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Arsenic: The Dark and the LightJohn Emsley

30 million rolls of wallpaper made per annum in Britain by the 1870s. ... in Liverpool indicated that Atoxyl was effective in treated infected animals. ...

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Arsenic: The Dark and the LightJohn Emsley

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    Slide 1: Arsenic: The Dark and the Light John Emsley, The Elements of Murder, Oxford: Oxford UP, 2005  

    Slide 2:Arsenic

    In the C19 arsenic was used extensively. Examples: wallpapers, textiles contained arsenic. Scheele’s green (copper arsenite), or CCA, was used as a wood preservative in treated pine until relatively recently. Essential element? Ca 0.1 ppm in humans

    Slide 3:Insidious Arsenic

    30 million rolls of wallpaper made per annum in Britain by the 1870s. 4/5 contained arsenic. Thought dangerous from 1815. Initially dust was suspected. Microbes shown to be involved. Eventually confirmed in 1932 that trimethylarsine was the culprit.

    Slide 4:One for the X-Files

    The US Ambassador to Italy suffered arsenic poisoning in the 1950s. The Ambassador, Clare Boothe Luce, had chosen to sleep in a room not previously used as a bedroom. The ceiling was highly decorated and arsenic pigments had been used. Vibrations caused by a washing machine on the floor above caused the formation of arsenic-rich dust.

    Slide 5:Arsenic Eaters

    Peasants in the Styrian Alps, between Hungary and Austria, regularly consumed large doses of arsenic trioxide. Started with 30 mg twice a week, then increased the dose to around 100 mg per day. The Styrian Defence. Interferes with iodine metabolism – leading to thyroid problems.

    Slide 6:Lewisite

    Lewisite is a compound containing arsenic that was developed during WW I as a chemical weapon. BAL (British Anti—Lewisite) was developed prior to WW II as an antidote. BAL has been used in cases of heavy metal poisoning.

    Slide 7:Arsenic in Beer

    A case of mass arsenic poisoning occurred in Birmingham in 1900. About 6000 people poisoned. 70 died. Glucose that was used in beer-making was contaminated. The sulfuric acid used in preparing the glucose was made from iron pyrites with significant As present. Beer had ca 15ppm As (6pts = 45mg)

    Slide 8:Arsenic in Groundwater

    Much of Bangladesh is low-lying with a chronic problem being the supply of clean water for villages. A WHO sponsored project sank many tube wells in Bangladesh. Water and oxygen has caused the oxidation of arsenic-containing minerals – mobilising the As into groundwater. About 90% of Bangladeshis drink well water.

    Slide 9:Fowler’s solution

    Described in 1786 by Thomas Fowler, a medical practitioner in Stafford. Followed use of arsenic by Paracelsus and van Helmont. Used in C19 as a treatment for malaria. Found to have significant effect on a leukaemia patient in 1865. This use persisted until the 1940s.

    Slide 10:Sleeping sickness

    Livingstone recommended Fowler’s solution for the treatment of sleeping sickness. Sleeping sickness was found to be due to trypanosomes (T brucei). The trypanosomes could be temporarily eliminated by the administration of Fowler’s solution. Mortality could be as high as 75%.

    Slide 11:Atoxyl

    The compound known as Atoxyl was synthesised in 1863. Found to be inactive against trypanosomes in culture. Tests in 1905 in Liverpool indicated that Atoxyl was effective in treated infected animals. Used therapeutically would require constant medication for 6 mo., leading to blindness.

    Slide 12:Arsphenamine

    Analogues of Atoxyl were tried against trypanosomes with some success. The compounds that Ehrlich and colleagues had developed were tested on Treponema palladium, the causative agent of syphilis (isolated 1905). Once efficacy had been proved 65000 samples sent to physicians for trial. Marketed as Salvarsan.

    Slide 13:Arsenic and cancer

    In the late C19 it was discovered that users of Fowler’s solution developed skin cancers. Inorganic arsenic is the problem. Implicated in bladder, lung and liver cancer. Trisenox is used in the treatment of acute promyelocytic leukaemia (APL). Trisenox is a modern version of Fowler’s solution.

    Slide 14:Trisenox

    Chinese physicians in Harbin reintroduced arsenicals as anti-cancer agents from the 1970s. Particularly successful in the treatment of APL. Low plasma concentrations (1-2mM) are effective – mild side effects. Remission rates between 85 – 93%. Therapy being trialled for other leukaemias.

    Slide 15:Other references

    Walter Sneader, Drug Discovery: A History, New York: Wiley, 2005. John Timbrell, The Poison Paradox, Oxford: Oxford UP, 2005. Gielen and Tiekink, (eds.), Metallotherapeutic Drugs and Metal-based Diagnostic Agents, New York: Wiley, 2005.

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