MacFormat 1996 July/macformat-039.iso/DATABASE/BODY/CU52.TXT

Text File | 1996-03-11 | 4.5 KB | 90 lines | [TEXT/????]

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
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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.