- Email: [email protected]
Ludwik Fleck (1896-1962) and his contribution to dermatology
Clinics in Dermatology (2012) 30, 663–667
CARETAKER OF THE SKIN Edited by Andrzej Grzybowski, MD, PhD, MBA
Ludwik Fleck (1896-1962) and his contribution to dermatology Andrzej Grzybowski, MD, PhD, MBA a,b,⁎ . Department of Ophthalmology, University of Warmia and Mazury, Zołnierska 14 C, 10-561 Olsztyn, Poland b Department of Ophthalmology, Poznań City Hospital, Szwajcarska 3 61-285, Poznań, Poland a
Ludwik Fleck, Polish physician and microbiologist of Jewish origin, is mostly known today as a philosopher of science. His previously unknown treatise “Genesis and Development of a Scientific Fact” (Basel, 1935),1 was brought into international recognition by Thomas Kuhn in his The Structure of Scientific Revolutions (Chicago, 1962), one of the major books published in the 20th century in the field of philosophy of science. Kuhn wrote about Fleck in the introduction of his book, where he referred to his indebtedness to Fleck's findings. He has now achieved such prominence as a philosopher of science that the scientific center, “Ludwik Fleck Zentrum” (http://www. ludwikfleck.ethz.ch) in Zurich, was established to present analyses of his concepts and works, and international conferences on the subject are held. His scientific input in the field of philosophy of science and microbiology is well known and described elsewhere.2,3 Fleck was an accomplished scientist and was active also in other fields, including serology, immunology, and dermatology, which is much less known. This contribution is the first detailed analysis of his dermatology papers.
Biography Ludwik Fleck (Figure 1) was born in 1896 in Lviv, which belonged to the occupied Polish lands of the Austro⁎ Corresponding author. Tel.: +48 505 074 224. E-mail address: [email protected]. 0738-081X/$ – see front matter http://dx.doi.org/10.1016/j.clindermatol.2012.04.001
Hungarian Empire. From 1795 to 1914, Poland was partitioned by its three neighboring countries: Germany, Russia, and Austro-Hungary. There were strong political and economic differences between these three parts, with the Austro-Hungarian partition enjoying the most political, cultural, and educational freedom. Two major Polish universities with medical faculties, which quickly progressed, were founded: one in Cracow in 1364(just before the foundation of the universities in Vienna in 1365 and in Heidelberg in 1386) and another in Lviv in 1661. Most of the lectures in these universities were in Polish. In comparison, the German partition of the Polish state had no universities at all, and the Warsaw University in the Russian partition of the country was almost entirely under Russian influence, including the official language to be spoken. After graduating from Polish secondary school in 1914, Fleck began studying medicine at the Jan Kazimierz University in Lviv, where he graduated as a general practitioner and where he later obtained his PhD in 1922 (Figure 2).4 In the years 1920 to 1921, he assisted the famous Polish bacteriologist Rudolf Weigl (1883-1957) in his laboratory in Przemysl (about 50 km from Lviv) in his works on epidemic typhus. Weigl was the inventor of the first effective typhus fever vaccine, and although nominated nearly 50 times for a Nobel Prize, he never received the honor, which he deserved.5 Weigl was appointed to the chair of the University of Lviv Biology Department in 1921, and Fleck accompanied him as his assistant until mid-1923. Then, Fleck was appointed the head of the bacteriological-chemistry laboratory of the internal ward at the General Hospital in Lviv until 1925, and
664
A. Grzybowski
Fig. 1
Ludwik Fleck, 1896-1962.
later as the head of bacteriologic laboratory of the Skin and Venereal Diseases Department of the same hospital under Roman Leszczyński (1876-1940) until 1927. Leszczyński was a professor of dermatology and one of most prominent Polish dermatologists in the period between the First and Second World Wars, although for most of his life he was not related to a university department of dermatology. In 1927, Fleck spent 6 weeks at the Governmental Institute for Serotherapy in Vienna under Karl Kraus. In the years 1928 to 1935, he worked as the head of a bacteriologic laboratory of the local social assurance institution, and later until 1939, only in his private bacteriologic laboratory, which he had founded in 1923. During 1922 to 1939, without any academic position, Fleck conducted active research in many fields and published 39 scientific contributions in Polish and foreign journals, including Klinische Wochenschrift, Zentralblatt fur Immunitatsforchung unde experimentelle Therapie, Dermatologische Wochenschrift, and the British Journal of Dermatology and Syphilis. His main medical interests at that time were focused on bacteriology, serology, and dermatology. He devoted much time to his nonexperimental interests, including philosophy and methodology of science, which finally led him to the publication of his opus magnum, Genesis and Development of a Scientific Fact in 1935.1
This is extensively discussed elsewhere. 2,3 Despite different hindrances and problems, including the lack of an academic position and the instability of his employment, Fleck was at that time very active in research projects and publications. After the outbreak of World War II, Fleck became a head of the Municipal Sanitary-Bacteriology Laboratory in Lviv. Then, between 1940 and 1941, he worked as an assistant professor at the Department of Microbiology of the National Health Institute in Lviv, and until the outbreak of the German-Russian War, as head of the Department of Microbiology.4 During the German occupation, he was in charge of the bacteriologic laboratory in the Jewish Hospital in Lviv. At the beginning of 1943, Fleck was arrested and first transported to the Auschwitz concentration camp. In January 1944, he was moved to the concentration camp in Buchenwald, where he worked in the serology laboratories. He was liberated by the American Army in 1945. After short periods of recovery in various hospitals, he returned to Poland. In 1945, Fleck was given the position of head of the Medical Microbiology Department at CurieSkłodowska University in Lublin. He did his habilitation on exanthin reactions in 1946, and received the title of professor. In 1948, he worked as an expert for the International Military Tribunal for Germany in trials against Nazi physicians suspected of conducting medical experiments on concentration camp prisoners. Fleck moved to Warsaw in 1952, where he was appointed the head of the Department of Bacteriology and Immunology at the Institute of Mother and Child. In 1957, Fleck decided to move to Israel, where he joined his son Ryszard (born in 1924), and where he worked in the Weitzman Biological Institute, continuing his research on immunity in infectious diseases until his death in 1961.6
Fleck's scientific achievements Fleck is presently recognized predominantly as a philosopher of science. The discussions of his contributions in this field can be found elsewhere2,3; however, he was also a very productive researcher in microbiology, serology, and immunology. He was the author or a coauthor of approximately 170 original and review contributions. His bibliography and its analysis can be found elsewhere,7-9 but at least some of his major achievements deserve a brief description. From the very beginning, Fleck focused his interests in studies of spotted fever. He described a new skin test, named the exantin reaction, for the early detection of spotted typhus.10 In 1941and 1942, in the Lviv ghetto, he detected typhus antigenic substances in urine and then developed a new method of producing a vaccine against this disease, based on the presence of the antigen in the urine. This work was of a great practical value—a large number of vaccinated in the camp did not contract typhus although they were exposed to
Ludwik Fleck and dermatology
Fig. 2
665
Curriculum vitae of Dr Ludwik Fleck. Handwritten manuscript.
typhus infection.7,11-13 He continued his interest in typhus research until the end of his life.14 The second major field of his scientific interests was immunology and serology. During his stay in the Lviv ghetto in 1942, he was the first to observe the phenomenon of leukergy, a nonspecific leukocyte aggregation and adherence caused by different stimuli. Although his test was not standardized, the new test was welcomed by many international scientists with enthusiasm and made Fleck well-known. Fleck devoted many contributions to the investigation of leukergy and the function of leukocytes in health and disease.15,16 Although the term “leukergy” is no
longer used and seems to be out-of-date in modern immunology, the dysfunctions of leukocytes aggregation or adhesion properties, or both, are of a great interest in different disorders examined today, including heart and vascular diseases.17,18
Fleck's interests in dermatology In two contributions, Fleck and Laura Fullenbaum discussed the possible etiology of lupus erythematosus (LE). They showed that LE was not related to tuberculosis,
666 although they noted in LE a hypersensitivity to various bacterial agents. The evoking factor was, in their opinion, sunlight. They concluded that there was no specific microbe as an etiologic factor in LE but that various microbes could occur in different LE patients.19,20 They did not have any idea of the immunologic etiology of the disease. Fleck also described a case of anorectal changes, simulating syphilitic papules, under the name of pseudosyphiloma. Mycologic investigations, including cultures, have disclosed a new variety of scopulariopsis, and the cases of this type are called cladiosis. Serologic examination, using the extract of spores, showed positive cutaneous reactions that were invariably negative in control samples. The disease regressed with no therapy used. In this case, the glands were not involved. The transmission to guinea pigs and mice of the purulent content of cutaneous lesions was unsuccessful.21 His most interesting study was conducted in cooperation with Fryderyk Goldschlag, from the Department of Dermatology of the Lviv City Hopistal, who later became a professor of dermatology in Poland and in Australia. The study was related to an important discussion in those days about the etiopathogenesis of pemphigus. Eric Urbach and Stefan Wolfram, after a series of experiments, proposed the viral etiology of pemphigus.22-27 They showed positive serologic results by using the fluid from pemphigus blisters. Skin reactions were positive in 70% of patients with pemphigus and negative in control patientss. Suboccipital injections in rabbits produced severe changes and encephalomyelitis in a great number of animals. Fleck, being an accomplished immunologist, performed serologic studies in pemphigus with the goal of finding the etiologic factor of the disease.28 There were different opinions about a virus as an etiologic factor of pemphigus because results of bacteriologic studies were in general negative. Fleck and Goldschlag inoculated 15 rabbits with the blister fluid obtained from patients with pemphigus and dermatitis herpetiformis, which at that time was regarded a form of pemphigus. Inoculations performed by Wolfram, who accepted invitation to help with the study (to be sure that they were done in the same manner), were suboccipital, intracranial, intravenous, and intraperitoneal. Positive results were obtained in rabbits inoculated suboccipitally, but this route was not safe, often leading to cachexia and death. The changes of pemphigus were not produced in any animals. Serologic investigations—complement fixation using the antigen of Urbach—were also negative, and this, according to the authors, did not favor the viral etiology of pemphigus. Positive results of complement fixation by Urbach and Wolfram were interpreted as nonspecific. The authors concluded that there was no proof for a viral etiology of pemphigus.29 The controversy related to the viral etiology of pemphigus continued until the middle of the 20th century, and the contributions of Fleck and Goldschlag were often cited in that context as proofs for a nonviral etiology of the disease.30,31
A. Grzybowski Positive complement fixation results, found by Urbach and Wolfram in 75% of patients with pemphigus and in only 4.5% of healthy controls, can easily be explained: Pemphigus antibodies are known to be specific and pathogenic, and the passive transfer of pemphigus is possible by inoculation of these antibodies. The correct conclusion was not possible at that time due to the lack of knowledge in the field of immunology and a much simpler research armamentarium; however, one can be impressed by the concept and the precision of the experiments they conducted.
Acknowledgments Stefania Jabłońska, professor of dermatology at the Warsaw Medical Faculty, provided help and guidance in the discussion and analysis of Ludwick Fleck's contributions on dermatology, and Anna Fijałkowska provided proofreading of the text.
References 1. Fleck L. Entstehung und Entwicklung einer wissenschaftlichen Tatsache. Einführung in die Lehre vom Denkstil und Denkkollektiv. Basel: Benno Schwabe; 1935. 2. Löwy I. Ludwik Fleck, from philosophy of medicine to a constructivist and relativist epistemology. In: Löwy I, editor. The Polish school of philosophy of medicine. Dordrecht-Boston: Kluwer; 1990. 3. Shnelle T. Ludwik Fleck: Leben und Denken. Zur Entstehung und Entwicklung des sociologischen Denkstils in der Wissenschaftphilosophie. Freiburg: Hochschul-Verlag; 1982. 4. Fleck L. Curriculum vitae dr med. Ludwika Flecka. Handwritten manuscript. Archiv für Zeitgeschichte, ETH Zürich. 5. Szybalski W. The genius of Rudolf Stefan Weigl (1883-1957), a Lvovian microbe hunter and breeder—in memoriam. In: Stoika R, et al, editor. Presented at: International Weigl Conference, Sept 11-14, 2003, Lviv, Ukraine. Microorganisms in pathogenesis and their drug resistance—programme and abstracts; 2003. p. 10-31. Available at: http://www.lwow.home.pl/Weigl/in-memoriam.html. Accessed May 10, 2012. 6. Fleck L, Evenchik Z. Latex agglutination test with Brucella antigen and antiserum. Nature 1962;194:548-50. 7. Grzybowski A. Ludwik Fleck's studies in microbiology. Wurzbg Medizinhist Mitt 2007;26:110-9. 8. Schnelle T. Microbiology and philosophy of science. In: Cohen RS, Schnelle T, editors. Cognition and fact—materials on Ludwik Fleck. Dordrecht: Reidel Publishing Comp; 1986. p. 3-36. 9. Rubaszko I. Profesor doktor medycyny Ludwik Fleck (1896-1961). Annales UMCS Lublin—Polonia 1978/1979. Sectio I, Vol. III/IV:417-27. 10. Fleck L, Hescheles I. Uber eine Fleckfieber—hautreaction (die Exanthin-reaktion) und ihre Ahnlichkeit mit dem Dicktest. Klin Wochenschr 1931;10:1075-6. 11. Fleck L. Swoiste substancje antygenowe w moczu chorych na dur plamisty. Pol Tyg Lek 1946;21:663-6. 12. Fleck L. Specific antigenic substances in the urine of typhus patients. Texas Rep Biol Med 1947;5:168-72. 13. Weisz G. Dr Fleck fighting Fleck typhus. Soc Stud Sci 2009;XX/X: 1-9. 14. Fleck L, Kunicka A, Łukaszewicz J, Malinowska M, Steinhaus H. The renal excretion of specific microbial substances during the course of infection with murine typhus rickettsiae. Am J Hyg 1960;72:351-61.
Ludwik Fleck and dermatology 15. Fleck L. Leukergy and its role in immunity. [Article in French]Ann Inst Pasteur (Paris) 1957;92:380-95. 16. Fleck L, Rozenszajn L, Robinson E. Suppression by cortisone of leukergy induced by endotoxin. Texas Rep Biol Med 1961;19:60-75. 17. Grzybowski A. Ludwick Fleck's contribution to the medical science in relation to the contemporary medical research in Poland and abroad. In: Chołuj B, Joerden JC, editors. Studien zur Ethik in Ostmitteleuropa, Band 11, Von der wissenschaftlichen Tatsache zur Wissensproduction. Ludwik Fleck und seine Bedeutung fur die Wissenscheft und Praxis. Frankfurt: Peter Lang International Verlag der Wissenschaften; 2007. p. 237-44. 18. Gzybowski A. From Ludwick Fleck's leukergy to the present-day rheology of leukocytes in heart and vascular diseases. Kardiol Pol 2007;65:822-6. 19. Fullenbaum L, Fleck L. Experimentalle Beitrage zur Atiologie des Lupus erythematodes. Dermatol Wochenschr 1927;15:485-7. 20. Fleck L, Fullenbaum L. Clinical and experimental contribution on the etiology of lupus erythematosus. Urol Cutan Rev 1931;35:358-61. 21. Fleck L. Ein Foll Pseudophiloma anorectale mykotischer Aetiologie. Dermatol Wochenschr 1930;90:379-82. 22. Urbach E, Reiss F. Tierexperimentelle Untersuchungen zur Frage der infektiostöxischen Genese des Pemphigus vulgaris und der Dermatitis Herpetiformis Duhring. Arch Dermatol Syphilol 1931;162:713-25.
667 23. Urbach E, Wolfram S. Zur Virusgense der Pemphiguserkrankungen. Med Klin 1933;29:1619-21. 24. Urbach E, Wolfram S. Experimentelle und histologische Studien zur Frage der Virusgenese der Pemphiguserkrankungen. Acta DermatolVenerol 1934;15:120-53. 25. Urbach E, Wolfram S. Uber den Nachweis der Filtrierbarkeit des Pemphiguevirus. Arch Dermatol Syph 1934;170:389-96. 26. Urbach E, Wolfram S. Das Tierexperiment als differentialdiagnostische Methode bei Pemphigusverdachtigen Dermatosen. Klin Wochenschr 1934;13:1265-8. 27. Urbach E, Wolfram S. The virus of pemphigus and dermatitis herpetiformis. Arch Dermatol Syphilol 1936;33:788-806. 28. Fleck L, Goldschlag F. Further experimental studies of pemphigus. Br J Dermatol Syphilol 1939;51:70-5. 29. Fleck L, Goldschlag F. Experimentelle Beitrage zur Pemphigus Frage. Klin Wochenschr 1937;16:707-8. 30. Marchionini A, Nasemann Th. On the virus aetiology of pemphigus and dermatitis herpetiformis Duhring. J Invest Dermatol 1955;24: 267-74. 31. Welsh AL. Specificity of streptococci isolated from patients with skin diseases: studies on pemphigus, dermatitis herpetiformis, lupus erythematosus and erythema multiforme. J Invest Dermatol 1946;7: 7-42.
CARETAKER OF THE SKIN Edited by Andrzej Grzybowski, MD, PhD, MBA
Ludwik Fleck (1896-1962) and his contribution to dermatology Andrzej Grzybowski, MD, PhD, MBA a,b,⁎ . Department of Ophthalmology, University of Warmia and Mazury, Zołnierska 14 C, 10-561 Olsztyn, Poland b Department of Ophthalmology, Poznań City Hospital, Szwajcarska 3 61-285, Poznań, Poland a
Ludwik Fleck, Polish physician and microbiologist of Jewish origin, is mostly known today as a philosopher of science. His previously unknown treatise “Genesis and Development of a Scientific Fact” (Basel, 1935),1 was brought into international recognition by Thomas Kuhn in his The Structure of Scientific Revolutions (Chicago, 1962), one of the major books published in the 20th century in the field of philosophy of science. Kuhn wrote about Fleck in the introduction of his book, where he referred to his indebtedness to Fleck's findings. He has now achieved such prominence as a philosopher of science that the scientific center, “Ludwik Fleck Zentrum” (http://www. ludwikfleck.ethz.ch) in Zurich, was established to present analyses of his concepts and works, and international conferences on the subject are held. His scientific input in the field of philosophy of science and microbiology is well known and described elsewhere.2,3 Fleck was an accomplished scientist and was active also in other fields, including serology, immunology, and dermatology, which is much less known. This contribution is the first detailed analysis of his dermatology papers.
Biography Ludwik Fleck (Figure 1) was born in 1896 in Lviv, which belonged to the occupied Polish lands of the Austro⁎ Corresponding author. Tel.: +48 505 074 224. E-mail address: [email protected]. 0738-081X/$ – see front matter http://dx.doi.org/10.1016/j.clindermatol.2012.04.001
Hungarian Empire. From 1795 to 1914, Poland was partitioned by its three neighboring countries: Germany, Russia, and Austro-Hungary. There were strong political and economic differences between these three parts, with the Austro-Hungarian partition enjoying the most political, cultural, and educational freedom. Two major Polish universities with medical faculties, which quickly progressed, were founded: one in Cracow in 1364(just before the foundation of the universities in Vienna in 1365 and in Heidelberg in 1386) and another in Lviv in 1661. Most of the lectures in these universities were in Polish. In comparison, the German partition of the Polish state had no universities at all, and the Warsaw University in the Russian partition of the country was almost entirely under Russian influence, including the official language to be spoken. After graduating from Polish secondary school in 1914, Fleck began studying medicine at the Jan Kazimierz University in Lviv, where he graduated as a general practitioner and where he later obtained his PhD in 1922 (Figure 2).4 In the years 1920 to 1921, he assisted the famous Polish bacteriologist Rudolf Weigl (1883-1957) in his laboratory in Przemysl (about 50 km from Lviv) in his works on epidemic typhus. Weigl was the inventor of the first effective typhus fever vaccine, and although nominated nearly 50 times for a Nobel Prize, he never received the honor, which he deserved.5 Weigl was appointed to the chair of the University of Lviv Biology Department in 1921, and Fleck accompanied him as his assistant until mid-1923. Then, Fleck was appointed the head of the bacteriological-chemistry laboratory of the internal ward at the General Hospital in Lviv until 1925, and
664
A. Grzybowski
Fig. 1
Ludwik Fleck, 1896-1962.
later as the head of bacteriologic laboratory of the Skin and Venereal Diseases Department of the same hospital under Roman Leszczyński (1876-1940) until 1927. Leszczyński was a professor of dermatology and one of most prominent Polish dermatologists in the period between the First and Second World Wars, although for most of his life he was not related to a university department of dermatology. In 1927, Fleck spent 6 weeks at the Governmental Institute for Serotherapy in Vienna under Karl Kraus. In the years 1928 to 1935, he worked as the head of a bacteriologic laboratory of the local social assurance institution, and later until 1939, only in his private bacteriologic laboratory, which he had founded in 1923. During 1922 to 1939, without any academic position, Fleck conducted active research in many fields and published 39 scientific contributions in Polish and foreign journals, including Klinische Wochenschrift, Zentralblatt fur Immunitatsforchung unde experimentelle Therapie, Dermatologische Wochenschrift, and the British Journal of Dermatology and Syphilis. His main medical interests at that time were focused on bacteriology, serology, and dermatology. He devoted much time to his nonexperimental interests, including philosophy and methodology of science, which finally led him to the publication of his opus magnum, Genesis and Development of a Scientific Fact in 1935.1
This is extensively discussed elsewhere. 2,3 Despite different hindrances and problems, including the lack of an academic position and the instability of his employment, Fleck was at that time very active in research projects and publications. After the outbreak of World War II, Fleck became a head of the Municipal Sanitary-Bacteriology Laboratory in Lviv. Then, between 1940 and 1941, he worked as an assistant professor at the Department of Microbiology of the National Health Institute in Lviv, and until the outbreak of the German-Russian War, as head of the Department of Microbiology.4 During the German occupation, he was in charge of the bacteriologic laboratory in the Jewish Hospital in Lviv. At the beginning of 1943, Fleck was arrested and first transported to the Auschwitz concentration camp. In January 1944, he was moved to the concentration camp in Buchenwald, where he worked in the serology laboratories. He was liberated by the American Army in 1945. After short periods of recovery in various hospitals, he returned to Poland. In 1945, Fleck was given the position of head of the Medical Microbiology Department at CurieSkłodowska University in Lublin. He did his habilitation on exanthin reactions in 1946, and received the title of professor. In 1948, he worked as an expert for the International Military Tribunal for Germany in trials against Nazi physicians suspected of conducting medical experiments on concentration camp prisoners. Fleck moved to Warsaw in 1952, where he was appointed the head of the Department of Bacteriology and Immunology at the Institute of Mother and Child. In 1957, Fleck decided to move to Israel, where he joined his son Ryszard (born in 1924), and where he worked in the Weitzman Biological Institute, continuing his research on immunity in infectious diseases until his death in 1961.6
Fleck's scientific achievements Fleck is presently recognized predominantly as a philosopher of science. The discussions of his contributions in this field can be found elsewhere2,3; however, he was also a very productive researcher in microbiology, serology, and immunology. He was the author or a coauthor of approximately 170 original and review contributions. His bibliography and its analysis can be found elsewhere,7-9 but at least some of his major achievements deserve a brief description. From the very beginning, Fleck focused his interests in studies of spotted fever. He described a new skin test, named the exantin reaction, for the early detection of spotted typhus.10 In 1941and 1942, in the Lviv ghetto, he detected typhus antigenic substances in urine and then developed a new method of producing a vaccine against this disease, based on the presence of the antigen in the urine. This work was of a great practical value—a large number of vaccinated in the camp did not contract typhus although they were exposed to
Ludwik Fleck and dermatology
Fig. 2
665
Curriculum vitae of Dr Ludwik Fleck. Handwritten manuscript.
typhus infection.7,11-13 He continued his interest in typhus research until the end of his life.14 The second major field of his scientific interests was immunology and serology. During his stay in the Lviv ghetto in 1942, he was the first to observe the phenomenon of leukergy, a nonspecific leukocyte aggregation and adherence caused by different stimuli. Although his test was not standardized, the new test was welcomed by many international scientists with enthusiasm and made Fleck well-known. Fleck devoted many contributions to the investigation of leukergy and the function of leukocytes in health and disease.15,16 Although the term “leukergy” is no
longer used and seems to be out-of-date in modern immunology, the dysfunctions of leukocytes aggregation or adhesion properties, or both, are of a great interest in different disorders examined today, including heart and vascular diseases.17,18
Fleck's interests in dermatology In two contributions, Fleck and Laura Fullenbaum discussed the possible etiology of lupus erythematosus (LE). They showed that LE was not related to tuberculosis,
666 although they noted in LE a hypersensitivity to various bacterial agents. The evoking factor was, in their opinion, sunlight. They concluded that there was no specific microbe as an etiologic factor in LE but that various microbes could occur in different LE patients.19,20 They did not have any idea of the immunologic etiology of the disease. Fleck also described a case of anorectal changes, simulating syphilitic papules, under the name of pseudosyphiloma. Mycologic investigations, including cultures, have disclosed a new variety of scopulariopsis, and the cases of this type are called cladiosis. Serologic examination, using the extract of spores, showed positive cutaneous reactions that were invariably negative in control samples. The disease regressed with no therapy used. In this case, the glands were not involved. The transmission to guinea pigs and mice of the purulent content of cutaneous lesions was unsuccessful.21 His most interesting study was conducted in cooperation with Fryderyk Goldschlag, from the Department of Dermatology of the Lviv City Hopistal, who later became a professor of dermatology in Poland and in Australia. The study was related to an important discussion in those days about the etiopathogenesis of pemphigus. Eric Urbach and Stefan Wolfram, after a series of experiments, proposed the viral etiology of pemphigus.22-27 They showed positive serologic results by using the fluid from pemphigus blisters. Skin reactions were positive in 70% of patients with pemphigus and negative in control patientss. Suboccipital injections in rabbits produced severe changes and encephalomyelitis in a great number of animals. Fleck, being an accomplished immunologist, performed serologic studies in pemphigus with the goal of finding the etiologic factor of the disease.28 There were different opinions about a virus as an etiologic factor of pemphigus because results of bacteriologic studies were in general negative. Fleck and Goldschlag inoculated 15 rabbits with the blister fluid obtained from patients with pemphigus and dermatitis herpetiformis, which at that time was regarded a form of pemphigus. Inoculations performed by Wolfram, who accepted invitation to help with the study (to be sure that they were done in the same manner), were suboccipital, intracranial, intravenous, and intraperitoneal. Positive results were obtained in rabbits inoculated suboccipitally, but this route was not safe, often leading to cachexia and death. The changes of pemphigus were not produced in any animals. Serologic investigations—complement fixation using the antigen of Urbach—were also negative, and this, according to the authors, did not favor the viral etiology of pemphigus. Positive results of complement fixation by Urbach and Wolfram were interpreted as nonspecific. The authors concluded that there was no proof for a viral etiology of pemphigus.29 The controversy related to the viral etiology of pemphigus continued until the middle of the 20th century, and the contributions of Fleck and Goldschlag were often cited in that context as proofs for a nonviral etiology of the disease.30,31
A. Grzybowski Positive complement fixation results, found by Urbach and Wolfram in 75% of patients with pemphigus and in only 4.5% of healthy controls, can easily be explained: Pemphigus antibodies are known to be specific and pathogenic, and the passive transfer of pemphigus is possible by inoculation of these antibodies. The correct conclusion was not possible at that time due to the lack of knowledge in the field of immunology and a much simpler research armamentarium; however, one can be impressed by the concept and the precision of the experiments they conducted.
Acknowledgments Stefania Jabłońska, professor of dermatology at the Warsaw Medical Faculty, provided help and guidance in the discussion and analysis of Ludwick Fleck's contributions on dermatology, and Anna Fijałkowska provided proofreading of the text.
References 1. Fleck L. Entstehung und Entwicklung einer wissenschaftlichen Tatsache. Einführung in die Lehre vom Denkstil und Denkkollektiv. Basel: Benno Schwabe; 1935. 2. Löwy I. Ludwik Fleck, from philosophy of medicine to a constructivist and relativist epistemology. In: Löwy I, editor. The Polish school of philosophy of medicine. Dordrecht-Boston: Kluwer; 1990. 3. Shnelle T. Ludwik Fleck: Leben und Denken. Zur Entstehung und Entwicklung des sociologischen Denkstils in der Wissenschaftphilosophie. Freiburg: Hochschul-Verlag; 1982. 4. Fleck L. Curriculum vitae dr med. Ludwika Flecka. Handwritten manuscript. Archiv für Zeitgeschichte, ETH Zürich. 5. Szybalski W. The genius of Rudolf Stefan Weigl (1883-1957), a Lvovian microbe hunter and breeder—in memoriam. In: Stoika R, et al, editor. Presented at: International Weigl Conference, Sept 11-14, 2003, Lviv, Ukraine. Microorganisms in pathogenesis and their drug resistance—programme and abstracts; 2003. p. 10-31. Available at: http://www.lwow.home.pl/Weigl/in-memoriam.html. Accessed May 10, 2012. 6. Fleck L, Evenchik Z. Latex agglutination test with Brucella antigen and antiserum. Nature 1962;194:548-50. 7. Grzybowski A. Ludwik Fleck's studies in microbiology. Wurzbg Medizinhist Mitt 2007;26:110-9. 8. Schnelle T. Microbiology and philosophy of science. In: Cohen RS, Schnelle T, editors. Cognition and fact—materials on Ludwik Fleck. Dordrecht: Reidel Publishing Comp; 1986. p. 3-36. 9. Rubaszko I. Profesor doktor medycyny Ludwik Fleck (1896-1961). Annales UMCS Lublin—Polonia 1978/1979. Sectio I, Vol. III/IV:417-27. 10. Fleck L, Hescheles I. Uber eine Fleckfieber—hautreaction (die Exanthin-reaktion) und ihre Ahnlichkeit mit dem Dicktest. Klin Wochenschr 1931;10:1075-6. 11. Fleck L. Swoiste substancje antygenowe w moczu chorych na dur plamisty. Pol Tyg Lek 1946;21:663-6. 12. Fleck L. Specific antigenic substances in the urine of typhus patients. Texas Rep Biol Med 1947;5:168-72. 13. Weisz G. Dr Fleck fighting Fleck typhus. Soc Stud Sci 2009;XX/X: 1-9. 14. Fleck L, Kunicka A, Łukaszewicz J, Malinowska M, Steinhaus H. The renal excretion of specific microbial substances during the course of infection with murine typhus rickettsiae. Am J Hyg 1960;72:351-61.
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