1.5 Paul Ehrlich is the father of modern chemotherapy. His work has led to today's scientists being able to tailor-make drugs to kill particular bacteria. In his student days he used the synthetic aniline dyes to stain the blood cells and other body tissues. His finding that the dyes coloured the various parts of the cells in different ways laid the foundation for the science of haematology. Even more important, since aniline dyes were known to kill bacteria in the laboratory, the next step was to see whether they kill them in the body without harming it. He expressed himself thus: "Antitoxins and antibacterial substances are charmed bullets which strike into those objects for whose destruction they have been produced." He used variants of organic arsenicals to treat protozoal and spirochaetal infections in animals. At the age of 55 his long search was rewarded by the discovery of salvarsan, or "606", which was effective in killing spirochaetes within tissues and which reigned supreme in the treatment of syphilis until the introduction of penicillin. And the use of specially designed 'magic bullets', as they are now usually termed, has become a standard technique in modern medicine @ 2.3 A major advance in the fight against cancer may have been found after trials with a family of substances that should remove the rejection problem in tissue and organ transplants and transform the treatments for killing cancerous cells. The coming revolution depends on a new way of designing and mass-producing human antibodies, the natural agents in the blood that form the body's main weapons system to destroy poisons, ranging from snake venom to toxins, produced by infectious bacteria and viruses. Medical researchers have dubbed the method low-impact therapy. The advance is due in large measure to the achievements of research groups at Cambridge: at the University School of Clinical Medicine, Addenbrooks Hospital, and the Medical Research Council's Laboratory of Molecular Biology and its adjoining Interdisciplinary Research Centre for Protein Engineering. Their discoveries have spurred a multi-million pound, world- wide offensive in research into the refinement of the most promising tools for treating human disease in the past decade. Yet the new methods, which employ the most exquisite applications of the scientists' new-found abilities in genetic engineering, represent a third generation of a medical technology that originated precisely 100 years ago. The origins belong to the development of immunisation of children against diphtheria by 19th-century German bacteriologists Paul Ehrlich and Emil Behring, and a Japanese collaborator called Bron S.Kitasato. They showed that an animal inoculated with diphtheria toxin could produce a protective serum. Animal antisera were used for a variety of bacterial infections and neutralising toxins, which led to antibiotics and the start of the modern drug industry. Nevertheless, the scientists have continued research to understand how the body can make thousands of different antibodies, each one tailor-made to home in and smother a specific life-threatening bacteria, virus, poison or other foreign intruder, including a piece of graft tissue or transplanted organ. Since the mechanism the body uses to make antibodies to order is still not fully understood, the antibodies cannot yet be synthesised in the test tube. That breakthrough waited until 1975, when Dr Cesar Milstein and Dr Georges Kohler at the Laboratory of Molecular Biology, in Cambridge, discovered how to produce specialised antibodies. They were not made in a test tube, but by using mice. The substances are known as monoclonal antibodies because of their method of production. In the way that an animal was injected to stimulate an anti-diphtheria antibody, Dr Milstein and Dr Kohler injected mice with selected "foreign bodies", which the creatures reacted by producing specific antibodies. These antibodies could be extracted from the mouse, but grown in culture only for a short time. The scientists overcame this with an idea, which won them a Nobel prize. They took from another mouse a different type of cell from bone marrow. The cell was chosen because it was a cancerous one and therefore capable of reproducing continuously. Hence, the scientists created a so-called "hybridoma": a half- antibody, half-cancer cell. It provided a limitless supply of highly specific monoclonal antibodies, or Mabs. The discovery has opened a great range of medical applications.