Pharmacosis: the Day the Music Died

Syphilis appeared in Italy in 1498 just after Columbus had returned from the New World. This later led to suggestions that it had been brought back from the New World, in exchange for the many European illnesses that decimated the populations of North American Indians.

Exposed to a virgin population new infections can be particularly virulent and during the subsequent century in Europe syphilis led to severe physical complications and often death.

Thereafter its virulence eased, until around 1800 a new and terrible manifestation appeared – general paralysis of the insane (GPI). This was also called tertiary syphilis or dementia paralytica, a distinctive and horrifying madness. Patients cycled through profound depression to extreme elation, psychosis and later dementia before dying.

Stepping back from the illness, doctors could distinguish it from dementia praecox (schizophrenia) by its course – patients cycled through the various stages before dying quite quickly. They were also much more likely to be male. Schizophrenia lasted for decades and was equally male and female. But at any one point in time patients with dementia paralytica and dementia praecox could look identical.

The first recognizable descriptions of both schizophrenia and GPI can be found in an 1809 book on insanity. It took a century to conclusively link GPI to syphilis. The development of the Wasserman reaction which tested for the spirochete, treponema pallidum, that we now know causes syphilis made it clear that this distinctive madness was invariably Wasserman positive. Before that a range of distinctive neurological features made doctors relatively confident in the diagnosis; these included changes to the pupils of the eye and others.

GPI was a late manifestation of the illness. Syphilis begins with a sore on the penis. For the first most virulent century these sores often extended all over the body – a mark of Cain. But later as the virulence declined they might only appear on the genitals and internal organs. One of the early discoveries was that a mercury salve could help. Administered topically as a paste, the sores sometimes healed. This led to a linkage between mercury and syphilis and the famous phrase of “a night with Venus and a lifetime with Mercury”.

Mercury helped but it didn’t cure. Physicians began to work on methods to get mercury into the body. These included getting the patient to sweat while exposed to mercury vapors, or drinking mercury in the form of Calomel – mercurous chloride. Finally in the 1780s Jacob van Swieten developed a mercuric chloride potion, Van Swieten’s liquor.

Van Swieten was working in Vienna and his brief was the health of the army, whose most serious affliction was syphilis. Soon after his liquor came on the market, the first cases of GPI appear. Could Mercury have caused or contributed to the creation of this mental illness?

Here’s the case against mercury. Many years later in 1925 shortly before he died Emil Kraepelin who coined the term dementia praecox for schizophrenia took a trip to North America to raise funds for an institute in Munich. One of his interests on this trip was to look at mental illnesses among North American Indians. He was struck by the lack of GPI – even though syphilis had supposedly come from North America.

It also turned out that GPI was rare among American Negroes. A later study in American Negroes infamous for its non-treatment of syphilis, the Tuskegee study, reveals that GPI was much less frequent among American Negroes than among Whites at the time.

Within Europe, Norway offered a striking exception – there were very few cases of GPI. The Norwegians preferred general hygienic measures for managing syphilis and apparently steered clear of Mercury.

Finally GPI was much more common in men than in women, except for one group of women – prostitutes. This seems unsurprising perhaps if syphilis was linked to sex. But if men were infected, their wives were too and should have gone on to GPI also, but didn’t. The initial signs of infection in a woman are more likely to be internal and were accordingly less likely to come to attention and be treated. Women therefore were less likely to take mercury. Except that is for the prostitutes who in a number of cities like Vienna were forcibly treated with mercury in order to reduce transmission.

Against the link to Mercury is the fact that when malarial fever therapy was introduced in 1917, it cured GPI. The conventional view is that the malarial temperatures killed off the spirochete. High fevers of various sorts like this might explain the benign course of syphilis in American Indians for instance.

But it is difficult to ignore the role of Mercury if only because the Mad Hatter made it clear to Alice that it can cause psychosis in its own right. Killing the spirochete may have stopped one contribution to psychosis.

This is important for a few reasons. It bears on the story of schizophrenia where a growing case can be made that lead neurotoxicity helped transform some other condition into the chronic psychosis we call schizophrenia (See Healy et al 2012).

Unlike lead, which was never used to treat schizophrenia (although there was a surprising amount of lead put into medicines in the 19th century), if Mercury did play a role in GPI, it offers a dramatic example of Pharmacosis – a distinctive and horrifying madness. For much of medicine’s history, doctors were a last resort as their treatments often killed. Hospitals were houses of death rather than cures. But the tally of deaths and injuries in the case of syphilis is particularly poignant.

There is some evidence Mozart contracted syphilis. He knew van Swieten’s son. In the short term mercuric chloride was more likely to cause kidney failure than GPI, which fits the bill for his possible death. Beethoven caught syphilis. Mercuric chloride causes deafness. Schubert caught syphilis and died far earlier than was likely to have happened had he been left untreated. Schumann caught syphilis and is more likely to have had GPI than manic-depressive illness.

In recent years, a bipolar industry has claimed that all great artists have had bipolar disorder – a vanishingly rare and much less common illness in the 1800s than GPI was. It’s much more likely that Van Gogh, Baudelaire, Flaubert and others along with Guy de Maupassant, Friedrich Nietzsche, and Oscar Wilde, had GPI rather than manic-depressive illness.

There is a real case today that many of the antipsychotics or mood stabilizers being given cause the psychoses they are supposed to treat or mood swings they are supposed to stabilize. Misled by a short term benefit, doctors often use these drugs in stupefying doses that eliminate any possibility of recovery – and patients are encouraged to cooperate by being told they are just like Schumann, Van Gogh or others.