- Email: [email protected]
Mind the microbes
Media Watch
Book Mind the microbes In 1822, French physician Antoine Laurent Bayle described a disease that is now called general paresis. Accompanied by delusions, mania, and dementia, the disease was common in the 19th century. At the time, doctors believed general paresis to be like any other mental illness—a punishment for depravity. But in 1857, on the basis of a statistical analysis of patients with paresis, German doctors Johannes Friedrich Esmark and W Jessen suggested syphilis as the cause. In the following years, evidence accrued that syphilis might cause paresis, such as when Treponema pallidum, the bacteria that causes syphilis, was isolated from the brains of patients with paresis. These findings gave hope that a cure for syphilis would likewise cure paresis. And the cure eventually came, in the mid-20th century, with penicillin. Nowadays, physicians treat syphilis immediately, partly to prevent paresis, which could otherwise emerge decades later. General paresis is now rare in the developed world, compared with only a century ago, when one in five patients in mental asylums had the disease in New York City. Harriet Washington, a journalist and bioethicist, recounts this story as a precedent for Infectious Madness, in which she explores the role of microbes in causing mental illnesses. Germ theory, she writes, eluded scrutiny as a paradigm for mental illness. “Paresis was recognized as infectious and then rooted out of the asylum by penicillin, but diseases like schizophrenia, depression, bipolar disorder, and obsessive-compulsive disorder remained the province of mental health”. Microbes, she acknowledges, are not the sole cause of mental illnesses: “the traditional risk factors of genetics, stress, and other environmental pressures are sure to apply as well. Yet most researchers into the infection connection estimate that known pathogens account for 10 to 20 percent of cases of mental illness.” As Washington explains through stories, research, and interviews with researchers, these potential pathogen– illness connections include Bacteroides fragilis and autism, influenza and schizophrenia, and group A streptococci and anorexia, obsessive–compulsive disorder, and Tourette’s syndrome. One hypothesis on which Washington focuses is whether some cases of schizophrenia are zoonotic, spread by cats that carry the parasite Toxoplasma gondii. She cites the work of American physician–scientists E Fuller Torrey and Robert Yolken, and begins by noting that cat ownership became popular in America in 1871, the year when US schizophrenia rates rose sharply. She describes some of the epidemiological research, writing that in 2008, “Yolken and Torrey published a study indicating that the peak age for becoming infected by T gondii, between eighteen and www.thelancet.com/infection Vol 16 March 2016
thirty-five, coincides with the peak age of the first signs of schizophrenia. They also noted that in areas where felines are rare, the prevalence rates of both toxoplasmosis and schizophrenia are low.” In addition, studies “found that children of mothers who contracted T gondii while pregnant did suffer higher rates of schizophrenia than other children. This association is highly suggestive, especially because the parasite is known to be neurotropic—to target brain cells. Collectively, these studies strongly suggest that infection with toxoplasma is a significant risk factor for the development of schizophrenia.” Importantly, as Washington presents these data, she dwells on caveats and misconceptions. One example is her discussion of Koch’s postulates and the Bradford-Hill criteria, highlighting the difficulty of establishing causation from association. Moreover, Washington cautions that twin studies do not necessarily reflect genetic heritability; instead, they might indicate a shared in-utero exposure. “Most identical twins—three of every five sets—share a placental circulation, and this circulation carries not only nutrients but also antibodies and pathogens like those suspected of causing schizophrenia—including Toxoplasma gondii”. She explains that if an in-utero exposure did underlie schizophrenia, “then twins who share circulations should have a higher percentage of concordance [of schizophrenia] than those who do not. And this is precisely the case.” In the latter chapters, Washington shifts away from discussing specific pathogen–illness hypotheses, to considering broader factors that might affect the link between microbes and mental illnesses. For instance, she highlights antimicrobial resistance and neglected tropical diseases as two problems that also contribute to the burden of mental illness caused by microbes. Washington also describes how sociopolitical obstacles can stifle progress in medical science. She proffers the example of Greek physician John Lykoudis, who, as early as 1958, proposed that Helicobacter pylori causes peptic ulcers. His assertion challenged the then-prevailing theory that high stress and spicy foods caused ulcers. But rather than being able to test his theory in a controlled study, Lykoudis was shunned by his government and medical society, despite reportedly curing his own ulcers with an antibiotic cocktail. For Washington, these series of events uncannily resemble those that decades later led Australian physicians Robin Warren and Barry Marshall to establish that H pylori causes peptic ulcers. Overall, Infectious Madness presents several intriguing hypotheses linking specific microbes to specific mental illnesses. Washington describes the underlying research
Infectious Madness Harriet A Washington Little, Brown and Company, 2015 Pp 304. $28·00 ISBN-13: 9780316277808 http://www.hachettebookgroup. com/titles/harriet-a-washington/ infectious-madness/978031627 7808/
Further reading Ledgerwood LG, Ewald PW, Cochran GM. Genes, germs, and schizophrenia: an evolutionary perspective. Perspect Biol Med 2003; 46: 317–48. Rigas B, Papavassiliou ED. John Lykoudis: the general practitioner in Greece who in 1958 discovered the etiology and a treatment of peptic ulcer disease. In: Marshall BJ, eds. Helicobacter pioneers: firsthand accounts from the scientists who discovered helicobacters, 1892–1982. Singapore: Blackwell Science, 2002: 75–84
301
Media Watch
in an accessible way for the lay reader. However, the degrees to which these associations suggest causation are unclear. And if pathogens do account for some cases of mental illness, the question remains: for any given case, how does one determine if a pathogen is the root cause? Understandably, these questions remain unanswered in the scientific literature, but these uncertainties about causation are not sufficiently conveyed in the book. Early in her book, Washington quotes American humourist Robert Benchley: “‘There may be said to be two classes of people in the world…those who constantly divide the people of the world into two classes, and those who do not.’” Physicians, she says, belong to the first
302
group, referring to the mind–body dualism codified by the Diagnostic and Statistical Manual of Mental Disorders. Despite its shortcomings, such categorisation ideally reflects our state-of-the-art understanding, with further research refining, and sometimes wholly redefining, our categories. The cause of paresis was redefined, from “depravity” to syphilis. Peptic ulcers were recategorised, now considered a common consequence of H pylori infection rather than stress or spices. In time, other diseases, including mental illnesses and their potentially microbial causes, might follow.
Mohsin Ali
www.thelancet.com/infection Vol 16 March 2016
Book Mind the microbes In 1822, French physician Antoine Laurent Bayle described a disease that is now called general paresis. Accompanied by delusions, mania, and dementia, the disease was common in the 19th century. At the time, doctors believed general paresis to be like any other mental illness—a punishment for depravity. But in 1857, on the basis of a statistical analysis of patients with paresis, German doctors Johannes Friedrich Esmark and W Jessen suggested syphilis as the cause. In the following years, evidence accrued that syphilis might cause paresis, such as when Treponema pallidum, the bacteria that causes syphilis, was isolated from the brains of patients with paresis. These findings gave hope that a cure for syphilis would likewise cure paresis. And the cure eventually came, in the mid-20th century, with penicillin. Nowadays, physicians treat syphilis immediately, partly to prevent paresis, which could otherwise emerge decades later. General paresis is now rare in the developed world, compared with only a century ago, when one in five patients in mental asylums had the disease in New York City. Harriet Washington, a journalist and bioethicist, recounts this story as a precedent for Infectious Madness, in which she explores the role of microbes in causing mental illnesses. Germ theory, she writes, eluded scrutiny as a paradigm for mental illness. “Paresis was recognized as infectious and then rooted out of the asylum by penicillin, but diseases like schizophrenia, depression, bipolar disorder, and obsessive-compulsive disorder remained the province of mental health”. Microbes, she acknowledges, are not the sole cause of mental illnesses: “the traditional risk factors of genetics, stress, and other environmental pressures are sure to apply as well. Yet most researchers into the infection connection estimate that known pathogens account for 10 to 20 percent of cases of mental illness.” As Washington explains through stories, research, and interviews with researchers, these potential pathogen– illness connections include Bacteroides fragilis and autism, influenza and schizophrenia, and group A streptococci and anorexia, obsessive–compulsive disorder, and Tourette’s syndrome. One hypothesis on which Washington focuses is whether some cases of schizophrenia are zoonotic, spread by cats that carry the parasite Toxoplasma gondii. She cites the work of American physician–scientists E Fuller Torrey and Robert Yolken, and begins by noting that cat ownership became popular in America in 1871, the year when US schizophrenia rates rose sharply. She describes some of the epidemiological research, writing that in 2008, “Yolken and Torrey published a study indicating that the peak age for becoming infected by T gondii, between eighteen and www.thelancet.com/infection Vol 16 March 2016
thirty-five, coincides with the peak age of the first signs of schizophrenia. They also noted that in areas where felines are rare, the prevalence rates of both toxoplasmosis and schizophrenia are low.” In addition, studies “found that children of mothers who contracted T gondii while pregnant did suffer higher rates of schizophrenia than other children. This association is highly suggestive, especially because the parasite is known to be neurotropic—to target brain cells. Collectively, these studies strongly suggest that infection with toxoplasma is a significant risk factor for the development of schizophrenia.” Importantly, as Washington presents these data, she dwells on caveats and misconceptions. One example is her discussion of Koch’s postulates and the Bradford-Hill criteria, highlighting the difficulty of establishing causation from association. Moreover, Washington cautions that twin studies do not necessarily reflect genetic heritability; instead, they might indicate a shared in-utero exposure. “Most identical twins—three of every five sets—share a placental circulation, and this circulation carries not only nutrients but also antibodies and pathogens like those suspected of causing schizophrenia—including Toxoplasma gondii”. She explains that if an in-utero exposure did underlie schizophrenia, “then twins who share circulations should have a higher percentage of concordance [of schizophrenia] than those who do not. And this is precisely the case.” In the latter chapters, Washington shifts away from discussing specific pathogen–illness hypotheses, to considering broader factors that might affect the link between microbes and mental illnesses. For instance, she highlights antimicrobial resistance and neglected tropical diseases as two problems that also contribute to the burden of mental illness caused by microbes. Washington also describes how sociopolitical obstacles can stifle progress in medical science. She proffers the example of Greek physician John Lykoudis, who, as early as 1958, proposed that Helicobacter pylori causes peptic ulcers. His assertion challenged the then-prevailing theory that high stress and spicy foods caused ulcers. But rather than being able to test his theory in a controlled study, Lykoudis was shunned by his government and medical society, despite reportedly curing his own ulcers with an antibiotic cocktail. For Washington, these series of events uncannily resemble those that decades later led Australian physicians Robin Warren and Barry Marshall to establish that H pylori causes peptic ulcers. Overall, Infectious Madness presents several intriguing hypotheses linking specific microbes to specific mental illnesses. Washington describes the underlying research
Infectious Madness Harriet A Washington Little, Brown and Company, 2015 Pp 304. $28·00 ISBN-13: 9780316277808 http://www.hachettebookgroup. com/titles/harriet-a-washington/ infectious-madness/978031627 7808/
Further reading Ledgerwood LG, Ewald PW, Cochran GM. Genes, germs, and schizophrenia: an evolutionary perspective. Perspect Biol Med 2003; 46: 317–48. Rigas B, Papavassiliou ED. John Lykoudis: the general practitioner in Greece who in 1958 discovered the etiology and a treatment of peptic ulcer disease. In: Marshall BJ, eds. Helicobacter pioneers: firsthand accounts from the scientists who discovered helicobacters, 1892–1982. Singapore: Blackwell Science, 2002: 75–84
301
Media Watch
in an accessible way for the lay reader. However, the degrees to which these associations suggest causation are unclear. And if pathogens do account for some cases of mental illness, the question remains: for any given case, how does one determine if a pathogen is the root cause? Understandably, these questions remain unanswered in the scientific literature, but these uncertainties about causation are not sufficiently conveyed in the book. Early in her book, Washington quotes American humourist Robert Benchley: “‘There may be said to be two classes of people in the world…those who constantly divide the people of the world into two classes, and those who do not.’” Physicians, she says, belong to the first
302
group, referring to the mind–body dualism codified by the Diagnostic and Statistical Manual of Mental Disorders. Despite its shortcomings, such categorisation ideally reflects our state-of-the-art understanding, with further research refining, and sometimes wholly redefining, our categories. The cause of paresis was redefined, from “depravity” to syphilis. Peptic ulcers were recategorised, now considered a common consequence of H pylori infection rather than stress or spices. In time, other diseases, including mental illnesses and their potentially microbial causes, might follow.
Mohsin Ali
www.thelancet.com/infection Vol 16 March 2016