Mental
Page 19
A few hours south is the Nevada National Security Site, previously the Nevada Test Site, an area established on January 11, 1951, for testing nuclear devices. Among all its other miraculous applications, lithium is also crucial in nuclear fusion reactions. Nuclear testing at the Nevada Test Site began with a 1-kiloton-of-TNT (4.2 TJ) bomb dropped on Frenchman Flat on January 27, 1951. The images of the nuclear era became so iconic that tourists would flock to Vegas hotels to watch the mushroom clouds from the atmospheric tests that could be seen from almost a hundred miles away. Local lore, I was told, is that the winds would blow residue of uranium north to the Valley and as silver mining dried up, outfits looking for alternate ways to make money “found” uranium. After more testing, they thought the soil was naturally rich in uranium. But they found lithium instead. Though mine is the word used for extracting lithium, it’s not quite right. The process is a mostly sun-driven evaporation process, with pools of brine captured in various stages of evaporation until the liquid transforms into salt. It’s also misleading to call Silver Peak a town—there used to be a gold mine and a silver mine here, like most of the abandoned places in the middle of Nevada. But all that ore had mostly run dry. What remained was a frontier mentality and a load of cash to be made by sifting something else from the earth.
In August 1966, Foote Mineral dedicated its plant in Silver Peak to prospecting for the lithium-laden brine that lay beneath the surface of the high desert hills. No one had thought to exploit the brine before because the technology simply hadn’t been developed. The company first established a method to extract lithium from the underground pools, then established its plant in the mineral-rich land. “The sun does the majority of the work,” USGS geologist Brian Jaskula told me. “They have this dry desert area but underneath it is a running brine solution. The process begins by pumping the brine into a big series of evaporation ponds. . . . The brine is pumped into trucks and brought over to the processing facility and certain chemicals are added like soda ash to make lithium carbonate. It’s made and bagged and shipped off to customers. It’s pretty amazing because it’s so low tech.” David Klawitter, a mechanic for Rockwood, showed me his swollen, red hands painted with a permanent layer of grit. “The lithium burns sometimes, but it’s fine; it eats sockets, though, rusts them up solid. You can see what it does to the trucks.” Tankers rolled by transferring the brine to various different pools. “We make medical-grade lithium here; we’re processing a pure form of lithium, the purest.” Rockwood Lithium, purchased by Albemarle in 2015, is the only operating lithium plant in America and sits on the fifth-largest deposit of lithium in the world. It’s more accessible than the findings in Afghanistan because there isn’t war breaking out above the brines. Its processing facilities are more advanced than anything in Bolivia, and the final product is easier to transport. But China, Australia, and Chile are capitalizing on an open market.
When the operation began, there was already a community of miners from the days of the gold and silver mines, a volunteer fire and police force, a bar called the Shifting Sands Saloon, and its rival the Dead Coon Saloon, which hosted local weddings that ended in bruises and brawls, new mothers-in-law included. It’s the kind of place where bodies were found mysteriously at the bottom of the town well. Silver Peak, when asked what it wanted from the spoils of mines, requested a swimming pool for the kids to offset the 100-plus-degree summer days. Along another dusty road between Silver Peak and Goldfield are the remnants of concrete pools near Alkali Hot Springs. There are two plunging tubs with a hose funneling in lithium water at around 100 degrees Fahrenheit. The springs were once the bathing grounds for tent city miners and cowboys like the Earp brothers, prospecting for gold at the turn of the century. The baths are still soothing, though the pool is full of catfish now.
Only 1 percent of lithium produced goes toward medication, but I imagine this is the spot where my pink pills come from. I like to think I was just ahead of the trend, that my taking lithium was prophetic to a future in which we all depend on lithium. I made my way to an old gold mining town, appropriately named Goldfield. I’d heard of a natural spring nearby and thought I might soak in lithium waters again. No one had a clear sense of where the hot springs were, except for a nudist website with vague instructions. There were no roads or roads with names or roads that made sense to me, so I pulled over to talk with an old miner who told me about the springs location but only after I bought a gold chip mined from his nearly inactive mine. He said to turn around, turn left, and then make another left and look for an oasis—an actual patch of paradise in the middle of the sand. I didn’t see one person or car or tree on the ride through the dirt roads. I was driving a tiny rental car that left a hurricane of dust announcing my presence. In some patches the road was only one-way and I drove cautiously, mostly nervous about being alone. When I pulled up to the springs wearing my bathing suit under layers, a truck was already parked there. That made me more nervous. The man I saw was an elderly gentleman with a Wilford Brimley mustache and a hunting-plaid shirt. He told me the waters were healing and pointed to a young man soaking in the hot springs, his “nephew.” I noticed his nephew had a fresh gash on his temple and seemed mentally impaired, like he couldn’t talk, or wouldn’t talk or had been locked in a basement too long to know if he should talk. He wouldn’t make eye contact with me. “It helps him calm down,” Brimley Mustache said. Wilford Brimley kept talking up the waters, and I kept imagining myself chopped up in the Clown Motel (a real place) back in Tonopah where I was staying. I thanked him for chatting and said I had to go. “It’s a shame you can’t stay for a soak,” he said through his mustache. But I had my Bolivia waters still fresh in my veins.
CHAPTER 20
LITHIUM’S LORE AND THE TRANSITION TO DEPAKOTE (TAKE 1)
LITHIUM WORKS IN mysterious ways and as I bid it good-bye, I wanted to get a sense of how it went from ancient Greek soaks to a pink pill. Despite the fact that people have benefited from its use for millennia, how lithium works on brains is largely unknown. “It has so-called trophic or fertilizing activity on the brain—that is, it stabilizes membranes,” James Kocsis, a professor of psychiatry at Weill Cornell Medical College in New York and an expert on lithium, told me. Lithium acts on many levels throughout the nervous system and within the functional integrity of the cell, including transmitting signals to the brain through cells. But the actual mechanics are a mystery. One way to think about its effect, though, is suggested by a 2007 UCLA study that found that bipolar patients taking lithium had significantly more gray matter than their counterparts in the study—both bipolar patients not taking lithium and people without bipolar disorder—especially in the region associated with a person’s capacity to maintain attention and emotional control.
In the second century AD, Soranus treated manic patients with the alkaline waters in his town, which contained very high levels of lithium. Since the fourth century BC, Therma, Ikaria, has been a known center for hydrotherapy—it’s even referenced in historical texts and archaeological remains for its ancient baths and facilities, which delivered “the cure” via its potent hot radion and lithium springs. Herodotus recommended bathing twenty-one days in a row at the Apollon Spa in the center of Ikaria. One of the first references to lithium in a neurological context appears in 1870 by a neurologist in Philadelphia named Silas Weir Mitchell—the same doctor who controversially employed bed rest for women suffering from nervous disorders. (Remember, “The Yellow Wallpaper”? That guy.) He recommended the compound lithium bromide as an anticonvulsant and a hypnotic for epileptic patients. Psychotropics were just starting to show results by newly implemented medical establishments. The following year, William Hammond, professor of diseases of the mind and nervous system at Bellevue, became the first doctor to prescribe lithium for mania: “Latterly I have used the bromide of lithium in cases of acute mania, and have more reason to be satisfied with it than with any other medicine calculated to diminish the amount of blood in the cerebr
al vessels, and to calm any nervous excitement that may be present.” Two decades later, Danish psychiatrist Frederik Lange explicitly referred to lithium in the treatment of “melancholic depression” and treated thirty-five patients with lithium carbonate. At the turn of the century, French physician Roger Reyss-Brion said the popularity of a fizzy soda tablet called “Dr. Gustin’s Lithium” may have undermined some medical testing because lithium was effectively being administered as a medicine already in the form of over-the-counter soda: “It’s quite simply for that reason that you don’t have a lot of manic-depressives in Marseilles,” he wrote. It’s also thought that mineral springs in France have unnaturally high amounts of lithium. More lithium in the waters, less need to medicate people because they’re getting small doses every day. Lithium may be the true reason why the French can sit in cafés for hours, eat cheese, and sip coffee slowly. They may, in fact, have a natural lithium chill embedded in their geography.
But by the early 1900s, medical lithium had largely been supplanted by other treatments. Ironically, in the 1930s and 1940s, the makers of 7-Up included mood-boosting lithium citrate in their soda formula, back when the health-minded sect of society was lithium-happy. There were “Lithia-Beers” and even a lithium version of Coca-Cola. Researchers now have come close to identifying why lithium functions as a mood stabilizer—it affects the levels of serotonin that act as a messenger regulating aspects of the nervous system such as sleep, memory, appetite, mood, sex, endocrine function. And studies have found that when lithium is prescribed chronically (for more than three weeks), the increase in serotonin is focused in the hippocampus rather than scattered all over the brain. However, the National Alliance on Mental Illness remains opaque: “Lithium is a medication that works in the brain to treat bipolar disorder.” It never explains how.
In 1947, John Cade, a psychiatrist working in a hospital outside Melbourne, Australia, rediscovered lithium’s medicinal potential. Cade was among the first to conclude that mental illness included bodily manifestations and thus should be treated with medication, not just talk therapy. “It required a change in how people understand mental illness,” I was told by Robert Beech, an assistant professor of psychiatry at Yale University who conducts studies on medical lithium. He described this insight as a shift from “more psychological, Freudian explanations to a biological explanation.” There seemed to be a cycle of psychohistory: Freud saw physical symptoms as evidence of troubles in the mind; later psychiatrists found physical symptoms were in fact biological; some doctors later combined both theories. What remains is a constant debate in psychiatric circles: What is the best combination (if any combination) of analysis and psychotropics?
Cade, whose father was also a psychiatrist, was at first simply trying to isolate the cause of mania. Having noticed that the urine of manic patients was unlike that of his stable subjects, he figured the distinguishing component, uric acid, was responsible for the mania. Seeking to produce that mania in his animal subjects, guinea pigs, he needed a solution in which to supply the uric acid to them, and used lithium urate (and later, lithium carbonate, the exact compound that I was taking). But his guinea pigs became lethargic; instead of inducing mania, he had accidentally discovered a treatment. Cade became convinced that lithium could cure many of his patients’ symptoms that we now associate with schizophrenia, bipolar disorder, PTSD, and dementia. To test its safety, he ingested lithium himself; later, he began a trial with nineteen patients. The ten manic subjects experienced a significant shift in mood and function, but one of Cade’s subjects died, probably from a high dose, which halted any significant steps toward employing the element as a medication. The therapeutic range of lithium is relatively small and has to be monitored closely, but that wasn’t known when Cade conducted his research. It didn’t help that toward the end of the 1940s, lithium’s use as a table-salt substitute for congestive heart patients in the United States proved lethal in at least two instances. Cade proved lithium’s efficacy nonetheless, and he did it by using the scientific method, a significant hurdle to the psychiatric community that had been previously regarded by some as a pseudo-science. Not only that, but Cade’s research marked the beginning of the psychopharmacological era.
Lithium trials continued in a number of countries regardless. Mogens Schou, a physician who specialized in clinical chemistry and happened to have his lab located in a large psychiatric hospital, tested Cade’s theories in double blinds; Poul Christian Baastrup set up his first lithium study in 1957; G. P. Hartigan, a psychiatrist in Canterbury, England, had noticed that lithium treatment seemed to inhibit mood swings in both manic and depressive directions after a small clinical trial. He spoke about his findings in 1959. Schou encouraged Hartigan and Baastrup to publish their findings, but both were reluctant. Schou wrote to Hartigan about lithium’s efficacy: “I am asking about this not only out of interest in the use of lithium in psychiatry; but also because one of my brothers has been suffering.” Hartigan responded, “In your brother’s case, it should be well-worth trying.” Schou administered lithium to his brother and his brother had no more bouts of mental illness. The three psychiatrists, now aware of each other’s continued trials and patients, started collaborating on research, convinced it could be a miracle drug. However, the British psychiatric community protested the findings, writing them off as a “therapeutic myth.” American psychiatrists were starting to champion the drug but its use was debated. The Food and Drug Administration (FDA) was still reeling from thalidomide the “wonder drug” and its consequent birth defects. Doctors and boards approving new medications were especially cautious. Barry Blackwell, an anti-lithium psychiatrist, wrote in response to an editorial written by American psychiatrist Nathan Kline, that lithium would “join Cinderella’s godmother in the pages of mythology. To transform ‘just plain old lithium’ into the elixir of life on the evidence available is an achievement second only to converting a pumpkin into a stagecoach.” In response, Kline wrote, “Dr. Blackwell’s delightful letter reads as though it was written by one of Cinderella’s spiteful step-sisters. . . .” But research in the States began nonetheless: Samuel Gershon’s arrival from Melbourne in 1960 at the Schizophrenia and Psychopharmacology Joint Research Project of the University of Michigan at the mental hospital in Ypsilanti, Michigan, introduced lithium to the U.S. Several other lithium studies began, as well: Nathan Kline at Rockland State Hospital in New York, Stanley Platman in Buffalo, Paul Blachly in Portland, and Eugene Ziskind in Los Angeles.
After dosages approached uniformity and careful monitoring became routine, lithium in various compounds was recognized as an acceptable treatment. Lithium gluconate was approved in France in 1961, lithium carbonate in Britain in 1966, lithium acetate in Germany in 1967, and lithium glutamate in Italy in 1970. Among the drug’s champions was American medical resident Ronald Fieve, who began experimenting with lithium in 1958, after his adviser at Columbia University returned from Australia with tales of Cade’s experiment. “It was so effective,” Fieve told me, that he was “treating the most severe bipolar 1 patients, and this lithium brought them back to normalcy in 10 to 15 days.” Fieve described running a lithium clinic in 1966—the first ever lithium clinic in the States, part of the New York State Psychiatric Institute and Columbia Presbyterian in New York City. The clinic was well regarded by Governor Rockefeller—it was a place where patients who were thought to be hopeless were rebounding and functioning. Fieve hosted Cade for a dinner in the 1970s and they swapped lithium stories. The breakthrough was that a medicine could cure a mental disorder, something that was and still is controversial and not fully resolved. “We needed a certain approach because therapists were still trying to talk to manic depressives, as if they could fix them,” Fieve told me. “I was becoming an expert in psychopharmacology. We used the clinics to house and treat these people. They were oriented toward drug therapy instead of only talk therapy. It was a medical approach to psychology. We still have that same paradigm, you come in, you g
et an examination, and after a thorough history of the family and your medical history and tests, we start patients on the lithium if they need it.”
When I talked with Fieve, in his eighties and still practicing on the Upper East Side of New York, he had not let go of lithium, including the medication’s uses beyond psychiatric implications. He’s been conducting a study on how lithium salts could possess cytoprotective actions, a process in which chemical compounds protect cells against harmful agents. It might prevent a variety of disease states such as cardiovascular diseases and neurodegenerative disorders. He’s not alone in the belief that lithium could treat other illnesses. De-Maw Chuang of the Mood and Anxiety Disorder Program at the National Institutes of Health in Bethesda, Maryland, found that lithium might help treat other brain conditions such as stroke and Alzheimer’s disease. In 2003, Chuang conducted several experiments. He gave lithium to rats after they experienced a stroke and studied the rats and their cells. After five days there were 30 percent more stem cells than normal. Meaning, lithium was potentially prompting the brain to replace damaged brain cells with healthy ones. The medication could act in a regenerative way, not just as a psychotropic. The most promising study was published by Chuang and several other colleagues from the National Institute of Mental Health and the National Institute of Health in 2014. In it, they argue that so much of lithium’s research has been related to “the protective and regenerative properties of lithium focused on neurons; in contrast, limited research has been conducted into lithium’s effects on white matter, which also plays an important part in Traumatic Brain Injury–related pathophysiology.” In other words, lithium has the potential to act “as a neuroprotective agent in a variety of neurological and neurodegenerative disorders, including cerebral injury.” But in spite of more than ten years of trials, the study, titled “A New Avenue for Lithium: Intervention in Traumatic Brain Injury,” was more of a plea to continue research. Unfortunately, continued research into lithium’s application in this realm seems unlikely. One of lithium’s characteristics—that it is an element on the periodic table—makes it unpatentable. There’s no incentive to continue studying lithium’s effect on brains because there’s no money in it.