The issues raised in Plague Time are not stagnantly awaiting resolution. Each week brings new developments in our understanding of the true nature of disease. New opportunities present themselves. Observers need to be sufficiently broad-minded to recognize them. Sometimes key bits of evidence have already been reported but have been overlooked. New observations and insights can then guide researchers to search for evidence in the literature years or even many decades after it was published.
One such relic was presented to me on a Friday afternoon last April by one of my students, Levi Ledgerwood. Stepping toward a chair in my office, Levi navigated his 6'6" frame and correspondingly large shoes around the piles of papers, journal articles and article rising from the carpet. He had been doggedly tracking the literature on schizophrenia for two semesters. As he researched evidence familiar to current experts, he also sniffed out older evidence that might have been overlooked or forgotten as a result of inattention or the biases of the times. His goal was to assess whether the entire body of evidence implicated infectious causation. Normally calm and collected, Levi on this afternoon was a bit jittery, a sure sign that he had something interesting in hand. "It's LSD, or something like it," he said as he handed over a research paper that had been published a half century ago.
The previous summer, schizophrenia expert Fuller Torrey told me that his research group was finding associations between Toxoplasma gondii infection and schizophrenia, a lead that I passed along in the hardcover edition of Plague Time, and that provided the impetus for Levi's detective work. T. gondii is a distant relative of the protozoan that causes malaria, but rather than being dispersed by the bites of mosquitoes, T. gondii is transmitted to cats when they eat rodents, and then transmitted back to other rodents when the rodents lick or eat things contaminated by cat droppings. Instead of being digested by the rodent, the parasite penetrates the intestinal wall and moves to the brain, causing the rodent to behave abnormally in response to important environmental stimuli; for example, when infected rats encounter the smell of a cat they do not seem to appreciate the gravity of their situation—good for the cat (it gets a meal), good for the parasite (it gets transmitted), bad for the rat (it gets eaten). T. gondii encysts in human brains as it does in rodent brains, but this similarity doesn't mean that T. gondii causes schizophrenia. It would be useful to know whether T. gondii-infected rodents became schizophrenic. But how can one tell whether a rat is feeling paranoid, hallucinating, or hearing voices that are not really there?
The paper that Levi handed to me provided a clue. The authors °f the article tested schizophrenics for infection with T. gondii and for the presence of LSD. Over half of their patients were infected with T. gondii, and these infected patients were almost always the same patients who tested positive in the LSD test. The production of LSD or an LSD-like compound in T. gondii-infected schizophrenics strengthens the case for T. gondii as a cause of the hallucinations experienced by schizophrenics, and, more generally, as a cause of schizophrenia.
After Plague Time went to press and while Levi was conducting his detective work, the data collected by Torrey and his colleagues were set in print. In accordance with the study published a half century earlier, almost half of their schizophrenic subjects tested positive for T. gondii whereas only about one in ten of the nonschizophrenic controls tested positive. Mothers of schizophrenics were almost five times more likely to be infected with T. gondii than mothers who did not have schizophrenic children, suggesting transmission during pregnancy as a major route of infection.
As Levi and I were mulling over these connections my peripheral vision picked up a figure in the doorway. Expecting a student, I was surprised to see Paul Sherman, an evolutionary biologist from Cornell. Levi went off to do more sleuthing while Paul and I headed down the hallway to catch up on things.
Both of us had developed an interest in evolution through studies of animal behavior and had then broadened this interest to consider questions pertaining to evolution and the health sciences, and human behavior. With an eye toward comparing notes, he asked me how medical audiences were responding to my lectures on the ideas in Plague Time. "Mixed," I replied and then went on in more detail. A typical audience contains at least a few for whom the light clicked on, an effect that alone can make a lecture worth giving. There are also territorial individuals who seem intent on picking a fight. Others lose the train of logic, but on the whole most are engaged, and their responses range from constrained enthusiasm to dismissiveness.