Rudolf Weigl (1883-1957)
The year 1967 is the 50th anniversary of the discovery by Weigl of the method of artificial infection of lice with the microbe of typhus fever, which led to the development of the first effective and practical vaccine against typhus fever. Rudolf Weigl, who died ten years ago, was an unusual scientist and personality. His complicated mentality and manner, as well as his approach to certain matters, have given rise to contrwersial judgements, as a result of which is not easy today to depict his image. From the perspective of 50 years, however an objective assessment and a new interpretation of Weigl’s work from the standpoint of contemporary microbiology should be possible, provided the facts are brought to light from the shadow of his famous vaccine, which today has only historical interest. We must learn to perceive that which is permanent and essential in his work - the development of a new and interesting, hitherto underestimated method The vaccine was only one of its practical applications, which at first brought its author world fame, but later impeded his scientific creativeness, and finally, during the Nazi occupation, played a role not only in controlling typhus fever, but also in the salvation of the Polish population of Lwów.
Rudolf Stefan Weigl was born on September 2, 1883, in Prerov in Moravia. Brought up in Poland, he learned to love his adopted country, its language, culture and customs. In 1907 he graduated in the natural sciences at the University of Lwów, where he became the assistant of the eminent scientist and teacher Prof. Nusbaum-Hilarowicz. He was habilitated in 1913 in zoology, comparative anatomy and histology. His earliest works, concerned with cell structure, especially with the Golgi-Kopsch apparatus, and transplantation won him wide renown in their time. His excellent mastery of histologic technique and his interest in cytology influenced Weigl's entire scientific career and inspired his admirable researches. Weigl distinguished three species of rickettsiae, described the development of R. prowazeki in the intestinal cells in lice, demonstrated their toxicity, described the course of rickettsial infection in lice, and elucidated the nature of the Neil-Mooser bodies. His work was continued by his students: Anna Herzig-Weigl, Stanislawa Woyciechowska and Albina Kuchta.
Weigl's interest in typhus fever began in 1914, when he was drafted to the army as a parasitologist. The epidemiologie role of lice was known from the time of Nicolle. Sergent's work pointed out the direction for research, and finally da Rocha-Lima described R. prowazeki. However, the work of the Brazilian microbiologist did not fulfill the postulates of Koch, and the etiology role of the microorganism remained unconfirmed because of lack of methods of culturing R. prowazeki and passaging it through the cycle guinea pig-louse-guinea pig. Weigl's invention of the method of intrarectal inoculation of lice with R. prowazeki made possible the final proof that R. prowazeki is the etiology agent of typhus fever and allowed differentiation between R. pediculi and R. rocha-limae.
Some Polish microbiologists have expressed the opinion that Weigl's vaccine was not an original achievement, but a modification of the earlier concept of da Rocha-Lima and Martini, who tried to immunize humans by the use of phenol suspensions of ground lice proviously fed on patients. This view, however, is based on a misunderstanding. The essence of Weigl's achievement was not production of a new vaccine from infected lice, but the development of a laboratory method of inoculating the arthropods artificially by a nonphysiologic route. Typhus fever, like other infectious diseases, is gradually becoming extinct. The advent of antibiotics has solved the problem of its treatment, and in secticides that of its prevention. The experimental method devised by Weigl, on the other hand, is a permanent achievement, which is applicable not only in experiments with R. prowazeki, but also in quantitative cytology studies. Today, Weigl's method has outstepped the limits of rickettsiology. Experiments in living germ-free medium, which are becoming common in bacteriology, are of three types: higher animals bred under sterile conditions, tissue cultures, and avian embryos. A fourth model consists of arthropods infected naturally per os or artificially per rectum, into a body cavity, or into the lymphatic system.
Western European and American microbiological researchers at first employed arthropods mainly in biological studies with the aim of controlling agricultural pests and in the medical epidemiology of infectious diseases. At present, insects and parasites are considered a new type of experimental animal, the breeding of which is inexpensive and which can be used in mass studies. It must not be forgotten that Weigl was the originator of this new experimental model and of the method of artificial inoculation. In his earlier work in the years 1918—1922, Weigl did not consider the louse only as a medium for culturing the causative organisms of typhus fever, but was interested chiefly in the dynamics of the process. He was particularly interested in comparing the course of the process evoked by infection with two different species of rickettsiae — R. prowazeki and -R. rocha-limae. Weigl was the first in the world literature to report the toxic properties of R. prowazeki. Weigl's concept of using lice and other insects of the order Anaplura as a new type of experimental animal was adopted by many investigators in studies on other microorganisms. Weigl's method, or its modifications, and infection through various membranes and in animals have been widely used in studies on other rickettsiae (Anigstein, Herzig-Weiglowa, Weyer, Różewicz, Fuller, Pszenicznow), spirochetes (Baltazard, Mooser and Weyer, Sparrow), intestinal bacilli, pasteurellae, staphylococci and bacilli (Alwerdes and Bieling, Flűgge, Kryński, Woyciechowska, Kuchta, Becla, Milner et al., Price, Wigand and Weyer) Toxicity of antibiotics has been studied in lice (Krynski), and rickettsiocidal and rickettsiostatic agents have been tested (Starzyk and Westtrych, Przybylkiewicz, Weyer, Przesmycki, Wojciechowski and Mikolajczyk, Krynski, Woyciechowska, Czyczwar, Radkowiak and Becla).
A long period of time elapsed between Weigl's invention and the development of studies on insects, but the author of the method himself made relatively little use of it. A number of reasons contributed to this.
Weigl carried out his work on the intrarectal inoculation of lice with R. prowazeki during the first world war, at a time when a certain epoch in the history of microbiology was coming to a close. Under the influence of Koch, the aim of bacteriologic techniques was based mainly on cultivation on artificial media, and only rabbits, guinea pigs and mice were used as experimental animals. Weigl's method was therefore looked upon as a rather inconvenient one for culturing R. prowazeki, to be replaced eventually by an artificial medium. Until now, however, such a medium has not been found. Virology, on the other hand, has demonstrated the necessity and possibility of using living media, including chick embryos and tissue cultures.
Another reason was Weigl's unwillingness to publish the results of his research. Accustomed as we now are to immediate dissemination of scientific information, we find it difficult to understand the researcher who published practically nothing. Nevertheless, in the 19th, and even in the beginning of the 20'th century, it was customary for many investigators to defer the reporting of their work until late in life. Weigl belonged to this category. At least 90% of his work remained unpublished or was communicated only by word of mouth. This includes all his experimental research with arthropods. Moreover, Weigl's method of documentation was so chaotic that his notes are practically illegible. After his death, an attempt to reconstruct his protocols by Herzig-Weiglowa and Krynski was unsuccessful. Stacks of preparations without comments or references proved practically worthless.
However, the chief reason why Weigl did not elaborate his method is connected with the vaccine itself. Weigl developed the vaccine at a time when typhus fever was claiming thousands of victims and will widely feared. Contemporary medicine awaited a vaccine eagerly; Together with his collaborators, mainly his wife Zofia, Weigl developed a method of production of the vaccine on the laboratory scale. His hesitation before introducing the vaccine for use in humans was based on extreme caution, enhanced by the fact that he himself was not a doctor of medicine, as a result of which he considered long preliminary laboratory experiments necessary before beginning immunization of humans.
After ten years he published his results in two papers: "On the nature and forms of the causative agent of typhus fever", and "Methods of active immunization against typhus fever".
Weigl's participation in the campaign of typhus vaccinations in the Belgian Catholic Missions in China brought him worldwide renown. He was awarded high papal and Belgian distinctions, was elected to many foreign scientific bodies, was proposed by the Polish authorities and foreign institutions as a candidate for the Nobel prize, and was visited by eminent foreign scientists. His decision to continue production of the vaccine personally became an obstacle to further scientific work on his part. The transformation of a university department into a vaccine production establishment was unfortunate. A talented experimental researcher and scientist became its head. The high quality of the vaccine produced in a small laboratory began to deteriorate in mass production; despite partial automatization which made production more economical, many important problems remained unsolved.
In the 1930s the scientific profile of Professor Weigl's department changed. The necessity of checking the walue of the vaccine in field trials resulted in greater emphasis on the epidemiology of typhus fever (Henryk Mosing, Piotr Radlo), involving also laboratory research (Jan Starzyk). The original line of cytological research, which could have led to deeper understanding of the biology of R. prowazeki, virology and wider use of arthropods in microbiological studies, was neglected.
In 1939 Weigl travelled to Addis Abeba to organize production of the vaccine in Abyssinia, where the epidemiological situation of typhus fever was serious. The impending war caused him to break off this work and to return to Poland.
In the first phase of the war, under the Soviet authorities in Lwów (Oct. 1939 — June 1941), the Department was expanded, but it's character did not change. The occupation of Lwów by the German army in 1941 created an entirely new situation, in which Weigl showed his greatness not only as a scientist, but as a citizen and patriot. The inclusion of the Department in the military Institut fur Fleckfieber und Virusforschung by the Germans created a dilemma for Weigl. Often helpless in much simpler matters, he displayed great courage and ability to undertake difficult decisions.
The complicated situation in which the Lwów academic circles found themselves in July 1941 resulted in Weigl's decision to continue to direct the Institute. In this way, he hoped to be able to come to the aid of professors and assistants who were deprived of work. The Institute grew in geometric progression. University members threatened with deportation as slave laborers in Germany, students and young people, members of the resistance movement were protected by fictitious employment in the Institute, forming a peculiar staff of the vaccine production establishment.
In this situation Weigl risked more even than in refusing to sign the Volksliste or to pay a visit to the General Governor. The vaccine produced during the occupation was of inferior quality which required maneuvering between the poor state of production and demands of the German authorities.
Under these difficult conditions Weigl nevertheless succeeded in creating a warm atmosphere of scientific research in the laboratories freed of German control. The direction of research again inclined to the Professor's early interests. Stefania Pokorny, Zbigniew Stuchly and Ewa Lomnicka-Broszkiewicz worked on the biology of lice; Tadeusz Korzybski's work on the metabolism of lice introduced the much-needed biochemical element. Stanislawa Woyciechowska contributed her histological experience in cytological and cytopathological studies. Stefan Krynski elaborated the problem of toxicity of R. prowazeki and its role in the process of reddening of lice, and in collaboration with Woyciechowska demonstrated that hemoglobin is an essential factor in the life of Lice. Henryk Meisel carried out studies in the cocca causing epizootic infections in lice. Unfortunately, the protocols of these experiments were lost. The results of the work of a team of researchers on trench fever were not published. Henryk Mosing continued epidemiological studies on the immunizing potency of Weigl’s vaccine and on the clinical symptoms of typhus in vaccines.
Some of Weigl's assistants considered him a poor teacher. More exactly, however, he was not a teacher at all. Although Weigl never taught others, much could be learned from him. He did not train his assistants or supervise their research; very often he probably did not even carefully read their papers. Those of Weigl's assistants who possessed personal initiative in research succeeded. Weigl was always accessible to discussions, however. Critical but tolerant, he was endowed with an unusual imagination and experimental talent, and was quick to detect experimental errors in the work of others. Scientists from other countries who visited him were charmed by his brilliant concepts and after leaving Lwów made use of them. Some of Weigl's students still consider that they wasted their careers in his department, but others continue under the spell of his scientific individuality.
When Weigl came to Cracow in 1945 the vice-minister of health, Dr. Morzycki, planned the foundation of a Rickettsia Institute, including the field of virology, with its seat in Poznan. However, he considered that Weigl should disengage himself from the direct production of the vaccine. Weigl, however, was of a different opinion, insisting on continuing personal supervision of the production, and the plan was dropped. Weigl was called to the Chair of General Microbiology of the Jagiellonian University, and later to the Chair of Biology of the Medical Faculty in Poznan. Production of the vaccine remained in Cracow.
The Department in Cracow, situated at 6 Sebastian street, administered by the Provincial Sanitary-Epidemiological Station, continued to produce the vaccine under unsatisfactory conditions, creating difficult problems for the Commission of Control of Sera and Vaccines of the State Institute of Hygiene and Sanitary-Epidemiological Department of the Ministry of Health. The Chair was neglected, bringing little benefit to the Professor, and none 'to his assistants. Thus were wasted the last ten years of Weigl's life.
Weigl was a great Polish scientist, and this must not be forgotten. He was a brilliant experimental researcher and creator of a new and unusual method, which in the past gave a vaccine and continues to possess great possibilities in the future. Nothing human was alien to; his merits were great as well as his errors and scientific achievements. His work was not only his own, but is a part of Polish science which must be defended, but not minimized.
Poland, Gdansk 6.II.1967.
Copyright Stefan Krynski
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