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 Merskyís views seems closer to the mark than Scullís 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 ëskillful and estimable' Dr. K., who deferentially presented the patient to
Esquirol. 'I commit to your care,' Dr. K. said to Esquirol ëa 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.í Esquirol conducted a half an hour ëconversationí
with the patient,during which he observed ësome hesitation in the pronunciation
of certain wordsí and an ëundue readinessí 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 ëterrifying mortalityí 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 ëearlier
writersí who had 'enjoined the employment of active antiphlogistic' treatments
such as ëlow diet, bleeding, leeching, cupping, purgatives, moxas,
...setons,...mercurial innunctions, antimony diuretics, and ...cold to the
head.í Although he wondered if these treatments had ësuffered from undue neglect
of late,í he did not encourage his readers to attempt curative
treatment.10 Indeed he insisted that ëas 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 ëirregular lives.í 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, ënot, strictly speaking of a syphilitic nature, but are none the less
of syphilitic origin.í18 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 ëhelpless...
bedridden... breathing, heartbeating automata,í as another doctor wrote, only to
recover spontaneously over a period of six weeks to three months. They then
appeared to have ërisen from the dead" and to be "almost well and like
themselves.í Such remissions typically lasted six months --though occasionally
five to six years--only to have ëthe symptoms return, often in rapid
progression, and usually lead to death after a variable interval of from six
months to a few years.í31 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 ëcerebral syphilisí 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 ëmanifestly
unfair.í35 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 ëimprovement.í Of these six, four were considered ëremissionsí 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 ëit 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.íSoon 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.í51In 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 ëphysician who injected
malaria into a paralytic, because he was in his eyes a criminal.í55 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 ëthose 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 ëthe 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, ìFrench Psychiatry's Initial
Reception of Bayle's Discovery of General Paresis of the Insane,î 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,
ìSyphilis and General Paresis,î 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, ìPatterns 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,îThe value of treatment in general paresisî 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,îCerebral Syphilis,î 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,î
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.