In 1927 the Viennese
psychiatrist Julius Wagner-Jauregg was awarded one of only two Nobel prizes
ever given to a psychiatrist for his discovery of the malaria treatment
of general paresis. Compared to his contemporary Sigmund Freud, Wagner-Jauregg's
name has almost disappeared from memory.1 Recently, Andrew Scull has suggested
that historians have passed over the malarial treatment, along with other
somatic treatments, in what he refers to as an 'embarrassed silence.' Indeed
in the late twentieth century, the idea, as Scull describes it, of breeding
'colonies of malarial mosquitoes with which to infect tertiary syphilitics
and so burn the offending parasites from their brains' seems more appropriate
for moral censure than than universal acclamation.2 Our relative silence
about malarial treatment may, however, have other sources than embarrassment.
Twentieth century psychiatrists have until recently been more interested
in psychological treatments than in somatic ones; while historians like
Scull have often been more interested in psychiatry's failures than its
successes. Moreover diseases like general paresis and pelagrous dementia
have been so nearly eradicated that it is hard to remember what a large
place they once played in psychiatric practice.
In order to appreciate
the significance of the malaria treatment at the time that Wagner-Jauregg
announced it in 1921, one must see this innovation in the context of the
history of the disease that it cured--general paresis of the insane. In
that context Harold Mersky’s views seems closer to the mark than Scull’s
facile dismissal. According to Mersky, 'any clinician today
(who) could achieve the sort of results with AIDS ... which Wagner-Jauregg
obtained with general paralysis, ...would receive the immediate acclaim
and the same ultimate rewards as those given for the introduction of malarial
treatment.'3 Mersky's comparisons with AIDS is apt in several ways. General
paresis was a uniformly fatal disease that most frequently struck people
(men far more often than women) between the ages of 20-40. A diagnosis
of general paresis was stigmatizing, both before and after it was understood
to be caused by syphilis. Before they died paretics became completely demented
and unable to care for themselves, dying most often in insane asylums.
As with AIDS there was initially great optimism that when paresis was discovered
to be caused by an infectious agent--treponema pallidum--that it would
yield conventional anti-syphilitic treatment. There was also great disappointment
when Salvarsan--the so-called magic bullet for syphilis, failed to interrupt
the fatal course of general paresis. Unlike AIDS, however, general paresis
had frustrated all attempts to find a cure for over one hundred years before
Wagner-Jauregg introduced his treatment.
General paresis of
the insane was first identified as a distinct disease by Antoine Laurent
Jessé Bayle in the 1820s. He characterized it as having both physical
and mental symptoms, a regular natural history and consistent post mortem
findings. Although psychiatrists differed over whether or not Bayle
had discovered a new disease, they all agreed that finding signs of paresis,
even subtle early signs, in an insane patient meant that the patient did
not have long to live. Indeed it was just the fact that general paresis
had such a uniformly short and fatal course that had allowed Bayle to see
it as a single disease. While psychiatrists were proud of their ability
to characterize this disease as thoroughly as they could and hopeful that
would soon be able to characterize others as thoroughly, they were nonetheless
embarrassed by their complete inability to cure patients of this
disease.4
This embarrassment was often concealed in callous demonstrations
of their prognostic acumen. J.E.D. Esquirol, one of the architects
of psychiatry's early nineteenth century therapeutic optimism, as well
as one of the first do describe paresis among the insane, for example,
boasted that his specialized expertise allowed him to detect signs of paresis
that had eluded a provincial colleague. The patient was a
'strong, robust' thirty year old man who had persuaded himself
that he possessed immense fortune and had yielded 'to all the excesses
of the most fashionable life.' He was brought to Paris by the ‘skillful
and estimable' Dr. K., who deferentially presented the patient to Esquirol.
'I commit to your care,' Dr. K. said to Esquirol ‘a very interesting patient,
who is but slightly excited, and whom I have withdrawn from scenes
calculated to augment his excitement, which you will speedily cure.’
Esquirol conducted a half an hour ‘conversation’ with the patient,during
which he observed ‘some hesitation in the pronunciation of certain words’
and an ‘undue readiness’ to remain in a hospital. On the basis of these
findings Esquirol disdainfully told his hopeful colleague, 'I think
that your patient is incurable; that he will not recover, nor survive a
year. Remain in Paris, and you will see, as the malady is making rapid
progress.'5 Displays of diagnostic and prognostic abilities such
as Esquirol's would be repeated by others during the nineteenth century
but such displays could never fully conceal psychiatry's impotence in the
face of this completely devastating and extremely common disorder.6
During most of the
nineteenth century, before syphilis was taken seriously as the cause of
general paresis, writing about the treatment of this disorder tended to
emphasize prevention and palliation rather than cure. Initially some like
Bayle held out some optimism that an understanding of the pathophysiology
of the disorder might lead to a cure. Although Bayle noted that the proportion
of deaths to cures was thirty to one, he nonetheless expressed confidence
that bleeding 'wisely administered' was the best hope to diminish the ‘terrifying
mortality’ of general paresis. 7 This proposal was based on his observation
of congestion of the blood vessels of the pia mater of paretics dying in
early stages of the disease. In spite of this sophisticated pathophysiological
rationale, Bayle's optimistic predictions for blood letting as a
treatment for general paresis were, of course, not borne out. In the final
stage of the illness, when the patient was weak, bedridden and demented,
there was general agreement that treatment should be humanely restricted
to palliative measures. Opinions about prevention were more varied, but
generally the advice given was, as in other forms of insanity, directed
at avoiding emotional turmoil and excesses of alcohol and sex.
Throughout the nineteenth
century, in spite of occasional claims of recoveries or remissions, general
paresis remained 'a deadly disease, almost invariably fatal.'8 Toward the
end of the century, Regis, in France, summarized the general opinion: 'the
medical treatment...of general paresis includes an infinite number of agents,
none of which, unfortunately, has up to this time, afforded any really
favorable results.'9 In England Julius Mickle, author of the first English
book devoted to general paresis, looked back nostalgically to ‘earlier
writers’ who had 'enjoined the employment of active antiphlogistic' treatments
such as ‘low diet, bleeding, leeching, cupping, purgatives, moxas, ...setons,...mercurial
innunctions, antimony diuretics, and ...cold to the head.’ Although he
wondered if these treatments had ‘suffered from undue neglect of late,’
he did not encourage his readers to attempt curative treatment.10
Indeed he insisted that ‘as soon as he is satisfied of the existence of
true general paralysis it is the duty of the physician to say at once that
the case is without hope, and curative art without reliable and permanent
efficacy.'11
SYPHILIS AND PARASYPHILIS
Although the treatment
of general paresis changed dramatically once it was agreed that syphilis
was the cause of the disorder, it took many years for this proposition
to gain universal acceptance. While Esmarch and Jessen had asserted that
syphilis caused general paresis as early as 1857, progress toward the general
acceptance of this idea was begun by the eminent nineteenth century 'syphilographer'
Alfred Fournier(1832-1914). The favorite student of the early nineteenth
century syphilographer Philippe Ricord, Fournier devoted himself to the
study of syphilis to the exclusion of almost everything else.12
He dominated French venereology in the last decades of the century
and was recognized throughout the western world as an expert on syphilis
second to none. 13 Engaged in an ambitious program of research and
public health propaganda aimed at showing how widely the effects of syphilis
had spread, Fournier's research drew on a card index of 50,000
cases that he had assembled over the years. Throughout the 1880s,
he collected data on the relationship between general paresis and syphilis,
which he presented in two essays in 1893 and a famous communication
read before the Academie de Médicine in on 30 October 1894.14
In that communication
Fournier marshaled a variety of evidence for a pathogenic connection between
syphilis and general paresis. Most importantly, he noted that
between 50 and 92 per cent of paretics could be shown to have had syphilis,
while the histories of ordinary insane people did not show nearly this
incidence of syphilis. He also noted that while paresis was found
rarely in rural areas, among the clergy or among women, it was found frequently
among women who lived ‘irregular lives.’ Finally having earlier established
to his satisfaction that tabes was due to syphilis he now pointed to the
high correlation between that disorder and general paresis. 15 Given
the large volume of his data, these were impressive observations. Nonetheless
he met skepticism. 'Several times,' Fournier complained, 'I had the experience
of having to diagnose syphilitic madness in the presence of very competent
and justly famous psychiatrists; and almost invariably my opinion was received
as a hypothesis which was possible, rational, perhaps tolerable, but singularly
adventurous and tainted with heresy.'16
While issues of professional
turf no doubt influenced some of this psychiatric skepticism toward Fournier's
diagnostic imperialism, there was one good scientific reason for this skepticism.
General paresis did not respond to antisyphilitic treatment. Mercury, for
example, had been used to treat syphilis from the early sixteenth century.17
During the nineteenth century, potassium iodide also came to have some
vogue in the treatment of syphilis. By the late nineteenth century,
doctors had convinced themselves that mercury and potassium iodide were
effective treatments for syphilis, even for syphilitic disorders of the
nervous system. The failure of general paresis to respond to these
treatments led Fournier to propose the peculiar concept of parasyphilis.Parasyphilitic
disorders, which in addition to general paresis also included such varied
conditions as tabes, neurasthenia and optic atrophy, were, according to
Fournier, ‘not, strictly speaking of a syphilitic nature, but are none
the less of syphilitic origin.’18 In other words, parasyphilis was a non-syphilitic
sequel of syphilis, a degenerative process, provoked, in susceptible individuals,
by syphilis. The concept of parasyphilis may have explained to Fournier's
satisfaction why general paresis did not respond to mercury and potassium
iodide but it didn't do much to persuade the skeptics.19
The riddle of general
paresis grew more perplexing with that series of brilliant laboratory findings
in the first years of the twentieth century that established conclusively
that paresis was caused by syphilis. In 1897 Krafft-Ebing inoculated nine
paretics with no history of syphilis with luetic material. When none of
them developed symptoms of syphilis, he inferred that they had been previously
infected.20 The pathology of paresis was made definite by the work
of Nissl and Alzheimer, published in 1904. In 1906 Wasserman introduced
a serologic test that not only confirmed the syphilitic nature of active
lesions but showed that a latent lesion could be present in an individual.
With evidence gained through the use of the Wasserman reaction the relation
of paresis to syphilis was rather generally accepted. In 1913 all doubt
about the syphilitic nature of paresis was finally eliminated when Noguchi
and Moore demonstrated spirochetes in the brains of paretics.
With the conclusive
linking of paresis and syphilis, general paresis of the insane finally
became a public health concern. As long as general paresis was thought
to be due to heredity, nervous shock or excess venery, its epidemiology
was not a source of great consternation. With the link between syphilis
and general paresis established, the anxiety provoked by syphilis spread
to paresis. Rigorous estimates of the percentage of syphilitics who developed
general paresis were hard to come by. The first extensive study arrived
at a figure of just under five per cent.21 Some studies, however,
put the figure as high as ten per cent.22 There was a strong feeling
that the frequency of paresis and other syphilitic disorders of the nervous
system were increasing and that the same factors that were leading to the
increase in syphilis were leading to increases in paresis.23
In 1914 Salmon, adopting a public health stance toward paresis, pointed
out that death from paresis made it the eighth leading infectious disease
for mortality.24 At the same time Meyer argued for the value
and acceptability of putting the assets of patients with positive Wasserman
reactions, but no symptoms of paresis, in trust.25
THE MAGIC BULLET
The conclusive demonstration
spirochetes in the brains of paretics also catalyzed a wave of enthusiasm
for the idea that paresis might be cured with anti-syphilitic treatments.
The reason for this enthusiasm was the fact that Noguchi and Moore's discovery
occurred very shortly after Erlich and Hata, in 1909, were able to show
that arsphenamine, better known as Salvarsan, was an effective anti-syphilitic.
Salvarsan, it was hoped, would prove to be as powerful a 'magic bullet'
in the treatment of paresis as it initially seemed to be in the treatment
of other forms of syphilis.26 There was, however, resistance
to treating paretics at all. Critics argued against anti-luetic treatment
for paresis on theoretical and empirical grounds. Prior experience
showing that paresis was uninfluenced by mercury and iodide
had led to a nihilistic attitude toward antisyphilitic treatment.
Fournier's ideas about parasyphilis helped create a theoretical basis for
pessimism as well. Frederick Mott,the leading early twentieth century British
neuropathologist, for example, argued that the paretic process simply could
not be modified by anti-luetic treatment and strongly advised against using
it. There were even questions as to whether treated cases did more poorly
than untreated cases.27 A questionnaire sent to two hundred hospitals,
during this period, indicated that only thirty five per cent of those responding
were using any antiluetic treatment.28 As Henry Head and E.G.Fearnsides
noted:
the treatment of syphilis by modern measures is so
expensive and troublesome that few inmates of our
Asylums and Workhouse Infirmaries receive adequate
injections of neosalvarsan or even effective mercurial
treatment. No one wastes time and money on persons
supposed to be obvious cases of 'general paralysis,' and
we have received letters from medical officers ...
expressing wonder that we should 'take so much trouble
over such a straightforward case of general paralysis.29
Watching patients
die from general paresis in the days before fever therapy was a grim business
that occurred in a pessimistic and gloomy atmosphere. As one doctor
put it, 'nothing is more depressing to me than to see ... cases of paresis
in the last stage of the disease, demented and deteriorated, untidy, living
a vegetative existence, bedridden with numerous decubitus ulcers, a burden
to themselves and others,...'30 Remissions, however, could be even
more painful to watch because they did not last. Such patients might
be reduced to ‘helpless... bedridden... breathing, heartbeating automata,’
as another doctor wrote, only to recover spontaneously over a period of
six weeks to three months. They then appeared to have ‘risen from the dead"
and to be "almost well and like themselves.’ Such remissions typically
lasted six months --though occasionally five to six years--only to have
‘the symptoms return, often in rapid progression, and usually lead to death
after a variable interval of from six months to a few years.’31 Some doctors
became hardened by such experiences and objectified and denigrated their
paretic patients. Textbook descriptions of patient's grandiose delusions
often seem, at least to a late twentieth century reader, to be mocking
in tone.32 Braslow has also recently noted from a study of hospital records
that paretics in the pre-malarial therapy period were often referred to
as 'lazy,' 'silly,' 'childish,' 'obscene,' 'vile,' 'vulgar,' and 'stupid.'33
In the face of both
the arguments against treatment and the atmosphere of pessimism,
advocates of Salvarsan not only hoped for dramatic results but needed them.
There were, however, many difficulties in determining the value
of treatment. Possible cures might be discounted. Some patients who
improved, it was argued, were actually suffering from ‘cerebral syphilis’
and not paresis, though distinguishing between these two disease states
was extremely difficult. It was also suggested that untreated paresis was
running a milder course than in former years. Because sample sizes were
initially quite small, it was also difficult to allow for the differing
effects of treatment on early and late cases.34 Efforts at controlled studies
were crude and, as one author admitted of his study, comparison between
results with treated and untreated patients was ‘manifestly unfair.’35
Furthermore, because there was so little data on the natural history of
the disease, it was difficult to take into account the frequency
of spontaneous remissions.
Efforts to evaluate
the treatment of general paresis stimulated work on this problem.
In an effort to characterize the natural history of untreated, hospitalized
paretics, Raynor described the fate of 1004 patients admitted to his hospital
between 1911 and 1918. Of these 87% had died, 78% during the first admission.Nine
per cent, however, had improved and 3.5% had improved sufficiently to be
regarded as remissions.36
Salvarsan was almost immediately tried on syphilitic lesions
of the nervous system. The results in cases of general paresis were,
however, meager and disappointing. In one series of twenty paretics, six
showed ‘improvement.’ Of these six, four were considered ‘remissions’ one
of which lasted six months and two of which allowed the patients to return
to work. In another series of fifty-one cases, Bernard Sachs noted that
the results were not much better than those achieved with mercurials in
previous years.37 In 1911 a standard textbook noted that, 'Erlich's
Salvarsan ('606') has been used in a great many cases, but so far with
rather more harmful than beneficial results.'38 In the same year
Albert Neisser noted that 'The more I see, the more I am under the impression
that the paralytic process is hastened by '606.'' 39
Because many did believe
that Salvarsan should work, efforts were undertaken to deliver the magic
bullet more directly to the brain. Salvarsan was initially used intramuscularly
without benefit and then, in the first of a series of increasingly invasive
maneuvers, it was injected intravenously without great improvement in results.The
failure of intramuscular and intravenous Salvarsan to relieve paresis was
explained as due to its failure to reach the central nervous system. In
response to this obstacle, Swift and Ellis in 1912 proposed the intrathecal
injection of arsphenamized serum. This method produced favorable clinical
and serological results in meningeal, vascular and tabetic neurosyphilis,
but was was without effect in paresis. This led others to inject Salvarsan
into the subarachnoid space, the cisterna magna and the lateral ventricles.40
While published reports argued that these techniques were safe, the use
of such invasive methods still stirred up much anxiety.41 None of these
invasive procedures produced results worthy of the risk. A series of additional
drugs including bismuth and neosalvarsan were later introduced but also
failed to affect general paresis. The shortcomings of Salvarsan could be
seen in the recommendation that it be used only as an adjuvant of mercurial
treatment.42
FEVER THERAPY
Long before the wave
of enthusiasm for using Salvarsan in general paresis, psychiatrists had
occasionally observed mentally ill patients who recovered following an
intercurrent illness with a high fever. Remissions and even cures had often
been reported following cases of typhoid, which was common in asylums.
There were also sporadic reports of doctors trying to treat psychiatric
disorders by inducing fevers. Generally these reports did not distinguish
between paretics and other patients. In 1876 Alexander S. Rosenblum reported
that eleven out of a mixed group of twenty-two psychiatric patients
were cured after an attack of recurrent fever. Although he presumably induced
this fever, the controversial nature of this procedure led him to omit
this fact from his report.43 In 1877 Meyer reported curing eight of fifteen
paretics, who he had treated over a period of fifteen years, by rubbing
Autenrieth's ointment onto their scalps to induce a deep suppuration. In
1883 Keirnan, in the United States, reported efforts to treat psychiatric
patients by vaccinating them for smallpox.44
Wagner-Jauregg became
interested in the idea of treating psychoses with fever,shortly after taking
up his first position as a psychiatrist in 1883. He observed a female patient
who recovered from a psychosis after a bout of erysipelas. In a review
of the literature which he published in 1887 he reported on 163 incidents
of psychoses remitting after typhoid, and intermittent fevers as well as
erysipelas. While Wagner-Jauregg clearly found the idea of treating
mental illness by inducing a febrile illness quite attractive, he pursued
his research cautiously and with what appears to have been great concern
about community disapproval of this approach. In 1888 he began
his experiments by injecting several patients with a culture of streptococci
taken from a case of erysipelas. Among his reasons for giving up
this line of investigation was the fact that 'medical science of
that period looked with disfavor at experimentation on human beings.' The
depth of his concern about community judgment is suggested by his mention
of a colleague who inoculated nine paretics with syphilis and 'almost went
to prison for his zealous scientific endeavors.' In the winter of 1890/91
Wagner-Jauregg began injecting the newly introduced tuberculin to induce
a febrile reaction 'without resorting to an infectious disease.'
He later wrote that he discontinued this treatment 'prematurely because
tuberculin was soon considered a dangerous preparation' and ‘it had
become practically a crime to use it.'45
In 1895 after Wagner-Jauregg
had returned to using tuberculin and other bacterial proteins to induce
fever, he first noticed that paretics did better with fever therapy than
other psychotics. In 1902 he combined this treatment with mercury and iodide
after he became convinced of the syphilitic origin of paresis. In this
period others also attempted to induce fevers by injections of sodium nulleinate
boiled milk and milk protein. The results of these efforts were poor, perhaps,
it has been suggested, because high fevers were not obtained.46 Collateral
support for the value of fever in the treatment of neurosyphilis was available.
In 1913 one of Wagner-Jauregg's assistants published a significant statistical
study 4134 cases of syphilis and observed that those patients who had contracted
a febrile disease during the early years of their syphilitic infection
almost never developed neurosyphilis. Others also noted that the incidence
of neurosyphilis was low in areas where malaria was endemic.47
Although Wagner-Jauregg
had suggested the use of artificial tertian malaria to produce fevers as
early as 1887, he only began to use this treatment in 1917. The serendipitous
presence of a soldier with malaria in his neuro-psychiatric hospital
gave Wagner-Jauregg the opportunity that he had been, in a sense,
preparing for for thirty years. He also suggests that the brutalities of
war may have made him less sensitive both to the glory of discovering
a cure for a dread disease and to the possible censure for experimentally
infecting sick people with a new disease. As Wagner-Jauregg recalled:
'We were already in the third year of the war, and its emotional implications became more manifest from day to day. Against such a background a therapeutic experiment could stir me little, in particular since its success could not be
foreseen. What meant a few paralytics,would possibly be saved, in comparison to the thousands of able-bodies and capable men who often died on a single day as the result of the prolongation of the war.'48
Wagner-Jauregg
took blood from his serendipitously encountered malaria patient and injected
into two paretics. Six of his first nine patients showed improvements though
four of these eventually suffered relapses.When one patient died because
he was inadvertently given malaria tropica rather than the tertian type,
Wagner-Jauregg gave up the treatment for a year.He resumed treating paretics
only after he was able to obtain a steady supply of the tertian type.49
In 1921 Wagner-Jauregg was able to report that 25% of his first two hundred
patients were able to return to work. In 1922 one of Wagner-Jauregg's assistants
reported that over 60% of 400 cases observed for over two years had achieved
remissions of varying degrees.50
Following the war the use of malaria therapy spread quickly to
many countries.’Soon it was definitely established that the progress of
the disease could be halted in approximately 70 per cent of cases and that
marked improvement could be obtained in 20 to 40 per cent of the cases,
the final result depending to a large extent on the amount of damage that
had occurred prior to the beginning of the treatment.’51In a review of
2460 cases recorded in the literature by 1926 27.5% were found greatly
improved and another 25.6% moderately improved.52 In 1929 there were reports
from the Soviet Union of remissions in 64% of treated cases.53
Praise for the
treatment appears to have been quite general. Malaria therapy was referred
to as a 'therapeutic noble deed,' the 'right way to treat a hopeless disease,'
and 'the best treatment available.' The success of the treatment seems
to have stifled most open criticism of the method. Even in 1946 Merritt,
Adams and Solomon could only speak of 'the transmission of the infection...by
inoculation of blood from a syphilitic who has been previously been given
malaria (as) a practice which offends the esthetic sense of many individuals.'
(emphasis added)54 Wagner-Jaurreg's Nobel Prize was, however, held up because
B. Gadelius, a Swedish professor of psychiatry, and a member of the prize
committee, could not be persuaded to recommend the award to a ‘physician
who injected malaria into a paralytic, because he was in his eyes a criminal.’55
There was also some ambivalence about the results of malarial treatment,
even by enthusiastic promoters of the cure. Henry A. Bunker, for example,
following a presentation of the benefits of malarial treatment noted that
‘those patients who achieve merely an arrest of their disease...and
remain in a stationary stage for four, five and more years are not examples
of any great accomplishment from a practical standpoint. In fact my personal
opinion is that many of such stationary but permanently institutionalized
patients would be better off if they were dead.'56
Malaria treatment
continued to be used into the early 1950s. As late as 1946 Merrit, Adams
and Solomon still insisted that it was ‘the simplest and most effective
method of treatment of paretic neurosyphilis.' 57 There is no question
that it was a desperate treatment.Even so there was reason to be proud
of it. After a hundred years of hopelessness and despair, it
offered hope for people afflicted with a devastating disease. Moreover,
as Braslow has recently shown, it even an increased measure of respect
for patients had previously been scorned and mocked.58
Notes
1.Magda Whitrow's biography Julius Wagner-Jauregg (1857-1940)
(Smith-Gordon, London, 1993) now provides a comprehensive review of his
life and work.
2.Andrew Scull, "Somatic treatments and the historiography of psychiatry,"
History of Psychiatry, 5(1994), 8.
3 .Harold Mersky, "Somatic treatments, ignorance, and the historiography
of psychiatry," History of Psychiatry, 5(1994), 387-91.
4 Edward M. Brown, “French Psychiatry's Initial Reception of Bayle's
Discovery of General Paresis of the Insane,” Bulletin of the History of
Medicine 68 (1994), 235-253.
5 .J.E.D.Esquirol, Mental Maladies, A Treatise on Insanity, Facsimile
of the English Edition of 1845, (Hafner, New York and London 1965),436
6.For example Henry Maudsley,Responsibility in Mental Disease (New
York, D.Appleton and Company, 1899),80-1
7 .A.L.J. Bayle, Traite des Maladies Du Cerveau et de ses Membranes
reprint of the 1826 edition,(New York, Arno Press,1976),574-587
8 .W.Julius Mickle,"General Paralysis," in D.Hack Tuke (ed.) A Dictionary
of Psychological Medicine (Philadelphia,P. Blakiston,Son & Co,, 1892),
532
9 .E. Regis, A Practical manual of Mental Medicine (Philadelphia, P.Blakiston,
Son & Co.,1895), 462.
10 .W.Julius Mickle. General Paralysis of the Insane (London, H.K.Lewis,1880),171
11. Mickle, General Paralysis of the Insane,.165-75
12. M.A. Waugh, "Alfred Fournier, 1832-1914: His Influence on Venereology,"
British Journal of Venereal Disease 50(1974),232.
13. John T. Crissey, The Dermatology and Syphilology of the Nineteenth
Century (New York ,Praeger), 221
14 .Crissey,The Dermatology and Syphilology of the Nineteenth Century
, 223. Alfred Fournier, “Syphilis and General Paresis,” in Selected Essays
and Monographs, (London, New Sydenham Soc.(161), 1897),.375-92
15 .Gazette Medicale de Paris, no.44, (Nov.3,1894),522-4.
16 .Claude Quétel, History of Syphilis (Johns Hopkins University
Press, Baltimore, 1992),163
17. H Houston Merrit, Raymond Adams, Harry C. Solomon, Neurosyphilis,
(Oxford,Oxford University Press, 1946),393
18 .Alfred Fournier, The Treatment of Syphilis, trans. C.F. Marshall,
(New York, Rebman Company, 1906),253..M.A. Waugh, "Alfred Fournier, 1832-1914:
His Influence on Venereology," British Journal of Venereal Disease 50(1974),
233.
19 .J. Darier, "Alfred Fournier:1832-1914," Annales de Dermatologie
et de Syphiligraphie 5(1915), 522-8. One biographer suggested that Fournier
was not interested in this concept as a discovery of a law of pathogenesis
but only as a conquest in the domain of etiology. Fournier did not attempt
to explicate the distinction between "origine" and "nature" which were
crucial to the concept of parasyphilis. "It sufficed for him to have charged
the dossier of syphilis with some more atrocities." cited in Crissey,
The Dermatology and Syphilology of the Nineteenth Century .223
20 . George Rosen, “Patterns of Discovery and Control in Mental Illness,"
in Madness in Society, (Harper,New York, 1968),247-62.
21 . Thomas W. Salmon, "General Paralysis as a Public Health Problem,"
American Journal of Insanity 71(1913-4),44 cites a study by Pilcz and Mattauschek
of 4,134 officers in the Austrian army who had contracted syphilis between
1880 and 1890 which showed that 4 9/10 per cent had developed general paralysis
by 1912.
22 . D.K. Henderson, "Cerebral Syphilis," American Journal of Insanity
70(1913),282
23 . Charles P. Bancroft, "Is There an Increase Among the Dementing
Psychoses." American Journal of Insanity 71(1924-15),59-73. D.K.Henderson,
American Journal of Insanity 70(1913)282."Mott asserts... that owing to
the increased strain of living and owing to the conversion of a rural into
an urban population, syphilitic affections of the nervous system are greatly
on the increase."
24 Salmon, Thomas, "General Paralysis as a Public Health Problem,"
American Journal of Insanity 71(1913-4),44
25 . Adolf Meyer, "Differential Diagnosis of General Paresis," American
Journal of Insanity 71(1914-15),51-58
26 . Harry C. Solomon,”The value of treatment in general paresis” Boston
Medical and Surgical Journal, 188(1923),635
27 .Harry C.Solomon Boston Medical and Surgical Journal 188(1923)636
cited observations that that treated cases lived only half as long
as untreated cases and also urged against treatment.
28 . H Goldsmith, "A Plea for Standardized and Intensive Treatment
of the Neurosyphilitic and Paretic," American Journal of Psychiatry. 82(1925),251-61,
29. Henry Head and E.G. Fearnsides,"The clinical aspects of syphilis
of the nervous system in the light of the Wassermann reaction and treatment
with neosalvarsan," Brain 37(1914), 134.
30 . H. Goldsmith, op.cit., 256
31 . William A. White and Smith Ely Jelliffe, Modern Treatment of Nervous
and Mental Diseases, (Lea & Febiger, Philadelphia and New York,1913),249
32 .See for example, E.C. Spitzka, Insanity, Its Classification, Diagnosis
and Treatment,(New York, Bermingham & Co. 1883), 195 ""The patient
claims to be the most powerful, the richest and ablest man in his community,
He can raise the asylum with his little finger, he has trunks filled with
gold in every city in the Union, he is married to all the handsome women
in the world, can speak all the living and dead languages, has the best-developed
sexual organs extant, and is the intimate friend of every contemporary
great man, sometimes himself Napoleon, Caesar, Shakespeare, Grant, Buffalo
Bill, and every other celebrity in one person, and the fortunate owner
of numerous patents." Spitzka goes on to itemize the extravagant list of
"possessions" of a paretic former stock-broker.
33.Joel T. Braslow, "Effect of Therapeutic Innovation on Perception
of Disease and the Doctor-Patient Relationship: A History of General Paralysis
of the Insane and malaria Fever Therapy, 1910-1950," American Journal of
Psychiatry, 152(1995)660-65.
34 .Harry C. Solomon, op. cit., 635
35 I.J.Furman,"Treatment of General Paralysis," Archives of Neurology
and Psychiatry, 12(1924),359-69 .
36. Mortimer Williams Raynor, "Remissions in General Paralysis." Archives
of Neurology and Psychiatry 12(1924), 419-425.
37 .New York Neurological Society: Proceedings of joint meeting with
Philadelphia and Boston Neurological Societies, November 14,1911, "Use
of Salvarsan in Syphilis of the Nervous System," Journal of Nervous and
Mental Diseases, 39(1912),180-86
38 .Archibald Church and Frederick Peterson, Nervous and Mental Diseases,(Philadelphia
and London, W.B.Saunders Company,1911),818
39 Albert Neisser,On Modern Syphilotherapy with particular Reference
to Salvarsan, translation of a 1911 article, (Baltimore Johns Hopkins Press
1945),22.
40 .Walter F. Shaller and Henry G. Mehrtens, "Therapy in Neurosyphilis
with Particular Reference to Intraspinal Therapy," Archives of Neurology
and Psychiatry, 7(1922),89-97 "...every case of cerebrospinal syphilis
improved...Patients with paresis, as a whole, did poorly." Franklin
G. Ebaugh, "The Treatment of General Paresis by the Intracistern Route,"
Archives of Neurology and Psychiatry 7(1922),325-31."The clinical results
of intercisternal therapy have been disappointing.". H. McKusker, "Some
observations on Cistern Puncture," Journal of Nervous and Mental Diseases
53(1921),453.
41 . H. Goldsmith, op. cit.,253 "It has only been in recent years that
spinal puncture has become general and attended by very few untoward results.
I can remember when any medicine to be injected intravenously was attended
by preparations equal almost to that of a major operation and spinal puncture
was approached wit fear and trembling."
42 .D.K. Henderson,”Cerebral Syphilis,” American Journal of Insanity,
70 (1913),282.
43 .Magda Whitrow, "Wagner-Jauregg and Fever Therapy," Medical History,
34(1990), 294-310.
44 . James G Kiernan, "Variola and Insanity," American Journal of Neurology
2(1883)365-72.
45 .Julius Wagner-Jauregg, "The History of the Malaria Treatment of
General Paralysis," American Journal of Psychiatry 102(1945-6),577-82
46 H. Houston Merrit, Raymond Adams, Harry C. Solomon, op. cit.,397
47 .E.Mattauschek and A. Pilcz, "Aweite Mitteilung uber 4134 katamnestisch
verfolgte Falle von luetischer Infection," Ztschr.f.d.ges.Neurol.u.Psychiat.
15(1913)608 as discussed in H. Houston Merrit, Raymond D. Adams and Harry
C. Solomon, op. cit.,,396
48 .Julius Wagner-Jauregg,"The History of the Malaria Treatment of
General Paralysis," American Journal of Psychiatry 102(1945-6),580
49 .Whitrow, "Wagner-Jauregg and Fever Therapy," Medical History 34(1990),294-310.
incident reported on p.304-5.
50 . Magda Whitrow "Wagner-Jauregg and Fever Therapy," Medical History
34(1990),306.
51 . H. Houston Merrit, Raymond Adams, Harry C. Solomon, op. cit.,.397.
52 .J.R. Driver,J.A. Gammel,L.J. Darnosh, "Malaria Treatment of Central
Nervous System Syphilis, Journal of the American Medical Association 87(1926),1921
cited in Bunker,"Recent Treatment of General Paralysis,”
53 . A.L. Lestchinsky, "Treatment with Malaria Inoculation in Paresis,"
abstract in American Journal of Psychiatry 86(1929-30), 589..
54 . H. Houston Merrit, Raymond Adams, Harry C. Solomon, op.
cit..397.
55 . Magda Whitrow "Wagner-Jauregg and Fever Therapy," Medical History
34(1990),310
56 .Henry A. Bunker Jr. "Recent Methods in the Treatment of General
Paralysis,"American Journal of Psychiatry. 85(1928-9), 681-94,
57 .H. Houston Merritt, Raymond Adams, and Harry C. Solomon, op. cit..406
58 Joel T. Braslow, "Effect of Therapeutic Innovation on Perception
of Disease and the Doctor-Patient Relationship: A History of General Paralysis
of the Insane and malaria Fever Therapy, 1910-1950," American Journal of
Psychiatry, 152(1995),660-65.