{book review} lithium: a doctor, a drug, and a breakthrough

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Lithium, as its subtitle suggests, tells three interwoven stories: that of the life of John Cade, the doctor who discovered lithium’s most important medical use; that of lithium itself from its first discovery as an element to its recognition as both a drug and a toxin; and that of lithium’s bumpy road to acceptance through research trials, scientists’ feuds, and governmental wariness.

While the third story has arguably the most to cover, and while the book does a good job of presenting the clinical trials, publications, detractors, and advocates involved, that was probably my least favorite theme. There are a lot of players, since most science takes place in teams and between teams as ideas bounce around and hypotheses are tested, and it can be hard to feel connected to any of them. I did appreciate here the discussion of different types of clinical trials (such as double-blinded trials, where neither the patient nor the clinician knows whether the drug being administered is a placebo or the experimental substance), the ethics involved in setting up clinical trials (for example, if a drug is almost certainly preventative with regards to a major mental illness, is it ethical to consign certain patients to a placebo for long enough to measure prophylaxis?), and the statistical problems raised by studying a fairly uncommon condition.

The second storyline was where lithium itself took a starring role, and was also where bipolar disorder was explained in detail – in essence, setting the two up as the protagonist and antagonist. I am (obviously) a bit of a biology nerd and I would have loved even more depth about the chemistry of lithium, the biology of bipolar disorder, and the hypotheses about how the two meet at the molecular level – but Lithium stays at a level that I believe would be understandable by the average educated adult, with no need for specialized medical or scientific knowledge. Still, it was fascinating. On the one hand, there was the crippling effect of uncontrolled mania or spiraling depression, historically consigning patients to lives cycling in and out of hospital psychiatric wards – and then on the other is a substance that promises to restore balance and moderation at the expense of exposing your body to a toxin that can cause thyroid and kidney damage after long-term use and brain damage and even death at doses just slightly higher than medically necessary.

One of the most interesting aspects of lithium as a drug, to me, is its influence on the rate of suicide. Bipolar patients have a 10-20 fold increased risk of suicide, and lithium is the only psychiatric drug that is able to significantly reduce that risk (about a 10-fold reduction, actually, bringing the risk back into the normal range). As the author writes,

“Experts speculate that lithium may modify one or more of the psychological or brain processes that give rise to suicide. Thus, lithium may have a place in the treatment of patients who are at high risk for suicide, whether or not they have manic-depressive illness. […] About a dozen studies, most conducted in the past decade, have shown with reasonable consistency that a relatively high concentration of lithium in a region’s drinking water is associated with a relatively low rate or suicide. These studies have been carried out in Texas, Japan, Austria, Greece, and elsewhere. There is no ready explanation for this association […] One expert has suggested that even though the lithium imbibed with drinking water is insufficient to have any immediate psychological or biological effect, when taken over a long time it might.” – Lithium, Epilogue

The final storyline of the book (or the first, according to the subtitle) is that of John Cade: a devout Catholic, a military doctor, and the leading psychiatrist of Australia. Unlike the majority of the scientists involved in Lithium‘s “breakthrough” storyline earlier, Cade’s character truly comes to life. His resilience and ingenuity shine in his years spent in a Japanese prisoner-of-war camp during WWII, where he served as the psychiatric doctor to both American and British soldiers, analyzed the nutritional quality of scavenged food to help prevent malnutrition among his fellow inmates, and memorized the news he heard in stolen moments airtime on secret radio to retell to the rest of the camp. His dedication and concern for his patients are seen in his willingness to ban lithium in his jurisdiction over toxicity concerns despite his personal investment in the success of the treatment, and his readiness to allow it again when other researchers showed how that toxicity could be managed – he always strove to put the patients’ best interests first, rather than picking a side in an argument and prioritizing being right. And above all, he is depicted as a continual observer, his mind constantly curious, always seeing the wonder of the world around him.

“It seems that Cade’s brain never stopped simmering. His talent for educated speculation, for weaving disparate facts into more or less plausible hypotheses, was a particular strength.” – Lithium, Epilogue

“[Cade’s] curiosity about the natural world and the satisfaction he got from his ‘discoveries’ about it (not diminished at all by the fact that other had made the same discoveries) were, according to his friends and family – and by his own admission – among his foremost qualities. […] Cade’s inclination [was] to thoroughly examine the world around him […]. Most of us see only what we expect to see. More troublesome, most of us ignore or fail to perceive the unexpected. But Cade seemed to have an aptitude for taking in the unforeseen.”- Lithium, chapter 2, The Naturalist

Overall, Lithium was a solidly good book – non-fiction with enough detail to immerse the reader in the story and enough diversity to keep interest and motivation high (I read the book in just two days). I learned a lot about the history of the discovery of lithium as a treatment for bipolar that I had never known before, despite some family history that intersected with key years in lithium’s journey. And I came away inspired by John Cade’s persistent wonder and inner strength, ready to see the world around me with renewed curiosity and attention.