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'Lithium' Is A Homage To A Drug — And To The Renegade Side Of Science

Aug 14, 2019

Like any good story about a scientific discovery, Walter A. Brown's account of the history of lithium features plenty of improvisation, conjecture and straight-up kismet.

Unlike many such stories, though, it also features a fair share of personal bias, senseless puttering and random speculation — on part of these scientific researchers.

Brown, a practicing psychiatrist and university professor of more than 40 years, seems to have been drawn to write Lithium: A Doctor, A Drug and a Breakthrough as much because of lithium's fluky history and overlooked importance (for many years, he argues, it was "the Cinderella of psychiatric drugs") as by the profound impact it's had on countless sufferers of bipolar disorder and depression.

Lithium is a homage, not just to a drug, but to the renegade side of science. Its heroes are researchers scattered around the globe, short on funding and frequently unaware of each other's work, without whom a commonly available substance would never have been recognized as a treatment for one of the most baffling psychiatric illnesses. By celebrating these men, Brown hopes to do a lot more than simply raise awareness about an underappreciated substance. He aims to demolish what remains of the myth that scientific progress is driven by rigorous dispassion.

The story of lithium's use in medicine is certainly colorful, as is the history of the illness it's become known for. Brown doesn't stint on either tale. He goes all the way back to the first century to find a would-be description of manic depression by the Greek doctor Aretaeus of Cappadocia. These patients, Aretaeus wrote, "'laugh, play, dance night and day, and sometimes go openly to the market crowned, as if victors in some contest of skill,'" only to become "'torpid, dull and sorrowful.'"

Before lithium, Brown notes, the treatments for this enigmatic condition ranged from merely ineffective to out-and-out grotesque. Over the centuries patients have been bled and purged, dosed with opium, infected with malaria, placed in medically induced comas and had their teeth, tonsils or organs removed. Some alarming treatments are distressingly contemporary: Lobotomy, the procedure in which a patient's frontal lobe is surgically severed from the rest of the brain, dates from the first half of the 1900s.

It was a century earlier that scientists first isolated lithium. Doctors noticed that the element could dissolve uric acid, which was blamed at the time for a wide variety of illnesses, and lithium was used to treat everything from headaches to obesity. For a while lithium water was a popular cure-all, and lithium was once used as a salt substitute. But it was only in 1949, when the Australian psychiatrist John Cade published a paper showing it could help patients with mania, that modern lithium therapy was first contemplated.

Cade is the star of Brown's book, not just for his pioneering status, but for his unique outlook and temperament. He had wide-ranging scientific interests, studying everything from variant magpie species to a possible link between schizophrenia and fruit consumption. His son recalled his father deducing, based on the fact that gum moth caterpillars' tiny scat pellets had six sides, that the caterpillars' anuses were six-sided too. "Cade's inclination to thoroughly examine the world around him was a characteristic in short supply," Brown writes. "Most of us see only what we expect to see... most of us ignore or fail to perceive the unexpected."

Cade investigated lithium while working at a small mental asylum where his only laboratory was an abandoned kitchen. He tested dosages on guinea pigs kept in his backyard (they doubled as his kids' pets) and stored urine samples in the family refrigerator. And yet, Brown notes, Cade's "small study, which would probably not be published today and which lacked the standardized assessment methods, statistical niceties and other accoutrements of contemporary research, yielded results that changed the practice of psychiatry and mended the lives of millions."

Cade wasn't alone in his attention to lithium; though fears about toxicity and a lack of funding deterred studies for many years, several independent-minded researchers around the world investigated the drug's effectiveness in treating bipolar disorder and regular depression. But among the scientists he discusses, Brown is most passionately drawn to those who, like Cade, approached the process of discovery with an unorthodox spirit.

The book's other standout figure is Danish researcher Mogens Schou, who confirmed that lithium was an effective treatment for mania. Schou endured much criticism because he had a personal interest in his investigations: He used lithium to help his younger brother, who'd suffered regular depressive episodes for 25 years. "As a consequence of his readiness to talk about his brother's excellent reaction to lithium, Schou was accused by some of being biased," Brown writes, "a 'believer' rather than an objective scientist."

Brown is as determined to puncture such attitudes as he is intrigued by lithium itself. It's this emphasis, itself rather quixotic, that makes Lithium memorable. Lots of science books describe how early breakthroughs almost didn't happen and deplore the state of corporate-funded research. Brown makes a more nuanced point: That some pioneers are set apart, not by their stubbornness or seat-of-the-pants circumstances, but by qualities that the scientific world usually ignores.

Cade described himself as "an enthusiastic amateur, full of curiosity, with... inadequate knowledge and woeful technique," adding that "even the small boy, fishing after school in a muddy pond with string and bent pin, occasionally hauls forth a handsome fish." It's in that small fisherman's spirit that Brown places his hope for the future.

Etelka Lehoczky has written about books for The Atlantic, The Los Angeles Review of Books and The New York Times. She tweets at @EtelkaL.

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