A 24 year old volunteer died of respiratory and renal failure after inhaling hexamethonium during a clinical research project at John Hopkins University.
According to the US Office of Human Research Protections, the researchers failed to obtain published literature about the known association between hexamethonium and lung toxicity.
How were these articles missed? The answer, it seems is that all were published before 1966 and as a result none appeared in a search of the PubMed database.
Eugene Garfield, who pioneered many aspects of bibliometrics, including citation analysis, and founded the Institute of Scientific Information, agreed that "the older literature is frequently overlooked".
Several cases of respiratory failure attributable to a 'fibrinous pneumonitis' syndrome were reported in the '50s in patients receiving hexamethonium.
Neuroscientist Douglass S DeWitt observed that "it is all too easy to assume that MEDLINE encompasses the whole of the medical literature".
As researchers discover new uses for old drugs – as in the current test of the 1940s malaria drug quinacrine for variant Creutzfeldt-Jacob disease – it seems certain that new questions that might be answered in the old literature will continue to arise.
1966 and all that - when is literature search done?
Faith McLellan
The Lancet – Volume 358 – August 25, 2001