monoclonal antibody will attach itself to only one antigen on one kind of bacterium or virus, antibodies can be used to diagnose infectious diseases with unprecedented speed and certainty.

Humanised monoclonals

One of the most successful ways in which they have been used has been in the field of diagnosis. If a monoclonal is "tagged" with a fluorescent dye, a doctor can see immediately when it has attached to a specific antigen. This method can be used to tell a woman she is pregnant or that she has cancer.

The Laboratory of Molecular Biology in Cambridge has produced many Nobel Prize winners
Because monoclonals can identify exactly which proteins (working parts) of living cells are being produced and are active at any time, they have fulfilled their promise in helping scientists understand the development and working of the human body.

But it has to be said that the third part of the dream, of using them widely in therapy, has taken much longer to realise.

This has been because the first monoclonals to be made were mouse or rat antibodies, and when these were used to treat human disease they were recognised as foreign and rejected by the human body's immune system.

It took several years for this problem to be overcome, by another Cambridge scientist, Dr Greg Winter.

Cruise missile

He invented first a way to "humanise" mouse or rat antibodies so they closely resembled human antibodies, and then a way to make completely human antibodies outside the human body.

Winter LMB
Greg Winter made the next vital step
These two achievements did away with the rejection problem and opened the way to putting antibodies to work to target and destroy the causes of disease with unprecedented precision.

Antibody therapy is to conventional drugs what cruise missiles are to ordinary bombs.

These and other advances have allowed antibodies to be used to treat diseases including rheumatoid arthritis, multiple sclerosis, forms of cancer and viral infections.

At least forty different antibodies are in the pipleline awaiting approval for use in medicine. Dr Milstein thinks the next big breakthrough may come in the development of antibodies able to penetrate the surfaces of cancer cells and target the abnormal proteins inside. That could lead to a revolution in cancer therapy.

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