Isolation, Contamination, and Pure Culture: Monomorphism and Polymorphism of Pathogenic Micro-Organisms as Research Problem 1860-1880

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Christoph Gradmann

Perspectives on Science, Volume 9, Number 2, Summer 2001, pp.147-172 (Article)

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Isolation,Contamination, and PureCulture: Monomorphismand Polymorphism ofPathogenic Micro-Organisms as ResearchProblem 1860–1880

Christoph GradmannUniversity of Heidelberg

This article analyzes German debates on the microbiology of infectious dis-eases from 1865 to 1875 and asks how and when organic pollution in tis-sues became noteworthy for aetiology and pathogenesis. It was with ErnstHallier’s pleomorphistic microbiology that the organic character of alien ma-terial in tissues came to be regarded as important for pathology. The processthat followed saw both vigorous biological critique and a number of medicalapplications of Hallier’s work. Around 1874 contemporaries reached theconclusion that pleomorphous vegetation was most likely of little importanceif not accidental in relation to the aetiology of infectious diseases whereas theidea of monomorphous micro-organisms facilitated a causal explanation. Itwas only then that notions such a pure cultures, bacterial speciªcity, etc. fa-vored by Ferdinand Julius Cohn and his school became popular in medicalcircles.

A Science of Purity and ContaminationThe rise of medical bacteriology with its concept of pathogenic germs ascausal agents of diseases is commonly held to be one of the fundamentalchanges occurring in nineteenth century medicine.1 The notion that par-ticular infectious diseases are caused by particular pathogenic microbeswhose presence or absence almost deªnes such diseases seems a common-place. Even if the knowledge of the existence of bacteria can only be at-tained by experts who themselves have to rely on necessary technology

I thank Sarah Jansen (Cambridge, Mass.) for translating nineteenth Century German bo-tanical terminology and Alexandre Métraux (Dossenheim) for a critical reading.

1. For an introduction see: Gradmann and Schlich (1999); Tomes and Warner (1997);Worboys (2000). On the peculiarities of the bacteriological understanding of diseases:Cunningham (1992); Carter (1985); Schlich (1999).

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Perspectives on Science 2000, vol. 9, no. 2©2002 by The Massachusetts Institute of Technology

everybody takes their existence for granted and agrees that isolation,cleanliness, and disinfection are appropriate ways to deal with such dan-gerous intruders (Gradmann 2000b; Kraut 1994; Martin 1994; Tomes1998). That man’s relations to microbes are of an antagonistic sort is acommonly shared view and we even try to avoid getting in touch withbacteria by hygienic measures—despite the fact that this is not a verypromising endeavor given their invisibility (cf. Canetti [1960] 1984,p. 47).

The aim of this article is to shed some light on the development ofsome central notions of this concept of pathogenic germs which cause dis-eases and in whose control we tend to see an angle to ªght diseases(Schlich 1999). When and how did notions such as puriªcation, contami-nation, and isolation which contain, as a recent historian of AIDS noted,“the mission of biomedicine in a nutshell” (Epstein 1996, p. 31) acquiretheir speciªcally bacteriological semantics and their the enormous impor-tance for medical bacteriology?

In a broad sense the genesis of the concept of pathogenic germs can beplaced into the history of the nineteenth century. It was in this periodwhen a healthy and clean human body became re-deªned as germ-freebody and when the threats posed to it by an outside world appeared in thenew form of dangerous bacteria.2 Aided by hygiene, anti-sepsis etc. menattempted to ªght off diseases and their embodiments, bacteria. The newrelation of men and microbes became part of societies, when “the hygien-ists introduced the notion of a microbe as the essential cause of infectiousdisease, they did not take the society to be made up of rich and poor, butof a rather different list of groups: sick contagious people, healthy butdangerous carriers of microbes, immunized people, vaccinated people andso on” (Latour and Woolgar 1987, p. 116). Microbes became pathogens inthe late nineteenth century and the semantics of their antagonistic rela-tionship to men has turned out to be a remarkably stable cultural patternof our time (Kraut 1994; Martin 1994).

This rise of this popular bacteriology has to be seen in intimate connec-tion to the history of the science of medical bacteriology, on which this pa-per will focus. From the 1860s, on microbiology and pathology came tobe related in a way that helped to envision invisible microbes as embodi-ments of diseases and to create the above mentioned notions: to see bacte-ria inside organisms as contamination, to foster the idea of a human bodythat needed to be kept free from pathogenic germs which in turn needed

148 Isolation, Contamination, and Pure Culture

2. On popular bacteriology see Gradmann (2000b); Kraut (1994); Martin (1994);Tomes (1998); Brecht and Nikolow (2000); Vigarello (1988); Lachmund and Stollberg(1995, pp. 186–92).

to be isolated and controlled. Just as hygienic medicalization of societiesmeant that contemporaries had to adapt to new patterns of perception andbehavior, medical bacteriology grounded itself in a novel understanding ofthe microcosm and its inhabitants which was now considered to be caus-ally responsible for aetiology and pathogenesis of infectious diseases.3

In the process of establishing that order, scientiªc concepts and tech-nologies of purity and contamination such as bacterial speciªcity, purecultures or disinfecting, acquired a high importance. The image of ‘classi-cal’ medical bacteriology such as devised by Robert Koch and his school isclosely related to technologies like bacterial staining, pure cultures, mi-cro-photography, or solid culture media, and on the theoretical level foundits most veritable icon in the famous postulates that had to be fulªlled toestablish bacterial aetiologies.4 The enormous accent that Koch and othermedical bacteriologists put on bacterial speciªcity, isolation, and puri-ªcation is usually explained by contrasting their achievements with con-temporary German and French research. Koch’s accent on technologiesand concepts safeguarding speciªcity and stability of bacterial species ap-pears as an attempt to establish his school of bacteriology by contrasting itwith other microbiological research such as Pasteur’s theory of bacterialvirulence, Naegeli’s bacterial transformism or Pettenkofer’s localistic the-ory of infectious diseases.5

Even if the contrast with Pasteur, Naegeli, or Pettenkofer helps to un-derstand the peculiarities of Koch’s emphasis on stability and speciªcity ofbacterial species, one might also ask how Koch’s conceptions related to on-going contemporary discussions on the microbiology of infectious diseasesin Germany. This issue had been a heatedly discussed topic in Germanyfrom about 1865 on and it is remarkable to see how contemporaries ini-tially succeeded in discussing the microbiology of infectious disease with-out employing notions of purity and contamination (Diepgen 1926; Faber1930, pp. 95–94). It was rather—as this paper will demonstrate—thatthe discussions started with the discovery of manifold organic pollution inthe intestine of cholera-victims or in septic wounds. What followed fromca. 1865–1875 was a process of conceptual and experimental speciªcationand puriªcation of such ‘vegetation’. The result was a reductionist modelof the aetiology of infectious disease, and most of the earlier experimental

Perspectives on Science 149

3. On the history of bacteriology see Bulloch ([1938] 1960); on medical bacteriologysee Foster (1970); Worboys (2000); See also Mendelsohn (1996).

4. On Koch and his school see Gradmann (2001, encyclopaedia article). On the devel-opment of his school in particular see Mazumdar (1995); Mendelsohn (1996); Weindling(2000). On Koch’s postulates see Carter (1985); Schlich (1997).

5. On Pasteur see Geison (1995); Mendelsohn (1996); on Naegeli see Mazumdar(1995); on Pettenkofer: Hubenstorf (1993); Jahn (1994).

work came to be regarded as technically inadequate, e.g., working withmixed cultures, using inefªcient technologies of isolation and so forth.6

However, initially such research gave plausible answers to the microbiol-ogy of infectious diseases and we may well ask how experimental evidencefor pathogenicity was produced, which role questions of purity and con-tamination played in this context, how they entered the debates, and howthis adds to our knowledge about the early days of medical bacteriology.

Classification and TransformationEven though the existence of a microcosm of microbial life was wellknown to contemporaries and research on the nature of lower organismswas extended, disagreement on the nature and order of microbial life wasfundamental in mid nineteenth century (Jahn 1990, pp. 351–364). Theidea that these organisms could be sorted into distinct and constant spe-cies was—all in all—a minority opinion. Its most prominent spokesmanaround 1860 was Ferdinand Julius Cohn, a botanist from Breslau. He haddeveloped a taxonomical system of bacteria which he clearly separatedfrom microscopic fungi or algae and distinguished four basic types thatcould be subdivided on the basis of morphology.7 However, such system-atic aspirations were far from being uncontested: Cohn’s constant bacterialspecies could easily be contrasted with opposing observations where oneform could turn into another (transformation) or appear in diverse forms(pleomorphism). Apart from this, smaller structures that could be ob-served through a microscope simply appeared as pellets or granules thatwithstood any attempt to make distinctions.

Thus the obvious alternative to Cohn’s views was that the microcosmconsisted not of a large number of species that were hard to distinguish,but of a small number of different organisms that were much moreºexible. Even if spontaneous generation as such was rarely argued in theGerman situation in the 1860s, transformation and polymorphous appear-ance seemed quite important and plausible. Whether a given observationof changing shape and properties of a micro-organism testiªed for its poly-morphous, nature or had to be attributed to insufªcient experimentaltechnology, was almost impossible to decide.8


6. See e.g., a public speech in 1909, where Koch gave a satirizing picture of these daysand even claimed that prior to his work virtually no medical bacteriology existed (Koch[1909] 1912).

7. On Cohn see Hoppe (1983); Mazumdar (1995, pp. 46–67). Cf. Cohn (1875a); Cohn1875b).

8. Pasteur’s refutation of spontaneous generation has been analyzed as a classical exam-ple to this case (Farley 1977, pp. 92–120; Geison 1995, pp. 110–142).

One feature of contemporary discussions has to be kept in mind: If ex-planations of microbial life could follow two alternative strategies of ei-ther establishing constant species or explaining variability, the latter onewas more in line with the scientiªc spirit of the age. Physiological researchinto the nature of microbial life seemed more modern than taxonomic in-vestigations that carried an air of deductive thinking and a ‘system’ withit. What was at stake in German microbiology of the 1860’s was the orderof cryptogamic life and, as an observer noted, it seemed a lot more appro-priate to take morphological differences to indicate development than tocarry on with the traditional task of dividing species along the lines ofmorphology:

Up until now everybody who saw a new form of fungi, gave a de-scription, a picture, and a name. Now it becomes clear that most ofthese forms are just temporary developmental stages. [ . . . ] To estab-lish a new and sufªcient system out of the solid remains seemsquite impossible for the time being. What seems much more im-portant for us medical people is to keep our mind free from theolder, orthodox systematics that held on to ªxed species and genera(Richter 1867, pp. 90–91).9

It was Matthias Schleiden who had, around mid-century, attempted tomake botany an inductive science in this sense. Two decades later Carl vonNaegeli, a leading botanist, could maintain that bacterial species are notnatural objects but could be transformed into one another: “For ten years Ihave been investigating thousands of different forms of dividing yeast[Spalthefe] and I really could not say that even a division into two differentspecies is compelling” (Naegeli 1877, p. 20; Cf. Mazumdar 1995,pp. 15–45). On the contrary, Cohn “had reached the conclusion that bac-teria should be divided into distinct species just like lower plants and ani-mals” (Cohn 1875a, p. 133) and had to face suspicions that he remainedfaithful to a system instead of relying on scientiªc observation. Thespeciecistic concept suffered from a shortage of empirical evidence:


9. “Während bisher Jeder, welcher eine neuen Form von Pilzen sah, dieselbe beschrieb,abbildete u. mit einem neuen Namen versah: Tritt jetzt immer mehr hervor, daß dieseFormen grossentheils blos vorübergehende Entwicklungszustände sind. [ . . . ] Ein neues,befriedigendes System aus dem haltbaren Reste zu schaffen, ist im gegenwärtigenAugenblick vielleicht gar nicht möglich. Um so nothwendiger ist es für uns Medicinerjetzt, den Geist ganz frei zu halten von der älteren, rechtgläubig die Fixität der Arten u.Gattungen festhaltenden Systematik.” Emphasis in the original. From 1867 on the Journalthat Richter edited Schmidt’s Jahrbücher der gesammten in- und ausländischen Medicin began topublish a whole series of reviews of the growing ªeld of research (Richter 1868; Richter1871; Richter 1873; Richter 1875; Birch-Hirschfeld 1872; Birch-Hirschfeld 1875).

Whereas changes in form were frequently observed, no single bacterialspecies had actually been proven stable around 1860 (cf. Farley 1977,pp. 92–120).10 Speciecists had to rely on the messy criterion of morphol-ogy and in vain tried to describe a single species in what they called pureculture.11

Cholera FungiIn this situation, when physiological investigations of microbial lifeseemed to be more promising than taxonomic studies, a ªrst attempt wasmade to give a full explanation of the microbiology of infectious disease.Its proponent was the botanist Ernst Hallier (1831–1904), a nephew ofMatthias Schleiden, who like the latter spent most of his career at the uni-versity of Jena.12 Hallier’s theories and experiments were based on the phe-nomenon of pleomorphism, a heatedly discussed issue in those days.Ironically, it had been Anton De Bary, a proponent of speciecistic botany,who had initially applied the concept in a fairly technical manner, namelyto describe changing forms of some microscopic fungi (Jahn 1990,pp. 361–362). Polymorphism, however, could also be seen as a basic prop-erty of any organism and explained using something as ordinary as a po-tato:

If we would not know better, would we recognize the same creationin the nodule of a potato, in the long sprouts which it produces in acellar and in the plant with leaves and fruits? (Richter 1867,p. 89).13

Prominent scientists of the time like Lister or Huxley held pleo-morphism to be of fundamental importance (Bulloch [1938] 1960,


10. Even if Louis Pasteur was convinced that the fermentative processes that he was in-vestigating were controlled by speciªc micro-organisms, the liquid culture media that heemployed were less suited to investigate the issue and his reluctance with regard to the useof the microscope indicates small interest in the issue (Bulloch [1938] 1960, p. 187;Mendelsohn 1996, chapters II-III).

11. The term ‘pure culture’, which came to be applied to mass cultures of bacteria lateron, had a different meaning in those days: it meant the demonstration of the life cycle of adesirably single bacterium. The concept was pioneered by Oscar Brefeld (Bulloch [1938]1960, pp. 220–222).

12. On Hallier see Gradmann (2000a); Jahn (1966); Théodoridès (1972). On his mi-crobiology see Bulloch ([1938] 1960, pp. 190–191); in more detail see Löfºer (1887,pp. 75–85); Eidam (1872, pp. 165–71), which is rather critical, written by one of Cohn’sassistants.

13. “Wer würde, wenn er es nicht längst wüßte, in der Knolle der Kartoffel, in denlangen Keimausläufern, welche sie im Keller treibt, und in der blätter- u. früchtetragendenKartoffelpºanze ein u. dasselbe Geschöpf erkennen?”

p. 177) and Hallier took it to its extremes: He devised a system of chang-ing forms of microbial life that integrated an enormous mass of observa-tions (Hallier 1867b). It could be tested experimentally and contained ahighly elegant hypothesis on the aetiology of infectious diseases. ForHallier, polymorphism was a natural law governing microbial life: micro-scopic fungi, yeast, and moulds were not genera, but so called morphs, de-velopmental stages into which a basic fungal entity (Pilzwesen) wouldgrow under changing environmental conditions. A fairly restricted num-ber of these fungal entities and an equally restricted number of morphs re-sulted in what Hallier called morphic cycles (Formenkreise). These helpedto organize descriptions of a multitude of morphologically differentmicro-organisms.

Hallier’s morphic cycles combined knowledge about the manifoldforms of microbes with what was known about their living conditionssuch as reaction of cultures to acid or basic culture media, nutritive re-quirements of carbohydrates, nitrogen, oxygen, etc. The basic form of afungal entity that Hallier called granulous protoplasm would develop intoa mould-morph, if exposed to air, or into yeast, if isolated from it. Any re-sult varied according to the nutrition that was offered, there where numer-ous transitory forms, simultaneous appearance of different morphs waspossible, and any development was reversible (Hallier 1867b; cf. Richter1868, p. 103; Eidam 1872, pp. 165–71, who gives a critical assessment).Suitable experiments for such a theory consisted in exposing preparationsto a variety of environmental and nutritive conditions, thereby identifyingthe multitude of observed structures with one of the known fungal enti-ties, or discovering a new one. Of these entities Hallier claimed to haveidentiªed about twenty. The central concept of Hallier’s micro-biologycan be characterized by contrast to Pasteur’s: Whereas the presence of aspeciªc micro-organism would deªne the result of a fermentative processfor Pasteur, for Hallier it was the milieu that deªned into which morph afungal entity would develop.

Hallier had devised two speciªc experimental devices to test his theo-ries, one for isolation, the other for cultivation (see Figures 1 and 2). Theªrst one of these, visibly a variation on common technology of the time,14

remained unopened during the experiments and served to control the pro-cess of cultivation. The culturing apparatus instead was the experimentaldevice. The central ºask could be opened and allowed modiªcations suchas changes in the nutritive medium or the removal of material for micro-scopic inspection. Both apparatuses allowed for the supply of fresh air and


14. That is, the use of strong acids, ªlters made of cotton wool, etc. (Bulloch [1938]1960, chapter 4).

facilitated long periods of observation that could last for weeks. The iden-tity of the ªnal result in both apparatuses testiªed for an undisturbed ex-periment.

A series of such modiªcations and examinations would result in themorphic cycle of a fungal entity which would then be documented bydrawings. One such entity was for example the well known fungusPenicillium crustateum. (Figure 3 shows a selection of some of the close to 30


Figure 2. Cultivation apparatus (Hallier 1867b).

Figure 1. Isolation apparatus (Hallier 1867b).


Figure 3. A few morphs from the morphic cycle of Penicillium crustateum(Hallier 1867b).

different morphs that Hallier had identiªed in this case.) The experimen-tal strategy was dependent on a certain ingeniousness with regard to thechosen culture media. Thus, in the case of Penicillium crustateum asidesfrom a common culture medium like broth, less common ones like milk,blueberry juice, dog faeces, or dark beer (all of them sterilized by boiling),were used.

Based on his model and experimental strategy Hallier also did experi-ments on the aetiology of infectious diseases. Taking his departure fromdiseases of the skin he aimed at identifying the vegetation found in in-fected tissues with one of his fungal entities.15 In all the diseases thatHallier investigated it turned out that it was always a particular morphicstate of a given fungal entity which was present in the context of infec-tions, a peculiar form of yeast, small granules that Hallier called “mi-cro-coccus” (Hallier 1867b, pp. 76–91). This meant that Hallier’s theorycontained a very plausible model for proliferation and causation of dis-eases: outside of the human body a given fungal entity would appear as amould and spores accounted for the spread of diseases over distances.Given the changed environmental conditions inside the human body thesespores would then germinate pathogenic cocci which in turn, due to theirsmall size, could easily spread in tissues and vessels.

Hallier’s fame rose in the aftermath of the cholera-epidemic of 1866.16

In May 1867 he succeeded in cultivating a micrococcus from faeces andintestinal tissues of cholera-victims. This coccus could be identiªed as thepathogenic morph of a fungus called Urozystis cholerae, growing—asHallier claimed—on rice plants in India. Thus the pathogen of cholerahad been identiªed (Hallier 1867a). In the years around the discovery ofhis cholera-fungus, Hallier identiªed many other pathogenic fungi, pub-lished an enormous number of papers and books, issued his own journal(the “Archiv für Parasitenkunde”), and founded an institute for the pro-motion of his studies at the University of Jena.

It is illuminating to evaluate Hallier’s microbiology with regard to histreatment of issues of purity and contamination. What he aimed for was toprevent the investigative process from being contaminated. He sterilizedthe air inside his experimental apparatuses by the use of contemporarytechnology such as cotton wool or acids and demanded the use of sterilizedculture media. His two parallel apparatuses gave the opportunity to testwhether isolation in this sense had been achieved. However, he nowhereconsidered the issue of the composition of the material he used for cultiva-


15. For an overview see Richter (1868); cf. Löfºer (1887, pp. 81–82).16. On the cholera-epidemic see Evans (1987, pp. 260–261). On Hallier’s success see

Löfºer (1887, p. 82); cf. Gossel (2000, p. 85).

tion to be a problem. This may seem surprising, but was consistent withhis thinking. After all, what he aimed for was an experimental documen-tation of a transition of forms. The appearance of morphologically differ-ent structures at the same time was thus essential to his experimentalstrategy and biological theory, and certainly not a sign of contamination.

Nonsense and Penicillium glaucumAmongst physicians in particular, Hallier’s system seems to have enjoyedsome support initially (Löfºer 1887, pp. 82–85),17 whereas from botanyharsh criticism was raised quickly. It was Anton De Bary in particularwho, in a review of Hallier’s research, insisted that Hallier’s experimentswere full of technical errors which, once corrected, left his theory in ruins.For De Bary the morphic cycles did not document developments, whichHallier had in fact nowhere observed to happen. Instead they resultedfrom insufªcient laboratory technology, most of all from the initial pres-ence of different organisms in Hallier’s preparations, and insufªcientlysterile culture media. De Bary refuted Hallier’s research in detail and putparticular emphasis on the point that evidence of the process of transitionitself had nowhere been given. In fact, instead of proving a succession ofdifferent morphs of fungal entities, Hallier’s preparations just gave evi-dence of the simultaneous presence of entirely different organisms:

It is clear that the proof of one organism being a developmentalstage or a product of another one can only be attained by direct ob-servation of organic continuity, which has to be given between twodevelopmental stages or generations at some time; to put in a pop-ular way: by showing that and how A germinates from B after hav-ing established that A has not been intruding B earlier on. Neigh-boring existence or succession of two or more forms in the sameplace proves nothing with regard to the generic connection of or-ganisms. It is this kind of a proof of a connection of organisms[ . . . ] that is not even attempted in Hallier’s text (De Bary 1867,p. 244).18


17. Theodor Billroth remembered that he had been deeply inºuenced by Hallier whileworking on his bacteriological work on wound infections (Löfºer 1887, p 142). The threeoldest books in Robert Koch’s scientiªc library were actually by Hallier (Roudolf 1960,p. 448; cf. Gossel 2000, p. 85).

18. “Es ist klar, dass der Nachweis dafür, dass ein Organismus ein Entwick-lungszustand oder Entwicklungsprodukt eines anderen ist, sich nur liefern lässt, durch diedirecte Beobachtung der organischen Continuität, welche zwischen zwei Entwick-lungszuständen oder Generationen einer Spezies zu irgendeiner Zeit einmal bestehenmuss; Dadurch, um populär zu werden, dass und wie A aus B herauswächst, nachdem manfestgestellt hat, dass A nicht etwa vorher in B eingedrungen war. Geselliges Vorkommen

The critique was underpinned by a devastating analysis of Hallier’s chol-era-fungus. De Bary took a drawing of Urozystis cholerae, illustrating thecysts of the fungus containing micro-cocci ready to swarm, and describeda totally different development. What followed was not a dissemination ofcocci, but the germination of a well known fungus. Hallier’s ‘cocci’ turnedout to be fat granules and his cholera fungus was just a sprout of a wide-spread fungus called Urozystis occulta (See Figures 4 and 5). In this contextDe Bary reminded his readers of Hallier’s dilettante management of prep-arations. The material used in the experiments had in fact been a monthold when used for that purpose, and Hallier had never checked his experi-mental results against the pathological anatomy of cholera victims (DeBary 1867, p. 249).

De Bary’s critique culminated in the verdict that Hallier’s “tales of hischolera-fungus and his imaginations of forms and their development aretotally beyond any kind of science” (De Bary 1867, p. 251). It was indeedconspicuous that it had mostly been very common fungi that Hallier hadidentiªed as basic forms of his fungal entities. Thus what had appeared tobe a breakthrough in the beginning turned out to be a showcase of badlaboratory technology. Oscar Brefeld, a pupil of De Bary, coined the sati-rizing quote that “without pure cultures all you get is nonsense andPenicillium glaucum” (Quoted in Bulloch [1938] 1960, p. 192). He wasthereby not only mocking one of Hallier’s most popular fungi but draw-ing a lesson from the disaster by naming what he called pure culture as aremedy to prevent such errors in future. Around 1860 such a pure culturemeant to get around the problems of descriptive morphology by doingcultivation experiments, not with mass cultures as Koch would do it a fewyears later, but by demonstrating the generational cycle of—ideally—asingle germ. The technology was developed by Brefeld.19

De Bary’s critique was centered on Hallier’s botany. Notably, there wasless to complain about from a medical point of view. Even if Hallier hadnot supplied his model with knowledge from pathological anatomy, thepresence of vegetation in infected tissues was undeniable, and that he haddone no animal experiments could not be objected to within the frame-work of his theory: aetiology depended not on the presence of micro-organisms but on their morphic transitions. Thus, the presence or absenceof particular fungi inside a human body gave few clues on aetiologies. Thereliance of any aetiology on the morphic cycles meant that animal experi-


oder Aufeinanderfolge zweier oder mehrerer Formen an demselben Orte beweist für ihrgenetisches Zusammengehören nichts. [ . . . ] Von einer derartigen Nachweisung desgenetischen Zusammenhangs der Organismen [ . . . ] ªndet sich in der Hallier’schenSchrift nicht einmal ein Versuch.”

19. Bulloch ([1938] 1960, pp. 221–222). On Koch’s pure cultures see Schlich (1997).


Figure 4. Urocycstis cholerae (Hallier 1867a).

Figure 5. Seeds of Urocystis occulta (De Bary 1867).

ments could be expected to be too complicated, drawn out, and of a re-stricted value.

Impure BacteriologyHallier’s fungal entities enjoyed only a short career. However, the issuethat they could explain—the presence of manifold organic substances ininfected tissues—remained on the agenda and had still found no answer.Even if the disaster of Hallier’s theory increased the credibility of thework of speciecistic botanists, their position was far from being unani-mously accepted. On the contrary it seems that Hallier’s research lingeredon in much of the medical research that was to follow. This is mostobvious if we take a look at the piece de resistance of medical research intoinfections diseases around 1870, the aetiology of wound infections knownunder the names of septicaemia and pyaemia. It was in particular in thecontext of these diseases where Hallier’s coccus-structures undeniablypresent in masses.20 Even an outspoken critic of Hallier admitted “that heundoubtedly deserves substantial merit for having been the ªrst to subjectthe question of ferments and contagion to direct microscopic investiga-tions prolonged for years” (Cohn 1875a, p. 128; cf. Löfºer 1887,pp. 86–89).

Even without the context of his theory, many of Hallier’s observationsremained valid. His short-lived theory provided German pathologicalanatomy with the heritage of the indisputable presence of organic pollu-tion in infected tissues—an aspect which had attained a new importance.Alien material inside the human body, if it appeared in organic form,could be expected to be relevant for aetiology and pathogenesis: Whereasin the context of a mechanical theory of inºammation the role of alien ma-terial, such as a splinter, was usually thought to be merely occasional, thepresence of alien organic substances in inºamed tissues rendered a morefundamental causal connection possible. Alien material began to bespeciªed into a pathogen, and in 1872 the pathologist Felix VictorBirch-Hirschfeld noted that the vegetation present inside the human bodywas about to win a prominent place in pathology:

Whereas earlier communications on the presence of fungi inside theorganism were insufªcient with regard to pathology and anatomythis backlog has now been ªlled for a certain group of diseases.Who cares to inspect without prejudice the results achieved by em-inent scientists will hardly retain the opinion that in relation to


20. On inºammation and wound infections in the 1860/70’s see Bauer (1989,pp. 95–115); Diepgen (1953); Rather (1968).

those affections the presence of fungi inside the body is merely un-essential and accidental (Birch-Hirschfeld 1872, p. 107).21

Even if the numbers of microbes that could be seen under a microscopewas steadily increasing around 1870 their conceptual status for pathologywas still by no means agreed upon. The dramatic failure of Hallier’s theorydid not imply that other technology like pure cultures and theories likebacterial speciªcity were better suited. Nor was it clear that Hallier hadbeen entirely wrong and it is not surprising that in the research of theearly 1870s many of Hallier’s assumptions lingered on. A good examplefor this is Edwin Klebs’s study on the pathological anatomy of gun-shotwounds which was commonly regarded as a major contribution to the pa-thology of wound infections (Klebs 1872).22 In numerous dissections hehad done in a ªeld hospital during the Franco-Prussian war Klebs had reg-ularly identiªed micro-organisms in septic wounds: “they contained in al-most any case those lower organisms that one calls bacteria, monads, etc.”(Klebs 1872, p. 106). Morphologically his ªndings were highly diverseand Klebs gave a vivid description of the chaos that he encountered in hispreparations:

I found stick-like structures, so called bacteria, without movement,not seldom in a row so that threads made from longish links ap-peared. Further numerous micro-spores, extremely minute andshining structures, their diameter could be less than half a microm-eter. These could lie around free, isolated, and would in this caseshow oscillatory movements, they could also appear in groups(zoogloea formed) or in threads lined up like a rosary (Klebs 1872,p. 106).23


21. “Liess die Mehrzahl der früheren Mittheilungen über das Vorkommen von Pilzenim Organismus gerade in pathologisch-anatomischer Hinsicht viel zu wünschen übrig: soist für eine gewisse Gruppe von Krankheiten jetzt diesem Uebelstande abgeholfen. Wervorurtheilsfrei die Resultate dieser Beobachtungen anerkannter Forscher erwägt, der wirdschwerlich die Ueberzeugung gewinnen können, dass bei den betreffenden Affektionen diePilze nur als zufällige unwesentliche Elemente im Körper vorhanden waren.”

22. On Klebs’ work see Bulloch ([1938] 1960, p. 376); Köhler and Mochmann (1988);Stürzbecher (1977).

23. “Ich fand stäbchenartige Körper, sogenannte Bacterien, ohne Bewegung, nichtselten zu mehreren aneinander gereiht, so dass langgliedrige Fäden entstanden, fernerzahlreiche Microsporen, glänzende, ausserordentlich kleine Körperchen, derenDurchmesser höchstens die Hälfte eines Mikromillimeters betragen mag, die entwederfrei, vereinzelt lagen und dann oscillatorische Bewegungen machten, oder in Gruppenzusammenlagen (Zooglöaformen), oder zu rosenkranzartigen Fäden aneinander gereihtwaren.”

The interpretation that Klebs gave of these ªndings echoed Hallier’sideas. He took the morphologically different micro-organisms to be devel-opmental stages of a basic fungal being that germinated under the condi-tions given in wounds. The name that he chose, Microsporon septicum, indi-cates that he considered the microbiology inside wounds to be of apleomorphous nature. At the same time Klebs was determined that “theseparasitic organisms are the causes of the severe phenomena [septic infec-tions]” and that the nature of that causation was not mechanical, but—asKlebs put it—’physiological’. In other words: the symptoms of the diseasedepended on the biology of the pathogen.

Klebs’s claims were essentially based on pathological anatomy to whichcultivation experiments gave subsidiary evidence (Klebs 1878, p. 45).24 Inthese experiments he had used a method that he called “fraktionierte Kul-tur”: A desirably small quantity of material was picked by an elaborateprocedure, puriªed and applied to a liquid culture medium while sterilitywas observed in any of these steps. However, Klebs’s experiments sufferedfrom the same weakness as Hallier’s: Even if his precautions against pollu-tion during the experimental process were impressive, his preparationswere of heterogeneous character. This was not in itself problematic, if theMicrosporon septicum was a pleomorphous organism. A pathologist likeBirch-Hirschfeld, however, who favored Cohn’s micro-biology, restrictedhis praise for Klebs to pathological anatomy and doubted the value of hisculturing experiments:

If the expression ‘Microsporon septicum’ goes to say that Klebs re-gards the organisms that he has described and which are peculiar tosepticaemia as lower morphs of a certain fungal species, the very ex-istence of the latter one has to be proven in the ªrst place(Birch-Hirschfeld 1872, p. 108).25

Another clear echo of Hallier’s theories was to be found in TheodorBillroth’s studies on the microbiology of wound infections, which he pub-lished from 1874 on (Billroth 1874).26 He identiªed a group of bacteria


24. Klebs held that aetiology could usually be established on the level of pathologicalanatomy. Only in cases of inconclusive evidence cultivation of bacteria and animal experi-ments had to be done. Klebs ideas on this issue are an important source of Koch’s postu-lates (Carter 1987, pp. 84–86).

25. “Soll aber mit dem Ausdruck ‘Micosporon septicum’ bezeichnet sein, dass Klebsdie von ihm beschriebenen, der Septicämie eigentümlichen Organismen für niedereMorphen einer bestimmten Pilzspezies halte: so wäre eben die Existenz dieser erstnachzuweisen”. The praise for Klebs descriptions of pathological anatomy was widespread:Bulloch ([1938] 1960, pp. 146–147); Diepgen (1953, p. 83).

26. For a overview of Billroth’s research see Löfºer (1887, pp. 142–150).

that differed in morphology and constellation. He held these to bepleomorphous appearances of a fungus and chose the name Coccobacteriaseptica. Whereas Klebs had maintained that his vegetation caused thepathological symptoms, Billroth insisted that they were instead an effectof septic infections. The peculiar conditions inside inºamed wounds facili-tated the growth of various forms of micro-organisms that could alsobe found in healthy tissues in very small numbers. Depending on the situ-ation given they could appear in diverse constellations to which Billrothgave names, which sound familiar to the modern observer: Mono-, Diplo-,Strepto-, Staphylococcus, etc. For Billroth the problems that Cohn,Brefeld, and others had encountered in producing pure cultures wereless of a technical than of a principal sort: Success, if achieved, indicatednot the stability of species but of experimental conditions—pure cultureswere in fact artifacts! On Cohn’s system of bacteria and the group ofpathogenic cocco-bacteria that it contained Billroth gave an ironic com-ment:

Cohn has made his reverence to the physicians by establishing a ge-nus ‘pathogenic cocco-bacteria’ and has added the ‘Bacillusanthracis’ from the genus bacilli to these. I call this a concession tothe spirit of the modern age. [ . . . ] I do not ªnd any substantialmorphological differences between the manifold forms of vegeta-tion of what is called septogenic and pathogenic cocci and bacteria.Whether differences with regard to their chemical effects exist isever more uncertain.” (Billroth, quoted in Löfºer 1887, p. 148).27

Positions like Billroth’s explain why even the whole set of innovative cul-turing techniques that Cohn and his collaborators had developed in theprevious years did not really convince those who mistrusted their conceptas such. For example the differentiation of morphologically identical bac-teria by testing their chromatogenic properties was only suited to stabilizebacterial species if such properties were constant.28 Since, however, nobodyin the early 1870s had succeeded to produce what was called a pure cul-ture of a bacterium that is to demonstrate a full generational cycle of a


27. “Die von Cohn mit liebenswürdigen Pietät gegen die Ärzte aufgestellte Gattung‘Pathogene Kugelbacterien’ mit vier Arten, zu denen noch ein Art ‘Bacillus antracis’ ausder Gattung Bacillus hinzukommt, halte ich nur für das Resultat einer Conzession an diemoderne Zeitströmung. [ . . . ] ich ªnde gar keine wesentlichen morphologischenDifferenzen zwischen den mannigfaltigen Vegetationsformen der sogenannten septogenenund pathogenen Coccos und Bacterien. Ob Differenzen in den chemischen Wirkungenexistieren, weiss man noch viel weniger.”

28. Work on the issue was done by Cohn’s collaborator Joseph Schröter (Schroeter1870). Cf. Bulloch ([1938] 1960, p. 220).

—desirably—single bacterium, the speciecistic claims were in need of val-idation even for those who adhered to them.

AetiologyIf we compare the situation of the mid-seventies with the one that wasgiven when Hallier published his results a decade earlier, things had cer-tainly changed: In Halliers work it was ªrst of all pathological anatomythat had been missing. Looking at Klebs, Billroth’s and other studies pub-lished in the period,29 it now seemed as if despite strong evidence from pa-thology microbiological research appeared to be inconclusive. Even if mi-crobes were now regularly identiªed in connection with many infectiousdiseases, it seemed quite impossible to negotiate their multiple formswith known disease entities in a satisfying way.

The microscopic picture of diseased tissues had been rapidly crowdingwith microbial life. The relevance of these microbes for aetiology andpathogenesis, however, could only be suspected. Even Birch-Hischfeld,who was certainly aiming at medical bacteriology, admitted that the in-crease in information had so far mostly produced chaos. On the example ofwound infections he noted in 1875 that “with regard to the relevance oflower organisms for the origin of septicaemia or pyaemia researchers havecarried their contradictions to a point where not a single fact appears tobe an undisputed gain.” He continued that “for those in search of thetruth this is a confession of a depressing sort” (Birch-Hirschfeld 1875,p. 198).

With regard to the questions discussed in this text, it is important tonote that issues of contamination, isolation, and pure cultures were notonly disputed in their factual content, but actually denied in their rele-vance by some: Edwin Klebs was convinced that even on the basis of a pro-visional knowledge of his Microsporon septicum the problem of the aetiologyof wound infections had been settled deªnitively. Just like Hallier orBillroth he was convinced that the localized character of the pathologicalsymptoms indicated a connection of those alien organic structures thatcould be identiªed in infected tissues. Morphological variety among thosestructures was not taken to be a decisive argument against such aetiolo-gies. Pure cultures that Cohn and other botanists demanded were seen as akind of an unworldly botanists’ sport, impractical for pathology.30


29. For an overview see Birch-Hirschfeld (1875).30. Even Robert Koch, certainly a propagator of Cohn’s botany, stated in 1878 that

aetiological questions could hardly wait “until the botanists have succeeded to differentiatebacterial species by pure cultures and cultivation from spore to spore” (Koch [1878] 1912,p. 102).

It was only in 1874 that the medical discussions picked up on the re-cent botanical research and came to realize that mono- and polymorphismhad to be seen as opposing concepts and—what turned out to be essen-tial—that the operational value of these two for medicine differed sharply.It was at about this time when the argument was raised that variable mi-cro-organisms appeared to be very unlikely candidates indeed as causativeagents of disease—in this case another, so far totally unknown factorwould be decisive. If, however, micro-organisms could be sorted into con-stant biological species their aetiological role appeared very plausible. Theproblems one would encounter by following the latter line of argumentcould be expected to be of a merely technical nature: to improve one’stechnical skills to a point where ªxed species could be detected in the sofar indistinguishable masses of cocci. It was Germany’s leading patholo-gist, Rudolf Virchow, who, in a public speech, gave the up-to-datedeªnition of the problem:

To me it seems without doubt that [ . . . ] only two interpretationsare possible. Either the micro-organisms of all infectious diseasesnamed so far are identical. In this case [ . . . ] we are referred topeculiar toxic substances that have to be present besides fungi or al-gae. Or these micro-organisms, despite their apparent identity, aredifferent and are the vehicles and agents of the most dangerous pro-cesses in the body, they are the essential causes of disease. To me, athird [point of view] seems impossible (Virchow 1874, p. 28).31

Putting it that way was, of course, suited to support the position of spe-ciecists like Cohn or Birch-Hirschfeld. It is therefore not really surprisingthat Virchow pursued his argument by adopting one of Cohn’s central hy-potheses, namely that biological properties of bacterial species were just asconstant as their morphology and that the ability to cause diseases was oneof these:

If identical structures have totally different effects they have to bedifferent internally. [ . . . ] If it is shown by some inoculation or bypathological incident that some bacteria, which are identical tothose of ordinary putrid infusions, produce anthrax, whereas bacte-


31. “Es scheint mir unzweifelhaft, dass [ . . . ] nur zweierlei Deutungen möglich sind.Entweder sind die Mikroorganismen aller genannten Infektionskrankheiten identisch, unddann wird man [ . . . ] auf besondere giftige Substanzen hingewiesen, welche noch nebenden Pilzen oder Algen vorhanden sein müssen. Oder die Mikroorganismen sind trotz ihreranscheinenden Übereinstimmung verschieden und bilden die Träger und Erreger dergefährlichsten Vorgänge im Körper, sie sind die eigentlichen Krankheitsursachen. EinDrittes scheint mir nicht möglich.”

ria of ordinary putrid infusion fail to do so, we have to concludethat the bacteria of anthrax and those of infusions are as different ashemlock and parsley (Virchow 1874, pp. 33–34).32

Thus, Virchow’s objection to the studies of Billroth, Klebs and others wasnot only that he denied the factual basis, but that such knowledge was im-practical. No medical action could follow from it. If someone was askingfor bacteria to be relevant for aetiology and pathogenesis of infectious dis-eases he had to presuppose that those micro-organisms could be dividedinto constant species, even if the opposite was apparent. To establish sucha stability of bacterial species required the use of the technology that Cohnand his school had devised: solid culture media, pure cultures, isolation,staining etc.

Medical BacteriologyIt comes as no surprise that Robert Koch in his “Studies on Wound Infec-tions” of 1878 gave an almost literal quote of Virchow’s statement (Koch[1878] 1912, p. 75). Koch’s work was based on Cohn’s micro-biologywhich he attempted to make useful for medicine. The practical task ofKoch’s studies on wound infections was to differentiate bacteria that ap-peared similar or hard to distinguish at the basis of morphology. The tech-nological ªxes that enabled Koch to successfully pursue this aim are notpart of our investigation, but what he succeeded in indicates the endof our story about the ‘messy and polluted’ medical bacteriology ofthe 1860s and 1870s: The manifold vegetation that Hallier, Klebs, Bill-roth and others had been investigating was about to disappear as an objectof inquiry. What remained was an initially small number of distinctand stable bacterial species that coincided with no less distinct patholo-gies.

We can conclude that on the way to medical bacteriology notions likepurity, stability, isolation, etc., which appear to be quite essential to us, re-mained fairly unimportant for a long time. What the process originatedfrom was not the question if bacteria cause diseases, but the discovery ofapparently polymorphous organic pollution in infected tissues. Initially it


32. “Bringen dieselben Formen ganz verschiedene Wirkungen hervor, so müssen sieinnerlich verschieden sein. [ . . . ] Ergiebt sich daher durch eine Impfung oder durch denpathologischen Zufall, dass durch Bakterien, welche denen gewöhnlicher faulenderInfusionen völlig gleichen, Milzbrand entsteht, während die Bakterien der gewöhnlichenInfusionen ihn nicht erzeugen, so werden wir immer schließen müssen, dass die Bakteriendes Milzbrandes von Bakterien der Infusion so verschieden sein müssen, wie Schierling vonPetersilie.”

seemed more interesting to explain conditions of growth as a physiologi-cal process of this vegetation than to sort it into species. With regard topathology, the localized character of the pathological symptoms seemed totestify to the identity of the vegetation present in it. It was dissatisfactionwith the results achieved that changed the agenda and in a second step theintroduction of notions of purity and speciªcity lead to a puriªcation ofthese masses and the creation of the idea of a speciªc, monomorphous,bacterial pathogen.

If we compare this intense discussion from 1865 to 1875, which wehave followed on the previous pages, with the knowledge about pathogensthat could be found in the works of Schwann, Bassi, Henle and other au-thors of the earlier nineteenth century,33 the road to medical bacteriologyappears to be a remarkable detour. It was with micro-biology like ErnstHallier’s that the infected macro- and the infecting micro-organism en-tered pathology in the 1860s. Criticizing Hallier essentially meant to re-place his extended, drawn out and complicated ideas with much morereductionist models. In this way most of the micro-life that Hallier orKlebs thought to be essential for infectious diseases came to be regarded asa contamination, not to the body but to a medical understanding of infec-tious diseases that was based on some speciªc bacteria while others becamewaste.34

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Isolation, Contamination, and Pure Culture: Monomorphism and Polymorphism of Pathogenic Micro-Organisms as Research Problem 1860-1880

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