Edward Trautner (1890–1978), a pioneer of psychopharmacology
2023; Taylor & Francis; Volume: 33; Issue: 1 Linguagem: Inglês
10.1080/0964704x.2023.2226710
ISSN1744-5213
Autores Tópico(s)Neurology and Historical Studies
ResumoABSTRACTThis article examines the scientific career of Edward Trautner, who did pioneering research in the 1950s on lithium treatment for psychiatric disorders. Trautner was the first scientist to study the mechanism of action of lithium as a psychiatric medication. His research established that lithium could be used safely and rationally, and anticipated by a decade the large volume of research in the 1960s and 1970s that led to international acceptance of lithium treatment for mood disorders. Trautner was a pioneer of biological psychiatry who considered pharmacology to be a useful therapeutical tool rather than a permanent cure for putative chemical imbalances. His research involved cross-disciplinary collaborations that combined clinical and laboratory research in the disciplines of psychiatry, physiology, biochemistry, teratology, and even oncology. Trautner himself had a multidisciplinary background that included publications in literature and philosophy.KEYWORDS: Biological psychiatry (history of)bipolar disorderJohn Cadelithium therapy (history of)Mogens Schouneuropharmacology (history of)psychopharmacology (history of) AcknowledgmentsThe research published in this article was conducted within the larger horizon of the International Trautner Project, a collective effort to rediscover the life and work of Edward Trautner, which has brought together researchers in two language spheres and two continents, working without grant funding. Beside ourselves, the other core contributors to the project are Michael Messer (Trautner's student at the University of Melbourne in the 1950s), Beverly Close (Hervey Bay Family History Association, Queensland, Australia), Aoife Naughton (Dublin, Ireland), and Christa Steinle (former director of the Neue Galerie Graz/Universalmuseum Joanneum).For the present article, thanks are due in particular to Sam Gershon, F. Neil Johnson, Derek Denton, Walter A. Brown, Brandon Reines, and Barry Ninham for their advice and insight on scientific matters; and to Juliet Flesch (author of Life's Logic) and Carol Bunyan (a coauthor of Dunera Lives) for advice and help with historical matters. We thank Tracy McDonald and Sandra Dayao (Cumberland Hospital Library) for help in locating scientific papers; Peter Gill for archival work in the face of Covid lockdowns; and Sophie Garrett (University of Melbourne Archives) for patient help in locating documents. Christian Fiedler (bamberger-bier.de) helped reconstruct Trautner's schooling; and Thomas Kruckemeyer (German Language Services, Adelaide, Australia) provided valuable help with translation.For their first-hand testimony, we again thank Sam and Lisl Gershon, F. Neil Johnson, and Derek Denton; we also thank Kit Noack-Corris, Barbara Noack-McNamara, Margaret Goding, and Meriel Wilmot-Wright.Disclosure statementNo potential conflict of interest was reported by the authors.Notes1 Over the course of the 1960s, Schou became the world leader in lithium research; in 1984, F. Neil Johnson would call him "the driving force behind the modern use of lithium on a worldwide scale" (Johnson Citation1984b, p. xi).2 Trautner's theorizing often remained unpublished, or confined to the briefest discussions in his published works. This was not to his liking, and he complained for instance that editors had forced him to cut whole paragraphs of speculative material from a paper (Trautner to Mogens Schou, September 28, 1955, in "Trautner-Schou correspondence 1953–1975"). In the present article, we have retrieved Trautner's theoretical insights from unpublished records, and also attempted to reconstitute the thinking behind the logical development of his research.3 Sam Gershon, interview with G. de M., October 20, 2010. R. D. Wright, letter to F. Neil Johnson, August 26, 1981, quoted in Johnson (Citation1984b, p. 63). Wright's original letter, and all the other documents collected by Johnson in preparation of his book, have unfortunately been lost, as Johnson related in an e-mail to W. W. of April 24, 2020.4 Johnson (Citation1984b, pp. 61–62 and footnote 17). Contacted recently by us, Johnson expanded: "When I started work on the History and, in the course of doing so, corresponded or met with Mogens Schou and others, my interest in Trautner's work blossomed and I began to realize just how important his contribution had been to the early acceptance of lithium therapy. Indeed, if I recall correctly, I expressed the opinion that, in this respect, his 1951 and 1955 papers had probably been more influential than those published by John Cade—a view also voiced on a number of occasions by Mogens and others" (e-mail to W. W. of March 13, 2021).5 See Trautner and Shaw (Citation1945); Loftus-Hills, Trautner, and Rodwell (Citation1945); Trautner and Neufeld (Citation1946); Trautner (Citation1946); Loftus-Hills, Trautner, and Rodwell (Citation1946); Trautner and Neufeld (Citation1947); Trautner (Citation1947); Mitchell and Trautner (Citation1947); Trautner and Polya (Citation1948); Trautner, Neufeld, and Rodwell (Citation1948); Trautner and Roberts (Citation1948); Trautner and Neufeld (Citation1949); Trautner (Citation1949); Trautner and McCallum (Citation1950).6 See the sections titled "The game gets under way," "The ionotropic mechanism," "The metabotropic mechanism," and "Lithium shock."7 These unpublished notes are cited and discussed below in the sections titled "The game gets under way," "The ionotropic mechanism," "The metabotropic mechanism," and "Lithium shock."8 See the section "Lithium shock."9 See sections "Lithium shock" and "The ionotropic mechanism."10 The lecture was given on March 2, 1914, as noted in Bericht des Naturwissenschaftlichen Vereins für Schwaben [Report of the natural-science club for Swabia], vol. 42, p. IV.11 The evidence for Trautner's career intentions at this stage are (a) his studies and first job, which were oriented toward a teaching career rather than a medical license or a doctorate; (b) the magazine piece published in 1914; (c) a description of him in 1919 as a "young teacher and writer" and an "idealist trained in the new pedagogical teachings" (Hiller Citation1919); and (d) the magazine Trautner edited in 1919, Der Weg, whose first publisher was an anthroposophist and whose ideological content leaned at times toward the ideas of that movement.12 On August Bier (1861–1949) see the biographical notice on the Deutsche Biographie website; also P. Freyschmidt-Paul, August Bier: das chirurgische Werk, thesis, Ruhr Universität Bochum (Germany), 1999. James or Johannes Fraenkel (b. 1879) was for many years the head of the orthopedic division of Bier's surgical clinic (see K. Vogeler-Stettin, "Die Chirurgie unter Bier", in Das Universitätsklinikum in Berlin, ed. P. Diepgen and P. Rostock. pp. 124 and 132. Leipzig: J. A. Barth, 1939).13 Trautner described this research in an application for a temporary medical license, which he submitted to the Australian "Alien Doctors Board" on March 27, 1942 (Files of the Central office of the Australian Department of Health, National Archives of Australia: item ID 143378, digital pages 288–290). Fraenkel's wartime research on choline is described in his papers, Über erweichende Behandlung [on emollient treatment], Muenchener Medizinische Wochenschrift vol. 62:2 (1915), no. 41/42, pp. 1401–03; and Zur Behandlung der Kontrakturen (Bedingungen der Cholin behandlung) [For the treatment of contractures (conditions of choline treatment)], Zentralblatt für Chirurgie 1917, Nr. 31 (both cited by Trautner Citation1920).14 On Oscar A. Mendelsohn (1896–1978), see the notice by Ray Marginson in the Australian Dictionary of Biography. Trautner's work at Mendelsohn & Co. is attested in a memo from the Chairman of the Commonwealth Alien Doctors' Board, J. H. L. Cumpston, dated May 16, 1942, found in the correspondence files of the Australian government's Department of Health (National Archives of Australia: item ID 143394, digital page 173).15 University of Melbourne, Registrar's Correspondence (University of Melbourne Archives, series UM 312 / accession no. 1999.0014), year 1942, file 498: "Physiology: Staff."16 See list of publications cited in note 5.17 On Roy Douglas "Pansy" Wright, see the biography by McPhee (Citation1999). On wartime phytochemistry research at the University of Melbourne, see Foley (Citation2006), and Price, Lamberton, and Culvenor (Citation1992). Trautner's change of direction in 1947 is attested in "Trautner-Wright correspondence 1946–1948." See also the University of Melbourne's Research Reports for 1947–1949.18 See Bradley et al. (Citation1950), Trautner and McCallum (Citation1950), Trautner and Bradley (Citation1951), and Trautner (Citation1951).19 Lithium's biophysical properties are discussed by Jakobsson et al. (Citation2017), and Alfredsson et al. (Citation2021).20 See Kent and McCance (Citation1941); Radomski et al. (Citation1950); Davenport (Citation1950); Talso and Clarke (Citation1951); Foulks, Mudge, and Gilman (Citation1952). Trautner himself contributed to scientific knowledge on this subject (Trautner et al. Citation1955). Radomski's research, conducted in dogs, was aimed at understanding the mechanism of lithium toxicity. As such it was an important precursor for Trautner's study of the mechanism of action of lithium as a psychiatric drug.21 See de Moore and Westmore (Citation2016, p. 166) and Johnson (Citation1984b, pp. 59–60). Within a year of Cade's publication, more than 100 patients in the Melbourne area were being treated with lithium, and several dozen also in Sydney, Perth, and Tasmania. Cade's findings were known in the Melbourne area before they were even published, according to later testimony by the psychiatrist J. V. Ashburner (quoted in Johnson Citation1984b, pp. 59–60). The enthusiasm for lithium spread rapidly within weeks of the publication, as attested by letters received by Cade (quoted by de Moore and Westmore Citation2016, p. 166, from originals in the Cade family archives and in the papers of Edmond Chiu). In September 1950, Ashburner, the superintendent of a Melbourne-area mental hospital, reported that his hospital had given lithium to 50 patients, in some cases for as long as 12 months (Ashburner Citation1950). In their August 1951 paper, Noack and Trautner reported giving lithium to 100 patients over the course of two years at a Melbourne-area hospital (Noack and Trautner Citation1951); and by 1953, Trautner's group had treated more than 300 patients (Trautner to Schou, September 28, 1953, in "Trautner–Schou correspondence 1953–1975"; and Trautner et al. Citation1955, p. 288, col.1).The spread of lithium treatment in Australia outside of Melbourne appears to have been based on contact with Cade. For example, F. J. Scanlan, the superintendent of Parramatta Mental Hospital in the Sydney area, wrote to Cade in October 1949 to ask where lithium supplies could be obtained (letter dated October 6, 1949, cited in de Moore and Westmore Citation2016, p. 166). Charles Brothers, the director of mental hygiene in the state of Tasmania, wrote to Cade in June 1950 that lithium was in such widespread use there that hospitals were having a hard time maintaining adequate supplies (unpublished letter, Cade family archives). Five years later, a Tasmanian psychiatrist reported that trials of lithium at his hospital "were started some years ago," and that lithium treatment "has evidently become a routine procedure in several Australian mental hospitals since Cade's paper was published in 1949" (Margulies Citation1955). In Western Australia, lithium was given to 104 patients between 1950 and 1954 at the Claremont Mental Hospital, where Cade's friend Frank Prendergast was the superintendent (Glesinger Citation1954). However, lithium treatment was not the norm throughout Australia: John Cawte, the acting superintendent of a large mental hospital in South Australia, did not mention lithium in an account of how acute mania was being managed at his hospital in 1952 (Cawte Citation1952). Cawte would later remember that time period as being "before the advent of lithium, chlorpromazine, or haloperidol" (Cawte Citation1988, p. 82; see also p. 78).22 The first death in Australia due to psychiatric lithium occurred in December 1949; this was followed by a second death in March 1950, and then the death of Cade's patient in May 1950. The first death was published as a case report in the Medical Journal of Australia in August 1950 (Roberts Citation1950). The second was described within a larger case series published in 1954 (Glesinger Citation1954). Cade never published an account of the third death (Brown Citation2019; de Moore and Westmore Citation2016). In fact, no other Australian lithium death was ever published, either in medical journals or in the media, although at least four more did occur in the state of Victoria (Public Records Office of Victoria, inquest nos. 1952/941, 1952/1866, 1952/1884, and 1953/1925). Despite the lack of public disclosure, these lithium deaths were widely known within the medical community of the state of Victoria (see de Moore and Westmore Citation2016, pp. 183–184 and 170–171; and Westmore Citation2002, pp. 164–167).23 See de Moore and Westmore (Citation2016, chap. 20); for a more detailed discussion, see Brown (Citation2019, chap. 5). See also Johnson (Citation1984b, chap. 4) and Schioldann (Citation2009, chap. 23). The American lithium toxicity cases (including several deaths) were reported in Australian newspapers in February 1949 (e.g., see the Melbourne Herald of February 19, 1949, p. 1). Clinical details were summarized in the Medical Journal of Australia of July 30, 1949, i.e., about one month before Cade's paper appeared there (Anonymous Citation1949).Newspapers in Australia were silent about psychiatric lithium toxicity, and silent also about the benefits of psychiatric lithium. We conducted a search of the Trove database of Australian newspapers between January 1949 and December 1955, looking for mentions of psychiatric lithium: this returned only one hit, a 1950 piece on mental hospital management in Western Australia (The West Australian, April 6, 1950, p. 3). We have argued elsewhere that this silence in the press, as well as evidence from coroner's depositions, suggests that a de facto clinical trial of lithium was occurring in Australia's public mental hospitals, with unofficial support from regulatory authorities (de Moore and Westmore Citation2016, p. 186).24 John Cawte, mentioned in note 21, later befriended Cade, and he recalled that Cade had "become frightened" of lithium (Cawte Citation1988, pp. 21–22; Citation1999). R. D. Wright recalled that Cade regarded lithium as "too dangerous" (Wright Citation1981). Cade's motives for withdrawing from lithium research have been discussed by de Moore and Westmore (Citation2016, pp. 116, 119, 176–177, 235, 250, 279), Brown (Citation2019, pp. 165–171), and Schioldann (Citation2009, p. 246).25 According to Trautner himself, "The clinical use of the drug was started by Dr. Cade in 1949 [sic], the physiological and pharmacological investigation in the Department of Physiology in 1950" (E. Trautner, "Application for Grant from Mental Health Research Funds—1957," typescript with cover letter dated December 11, 1956, in "Physiology MHRF file").26 John Harold Talbott (1902–1990) was the chief of medicine at the Buffalo General Hospital in Buffalo, New York. He would later serve as editor of the Journal of the American Medical Association and of the Merck Manual.27 Cade (Citation1949) recommended starting doses of 60 grains per day of lithium citrate or 30 grains per day of lithium carbonate (i.e., respectively, 42 mEq and 52.5 mEq per day of lithium ion). The lithium salt substitutes were typically consumed at well under 0.5 grams per day of lithium chloride (i.e., 12 mEq per day of lithium ion; Talbott Citation1950).28 Trautner to Mogens Schou, September 28, 1955, in "Trautner–Schou correspondence 1953–1975."29 See Wright (Citation1981). Wright's recollection came 30 years after the fact, but his chronology is confirmed by Trautner's writeup of his work in the Research Report for 1950, and in his 1951 paper with Noack (Noack and Trautner Citation1951).30 Physiology department rosters named Trautner as "research staff" as opposed to "teaching staff" (University of Melbourne Archives; see also the Research Reports). It is unlikely he would have taught a full lecture course. The diploma in psychological medicine (DPM) was a postgraduate degree awarded after completion of residency training in psychiatry. This diploma did require six lecture classes given over a two-year period, but physiology was just one of the six required classes. If Trautner gave lectures, his role was probably confined to teaching a module on brain metabolism within the larger physiology lecture course. (For the dates and subjects of lectures in the DPM program, see the Faculty of Medicine Handbook published by the University of Melbourne.)31 Charles Hugh Noack (1917–1969) grew up in Adelaide, obtaining his bachelor of medicine degree in 1941 at the University of Adelaide. He served in the Royal Australian Air Force from 1942 to 1946, then opened a general practice in Longford, Tasmania. In January 1949, Noack sold his practice and moved to Beechworth, Victoria, to work as a resident at the mental hospital there. His career in psychiatry took him through the following appointments: Beechworth (January to c. August 1949), Mont Park (c. September 1949 to c. June 1953), Bundoora (c. June 1953 to c. January 1955), Sunbury (1955–1956), Observatory Clinic (1956–1963), and private practice (1964–1969). This chronology was assembled from documents and testimony provided by Noack's eldest daughter, Kit Noack-Corris; institutional affiliations given in Noack's scientific papers; newspaper stories; and Australian government files (National Archives of Australia item ID nos. 5251653, 5251654, and 1804806).Against Wright's recollection that Trautner first met Noack as a student in his class, student records kept by the University of Melbourne Archives show that Noack did not matriculate at the university until May 18, 1950, and that he was dispensed from first-year lectures in physiology on the grounds of his experience as an Air Force doctor. But Noack and Trautner began their lithium research in 1950, as attested by Trautner in a 1956 grant application (cited above, note 25). Thus, the likelihood is that R. D. Wright himself brokered the partnership with Trautner, as he would later broker Trautner's partnerships with his two other chief collaborators in lithium research, Michael Messer and Sam Gershon. (This was attested by Messer and Gershon in interviews with G. de M. of November 12 and October 20, 2010, respectively.) However, neither of these collaborations was limited to lithium. Noack, for example, would work with Trautner concurrently on tigloidine (for reference, see note 48 below) and later also on succinate (see note 62).32 R. D. Wright's interest in promoting lithium research is attested by a noteworthy piece of circumstantial evidence. Noack and Trautner's 1951 lithium paper was the lead research paper in the August 18, 1951, edition of the Medical Journal of Australia, and it was immediately preceded in the journal's pages by the text of an important public lecture given by John Cade, suggesting an editorial intent to link them (Cade Citation1951; Noack and Trautner Citation1951). Cade's lecture was a general review of the state of psychiatry in 1951, which ended with the prediction that biochemistry was about to revolutionize the field. The very next page carried Noack and Trautner's pioneering study of psychiatric lithium treatment, which relied on biochemical measurements in tissue samples. Cade's lecture had been chaired by Wright, so this meaningful juxtaposition in the journal may well have been Wright's own doing. (Westmore Citation2002, p. 154.)33 See Hewat (Citation1990, chap. 2), McPhee (Citation1999, pp. 104–106), and Flesch (Citation2012, p. 104).34 Flesch, ibid. The funding came from the Australian government's National Health and Medical Research Council.35 Ray Bradley, interview with Peter McPhee, cited in McPhee (Citation1999, p. 222, note 91). Trautner's quip was a pun on the double meaning of "ionic," because "doric" and "ionic" are also names for ancient Greek architectural styles.36 This connection was established by F. Neil Johnson, who interviewed Wynn for his book The History of Lithium Therapy. Johnson noted: "Trautner thus found himself in an environment in which notions of ionic regulation were being actively discussed, and in which the means for studying quantitative aspects of electrolytes were readily available" (Johnson Citation1984b, p. 61).37 See Cade (Citation1949), Noack and Trautner (Citation1951), and Trautner et al. (Citation1955). Derek Denton's habit of expressing concentrations in milliequivalents per liter was a sore point with older doctors in Melbourne (Hewat Citation1990, p. 31).38 Spectrophotometers (Figure 3) were invented in the 1930s and first commercialized in the 1940s, after which they proceeded to revolutionize all fields of chemistry. (An early example of their use to measure lithium levels in clinical tissue samples is Kent and McCance Citation1941.) Before the advent of the spectrophotometer, clinical chemistry had been cumbersome, and it took a long time to get from a clinical sample to a measured value. Moreover, standard laboratory tests did not actually produce a measured value for electrolytes. Instead, they reported "predicted values" based on chemical reactions of the blood with standard reactants (Morris and Travis Citation2002; Rosenfeld Citation2002).The "flame attachment" to the spectrophotometer (Figure 4) enabled the sample to be vaporized and heated instantly, meaning that measurements could be taken from smaller and more freshly prepared biological samples, such as a blood sample taken directly from a hospital patient. The flame attachment was first used during secret wartime research on the manufacture of penicillin, for which it proved crucial. The first published accounts of its use with clinical samples date to the immediate postwar period (e.g., Fox and Bauer Citation1947; Hald Citation1947).39 Wynn et al. (Citation1950) provided a visual illustration of the instrument (Figure 4). Wynn's spectrophotometer was also described to us by Sam Gershon (interview with G. de M., October 22, 2010), and the room housing it was described by Michael Messer (e-mails to W. W. dated May 10, 2020, January 5, 2021, and July 7, 2021). According to Wynn, the spectrophotometer used by his group cost £500 (equivalent to about US $25,000 today), but the shipping cost another £500; R. D. Wright paid for the instrument using funds from a Rockefeller Foundation grant, and Wynn himself personally paid for the shipping. (Wynn, cited by Hewat Citation1990, 24; the Rockefeller Foundation funding is also acknowledged by Wynn et al. Citation1950.)40 Noack and Trautner (Citation1951, p. 221, col. 2) indicated that Cade had communicated with them about his clinical experience regarding the deaths of two psychiatric patients from lithium toxicity: one was Cade's own patient, and the other was a patient in Western Australia, probably at Claremont Mental Hospital in Perth, where Cade's friend Frank Prendergast was the superintendent (Western Australian Death Index, reg. no. 526, 1950).Trautner recorded that he and Noack began their lithium research in 1950 (cited above, note 25). However, two cases reported in their 1951 paper have treatment dates beginning in September 1949 (Noack and Trautner Citation1951, p. 221, case reports for Cases I and II). This suggests that Noack may have included data from lithium patients already under his care prior to meeting Trautner. This may have been done under supervision from John Cade, as Noack and Cade worked across the street from each other in 1949, at Mont Park and Bundoora hospitals. In fact, the Noacks and Cades were family friends in the early 1950s, and the Noack family were invited to parties at the Cade household (Kit Noack-Corris, interview with W. W., September 10, 2020).41 R. J. H. Morris, letter to F. N. Johnson dated September 11, 1981 (quoted in Johnson Citation1984b, p. 160). Surprisingly, Morris was not credited on Noack and Trautner's 1951 paper, though his collaboration with them had begun in 1950, as attested by that year's edition of the Research Report. The fault would later be remedied somewhat by giving Morris coauthorship on the 1955 paper (Trautner et al. Citation1955).42 In his letters, Trautner was always highly conversant with the details of lithium treatments carried out under his supervision (e.g., see "Trautner-Schou correspondence 1953–1975"). Sam Gershon recalls of a slightly later time that he used to drive out to outlying mental hospitals to help Gershon with patient interviews. They would conduct the interviews together, to assess the suitability of patients for a lithium trial or to check on the patients' progress (Sam Gershon, interviews with G. de M., October 22, Citation2010, and with W. W., February 23, 2021).43 Under the terms of a program for refugee doctors,Trautner received a temporary medical license issued on May 2, 1942 and valid until December 31, 1943 (Security Service, New South Wales [sic], Book of Licenses for Alien Doctors, 1942, National Archives of Australia: item ID 448841). A 1943 letter Trautner wrote to the Australian Minister of the Interior in support of his application for citizenship, shows how his medical license added to his status and desirability as an immigrant; it is preserved in the Correspondence files of the Department of Immigration's Central Office (National Archives of Australia: item ID 1924692, digital page 88). After being awarded Australian citizenship in November 1947, Trautner applied for a permanent medical license, even though by then he was stably employed as a researcher. The license was clearly intended to support his claim to citizenship, as attested by many remarks in Trautner's correspondence with R. D. Wright ("Trautner–Wright correspondence 1946–1948," letters dated December 4, 1946; January 24, 1947; August 25, 1947; October 21, 1948). Trautner received his permanent license in June 1948, and he is listed after that time in the Victoria Government Gazette's annual inventory of physicians (e.g., January 8, 1949; January 31, 1950; and subsequent editions). (N.B.: Trautner's name does not appear in the main alphabetical list, but on the last page, on a separate list of "persons registered under the provisions of the Medical Practitioners Registration Act 1946.")44 The subject matter of the 1955 paper was described as early as 1950 in the Research Report for that year, which lists a project titled "Action of lithium on the healthy and the maniacal patient." This indicates that the 1951 and 1955 papers really stem from a single continuous research project. Likewise, the 1951 paper includes a preview of the findings of the 1955 paper, and states that "a detailed investigation of the changes caused in the ionic composition of blood, plasma and urine in the healthy as well as in the maniacal patient is being carried out and will be reported in a following publication" (Noack and Trautner Citation1951, p. 220).45 For an example of the procedure, see Darnell and Walker (Citation1940). For context, see Arden (Citation1938).46 The investigation of lithium's effect on healthy volunteers is mentioned in the Research Reports for 1950, 1952, and 1953. This was based on self-administration, as discussed in Noack and Trautner (Citation1951) and Trautner et al. (Citation1955).47 See "Interim Research Report 1951."48 On the discovery of tigloidine and its use in experimental neurology, see Williams (Citation2013, p. 396). Williams does not mention Trautner's name, but most of the research she profiles was done by him. Tigloidine was first characterized by William Mitchell during the course of doctoral research at the University of Edinburgh (see, e.g., Barger, Martin, and Mitchell Citation1937). Trautner became aware of it during his wartime work on alkaloids of Duboisia, and during a stint at Oxford in 1947 he collaborated with Mitchell on a publication (Mitchell and Trautner Citation1947). Upon his return to Melbourne, Trautner then tested tigloidine and other substances to discover candidate drugs active at the neuromuscular junction (Trautner and McCallum Citation1950). This work identified tigloidine and procaine as candidate anti-Parkinsonian drugs, and Trautner then performed clinical tests of each substance with the help of Noack (Trautner and Noack Citation1951; Trautner Citation1951).There ensued a seven-year hiatus in Trautner's publications on tigloidine, mainly because he could not obtain it in sufficient quantity to perform clinical studies. After attempting to synthesize it himself, he was able to persuade T & H Smith and Co. of Edinburgh to do so, and in 1953 he resumed testing it on patients with Parkinson's disease and Huntington's chorea (Research Reports for 1952 and 1953). However, by 1954 his supply was still very limited, and he was saving it to treat a few cases of Huntington's chorea (unpublished interim research report dated July 15, 1954, in University of Melbourne Archives, R. D. Wright Papers (accession no. 1968.0003), item no. 6/12: "Succinic Acid Committee," p. 18 of 45). Finally, in November 1958, Trautner published a case series of 12 Huntington's patients (Trautner and Gershon Citation1958). In subsequent years he published two further papers on related topics (O'Rourke et al. Citation1960; Trautner and Gershon Citation1959).49 "Interim Research Report 1951" (emphasis in the original).50 Trautner had observed that the different salts of lithium (chlori
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