Science: It destroyed limbs, can it save lives?: Thalidomide, already used to treat leprosy, may help to combat Aids, says John Emsley
Monday 23 August 1993
Although thalidomide is no longer prescribed in Britain, it is still used in the Third World to treat leprosy. But it may soon return to Britain in the fight against Aids. A group of doctors, led by Professor Angus Dalgleish at St George's Hospital Medical School, London, has sought permission to begin trials on 40 male volunteers who are HIV-positive.
Thalidomide was banned in Britain in 1961 after about 460 babies were born with malformed and tiny limbs. Each family received pounds 60,000 compensation - about pounds 500,000 today - from the UK distributor, Distillers. If thalidomide were introduced now, there would be no risk of malformed babies as chemical advances would ensure it was safe.
Chemie Gruenenthal, the German company that developed thalidomide in the Fifties, tested it as a sedative and found it was safer than the antidepressants then available. Massive doses were not lethal - an adult could take up to 350gm (12oz). What the company failed to realise was that while half the thalidomide molecules were safe, the other half contained a poison.
Both forms have the chemical formula C13 H10 O4 N2 , and consist of the same groups of interlinked rings of atoms. But each molecule is the mirror image of the other. Just as there are left and right pairs of hands, so there are pairs of many molecules, among them thalidomide. Chemists label them not left or right but S (from the Latin sinister) or R (rectus).
R-thalidomide is fine, but the S form taken on certain days of pregnancy interferes with the replicating DNA and deforms the foetus. As it was manufactured, thalidomide consisted of R and S molecules in equal numbers. Now, chemists can separate them easily for a variety of R and S pairs; indeed, all new pharmaceuticals must now be tested in both versions.
In 1958 thalidomide was launched in Germany, as Contergan, by Gruenenthal, which felt it safe enough to be sold without prescription. Within a few years the drug was available in more than 40 countries. The liquid form was known as Germany's best babysitter, as it was superb for sending children to sleep. 'Completely harmless, even for infants,' said the leaflet. There were side-
effects, such as constipation, lowered blood pressure and dizziness, but these are to be expected with any drug.
In Britain, the drug, called Distaval, was often given to control morning sickness. Its UK patent made no reference to the fact that it was a mixture of two forms.
Today thalidomide is manufactured in Brazil using the original recipe and is used to treat leprosy. It is still not purified into the two forms, but if it is not taken by pregnant women, there is no risk.
Sir Colin Berry, professor of morbid anatomy at the Royal London Hospital, says: 'Thalidomide minimises the adverse effects that can follow any treatment which involves destroying bacteria in large numbers, and this is what happens in leprosy.' Thalidomide may also be useful in treating inflammatory conditions such as rheumatoid arthritis, and even preventing the rejection of organ transplants, as it suppresses the immune system.
It was while investigating thalidomide's anti-inflammatory action that Dr Gilla Kaplan, at Rockerfeller University, New York City, discovered it blocked an agent that cells produce when infected with toxins. This agent, a protein, is responsible for fevers, aches and inflammation. It is also used by HIV to reproduce itself in other cells - and, as thalidomide reduces the agent's activity, it thereby delays the onset of Aids.
The author is science writer in residence at the Department of Chemistry, Imperial College, London.
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