34

Lousy Research: The History of Typhus Vaccine Production, 1915–1945

Martina Schlünder

Figs. 34.1a, 34.1b The box and the imprinting of its content: During and after feeding the lice (source: National Museum, Przemyśl, Poland)

Box: cages for breeding lice as experimental animals, with the goal of producing a vaccine against typhus. Size and shape: 3 cm x 5 cm x 1.5 cm rectangular box with a lid; the opposite side open, covered with a mesh fabric, also having a buckle for attaching straps. Box species or specific variant: larger or smaller boxes adjusted for specific purposes (i.e. breeding). Principles/Behaviour: Chinese boxes, similar to Matryoshka dolls, nested boxes, system of boxes. Subtypes: pill boxes, socks, glass cases. Material: plywood, plastics like Bakelite and Galalith, glass, felt, metal. Colour: brown, beige, silvery, transparent. First sightings: beginnings of First World War, around 1915. Habitat: human skin, strapped to the forearms or calves; microbiology labs. Distribution: during First World War and interwar period found in labs all over Europe, especially in Poland. Migration: during the Second World War they moved to research sites in concentration camps. Status: extinct, some specimens can be seen in museums (Przemyśl/Poland) or on the internet.

Keywords: confining, protecting, carrying, mobilising, caring, practising, killing

Louse in a Box

Profoundly exhausted, she leaned against the wall, her fingers still clenching the railing of the balcony. Then a new coughing fit shook her body. When it ebbed away she immediately checked the little boxes that were strapped with a rubber belt around her forearm. Everything seemed to be okay; the boxes were firmly secured and in place. She couldn’t find any of the tiny creatures wandering along her arm or hand. Her coughing fit hadn’t allowed any to escape. She wondered what it would be like to live without them. On any given day, for more than twenty-five years without pause, her body had been home to no fewer than five hundred lice. Of course, the individuals changed from time to time; once she succeeded in breeding a very successful strain up to the eleventh generation in the crook of her arm (Sikora 1944: 543, 551). When she was just starting out in her research, she had kept the creatures in little glass jackets that she hid in the pockets of her lab coat. To feed them, she had to put them one by one on a bridge made of thread across which they could climb out of the glass tube down to her skin to drink her blood. In this way, she was able to study them very closely. After a while, she thought she could distinguish a few individuals. She would use the tip of a pair of tweezers to nudge those that had fallen asleep, and let time slip away as the lice fed, often forgetting to enjoy her own meal (Sikora 1915: 524). Naturally, breeding hundreds of lice demanded continual sacrifices.

She started breeding lice in 1915, during the First World War, when she was working for Stanislaus von Prowazek (1875–1915) at Hamburg’s Institute for Maritime and Tropical Diseases. Some years before, in 1909, Charles Nicolle (1866–1936) had identified body lice as the vector of epidemic typhus, and now the hunt for the pathogenic agent – hidden in the lice – was underway. But it seemed more difficult to identify and much more dangerous to get close to the microbe than in the golden age of Robert Koch’s bacteriology. Howard Ricketts (1871–1910) had fallen prey to the microbe during his research in Mexico. Five years later, Prowazek caught typhus while studying an outbreak of the disease in a prisoner of war camp in Germany. It seemed wise to study lice (the container of the microbe) more carefully, since this had not been done before. After Prowazek’s death, she, Hilda Sikora, had courageously plunged into her work, and had published one of the first monographs on the anatomy of the body louse Pediculus vestimenti (Sikora 1916).

To study lice in the lab it was necessary to know how to breed them so that new strains of healthy lice could be built. Developing containment and feeding techniques were the keys for the successful breeding of lice. Hilda developed a set of different boxes that were later named after her (Figure 34.2).

Fig. 34.2 A set of Sikora boxes and its kin species (source: Sikora 1944: 542)

A ‘Sikora-cage’ was the prototype of a louse box that could be easily modified and adjusted to particular needs: the size of the strain, its morphology, and its purpose (either for use in experiment or later, for mass breeding for vaccine production). The frame of an average Sikora-box was made from either plywood, Bakelite or Galalith.1The chamber was closed on the top by a hinged lid. On the bottom it consisted of cloth mesh. The cages were small and flat, about three and a half centimetres long and half to one and a half centimetres high, each accommodating about one hundred lice. The flatter the boxes, the easier it was to secure them firmly in place by straps around the arm or the leg. A couple of holes were drilled into the lid for ventilation. All the holes had to be covered with mesh cloth that was glued to the frame with a specially formulated glue. Every precaution was taken to prevent lice from escaping.2 The boxes could remain attached to the body of the researcher for days and nights at a time, preferably in a position where they would not interfere with the performance of other lab activities while the lice sucked blood whenever they needed.

To maintain a steady flow of lice, boxes had to be constantly replaced, cleaned, and adjusted to meet the increasing demands and size of the young. As important as it was to seal the boxes to prevent lice from escaping, it was a similar priority to grant continual access to the skin for their nourishment. Thus the correct size of the apertures in the weave of the mesh cloth was an important issue of research. The width of the openings had to be exactly measured with a thread counter, a tool used in sieve making. Twenty-six holes per square centimetre was the smallest opening through which the lice could still feed, but only if the threads were half as wide as the holes (Sikora 1944: 545). Conveniently, these were the same parameters that prevented the smallest lice from escaping. Confinement and openness had to be balanced in the most delicate ways.

Hilda knew that her attitude toward her lice, her devotion to every single tiny individual louse, bewildered people in the institute. But she was unable to separate curiosity and research from care and love.3 Now, though, she knew that her long experience of interspecies conviviality would have to come to an end. Over the preceding months, the allergic reactions had increased. The asthma attack that kept her on the balcony that night confirmed that she would have to part with her creatures. But who else could take care of them?4

Louse as Box

The louse shares with us the misfortune of being prey to the typhus virus. If lice can dread, the nightmare of their lives is the fear of some day inhabiting an infected rat or human being. […] If only for his fellowship with us in suffering, he should command a degree of sympathetic consideration.

(Hans Zinsser, Rats, Lice, and History 1935: 168)

What kind of mesh could get hold of the history of lice? How densely must we weave the threads to grasp even tinier creatures? Are boxes of any help? In bacteriology it turned out to be so. Organisms can work like boxes in which smaller boxes are hidden, the hidden organism often more dangerous than its container. You can put lice in a box to study and nurture them. You can also treat lice as a box that you can fill up or empty. Of course, you first have to create a lot of empty boxes – healthy lice – which later can be filled with microbes (full boxes, sick lice). But often one can’t control how boxes are nested, since in microbiology one is working with sets of living boxes, with an ‘emboxed’ (Engstrom, this volume) assemblage of living organisms. The historian can follow these arrangements and study how these interspecies ensembles were put together – or separated – in specific historical situations.

With the start of the First World War, bacteriology became lousy. Hilda was a unique female voice in a chorus of male scientists who were eagerly conversing with each other about the body louse, Pediculus vestimenti, the species that lives in the clothes of humans. At least twice a day these lice leave their hiding places in seams and under buttons to climb down to the skin to nourish themselves by sucking blood. In a vast array of scientific publications, microbiologists and doctors who were wartime enemies discussed passionately how to chase and catch lice, where to contain them, how to breed a strain, where to breed it, and how to feed the hatchlings. Papers abounded with technical details and bore witness to the emergent material culture of lice in bacteriological labs. Even though Hilda’s love for lice might have been unique, she was not the only researcher who was hosting lice on her body. Most of her male colleagues’ bodies also turned into incubators. They tried other kinds of containers too, like glass casings, metal pill boxes, boxes made of felt or cloth, and even stockings. Each method made lice into a box, turning them from a disease vector into an experimental animal, a technical ‘apparatus’ (da Rocha Lima and Sikora 1925: 770). The purpose of this ‘apparatus’ was to apprehend, isolate, and culture the pathologic agent of typhus that obviously lived in the louse box and was transmitted through it to humans.

Hidden within layers of enclosure like a Chinese box or a Russian doll, the microbe nested in the lice that were hiding in the clothes of humans. To breed healthy lice in the lab was thus a way to bring this dangerous ‘emboxed’ assemblage under control. To precisely follow the path of infection, healthy lice from the labs, nurtured on the typhus-free blood of the researchers, were brought to the typhus wards. Secure in Hilda’s cages, the lice then sucked the infectious blood of the patients and were turned into typhus-infected lice that could be studied in the lab (Figures 34.3a, 34.3b).

Figs. 34.3a, 34.3b Empty boxes (healthy lice) and full boxes (filled with Rickettsia prowazeki) (source: Emil von Behring Archiv, Philipps Universität Marburg, No. 2261,09–03 W II, Lade 11)

Even though everybody knew that the microbe lived in the louse, it was extraordinarily difficult to identify – and dangerous, too. After Prowazek’s death, his Brazilian collaborator, bacteriologist Henrique da Rocha Lima (1879–1956), analysed the data Prowazek had collected, and continued with experiments in the lab. In 1916, he described the unknown microbe under scrutiny ‘as somewhat smaller than the smallest bacteria’ (da Rocha Lima 1916: 568). It was able to invade and propagate massively in the digestive tract of lice. Thus was typhus contracted by a contamination with lice faeces. Rocha Lima named the microbe in honour of its two most famous victims: ‘Rickettsia prowazekii’. Though it had a name, the microbe remained a bacteriological enigma. Rocha Lima’s evidence relied on histopathology; he wasn’t able to cultivate the microbe on an artificial medium like solid gelatine. Thus his proof didn’t follow the gold standard of the Koch postulates (Harden 1987). The microbes seemed to possess a bacterium-like morphology, but they were too small for typical bacteria. They were difficult to stain and impossible to culture outside living organisms. Microbiologists at that time had no idea how to find the right box, how to classify rickettsia: was it a virus, a new class of bacteria, the product of cell lysis, or simply a variant of another organism that turned into a pathologic agent under specific conditions?5 The difficulty of classifying rickettsiae, and the impossibility of culturing them outside living organisms, was not only of purely theoretical importance, but was also a hindrance for treatment and especially for the problem of vaccine production.

De-Lousing: Disentangling, Containment, and Mobility

He felt that something was utterly wrong but couldn’t grasp what. Shouldn’t people treat him – the king, the emperor even – more respectfully? Yesterday somebody put something on his head; had it been a crown, perhaps? He wasn’t sure. Why was everyone so jealous? They obviously envied the fact that he was able to fly. Why else would he have been strapped to his bed? In Peter Englund’s 2011 history of the First World War, he tells the story of Vincenzo d’Aquila, an American-Italian who came as a war volunteer to Italy and soon attracted epidemic typhus. In his visions he believed himself to be a king or a pregnant woman who could fly. Besides high fever, intense headaches, and a rash, patients undergo a stage of nervous excitement, with paranoia, delirium, and manic episodes. The word typhus – meaning hazy or smoky – points to these most striking symptoms. Englund gives a lively account of how typhus patients experienced their own illness, and how a ward with typhus patients might have looked. Patients often had to be strapped to their beds to protect the staff from being attacked, or to prevent the patients from harming themselves based on manic or delirious misperceptions of their surroundings and their bodies (Allen 2014: 22–23).

Epidemic typhus is the medical label of a disease that has been known under many names. ‘Jail fever’, ‘famine- and war-typhus’, or ‘typhus ambulatorius’ (ambulant typhus), all spell out the dire conditions under which the disease usually emerged. In contrast to traditional bacteriological accounts that understand infectious diseases to be uniquely defined by their pathogenic agents, it is worthwhile to consider typhus as arising from specific encounters that usually occur in the circumstance of war, famine, and living in barracks. The notion of ‘ambulant typhus’ highlights the fact that the mass movement of people, such as refugees, itinerant army troops, or a starving population wandering in search of food, are crucial ingredients for the emergence of typhus. The congestion of flows and the collapse of infrastructures trigger dangerous encounters between rickettsia, lice, and humans, and that finally produces typhus by making this deadly entanglement more likely to happen, and their mutual emboxment more stable.

This was especially true of the ferocious outbreak of epidemic typhus in Serbia during the first winter of the First World War. Within about six months, by the beginning of June 1915, more than 150,000 people had been killed.6 Troops from the Austrian and Serbian armies, their wounded soldiers and prisoners of war, and a starving Serbian population of about 250,000 people moved through the country. When the winter set in, soldiers, casualties, refugees, and prisoners of war took shelter in improvised, badly equipped camps and hospitals. Roads in the territory were constantly congested, the railroad overcrowded, and the transport of the sick and wounded could not be guaranteed. The lack of adequate infrastructure, not only in terms of transportation but also in terms of accommodation, shelter, and public health more generally certainly promoted the outbreak of the typhus epidemic. The situation attracted considerable international attention. Sanitary commissions from France, the UK, and the US were sent to Serbia. Beyond their humanitarian mission, these commissions also had a scientific interest, since the Serbian outbreak was the first significant one since Charles Nicolle’s discovery of lice as the vector of typhus.

The public health strategy of these commissions was aimed at disentangling lice (and thus rickettsiae) from humans. Since mobility lay at the heart of the spread, it was seen as a major task to control and contain railways and roads. People needed travel permits to use the train, the number of trains was reduced, and the unburdened railway infrastructure was used for the circulation of mobile disinfestation trains (Figures 34.4a, 34.4b).

Sanitary trains usually consisted of three freight cars. One was reserved for a boiler supplying steam, a second for disinfecting clothes and a third for showers and baths. The train stopped at specifically marked locations where huge tents were erected, beneath which the local population gathered, and several hundred at a time were asked to undress. Then their hair was cut and their clothes hung in the disinfection car while they were taking showers (Strong et al. 1920: 31–32). Sanitary trains were thus arranged as a sequence of boxes, each car containing one of a variety of methods for disentangling and separating the emboxed assemblage of microbe-lice-humans.

Figs. 34.4a, 34.4b A sanitary train during the Serbian typhus epidemic of 1915, and men leaving the train after having been de-loused in the steam bath (source: Strong et al. 1920, Fig. 1 Plate XII, Fig. 1 Plate XIII)

Re-Lousing: Re-entangling Lice Emboxment

If the lice will not swallow the cocktail of Rickettsias,

the contagious fluid will be served to the pests by rectum.

Rudolf Weigl

In the labs, a different strategy prevailed: instead of disentangling humans-lice-and microbes, the goal was to bring them as close together as possible, but in very controlled and manipulated ways. Usually a vaccine is made of a microbe in its weakened, dead, inactivated, or fragmented form. How to prepare a vaccine from a microbe that, so far, had not been isolated, let alone cultured? Since there was no known way of growing rickettsia on an artificial medium, a living form had to be found in which to culture the microbe. It was Rudolf Weigl, an Austrian-Polish biologist from Lwów, who came up with a way to manipulate the emboxment of ‘humans-lice-microbes’, and transform their deadly entanglement into a vaccine- producing assemblage. The most important step in the direction of a vaccine was Weigl’s development of an intrarectal inoculation technique for lice in 1919 (Weigl 1919: 372–75; Allen 2014: 19–20). This rendered possible the injection of a suspension made of infected lice containing rickettsiae into the rectums of healthy lice, thus turning them into a box that contained the dangerous and precious microbe. In this way Weigl systematically cultivated and built up stocks of the microbe. He no longer depended on the presence of typhus patients whose blood had formerly been used to infect healthy lice for the purposes of research.

Weigl took his time bringing the different steps of the vaccine to perfection. From the 1930s onwards, he was constantly urged by the Polish government to test his vaccine. Doing so would have meant upscaling the very cumbersome procedures that differed substantially from standard industrialised forms of vaccine production. Weigl succeeded in turning lice into vaccine producers by transforming the normally deadly emboxment into a carefully designed and controlled interspecies assembly line. He did so by navigating the passage of the microbe through an ensemble of living boxes, sequencing the stages of the passage and its temporalities. He reorganised his laboratory according to a Fordist division of labour, and accelerated the vaccine production, making it more secure and more efficient. The production started in so-called ‘breeding units’ consisting of a supervisor and twelve to fifteen lice feeders. The breeding units produced healthy lice that were then transferred to the ‘injection units’ where specially trained ‘injectors’ inoculated lice manually with the infected rickettsia suspension. They were also responsible for feeding the injected (sick) lice on their blood. The injector units thus consisted of people who had survived a typhus infection and had consequently acquired immunity against rickettsia. Highly skilled and experienced injectors could inoculate 2000 lice per hour. After five days, the sick lice were brought to the ‘dissector’s station’ where specially trained dissectors harvested the guts of the lice that contained the highest concentration of rickettsiae (Figures 34.5a, 34.5b).

Figs. 34.5a, 34.5b Dissecting lice, emptying the box. Dissecting units at the Behring Institute, Lwów (Fleckfieber-Forschungsstätte Lemberg) around 1942 (source: Emil von Behring Archiv, Philipps Universität Marburg, No. 2261,09–03 W II, Lade 11)

On average, a trained dissector could process three hundred lice per hour. A standard vaccination against typhus comprised three injections over three weeks, and contained the equivalent of the guts of ninety lice, and so one dissector could prepare vaccines for about thirty people a day. Even after the ‘Fordist’ reorganisation of his lab, production of the Weigl vaccine remained very difficult and cumbersome (Krynski et al. 1974; Szybalski 1999; Allen 2014: 67–72).

Lousy Research – Hiding and Killing

‘When you put on the lice cages […] the first feeling is like a hot iron, as five hundred or one thousand of them pierce your skin. You don’t want that to be repeated, so you try not to move the cages, because then the lice lose their place and have to bite again’. Wacław Szybalski (Allen 2014: 150) clearly remembers his first time as a lice feeder. Later, after the occupation of Lwów by Nazi Germany in June 1941, he would become supervisor of a breeding unit. Already, for the mass production of the vaccine during the 1930s, Weigl had had to hire about fifty louse feeders, since there was not enough staff to produce the quantities of lice that would meet the increasing demand. The scene changed dramatically with the occupation of Poland by Nazi Germany. Germany hadn’t prioritised the study of epidemic typhus since the First World War, and as the disease was not endemic in Germany it was difficult to research. Now, in the middle of the next war, it became clear that Germany was not well equipped to protect its own soldiers. Epidemic typhus was back, and vaccine production was crucial to the war effort. The Weigl vaccine was known as the only reliable one, whereas other types were still under scrutiny (Weindling 2000: 345–52). Due to its intricate production method, and Weigl’s notorious perfectionist reluctance to publish, the German occupiers couldn’t easily appropriate the knowledge to make the vaccine themselves. They were therefore entirely dependent on his help. Weigl advised several newly established research and production sites that were set up by the Germans (e.g. the Behring Institute in Lwów), and he once again expanded the production scale at his institute (Figure 34.6).

Fig. 34.6 Louse feeders at the Behring Institute, Lwów ca. 1942 (source: Emil von Behring Archiv, Philipps Universität Marburg, No. 2261,09–03 W II, Lade 11)

Almost 3,000 lice feeders were provided with official identification documents proving that their holders were involved in strategically important German war efforts. Weigl’s institute became an (almost) safe space for persecuted non-Jewish Poles in an otherwise nightmarish environment: ‘Anyone who needed saving became a louse feeder’, one of Weigl’s assistants claimed after the war (Allen 2014: 136). His institute became a kind of safe haven, as German occupiers were frightened of lice and all things typhus related – things that had been created through their own policies of deportation, ghettoisation, and barracking.

The encounter and emboxment of rickettsiae, lice, and humans, usually results in epidemic typhus and ends with the deaths of lice and people. Weigl’s manipulation of this living assemblage allowed researchers to control the passage of the microbe through the lice as through a living box. In the end, the lice alone died, thereby producing the ingredient for the most desired vaccine. But the complex interspecies ensemble could also be differently arranged yet again, as research carried out at Buchenwald concentration camp shows. This was where most of the different products of the attempted vaccination methods were tested. Besides a trial and a control group, so-called ‘passage persons’ were also infected with the microbe. Their only purpose was to serve as a reservoir, as a living box for rickettsia that needed living cells to grow (Weindling 2000: 354–55; Werther 2004: 117–18). Before they died, other ‘passages’ had to be infected. Thus these ‘passages’ took the position that the lice had occupied in Weigl’s vaccine production line. It might be more precise to say that passage people were not a container for the microbe, but rather that in the laboratory setting they were treated like microbes, since the difference between container and content had vanished. A corresponding position in the living assemblage of humans-lice-microbes was assigned to the Jews. Nazi ‘racial hygiene’ didn’t claim that they were dirty and filthy, thus attracting lice, thus spreading typhus. According to the de-humanising logics and logistics of the Holocaust, the Jews were, simply, lice. They were killed with the same technology – and ‘the same routinised indifference’ (Raffles 2007: 528). The boundary of a metaphor and the boundary between container and content – so crucial for Weigl’s work – completely collapsed into the ‘box’ of the parasite (Figure 34.7).

Fig. 34.7 Jews-Lice-Typhus, Nazi propaganda poster, 1941 (source: Bundesarchiv Berlin, Plak 003–039–001)

With the emergence of antibiotics after the Second World War passages through emboxed interspecies assemblages disappeared in the field of epidemic typhus. One burning question however remains: do anthropocentricism and dehumanisation entail each other? If yes, new questions arise: what kind of Enlightenment would get us out of this cul-de-sac?

Acknowledgements

This project has been supported by OPO Foundation Zurich and the Ludwik Fleck Center at Collegium Helveticum, Zurich, as part of a research project on Ludwik Fleck and the material culture of laboratories. I thank Oriana Walker for thoughtful discussions about lice and the careful editing. I would also like to thank Ulrike Enke (Emil von Behring Archiv Marburg) and Urte Brauckmann (Max Planck Institute for the History of Science library in Berlin) for helping me to access archival material, images, and image permissions.

Notes

1 Bakelite and Galalith are both early synthetic plastics. Bakelite is best known through the iconic black telephones of the 1920s and 1930s, see e.g. <http://www.ericssonhistory.com/products/the-telephones/The-Bakelite-telephone-1931> [accessed 12 October 2016].

2 A meticulous instruction in how to construct the boxes can be found in da Rocha Lima and Sikora 1925: 773–78.

3 The ethical, epistemic, and political importance of care in research has been studied intensely over the last years in STS. See Despret 2004, Mol, Moser, and Pols 2010, Puig de la Bellacasa 2011, Martin, Myers, Viseu 2015, and especially Schrader 2015 for a similar case about the study of insects (leaf bugs after Chernobyl).

4 Allen summarises the comments of Hilda’s colleagues towards her attitude to lice as an ‘attentiveness that tottered perversely on the border of love’ (Allen 2014: 63–64). On Hilda Sikora (1889–1974), who never trained as an academic scientist and was hired initially as an illustrator, see Lindenmann 2005 and Hulverscheidt 2013.

5 The classification of rickettsiae remained unclear until the 1960s (Harden 1987: 295). Nowadays they are included among bacteria since they maintain a metabolism independent of their host, but at the same time they are – similar to viruses – strictly intracellular parasites and cannot be cultivated on artificial media. In 1938, Herald Cox developed a method of growing rickettsiae in egg yolk sacs that was later used for the development of the Cox vaccine against typhus (Harden 1987: 295). An overview of all the attempts to produce a vaccine, most of them unsuccessful, is given in Weindling 2000: 435–36.

6 For comparison, the 2014–2016 outbreak of Ebola in West Africa resulted in a loss of ca. 11,325 lives over two years (see <https://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html> [accessed 7 September 2016]). The WHO believes that a large percentage (up to 70%) of cases and deaths were not reported.

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