olga amsterdamska - waseda universitysince the late nineteenth century, the study of microorganisms...

P1: JYD9780521572019c17 CUUS457/Bowler 978 0 521 57201 9 January 6, 2009 0:21

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MICROBIOLOGY

Olga Amsterdamska

The only constant characteristics of a research area that we can, anachronis-tically, describe as microbiology might be the minute size of the organismsit studies and its reliance on instruments and a set of techniques that allowus to see beyond the range of what is visible to the naked eye. Stability orcontinuity are difficult to find elsewhere – either in the range and classifica-tion of microorganisms, in the types of questions asked about them, in thetheoretical or practical goals of research, in the institutions in which investi-gations were conducted, or in the composition of the group of scientists towhom these microscopic organisms were of interest.

The range of organisms encompassed by these investigations has changedmany times during the last two centuries. Relatively undifferentiated infu-soria gave place to protists and schizomycetes, and later to protozoa, bacte-ria, fungi, and algae; the invisible filterable viruses, obligate parasites, andlytic principles appeared only temporarily, to be replaced by rickettsia andviruses. These microorganisms were investigated by a heterogeneous assem-bly of amateurs, botanists, zoologists, biologists, pathologists, biochemists,geneticists, medical doctors, sanitary engineers, agricultural scientists, veteri-narians, public health investigators, biotechnologists, and so on. Specialismsand disciplines devoted to specific groups of microorganisms – bacteriol-ogy, virology, protozoology, and mycology – have disparate though oftenoverlapping institutional and intellectual histories, and although the term“microbiology” dates from the last decades of the nineteenth century, it didnot come to designate a discipline that could claim its own sphere of concernuntil after the Second World War. Even then, the discipline remained bothintellectually and institutionally heterogeneous.

Since the late nineteenth century, the study of microorganisms has beendominated by practical concerns such as the protection of public healthand the struggle against human or animal disease, or the production ofwine, beer, foodstuffs, or industrial chemicals. Today, genetic manipulationof microorganisms plays an important role in biotechnological innovations.

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Microbiological research also played a pivotal role in many fundamentaltheoretical controversies within biology – in the debates on spontaneous gen-eration, cell theory, the nature of life, classification, speciation, heredity andits mechanisms, and others – and in some of its more revolutionary tran-sitions, such as those from descriptive, morphological, or “natural history”styles of research to experimental biology, or in the development of generalbiochemistry and, later, molecular biology.

Microorganisms were only rarely studied for their own sake. As the small-est living creatures, they were expected to yield a critical understanding ofmacroscopic life. They provided a limit – as the simplest organisms, themost bountiful and ingenious ones, the earliest and most primitive, the mostadaptable, the most varied and changeable, the most quickly reproducing, orthe easiest to transform – against which a variety of general biological claimswere tested. As organisms responsible for various fermentations, microor-ganisms could be used to probe and manipulate the production of manyfoodstuffs and chemicals, but also to study general biochemistry. As littlemetabolic factories, they could be harnessed – and today also changed andmanipulated – to produce useful substances. When regarded as pathogens,their study promised a means to understand and control human, animal, orplant disease. In genetic or biochemical research, microorganisms were likelyto be used as laboratory tools or instruments and to provide insight intometabolic pathways or mechanisms of hereditary transmission.

Given this variety of contexts and concerns, it is difficult to write a historyof microbiology that does justice to both the intellectual and institutionalcomplexity of the field’s development.1 In the discussion here, an attempt ismade to emphasize the changing interactions between studies of microorgan-isms conducted in different intellectual and institutional contexts, betweenresearch in which microorganisms were used as tools and research that focusedon microbes as distinct organisms, and between studies that aim to answerbasic biological questions and those devoted to the practical applications ofmicrobiological knowledge.

SPECIATION, CLASSIFICATION, AND THE INFUSORIA

Throughout the eighteenth century, microorganisms were difficult to see andeven harder to understand. The use of microscopes – especially of single-lens

1 All existing general histories of microbiology (and bacteriology) are by now fairly dated, but themost comprehensive ones are Hubert A. Lechevalier and Morris Solotorovsky, Three Centuries ofMicrobiology (New York: McGraw-Hill, 1965), and Patrick Collard, The Development of Microbiology(Cambridge: Cambridge University Press, 1976). The history of medical bacteriology until WorldWar II is discussed in William Bulloch, The History of Bacteriology (Oxford: Oxford University Press,1938), and W. D. Foster, The History of Medical Bacteriology and Immunology (London: Heinemann,1970).



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instruments – required a substantial degree of skill and patience, while theimages produced by compound microscopes were often blurred, with eachobject surrounded by a fringe of colors. Working with microscopes that pro-duced as much doubt as conviction, and without a framework into which tofit their observations of the “infusoria” – as microscopic organisms have beencalled since the 1760s – only a few eighteenth-century naturalists attemptedmore than detailed descriptions of the individual miniscule creatures firstobserved by the Dutch draper Antoni van Leeuwenhoek (1632–1723). CarlLinnaeus himself placed all microorganisms in an order “Vermes” in a classhe referred to as “Chaos.”

In the course of the nineteenth century, however, studies of microorgan-isms became more important, and disputes about them came to reflect anumber of interrelated controversies in biology. After the 1820s, new achro-matic microscopes became available, increasing both the magnification andthe sharpness of the images. But the steadily increasing ability to differentiatethe organization of the various microorganisms and to see infusoria that hadpreviously been invisible did not settle the existing disagreements amongexperts. Learning to prepare the specimens and to see through a microscopewas a complex process, and it often generated new foci of opposition andcontroversy among the microscopists.

One such controversy surrounded the theories of the German naturalistChristian Gottfried Ehrenberg (1795–1876), whose classification of infuso-ria was an elaboration and extension of an eighteenth-century classificationof the Danish naturalist Otto Friedrich Muller (1730–1784). In Die Infu-sionsthierchen als vollkommene Organismen (1838), Ehrenberg described andclassified hundreds of microorganisms and attempted to show that despitethe great variety of their forms, all infusoria had a full set of organ systemsand functions. Ehrenberg particularly emphasized the ubiquity and com-plexity of their digestive system, which his new achromatic microscopesallowed him to see.2 In 1841, this “polygastric theory” of infusoria wasvehemently criticized by the French zoologist Felix Dujardin (1801–1860).Although Dujardin used an admittedly inferior microscope, he concludedthat Ehrenberg “has yielded too easily to the rapture of his imagination.”3

The disagreements between Ehrenberg and Dujardin were related less to thedifferences between what they could or could not see through their respectivemicroscopes than to their more general beliefs about the nature of the organicworld.

Questions of general biological interest – how, if at all, infusoria were to beclassified, the nature of their morphological structure, how they develop and

2 Frederick B. Churchill, “The Guts of the Matter – Infusoria from Ehrenberg to Butschli: 1838–1876,”Journal of the History of Biology, 22 (1989), 189–213.

3 John Farley, The Spontaneous Generation Controversy from Descartes to Oparin (Baltimore: JohnsHopkins University Press, 1974), p. 55.



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evolve, and how they fit into the rest of the plant and animal world – werethe basis of botanists’ and zoologists’ interest in microorganisms from the1840s through the 1870s. In 1845, Karl Theodore von Siebold (1804–1885), azoologist at the University of Freiburg, reclassified the infusoria by drawinga distinction between bacteria and other microorganisms, which he calledprotozoa. A proponent of the cell theory, he removed bacteria to the plantkingdom (because their motions were involuntary rather than directed) andinstalled “unicellular” microorganisms as the simplest forms of organismsboth in the plant and in the animal kingdoms. The precise relevance ofthe cell theory and of evolutionary theory to the understanding of protozoacontinued to be debated in the work of zoologists such as Friedrich Stein,Ernst Haeckel, and Otto Butschli.4

Concerns about classification and the nature of life were also central inthe disputes between the botanist Carl von Nageli (1817–1891), professor atZurich and then Munich, and his Breslau counterpart Ferdinand Cohn (1828–1898). At a philosophical level, this dispute opposed materialist and mechanistbiologists, who believed in some form of evolutionary transformation ofspecies and emphasized the unity of laws governing both inanimate andanimate nature, against others who argued for the unique character of life,strict natural classifications, and division among and fixity of species. PaulineMazumdar describes this controversy as the long-standing debate between“the Unitarians” and “the Linnaeans,” with von Nageli representing the firstgroup and Cohn the second. Von Nageli not only developed his own theory ofevolution and claimed the possibility of spontaneous generation, but he alsobelieved that bacteria (or schizomycetes, as he called them) are pleomorphic –subject to a variety of transformations – so that it makes little sense todivide them into species. Ferdinand Cohn, in contrast, spent much of his lifecataloging and classifying the variety and distinctiveness of bacterial species.Although initially not anti-Darwinian, Cohn basically was not interested inevolutionary ideas and emphasized the fixity and stability of the species heidentified. As opposed to von Nageli, Cohn saw no need for spontaneousgeneration. These debates between Cohn and von Nageli were also of centralimportance in the bacteriological revolution.5

In the context of German academic botany, the differences between vonNageli and Cohn appeared primarily as issues in the philosophy of biology.Because they concerned such fundamental questions as the nature of lifeand its evolution, the debates often also had religious and political compo-nents. Gerald Geison has argued that such fundamental philosophical issues(linked to religious and political views), rather than the more immediate and

4 Natasha X. Jacobs, “From Unit to Unity: Protozoology, Cell Theory, and the New Concept of Life,”Journal of the History of Biology, 22 (1989), 215–42.

5 Pauline M. H. Mazumdar, Species and Specificity: An Interpretation of the History of Immunology(Cambridge: Cambridge University Press, 1995), pp. 15–67.




pragmatic concerns, were centrally important in the initiation of microbio-logical research by Louis Pasteur.6

WINE, LIFE, AND POLITICS: PASTEUR’S STUDIESOF FERMENTATION

Louis Pasteur (1822–1895), a chemist by training, turned to the study ofmicroorganisms in the 1850s when he became interested in processes of fer-mentation.7 According to the traditional account, Pasteur’s initial interest inthe study of alcoholic fermentations was aroused when he was approachedby the Lille industrialist Mourier Bigo, who was experiencing difficultieswith the production of alcohol from beets. Geison has questioned the sig-nificance of this practical incentive for the change in Pasteur’s research focusby pointing to the continuities between Pasteur’s chemical studies and hisearly microbiological work, both of which reflect his abiding interest in thedistinction between life and nonliving matter.

Pasteur was not the first scientist to argue that fermentation was a result ofthe vital activities of living vegetable matter (yeast). Such arguments had beenmade since the late 1830s by scientists such as Charles Cagniard de Latour(1777–1859), Theodor Schwann (1810–1882), and Friedrich Kutzing (1807–1893). But Justus von Liebig (1803–1873), the preeminent organic chemist,regarded fermentation as an act of chemical decomposition analogous to thedigestion of food by pepsin, and he ridiculed the idea that live microorganismsare involved in the process. (Pasteur’s conclusions were later modified byEdouard Buchner (1860–1907), who demonstrated in 1897 that fermentationcan be accomplished by a cell-free extract from yeast that he called “zymase”).8

Pasteur identified yeast “globules” as living organisms necessary for fer-mentation to take place, and he demonstrated that they could grow andmultiply in the absence of free oxygen, and that each specific type of fermen-tation (lactic, alcoholic, acetic, butyric, etc.) was caused by a characteristicliving ferment. Defining fermentation as “life without air,” Pasteur empha-sized the importance of the process of fermentation and putrefaction in thegeneral “economy of nature.”9

6 Gerald L. Geison, The Private Science of Louis Pasteur (Princeton, N.J.: Princeton University Press,1995).

7 The literature on Pasteur is voluminous. See, among others, Rene Dubos, Louis Pasteur: Free Lanceof Science (Boston: Little, Brown, 1950); Emile Duclaux, Pasteur: The History of a Mind, trans. ErwinF. Smith and Florence Hedges (Philadelphia: Saunders, 1920); Rene Valery-Radot, La vie de Pasteur,2 vols. (Paris: Flammarion, 1900); Claire Salomon-Bayet, ed., Pasteur et la revolution pastorienne (Paris:Payot, 1986); Geison, Private Science of Louis Pasteur; Gerald L. Geison, “Louis Pasteur,” Dictionaryof Scientific Biography, vol. 10, 350–416.

8 On Buchner’s discovery and its implications, see Robert E. Kohler, “The Background to EdouardBuchner’s Discovery of Cell-Free Fermentation,” Journal of the History of Biology, 4 (1971), 35–61.

9 James Bryant Conant, “Pasteur’s Study of Fermentation,” in Harvard Case Histories in ExperimentalScience (Cambridge, Mass.: Harvard University Press, 1957), vol. 2, pp. 437–85.



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Pasteur’s work on fermentation permanently shifted his own researchtoward the study of microorganisms. He showed that the “infinitely small”organisms are not only biologically interesting but also of practical impor-tance in human activities (as in the production of wine, beer, vinegar, andcheese) and that the scientific study of microbes can be used to address bothpractical problems and biological quandaries. Pasteur’s attempts to contributeto the solution of practical problems in the agricultural-industrial world ofnineteenth-century France initiated a long tradition of industrially, and latermore specifically biochemically, oriented studies of the metabolic processesperformed by microorganisms.

The role of microbes in fermentation also offered a compelling analogy forthe study of human and animal disease at a time when diseases were often seenas kinds of fermentation or putrefaction. The demonstration that differentmicrobial organisms were involved in different types of fermentation helpedto establish a notion of specificity that later played an important role in thedebates on the germ theory of disease. Finally, in the course of his research onfermentation, Pasteur developed a number of procedures and techniques forthe isolation and purification of microbes that were to prove central in laterresearch. This experimental manipulation of microbial organisms moved thestudy of microorganisms away from natural-historical observation and intothe forefront of experimental biology.

The difference between life and inanimate nature, and the associated philo-sophical, religious, and political issues, also figured in Pasteur’s debate withFelix Archimede Pouchet (1800–1872) on spontaneous generation.

Debates about spontaneous generation punctuated nineteenth-centurybiology. As John Farley has argued, all these debates – whether oppos-ing Georges Cuvier and Etienne Geoffroy Saint-Hilaire to Jean-BaptisteLamarck, or the Naturphilosophen to the Physicalists, or H. Charlton Bastianto John Tyndall – were religious and political as well as biological, thoughtheir significance changed in the course of the century and was differentin the different countries. In Germany, the idea of spontaneous generationwas associated with the Naturphilosophen who posited a unifying vital forcesuffusing all of nature. When, in the mid-nineteenth century, the vitalismof the Naturphilosophen was rejected by physicalists such as Hermann vonHelmholtz, Emil du Bois Raymond, Carl Ludwig, and Ernst Brucke, theidea of spontaneous generation lost popularity, only to be invoked again bythe materialist and unitarian evolutionists (e.g., Ernst Haeckel) who believedspontaneous generation to be a prerequisite for a fully materialist explanationof life. In France, the view that organisms (or their precursors) can developspontaneously, from either organic or inorganic materials, had been associ-ated with materialist evolutionary philosophies of nature at the beginningof the nineteenth century, and, by extension, it also came to be associatedwith antireligious and republican views. Thus, the doctrine of spontaneousgeneration was linked with political ideas, materialism, and atheism, forces




from which Pasteur – a lifelong defender of the forces of order – might havewished to dissociate himself. At the same time, Pasteur’s opposition to spon-taneous generation was directly related to his theory of fermentation. Notonly was heterogenesis “politically suspect,” but it also failed to accord withPasteur’s insistence that microorganisms are the cause (and not the result) offermentation, or with his notion of microbial specificity, which rested on abelief that “like begets like.”10

Much has been written about the ingenuity and, recently, about the log-ical insufficiency and circularity of Pasteur’s experiments designed to showthat microbial life is generated not from the interaction between organicmatter and air (or oxygen) but from the germination and reproduction ofmicroorganisms always present in the air or contaminating the experimentalapparatus (e.g., the mercury bath of Pouchet). Thus, some historians havecelebrated the inventiveness of Pasteur’s swan-necked retorts (which allowedair but not microorganisms to enter the vessels in which various fluids werekept sterile), the discipline of his experimental procedures, and the logicalrigor of his demonstrations, all of which enabled him to show that germssuspended in the air, and not some invisible “vital” forces, were responsi-ble for the introduction of microscopic life into organic infusions.11 Otherhistorians dispute the decisive nature of these experiments by showing thatPasteur never replicated Pouchet’s experiments exactly, and that the precon-ceived ideas of Pasteur and his allies were more important than experimentalevidence. They argue that Pasteur, like other critics of spontaneous genera-tion, could never prove that spontaneous generation is impossible; at best,he could show only that individual experiments purporting to prove thephenomenon were flawed. In his attempts to disprove spontaneous gener-ation, Pasteur in effect is alleged to have presupposed its impossibility andused it as a criterion for evaluating the success or failure of individual exper-iments.12 Based as they are on two opposing philosophies of science, thesetwo kinds of accounts cannot be fully reconciled. But the impossibility ofachieving absolute “logical” sufficiency in an experimental demonstration isno warrant for according it a subordinate “historical” role in the creation ofscientific consensus, or for reducing Pasteur’s experimental skill to that of a“prestidigitator who could produce the desired results ‘at will.’”13

10 Farley, Spontaneous Generation Controversy from Descartes to Oparin; John Farley and Gerald L.Geison, “Science, Politics and Spontaneous Generation in Nineteenth Century France: The Pasteur-Pouchet Debate,” Bulletin of the History of Medicine, 48 (1974), 161–98; Geison, Private Science ofLouis Pasteur, chap. 5, pp. 110–42; Glenn Vandervliet, Microbiology and the Spontaneous GenerationDebate during the 1870’s (Lawrence, Kans.: Coronado Press, 1971).

11 See, for example, N. Roll-Hansen, “Experimental Method and Spontaneous Generation: The Con-troversy between Pasteur and Pouchet, 1859–64,” Journal of the History of Medicine and Allied Sciences,34 (1979), 273–92.

12 Farley, Spontaneous Generation Controversy from Descartes to Oparin; Geison, Private Science of LouisPasteur.

13 Geison, Private Science of Louis Pasteur, p. 133. See also Bruno Latour, “Le theatre de la preuve,” inSalamon-Bayet, Pasteur et la revolution pastorienne, pp. 335–84.



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Pasteur’s demonstrations ended the debates about spontaneous genera-tion in France in the 1860s, but such debates continued elsewhere until the1880s. The rejection of the possibility of spontaneous generation, just likethe principle of specificity established in fermentation studies and throughthe classification studies of Ferdinand Cohn, created a biological contextin which what we now consider “the bacteriological revolution” could takeplace.

THE BACTERIOLOGICAL REVOLUTION

Although the “bacteriological revolution” is most commonly associated withthe work of Louis Pasteur, Robert Koch (1843–1910), and Joseph Lister (1827–1912), it was a complicated and lengthy process that involved changes inideas of disease causation and specificity,14 a new biological understanding ofmicroorganisms, and radical innovations in the manner in which microor-ganisms (and diseases) were to be studied in the laboratory. Even if the con-fluence of innovations in these three areas is most clearly found in the workof Pasteur and Koch, various elements were being articulated by a numberof researchers from the middle of the century.

What is today understood as “the” germ theory of disease – the notionthat specific microorganisms cause specific diseases – was far from a singleunified theory. A variety of such theories of infection and contagion werebeing articulated by scientists as well as practicing physicians, veterinarians,and epidemiologists in the middle decades of the nineteenth century.15 Thegerm theory was also formulated differently by the Pastorians and by the“German school” of Robert Koch. Andrew Mendelsohn has argued thatPasteur’s contribution to medicine was driven by a distinct set of beliefsabout the nature of life and the place of microbes in the general economyof nature, including their role in disease. Pasteur, who had studied beneficialuses of microbes in the agricultural industries of France, saw microbial lifein more physiological and ecological terms, as more pliable and subject toenvironmental modification. Koch, a physician who had served in the Franco-Prussian War and later surrounded himself with other army doctors, had astrictly medical – and, one might say, almost military – view of bacteria

14 K. Codell Carter, “The Development of Pasteur’s Concept of Disease Causation and the Emergenceof Specific Causes in Nineteenth Century Medicine,” Bulletin of the History of Medicine, 65 (1991),528–48.

15 The history of these theories in the United Kingdom is traced in Michael Worboys, SpreadingGerms: Disease Theories and Medical Practice in Britain, 1865–1900 (Cambridge: Cambridge UniversityPress, 2000). See also Nancy J. Tomes and John Harley Warner, “Introduction to Special Issue onRethinking the Reception of the Germ Theory of Disease: Comparative Perspectives,” Journal of theHistory of Medicine and Allied Sciences, 52 (1997), 7–16; Christopher Lawrence and Richard Dixey,“Practicing on Principle: Joseph Lister and the Germ Theories of Disease,” in Medical Theory, SurgicalPractice: Studies in the History of Surgery, ed. Christopher Lawrence (London: Routledge, 1992),pp. 153–215.




as deadly invaders to be eradicated.16 These differences clearly affected theways in which their respective research programs developed. Pasteur quicklyturned his attention to attenuation of virulence and immunity, while Kochidentified the invisible enemies in all nooks and crannies in order to directtheir eradication. Nevertheless, the two founders of medical bacteriology didshare a belief that infectious diseases were specific entities and that specific(though, according to Pasteur, physiologically complex and environmentallylabile) microorganisms were causally implicated in their origin and spread.

By the mid-nineteenth century, clinical and pathological studies had ledto the delineation of individual specific diseases such as typhus and typhoid,tuberculosis, and diphtheria. But the differentiation of diseases in terms oftheir pathology or symptomatology was quite separate from either the etio-logical classification of diseases in terms of their causes or the epidemiologicalgrouping of diseases into classes that originated from similar sources or spreadin a similar manner. Thus, while the specific identity of many individual dis-eases had been elaborated prior to (and independently of ) their associationwith specific microorganisms, they were not seen as belonging to a singleclass, nor were they all believed to result from a unique set of causes.17 In themid-nineteenth century, theories of how the contagious and/or miasmaticdiseases are transmitted often involved the invocation of some particulate,usually organic and occasionally even living, matter (variously described as apoison, a germ of disease, a microzyme, a fungus, a bacillus, or a vibrio) thatwas either generated in particular locations (for example, from decomposingorganic matter), transmitted directly from person to person, or passed onindirectly via water or “fomites.” Many of the contagious diseases were seenas forms of putrefaction and fermentation, and given the popularity of thechemical theory of fermentation, the pathological process was believed tobe initiated by some chemical change affecting organic matter that made it“zymotic” and allowed for the transmission of its fermentative abilities tonew sufferers.18 This analogy between disease process and fermentation hadled Pasteur to claim already in 1859, before he actually turned his attentionto the study of infectious diseases, that contagious diseases are likely “to owe

16 John Andrew Mendelsohn, “Cultures of Bacteriology: Formation and Transformation of a Sciencein France and Germany, 1870–1914” (PhD diss., Princeton University, 1996); K. Codell Carter, “TheKoch-Pasteur Debate on Establishing the Cause of Anthrax,” Bulletin of the History of Medicine,62 (1988), 42–57; Henri H. Mollaret, “Contribution a la connaissance des relations entre Koch etPasteur,” Schriftenreihe fur Geschichte der Naturwissenschaften, Technik und Medizin, 20 (1983), 57–65.

17 Margaret Pelling, Cholera, Fever and English Medicine, 1825–1865 (Oxford: Oxford University Press,1978); Margaret Pelling, “Contagion/Germ Theory/Specificity,” in Companion Encyclopedia to theHistory of Medicine, ed. William Bynum and Roy Porter, 2 vols. (London: Routledge, 1997), vol. 1,pp. 309–33; Owsei Temkin, “A Historical Analysis of the Concept of Infection,” in Owsei Temkin,The Double Face of Janus and Other Essays in the History of Medicine (Baltimore: Johns HopkinsUniversity Press, 1977), pp. 456–71.

18 Christopher Hamlin, The Science of Impurity: Water Analysis in Nineteenth Century Britain (Berkeley:University of California Press, 1990).



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their existence to similar causes”19 as specific fermentations. The associationof fermentation and putrefaction with the action of “germs” in suppuratingwounds was also taken up in the initial work of Joseph Lister, who promotedantiseptic methods in surgery as means of preventing inflammation.20

The idea that living organisms are causally implicated in infectious diseaseswas also supported by experimental studies and microscopic observationsconducted by epidemiologists, veterinary doctors, anatomical pathologists,and physicians. One might mention here the work on anthrax by the Frenchveterinarian Casimir Davaine (1812–1882), the inoculation experiments oncattle plague performed in England by John Scott Burdon Sanderson (1828–1905),21 the research on the fungal etiology of muscardine by the Italian civilservant Augusto Bassi (1773–1856), and the claims of the British epidemi-ologist William Budd (1811–1880), who reported the presence of fungi inthe discharges of cholera victims or water contaminated with the choleraicexcreta.22

It is somewhat misleading to place all these observations and claims sideby side and discuss them as precursors of the germ theory. They were madein a variety of independent contexts, by researchers working in differentfields, using a variety of different terminologies to describe the contagiumvivum, and differing in their understanding of how the living “contagia”they observed caused or transmitted disease. The historical interest of theseearly observations and inoculation experiments on animals lies perhaps notso much in how much they anticipated the later demonstrations of thebacterial etiology of any specific disease, as in their functioning as catalystsfor discussions of what kind of evidence would be considered necessary toestablish a causal relation between a microorganism and a disease.

The kinds of conditions required to demonstrate that live microorganismscause diseases had been explicitly spelled out already in 1840 by the Germanpathologist Jacob Henle (1809–1885), who argued that in order to show thata given agent is causally implicated in disease it must be shown to be alwayspresent in the diseased organism, and it must be isolated and tested in its iso-lated state to see whether it can reproduce the disease. In 1872, a similar set ofcriteria for establishing a causal relation was articulated by another anatomi-cal pathologist, Edwin Klebs (1834–1913), in his study of gunshot wounds.23

Klebs’s formulation of the ideal experimental strategy, as well as Koch’slater refinement and use of this strategy in his studies of anthrax, wound

19 Quoted in Nancy Tomes, The Gospel of Germs: Men, Women, and the Microbe in American Life(Cambridge, Mass.: Harvard University Press, 1998), p. 31.

20 Lawrence and Dixey, Medical Theory, Surgical Practice.21 Terrie M. Romano, “The Cattle Plague of 1865 and the Reception of ‘The Germ Theory’ in Mid-

Victorian Britain,” Journal of the History of Medicine and the Allied Sciences, 52 (1997), 51–80.22 K. Codell Carter, “Ignaz Semmelweis, Carl Mayrhoffer, and the Rise of Germ Theory,” Medical

History, 29 (1985), 33–53.23 K. Codell Carter, “Koch’s Postulates in Relation to the Work of Jacob Henle and Edwin Klebs,”

Medical History, 29 (1985), 353–74.




infection, cholera, and tuberculosis, took place in the context of debatesamong medical researchers, physicians, veterinarians, hygienists, and publichealth workers as to whether microorganisms were not just “innocent” con-taminants, accompanying rather than causing disease, whether they followedrather than initiated the disease process, or whether they could be generatedde novo or change from saprophytic to pathological under certain as yetunknown environmental conditions. How important are microbes in thecomplicated causal nexus that leads to a person becoming sick? Is the pres-ence of microbes a sufficient cause or only a necessary precondition? Why doepidemics come and go? If microbes are everywhere, why doesn’t everybodybecome sick? The elaboration of what later came to be known as “Koch’s pos-tulates” thus came in a context of controversies between those skeptical of thegerm theory and proponents seeking to demonstrate the causal link betweenmicrobes and disease. The issue was not only whether (specific) germs cause(specific) diseases, it also concerned the nature of the causal connection andits practical – medical and epidemiological – ramifications.

The reception of Koch’s famous 1876 demonstration that anthrax bacilliproduce heat-resistant spores has to be seen in this context. Koch’s presen-tation of his experiments in the Breslau laboratories of Ferdinand Cohngenerated enthusiasm not only because it posited a credible mode of trans-mission of anthrax and explained the known epidemiological facts aboutthis disease, but also because Koch’s new experimental techniques advancedthe researchers’ ability to manipulate microorganisms in the laboratory andsuggested new ways of conducting etiological investigations.24

Koch’s commitment to the idea of the specificity, stability, and distinctive-ness of bacterial species played a key role in his research program. This ideawas a central theoretical foundation for his etiological investigations that asso-ciated specific and stable bacterial species with specific diseases. It served as animportant methodological regulator, one of the criteria for deciding whethera culture has been kept pure, and it assured the medical and epidemiologicalrelevance of Koch’s studies of the etiology of infectious diseases. Both themedical and the biological ramifications of Koch’s position were broughtout in his disputes with botanists such as von Nageli and his student HansBuchner (1850–1902), and hygienists such as Max von Pettenkoffer (1818–1901), who argued that microorganisms were not the most significant causesof disease because under different local conditions the same microorganism(or schizomycete) could be either pathogenic (like the anthrax bacillus) orsaprophytic (like the hay bacillus). Koch returned to this issue repeatedly – inhis study of wound infections, in his further papers on anthrax, and, later, inhis work on tuberculosis and cholera. Aligning himself with the “Linnaean”botanist Cohn, Koch cited his own experimental results as evidence that

24 On Koch, see Thomas Brock, Robert Koch: A Life in Medicine and Bacteriology (Madison, Wis.:Science Tech, 1988); Mendelsohn, “Cultures of Bacteriology”; Mazumdar, Species and Specificity.



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bacterial species bred true and did not undergo any significant morpho-logical or physiological variation. At the same time, he attributed contraryobservations or claims of variability to unrecognized errors in the experimen-tal procedures of his opponents such as contamination, lack of purity, or theuse of mixed cultures.25

Koch’s insistence on specificity, as well as a series of technical innovationssuch as the development of pure culture methods, solid and selective culturemedia, differential staining, and microphotography, led to a long series ofdemonstrations of the specific etiologies of a number of infectious diseases.During the decade following Koch’s famous 1882 demonstration that thetubercle bacillus was the bacterial agent responsible for tuberculosis, Kochand his students and collaborators identified the specific microorganismsresponsible for diphtheria (by Loeffler in 1884), glanders (Loeffler in 1882),typhoid (Gaffky in 1884), cholera (Koch in 1884), and tetanus (Kitasato in1889). Others, using Koch’s methods of isolation, pure culture, and inocula-tion, identified and described the specific organisms responsible for dysentery,gonorrhea, meningitis, and pneumonia, among other diseases. This simplelist does not do justice to the complexity of the research and technical ingenu-ity required to isolate and identify the various bacterial strains and to transmitthe disease to experimental animals reproducing specific disease symptoms.Many of the claims made by the students of bacteria and disease in this earlyheroic period were disputed at the time, some bacterial etiologies were laterrejected or drastically modified, and many of the “proofs” were completedgradually by a number of bacteriologists, pathologists, or physicians workingin laboratories around the world. In some cases, the difficulty of transmittingthe disease to an experimental animal (cholera is the most famous example)or of reproducing the specific pathology – and thus the impossibility of ful-filling all of Koch’s postulates – meant that the debates on the causative role ofparticular bacteria continued for decades.26 These etiological debates aboutinfectious diseases continued through the 1920s and 1930s, when attempts toidentify specific pathogenic viruses (known then as “filterable viruses”) weresubjects of lively dispute.27

While Koch and his students in Germany were busy with studies of etiol-ogy, Pasteur and his collaborators turned their attention to the attenuation

25 Olga Amsterdamska, “Medical and Biological Constraints: Early Research on Variation in Bac-teriology,” Social Studies of Science, 17 (1987), 657–87. See also Mazumdar, Species and Specificity;Mendelsohn, “Cultures of Bacteriology.”

26 See, for example, William Coleman, “Koch’s Comma Bacillus: The First Year,” Bulletin of theHistory of Medicine, 61 (1987), 315–42; Ilana Lowy, “From Guinea Pigs to Man: The Development ofHaffkine’s Anticholera Vaccine,” Journal of the History of Medicine and the Allied Sciences, 47 (1992),270–309.

27 On debates about the etiology of one such disease, influenza, see Ton Van Helvoort, “A BacteriologicalParadigm in Influenza Research in the First Half of the Twentieth Century,” History and Philosophyof the Life Sciences, 15 (1993), 3–21. On the history of virology more generally, see S. S. Hughes, TheVirus: A History of the Concept (London: Heinemann, 1977); A. P. Waterson and L. Wilkinson, AnIntroduction to the History of Virology (Cambridge: Cambridge University Press, 1978).




of microbes and the development of specific vaccines. The initial success inproducing a vaccine against chicken cholera (1880) was followed by a vaccineagainst anthrax, which was tested in famous trials in Pouilly-le-Fort in 1881,and a vaccine to treat rabies, first used on humans in 1885.28 Pasteur’s researchon immunity and attenuation inaugurated a variety of efforts to develop vac-cines and attempts to explain the phenomenon of immunity to infection.By the mid-1890s, immunological research also led to the development ofnew techniques of bacterial identification and diagnosis (such as the Widalreaction for the diagnosis of typhoid, based on the 1896 work of Max Gruberand Herbert Durham on the clumping or agglutination of typhoid bacilli inimmune serum). In the following decades, the development of immunolog-ical theories and techniques was closely linked to developments in medicalbacteriology, and a strict separation of the two areas prior to World War II ishardly possible.

By 1900, despite the development of Pastorian vaccines and a serum treat-ment for diphtheria (by Behring in 1890), the hopes that bacteriological dis-coveries would quickly lead to efficient therapies had been moderated. Thegerm theory, however, penetrated deeply not only into the physicians’ andscientists’ understanding of diseases but also into the public consciousnessand daily sanitary practices.29 The germ theory was a prime example of whatlaboratory research in medicine could accomplish, even if some epidemiolo-gists or physicians had doubts about particular etiologies, the sufficiency ofbacteriological explanation, or the relevance of specific laboratory findingsfor the management of infectious diseases.30

INSTITUTIONALIZATION OF BACTERIOLOGY

The bacteriological revolution profoundly altered the organization of medicalresearch and the manner in which studies of microorganisms were institu-tionalized. In the course of a few decades, microorganisms became the centralpreoccupation of a variety of medical researchers and physicians working inhospitals, public health laboratories, and medical schools and faculties. This

28 Geison, Private Science of Louis Pasteur.29 See Tomes, Gospel of Germs.30 On some aspects of opposition to bacteriology, see Russell C. Maulitz, “‘Physician vs. Bacteriologist’:

The Ideology of Science in Clinical Medicine,” in The Therapeutic Revolution: Essays in the SocialHistory of American Medicine, ed. Morris J. Vogel and Charles E. Rosenberg (Philadelphia: Universityof Pennsylvania Press, 1979), pp. 91–107; Michael Worboys, “Treatments for Pneumonia in Britain,1910–1940,” in Medicine and Change: Historical and Sociology Studies of Medical Innovation, ed. IlanaLowy et al. (Paris: Libbey, 1993); Anne Hardy, “On the Cusp: Epidemiology and Bacteriology atthe Local Government Board, 1890–1905,” Medical History, 42 (1998), 328–46; Anna Greenwood,“Lawson Tait and Opposition to Germ Theory: Defining Science in Surgical Practice,” Journal of theHistory of Medicine and the Allied Sciences, 53 (1998), 99–131; Nancy J. Tomes, “American Attitudestowards the Germ Theory of Disease: Phyllis Allen Richmond Revisited,” Journal of the History ofMedicine and the Allied Sciences, 52 (1997), 17–50.



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process of institutionalization proceeded somewhat differently in variouscountries: In Germany, for example, bacteriologists tended to be appointedto chairs of hygiene, many of which were created in the wake of Koch’sdiscoveries and occupied by his students and collaborators.31 In the UnitedStates and the United Kingdom, bacteriology was more often regarded asa specialization within pathology. Independent university departments ofbacteriology were established in the United States in the first decades ofthe twentieth century. In the United Kingdom, this process of institution-alization proceeded more slowly. Pathological and bacteriological researchwas conducted mainly in teaching hospitals and a few of the newer urbanuniversities, and laboratory diagnostic work had relatively low status in a sys-tem dominated by elite clinicians. Moreover, bacteriological laboratories inBritish teaching hospitals and universities were often swamped with routinediagnostic work performed at the request of physicians or for public healthauthorities.32 A similar domination of clinicians in the teaching hospitalsof Paris also tended to marginalize laboratory research, and the few chairsof microbiology established before World War I “were often ‘waiting chairs’,occupied by physicians who aspired to a clinical chair and were not interestedin microbiological research.”33

But even if the existing institutional and disciplinary structures were rel-atively slow to make room for bacteriology as an independent discipline,the bacteriological revolution was followed by a significant innovation in theorganization of (medical) research: the establishment of major research insti-tutes devoted to medical, and especially bacteriological, research. In 1888,following Pasteur’s successful treatment of rabies, a public collection and agift from the French government provided funds for the establishment of thePasteur Institute in Paris. Three years later, a government-funded Institutefor Infectious Diseases was opened for Koch in Berlin. There followed theLister Institute in London (1893), the Institute for Experimental Medicine inSaint Petersburg (1892), the Serotherapeutic Institute in Vienna, the Institutefor Experimental Therapy in Frankfurt am Main (1899), and the RockefellerInstitute for Medical Research in New York (1902). All of these institutesshared a commitment to laboratory studies of disease, although they differed

31 Paul Weindling, “Scientific Elites and Laboratory Organisation in fin de siecle Paris and Berlin: ThePasteur Institute and Robert Koch’s Institute for Infectious Diseases Compared,” in The LaboratoryRevolution in Medicine, ed. Andrew Cunningham and Perry Williams (Cambridge: CambridgeUniversity Press, 1992), pp. 170–88.

32 Keith Vernon, “Pus, Sewage, Beer, and Milk: Microbiology in Britain, 1870–1940,” History of Science,28 (1990), 289–323; Patricia Gossel, “The Emergence of American Bacteriology, 1875–1900” (PhDdiss., Johns Hopkins University, 1989). See also Paul F. Clark, Pioneer Microbiologists of America(Madison: University of Wisconsin Press, 1961); Russell Maulitz, “Pathologists, Clinicians, andthe Role of Pathophysiology,” in Physiology in the American Context, 1850–1940, ed. Gerald Geison(Bethesda, Md.: American Physiological Society, 1987), pp. 209–35.

33 Ilana Lowy, “On Hybridizations, Networks, and New Disciplines: The Pasteur Institute and theDevelopment of Microbiology in France,” Studies in the History and Philosophy of Science, 25 (1994),655–88, at p. 670.




in the scope of the research that was envisaged and performed (for example,the Rockefeller Institute concentrated on experimental medicine broadlyunderstood, while the Pasteur Institute focused on the study of microor-ganisms, including their nonmedical facets, and Koch’s Institute for Infec-tious Diseases was focused on medical bacteriology). They were also fundeddifferently: by government support, public collections and donations, indus-trial or philanthropic funding, or by generating additional income from theproduction of biological materials such as the antidiphtheria serum. Thusthey differed also in the degree of their financial and institutional indepen-dence, in the nature of their relations to the research of a senior “founding”figure, and in their internal organizational structures. They provided a settingfor advanced, often collaborative, research and training for future researchers,public health workers, laboratory workers, and clinicians. Of special impor-tance for the dissemination of medical bacteriology were the month-longcourses offered by Koch and his collaborators, initially at the Hygienic Insti-tute at the Berlin University and later at the Institute for Infectious Diseases,which were attended not only by hundreds of German physicians but alsoby large numbers of foreign visitors. The courses emphasized practical expe-rience and the learning of laboratory skills and methods, and they providedstudents with an opportunity to acquaint themselves with the organizationof bacteriological research and teaching. When the Pasteur Institute openedits doors in 1888, Koch’s course served as a model for the course offered thereby Emile Roux (1853–1933), which soon attracted a similarly internationalaudience.34

Perhaps the most obvious, though still not fully explored, aspect of the bac-teriological revolution was that it moved the study of microorganisms froma marginal subject of research for a small group of botanists and zoologists tothe center of attention among a wide group of researchers working in a vari-ety of research fields. Although the medical and public health settings werethe most dominant and produced the most celebrated achievements, aroundthe turn of the century microorganisms continued to be studied by someacademic biologists and were becoming important in agricultural researchsettings – in veterinary medicine, plant pathology, and soil studies – and ina few laboratories exploring the uses of these organisms in the fermentationand processing industries. Although in the first half of the twentieth cen-tury microbiology continued to be both organizationally and intellectually

34 Weindling, “Scientific Elites and Laboratory Organisation in fin de siecle Paris and Berlin”; Mendel-sohn, “Cultures of Bacteriology”; Gossell, “Emergence of American Bacteriology”; Lowy, “Hybridiza-tions, Networks, and New Disciplines.” See also Henriette Chick, Margaret Hume, and MarjorieMacfarlane, War on Disease: A History of the Lister Institute (London: Deutsch, 1972); George W.Corner, The History of the Rockefeller Institute for Medical Research (New York: Rockefeller Uni-versity Press, 1964); Michel Morange, ed., L’Institut Pasteur: Contributions a son histoire (Paris: LaDecouverte, 1991).



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scattered, substantive methodological and institutional links existed betweenresearchers working in a variety of settings.

The dispersed state of the field was often criticized, and some bacteriol-ogists argued for the unity of the field as a means of establishing a degreeof professional and disciplinary autonomy. Such unification was, for exam-ple, an explicit goal of the Society of American Bacteriologists, founded in1899. Its founders wanted to “emphasize the position of bacteriology as oneof the biological sciences” and to “bring together workers interested in thevarious branches into which bacteriology . . . [was] . . . ramifying.”35 In addi-tion to publishing the generalist American Journal of Bacteriology (foundedin 1916), the society also sponsored work aiming at the standardization ofmethods of studying bacteria and the establishment of a uniform systemof bacterial classification. Such standardization was not only of practicalimportance for the development of efficient communication in the field, itwas also meant to enhance the disciplinary status of bacteriology as a biolog-ical field and not just a “handmaiden” of medicine, pathology, or agriculturalresearch.36

BETWEEN PROTOZOOLOGY AND TROPICAL DISEASES

It is extremely difficult to locate the position of studies of microorganismsin the context of early twentieth-century academic biology. Studies of pro-tozoa in Germany around the turn of the century illustrate this complexity.Protozoa came to constitute the research object of the specialized disciplineof protozoology, with its own research institutes, a journal (Archiv fur Pro-tistenkunde, founded by Richard Hertwig in 1902), and textbooks. Protozoaand other unicellular organisms also served as models and research toolsin cytological research aiming to unravel the physiology and morphologyof the living cell at a time when experimental cell research was regarded inGermany as the unifying ground for all biology.37 At the same time, protozoawere studied as agents of disease, especially in colonial or tropical medicine,and much of the institutional support for their study was clearly linked tothis last interest (as witnessed by the establishment of a protozoological divi-sion in Koch’s Institute for Infectious Diseases, and of research institutessuch as the Hamburg Institute for Naval and Tropical Diseases in 1901). The

35 H. Conn, “Professor Herbert William Conn and the Founding of the Society,” BacteriologicalReviews, 12 (1948), 275–96, at p. 287.

36 Gossel, “Emergence of American Bacteriology”; Patricia Gossel, “The Need for Standard Methods:The Case of American Bacteriology,” in The Right Tools for the Job: At Work in Twentieth Century LifeSciences, ed. Adele H. Clarke and Joan H. Fujimura (Princeton, N.J.: Princeton University Press),pp. 287–311.

37 Jacobs, “From Unit to Unity”; Marsha Richmond, “Protozoa as Precursors of Metazoa: German CellTheory and Its Critics at the Turn of the Century,” Journal of the History of Biology, 22 (1989), 243–76.




research conducted by protozoologists often fell into more than one of thesecategories. Thus, a protozoologist such as Fritz Schaudinn, remembered inmedicine for his identification of Treponema pallidum (1905) – which wasnot a protozoan but a spirochete – as the etiological agent of syphilis andfor his work on blood parasites (malarial plasmodia and trypanosomes), wasalso deeply involved in debates about theories of protozoan reproduction andlife cycles. A similar combination of physiological and cytological studies ofprotozoa with investigations of other pathological microorganisms – bacte-ria, rickettsia, and viruses – characterized the work of Schaudinn’s coworkerand successor as the director of the Hamburg Institute of Tropical Diseases,Stanislaus von Prowazek.

But it was not in the academic biological settings but in the context ofcolonial and military medicine that the most important protozoan parasiteswere initially identified and their life cycles and modes of spreading throughanimal vectors established. Thus, in 1880 the French Army doctor AlphonseLaveran identified merezoites in the blood of malaria victims; in 1898, RonaldRoss of the Indian Medical Service described the role of the mosquito inthe transmission of malaria and traced the life cycle of the parasite in themosquito; in 1895, David Bruce of the Royal Army Medical Corps studiedtrypanosomes and the role of the tsetse fly in the transmission of the cattledisease nagana; and in 1903 W. B. Leischman of the Royal Army MedicalCorps elucidated the etiology of kala-azar. Patrick Manson’s definition oftropical diseases as those caused by protozoa and transmitted through avector meant that although many diseases affecting the populations of Asiaand Africa were not protozoan (nor necessarily spread by an animal vector),the close connection between tropical (colonial) medicine and protozoologycontinued in the first half of the twentieth century in the research performedin settings such as the Liverpool School of Tropical Medicine (establishedin 1899) and the London School of Tropical Medicine (established in 1899;after 1927, thanks to a grant from the Rockefeller Foundation, it becamethe London School of Hygiene and Tropical Medicine).38 Still, by the 1920sand 1930s, some of the research conducted in these locales in Britain or inanalogous laboratories and institutions in France or Germany was also onlydistantly related to specific medical problems and addressed issues such asprotozoan morphology, life cycles, nutrition and biochemistry, or genetics,as for example in the work on nutrition of protozoa and growth factorsconducted by Andre Lwoff (1902–1994) at Felix Mesnil’s laboratory at thePasteur Institute.

38 Michael Worboys, “Tropical Diseases,” in Bynum and Porter, Companion Encyclopedia to the His-tory of Medicine, vol. 1, pp. 512–35; Michael Worboys, “The Emergence of Tropical Medicine,” inPerspectives on the Emergence of Scientific Disciplines, ed. Gerald Lemaine et al. (The Hague: Mouton,1976), pp. 76–98.



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BACTERIOLOGY BETWEEN BOTANY, CHEMISTRY,AND AGRICULTURE

A similar intersection of various institutional and intellectual contexts isapparent in the development of the tradition of microbial studies initiatedby Sergei Winogradsky (1856–1953) and, independently, by Martinus WillemBeijerinck (1851–1931). Both Beijerinck and Winogradsky were trained asbotanists and learned microbiological techniques in the 1880s at the botanicallaboratory of Anton de Bary at the University of Strasbourg. De Bary, a rathertypical representative of the new botany, investigated morphological struc-tures, physiological processes, and the development of cryptogams, especiallyfungi. He was also interested in antagonistic and symbiotic relations amongorganisms. Beijerinck’s and Winogradsky’s more ecological approaches tothe study of microorganisms were rooted in this background in plant mor-phology and physiology, reflected an interest in more fundamental biologi-cal questions concerning growth, heredity, and physiology, and emphasizedinteractions between an organism and its environment and among differentmicroorganisms living in the same environment. This ecological perspectiveis evident not only in their critiques of standard (medical) bacteriologicaltechniques but also in their methodologies: the use of elective, enrichment,or accumulation culture methods in which the isolation of bacteria was madepossible by adjusting the chemical composition of the culture medium soas to favor the growth of a particular physiological type of microorganism.Using these methods, Winogradsky, at that time working in Zurich, iden-tified sulfur and iron bacteria (1889) and in the 1890s studied groups of soilbacteria responsible for nitrification – the fixing of atmospheric nitrogenand the transformation of nitrite into nitrate. Beijerinck emphasized thefact that accumulation cultures provide an opportunity to study bacterialvariation and, by simulating environmental conditions occurring in nature(rather than using the “artificial” media of medical bacteriology), they madeit possible to study microbial ecology.

Winogradsky’s studies of the physiology and biochemistry of autotrophicbacteria clearly had general biological and biochemical implications, but theissues he raised were later taken up predominantly not in academic biol-ogy, but in agricultural research settings where funding was more abundantand where research in soil microbiology was legitimized by its relevance toagriculture.39

Beijerinck’s research program was even more obviously and explicitlylinked to the current problematics in botany and biology. He studied anenormous variety of microorganisms (including yeast, algae, lichens, and

39 S. A. Waksman, Sergei Winogradsky, His Life and Work (New Brunswick, N.J.: Rutgers UniversityPress, 1953).




viruses) and was interested in systematics as well as microbial physiology andvariability. Questions of growth, heredity, and variation gave unity to all ofBeijerinck’s work. There can be no doubt that Beijerinck – who is remem-bered for his identification of nitrogen-fixing bacteria in the root nodulesof leguminous plants, his demonstration that the tobacco mosaic disease iscaused by a contagium vivum fluidum (a virus), and his work on microbialvariation – pursued research questions that were more relevant to academicbiologists than to agricultural practice or the industrial uses of microorgan-isms. And yet Beijerinck taught at an agricultural school and worked in anindustrial laboratory before returning to the “more academic” though stillpractice-oriented setting of the polytechnical university at Delft.40

In the following decades, agricultural research stations and agriculturalcolleges in the United States and the United Kingdom became important set-tings for the study of soil microorganisms, and at least some of this research –the history of which still remains to be written – adopted the ecological andphysiological perspectives of Beijerinck and Winogradsky. These perspectivesare clearly apparent in the research on soil microbiology conducted at theNew Jersey Agricultural Experiment Station at Rutgers University by JacobG. Lipman and then by Selman Waksman and their students.41 By the 1940s,this research was redirected toward more medical (and industrial) goals asWaksman’s laboratory turned to work on antibiotics.

Most of the microbiological research in agricultural research settings –such as experimental stations, agricultural colleges, and the Federal Bureaus ofPlant Research and Animal Industry of the U. S. Department of Agriculture –was focused not on soil microbiology but on plant and animal diseases.In the United States, such studies were particularly well funded, thoughmany of the scientists engaged in studies of plant and animal diseases had tobattle with the competing pressures of providing direct service to farmers andof conducting more fundamental research.42 Simplifying grossly, one couldsay that studies of animal diseases were closely related to other aspects ofmedical bacteriology and parasitology (as in the work of Theobald Smith),dairy bacteriology was closely linked to sanitary or public health bacteriology

40 Bert Theunissen, “The Beginnings of the ‘Delft Tradition’ Revisited: Martinus W. Beijerinck andthe Genetics of Microorganisms,” Journal of the History of Biology, 29 (1996), 197–228. See also G.van Iterson, L. E. den Dooren de Jong, and A. J. Kluyver, Martinus Willem Beijerinck: His Life andWork (orig., 1940; repr. Ann Arbor, Mich.: Science Tech, 1983).

41 Jill E. Cooper, “From the Soil to Scientific Discovery: Rene Dubos and the Ecological Model forMicrobial Investigation, 1924–1939,” paper presented at the meeting of the History of Science Society,Atlanta, Georgia, November 1996.

42 Charles E. Rosenberg, “Rationalization and Reality in Shaping American Agricultural Research,1875–1914,” in The Sciences in the American Context: New Perspectives, ed. Nathan Reingold (Wash-ington, D.C.: Smithsonian Institution Press, 1979), pp. 143–63; Charles E. Rosenberg, “The AdamsAct: Politics and the Cause of Scientific Research,” in Charles E. Rosenberg, No Other Gods: OnScience and American Social Thought (Baltimore: Johns Hopkins University Press, 1961); MargaretRossiter, “The Organization of the Agricultural Sciences,” in The Organization of Knowledge in Mod-ern America, 1860–1920, ed. Alexandra Oleson and John Voss (Baltimore: Johns Hopkins UniversityPress, 1979).



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(as in the work of Herbert William Conn), and the links with botany weremore likely to be maintained by those who studied plant diseases (such asThomas J. Burill and Erwin F. Smith).

MICROBIOLOGY BETWEEN THE BREWING INDUSTRYAND (BIO)CHEMISTRY

Following the work of Pasteur, it might appear that the study of the chemicalactivities of microorganisms should have developed in connection with thevarious fermentation industries, yet only a few such enterprises employedmicrobiologists and relied on their expertise. Insofar as microorganisms werestudied in these settings, the research was often conducted by chemists.The most prominent exception was the institute at the Carlsberg Breweryin Copenhagen, founded in 1876, where Emil Christian Hansen (1842–1909) studied pure yeast cultures and the problems that arose when wildyeasts contaminated the brews. In the first decades of the twentieth century,researchers at the Carlsberg Institute studied a variety of enzymatic processesin microorganisms.43 Prior to the First World War, studies of fermentationwere also conducted by Max Delbruck (1850–1919) at the Berlin Institut furGarungsgewerbe44 and by August Fernbach at the Pasteur Institute.

Awareness of the economic possibilities of fermentation research receiveda considerable boost in the years just prior to and during World War I, whenanother organic chemist (and future first president of the state of Israel),Chaim Weizmann (in collaboration with Fernbach), isolated a bacteriumable to convert starch to acetone and butanol and on this basis developed theprocess for the production of these two compounds. Although the initial hopewas that the butanol-acetone process would be important in the productionof synthetic rubber, it achieved real economic success during the war, whenit was employed for the production of explosives.

Robert Bud has linked the origins of biotechnology with the establishmentof institutes for the study of fermentation technologies in agricultural andindustrial schools and research institutions, and with the broadening of thepotential scope of fermentation industries to processes other than brewing.45

In the immediate post–World War I period, visions of how microorganismscould be used as small but efficient chemical factories were repeatedly artic-ulated, and the term biotechnology was coined. But, quite apart from theimportance of these visions for the actual development of biotechnology, thevarious research institutes serving the interests of the processing industries

43 H. Holter and K. Max Møller, The Carlsberg Laboratory 1876/1976 (Copenhagen: Rhodos, 1976).44 F. Hayduck, “Max Delbruck,” Berichte der Deutschen Chemischen Gesellschaft, 53 (1920), 48–62.45 Robert Bud, “The Zymotechnic Roots of Biotechnology,” British Journal of the History of Science,

25 (1992), 127–44; Robert Bud, The Uses of Life: A History of Biotechnology (Cambridge: CambridgeUniversity Press, 1993).




provided opportunities for more chemically oriented studies of microbialphysiology.

Such research was, for example, performed by Sigurd Orla-Jensen, pro-fessor of fermentation physiology and agricultural chemistry (later renamedbiotechnical chemistry) at the Copenhagen Polytechnic. Reflecting the chem-ical perspectives on microorganisms that dominated the research on fermen-tation practices, Orla-Jensen attempted to classify bacteria not in terms oftheir morphology or pathogenicity but in terms of their metabolism.

Another setting for research on the physiology of microorganisms whereindustrial orientation was combined with biochemical interests was the DelftPolytechnic, where Albert J. Kluyver (1888–1956), the successor to Beijerinck,managed to combine the training of chemical engineers in microbiology,and lively contacts with Dutch enterprises using microorganisms in indus-trial production, with an extensive research program on bacterial metabolismbased on the idea of the unity of biochemistry. While grooming his studentsfor positions in industry and allowing them to extend their chemical back-ground in their work on microorganisms, Kluyver attempted to develop ageneral biochemical model of both fermentative and oxidative metabolismwhile remaining committed to the study of microbial physiology.46

In the 1920s and 1930s, studies of microbial physiology were thus linkednot only to industrial concerns or biotechnological visions but also to thedevelopments in academic biochemistry. In addition to working on chemicalproblems involving the use of microorganisms in the fermentation industriesor in medicine, some biochemists used bacteria or yeast as convenient toolsin their attempts to isolate and purify enzymes or to analyze the chemi-cal steps involved in metabolic processes, while others became interested inmicroorganisms as biological systems with their own distinctive physiology.47

At the Dunn Institute of Biochemistry at Cambridge, for example, bacte-rial biochemistry was first studied by Harold Raistrick (1890–1971) and thenby Judah Quastel (1899–1987) and Marjorie Stephenson (1885–1948). Theystudied bacterial enzymes, especially dehydrogenases, and developed the so-called resting cell method to study metabolic reactions in viable but notreproducing cells. Whereas Quastel’s interests eventually reverted to thoseof mainstream biochemistry, where bacteria served primarily as convenienttools, Stephenson (and her students) continued to combine general bio-chemistry with microbial physiology by studying bacterial adaptation, nutri-tional requirements of different bacteria, and the physiological regulationof metabolic processes in a living cell. Stephenson objected to biochemists’

46 Olga Amsterdamska, “Beneficent Microbes: The Delft School of Microbiology and Its IndustrialConnections,” in Beijerinck and the Delft School of Microbiology, ed. P. Bos and B. Theunissen (Delft:Delft University Press, 1995); A. F. Kamp, J. W. M. la Riviere, and W. Verhoeven, eds., Albert JanKluyver: His Life and Work (Amsterdam: North-Holland, 1959).

47 Neil Morgan, “Pure Science and Applied Medicine: The Relationship between Bacteriology andBiochemistry in England after 1880,” Society for Social History of Medicine Bulletin, 37 (1985), 46–9.



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treatment of microorganisms as “bags of enzymes.”48 Her work and thatof her collaborators (especially John Yudkin) on the regulation of bacte-rial metabolism and the phenomenon of adaptation served as one of thesources for the later work of Jacques Monod (1910–1976) on diauxie, adap-tive enzymes, and their genetic inhibition.

In the 1920s and 1930s, studies of bacterial physiology were also pursuedby some medical bacteriologists. The nutritional requirements of variousspecies of bacteria were often examined when bacteriologists tried to dif-ferentiate and classify bacterial strains or to develop diagnostic methods. Asystematic program on bacterial nutrition was developed, for example, at theLondon Middlesex Hospital by Paul Fildes (1882–1971), working togetherwith a number of biochemists.49

Studies of bacterial physiology in the 1930s and 1940s served as one of theimpulses behind new attempts to counter the institutional and intellectualdispersal of the studies of microorganisms by promoting general microbiol-ogy. In 1930, a number of scientists working in a variety of settings and busywith practical as well as purely scientific problems founded a new journal,Archiv fur Mikrobiologie, which was supposed to bring together research onmicroorganisms then appearing in botanical, biochemical, and morphologi-cal journals. Calls for general microbiology could also be heard in the UnitedStates and the United Kingdom, and they came in part from the same con-stituency. It was Cornelis Van Niel (1897–1985), Kluyver’s most successfuldisciple and an expert on photosynthetic bacteria, who initiated courses ingeneral microbiology at the Hopkins Marine Station of Stanford Univer-sity. Van Niel promoted a broad concept of microbiology that would bringtogether biochemical and genetic, as well as environmental and evolution-ary, investigations of microorganisms.50 His students included such leadersof postwar general microbiology as Roger Stanier (1916–1982) and MichaelDoudoroff (1911–1975). A similar aim to bring together microbiologists fromdiffering backgrounds and establish a common ground between all forms ofmicrobiology united the founders of the British Society for General Micro-biology, which was formally inaugurated in 1945.

GENETICS OF MICROORGANISMS AND MOLECULARBIOLOGY

Just as research on bacterial physiology was initially an offshoot of a variety ofstudies in which industrial, medical, agricultural, and biochemical interests

48 Robert E. Kohler, “Innovation in Normal Science: Bacterial Physiology,” Isis, 76 (1985), 162–81.49 Robert E. Kohler, “Bacterial Physiology: The Medical Context,” Bulletin of the History of Medicine,

59 (1985), 54–74.50 Susan Spath, “C. B. van Niel and the Culture of Microbiology, 1920–1965” (PhD diss., University

of California at Berkeley, 1999).




crisscrossed and overlapped, so also were studies of microbial genetics initiallya by-product of other investigations. Until the 1940s, genetic questions werenot of primary concern in any of the contexts in which microorganisms werestudied. Beijerinck’s attempts to place the study of bacterial variation andgrowth in the context of De Vries’s theory of mutation and to relate them tothe enzymatic theory of heredity had not been followed up, even if researcherssometimes raised questions about the nature of bacterial inheritance. Thissituation changed profoundly in the 1940s when microorganisms becamethe preferred tools of biologists promoting and developing a new “molecu-lar vision of life,” a vision initially supported by philanthropic organizationssuch as the Rockefeller Foundation and one that received a tremendous boostin the postwar period when large-scale government funds began to flow intofundamental biological research.51 A large number of microbiologists, as wellas geneticists and biochemists who chose microorganisms as tools for theirstudies of the physicochemical basis of vital processes, participated in thisinterdisciplinary and international endeavor, which we now refer to as molec-ular biology.52 Support from foundations, and then government, encouragedthe development and deployment of new scientific instruments and tech-niques – ultracentrifuges, electrophoresis apparatus, electron microscopes,and radioactive isotope tracers – the use of which transformed all areas ofmicrobiological research.53

Until the early 1900s, Koch’s belief in the morphological and physiologi-cal stability of bacterial species was the dominant – but never a universallyaccepted – article of faith among medical bacteriologists. Only when theinterests of medical bacteriologists turned toward immunological and chem-ical diagnostic methods did bacterial variation – changes in the antigenicand fermentative properties of bacteria, or in cell and colony morphology(especially the so-called S/R dissociation) − again become a subject of con-cern. During the interwar period, medical bacteriologists studied dissociation

51 On the role of the Rockefeller Foundation, see R. E. Kohler, “The Management of Science: TheExperience of Warren Weaver and the Rockefeller Foundation Program in Molecular Biology,”Minerva, 14 (1976), 249–93; Pnina Abir-Am, “The Discourse of Physical Power and BiologicalKnowledge in the 1930s: A Reappraisal of the Rockefeller Foundation’s Policy in Molecular Biology,”Social Studies of Science, 12 (1982), 341–82; Lily E. Kay, The Molecular Vision of Life: Caltech, TheRockefeller Foundation, and the Rise of the New Biology (New York: Oxford University Press, 1993).

52 Pnina Abir-Am, “From Multi-disciplinary Collaboration to Transnational Objectivity: InternationalSpace as Constitutive of Molecular Biology, 1930–1970,” in Denationalizing Science: The InternationalContext of Scientific Practice, ed. E. Crawford, T. Shinn, and S. Sorlin (Dordrecht: Kluwer, 1993),pp. 153–86.

53 On the use of the electron microscope in morphological studies of bacteria and in research on bacte-riophages, see Nicolas Rassmussen, Picture Control: The Electron Microscope and the Transformation ofBiology in America, 1940–1960 (Palo Alto, Calif.: Stanford University Press, 1997), especially chaps. 2and 5. On the debates that the use of new methods sometimes generated among microbiologists, seeJames Strick, “Swimming against the Tide: Adrianus Pijper and the Debate over Bacterial Flagella,1946–1956,” Isis, 87 (1996), 274–305. See also Abir-Am, “The Discourse of Physical Power andBiological Knowledge in the 1930s”; Lily Kay, “Laboratory Technology and Biological Knowledge:The Tiselius Electrophoresis Apparatus, 1930–1945,” History and Philosophy of the Life Sciences, 10(1988), 51–72.



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primarily because it was linked to changes in pathogenicity and in immuno-logical properties of bacteria, though they also speculated about the mech-anisms of dissociation, appealed to various theories of genetics to explaintheir findings, and tried to test whether the changes were heritable and per-manent or dependent on the environment in which bacteria were cultivatedand readily reversible. Their research was largely structured by medical ratherthan genetic questions.54

The medically relevant implications of dissociation were, for example,central to the research on the transformation of pneumococci developed byOswald Avery (1877–1955) and his group at the Rockefeller Institute Hospital.Avery and his coworkers were primarily interested in treatments for pneumo-coccal pneumonia, and their work on transformation fitted smoothly intotheir immunochemical research program. By 1943, however, when the in vitrosystem was fully perfected and Avery had managed to identify the responsiblesubstance as DNA, the implications of his finding went far beyond medicalbacteriology.55

In contrast with Avery’s medical motivation, most new research on micro-bial genetics in the 1940s and 1950s resulted from biologists’ (and some physi-cists’) belief that microorganisms can serve as convenient experimental toolsto pursue fundamental questions about the mechanisms of heredity and thegenetic control of biochemical processes. Such, for example, was the moti-vation of the physicist-turned-geneticist Max Delbruck (1906–1981), who inthe late 1930s chose the bacteriophage (a bacterial virus) as the experimen-tal object with which he could attempt to solve “the riddle of life”: Phages(bacterial viruses) appeared to Delbruck as “atoms in biology,” elementarybiological units able to self-replicate and thus the preferred experimentalmodels and conceptual tools to understand gene action.56

General biological questions, rather than an interest in microorganismsper se, also led the geneticist George Beadle (1903–1989) and the bacterialbiochemist Edward Tatum (1909–1975) to choose the bread mold neurosporaas an organism particularly well suited for investigating the genetic control

54 Olga Amsterdamska, “Medical and Biological Constraints”; Olga Amsterdamska, “Stabilizing In-stability: The Controversies over Cyclogenic Theories of Bacterial Variation during the InterwarPeriod,” Journal of the History of Biology, 24 (1991), 191–222; William Summers, “From Culture asOrganism to Organism as Cell: Historical Origins of Bacterial Genetics,” Journal of the History ofBiology, 24 (1991), 171–90.

55 Olga Amsterdamska, “From Pneumonia to DNA: The Research Career of Oswald T. Avery,” Histor-ical Studies in Physical and Biological Sciences, 24 (1993), 1–39; Rene Dubos, The Professor, the Instituteand DNA (New York: Rockefeller University Press, 1976); Maclyn McCarty, The Transforming Prin-ciple: Discovering that Genes Are Made of DNA (New York: Norton, 1985); Ilana Lowy, “Variancesof Meaning in Discovery Accounts: The Case of Contemporary Biology,” Historical Studies in thePhysical Sciences, 21 (1990), 87–121.

56 Lily E. Kay, “Conceptual Models and Analytical Tools: The Biology of Physicist Max Delbruck,”Journal of the History of Biology, 18 (1985), 207–46; Thomas D. Brock, The Emergence of BacterialGenetics (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 1990); John Cairns,Gunther Stent, and James Watson, eds., Phage and the Origins of Molecular Biology (Cold SpringHarber, N.Y.: Cold Spring Harbor Laboratory Press, 1966).




of biochemical mechanisms. Following Beadle’s (and Boris Ephrussi’s) inves-tigations of the genetic control of eye color in Drosophila, Beadle, workingtogether with Tatum, shifted his attention to neurospora because he hopedit would provide a simpler experimental model for which the biochemistrywas better known and easier to control than that of Drosophila. Neurosporaproved to be a convenient and productive experimental tool, and the onegene, one enzyme concept that emerged from this work served as a theoreticalbasis for the investigation of metabolic pathways using genetic mutants.57

A desire to make bacteria into organisms suitable for genetic research alsomotivated Joshua Lederberg to undertake his studies of mating in Escherichiacoli in experiments using double nutritional mutants and phage resistanceas markers.58 The nature of the mating process and its physiology, geneticsignificance, and the organization of genetic material in a bacterial cell werestudied in the 1950s and 1960s by a number of researchers, with particu-larly important work being conducted by William Hayes in Britain, and byFrancois Jacob and Elie Wollman at the Pasteur Institute.

The fact that microorganisms, after the Second World War, became thepreferred tools for the study of the physical and chemical basis of vital phe-nomena common to all living organisms signaled a triumph of the unitarianand reductionist biology, famously captured in Jacques Monod’s dictum thatwhat is true of E. coli is also true of an elephant. Because E. coli is simpler andeasier to manipulate in a laboratory than an elephant, advances in molec-ular biology have resulted in an unprecedented development of knowledgeabout the molecular processes taking place in microorganisms and in thedevelopment of new arenas of collaboration and practice for microbiologists.

CONCLUSIONS

The molecularization of microbiology and the use of microorganisms inmolecular biological research and biotechnology have resulted in the unprece-dented growth and diversification of microbiological research. Today, theAmerican Society for Microbiology, with its 40,000 members and sometwenty-four specialized subsections, boasts of being the world’s largest orga-nization for professionals in a single life science, and microbiologists workin a variety of institutional locations and settings.

But parallel with the laboratory and industrial domestication of a greatnumber of different types of microorganisms, and our increased ability to

57 Robert E. Kohler, “Systems of Production: Drosophila, Neurospora, and Biochemical Genetics,”Historical Studies in the Physical and Biological Sciences, 22 (1991), 87–130; Lily E. Kay, “Selling PureScience in Wartime: The Biochemical Genetics of G. W. Beadle,” Journal of the History of Biology,2 (1989), 73–101.

58 Joshua Lederberg, “Forty Years of Genetic Recombination in Bacteria,” Nature, 324 (1986), 627–9;Joshua Lederberg, “Genetic Recombination in Bacteria: A Discovery Account,” Annual Review ofGenetics, 21 (1987), 23–46.



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manipulate and engineer microbial life in the test tube and the fermentationreactor, recent decades have also underscored the continuing difficulties ofcontrolling microorganisms beyond the laboratory walls. The resurgenceof infectious diseases, such as tuberculosis, whose control had previouslyappeared to be imminent, and the emergence of new epidemics, such asAIDS, emphatically testify to this disparity between the laboratory and theoutside world.


olga amsterdamska - waseda universitysince the late nineteenth century, the study of microorganisms...

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