Lithium is a silvery-white metal that is so light it can float on water and so soft it can be cut with a butter knife. Along with hydrogen and helium it was produced during the Big Bang and so formed the universe before the emergence of the galaxies. It is employed to harden glass and to thicken grease, but its best-known industrial use is in the manufacture of rechargeable batteries. Lithium salts are found in considerable quantities in brine and igneous granite and the element is present in trace quantities in the human body. Lithium is also one of the few metals – along with platinum for cancer, gold for rheumatoid arthritis and bismuth for dyspepsia – that are used as medicines.
In 1949, a 37-year-old Australian doctor called John Cade produced a paper reporting that lithium quietened patients suffering from acute manic excitement. He reminded readers that lithium salts had been commonly used in the 19th century to treat gout and other disorders believed to be associated with high uric acid levels but had disappeared from the pharmacopoeia due to safety concerns. He then went on to describe a series of preclinical experiments he had carried out in a disused kitchen that had led him to consider lithium as a treatment for both manic depression (now often called bipolar disorder) and epilepsy. When injected into guinea pigs, urine collected from patients with mania caused more convulsions and fatalities in the animals than urine from healthy volunteers. Cade suspected that urea might be the toxin responsible for this but was unable to show that the patients with mania had higher levels of it in their urine. Undeterred, he carried out further experiments, which showed that uric acid enhanced the poisonous effects of urea and also neutralised the protective effects of urinary creatinine. Based on knowledge from the existing literature that lithium could dissolve kidney stones containing uric acid, he then injected urea, saturated with lithium urate, into the guinea pigs. The animals did not convulse or die; they became docile and immobile for several hours before fully recovering. Encouraged by this finding, he then started to take lithium salts himself to test their safety, before proceeding with observational trials in patients with life-threatening mania.
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