Samuel Gershon: Lithium history

Malcolm Lader’s Comments

It is indeed a great privilege to be asked to comment on the article by an esteemed nonagenarian,Sam Gershon, regarding a puzzling anomaly in the discovery of the mood-regulating properties of the simple element, Lithium, number 3 in the periodic table. Points raised include the responsibilities of a researcher to provide the background to the purported discoveries and to make honest attributions of others’ prior work. Sam not only gives a comprehensive account of Cade’s work in establishing the utility and toxicity of lithium as a psychiatric therapeutic agent but provides erudite references to key studies in the 1940s and 1950s.

The starting point is Johan Schioldann’s magnum opus on the history of the introduction of lithium as the marker for the birth of modern psychopharmacology. The book is coruscating and compendious. Whether lithium was truly the start of modern psychopharmacology depends on the meaning of the term “modern”: there is some danger of a circular argument.

Be that as it may, one is left with an uncomfortable feeling that a hidden agenda exists – why did Cade notacknowledge the antecedents of his work? Numerous authors were easily citable, many years before the advent of computer searches.

The animal studies werecrude, to say the least, and Schoustated that he could not replicate them. Has anyone else tried: they are surely not difficult to repeat?

However, whatever the animal findings,probably of intoxication (as Sam notes), the crucial issue is the findings in man. How Cade elided from animal to human experiments remains obscure. Lithium has a narrow therapeutic index (Schou, 1957), so the choice of dose is an overriding issue. But experience had long been accruing in other areas of medicine so the appropriate dosage range was already ascertainable.

Like Schioldann, I am also not convinced by the evocation of serendipity as the mechanism of Cade’s discovery.I have had reservations as to the provenance of lithium’s therapeutic and toxic effects (Shepherd, Lader and Rodnight 1968). Horace Walpole used this term to describe an unplanned fortuitous discovery as the three Princes of Serendip did on their travels. Rather, Cade was following a planned approach stemming from his ideas on diet and mental illness. He rediscovered the effects of lithium, first in guinea pigs and then in patients (of mixed diagnoses). I agree with Sam that the process and background thinking is important to document, at least to give due credit. Cade did not cite previous work. Did that reflect academic isolation as a hospital superintendent? Perhaps Sam can enlighten us. Or is there a darker interpretation? Cade cannot defend himself or his reputation but clarification by others is essential:could Sam repeat his version of events?

Sam credits W. A. Hammond as the first person to describe the use of lithium to in the treatment of mania in 1871 in his compendious textbook. This seems right and we should correct the record.

He concludes by casting significant doubts “as to how this history has become legend.” I have always had my concerns. Having recently completed an M.A. in history, I know how important primary sources are, even more so than personal testimony. Sam has done the psychopharmacology scientific community a great service by raising doubts both from written sources and, I assume, from bearing witness at the time. Yet in the final analysis we have a useful therapy which can be a boon when used with the appropriate safeguards as followed byNoack and Trautner and published as early as 1951.              

References:

Hammond WA. A Treatise on Diseases of the Nervous System. New York: Appleton; 1871. pp. 754.

Noack CH,Trautner E.M.  The lithium treatment of maniacal psychosis.  Med J Aust. 1951; 18; 219-22.

SchioldannJ. History of the Introduction of Lithium into Medicine and Psychiatry; Birth of Modern Psychopharmacology 1949.Adelaide: Adelaide Academic Press; 2009.

SchouM. Biology and pharmacology of the lithium ion.Pharmacol Rev.1957; 9:17-58.

Shepherd M., Lader M, Rodnight R. Clinical Psychopharmacology, London: English Universities Press; 1968.

September 27, 2018