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.

 a distinctive and horrifying madness

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.

a lifetime with Mercury

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?

No Mercury no GPI

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.

the Mad Hatter made it clear to Alice 

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).

Pharmacosis – a distinctive and horrifying madness.

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.

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  1. Could we be seeing a combination of genetic predisposition combined with viral infection or environmental toxins? I did some research a few years ago on spinocerebellar atrophy mainly in the Nebraska kindred. This family is identified in the literature and can trace its roots to one Dutch ancestor. The family still exists in the Netherlands but although the American branch has developed an autosomal dominant disease, with the aberrant gene now identified, not one member of the family still in Holland has ever been affected. If we also consider the ALS-Parkinson-Dementia of Guam, it was decided that the disease could be traced to a food that was toxic if not thoroughly washed. In one year, in Toronto, I had four patients, all presenting clinically differently, who came to autopsy as part of a large research study and were found to have ALS-PD-Dementia. The transport of syphilis from the Americas to Europe might be of the same nature e;g; a food stored for the return journey, an environmental toxin to which the indigenous peoples had developed an immunity etc. HIV appeared just as suddenly for reasons that remain obscure for all the billions that have been spent on investigation. Perhaps some previously unencountered fauna of the “New World” played a part. in the development of syphilis. We know that many of our common environmental toxins cause damage to the DNA but perhaps were not so common in the days of Beethoven, Mozart et al. Treating a disease with such obvious poisons as mercury and then arsenic can hardly fail to strike one as supremely harmful but, as we know, all medications are tiny doses of poison – consume enough and they’ll all kill you.

  2. Thanks so much for writing about this. Regarding the higher number of males than females with GPI, I have read that mercury tends to affect males worse than females.
    “Mercury studies in mice and humans consistently report greater effects on males than females, except for kidney damage (57). At high doses, both sexes are affected equally; at low doses only males are affected (38,40,127).”
    p. 467 at

    “Testosterone and estrogen-like compounds give vastly different results. Using female hormones we found them not toxic to the neurons alone and to be consistently protective against thimerosal toxicity. In fact, at high levels they could afford total protection for 24 hours against neuronal death in this test system (data not plotted). However, testosterone which appeared protective at very low levels (0.01 to 0.1 micromolar), dramatically increased neuron death at higher levels (0.5 to 1.0 micro- molar). In fact, 1.0 micromolar levels of testosterone that by itself did not significantly increase neuron death (red flattened oval), within 3 hours when added with 50 nanomolar thimerosal (solid circles) caused 100% neuron death. Fifty nanomolar thimerosal at this time point did not significantly cause any cell death.”

    Mark Blaxill and Dan Olmsted recently wrote an excellent book about the history of mercury in medicine: “The Age of Autism: Mercury, Medicine, and a Man-Made Epidemic”.

  3. Johanna says:

    Is there anything in official medical histories about the use of mercury to TREAT depression and other mental ailments? It looks like this may have happened in the case of Abraham Lincoln – with ghastly results. This blog post inspired me to do some checking up on our 16th president, probably the most famous allegedly-bipolar Great American. It’s well-known that he suffered from spells of depression, which could be profound at times, all his adult life. This article by medical historian Norbert Hirschhorn et al. claims that Lincoln took a mercury preparation called “Blue Mass” to treat his condition:

    Apparently doctors of the time labeled his condition “hypochondriasis” – a combination of depression, anxiety and loosely defined digestive complaints. Following the ancient Greeks, it was often attributed to black bile, and Benjamin Rush among others recommended mercury as a treatment. Lincoln himself referred to his bouts of melancholy as hypochondriasis or “the hypo.” There is fairly good evidence that at some point in the 1850’s he started taking “Blue Mass” pills. Among the effects were tremors, memory lapses, outbursts of uncontrollable rage and what some observers swore was worsening melancholy. Shortly after his inauguration in 1861 he told a friend he’d stopped taking the pills because they “made him cross.” For the rest of his life, through the storm and stress of the Civil War, he was known for his almost superhuman steadiness of character, and no more episodes of rage were reported.

    If it’s true, then ours is not the first era in which depression sufferers were given treatments with side effects that seemed to mimic the worst features of the illness – and were probably mistaken for a worsening of the illness itself. And apparently it took a brilliant man, with access to the best doctors in America, years to figure out what was happening.

  4. Winston Churchill fought all his life from his “black dog”.
    “I don’t like standing near the edge of a platform when an express train is passing through”, he wrote.” I like to stand right back and if possible get a pillar between me and the train. I don’t like to stand by the side of a ship and look down into the water. A second’s action would end everything. A few drops of desperation.”
    In 1911 a friend of Churchill’s claimed to have been cured of depression by a doctor but no details survive or none that I have been able to find.
    Churchill’s doctor, Lord Moran, wrote a memoir about his patient, emphasizing the black dog with plenty of symptoms but no treatment which was probably very fortunate for the eventual fate of Great Britain and the outcome of WWII.
    Interestingly, with respect to a previous post on GPI, his father, Lord Randolph Churchill died at age 45 supposedly of syphilis although there remains controversy about the accuracy of the diagnosis.

  5. Johanna says:

    Apparently Abe Lincoln’s “treatment” with mercury pills for melancholy was not an exception. Calomel and other mercury concoctions were an accepted treatment for mental illness, according to this 1865 medical text, “A Manual Of Practical Therapeutics”, by Edward John Waring:

    1392. In Insanity, the administration of mercurials is occasionally productive of benefit, but much discrimination is required in their use. Dr. Copland’s* observations on this point are well worthy of attention. Mercurials, he remarks, are employed for mental disorders, with three intentions, – 1st, to evacuate biliary and fAecal accumulations; 2nd, to improve the secretions, particularly that of the liver; and 3rd, to produce a copious flow of saliva. To fulfil the first of these intentions, Calomel is particularly useful, especially in melancholia and in mania; but should be conjoined with or followed by other purgatives. To produce the second effect, any of the mercurial preparations may be employed, either alone, or with Tartar Emetic, Digitalis, Camphor, &c. To accomplish the third end, Calomel, or Corrosive Sublimate, or Blue Pill, may be given, either combined as above, or alone.

    The employment of mercurials to an extent likely to produce salivation is of very doubtful propriety, although recommended by some writers. Dr. Prichard remarks, that it is by no means a general remedy for maniacal diseases; but in cases of torpor, with suppression, or a very scanty state of any of the secretions, it is frequently advantageous ” Several instances of cure effected by salivation,” continues Dr. Copland, “have been recorded by authors; still I believe,” he adds, ” that Mercury exhibited to the extent necessary to produce the effect, and especially when it fails of causing it, is quite as likely to be as injurious as beneficial – to cause partial insanity, melancholia, and mania, particularly in weak, susceptible, and irritable constitutions. Unfortunately, we know nothing of the symptoms of insanity which indicate probable advantage from mercurial salivation. The most likely conditions are mania or melancholia consequent upon apoplexy, or complicated with hepatic disease. Mercurials, and particularly salivation, are most likely to prove injurious in every form of insanity which has been occasioned by depressing moral, or by exhausting physical causes, and especially by prolonged anxiety or by masturbation. Corrosive Sublimate, however, in minute doses, as an alterative in conjunction with tonics, is sometimes of service in several forms of mental disorder, and particularly in scrofulous constitutions.”

    This book, by a British Army doctor, at least recognizes the risk that high doses of mercury could themselves cause “partial insanity, melancholy and mania.” In that sense at least, he’s ahead of most contemporary psychiatrists, who tend to double the dose when their pills cause symptoms. If Lincoln were alive today he might be told he had rapid-cycling bipolar disorder and the Blue Pills had merely “unmasked” it!

  6. It’s amazing the number of “studies” diagnosing artists from other centuries.
    Van Gogh has already received all the diagnostics.
    I once watched a documentary about a kind of epilepsy that makes some lights…
    I don’t remember but… Van Gogh was on the list and, of course, if affected his
    Someone gave me a book of a French therapist who not only explained his disease but also found in his paintings the “prove”: a certain pattern on the wall clearly is a sign of his loneliness.
    I didn’t read the entire book.
    Few people can see his work detached from his mental illness. His biography is known by everybody.
    This is sad.

  7. I have some comment to make about Paresis differential diagnosis.
    I’m a french jurist (i hope you will forgive my terrible english !) and developpe obstinate interest for study of syphilis and other STS, and more specifically neurologic manifestations of the disease. I wish to tell you a few words about the encephalitis called dementia paralytica or general paralysis.

    Differenciation between disorders like Dementia praecox and circular insanity with Paresis is a difficult task but some clues can help :

    1. Paresis is a insidious disease, it begin quite rarely in a abrupt manner, patient show signs of incipiens dementia some time before maniac or depressive onset appears.
    2. Paresis is excessively rare before 25 years and rare before 30.
    3. Paretic rarely show premorbid personality of circular or schizophrenic or their familiar story.
    4. Time between first mental manifestations and diagnosis rarely excede 3 years.
    5. Time between first manifestations and death is, on average, 27 months, survival over 5 or 6 years is quite unusual.
    6. Survival 3 years after dementia become incapaciting (or after admission in asylum) is unusual, survival more than 5 years after is quite rare (diagnosis become doubtfull, even if autopsy proved cases duration of 20 years or more exist). Perhaps 1 per cent of paretic live more than 7 or 8 years, in a study of 346 cases maximal duration was 111 months.
    7. In upper class most males can give a story of syphilis, and the remain have usually a story of probable syphilis or penile chancre. The more intelligent patient give a story suggesting syphilis in 90/100 cases.
    8. Paresis clinical diagnosis is made no on mental manifestations alone but on neurologicals sign, slurred speech is the main symptom. Tremor, ataxia et gait disturbance come in second. Of all ocular signs only complete loss of light reflex is really ominous, miosis have some specificity.
    9. Global and rapidly progressive dementia is the main feature of paresis, depressive disorder, megalomaniac outburst are less importants. As dementia increase others psychiatric manifestation usually die out. Memory and judgment disturbances are ominous, loss of insight appears usually quite early, in advanced cases dementia is complete, the clinical presentation is somewhat similar to frontotemporal dementia but memory loss is more marked.
    10. Clinical accuracy of diagnosis is 85 to 95 per cent on average. Some experts reach nearly 100 per cent. Diagnosis of paresis is made frequently on historical figures in an abusive manner, Nietzsche is the most famoux example.
    I want to give my own amateurish diagnosis : no clear neurological pattern of paresis, like dysarthria, no history of syphilis, 11 years survival after diagnosis (!), diagnosis error extremely likely.
    De Maupassant is clearly a paretic but he presents both typical history with syphilitic anamnesis, typical clinical presentation and expected course. You can remark his litterary production end as soon as Paresis became clinically evident.

    Best regard

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