Arsenic: The Dark and the Light

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• Arsenic The Dark and the Light
• John Emsley, The Elements of Murder, Oxford
  Oxford UP, 2005  

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Arsenic

• In the C19 arsenic was used extensively.
• Examples wallpapers, textiles contained arsenic.
• Scheeles 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

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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.

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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.

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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.

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Lewisite

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

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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)

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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.

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Fowlers 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.

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Sleeping sickness

• Livingstone recommended Fowlers 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 Fowlers solution.
• Mortality could be as high as 75.

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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.

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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.

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Arsenic and cancer

• In the late C19 it was discovered that users of
  Fowlers 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 Fowlers
  solution.

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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.

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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.