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Arsenic and modern medicine

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Salvarsan treatment kit for syphilis, also known as the

Source: Science Museum, London, Wellcome Images

Salvarsan was a synthetic drug produced to treat the STI syphilis. The drug was developed by Paul Ehrlich (1854-1915), a German medical scientist, and his team in 1909 after three years of research. Ehrlich coined the phrase ‘magic bullet’ to describe this new wonder drug. The drug in the kit was made by a German manufacturer Farbwerke vorm Meister Lucius & Bruning AG and is stamped with the date “3 February 1912”. It was sold by a British chemist, W Martindale, who added all the equipment to prepare injections.

A hundred years ago this month, one of the first casualties of the Great War was a German chemist, Alfred Bertheim, who died on 17 August 1914. An early volunteer in the German army, he donned his uniform, tripped over his spurs, fell down a flight of stairs and broke his neck. However, his main claim to fame is not the manner of his death but his role in the development of the first modern chemotherapeutic agent.

In 1905, Bertheim was recruited to help Paul Ehrlich, a German physician who was trying to synthesise chemicals that were toxic to micro-organisms but had minimal adverse effect on the host. As a starting point for his research, Ehrlich had chosen atoxil, an organic arsenic compound known to be active against trypanosomes but with side effects too severe for clinical practice.

Bertheim elucidated atoxil’s chemical structure and the pair went on to synthesise a range of modified molecules. Eventually, with a compound that they numbered 606 (because it was sixth in the sixth group to be tested), they came upon a substance that, although ineffective against trypanosomes, had antisyphilitic activity and an acceptable side effect profile. This “magic bullet” was arsphenamine (Salvarsan or “606”). It was launched on the market in 1910 and brought worldwide fame to Ehrlich — though not to Bertheim.

Arsphenamine and its derivatives remained the drugs of choice for syphilis until penicillin arrived in the 1940s. Although arsphenamine was of no use for trypanosomiasis, a newer organic arsenic compound, melarsoprol, is now part of a standard treatment, although used only under careful supervision because of adverse effects.

Before the advent of organic arsenicals, arsenic trioxide was for centuries used in a wide range of medical conditions, including various infectious diseases, although toxic effects always precluded widespread adoption. However, despite its toxicity, potential therapeutic roles are still being investigated.

Some years ago, researchers in China discovered that arsenic trioxide was a common ingredient across a range of traditional Chinese medicines used in cancer. They investigated the compound in a number of cancer types and achieved a 90 per cent remission rate in relapsed acute promyelocytic leukaemia (APL).

Further studies in Europe and North America produced similar results, and regulatory agencies subsequently approved arsenic trioxide for use in relapsed or refractory APL. And it may in future have other anticancer uses, since researchers have also demonstrated its activity in end-stage, high-risk multiple myeloma.

It is well over 2,000 years since arsenic trioxide was first used as both a poison and a therapeutic agent. And now it seems to be making a comeback in medicine.

 

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From: Beyond pharmacy blog

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