Chapter V

The Bacterium as Organism and Instrument

A. Introduction

On March 2, 1961, microbiologist Roger Stanier, professor at the University of California, Berkeley, addressed the Société de Microbiologie in Paris. Before that audience, he proposed to answer a deceptively simple question: What is a bacterium? The question had haunted Stanier for almost twenty years. To frame a detailed answer, he turned not to his colleagues at the Pasteur Institute where he was spending his sabbatical, but to his revered mentor in microbiology, C.B. van Niel. For Stanier and van Niel, the question lay at the core of their ambitions to establish microbiology as a general science of life:

Since the earliest days of microbiology, the biological nature and relationships of the bacteria have been subjects of perennial discussion. Why have these questions obsessed some members of each succeeding generation of microbiologists? There can be no doubt about the principal reason. Any good biologist finds it intellectually distressing to devote his life to the study of a group that cannot be readily and satisfactorily defined in biological terms; and the abiding intellectual scandal of bacteriology has been the absence of a clear concept of a bacterium.⁽¹⁾ By the early 1960's, it was both possible and necessary for Stanier and van Niel to resolve this question. New research practices in which bacteria served as crucially important tools made it necessary; new evidence about the cytology and heredity of bacteria made it possible. In their joint article, "The Concept of a Bacterium," Stanier and van Niel defined bacteria by conceptualizing two new biological entities, "procaryotes" and "eucaryotes." They argued that the cells of all living things were either procaryotic or eucaryotic, depending on their pattern of cellular organization. They defined eucaryotes as cells containing membrane-bound structures called organelles, the most important of which was the nucleus. By this definition, all cells of multi-cellular plants and animals were eucaryotes. Cells that lacked membrane-bound cell nuclei, like bacteria and blue-green algae, were designated procaryotes. The term procaryote implicitly elevated bacteria to equivalent biological status with all other organisms, to be known as eucaryotes. Defining bacteria as procaryotes gave them an identity commensurate with their new value in biological research and new position in the order of nature.

For Stanier and van Niel, the very possibility of formulating the procaryote/eucaryote distinction reflected the realization of their ambitions to integrate the study of bacteria into the theory and practice of general biology. It represented a success for their conception of general microbiology. By the late 1950's, general microbiology had become well-established as an important experimental science of life with its own identity, integrity, and coherence. At the same time, the organisms, techniques, and substantive content of general microbiology supported the consolidation of a new research specialty, called "molecular biology" by its practitioners, directed at the investigation of molecules, especially macromolecules. In this context, bacteria were more valuable as instruments for the study of genes and proteins than as biological entities.

By the middle of the 1950's, a deluge of studies on bacterial heredity and cytology had provided evidence that bacteria shared important genetic and cytological properties with more complex organisms. By formulating new terminology for the phenomenon known as enzyme adaptation, Stanier contributed to the demise of the viewpoint that bacteria were Lamarckian organisms. New cytological investigations showed that bacteria contained a cell nucleus like that in more complex cells. This kind of evidence made possible the acceptance of bacteria as valid representatives of living things in general. Once this was achieved, bacteria could legitimately be used as tools for investigation for general biological problems. By the middle of the 1950's, bacteria had become the organisms of choice for investigations of a wide range of biological and biochemical phenomena, from enzyme synthesis to gene activity.

In his study of the research culture centered on the genetics of the fruit fly Drosophila, historian Robert Kohler has written about the intrinsic dual nature of experimental organisms as both technical and natural entities. He argues persuasively that, in the hands of experimentalists, organisms become technological instruments used for generating data.⁽²⁾ At the same time, he argues, these organisms retain their biological identities. In Kohler's presentation, the technical and biological character of organisms coexist unproblematically. Their dual character is simply intrinsic to experimentation, he suggests.

Writing in a more technically philosophical vein, philosopher of science Hans-Jörg Rheinberger has made experimental systems the subject of analysis. He divides experimental systems into "epistemic things," his term for the phenomenon under investigation, and "technical objects," his term for the elements that make up the experimental conditions. Rheinberger has studied the development and functioning of experimental systems for the analysis of protein synthesis.⁽³⁾

For an emerging group of practitioners in the late 1950's, molecules, especially macromolecules, became the important epistemic things. For these investigators, bacteria served as technical objects. For van Niel and Stanier, however, bacteria had always been fundamentally and crucially epistemic things. While many of their colleagues took up the study of genes and proteins, van Niel and Stanier remained committed to their conception of general microbiology. Between 1955 and 1965, both scientists continued to cultivate microbiology as a biological field. For van Niel and Stanier, microbiological knowledge consisted in understanding the biochemistry, morphology, physiology, ecology, and evolutionary relationships of microorganisms.

By 1961, the question of defining bacteria in biological terms had acquired a new urgency. Bacteria were being used as crucial elements in highly productive research projects concerned with fundamental biological problems, including protein synthesis, the replication of DNA, and the nature of the genetic code. For practitioners interested primarily in molecules, legitimizing bacteria as biological organisms legitimized their tool of investigation. For Stanier and van Niel, defining the biological nature of bacteria and specifying their place in nature constituted core questions for general microbiology. Disciplinary politics, new scientific ideas, and new laboratory practices interacted to stimulate their reconceptualization of the bacterium. The term procaryote, set in opposition to eucaryote, signified the new place for the bacterium in biological practice and its new place in the order of nature. It signified the dual nature of the bacterium as organism and as technology.

In the 1960's and 1970's, as molecular biology became a new professional identity, practitioners began to produce historical narratives to account for its origins. Those histories minimized almost to the vanishing point the connections of molecular biology to general microbiology. The establishment of molecular biology as a cohesive and powerful enterprise entailed a rejection of the conceptual framework of microbiology, its disciplinary organization, and its official history. The success of molecular biology has obscured its significant debts to general microbiology and the importance of this field in its own terms. Understanding the technical, social, and conceptual interconnections between microbiology and molecular biology contributes to a more complete history of both fields.

B. Reconstructing the Bacterium -- Heredity and Cytology

The development of bacteria into instruments of research occurred in conjunction with the generation of new conceptions of bacterial heredity and cytology. Bacteria could be valuable as instruments of research for general biological problems only if their biology were fundamentally similar that of more complex organisms. Van Niel's research on photosynthesis in the 1930's had demonstrated that bacterial and plant photosynthesis shared fundamental features despite their apparent differences. By 1955, two great questions about the biological nature of bacteria appeared to have been solved. The first concerned bacterial heredity. Did bacteria possess genes like those in more complex organisms; or were they Lamarckian organisms capable of adapting to their environment and transmitting their new characters to their descendants? In the 1940's and 1950's, this question became the focus of a vigorous debate with both intellectual and political ramifications. In 1951, while working at the Pasteur Institute with Jacques Monod, Stanier became intimately involved in creating new language to express and reinforce new conceptions of bacterial heredity as non-Lamarckian. By 1955, most researchers investigating bacterial genetics were convinced that bacterial heredity was fundamentally analogous to that of more complex organisms.

A second major question about bacteria concerned their cytological properties. Did bacteria possess an organized cell structure; or were they merely structureless "bags of enzymes," devoid of the attributes of more complex cells, most importantly the cell nucleus? At mid-century, several technical innovations permitted more detailed images of bacterial cell structure. The invention of the electron microscope in 1939, the development of phase contrast microscopy, and the introduction of new staining techniques made possible new interpretations of bacterial cytology.⁽⁴⁾ The new research on bacterial heredity and cytology had a special meaning and importance to van Niel and Stanier. They consistently endeavored to integrate these new findings into the context of general microbiology. These lines of research had important implications for the question van Niel and Stanier considered fundamental to general microbiology: What in biological terms is a bacterium?

In the 1940's and 1950's, the phenomenon known as "bacterial adaptation" or "enzyme adaptation" provided the grounds for a major contest over the nature of bacterial heredity. At the Pasteur Institute, Jacques Monod developed the analysis of lactose metabolism in the bacterium Eschericia coli into a highly productive line of work. In the United States, Sol Spiegelman, a microbiologist at the University of Illinois, studied adaptive enzymes in yeast. At Berkeley, Stanier undertook studies on the mandelate pathway in Pseudomonads. In Britain, Martin Pollock, a medical researcher supported by the Medical Research Council, undertook research on the adaptation of bacteria to antibiotics. This group of investigators launched a major attack on the conventional notion that bacteria were Lamarckian organisms.⁽⁵⁾ At the same time, the British physical chemist and Nobel laureate Sir Cyril Hinshelwood continued to champion the Lamarckian conception of bacterial inheritance in his influential monograph of 1946, The Chemical Kinetics of the Bacterial Cell.⁽⁶⁾ Hinshelwood defined a position that Stanier, Pollock, Spiegelman, and the group of researchers at the Pasteur Institute set out to combat. Between 1951 and 1953, Stanier and Monod endeavored to create new terminology with new conceptual content to describe the synthesis of enzymes in bacteria. This new language contributed to the adoption of new conceptions of bacterial genetics.

Conceptions of bacteria as Lamarckian organisms had persisted since the nineteenth century, when observers had noted that some strains of bacteria would change morphologically and/or physiologically in response to new environments.⁽⁷⁾ In the 1930's, Hennig Karström, a student of the Finnish microbiologist Arturri I. Virtanen, carried out the first biochemical studies of the adaptation of bacteria to new sugar sources. Karström noted that when a strain of bacteria now called Enterobacter aerogenes was cultivated in media containing glucose, the cells could metabolize only glucose and not other sugars, for example, galactose, arabinose, maltose, or lactose. However, cells exposed to any one of these sugars for a period of time could acquire the ability to metabolize it. Karström observed that the bacteria could always metabolize glucose, regardless of which type of sugar they had previously been provided. He introduced the term "constitutive enzyme" to refer to enzymes the cells always produced, regardless of the sugars provided in the growth medium. Karström proposed the term "adaptive enzyme" to refer to those produced only when needed as an adaptation to a new sugar in the growth medium. Working in the laboratory of F.G. Hopkins at Cambridge, Marjory Stephenson also took up the study of "adaptive enzymes" in the 1930's. Along with her student J. Yudkin, Stephenson published several studies demonstrating the adaptation of bacteria to different biochemical environments.⁽⁸⁾

A second research group in Britain, working on bacterial nutrition, came to similar conceptions of bacterial heredity. Bacteriologist Sir Paul Fildes, working at the Middlesex Hospital in London, analyzed the requirements for tryptophan in the Bacterium typhosum (now called Salmonella typhosa). His studies in the early 1930's showed that naturally occurring isolates of B. typhosum required the amino acid tryptophan in their growth medium. He found that samples from a culture would survive and grow if transferred to a medium containing a slightly lower concentration of tryptophan. This process could be repeated until a culture was obtained that could grow without any tryptophan. Fildes called this process "training." He concluded that bacteria acquired the ability to synthesize tryptophan by adapting to the environment.⁽⁹⁾

In the 1940's, research by Max Delbrück, Salvador Luria, and Joshua Lederberg, among others, had begun to establish a body of evidence that undermined Lamarckian interpretations of bacterial heredity.⁽¹⁰⁾ To demolish that view, the phenomenon of enzyme adaptation required a new explanation. In 1951, Stanier spent his sabbatical at the Pasteur Institute in Paris, where he worked closely with André Lwoff and Jacques Monod in the Service de Physiologie Microbienne (Department of Microbial Physiology). By 1951, Monod's research on the synthesis of the enzyme ß-galactosidase in E. coli was moving ahead rapidly. Monod's research on this phenomenon complemented beautifully the new work on bacterial genetics led by Lederberg, whose work sometimes yielded mutants affecting lactose metabolism. Biochemical and genetic approaches made a powerful combination.⁽¹¹⁾

In 1948, the American immunologist Melvin Cohn joined the group at the Pasteur to work with Monod. They carried out a series of experiments that undermined the Lamarckian conception of enzyme adaptation. In 1950, Cohn synthesized several compounds that could act as artificial substrates for the enzyme ß-galactosidase. Like the natural substrate lactose, some of these artificial substrates stimulated the cell to synthesize the enzyme. Others, however, did not. That is, not all metabolizable substrates caused the cell to make the relevant enzyme. Further, some artificial galactosides (sugars related to the usual substrate, lactose) that could not be metabolized did have the effect of inducing the synthesis of the enzyme. In other words, not all inducers were substrates, and not all substrates were inducers. The synthesis of the enzyme occurred independently of its activity as a catalyst. These observations implied that the cell did not adapt as a direct response to the presence of metabolizable substrates.⁽¹²⁾

In 1951, Stanier and Monod began a discussion of the conceptual implications of the terminology used to describe enzyme adaptation. Both scientists found the term "adaptation" problematic. Particularly troublesome to Stanier was that adaptation had a specific biological meaning in the context of Darwinian evolutionary theory. In a 1951 review article, he wrote:

'Adaptation' is used by biologists with two radically different meanings. Applied to a species, 'adaptation' describes modifications of structure or function that fit the species in question for its particular ecological niche (e.g., long necks on giraffes); implicit in this usage is the assumption of genetic change as a mechanism. Applied to an individual organism, 'adaptation' describes transient modifications under direct physiological control (e.g. color change in fishes) whose mechanism is clearly non-genetic.⁽¹³⁾Stanier believed that the use of the same word for two very different kinds of biological phenomena had muddled the minds of many microbiologists: "The dangers are obvious, and it can hardly be doubted that the persistent failure of certain authors to differentiate (or sometimes even to grasp the distinction) between enzymatic adaptation sensu stricto and mutational changes modifying enzymatic constitution is partly attributable thereto."⁽¹⁴⁾ In 1951, Stanier recommended that "enzymatic adaptation" be used only to refer to biochemical changes not involving mutations or changes in genotype.

Stanier and Monod found the word "adaptation"problematic for a second reason; it had Lamarckian connotations. To call a process "adaptive" implied that it resulted from an intentional response to an environmental stimulus. Stanier rejected this implication primarily on intellectual grounds. For Monod, reforming bacterial heredity had both political and intellectual significance. In the 1940's and 1950's, Lamarckian concepts were tightly associated with the Soviet geneticist Trofim Denisovich Lysenko. In the 1940's, Monod had been an active member of the French Communist Party. His decision to break with Lamarckian conceptions constituted a decisive break with official Communist ideological positions.⁽¹⁵⁾

Stanier and Monod reached an important conclusion: to expunge the term "adaptation" from discussion of the transient synthesis of new enzymes induced by environmental factors. They then faced the challenge of creating a new way of describing the phenomenon. After Stanier's return to Berkeley, Monod and Stanier corresponded. The letters they exchanged indicate that Stanier and Monod jointly instigated the project to formulate new terminology for enzyme adaptation. They then recruited their colleagues who worked on enzyme adaptation, Cohn, Pollock and Spiegelman, to give the new language their respective seals of approval.

In 1952, for example, Monod wrote to Stanier to ask for a culture of Pseudomonas fluorescens adaptable to tryptophan. "What about nomenclature?" he added in a postscript.⁽¹⁶⁾ In response, Stanier sent Monod a manuscript that proposed new language for describing the phenomena previously known as enzyme adaptation. In December, Monod thanked Stanier for the new version of the manuscript. "I find it excellent," he wrote, except for the word "eduction" which he found to be "completely impossible." He went on to say that Pollock was still "extremely reticent" and might not join the nomenclature project, which Monod considered to be "regrettable."⁽¹⁷⁾ Monod suggested to Stanier that they meet with Cohn, Pollock, and Spiegelman at the meeting of the Society for General Microbiology in April 1953 in London. The topic for the meeting, "Adaptation in Microorganisms," would attract most of the major players in the field, including the physical chemist Hinshelwood, still enthusiastically defending Lamarckian conceptions of bacterial heredity.⁽¹⁸⁾

At the meeting, Stanier gave a paper in which he again attempted to distinguish between physiological and evolutionary adaptation. He cast his discussion in broad biological terms and emphasized the special capacity of microorganisms to respond to rapidly fluctuating ecological conditions.⁽¹⁹⁾ While in London for the meeting, Stanier, Monod, Pollock, Cohn, and Spiegelman met to discuss new terminology proposed initially by Stanier and Monod. Pollock at first refused to endorse the new language. He later recalled that he had been violently against it because it represented the dogmatic imposition of the opinions of a clique. He also thought the word "adaptation" was useful, especially for describing the response of the immune system. Nonetheless, he eventually succumbed to the pressure of his colleagues.⁽²⁰⁾ In May 1953, Monod wrote to Stanier to say that Pollock's assent to sign the note had been won at the price of a few minor concessions. He promised to submit the note to Nature as soon as he had the approval of Spiegelman and Stanier.⁽²¹⁾

In print, the group of researchers, which Cohn liked to call the "Adaptive Enzymes College of Cardinals," presented a unified front.⁽²²⁾ The two-page article, "Terminology of Enzyme Formation," signed by Cohn, Monod, Pollock, Spiegelman, and Stanier, appeared in the December 12, 1953 issue of Nature.⁽²³⁾ The article recapitulated the distinction made by Stanier in his earlier work between adaptation in the evolutionary sense and short-term physiological changes. It introduced a new set of terms in which to discuss enzyme adaptation. As a first step, the authors advocated replacing the word adaptation with a term that could be defined with biochemical precision. They proposed the term "induction" to refer to the increased rate of synthesis of an enzyme elicited by the presence of a specific substance. An adaptive enzyme became, in the new language, an induced enzyme. The substance that caused enzyme induction would then be called an "inducer." The authors retained Karström's term "constitutive" to refer to enzymes synthesized in the absence of inducers. The phenomenon Stanier had called "simultaneous adaptation" was re-named "sequential induction." The new language distinguished between the activity of the enzyme and the conditions of its synthesis. The authors pointed out, "Thus, 'constitutivity' and 'inducibility' are properties of enzyme-forming systems, not of enzymes per se." Noting that enzyme induction had recently been found in mammals, the authors anticipated that this process would "prove to be a general property of biological systems." Making this comparison implied that studies on enzyme induction in bacteria would have general biological relevance.

The new language redefined a phenomenon previously treated as an adaptive behavior of an organism in terms of the properties of a biochemical and genetic system. It made possible the formulation of new questions that could be translated into experiments: How did enzyme induction occur? How did the presence of an inducer specifically elicit an increased rate of enzyme synthesis? The analysis of the biochemical details of enzyme induction led Monod and Francois Jacob to their Nobel Prize-winning work on the regulation of gene function, carried out in the late 1950's. Analysis of the regulation of inducible enzymes became a major endeavor in molecular biology in the 1960's.

Thus, Stanier played an important role in formulating concepts that became a part of the substantive content of molecular biology. Previous accounts have neglected Stanier's involvement in creating the new concepts and terms.⁽²⁴⁾ It was typical of Stanier to involve himself in a problem of this nature. His conception of general microbiology required him to pay close attention to basic definitions and concepts concerned with the properties of microorganisms.

Redefining enzyme adaptation in bacteria as enzyme induction gave bacteria an important property in common with more complex organisms. In the 1940's and 1950's, researchers in bacterial genetics frequently emphasized the similarity between bacteria and more complex organisms. Language standard for more complex organisms was often recruited to describe processes newly discovered in bacteria. In the 1940's and 1950's, genetic recombination in bacteria was routinely described as "sexual reproduction" or as "bacterial sex." High rates of recombination in some strains of bacteria were attributed to so-called "fertility" factors. When bacterial mating was found to be uni-directional, the cell donating genetic material was identified as "male" and the recipient "female."⁽²⁵⁾ The importance of this language is that it eroded the barriers distinguishing bacteria from "higher cells" and promoted the impression of their basic similarity.

Research in the 1940's and 1950's led to revised conceptions of bacterial cytology as well as heredity. By the middle of the 1950's, many of the characteristics once thought to distinguish bacteria from more complex organisms had been revised or rejected. New microscopic methods provided images of bacteria that showed that they were not structureless bags of protoplasm, but possessed a distinctive form of organization. The most important revision of conceptions of bacterial cytology concerned the question of the cell nucleus. Whether or not bacteria possessed nuclei had been debated for decades. In the nineteenth century, the German zoologist Ernst Haeckel believed that organisms like bacteria, which he called Monera, were not differentiated into protoplasm and nucleus, as were the cells of more complex organisms. Therefore, he concluded, Monera were not composed of cells at all; they were simply particles of Urschleim.⁽²⁶⁾

By the 1940's, bacteria were generally accepted as cellular organisms, but the status of the nucleus was unclear. In 1945, microbiologist René Dubos identified eight different interpretations of the bacterial nucleus under discussion by bacterial cytologists.⁽²⁷⁾ Studies by Canadian cytologist Carl F. Robinow were especially influential in reviving the debate over the bacterial nucleus. Initially published in a British medical journal during the Second World War, Robinow's work became better known as an addendum to Dubos's widely read monograph of 1945. Robinow obtained images of bacteria with a distinctive densely-staining, round body localized in the center of the cells. He concluded that these bodies were nuclei and that they underwent a division process as well.⁽²⁸⁾ Robinow carried out an extensive correspondence with Stanier concerning his research. In 1947, he described some of his results: "I had some fine results with the light microscope after weeks with the still much less vocal electron instrument, and feel happy in my increasingly securely grounded ideas on the structure of the cells of the aerobic spore-formers [a kind of bacteria]...there are now contacts with general cell physiology." Robinow then described the cytoplasm, nucleus, and a layer of cytoplasm residing next to the cell membrane called the cortical region in these bacteria.⁽²⁹⁾

In the late 1940's, the French cytologist R. Tulasne, among others, confirmed Robinow's interpretations of the bacterial nucleus. Modifying Robinow's techniques, Tulasne showed that cells treated with the enzyme ribonuclease and then stained for DNA yielded clear images of nuclear structures. Other studies showed that treatment with desoxyribonuclease destroyed the bacterial cell nuclei.⁽³⁰⁾

The development of the electron microscope made possible the examination of material at a much greater level of resolution, on the order of millimicrons, compared to a theoretical limit of 0.16 microns for light microscopy. By using the electron microscope, investigators could visualize the interior of bacterial cells, many of which were 1 micron or less in diameter.⁽³¹⁾ Some of the first studies on bacteria appeared to indicate the presence of a cell nucleus.⁽³²⁾ In 1953, two research groups introduced independently a new technique for preparing ultra-thin sections of cells, which promised to yield clearer images in the electron microscope.⁽³³⁾ James B. Hillier, a researcher at a laboratory operated by the RCA corporation in Princeton, produced some of the first micrographs of ultra-thin sections of bacteria. Hillier and George B. Chapman, a graduate student at Princeton, published micrographs that could be interpreted to mean that the bacterial cell had structure. In particular, the central area of the cell appeared markedly different from the surrounding cytoplasm. Chapman and Hillier interpreted these images as evidence for the existence of the bacterial nucleus.⁽³⁴⁾

Research on bacterial genetics in the 1940's and 1950's exerted a significant impact on interpretations of bacterial cytology.⁽³⁵⁾ In 1948, Tatum, a co-discoverer with Lederberg of bacterial sex, asked Robinow to give a lecture at Yale on the structure of bacteria.⁽³⁶⁾ Increasing confidence in the reality of bacterial genetics created an incentive to identify a morphological nucleus. By the middle of the 1950's, bacteria were widely believed to contain nuclei. The conviction that bacteria contain nuclei became so overwhelming by the early 1950's, that some investigators began to report the occurrence in bacteria of a nuclear division process, or mitosis, completely analogous to that in more complex cells. At the CSH meeting in 1951, Edward D. DeLameter, the leading proponent of mitosis in bacteria, gave a presentation that reflected the convergence between conceptions of bacterial genetics and cytology. In a lecture entitled, "A New Cytological Basis for Bacterial Genetics," DeLameter described a mitosis in the bacterium Bacillus megatherium, complete with centrioles, mitotic spindles, and metaphase plates, the prominent features of cell division in more complex cells. ⁽³⁷⁾ Many contemporary microbiologists criticized DeLameter's interpretations, which were later seen as absurd. However, even some of DeLameter's harshest critics were fully prepared to believe in the existence of a bacterial nucleus.⁽³⁸⁾ Even if the reality of bacterial mitosis was in doubt, the nucleus was not. In 1953, microbiologist Stuart Mudd reviewed both genetic and cytological evidence for the bacterial nucleus at a symposium on bacterial cytology at the Seventh International Congress of Microbiology. Mudd concluded, "The existence of a true nucleus in bacteria, which was controverted for so many decades, can hardly be questioned seriously now."⁽³⁹⁾

For Stanier and van Niel, the question of the bacterial nucleus had important implications for their ongoing attempts to define bacteria in biological terms. In 1941, they had argued that the bacteria and blue-green algae should be united in their own kingdom, to be called the Monera. To define this kingdom, they had relied on three criteria: the lack of a "true" nucleus, the absence of sexual reproduction, and the absence of membrane-bound structures within the cytoplasm. By 1955, the first and second of these criteria had fallen.   Bergey's Manual, the standard handbook for bacterial taxonomy published by the SAB, continued to treat bacteria as a class within the Plant Kingdom. The sixth edition, published in 1948, described bacteria as, "Typically unicellular plants."⁽⁴⁰⁾

In 1955, van Niel revisited the question of the nature of bacteria and their place in nature. In light of the previous two decades of research, he presented a review of bacterial taxonomy and classification for a book in honor of the centennial of the California Academy of Sciences.⁽⁴¹⁾ Here van Niel demonstrated his continuing sympathy for natural historical questions that were perceived as obsolete by many of his contemporaries.⁽⁴²⁾ In 1955, as in 1941, it appeared evident to van Niel that bacteria should be united with the blue-green algae within their own kingdom. The problem was how to define one:

Recent developments have raised difficulties great enough to threaten the very basis of the characterization of the kingdom. The most important of these deal with the problem of the 'bacterial nucleus.'...Even though convincing demonstration of nuclei has not yet been accomplished for more than a few bacterial and myxophycean types, it may be confidently expected that future work will fill the existing gap.⁽⁴³⁾In his discussion, van Niel included references to works on mitosis in bacteria, suggesting that he considered it to be a real possibility. Van Niel was forced to admit that it was no longer possible for microbiologists to define a taxonomic category that included the bacteria and blue-green algae, but excluded all other microorganisms. On the other hand, he believed it to be an important goal:

Thus, it is clear that the criteria for a kingdom of organisms without nuclei do not apply to the bacteria and blue-green algae. This does not mean, however, that the notion of establishing a separate kingdom for these organisms should be abandoned...there are good reasons to for subscribing to the idea that we must reckon with the existence of organisms that are neither plants nor animals and represent the descendants of precursors of both these groups. The difficulty will be to devise adequate criteria for such a taxon; this remains a task for the future.⁽⁴⁴⁾ It was embarrassing for the microbiologists, especially the theoreticians Stanier and van Niel. They could not say with any precision in biological terms what bacteria were. In the middle of the period in which bacteria had achieved a new importance in biological practice and new biological properties, the microbiologists could only conclude that the old definitions no longer applied. A new way to define the biological nature of bacteria and their place in nature remained to be devised.

C. Microorganisms and Macromolecules

By the mid-1950's, research on bacterial heredity and cytology had made it possible to conceive of bacteria as valid representatives of general biological phenomena. It also provided assurance for investigators who had invested their research programs in the study of bacteria. They could assume that their research had wide applicability and did not pertain exclusively to a group of marginal, idiosyncratic organisms. In 1954, Jacques Monod expressed this point in a widely quoted phrase: "What's true for E. coli is true for an elephant."⁽⁴⁵⁾

In some respects, the acceptance of bacteria as legitimate organisms represented a success for van Niel's ambitions for general microbiology. In the middle of the 1950's, however, van Niel sensed an increasing divergence of interest between researchers engaged in analysis at the biochemical level and those committed to studies of organisms in a general biological context. He observed that some investigators regarded bacteria merely as a useful instruments for the study of molecules, rather than as biological entities. Van Niel viewed this attitude with dismay because it undermined the importance of the questions that lay at the core of his disciplinary ambitions and his life's work. During the last decade of his scientific life, van Niel continued to cultivate microbiology as a general science of life in which biochemistry, morphology, physiology, and ecology provided complementary perspectives, each indispensable for achieving a complete understanding of the living world. He consistently integrated new evidence about microbial biochemistry and genetics into a broad biological context.

Van Niel expressed his concerns about emerging new attitudes at the opening of the Institute for Microbiology at Rutgers in 1954, when he delivered an address called "The Microbe as a Whole." In his lecture, van Niel gave a reprise of the main points of his lecture on the "Delft School" in 1949. Once again, he celebrated the recent expansion of general microbiology and its emancipation from medical bacteriology. He again paid tribute to Kluyver's statement of the principle of the unity of biochemistry. As before, he noted with satisfaction the importance of microorganisms in recent biochemical research:

The microbes became the material par excellence for studies of special nutritional problems and of enzyme systems. And when at last methods were perfected for the extraction of enzymes from bacteria, yeasts, molds, and other microbes...our understanding of the details of biochemical reaction mechanisms through the use of microorganisms advanced rapidly. Unquestionably, biochemistry has profited greatly from these developments.⁽⁴⁶⁾ At the same time, van Niel expressed new concerns. He perceived a new threat to general microbiology, an emerging reductionist viewpoint: "There is now developing a strong tendency to equate 'general' microbiology, as contrasted to 'medical' microbiology, with biochemistry and to consider the study of microorganisms as truly significant only if it is directed towards biochemical investigations."⁽⁴⁷⁾ Especially disturbing to van Niel was a new attitude toward the microorganism:

The microbiologist receiving a request for a pure culture of some bacterium...from a biochemist who wishes to use it for a specific biochemical investigation cannot always escape the conclusion that the culture in question will be considered as little more than a potential enzyme preparation...the microbiologist is likely to be somewhat apprehensive when his material is treated as a chemical reagent.⁽⁴⁸⁾ Here van Niel confronted an essential and inescapable tension in experimental biology: the very execution of an experiment makes an organism into a technical object, to use Rheinberger's term. To restore it to the status of epistemic thing requires an intellectual act. To van Niel, the purpose of biochemical and biophysical investigation was to understand the properties of living things. Studies of whole organisms and biochemical analysis were essential, van Niel held, for:

the attainment of a better comprehension of the manifestations of matter on a level of complexity such as characterizes a microbe, implying organization, growth, and responses to environmental factors through irritability, variability, and adaptation, all of which may be combined in the term 'individuality.'⁽⁴⁹⁾ In drawing attention to these complex phenomena, van Niel did not intend a return to vitalism: "I do not mean to express a belief that such phenomena cannot ultimately be explained on the basis of physico-chemical events."⁽⁵⁰⁾ He sensed, however, a new intolerance by biochemists and biophysicists toward scientists who continued to study the organismal level. This was both socially irritating and intellectually costly:

I believe that in the end science would benefit if the tentative and often unrewarding probings into the behavior of microorganisms on a level now beyond the scope of biochemical and biophysical experimentation were not merely tolerated but encouraged. The tendency to look down on the efforts of microbiologists who do not follow the current trends, and to brand such studies as rather primitive dabblings in the natural history of microorganisms, seems to me short-sighted.⁽⁵¹⁾ From van Niel's point of view, the transformation of bacteria into research instruments was extremely problematic. The result was not a simple, harmonious coexistence of different identities, but increasing strain with intellectual and social consequences. He perceived the possibility that a disciplinary division of labor could develop. As long as the microbiologists concerned themselves with the biological properties of microorganisms, biochemists, biophysicists, and later, molecular biologists would be free to ignore them. Potentially, general microbiology could be made into a service discipline for researchers working at the biochemical level.

While microbiology continued to enjoy a prestigious position in the late 1950's, a new disciplinary rival emerged. The structure and function of macromolecules, especially proteins and nucleic acids, began to attract more and more attention. By the end of the 1950's, the term "molecular biology" began to be used to designate institutions, funding categories, and professional identities. The realignment of research problems and professional identities under the category molecular biology is still poorly understood. The research now available, while valuable, does not provide a complete account of this complex process. What constitutes molecular biology and how its history should be approached is under discussion by a number of scholars.⁽⁵²⁾ I will not attempt to resolve those issues here. From any point of view, however, it is undeniable that the study of the structure and function of proteins and nucleic acids acquired an entirely new importance for the experimental life sciences in the late 1950's. The recognition between 1953 and 1955 that both nucleic acids and proteins consisted of specific, stable sequences made possible a new conception of the classic problem of the relationship between genotype and phenotype. Protein synthesis, the genetic code, and regulation of gene activity developed into new foci of research in the late 1950's.⁽⁵³⁾

As van Niel feared, for many researchers interested in the structure and function of genes and proteins, the dominant identity of the bacterium became that of instrument. Research undertaken by four graduates of van Niel's course illustrate the point. Soon after hearing of Watson and Crick's structure for DNA, the physicist-turned-biologist Seymour Benzer set out to determine if genetic mutations could be correlated to single nucleotide changes in the nucleotide sequence of DNA. In 1955, working with bacteriophage, he succeeded. His work made it possible to identify precisely the physical-chemical basis of certain kinds of mutations.⁽⁵⁴⁾ Arthur Kornberg, working first at Washington University and then at Stanford, took up the identification and isolation of the enzymes involved in the replication of the DNA in the late 1950's. The bacterium E. coli served as the source for his experimental materials.⁽⁵⁵⁾ Kornberg's colleague Paul Berg investigated the enzymatic and energetic requirements for linking amino acids to ribonucleic acids in the process of protein synthesis. He, too, worked with bacteria.⁽⁵⁶⁾ At Berkeley, Bruce Ames took up the study of the regulation of the synthesis of enzymes involved in the synthesis of the amino acid histidine. He made the important observation that the presence of histidine repressed the synthesis of four different enzymes involved in its synthesis.⁽⁵⁷⁾

In these lines of investigation, the bacterium served as a valuable instrument, not the phenomenon to be investigated. The bacterium became the reaction vessel in which the interesting molecular phenomena occurred. The question of their nature as biological entities receded into the background. As Berkeley molecular biologist Bruce Ames expressed it, "I worked with bacteria most of my life," he said, "but it was more a tool to understand biochemical genetics and how DNA worked."⁽⁵⁸⁾ Ames's comments reveal that bacteria as organisms or biological entities interested him little if at all. Rather, as he readily admits, he valued bacteria as useful instruments for investigating the structure and the function of DNA. Ames sought to understand the behavior of molecules, not microorganisms.

While van Niel objected to the treatment of bacteria primarily as instruments, he appreciated the importance of the new developments in molecular genetics. He sought to integrate them into his conception of microbiology. In 1954, he wrote to the RF detailing his plans for a sabbatical in Europe. He emphasized that he especially wanted to visit Lwoff at the Pasteur Institute:

I should like to reach the stage where his philosophy of lysogeny and related problems has become thoroughly familiar to me. Since there are many phenomena which appear to me capable of being further integrated with this outlook, I hope that a prolonged sojourn in Paris may help me to determine whether there are prospects for arriving at some more general concepts which will include genetics, induced enzyme synthesis, and adaptations in general.⁽⁵⁹⁾ In March of 1955, van Niel sailed to Europe with a Guggenheim Fellowship and special grant from the RF in hand for his second sabbatical year. In London, his first port of call, he gave the second Marjory Stephenson Memorial Lecture to the Society for General Microbiology. For the occasion, he chose a decidedly biological topic: "Natural Selection in the Microbial World."⁽⁶⁰⁾ He then traveled Norway to attend the inauguration of his former graduate student Helge Larsen as Professor of Microbiology at the University of Trondheim. For a few months, he worked hard with Kluyver in Delft on the manuscript of The Microbe's Contribution to Biology. He then visited several important microbiology laboratories in Europe. At the Pasteur Institute, van Niel immersed himself in the new developments in microbial biochemistry and genetics underway in the laboratories of Lwoff, Monod, Jacob, geneticist Eli Wollman, and biochemist George Cohen.⁽⁶¹⁾

Van Niel spent three months in Lwoff's laboratory, an experience he later called the "scientifically most exciting" period of his sabbatical.⁽⁶²⁾ By 1955, Lwoff had made considerable progress in elucidating the nature of the phenomenon called lysogeny. In Lwoff's new interpretation, when a bacteriophage entered a bacterial cell, it had two possible fates. In one pathway, the bacteriophage would reproduce itself many-fold by taking advantage of the bacterium's cell constituents and energy supply. Alternatively, the genes of the bacteriophage could become inserted into specific locations on the chromosome of the bacterial host, where they would remain quiescent until activated by specific physical or chemical stimuli. He called this latent form of the bacteriophage, the prophage.⁽⁶³⁾

At the Pasteur Institute, a new institutional structure reflected the increasing emphasis on research at the molecular level. In 1954, Monod had become the head of the newly established Service de Biochimie Cellulaire. He continued his research on the genetics and biochemistry of enzyme induction.⁽⁶⁴⁾ With Cohen, he began an investigation of enzymes called permeases that transport sugars from the outside of the bacterium through the cell membrane into the cell interior where they can be metabolized.⁽⁶⁵⁾

After visiting the Pasteur Institute, van Niel spent a month at the Weizmann Institute in Israel, and then ten days at the University of Strasbourg. He paid a final visit to Kluyver in Delft two days before departing for home. News of Kluyver's death reached van Niel during his journey by steamship back to California. It was not unexpected, but saddened van Niel nonetheless.⁽⁶⁶⁾

Van Niel's return to the Hopkins Marine Station meant writing numerous obituary notices and contributing to a memorial volume to Kluyver.⁽⁶⁷⁾ These tasks were lightened by the continued activity in the laboratory and by teaching his summer course. Between 1956 and 1962, sixteen postdoctoral fellows spent a year or more in van Niel's laboratory. They represented a broad range of interests within the domain of general microbiology.⁽⁶⁸⁾ Hans Veldkamp in 1956 and J.W.M. LaRivire, Kluyver's last student, maintained the Dutch connection. Veldkamp undertook studies of marine agar-decomposing myxobacteria. Robert K. Neff studied the distribution of soil amoebae in nature and the conditions for their cultivation in the laboratory. Edwin H. Battley developed a thermodynamic analysis of the growth of the yeast Saccharomyces cerevisiae. Jeanne Poindexter, a doctoral student with Stanier, undertook a survey of the general biology and taxonomy of the Caulobacter group of bacteria.

Many students and colleagues speak of working with van Niel in intensely emotional terms. Some attest that van Niel had extraordinary impacts on their lives. "The year I spent with van Niel was the year I discovered it was possible to be happy," said Veldkamp. He cited the beautiful surroundings of the marine station and the sense of being close to nature as contributing to his happiness. Even more important, Veldkamp said, was the opportunity to learn from a master microbiologist who "knew everything," and at the same time gave his students and colleagues complete freedom in research.⁽⁶⁹⁾ Veldkamp returned to the Netherlands to the Rijksuniversiteit Groningen, where he established a strong program in microbial physiology and ecology very much like van Niel's.

Oceanographer and microbiologist Holger Jannasch has also recorded a profound debt to van Niel. While technically a postdoctoral fellow at the Scripps Institute for Oceanography, Jannasch convinced van Niel to allow him to audit the summer course in microbiology in 1958. Van Niel's high intellectual standards, broad cultural knowledge, and sensitivity as a teacher all deeply impressed Jannasch. He went on to a distinguished career as a marine microbial ecologist, spending most of his career at the Woods Hole Oceanographic Institute, which he joined in 1962. In 1970, he became director of a summer course in microbial ecology at the nearby Marine Biological Laboratory. He turned to van Niel and Stanier for advice and invited many of their former students and colleagues to lecture in the course.⁽⁷⁰⁾ Jannasch became the world leader in exploring the array of microbial organisms inhabiting the extreme conditions of deep sea hydrothermal vents.⁽⁷¹⁾ Toward the end of his career, he felt indebted to van Niel for giving him the confidence that he could accomplish something of value in science.⁽⁷²⁾

The German microbiologist Norbert Pfennig obtained basic training in his field at the only institute for microbiology in Germany in 1946, at the University of Göttingen. As a postdoctoral fellow, he became interested in the new species of purple bacteria present in a sample of pond water smuggled in from the Soviet Union. As an enthusiast of the ecology of the purple bacteria, Pfennig arranged to spend a year at the HMS to work with van Niel. He audited van Niel's course in the summer of 1962, the last time it was given. "It was an exciting experience and we all got the impression that this is the way in which science should be taught....van Niel followed his view that the main task of the academic teacher is to present, together with established knowledge, the open questions, unsolved problems, and neglected fields of work," he recalled.⁽⁷³⁾ During his stay in California, Pfennig collaborated with Stanier and Cohen-Bazire at Berkeley as well. Together, they examined the green bacterium Chlorobium through electron microscopic methods. They found that these organisms contained vesicles that house some of the pigments involved in photosynthesis.⁽⁷⁴⁾ Pfennig returned to Germany as professor first at the University of Gttingen and then at Constance. He pursued an active research program in microbial ecology for three decades.⁽⁷⁵⁾

Many scientists who are not identified as microbiologists have also recorded debts to van Niel's teaching. Konrad Bloch, Professor of Chemistry at Harvard in the 1960's and 1970's took van Niel's course in microbiology in 1957. He later wrote, "The exceedingly demanding course, a bravura performance, and a model of pedagogy, taught me important lessons that were to influence much of my later research."⁽⁷⁶⁾ Bloch analyzed the synthesis of complex organic compounds built of ring-shaped structures called pyrolles, such as the lipid cholesterol. He won the Nobel Prize in 1964.

By the late 1950's, van Niel and the Hopkins Marine Station faced changing institutional conditions. At Stanford, President J.E. Wallace Sterling had appointed the electrical engineer Frederick E. Terman as Provost in 1954 to oversee a major initiative to build up research programs capable of securing large government grants. Small programs were targeted for elimination.⁽⁷⁷⁾ In 1958, Stanford succeeded in enticing both Arthur Kornberg and Paul Berg away from Washington University to establish a Department of Biochemistry at the School of Medicine. When Lederberg, who won the Nobel Prize in 1958, also agreed to join the department, it became a major center for research in molecular biology. Kornberg's Nobel Prize in 1959 contributed to the growing prestige of the new department. On the main campus, Victor Twitty, an embryologist and chair of the Department of Biology, tried to maintain a balance of viewpoints including organismal biology and the newer molecular approaches. When Donald Kennedy became chair of the department, he succeeded in retaining a strong program in population biology, while agreeing to eliminate the museum of natural history.⁽⁷⁸⁾

In the late 1950's, as research programs aimed at the study of genes and proteins achieved a new currency, so did the term molecular biology. At Cambridge, where Watson and Crick had determined the structure of DNA, negotiations for a Laboratory of Molecular Biology began in 1957. It was the first major institution to adopt that name.⁽⁷⁹⁾ In some institutions, as at Stanford, biochemistry departments provided institutional locations for research programs later identified as core aspects of molecular biology. Historians of science have begun to examine the articulation of boundaries between biochemistry and molecular biology.⁽⁸⁰⁾

Similarly, establishing institutional and intellectual boundaries between microbiology and molecular biology required negotiation, a process that has been little explored by historians. In late 1950's, this process had begun but was not complete. Microbiologists continued to claim any major research accomplishments carried out with microorganisms as evidence of the importance and power of their discipline. In a grant proposal to the NSF in 1959, a committee of SAB leaders wrote, "Recent discoveries in the genetics of micro-organisms and the synthesis of nucleic acids by bacterial enzymes, as exemplified by the awarding of the Nobel Prize to Lederberg, Beadle and Tatum in 1958, and to Kornberg and [Severo] Ochoa in 1959, have called attention to the almost limitless chance for both fundamental and applied work with bacteria, viruses, yeast, molds and other microorganisms."⁽⁸¹⁾ The committee proposed to prepare a booklet to be entitled "Bacteriology as a Career," as if these discoveries were representative of the work of bacteriologists. The evolution of microbial genetics into molecular genetics and the development of molecular biology as a field of work distinct from microbiology invite further study.

D. A New Order of Things -- Roger Stanier, C.B. van Niel, and the Procaryote/Eucaryote Distinction

In the late 1950's, Roger Stanier continued to preside over the cultivation of general microbiology at Berkeley. Active in campus-wide and departmental politics, he served on numerous committees and earned a reputation as a brilliant and energetic scientist, and as an aggressive and sometimes domineering personality.⁽⁸²⁾ Like van Niel, Stanier remained committed to a conception of microbiology as a general science of life. At the same time, he kept a close watch on developments in biochemistry, virus research, and bacterial genetics. At Berkeley, he was in frequent contact with researchers at the Virus Laboratory like Stanley, whom he detested, and Stent, a close friend. To maintain his connections with the leaders of research in bacterial genetics, Stanier corresponded frequently with Lederberg, Luria, Novick, and Monod. Stanier's own research in the late 1950's centered on photosynthesis in bacteria, especially the control of the synthesis of photosynthetic pigments and the role of carotenoids. Stanier carried out many of these studies in collaboration with his student William Sistrom, a postdoctoral fellow, Mary Griffiths, and Germaine Cohen-Bazire.⁽⁸³⁾ Within the Bacteriology Department, conflicts between the general microbiologists and the pathologists continued unabated. Disagreements over curriculum, positions, and the relationship of the department to the Naval Biological Laboratory (NBL) created constant discord.

In the late 1950's, the nature of bacteria as biological entities, the status of bacteria as objects of research, departmental politics at Berkeley, and the definition of the field of general microbiology occupied Stanier's attention as a set of intertwined problems. In 1961, he and van Niel attempted to articulate a formal biological definition for bacteria, as they had two decades before. This time, they succeeded. By taking advantage of the previous two decades of research on bacterial cytology and genetics, Stanier and van Niel devised a new concept of the bacterium and, as a consequence, proposed a new order of nature.

In the late 1950's, Stanier undertook several projects in which he compiled and consolidated the rapidly expanding body of knowledge about microbial biochemistry, genetics, physiology, and cytology. In 1952, he, Doudoroff, and Adelberg started to write a textbook in general microbiology suitable for undergraduate teaching. The first edition of The Microbial World, published in 1957, represented an attempt to express in print the principal messages of van Niel's course in microbiology. The authors organized their subject into three main sections. "The Properties of Microorganisms" covered the discovery of microorganisms and the methods of microbiology, surveyed the algae, protozoa, fungi, and bacteria, and discussed microbial physiology in detail. One of the first nineteen chapters discussed mutation and genetic recombination in bacteria. "The Ecology of Microorganisms," the second major section, included microorganisms as geochemical agents, their role in the cycling of matter through the biosphere, and symbiotic interactions. The authors treated disease as a special case of host-parasite relationships. A chapter on the practical uses of microorganisms in the making of beer, wine, vinegar, lactic acid, butyric acid, antibiotics and other chemicals came last. The third section of the book, "The Biological Background," gave a summary of the cell theory, cell physiology, genetics, evolution, classification, and metabolic biochemistry. In the introduction, the authors attested to the new importance of microorganisms and the discipline of microbiology for general biology:

Microbiology was for a long time very largely an applied science, empirical in outlook, and isolated from the mainstream of biological thought. The past twenty years have produced a radical change in this situation. Many of the concepts of modern biochemistry have originated in work on the metabolism of microorganisms. Microbial geneticists have enriched modern genetics with new techniques and ideas....Microbiology is now making fundamental contributions to the concepts of biology as a whole. At the same time, microbiologists have come to realize that microorganisms, whatever their singularities, obey the same general laws as other living systems.⁽⁸⁴⁾The textbook became widely used for undergraduate microbiology courses.

Soon after finishing The Microbial World, Adelberg departed for a sabbatical year at the Pasteur Institute. He left behind intensifying hostilities between the general microbiologists and the pathologists in the Berkeley bacteriology department. In his absence, a major controversy broke out concerning the relationship of the NBL to the department. In 1957, Elberg was serving as both chairman of the bacteriology department and Acting Director of the NBL. With the agreement of the chancellor, Elberg apparently offered a proposed candidate for the directorship of the NBL a joint appointment as full professor in the Department of Bacteriology. Stanier and Doudoroff, who were not consulted about it, protested in vehement terms to the chancellor. They succeeded in blocking the appointment to the Department.⁽⁸⁵⁾ For Elberg, the controversy represented a breaking point. He requested the Dean of the College of Letters and Sciences to transfer him and the other faculty members interested in infectious disease to the School of Public Health. "The department has assumed a rather anomalous position because with the great growth of chemical microbiology the disease aspects have been subordinated," he complained.⁽⁸⁶⁾ Adelberg, slated to assume the chairmanship upon his return, received the news in Paris. "I wish to protest this as strongly as I can," he wrote to the dean, "Dr. Elberg is himself the most valuable man in our Department." In Adelberg's view, the dispute over the directorship of the NBL had generated unjust criticism against Elberg. Adelberg promised to restore peace: "As Chairman, I will see this group of brilliant but sometimes childish scientists working once again in harmony."⁽⁸⁷⁾ Adelberg's peace initiative was well received. When he returned, he did restore relative harmony and the integrity of the department appeared to be assured.

When not engaged in political battles, Stanier continued his productive program of research in microbial physiology. In 1957, he received a research fellowship from the Miller Institute, which relieved him of all university teaching and committee responsibilities for two years. During this time, he reinvestigated the phenomenon that had brought van Niel and Hans Gaffron into conflict in 1935, the uptake of acetate in non-sulfur purple bacteria. Gaffron had proposed that these bacteria could take up acetate in the presence of hydrogen gas in the light, a direct photo-assimilation of an organic compound. In 1935, this interpretation appeared to threaten the generality of van Niel's general theory of photosynthesis. Using radio-labeled carbon compounds, Stanier and two collaborators showed that the bacteria did carry out a direct photoreductive assimilation of acetate, operating independently of photosynthetic carbon fixation.⁽⁸⁸⁾ In the aftermath of these experiments, Stanier reviewed the contributions of studies on both bacteria and plants in the development of a unitary theory of photosynthesis.⁽⁸⁹⁾

Stanier undertook a second major effort to organize and synthesize the rapidly growing body of knowledge about bacteria. With microbiologist I.C. Gunsalus, Stanier edited a comprehensive multi-volume treatise on all aspects of the structure and function of bacteria.⁽⁹⁰⁾ This project, too, required him to consider the biology of bacteria from a wide view. In each of these projects, the textbook, the review, and the treatise, Stanier systematically assessed the similarities and differences of the biology of bacteria and more complex organisms. He could not, however, formulate a biological definition for bacteria that satisfied him.

In the late 1950's, Stanier was widely seen as the one of the world's leading microbiologists and a worthy heir to van Niel and all that he represented. In 1959, Harvard's Department of Biology made Stanier a very attractive offer, creating consternation at Berkeley. Adelberg and other Berkeley faculty urged the Berkeley administration to take whatever steps they could to retain Stanier. "Dr. Stanier occupies a unique eminence in the field of microbiology which is precisely why Harvard wants him," wrote one group of colleagues to Berkeley's chancellor. He "stands at the end of a distinguished line of microbiologists leading from Beijerinck through Kluyver and van Niel," they continued.⁽⁹¹⁾ Accelerated promotion, renovation of some of his laboratory space, and some secretarial assistance convinced Stanier to stay.⁽⁹²⁾

For his sabbatical year of 1960 to 1961, Stanier again chose to visit the Pasteur Institute and the laboratory of Jacques Monod. There he was subjected to a variety of pressures that gave renewed urgency to the question: What is a bacterium? Disciplinary and departmental politics at Berkeley, his local institutional environment, changing intellectual conditions of the late 1950's, and the opportunity to reflect on a long-standing problem converged upon Stanier. At every turn, it seemed, Stanier encountered the new realities of the bacterium's dual nature as organism and instrument.

In 1960, when Stanier arrived in Paris, the Pasteur group was in the midst of research that produced several fundamental concepts in molecular biology and would win a Nobel Prize for Lwoff, Monod, and Jacob in 1965. Nearly all of their research had been carried out with bacteria or bacterial viruses. The generality of their results and models depended on the legitimacy of bacteria as representatives for all of life. More generally, the year 1960 witnessed the solution to an extraordinary number of fundamental problems concerned with the function of DNA, the molecular basis of genetic recombination, the nature of the genetic code, the mechanisms of information transfer from DNA to protein, and the regulation of structural genes. In nearly all of these studies, bacteria or bacteriophage were central instruments of research.⁽⁹³⁾

During his sabbatical, Stanier reviewed systematically the recent dramatic transformations in the understanding of bacterial heredity when he assisted Monod's colleagues, Jacob and Eli Wollman, in their preparation of an English version of their monograph, Sexuality and the Genetics of Bacteria, published in 1961. The first chapter concluded with a concise statement of the new understanding of bacterial genetics and a forthright claim of its relevance to general genetics:

The bacteria are not a primitive group of organisms in which soma and germ plasm are blended, contrary to the general belief some twenty years ago. They possess a nuclear apparatus comparable to that in the cells of other organisms and one which, likewise, contains the determinants of hereditary characters. These bacterial determinants possess the individuality and specificity accorded to the genes of higher organisms. They control phenotypic characters the biochemical mechanisms of which have been analyzed with precision in many cases. Accordingly, the study of bacterial mutations has contributed to demonstrating the universality of genetic mechanisms and of the metabolic reactions they control.⁽⁹⁴⁾ By January of 1961, Stanier had decided to make a second concerted attempt to articulate a biological definition for bacteria. The presence of André Lwoff in the local environment may have been an important factor. In 1957, Lwoff had resolved a question that had vexed virologists since the 1890's: Are viruses macromolecules or microorganisms? Lwoff reach a simple and radical conclusion: they were neither. This conclusion raised a new question:

If a virus be neither organism nor molecule, what is its nature? What is a virus? It is a malady of our time that words are often deprived of their meaning. Many people like to think that a virus is something different from a virus. My ambition is to show that the word virus has a meaning, and I shall defend a paradoxical viewpoint, namely that viruses are viruses.⁽⁹⁵⁾Lwoff concluded that viruses constituted a unique and distinctive category that could be precisely defined. He defined viruses as "infectious, potentially pathogenic, nucleoproteinic entities possessing only one type of nucleic acid, which are reproduced from their genetic material, are unable to grow and to undergo binary fission, and are devoid of a Lipmann system."⁽⁹⁶⁾ The last criterion referred to the ability of living organisms to convert the energy of food into high energy bonds needed for biosynthesis. Lwoff's articulation of a definition for virus provided Stanier with a model for defining bacteria. It showed that the new definitions for old entities in experimental biology were needed and possible. It demonstrated that the previous two decades of research could provide the basis for revising old categories or even creating new ones.

While Stanier was in Paris, Lwoff was awarded the Leeuwenhoek medal by the Dutch Society for Microbiology. Given only every fifteen years, the medal was especially prestigious among general microbiologists. "No one, I believe, deserves it more!" wrote van Niel to Stanier, a generous comment for an obvious candidate for the award to make.⁽⁹⁷⁾ Given his immediate physical location, Stanier might easily have asked Lwoff to join him in framing such a definition. Nonetheless, Stanier turned not to Lwoff, but to van Niel to write a formal paper on the subject. The proposal delighted van Niel. "I would personally consider it a great pleasure once again to do a joint paper with you," he wrote from California.⁽⁹⁸⁾

Disciplinary politics within the Department of Bacteriology at Berkeley provided an additional stimulus to Stanier. Again, these events directed his attention to the high importance of securing the identity of bacteria as biological entities. While in Paris, Stanier received disturbing news from Berkeley. His close colleague Edward Adelberg was leaving Berkeley for Yale. Even worse, his replacement would be a medical bacteriologist. "I'm still quivering from the impact of your letter," he wrote to Adelberg, "However, bad news is an excellent tool for sharpening the wits, and I have been doing a lot of hard thinking since its receipt." Stanier objected to any change in faculty that would upset the balance of power between the general microbiologists and the medical bacteriologists. His tirade to Adelberg on departmental politics also highlighted the significance of the problem of bacteria as biological entities:

Our department is the only structure on the Berkeley campus that represents bacteriology as a field of biological science. As you well recognize, bacteria have become in the past ten years the principal experimental objects for pursuing the great objective of biology in our time: functional analysis in cellular and molecular terms. The structure and replication of DNA, the mechanism of information transfer, the synthesis of proteins, cellular regulation; these are all basic questions in biology, which are yielding in large measure through work with bacterial systems. This is why the study of bacteria as independent biological entities is such an overwhelmingly important phase of modern biology.⁽⁹⁹⁾ Stanier pointed out that the proposed new arrangement in Berkeley's Department of Bacteriology would leave five faculty members to handle immunology and pathology, and only two and a half for all of general microbiology. In his view, the latter included cytology, taxonomy, physiology, biochemistry, and genetics. He considered this distribution of personnel especially untenable for Berkeley:

If our department were in a medical school or school of public health, this distribution of strength might be justifiable, even though it is no longer the distribution that one finds in some leading medical schools of the country (Western Reserve, Harvard, NYU, to cite only 3 examples!). In a college of letters and sciences, at a great university with a long record of achievement in biology, it is grotesquely unbalanced and inadequate. In the midst of the crisis at Berkeley, Doudoroff felt the problem of finding a replacement for Adelberg with special urgency. Attempting to ward off maneuvering by the pathologists, Doudoroff assured Stanier that a new chairman would not be appointed without Stanier's approval. The crisis also brought into relief the increasing interest in molecules at the expense of studies on microorganisms as biological entities. "There is, of course, the problem of getting someone who is interested in microorganisms on a slightly higher than molecular level because none of the rest of us does any microbiology any more," Doudoroff wrote to Stanier.⁽¹⁰⁰⁾ Under these pressures, Stanier struggled with the question that had vexed him for two decades.

A conversation with Lwoff provided a crucial catalyst: the words "procaryote" and "eucaryote."⁽¹⁰¹⁾ Lwoff told Stanier that Edouard Chatton, the great French protozoologist and Lwoff's revered teacher, had introduced these terms in the 1920's. Chatton had proposed that the protozoans be divided into two categories: those that possessed a cell nucleus, or "eucaryotes," and those lacking a nucleus, or "procaryotes." The terms were based on the Greek root karyon, meaning kernel. In his writings, Chatton introduced this terminology casually without fanfare, not as a response to an urgent problem.⁽¹⁰²⁾

For Stanier, in contrast, these terms provided the key to the resolution of an intellectual problem that had troubled him for two decades. Crystallizing his thoughts, the term procaryote allowed Stanier to begin to state a definition for bacteria in positive terms. On March 2, 1961, he presented a new conception of bacteria in a lecture to the Société de Microbiologie, "La place des bactéries dans le monde vivant." The title indicates that, for Stanier, to define bacteria meant to identify their place in the order of nature. Stanier began his remarks by pointing out that since the late nineteenth century, bacteriologists nearly always agreed on whether or not an organism was a bacterium, even throughout the twentieth century as the vast diversity of bacterial morphology and physiology was revealed. Stanier remarked that this ease of identification in practice contrasted sharply to the difficulty of defining bacteria in biological terms.⁽¹⁰³⁾

An exception to this generalization provided Stanier with an important insight. For a century, Stanier told his audience, observers had noted the morphological similarities between organisms known as blue-green algae and bacteria. However, the blue-green algae, unlike bacteria, carried out a photosynthesis biochemically identical to that of plants. Physiologically, the blue-green algae could not be classified within the category bacteria or vice versa. By this reasoning, bacteria and blue-green algae were related but distinct groups of microorganisms. An argument could be constructed: If blue-green algae were physiologically like plants, and bacteria morphologically like blue-green algae, then both groups belonged to the plant kingdom.

Stanier analyzed the similarity and difference of these two groups from a different vantage point. He set out to characterize the basis for the perception of a morphological similarity between bacteria and blue-green algae. Most importantly, he chose to compare their pattern of cellular organization to other kinds of cells at the level of detail permitted by the science of 1961. Stanier observed that bacteria and blue-green algae shared the same pattern of cellular organization, a pattern he proposed to call "procaryotic." In contrast, Stanier observed, the cells of all other organisms, including all plants and animals, shared a form of organization that could be called "eucaryotic." By making cellular organization the primary criterion, Stanier defined a new set of fundamental categories of living things.⁽¹⁰⁴⁾

Several features distinguished these two patterns of organization. Both types of cells possessed nuclei. In eucaryotes, however, the nucleus was enclosed within a membrane; in procaryotes, it was not. Similarly, in eucaryotic cells, the photosynthetic apparatus and the energy-yielding systems were packaged in membrane-structures located in the cytoplasm. In procaryotic cells, these systems were not surrounded by membranes but resided either in the cytoplasm or the cell membrane. The organization of the genetic material differed in the two cell types as well. Assuming that E. coli was representative of procaryotes, these kinds of cells contained a single chromosome, whereas eucaryotes contained more than one. In procaryotes, DNA was packaged in a circle; in eucaryotes it was linear.⁽¹⁰⁵⁾

By creating the concept of the procaryotic cell, Stanier believed he had, at last, defined bacteria: "Thus, it is by the structure of the procaryotic cell that we define bacteria and establish their place in the natural world."⁽¹⁰⁶⁾ By conceptualizing the procaryotic cell, Stanier created a new biological category defined on the basis of the organization of the cell. It permitted a description of bacteria in positive terms. The new category gave explicit criteria for including bacteria and blue-green algae in the same fundamental category. At the same time, the meaning of this category derived from comparison to the category of eucaryotic cells. In effect, by defining the cells of all living things as either procaryotes or eucaryotes, Stanier proposed to create a new order of nature. In Stanier's formulation, the most fundamental biological difference lay between bacteria and the cells of more complex organisms. The procaryote/eucaryote distinction, then, represented a more fundamental division among living things than did the traditional bifurcation into plants and animals. At the cellular level, plants and animals had much more in common with each other than they had with procaryotes.

For a presentation of these ideas to a wider audience, Stanier awaited the opportunity to collaborate with van Niel. They arranged to meet in May 1961 at the annual conference of the American Society of Microbiology (ASM), the new name of the SAB.⁽¹⁰⁷⁾ The previous year, the membership had voted to change organization's name.⁽¹⁰⁸⁾ The society's Secretary, E.M. Foster, did not approve. "Don't ask me why," he wrote to a colleague, "Some of the boys got the bright idea that we ought to call ourselves microbiologists to keep up with the times. So that's what we're doing."⁽¹⁰⁹⁾ The term bacteriology was no longer acceptable to the Society's membership. It had come to sound old-fashioned.

Stanier and van Niel endeavored to provide an appropriately modern identity for the bacterium. Reviewing Stanier's manuscript on the subject, van Niel suggested a rhetorical improvement. "[A] definition is very helpful, but only if it be accepted by others," he wrote to Stanier. "This implies that it might be better to lead up to the definition, rather than start with it." He agreed that they could rely on Lwoff's definition of virus to make a clear separation between bacteria and viruses before proceeding to define bacteria.⁽¹¹⁰⁾ Back in California, Stanier visited van Niel in October of 1961 in Pacific Grove to work on their definition of bacteria.⁽¹¹¹⁾ Shortly thereafter, Stanier and van Niel submitted a completed manuscript on the subject to the Archiv für Mikrobiologie, an important European journal for microbiology. The article's title, "The Concept of a Bacterium," made implicit reference to Lwoff's article, "The Concept of Virus."

Van Niel recognized that defining bacteria in biological terms was a significant accomplishment with various ramifications. Just after completing the manuscript, he wrote a note to Stanier: "It was wonderful to see you again, and I am very, very grateful that you have been willing to let me be a co-author of the paper 'The Concept of a Bacterium.' During the week I have thought about it, off and on, and believe that it is really quite good."⁽¹¹²⁾

Appearing in print early in 1962, the article represented a reworking of the points raised in Stanier's lecture of 1961. Here, Stanier and van Niel offered a definition of bacteria in vastly different terms than they had in their first joint attempt in 1941. Unlike in the earlier work, they made no attempt to provide a general taxonomy for bacteria. In contrast, they cast their new definition, which required recently acquired information, in terms of cellular structure and function:

For a long time, biologists have intuitively recognized that the cell structure of bacteria and blue-green algae is different from that of other organisms, and should be characterized as "primitive"; but a satisfactory description of the difference has proved remarkably elusive. The revolutionary advances in our knowledge of cellular organization which have followed the introduction of new techniques during the past 15 years have changed this situation.⁽¹¹³⁾ They then asserted their principal conclusion:

It is now clear that among organisms there are two different organizational patterns of cells, which Chatton (1937) called, with singular prescience, the eucaryotic and procaryotic type. The distinctive property of bacteria and blue-green algae is the procaryotic nature of their cells. It is on this basis that they can be clearly segregated from all other protists (namely, other algae, protozoa and fungi), which have eucaryotic cells.⁽¹¹⁴⁾ Stanier and van Niel then described the basic differences between procaryotic and eucaryotic cells in terms that became canonical for the next three decades. Eucaryotes, they wrote, are characterized by the packaging of the units of sub-cellular function in membrane-bound compartments, notably the nucleus, by their distinctive mechanisms of cell movement, and by their division by mitosis. In procaryotic organisms, they wrote, the cell is the smallest unit of metabolic function, and contains no membrane-bound compartments. These kinds of cells contain one circular chromosome and divide by fission. Stanier and van Niel also compared the structures associated with cell movement in the two cell types, and described the unique features of procaryotic cell walls. The authors emphasized the structural difference and the functional equivalence of the two cell types:

The justification for using a single term, the cell, in describing the unit of structure of both eucaryotic and procaryotic organisms rests on the equivalence of function of these two kinds of entities....The differences between eucaryotic and procaryotic cells...reside...in differences with respect to the detailed organization of the cellular machinery.⁽¹¹⁵⁾In this formulation, the terms procaryote and eucaryote designated not simply a division of the protozoa, but the most fundamental division among living things. In this order of nature, bacteria occupied a crucially important location, at the primary branching point of the living world. Stanier and van Niel concluded: "If we look at the microbial world in its entirety, we can now see that evolutionary diversification through time has taken place on two distinct levels of organization." The authors left the strong impression that the procaryotic world, while diverse, represented one of the two great phylogenetic branches of living things.⁽¹¹⁶⁾

Recall that the protozoologist Chatton introduced the terms procaryote and eucaryote in the 1920's. Published in the French protozoological literature, the terms had little impact outside that field. Obscurity does not explain their lack of resonance from the 1920's through the 1950's, however. Chatton's distinction between procaryotes and eucaryotes was visible in Lwoff's widely known works.⁽¹¹⁷⁾ In L'Evolution physiologique (1944), for example, Lwoff used the terminology very clearly: "Nous divisons avec Chatton les Protistes en deux grands groupes...a) Les Procaryotes...b) Les Eucaryotes."⁽¹¹⁸⁾ Van Niel annotated his copy of this book very heavily and he made frequent reference to it in the 1940's and 1950's. Nonetheless, the terms procaryote and eucaryote seem not to have impressed him during this period. There is no evidence that he ever used the terms before 1960.

After 1960, the terms procaryote and eucaryote had an entirely new meaning and importance than three decades before. Even for Lwoff, the terms performed a new kind of conceptual work in 1960. In the late 1950's and early 1960's, Lwoff was responsible for giving a set of lectures on the bacterial cell, among other topics, for a year-long course in microbiology at the Pasteur Institute. In 1961, he used the terms procaryote and eucaryote as defined by Stanier and van Niel to organize his lectures on bacterial cell structure. In 1960, the words did not appear in Lwoff's lectures on these topics.⁽¹¹⁹⁾ Similarly, van Niel introduced the term procaryote in teaching his summer course in 1962, whereas he had not used the term before.⁽¹²⁰⁾ In the second edition of The Microbial World, published in 1963, Stanier, Doudoroff, and Adelberg used the procaryote/eucaryote distinction as the central organizing framework for discussing the similarities and differences in the structure and physiology of bacteria and other microorganisms.⁽¹²¹⁾

What made this distinction important in the 1960's? The baptism of the bacteria as procaryotes served several crucial functions. The procaryote/eucaryote distinction gave bacteria an identity commensurate with their new and central position in biological theory and practice. Set in opposition to eucaryote, the term procaryote elevated the bacteria to an equivalent status with all other kinds of cells. The procaryote/eucaryote terminology resolved the pernicious problem of the bacterial nucleus. The new terminology implicitly awarded bacteria their own kind of nucleus, functionally equivalent to its counterpart in "higher" cells. It merited, therefore, the name "nucleus," with one crucial refinement. In this framework, the bacterial nucleus was designated procaryotic, in contrastive relation to the eucaryotic nucleus. The terms effectively and economically expressed the conviction of the existence of two types of cells, functionally equivalent though morphologically different, and each containing their corresponding kind of nuclei. In the 1963 edition of the The Microbial World, the authors explicitly used the term procaryote to replace the old term "lower protists" and the word eucaryote to replace "higher protists." The terminology changed the implicit relationship of these two categories from one of biological superiority and inferiority to one of equivalence.⁽¹²²⁾ The abstractness and symmetry of the terminology also provided appropriate names for bacteria in their role as technical instruments for experimental research on the structure and function of genes and proteins. The procaryote/eucaryote distinction may be seen as the technical version of Monod's distinction between E. coli and the elephant.

The terminology introduced by Stanier and van Niel appears to have diffused widely through all branches of biology with little discussion. Further study would be needed to prove this point, but, with one exception, there is no evidence of any controversy or objections to the terminology. From the 1960's to the 1980's, the terms procaryote and eucaryote were usually defined without acknowledgment of their origin. They became as much a part of standard biological discourse as "molecule" or "DNA."⁽¹²³⁾ Only Ralph Lewin, a prominent algae specialist working at the Scripps Institute for Oceanography, held out against the concept of a procaryote. Adhering to old arguments about photosynthesis, he objected to classifying blue-green algae within the same category as bacteria.⁽¹²⁴⁾ Lewin represented a constituency of one, and ultimately lost both battle and war. By the 1980's, blue-green algae were commonly known as cyanobacteria.⁽¹²⁵⁾

The procaryote/eucaryote distinction implicitly expressed an important taxonomic proposition about the deepest phylogenetic division among living things. At the time it was formulated, it seemed obvious to Stanier and van Niel that the procaryotes, though diverse, belonged to a monophyletic category, as did the eucaryotes. The distinction provided the basis for ending a conviction about the natural world formalized by Aristotle in the fifth century B.C. and made sacred by Linnaeus in the eighteenth century: namely, that all organisms were either plants or animals. Though challenges to that conviction had been launched since the middle of the nineteenth century, none had achieved wide acceptance. The procaryote/eucaryote distinction, in contrast, ended the reign of the plant and animal kingdoms as the fundamental bifurcation of living things. When compared at the cellular level, it became evident that plants and animals were much more like each other than they were like procaryotes. Proposals that the living world could be divided into five kingdoms began to be taken seriously.⁽¹²⁶⁾

For three decades, procaryote and eucaryote denoted the central entities for the study of structure and function at the cellular and molecular levels. Once incorporated into biological discourse, the procaryote/eucaryote distinction came to appear as natural as the division between plants and animals. The procaryote/eucaryote distinction provided an important basis for conceptions of evolution, especially at the cellular level. An influential theory vigorously promoted by biologist Lynn Margulis since the 1970's holds that eucaryotic cells evolved from symbiotic associations of procaryotic cells.⁽¹²⁷⁾

The depth to which the procaryote/eucaryote distinction became incorporated into the thinking of biologists may be estimated by the difficulties encountered by scientists who set out to challenge it in the 1980's. Microbiologist and molecular biologist Carl Woese, the leader of one major challenge, has argued that the procaryote/eucaryote distinction gives a distorted impression of phylogeny as inaccurate as the plant/animal division. Largely on the basis of interpretations of sequences of ribosomal RNA and other molecular criteria, he has concluded that the category procaryote is not monophyletic, as most biologists assumed. He believes that uncritical faith in the concept of a procaryote obscures the fact that it is comprised of two evolutionarily distinct groups, as different from each other as they are from the eucaryotes.⁽¹²⁸⁾ His arguments met with considerable resistance in part because the term procaryote had become so deeply embedded in the discourse of biology of the 1960's and 1970's.⁽¹²⁹⁾ Woese has castigated Stanier and van Niel for introducing a dogmatic conception that has impeded progress in research on microbial evolution. He views the procaryote/eucaryote distinction as an obstacle:

This is not the unifying principle we once believed it to be. Quite the opposite. It is a wall, not a bridge. Biology has been divided more than united, confused more than enlightened, by it. This prokaryote/eukaryote dogma has closed our minds, retarded microbiology's development, and hindered progress in general. Biological thinking, teaching, experimentation, and funding have all been structured in a false and counterproductive dichotomous way.⁽¹³⁰⁾ The formulation of procaryote/eucaryote distinction does not appear in any of the histories of molecular biology produced in the 1960's and 1970's. During this period, neither practitioners nor historians of science perceived the distinction as a "discovery." Nonetheless, the evidence I have given here shows that the effective formation of this concept took place in direct connection with development of new conceptions of bacterial heredity and cytology and the deployment of bacteria as research tools. Historian Jean-Paul Gaudillire has pointed out that, from 1958 to 1960, the researchers at the Pasteur Institute redefined the biochemical elements derived from the studies on enzyme adaptation in order to formulate the operon model of gene regulation.⁽¹³¹⁾ Stanier's conception of bacteria as procaryotes occurred in the context of this work. Socially and intellectually, the formulation of the procaryote/eucaryote distinction was tightly linked to the formulation by Jacob and Monod of the operon model of gene regulation.

When Stanier returned to Berkeley after his sabbatical at the Pasteur Institute, he became embroiled in the ongoing struggle between the pathologists and the general microbiologists. Adelberg's departure left a major gap in the department, which missed both his scientific skills and his administrative talent. Stanier agreed to act as chairman of the bacteriology department for nine months, beginning in June 1961. He tried to arrange for the appointment of John Clark, a postdoctoral fellow who had been working with Adelberg, to the faculty.⁽¹³²⁾ Known more for his aggressiveness than for his diplomatic skills, Stanier did not succeed in reducing the hostilities between the pathologists and the generalists. The New Year of 1962 brought the dean an impassioned letter from the pathologists requesting the formation of a new Department of Immunology and Experimental Pathology without Stanier and Doudoroff.⁽¹³³⁾ Stanier agreed that the department should be split. He called experimental pathology "a special branch of vertebrate biology," whereas bacteriology, properly speaking, dealt with the study of bacteria as a biological group.⁽¹³⁴⁾

In principle, the department could be split by the departure of either the generalists or the pathologists. The question then arose: Where would they go? The medical bacteriologists had approached the School of Public Health in the past and been well received. Now, they were angling to expel Stanier and Doudoroff. Proposals for a possible new department of molecular biology emerged in the midst of the controversy among the bacteriologists. A department of molecular biology might provide a new place for Stanier and Doudoroff.⁽¹³⁵⁾ One proposal suggested that the general bacteriologists join the virologists working with Wendell Stanley to form the core of the new department of molecular biology. In 1962, the chancellor established a committee to plan a department "concerned with relating biology to the physical sciences." The early discussions at Berkeley reveal that administrators and researchers perceived general microbiology to be a major component of molecular biology. Some even identified the two fields.⁽¹³⁶⁾

Despite the conflicts among the faculty, the Bacteriology Department did not disband in 1962. In fact, the department had secured an important service role in the university. It supervised a popular major and its courses were well attended by students in a variety of fields.⁽¹³⁷⁾ The prestige of the department made administrators reluctant to dissolve it as well.⁽¹³⁸⁾

When Berkeley established a Department of Molecular Biology in 1964, it absorbed the Department of Virology entirely and provided joint appointments for Stanier and Doudoroff, who remained within Bacteriology. The same year, the Dean of the College of Letters and Sciences appointed a special committee to try to reconcile the warring parties in Bacteriology. Horace Barker, an ally of Doudoroff and Stanier, served as chairman. Disagreement over the undergraduate curriculum had become a major source of conflict. "In our thinking it is totally incomprehensible that students with an interest in experimental pathology should be required to sacrifice pertinent training in their area of interest in order to take courses in general microbiology," wrote Jacob Fong to Barker.⁽¹³⁹⁾ The crisis was temporarily quelled when Barker's committee recommended that the department set up two plans for undergraduate majors, one emphasizing general microbiology and the second, pathogenic organisms. A new name, the Department of Bacteriology and Immunology, would reflect the two viewpoints. Two years later, however, the agreement broke down and the pathologists left for the School of Public Health. Stanier and Doudoroff remained in Bacteriology with two immunologists, Leon Wofsy and Benjamin Papermaster.⁽¹⁴⁰⁾ Despite dire predictions to the contrary, the two programs in bacteriology at Berkeley survived and even flourished after their institutional separation, which allowed the two species of bacteriology to serve their complementary roles without coming into direct conflict.⁽¹⁴¹⁾ The Department of Bacteriology and Immunology lasted until 1989, when a major reorganization of the life sciences at Berkeley brought it to an end.

By 1971, sixteen students had completed Ph.D. degrees in microbiology under Stanier. Six more students completed degrees during the next decade. Benefitting from a period of expansion in American research universities and the continuing prestige of general microbiology, ten of Stanier's students went on to hold positions at major research universities while two took positions at teaching colleges. William Sistrom (Ph.D. 1954), for example, specialized in photosynthesis in bacteria at the University of Oregon. Jeanne Stove Poindexter (Ph.D. 1963) became an expert in the Caulobacter group of bacteria and eventually obtained a position at Barnard College in New York. One of Stanier's most prominent students, Ellis Englesberg (Ph.D. ca. 1950) became a professor at the University of California, Santa Barbara. His research moved toward the analysis of the regulation of gene activity. Leo Ornston (Ph.D. 1965) studied bacterial enzymes for his dissertation and eventually became a professor at Yale.⁽¹⁴²⁾

Despite this record of success and the relative calm in the Department of Bacteriology and Immunology, Stanier decided to leave Berkeley in 1971. The political situation of the United States, mired in the Vietnam war, and local political conditions on the campus, disrupted by frequent student protests, disturbed Stanier. The Pasteur Institute represented to Stanier a place where science could still be pursued as a cultural endeavor. "Disgusted and outraged by Nixon, Kissinger and their ilk, and deeply distressed by the chronic unrest at U.C., I sought a peaceful refuge, and found it at the Institut Pasteur," he wrote.⁽¹⁴³⁾ Stanier and Germaine Cohen-Bazire accepted permanent appointments at the Pasteur Institute where they remained for rest of their careers.

E. Van Niel as Moral Exemplar

The formulation of the procaryote/eucaryote distinction was the last major piece of scientific work to which van Niel contributed. In 1963, he carried out a last set of experiments on photosynthetic bacteria and retired from the Stanford faculty.⁽¹⁴⁴⁾ According to his own standards, he could judge his scientific life a success. He had conducted important, original research, trained a whole generation of important students, and contributed to the establishment of general microbiology as a significant and coherent field among the experimental life sciences. His summer course in general microbiology had provided the finest training to an elite group of practitioners. Van Niel's scientific contributions were of the highest order.

A second kind of contribution accompanied van Niel's scientific work. Throughout his life, he represented a certain conception of science and the scientist. He did not become a public spokesman for science, but he presented his views publicly when occasions to do so arose. From his lecture on the Delft School in 1949 to an autobiography he wrote in 1967, he consistently stated that science was fundamentally concerned with the comprehension of nature and the cultivation of mind. In his presidential address to the SAB in 1954, for example, van Niel provided a counterpoint to the view that the purpose of science was to provide the basis for technology:

Fundamentally, science is not concerned with the designing of automobiles or airplanes that move faster...nor with the production of new synthetic materials...nor with the development of mechanisms, material or immaterial, whereby man can destroy a civilization which has been slowly evolved in the course of thousands of years.⁽¹⁴⁵⁾ He offered a contrasting view: "To me the essence of science is concerned with the evolution of an attitude of mind." The scientifically trained mind, van Niel said,

...accepts experience as the guiding principle by which it is possible to test the relative merits of opposing viewpoints by means of carefully conducted, controlled experiments. On the other hand, it recognizes equally keenly that our knowledge and capacities are exceedingly limited not only if considered from the standpoint of the individual, but even with reference to the combined experience of the human race.Van Niel concluded that the practice of science cultivated the qualities of objectivity, tolerance, and compassion.⁽¹⁴⁶⁾

Van Niel described similar views in the preface to a 1958 edition of a popular biography of Antony van Leeuwenhoek. Van Niel feared that the practical results of science would overwhelm understanding of its spiritual importance, especially in the United States. "The American media of mass communication are prone to extol the medical and engineering applications of science," he lamented in 1958, with the "unfortunate result" that "the public is led to equate science proper with its applications." Rather, van Niel wrote:

It is of the utmost importance that it be more widely recognized that in essence science is a perpetual search for an intelligent and integrated comprehension of the world we live in....Viewed in this light science becomes a philosophy, a way of life.⁽¹⁴⁷⁾As he had in his previous statements of his philosophy of science, van Niel emphasized that scientific knowledge was provisional. The scientist must "abandon the notion that we can derive our concepts from some immutable starting point." Rather, he advised, "the scientist recognizes that he may not pretend to have attained final and ultimate truth, and that his efforts can only be directed toward the formulation of closer and more refined approximations."⁽¹⁴⁸⁾

Thus, van Niel presented himself as a scientist engaged in the pursuit of truth about nature, disinterested in the acquisition of power, and committed to the cultivation of the mind. The questions arises as to what extent van Niel might have been engaged in a project of "self fashioning."⁽¹⁴⁹⁾ There is no evidence to suggest that van Niel was self-consciously engaged in such a project, or that he cynically adopted these postures as strategies for success. The decisions he made in his professional life are in harmony with these ideals.

On the other hand, van Niel's representation of these ideals was strategically useful in practice. Fellow scientists and important patrons admired his capacity to represent science as he did. In 1954, for example, microbiologist Mortimer Starr, who had been a postdoctoral fellow with van Niel, wrote to the RF on behalf of the person he called, "King-of-the-Microbes." Starr went on, "This man (the designation seems so ordinary when applied to this god-like creature!) is about to go to Europe on what probably will be his last sabbatical year." Starr suggested that the RF volunteer to give van Niel a grant to help fund his trip: "I know, too, that this great person who has given the world so much and asked for nothing in return other than the pleasure of serving, should have a handful of money somehow."⁽¹⁵⁰⁾ Not many twentieth century scientists have had the honor of being called "god-like." This language is reminiscent of eighteenth century adulations of Isaac Newton. Although the RF officer professed at first not to know who was the "King of the Microbes," the Foundation did, in fact, respond favorably to this rather unusual request.⁽¹⁵¹⁾

Van Niel could maintain this conception of science and of himself as a scientist in part because of the conditions under which his life in science took place. Securing a position at Stanford's marine station meant that he could enjoy the benefits of both a small institution in an idyllic setting and the resources of a university engaged in building up research. He managed to secure adequate funding for research without ever actively applying for grants. Leonard Blinks, director of the HMS for three decades, marveled at van Niel's success. "Many sources of support came his way...All without his applying...[this] was before the days of NIH or NSF when one applied for a grant. Van Niel would never abase himself to do this. Yet support rolled in, not immense, but adequate. It worked!"⁽¹⁵²⁾

Van Niel shared his idyllic experience of science with others through teaching his summer course. In addition to its technical and conceptual value, the course provided a brief refuge from the increasingly commercial, competitive, and morally complicated realities of scientific careers in the postwar era. Participants in van Niel's course could enjoy the pursuit of knowledge in a stunningly beautiful location isolated from the usual distractions of urban life with a master of his discipline who was dedicated to their education. This interpretation helps account for the reverence with which many of van Niel's students describe their experience in the course and the special value they place on their notes from his lectures long after their scientific content became obsolete.⁽¹⁵³⁾

In 1963, President Lyndon B. Johnson awarded five eminent scientists the National Medal of Science. Four of the recipients were prominent physical scientists whose contributions lay in fields like high energy physics, electrical engineering, satellite communications, and cybernetics. Luis Walter Alvarez, then associate director of the Lawrence Radiation Laboratory was cited "for inspiring leadership in high energy physics...and contributions to the National Defense." He had carried out important research on the bubble chamber and elementary physical particles. Vannevar Bush was cited for work in electrical engineering, in the technology of computing machines, and for "mobilizing science, engineering and education in enduring ways in the service of the Nation." During World War II, Bush had directed the Office of Scientific Research and Development. John Robinson Pierce, the director of the communication systems division of the Bell Telephone Laboratories, received the award for his contributions to the development of radio communications via artificial satellites. Norbert Wiener, professor emeritus of mathematics at M.I.T., was cited for his versatile works in mathematics and engineering. He was well-known for his development of cybernetic theories.⁽¹⁵⁴⁾ Joining this company as the fifth recipient of the National Medal of Science was C.B. van Niel. He was cited for "fundamental investigations of the comparative biochemistry of microorganisms, for studies of the basic mechanism of photosynthesis, and for excellence as a teacher of many scientists."

What accounts for van Niel's presence in this company? Van Niel's scientific contributions were of a very different nature than those of the other recipients. I suggest that van Niel was valued by his colleagues for an additional reason, his capacity to represent the ideal of science as a search for truth about nature. The capacity of van Niel to represent this ideal of science, I suggest, served as a resource for the scientific community more broadly. The belief that science is fundamentally a search for truth has been an article of faith for American science.⁽¹⁵⁵⁾ To remain an article of faith, that belief requires constant renewal, continuous and credible demonstration. The existence of exemplars like van Niel may make it possible for other practitioners to maintain the conviction that the practice of science is fundamentally a moral good concerned with comprehension about nature, despite the complex moral, political, and economic realities in which they must operate. The existence of exemplars like van Niel may have been necessary to sustain the ideal of pure science, especially in the postwar decades as economic and political conditions made it increasingly difficult to realize.

When van Niel retired in 1963, there was no longer any place on the Stanford campus or at the marine station for the kind of science he represented. At Stanford, Sterling and Terman were continuing the campaign to develop large scale research programs capable of securing substantial federal grants. The small scale programs at the Hopkins Marine Station did not escape notice. Terman had ambitions to transform the small, quiet laboratory into a major oceanographic center. By the early 1960's, generous funding from the National Science Foundation supported the development of this possibility.⁽¹⁵⁶⁾ Stanford chose not to replace van Niel with a microbiologist. General microbiology no longer represented the cutting-edge of the experimental life sciences as it had two decades before. On the main campus, molecular and biochemical approaches to biology continued to win practitioners, funding, and institutional resources.

By the mid-1960's, van Niel felt that a new era in science had begun of which he was no longer a part. In 1965, Tatum, then professor at the Rockefeller Institute, asked van Niel if he would be interested in spending some time there as a visiting professor.⁽¹⁵⁷⁾ Van Niel replied that he was "flattered" by the letter and called the prospect of spending time at the Institute "most enticing." "But the trouble is that I don't have anything significant to contribute anymore," he concluded and declined Tatum's offer.⁽¹⁵⁸⁾

Van Niel had, however, contributed much of great significance to American biology. His work on photosynthesis in bacteria was a major piece of research in itself. It opened a new field of research that stimulated the biochemical analysis of photosynthesis. It contributed to the production of a detailed account of the mechanism of photosynthesis and allowed the formulation of a general theory of this crucial biological process. Van Niel's research demonstrated that experimental study of the biochemical and biophysical properties of bacteria could yield unique insights into fundamental processes of life. Van Niel's research and teaching provided a major contribution toward establishing general microbiology as a recognized, rigorous, and coherent science of life. The majority of his graduate students went on to hold important university positions, where they trained the next generation of students. From 1930 to 1961, van Niel's course in "General Microbiology" provided an important site in which elite researchers from a variety of backgrounds learned how to experiment with microorganisms. Many of the graduates of van Niel's course played major roles in establishing molecular biology as a distinctive and dynamic enterprise. The success of molecular biology institutionally and intellectually has obscured the substantial success of general microbiology on its own terms.

Index | Previous | Next

1. Roger Stanier and C.B. van Niel, "The Concept of a Bacterium," Archiv fr Mikrobiologie, 42 (1962), 17-35 on p. 17.

2. Robert E. Kohler, Lords of the Fly: Drosophila Genetics and the Experimental Life (Chicago: University of Chicago Press, 1994), pp. 6-11.

3. Hans-Jörg Rheinberger, Toward a History of Epistemic Things: Synthesizing Proteins in the Test Tube (Stanford: Stanford University Press, 1997). See also Adele Clark and Joan Fujimura, eds., The Right Tools for the Job (Princeton: Princeton University Press, 1992) for analysis of the development of organisms and other materials into instruments for research.

4. See Nicolas Rasmussen, Picture Control: The Electron Microscope and the Transformation of Biology in America, 1940-1960 (Stanford: Stanford University Press, 1997), especially Chapter 2, for a detailed account of the impact of electron microscopy on the investigation of bacterial cytology in the 1950's. The author is primarily concerned with the sociology and epistemology of the practice of electron microscopy. For depictions of bacteria, compare the first and second editions of Georges Knaysi, Elements of Bacterial Cytology (Ithaca: Comstock Publishing Company, Inc., 1944, 1952).

5. Thomas D. Brock, The Emergence of Bacterial Genetics (Cold Spring Harbor: Cold Spring Harbor Laboratory Press, 1990), 267-271.

6. Cyril Hinshelwood, The Chemical Kinetics of the Bacterial Cell (London: The Clarendon Press, 1946).

7. Emil Duclaux, Traité de Microbiologie (Paris: Masson et Cie., 1899). See also Pauline M.H. Mazumdar, Species and Specificity: An Interpretation of the History of Immunology (Cambridge: Cambridge University Press, 1995) and Chapter I of this study for a summary of debates between pleomorphists, who argued that bacteria were infinitely flexible, and monophorphists, who argued that bacteria occurred as discrete and stable species.

8. Marjory Stephenson and J. Yudkin, "Galactozymase Considered as an Adaptive Enzyme," Biochemical Journal, 30 (1936), p. 712; J. Yudkin, "Enzyme Variation in Micro-organisms," Biological Reviews, 13 (1938), p. 93. See also Marjory Stephenson, Bacterial Metabolism (London: Longmans, Green, and Co., 1930, 1939, 1948).

9. Brock, Bacterial Genetics (1990), pp. 267-271. See S.E. Luria, "Recent Advances in Bacterial Genetics," Bacteriological Reviews, 11 (1947), 1-40 for a contemporary critical review of bacterial heredity.

10. See, e.g., Chapter IV of this study for discussion of research on bacterial heredity presented at the Cold Spring Harbor meeting of 1946.

11. See, e.g., Jacques Monod, "Facteurs génétiques et facteurs chimiques spécifiques dans la synthèse des enzymes bactériens," In: Unités biologiques douées de continuité génétique (Paris: Centre Nationale de la Recherche Scientifique, 1949), 181-199.

12. See Melvin Cohn, "Contributions of Studies on the ß-galactosidase of E. coli to Our Understanding of Enzyme Synthesis," Bacteriological Reviews, 21 (1957), 140-168 for a review.

13. R.Y. Stanier, "Enzymatic Adaptation in Bacteria," Annual Review of Microbiology, 5 (1951), p. 36.

14. Ibid.

15. See Horace Freeland Judson, The Eighth Day of Creation: Makers of the Revolution in Biology (New York: Simon and Schuster, 1979), pp. 370-72 and Michel Morange, The History Molecular Biology (Cambridge: Harvard University Press, 1998), p. 152. Morange notes that four of six major publications by Monod between 1944 and 1947 contain the word adaptation in the title and that Monod later dropped the term. Morange concludes that political concerns fundamentally motivated Monod's interest in formulating new language for bacterial heredity. Morange makes no mention of Stanier's involvement in expunging the term "enzyme adaptation."

16. Monod to Stanier, October 10, 1952; JM.

17. Monod to Stanier, December 17, 1952; JM.

18. See Adaptation in Micro-organisms, Third Symposium of the Society of General Microbiology (Cambridge: Cambridge University Press, 1953) for the papers presented at that meeting.

19. R.Y. Stanier, "Adaption, Evolutionary and Physiological: or Darwinism Among the Micro-organisms," in Adaptation in Micro-organisms, Third Symposium of the Society of General Microbiology (Cambridge: Cambridge University Press, 1953).

20. Martin Pollock, "Un personnage passionant mais exaspérant," in André Lwoff and Agns Ullman, eds., Origines de la Biologie Moléculaire (Paris: Editions Etudes Vivantes, 1980), 61-74 on p. 67.

21. Monod to Stanier, May 27, 1953; JM.

22. Melvin Cohn, "In Memoriam," in André Lwoff and Agns Ullman, eds., Origines de la Biologie Moléculaire ((Paris: Editions Etudes Vivantes, 1980), 75-88 on p. 79.

23. M. Cohn, J. Monod, M.R. Pollock, S. Spiegelman, and R.Y. Stanier, "Terminology of Enzyme Formation," Nature, 172 (1953), 1096.

24. The account I give here emphasizes the role of Stanier. Morange attributes the new language exclusively to Monod. Morange, Molecular Biology (1998), p. 152. Judson refers only to Melvin Cohn in relation to the abandonment of the term adaptation by researchers concerned with the synthesis of ß-galactosidase. See Judson, Eighth Day of Creation (1979), p. 384.

25. See, e.g., Joshua Lederberg and Edward L. Tatum, "Sex in Bacteria: Genetic Studies," Science, 118 (1953), 69-175; W. Hayes, "Observations on a Transmissible Agent Determining Sexual Differentiation in Bacterium coli, Journal of General Microbiology, 8 (1953), 72-88. See Brock, Bacterial Genetics (1990), 88-105 for a summary. See Bonnie Spanier, Gender Ideology in Molecular Biology (Bloomington: Indiana University Press, 1995) for analysis of this language from a feminist perspective.

26. Jules Soury, Le Règne des Protistes (Paris: C. Reinwald et Cie., 1879), on 99; translation of Ernst Haeckel, Das Protistenreich (Leipzig: Ernst Günther, 1878).

27. René J. Dubos, The Bacterial Cell (Cambridge: Harvard University Press, 1945), pp. 22-28.

28. C.F. Robinow, "Nuclear Apparatus and Cell Structure of Rod-shaped Bacteria," addendum to Dubos, Bacterial Cell (1945). Robinow incubated bacterial cells for seven to ten minutes at sixty degrees centigrade in hydrochloric acid at a concentration of 1N. This treatment released material later identified as RNA from the cytoplasm of the cells. These cells were then treated with either the Feulgen or Geimsa reactions, which specifically stained the nucleus of plant and animal cells.

29. Robinow to Stanier, November 15, 1947; RYS 6/12. Stanier and Robinow corresponded frequently for the next two decades.

30. R. Tulasne, "Sur la mise en évidence du noyau des cellules bactériennes," Comptes Rendues de la Société de Biologie, 141 (1947), 411-13. R. Tulasne and R. Minck, "Mise en évidence des noyaux des cocci par la ribonucléase," Comptes Rendues de la Société de Biologie, 141 (1947), 1255-56.

31. The theoretical limit of resolution for electron microscopy is 0.01 millimicrons. The practical limit in the late 1950's was about 1-2 millimicrons. See Roger Y. Stanier, Michael Doudoroff, and Edward Adelberg, The Microbial World (Englewood Cliffs, N.J.: Prentice-Hall, Inc., 1957), pp. 10-24 for discussion of the evolution of microscopical methods and their impact on images of microorganisms.

32. Georges Knaysi and Richard F. Baker, "Demonstration, with the Electron Microscope, of a Nucleus in Bacillus mycoides Grown in Nitrogen-free Medium," Journal of Bacteriology, 54 (1947), 4-5.

33. George B. Chapman and James Hillier "Electron Microscopy of Ultra-thin Sections of Bacteria," Journal of Bacteriology, 66 (1953), 362-373. K.R. Porter and Joseph Blum also introduced the "Porter-Blum" ultra-microtome in 1953. See Rasmussen, Picture Control (1997), pp. 74-80, 90-94, and 111-13 for discussion of work of Hillier, Chapman, and Porter.

34. James Hillier, "Electron Microscopy," Annual Review of Microbiology, 4 (1950), 1-20.

35. See, e.g., K.A. Bisset, "The Genetical Implications of Bacterial Cytology," Cold Spring Harbor Symposia for Quantitative Biology, 16 (1951), 373-79.

36. Robinow to Stanier, April 10, 1948; RYS 6/12.

37. Edward D. DeLameter, "Cytological Basis for Bacterial Genetics," Cold Spring Harbor Symposia for Quantitative Biology, 16 (1951), 381-411; Edward D. DeLameter "Preliminary Observations on the Occurrence of a Typical Mitotic Process in Micrococci," Bulletin of the Torrey Botanical Club, 79 (1952), 1-5. DeLameter was professor of microbiology at the University of Pennsylvania Medical School where he collaborated with microbiologist Stuart Mudd. See Rasmussen, Picture Control (1997), pp. 70-102 for a detailed analysis of Stuart Mudd's research in bacterial cytology and his involvement in the debate over the bacterial nucleus.

38. See, e.g., Bisset's comments following DeLameter's 1951 CSH presentation.

39. Stuart Mudd, "Trends and Perspectives of Bacterial Cytology," Proceedings of the Seventh International Congress of Microbiology (Rome: Fondazione Emanuele Paterno, 1953), p. 5.

40. Robert Breed, E.G.D. Murray, and A. Parker Hitchens, Bergey's Manual of Determinative Bacteriology (Baltimore: Williams & Wilkins Co., 1948), p. 41.

41. C.B. van Niel, "Classification and Taxonomy of the Bacteria and Blue-green Algae," in A Century of Progress in the Natural Sciences 1853-1953 (San Francisco: California Academy of Sciences, 1955), pp. 89-114.

42. See Rebecca S. Lowen, Creating the Cold War University: The Transformation of Stanford (Stanford: Stanford University Press, 1998), pp. 166-74 for discussion of attempts to eliminate systematics and organismal biology at Stanford in the late 1950's.

43. Van Niel, "Classification and Taxonomy of the Bacteria and Blue-green Algae," (1955), p. 93.

44. Ibid., pp. 93-94.

45. Monod to Ephrussi, February 23, 1967; JM.

46. C.B. van Niel, "The Microbe as a Whole," in Selman A. Waksman, ed., Perspectives and Horizons in Microbiology (New Brunswick: Rutgers University Press, 1955), 3-12 on p. 5.

47. Ibid., p. 6.

48. Ibid., pp. 5-6.

49. Ibid., p. 7.

50. Ibid.

51. Ibid., p. 10.

52. Major monographs include Robert Olby, The Path to the Double Helix, (London: Macmillan, 1974); Judson, Eighth Day of Creation, (1979); Lily E. Kay, The Molecular Vision of Life: Caltech, the Rockefeller Foundation and the Rise of the New Biology, (New York: Oxford University Press, 1993); Morange, Molecular Biology, (1998). See also the important reviews by Pnina Abir-Am, "Themes, Genres and Orders of Legitimation in the Consolidation of New Scientific Disciplines: Deconstructing the History of Molecular Biology," History of Science, 23 (1985), 74-117; and, "'New' Trends in the History of Molecular Biology," Historical Studies in the Philosophical and Biological Sciences, (1994), 167-196. See also Richard M. Burian, "Technique, Task Definition, and the Transition from Genetics to Molecular Genetics: Aspects of the Work on Protein Synthesis in the Laboratories of J. Monod and P. Zamecnik," Journal of the History of Biology, 26 (1993), 387-407; Jean-Paul Gaudillire, "Molecular Biology in the French Tradition? Redefining Local Traditions and Disciplinary Patterns," Journal of the History of Biology, 26 (1993), 481-421; and Angela N.H. Creager, "Wendell Stanley's Dream of a Free-Standing Biochemistry Department at the University of California, Berkeley," Journal of the History of Biology, 29 (1996), 331-360.

53. See Judson, Eighth Day of Creation, (1979) for a lively account of the determination of the structure of DNA, the formulation and solution of the problem of the genetic code, the investigation of protein synthesis, and the development of models of gene regulation. These developments, while crucial, still represent only a fraction of the research incorporated into the canon of molecular biology. See Doris T. Zallen, "Redrawing the Boundaries of Molecular Biology: The Case of Photosynthesis," Journal of the History of Biology, 36 (1993), 65-87, for an account of the changing intellectual boundaries of molecular biology especially around 1960. See Rheinberger, Epistemic Things (1997) for a detailed study of the transformations in research in protein synthesis in the laboratory of Paul Zamecnik from 1947 to 1961. See Evelyn Fox Keller, "Physics and the Emergence of Molecular Biology: A History of Cognitive and Political Synergy," Journal of the History of Biology, 23 (1990), 389-409; and idem., Secrets of Life, (1992) for essays reflecting on the meaning of molecular biology in broad cultural terms.

54. Seymour Benzer, "Fine Structure of a Genetic Region in a Bacteriophage," Proceedings of the National Academy of Sciences U.S.A., 41 (1955), p. 344.

55. Arthur Kornberg, I.R. Lehman, Maurice J. Bessman, and E.S. Simms, "Enzymic Synthesis of Deoxyribonucleic Acid," Biochimica Biphysica Acta, 21 (1956) 197-98.

56. See Paul Berg, "Specificity in Protein Synthesis," Annual Review of Biochemistry, 30 (1961), p. 30 for a review.

57. Bruce N. Ames and B. Garry, "Coordinate Repression of the Synthesis of Four Histidine Biosynthetic Enzymes by Histidine," Proceedings of the National Academy of Sciences U.S.A., 45 (1959), 1453-461.

58. Interview by telephone with Bruce Ames, September 25, 1995.

59. Van Niel to Pomerat, December 12, 1954; RF 1.2, 205D, 6/43; RAC.

60. C.B. van Niel, "Natural Selection and the Microbial World," Journal of General Microbiology, 13 (1995), 201-17.

61. C.B. van Niel, "The Education of a Microbiologist: Some Reflections," Annual Review of Microbiology, 21 (1967), 1-30 on p. 26.

62. Ibid.

63. See André Lwoff, "Lysogeny," Bacteriological Reviews, 17 (1953), 269-337.

64. See Melvin Cohn, "Contributions of Studies on the ß-galactosidase of E. coli to Our Understanding of Enzyme Synthesis," Bacteriological Reviews, 21 (1957), 140-168 for a review.

65. Georges N. Cohen and Jacques Monod, "Permeases," Bacteriological Reviews, 21 (1957), 169-194.

66. Van Niel, "Education," (1967), p. 26.

67. E.g., C.B. van Niel, "A.J. Kluyver, Microbiologist," Science, 124 (1956), p. 308; C.B. van Niel, "Obituary Notice: Albert Jan Kluyver, 1888-1956," Journal of General Microbiology, 16 (1957), 499-521; A.R. Kamp, J.W.M. LaRivière, and W. Verhoeven, eds., Albert Jan Kluyver: His Life and Work (Amsterdam: North Holland, 1959).

68. Postdoctoral fellows in addition to those mentioned in the text included June Lascelles from England, Sanatkumar Vias from India, Kjell Eimhjellen from Norway, Ercole Canale-Parola, and Americans Carlton Bovell, Sydney Rittenberg, Jack London, John Bennett, Lynn Miller, Edward Leadbetter, and Roger Whittenbury. See van Niel, "Education," (1967), pp. 26-27.

69. Interview with Hans Veldkamp, Haren, The Netherlands; September 1993.

70. Holger W. Jannasch, "Small is Powerful: Recollections of a Microbiologist and Oceanographer," Annual Review of Microbiology, 51 (1997), 1-45.

71. See, e.g., Holger W. Jannasch and M.J. Mottle, "Geo-microbiology of Deep Sea Hydrothermal Vents," Science, 229 (1985), 717-725.

72. Interview with Holger Jannasch, Woods Hole, MA; August 18, 1991.

73. Norbert Pfennig, "Reflections of a Microbiologist, or How to Learn from the Microbes," Annual Review of Microbiology, 47 (1993), 1-29 on p. 12.

74. Ibid., p. 13.

75. See, e.g., Norbert Pfennig, "Photosynthetic Bacteria," Annual Review of Microbiology, 21 (1967), 285-324; Norbert Pfennig, "Phototrophic Green and Purple Bacteria. A Comparative, Systematic Survey," Annual Review of Microbiology, 31 (1977), 275-290.

76. Konrad Bloch, "Summing Up," Annual Review of Biochemistry, 56 (1987), 1-19 on p. 15.

77. See Lowen, Cold War University (1997) for a detailed examination of the nature and consequences of the changing relationship between Stanford and the federal government as promoted by Sterling and Terman.

78. Ibid., pp. 166-74

79. De Chadarevian, "Sequences and Structures," (1996).

80. Abir-Am, "Politics of Macromolecules," (1992); de Chadarevian, "Sequences and Structures," (1996); Creager, "Stanley's Dream of Biochemistry," (1996); Jean-Paul Gaudillire, "Molecular Biologists, Biochemists, and Messenger RNA: The Birth of a Scientific Network," Journal of the History of Biology, 29 (1996), 417-445.

81. Grant proposal to the NSF in 1959 for publication of booklet, "Bacteriology as a Career," submitted by C.A. Evans, E.M. Foster, and L.S. MacLung; Council and Committee Reports (1960), ASM.

82. See, e.g., Adelberg to Lincoln Constance, December 15, 1959, UCBC 34/42. At the time, Stanier was Chairman of the Committee on Biological Sciences of the College of Letters and Sciences, Chairman of the Committee on the Marine Biology Station, and a member of the Committee on Academic Freedom. See also the portrait of Stanier in Patricia H. Clarke, "Roger Yates Stanier, 1916-1982," Biographical Memoirs of Fellows of the Royal Society, 32 (1986), 542-568.

83. E.g., M. Griffiths, William R. Sistrom, "The Biology of a Photosynthetic Bacterium Which Lacks Colored Carotenoids," Journal of Cellular Comparative Physiology, 48 (1956) 473-516; Germaine Cohen-Bazire, William R. Sistrom, and R.Y. Stanier, "Kinetic Studies of Pigment Synthesis by Non-sulfur Purple Bacteria," Journal of Cellular Comparative Physiology, 49 (1957), 25-68.

84. Roger Y. Stanier, Michael Doudoroff, and Edward Adelberg, The Microbial World (Englewood Cliffs, N.J.: Prentice-Hall, Inc., 1957), on p. v.

85. See R.Y. Stanier, "The Journey, Not the Arrival Matters," Annual Review of Microbiology, 34 (1980), 1-48 on pp. 15-19 for Stanier's version of these events.

86. Elberg to Constance, June 10, 1957; UCBC 34/41.

87. Adelberg to Constance, June 28, 1957; UCBC 34/41.

88. Michael Doudoroff and R.Y. Stanier, "Role of Poly-ß-hydroxybutyric acid in the Assimilation of Organic Carbon by Bacteria," Nature, 183 (1959), 1440-42; R.Y. Stanier, Michael Doudoroff, Rio Kunisawa, and R. Contopoulou, "Role of Organic Substances in Bacterial Photosynthesis," Proceedings of the National Academy of Sciences, U.S.A., 45 (1959), 1246-260.

89. R.Y. Stanier, "Photosynthetic Mechanisms in Bacteria and Plants: Development of a Unitary Concept," Bacteriological Reviews, 25 (1961), 1-17.

90. I.C. Gunsalus and R.Y. Stanier, editors, The Bacteria, A Treatise on Structure and Function, Volume I., Structure (New York and London: Academic Press, 1960).

91. Adelberg to Constance, December 14, 1959; Adelberg, Ralph Emerson, I. Micahel Lerner, and Esmond E. Snell to Glen T. Seaborg, February 2, 1960; UCBC 34/42.

92. Adelberg to Constance, December 15, 1959; Seaborg to Clark Kerr, January 18, 1960; UCBC 34/42.

93. These examples are cited in Edward A. Adelberg, ed., Papers in Bacterial Genetics, (2^nd ed. 1965), p. i. This volume reproduces many of the most important research articles.

94. François Jacob and Elie L. Wollman, Sexuality and the Genetics of Bacteria, (New York and London: Academic Press, 1961), on p. 14. Stanier's assistance is acknowledged on p. xi.

95. André Lwoff, "The Concept of Virus," Journal of General Microbiology, 17 (1957), 239-253 on p. 240.

96. Lwoff, "Concept of Virus," (1957), p. 246.

97. Van Niel to Stanier, January 24, 1961; RYS 6/21.

98. Van Niel to Stanier, February 5, 1961; RYS 6/21.

99. Stanier to Adelberg, February 8, 1961; RYS 4/42.

100. Doudoroff to Stanier, February 25, 1961; RYS 5/11.

101. R.Y. Stanier, "Foreword," in N.G. Carr and B.A. Whitton, editors, The Biology of the Cyanobacteria, (Berkeley: University of California Press, 1982), on p. x.

102. Edouard Chatton, Titres et Travaux Scientifiques (1906-1937), (Sète: Sottano, 1938), on p. 50. Chatton first used terms in a diagram of protozoan phylogeny in "Pansporella perplexa. Rèflections sur la biologie et la phylogénie des protozoaires," Annales de Science Naturelle. Zoologie, 8 (1925), p. 5. The American protozoologist Ellsworth C. Dougherty apparently independently introduced the terms "prokaryous" and "eukaryous" in 1957 to refer to the nuclei of bacteria and more complex cells respectively. He was associated with Berkeley at this time. See Ellsworth C. Dougherty, "Neologisms Needed for Structures of Primitive Organisms. 1. Types of Nuclei," Journal of Protozoology, 4 supplement (1957), 14.

103. R.Y. Stanier, "La place des bactéries dans le monde vivant," Annales de l'Institut Pasteur, 101 (1961), 299-312.

104. Ibid., pp. 297-301.

105. Ibid., pp. 301-06.

106. Ibid., p. 301. "Donc, c'est par la structure de la cellule procaryote, qu'on définit les bactéries et qu'on établit leur place dans le monde vivant."

107. Van Niel to Stanier, May 19, 1961; RYS 6/21.

108. E.M. Foster, "What's in a Name?" Bacteriological News, 25 (1959), p. 3; "Report of Council Meetings," May 1, 3, 4, 1960; ASM 1-IV-D/8.

109. Foster to Joseph C. Kiger, May 16, 1961; ASM 1-IV-A/9.

110. Van Niel to Stanier, May 19, 1961; RYS 6/21.

111. Van Niel to Roger and Germaine Stanier, October 2, 1961; RYS 6/21.

112. Ibid.

113. Stanier and van Niel, "Concept of a Bacterium," (1962), pp. 20-21.

114. Ibid.

115. Ibid., p. 21.

116. Ibid., p. 33.

117. André Lwoff, Recherches sur la nutrition biochimiques des protozoaires (Paris: Masson et Cie, 1932); and André Lwoff, L'Evolution physiologique (Paris: Hermann, 1944).

118. Lwoff, L'Evolution physiologique (1944) p. 71.

119. Compare A. Lwoff, Lectures on "Anatomie Fonctionelle des Bacteries" for 1960-61 and for 1961-62 in "Cours de Microbiologie;" Service des Archives, Institut Pasteur.

120. Van Niel, transcript of tape recording of lectures, summer 1962; author's collection.

121. Stanier et al., Microbial World (1963), pp. 65-69, 80-81.

122. Ibid.

123. See almost any textbook for general biology or molecular or cell biology published after 1965. E.g. Stephen L. Wolfe, The Biology of the Cell, (Belmont, CA.: Wadsworth Publishing Company, 1972), pp. 11-14. Typical representations of the "Generalized Procaryotic Cell" and "Generalized Eucaryotic Cell," are portrayed in the widely used general biology text, E.O. Wilson, Thomas Eisner, Winslow R. Briggs, Richard E. Dickerson, Robert L. Metzenberg, Richard D. O'Brien, Millard Sussman, and William E. Boggs, Life on Earth, (Stamford, Conn: Sinauer Associates, 1973), on p. 15. In a typical use of the term, Francis Crick said that for molecular biological research, "One could choose the organism to study that was technically the most convenient. Thus, for a long time much of the research worked mainly with prokaryotes." Quoted by Judson, Eighth Day of Creation, (1979), p. 203. Judson does not discuss the origin of the term. Note also the variant spellings, prokaryote and eukaryote, often used by British and German scientists. American scientists use either spelling.

124. Ralph A. Lewin, "Naming the Blue-greens," Nature, 259 (1976), p. 360.

125. See, e.g., N.G. Carr and B.A. Whitton, eds., The Biology of the Cyanobacteria (Berkeley: University of California Press, 1982).

126. R. H. Whittaker, "New Concepts of Kingdoms of Organisms," Science, 163 (1969), 150-60; Lynn Margulis and Karlene V. Schwartz, Five Kingdoms: An Illustrated Guide to the Phyla of Life on Earth (New York: W.H. Freeman and Co., 2^nd ed. 1988).

127. Lynn Margulis, The Origin of Eukaryotic Cells (New Haven: Yale University Press, 1970); idem., Symbiosis in Cell Evolution (San Francisco: W.H. Freeman and Co., 1981). See Edward O. Dodson, "Crossing the Procaryote-Eucaryote Border: Endosymbiosis or Continuous Development?" Canadian Journal of Microbiology, 25 (1979), 651-674, for an early critical review. See Jan Sapp, Evolution by Association: A History of Symbiosis (New York: Oxford University Press, 1994) for historical analysis of the development of the endosymbiont hypothesis.

128. Carl R. Woese and George E. Fox, "Phylogenetic Structure of the Prokaryotic Domain," Proceedings of the National Academy of Science U.S.A., 74 (1977), 5088-5090.

129. Carl R. Woese, "Bacterial Evolution," Microbiological Reviews, 51 (1987), 221-271.

130. Carl R. Woese, "There Must Be a Prokaryote Somewhere: Microbiology's Search for Itself," Microbiological Reviews, 58 (1994), 1-9 on p. 6.

131. Jean-Paul Gaudillire, "Molecular Biology in the French Tradition? Redefining Local Traditions and Disciplinary Patterns," Journal of the History of Biology, 26 (1993), 481-421.

132. Constance to Edward Strong, June 1, 1961; UCBC 34/41.

133. Elberg, Fong, Kreueger, Madin Northrop, and Weiss to Constance, January 1, 1962; UCBC 75/10.

134. Stanier to Constance, January 26, 1954; UCBC 75/10.

135. E.W. Strong, handwritten note, November 11, 1962; UCBC 10/75.

136. See, e.g,. Alden H. Miller notes on a discussion with Dean Cornish in which one item on the agenda is given as "New Department of Microbiology or Molecular Biology," August 6, 1962; UCBC 75/33. Chemist Melvin Calvin, protecting his own turf which he called "chemical biodynamics," urged the administration to use the name microbiology and not molecular biology for the new department. Calvin to Fretter, June 13, 1963; UCBC 75/33.

137. Fong to Fretter, February 13, 1964; HAB 6/35.

138. See Alden Miller, "Notes," February 19, 1962; UCBC 75/10. Alden's notes on a conference with Karl Meyer who had been a major figure in the Department of Bacteriology from the 1920's to the 1940's and E.W. Strong, Berkeley's Chancellor, refer to reluctance to dismantle the department.

139. Fong to Barker, May 14, 1964, HAB 6/35.

140. Fong to Acting Chancellor Myerson, June 24, 1965; UCBC 75/10. Krueger, Northrop, Madin, Elberg, and Fong joined the School of Public Health.

141. Elberg expressed this assessment in "Graduate Education and Microbiology at Berkeley 1930-1989," (Oral history transcript, 1990), pp. 80-4 BANC.

142. Stanier to L.S. MacLung, August 23, 1979; RYS 17/7.

143. Ibid.

144. C.B. van Niel and L.R. Blinks, "The Absence of Enhancement (Emerson Effect) in the Photosynthesis of Rhodospirillum rubrum," In Microalgae and Photosynthetic Bacteria (Tokyo: Japanese Society of Plant Physiologists, 1963), 297-307.

145. C.B. van Niel, "On Radicalism and Conservatism in Science," Bacteriological Reviews, 19 (1955), 1-5 on p. 4.

146. Ibid., p. 5.

147. C.B. van Niel, "Introduction" in Dobell, ed., "van Leeuwenhoek's Little Animals," (1958), p. ii. I thank James Strick for drawing my attention to this passage.

148. Ibid.

149. See Stephen Greenblatt, Renaissance Self-Fashioning (Chicago: University of Chicago Press, 1980) for the original formulation of this concept.

150. Mortimer P. Starr to Harry M. Miller, September 8, 1954; RF 1.2, 205D, 6/43; RAC.

151. George W. Gray to Weaver, November 14, 1954; RF 1.2, 205D, 6/43; Trustees Confidential report; RF 1.2, 205D, 6/43; RAC.

152. Leonard Blinks, "The Hopkins Marine Station and Its Connections with Leonard Blinks," unpublished typescript, (1993), LRB.

153. This impression derives from conversations and interviews with scientists who had been in van Niel's course.

154. "Announcements," Science, 143 (1963), p. 30.

155. See, e.g., David A. Hollinger, "Science as a Weapon the Kulturkämpfe in the United States During and After World War II," Isis, 86 (1995), 440-54 for an examination of the faith of American intellectuals in an alliance between the pursuit of science and the defense of democracy.

156. Lowen, Cold War University, (1997), pp. 166-174

157. Tatum to van Niel, June 4, 1965; RU 450, T189, 12/1, RAC.

158. Van Niel to Tatum, July 19, 1965; RU 450, T189, 12/1, RAC.