George M. Weisz, MD, FRACS
University of New South Wales, Sydney, Australia
Andrzej Grzybowski, MD, Phd, MBA
Poznan City Hospital, Poland (Fall 2012)
Dr. Ludwik Fleck, a pioneer in the early diagnosis of infectious diseases, was born in 1896 in Lwow, then known as Lemberg and until World War I, part of the Austro-Hungarian empire. Graduating from Lwow University Medical School, Dr. Fleck became interested in medical research and by 1931 had made several contributions to the diagnosis of typhus (Fleckfieber), and in the new field of autoimmune diseases. He also became known for his philosophical publications.
In 1939, following the occupation of his city of birth, he was confined to the Lwow ghetto, where conditions were tolerable until mid-1941. Eventually he was taken into “protective custody” (shutzhaft), working in the Laokoon pharmaceutical complex from December 1942 until early February 1943. He was confined in the Lackiego Prison for two weeks before he was transferred to Auschwitz as haftling No.100967. He found the hard physical work exhausting, was beaten and kicked, and was admitted to sick bay with broken ribs, “pleurisy,” and a mild form of typhus (a condition ameliorated by previous self-vaccination). Once his specialty was recognized, he was assigned to work in a serology laboratory. In January 1944, as haftling No. 4934, he was transferred to Buchenwald, working on typhus serology for Dr. Ding’s Institute of Hygiene.
In April 1945, Dr. Fleck was liberated by the American Army. However before being able to return to Lwow, he required three months of rehabilitation. Troubled by lack of sleep and energy, he was admitted first to Buchenwald Hospital, later to Bunzlau (Boleslawiec) Hospital.In late 1945 he was in Lublin, working as head of the Microbiology Institute. His health started to fail and he suffered his first heart attack. Eventually, he was transferred to Warsaw as head of the Bacteriology Department. In 1957, Dr. Fleck moved to the Israel Institute of Biological Sciences in Ness Ziona, where he headed the Experimental Pathology Laboratory. He was accorded numerous international awards and published more than 170 articles. He suffered a fatal heart attack in 1961 whilst being treated for lymphoma.
Dr. Fleck’s described his work on typhus in the ghetto as follows:
“In the first months of 1942, I began research on the urine of typhus patients in the Ghetto Hospital in Lwow, to see whether, similarly to the urine of patients suffering from pneumonia, this urine contained certain substances which would cause the production of antibodies.” He also stated, “The future will show if the possibility of making a specific diagnosis from urine can be utilised also in other infectious diseases.”
Fleck’s pre-war original documents were lost on the way to Auschwitz and none of his work was officially published. It was referred to in an anecdotal narration by Adolph Volkmann, an escapee from Ghetto Lwow to Sweden who stated that: “A Jewish doctor named Fleck had just succeeded in producing a new and more effective serum against spotted fever.” In 1946 Prof. L. Hirszfeld, who survived the war in the Aryan side of Warsaw, acknowledged Fleck’s 1942 discovery, as did Australian researchers who in 1947 used the urine test in scrub typhus (tsutsugamushi disease), repeating Dr. Fleck’s experiments with a second strain of Rickettsia. Then in 1960, Fleck himself repeated his own experiments with a third strain of the Rickettsia obtained from patients admitted to two Israeli hospitals. The original publication of Fleck’s research from the Ghetto Hospital, published on May 27, 1942 in Lwow’s Jewish Gazette, has only recently surfaced and is the final confirmation of Fleck’s statement.
Dr. Fleck was not the first to discover urinary antigens. Metabolites in the urine of sufferers with pneumococcal infection had been reported as early as 1915. In 1926, Bronislawa Fejgin detected a cross immunological diagnosis between Rickettsia and Proteus. In 1942, Dr. Alberto Leon from Mexico published a study on typhus presenting a similar urine test, and a diagnostic later in the disease when the skin eruption was obvious some four months after Fleck. All these preliminary studies, however, remained in laboratories, and only Dr. Fleck’s test was used clinically in the diagnosis of typhus.
Since those early days, research on urinary antigen has continued: Spanish investigators have found S. pneumonia antigen in the urine in pneumonia patients and have used urine antigen detection in the early diagnosis of meningitis, as have workers in the United States, Japan, Russia, and Australia. Now, most infectious diseases are diagnosed by sophisticated, specific tests (biochemical, electrophoretic, mass spectrographic, and immunological). Dr. Fleck’s test, however, carried out in 15 minutes on a drop of urine, could find application when no such facilities are available, perhaps in remote rural hospitalsorinunderdeveloped countries. A simple bedside test, performed with a commercially available kit, would offer an initial rapid diagnosis and permit immediate accurate antibiotic therapy. More importantly, though, Dr. Fleck’s efforts are a shining example of how important scientific work can be carried out by determined investigators, even under the most adverse of conditions.
Austrian, R. “Oswald Avery the wizard of York Avenue.” Amer. J. Med. 107(1) Suppl. 1. (1999) pg 7-11, 26-27, 35-36.
Boulware, D. R., Daley, C. L., et al. Rapid diagnosis of pneumococcal pneumonia among HIV-infected adults with urine antigen detection. J. of Infect. (2007) 55(4):300-309.
Dominguez, J., Gali, N., et al. Detection of S. Pneumonia Antigen by a Rapid
Immunochromatic Assay in Urine Samples. Ches. (2001) 119:343-349.
Fejgin, B., Kaczynski, R., & Szwojnicka, S. De la bacteriologie du typhus exantematique chez l’home. Comp. Rend. Soc. Biol. 1927; 96-5: 341-2.
Fleck, L. Some observations and Experiments from the field oftyphus. Pol. Tyg. Lek. (1946) 10:307-309.
Fleck, L.Specific antigenic substances in the urine of typhus patients. Texas Reports on Biology and Medicine. (1947) 5(2):168-172.
Fleck, L., Porat, S., et al. The Renal Excretion of Specific Microbial Substances during the course of Infection with Murine Typhus Rickettsiae. Amer. J. Hyg. (1960) 72:351-361.
Grzybowski, A. Ludwick Fleck’s studies in Microbiology. Wurzburger medizinische Mitteilungen. (2007a) 26:110-109.
Grzybowski, A. From Ludwik Fleck’s leukergy to the present day rheology of leukocytes in heart and vascular diseases. Kardiologia Polska. (2007b) 65:822-826.
Guchev, I. A., Yu, V. L., et al. Management of Non severe Pneumonia in Military Trainees with Urinary Antigen test for S. Pneumoniae: An Innovative Approach to Targeted
Therapy. Clin. Inf. Dis. (2005) 40:1608-1616.
Hirszfeld, L. & Epsteinowna, T. Serological-bacteriological experiments for early identification of spotted fever, Preliminary announcement. Pol. Tyg. Lek. (in Polish) (1946)
Ishida, T., Hashimoto, T., et al. A 3-years prospective study of a urinary antigen detection test for S pneumonia. J. Infect. Chemo. (2004) 10(6):359-363.
Leon, AP. The precipitation of anti-typhus serum by urine of typhus patients: a new serological test for typhus fever. Revista del Institute de Salubridad y Enfermedades Tropicales (1942) 3:201-8.
Marcos, M. A., Jimenez de Anta, M. T., et al. Rapid urinary antigen test for diagnosis of pneumococcal community-acquired pneumonia in adults. Eur. Respir. J. (2003) 21(2):209-214.
Marcos, M., Martinez, E., et al. New rapid antigen test for diagnosis of pneumococcal meningitis. The Lancet. (2001) 357:1499-1500.
Neuman, M. & Harper, M. B. Evaluation of a Rapid Urine antigen Assay for the Detection of invasive Pneumococcal Disease in Children. Pediatrics. (2003) 112(6):1279-82.
O’Connor, J. L. & MacDonald, J. M. Excretionof Specific Antigen in the Urine in Tsutsugamushi Disease (Scrub Typhus). British Journal Experimental Pathology. (1954) 31(1):51-63.
Szende, S. The promise Hitler kept. Victor Gollancz Ltd. London. (1945)
Weatherall, C. & Gottlieb, T. Point of care urinary pneumococcal antigen test in the
emergency department for community acquired pneumonia. Emerg Med J. (2008) 25:144-8
Weisz, G.M. Dr. Fleck Fighting Fleck Typhus, Social Studies of Science. (2010) 40:145-53.
GEORGE M. WEISZ, MD, FRACS was trained as an orthopedic and spinal surgeon in Israel, the USA and Canada. He has been in practice in Sydney since 1975. His interest in history and the arts led to a BA degree in European History at the University of New South Wales and to an MA in Renaissance Studies at the University of Sydney. His present research continues on both medical and historical lines, more specifically on “ghetto doctors’ contributions to medicine” and “medical history hidden in Renaissance paintings.”
ANDRZEJ GRZYBOWSKI, MD, PhD, MBA is an Ophthalmology consultant for Wielkopolska Province, secretary of the Neuro-ophthalmology/Pediatrics/Strabismus/History of Ophthalmology section at European Association for Vision and Eye Research (EVER) and scientific program coordinator for the 2012 World Ophthalmology Congress (WOC).