In Science and the Practice of Medicine in the Nineteenth Century (1994), William F. Bynum maintains that nineteenth-century science shaped modern medicine, especially in the areas of public health and clinical diagnosis. The work of individual medical scientists, such as Lister, Pasteur, and Koch, transformed the conceptual foundations and the practice of medicine by applying scientific discoveries, in fields such as microbiology and physiology, to the understanding, management, and prevention of disease (xi-xiii, 118-141).
Subscribing to Bynum’s view, John Harley Warner, in “The History of Science and the Sciences of Medicine” (1995), observes that modern science and medicine are “bound together by their shared exploration of how natural knowledge is produced, organized, and deployed in concrete settings.” On the basis of this common epistemology, Warner urges historians of medicine to explore further “how science — as an ideal and as a body of knowledge — entered the physician’s workaday world” (165, 182). This work is warranted because later nineteenth-century American medical history has been glossed over with respect to how the natural sciences, such as chemistry and biology, directly benefited clinical practice (182).
Later Victorian medical professionals relied increasingly on observation and experiment in the practice of medicine, as Michael Worboys (2002) points out. As Victorian medicine became more scientifically “exact and empirical,” the etiologies of diseases were discovered, and doctors could then “make more precise and effective, diagnostic and curative interventions” (277). By understanding the interrelationship between pathology and bacteriology, Victorian scientists were able to standardize laboratory methods; and the interaction between disciplines improved medical treatment (277). In the late 1870s, Joseph Lister, John Tyndall, Lionel Beale, Edward Klein, William Watson Cheyne, and John Burdon Sanderson, all of whom advocated multidisciplinary practice in antiseptic surgery, initiated effective public health programs and designed new antibacterial therapies to deal with the predisposing and immediate causes of disease (288). Because germ theorists and bacteriologists helped to reform medicine “along scientific lines,” the linkages between laboratory work on germs and clinical practice continued to be reciprocal, and the benefits of this interchange of ideas and methods were realized in the development of vaccines (289-90).
The Pasteur-Lister interaction chronicled in this paper is an index of an intellectual, social, and methodological revolution in late nineteenth-century medical history; furthermore, this revolution demonstrates that advances in medical science depend upon international cooperation.1 This paper will show that, beginning in 1864, Joseph Lister’s medical innovations and surgical practice were directly indebted to Louis Pasteur’s research on fermentation and putrefaction; that, from 1864 to 1896, Lister meticulously replicated, verified, and lectured on Pasteur’s findings, advocating his work in the British medical community; and that, in turn, Pasteur promoted Lister’s medical applications of antiseptic surgery in French medical circles and personally encouraged Lister at every opportunity.
1857-1863: Microscopic Revelations
Five of Pasteur’s papers, published between 1857 and 1863, directly influenced Lister’s work on micro-organisms. In 1854, while professor of chemistry and dean of the school of science at the University of Lille, Pasteur experimented on beet sugar in alcohol fermentation and found that the process took place in the presence of living organisms, confirming what predecessors, such as Lazaro Spallanzani (1799), Theodore Schwann (1837), Charles Cagniard-Latour (1838), and Jacob Henle (1839), had reported (Dubos , 40). In “The Report on the lactic acid fermentation,” describing the biochemistry of souring milk, Pasteur implicated a micro-organism as the cause (“The Report,” 27-30): “ . . . the lactic fermentation, like the ordinary alcoholic fermentation, is always correlated with the production of a nitrogenous material which has all the properties of an organized body of the mycodermal [i.e., fungal] type, and is probably related to the yeast of beer” (29).
After being appointed manager and director of scientific studies at the École Normale Supérieure, Pasteur inquired further into the role of micro-organisms in fermentation, and, in the 1860 “Memoir on alcoholic fermentation,” presented evidence that living organisms in yeast (fungi such as Saccharomyces cerevisiae) were responsible for the fermentation (“Memoir,” 31-8). A related aspect of Pasteur’s experimentation, indispensable to Lister’s earliest understanding of bacterial sepsis, was presented in the 1861 paper “Animal infusoria living in the absence of free oxygen, and the fermentations they bring about” (39-41). Pasteur proposed in this paper that the ferment producing butyric acid was an anaerobe, a microbe living in the complete absence of free oxygen. He affirms that his discovery of an anaerobic “infusorium,” that is, of the micro-organism responsible for the ferment, was unprecedented, and he outlines plans for further experimentation: “We will have to consider how the relationship of the mode of life and the properties of these small animals, together with the same aspects of the plant ferments which can also live without free oxygen, are related to the processes of fermentation” (40).
Experiments described in the 1861 monograph, “On the organized bodies which exist in the atmosphere; examination of the doctrine of spontaneous generation,” investigated the hypothesis that life in boiled infusions arises from “solid particles which are suspended in the air.” Additionally, he determined that airborne microbes could be cultivated: thus, if “inseminated into a liquid previously boiled for sterility,” the very same organisms, upon exposure to the air, appeared and multiplied (“On the organized bodies,” 43-8). Two Pasteurian propositions summarize the work up to 1861:
1. There exist continually in the air organized bodies which cannot be distinguished from true germs of the organisms of infusions. 2. In the case that these bodies, and the amorphous debris associated with them, are inseminated into a liquid which has been subjected to boiling and which would have remained unaltered in previously heated air if the insemination had not taken place, the same beings appear in the liquid as those which develop when the liquid is exposed to the open air. 
The fifth influential paper in the series, the 1863 “Investigation into the role attributed to atmospheric oxygen in the destruction of animal and vegetable substances after death,” established that fermentation, putrefaction, and slow combustion destroyed organic substances and that these processes were necessary for “the maintenance of life on earth”; the slow combustion of organic material, in most cases, was connected with anaerobic micro-organisms; and experiments with blood and urine contributed to contemporary debates over spontaneous generation and fermentation (“Investigation”; Bulloch 67-145).
During this period, Pasteur articulated six points that would form the groundwork of Lister’s antiseptic system: (1) certain fermentations and putrefaction were caused by micro-organisms (as the Italian chemist Adamo Fabbroni had hypothesized in 1787; Edouard Buchner, in 1897, would show that enzymes also caused yeast to ferment) (Bulloch 42-3, 62-3, respectively); (2) microbes responsible for fermentation and putrefaction, abundant in the atmosphere, on solids, and in liquids, were vulnerable to heat and chemicals and were filterable; (3) specific organisms caused specific fermentations; (4) some derived oxygen from the air; others, called anaerobes, absorbed the gas metabolically; (5) organic or vegetable substances collected under sterile conditions neither fermented nor putrefied; and (6) spontaneous generation was invalid.
1852-1864: Lister’s Transition from Physiology to Antisepsis
Joseph Lister graduated with a degree in medicine from the University of London in 1852 and, after passing the examinations, was made a Fellow of the Royal College of Surgeons (Guthrie 34-5). In September 1853, he settled in Edinburgh after having completed his residency as House Physician and then as Surgeon at University College Hospital, London. In the period 1853-1863, while Pasteur was producing the fermentation and putrefaction papers described above, Lister was publishing eleven papers on physiology. This was a prolific time for both men, and their theoretical interests would soon converge.
After Lister’s appointment to the Edinburgh Royal Infirmary, he conducted animal experimentation on inflammation, on the causes and effects of blood coagulation, and on suppuration (the production of pus) (Godlee 43-57). He suspected, by 1867, that the physiological research and experimentation that he had undertaken from 1853 to 1863, along with that on antisepsis beginning in 1864, were likely connected to one another in terms of effect: both areas of enquiry possibly involved ways of controlling the growth of micro-organisms, suspected of being causally related to disease. In the 1860s, a period when the germ theory of disease had not yet been definitively established, Lister could not have intuited the fact that blood clots, suppuration, and antiseptics all had anti-microbial properties: clots (which trap and dispose of germs) and pus (the leukocytes and other cells of which destroy bacteria) are both immunological responses (Tortora & Derrickson, 354-7, 425-7). In fact, it was not until 1881 that he correctly stated, in “An Address on the Treatment of Wounds,” “that an undisturbed blood-clot has a special power of preventing the development of septic bacteria” (CP, vol. 2, 280-1). 2
In 1907, Lister considered interconnecting the physiological research of 1858-1863, along with unpublished essays, notes, and drawings, to the antiseptic and bacteriological work ongoing from 1864. While at Walmer in Kent, he planned, but never completed, an essay synthesizing the early research on physiology and antisepsis under the title, “On the Suppuration of Blood Clot.” Lister’s purpose, in 1907, might have been to clarify not only the linkage between physiology, bacteriology, and surgery, but also the trajectory of his thinking just prior to having read Pasteur’s 1857-1863 papers. In hindsight, Lister might have believed that the early physiological inquiries had prepared him, beginning in 1864, to receive, and eventually to adapt, Pasteur’s findings to medicine (Godlee, Appendix 3, 639-51; Cheyne 9; Fisher 121-22).
1864-1870: Lister Replicates, Verifies, & Adapts Pasteur’s Findings
In 1864, while Lister was in Glasgow, a chemistry professor and colleague, Dr. Thomas Anderson, drew his attention to the latest work of Pasteur, specifically to “On the organized bodies which exist in the atmosphere” (1861) and to “Investigation into the role attributable to atmospheric gas” (1863) (Fisher 121). The advice might have been serendipitous in that Lister began to read Pasteur’s papers at a time when he was struggling to control post-surgical infections. At the time of his appointment as head of the Glasgow Royal Infirmary in 1861, Lister had observed that hospitalism, a term coined by Dr. James Y. Simpson, was widespread. Simpson used this neologism in the 1869 study, “Hospitalism: Its Effects on the results of surgical operations.” Hospital cross-infections of this kind were dreadful complications to surgery (Cameron 50-2; Guthrie 16-19). 3
After leaving Glasgow for Edinburgh, Lister would publish an article on the problem in The Lancet of 1870, “On the Effects of the Antiseptic System of Treatment upon the Salubrity of a Surgical Hospital” (CP, vol. 2, 123-36). The article outlines the unhealthy conditions with which he had to contend and enumerates three endemic disorders responsible for hospitalism: pyaemia (purulent septicemia), erysipelas (inflammatory bacterial infection), and hospital gangrene (the death of healthy tissue due to interruption of blood supply or toxin-producing bacteria) (CP, vol. 2, 123-4). More alarming, for Lister, was the startling disclosure that, at the time of the 1849 cholera epidemic, coffins had been expeditiously interred just inches below the surface of the Glasgow Infirmary (CP, vol. 2, 124-5).
From 1864 on, Lister had been investigating whether Pasteur’s work on micro-organisms could be applied successfully to the management of wound infections through the use of antiseptics. To this end, he began experimenting with chemical compounds in the hospital, while replicating Pasteur’s bacteriological experiments not only to verify his findings, but also to gain a clearer understanding of the kinds of organisms endangering surgical patients. Lister had come to realize that the study of bacteria and the practice of surgery were interdependent sciences.
Lister composed a series of interdisciplinary papers exploring the relation of bacteria and surgery. In “On a New Method of Treating Compound Fracture, Abscess, Etc.” (1867), he tried to determine how atmosphere related to the decomposition of organic substances (CP, vol. 2, 1-36). Pasteur’s research and Lister’s everyday practice strongly suggested that microbes, rather than gas, constituted the “essential cause” of putrescence (CP, vol. 2, 2):
Turning now to the question how the atmosphere produces decomposition of organic substances, we find that a flood of light has been thrown upon this most important subject by the philosophical researches of M. Pasteur, who has demonstrated by thoroughly convincing evidence that it is not to its oxygen or to any of its gaseous constituents that the air owes this property, but to minute particles suspended in it, which are the germs of various low forms of life, long since revealed by the microscope, and regarded as merely accidental concomitants of putrescence, but now shown by Pasteur to be its essential cause, resolving the complex organic compounds into substances of simpler chemical constitution, just as the yeast plant converts sugar into alcohol and carbonic acid. [CP, vol. 2, 2]
At this juncture, Lister brought the incipient germ theory to bear on the case of a patient suffering from a punctured lung, caused by a fractured rib. An injury such as this one was extremely dangerous because of the risk of infection. Lister surmised that if an external wound were to penetrate the chest, and if it exposed the pleura to bacteria-laden surroundings, germs invariably entered the wound. For Lister, these circumstances raised questions to which he would give considerable thought for decades to come: how did harmful organisms enter and develop in the wound? What were the effects of their presence? And were inflammation, suppuration, and associated phenomena reactions to, or concomitants of, infection? In other 1867 papers, we see that Lister was acutely aware of how much he owed to Pasteur’s research of 1857-1863. “On The Antiseptic Principle in the Practice of Surgery” (9 August 1867), for one, emphasizes the theoretical importance of Pasteur’s research to medicine (CP, vol. 2, 37-45):
But when it had been shown by the researches of Pasteur that the septic property of the atmosphere depended, not on the oxygen or any gaseous constituent, but on minute organisms suspended in it, which owed their energy to their vitality, it occurred to me that decomposition in the injured part might be avoided without excluding the air, by applying as a dressing some material capable of destroying the life of the floating particle. [“Antiseptic Principle,” CP, vol. 2, 37]
The 1867 papers cited above reflect the early stages of Lister’s application of the germ theory to medicine and of the development of his antiseptic methods. Its surgical application had progressed in stages from possibility to certainty: hence, the “New Method” (or unprecedented technique), in the 9 August 1867 Lancet paper, had become a “Principle” or fundamental doctrine; and, ultimately, after sufficient clinical evidence had been compiled, it emerged as a bona fide “Antiseptic System”-that is, as an organized and established procedure.
Pasteur’s systematic activities in the laboratory inspired Lister to describe and afterwards to replicate his work. In “Illustrations of the Antiseptic System of Treatment in Surgery,” for example, Lister outlines one instance of the chemist’s study of bacteria, designed to prove that the atmosphere contained the spores of minute vegetation and infusoria, believed to be densely concentrated in cities and forests where life abounded (CP, vol. 2, 46-85). Pasteur’s experimentation led him to believe that, in the Alpine glacial regions that he had visited, airborne pathogens were less concentrated than in rural or urban regions because of the general scarceness of organic life. The experiment Pasteur devised to replicate the Alpine findings was ingeniously simple. According to Lister, Pasteur suspected that if he passed a stream of air through a narrow but contorted glass tube, microscopic particles would land in the twists and bends, while inflowing gases would contact the organic material at the bottom of the flask. Since the organic infusions in the experiment did not putrefy, this suggested that aseptic air itself was not responsible for decomposition.
At this point in the essay, Lister recalls having benefited from an analogy Pasteur had drawn, in the March and April 1865 edition of Annales des sciences Naturelle, between fermentation and putrescence, on the one hand, and infection, on the other: the analogy led Lister to suspect that the microbial processes involved in fermentation and putrefaction might be similar to those responsible for infections. Further, after viewing vibrio (comma or S-shaped bacteria) moving on the surface of bodily fluids, Lister surmised that pathological germs might also be motile and, as a result, have the capacity to invade and destroy tissue (CP, vol. 2, 47n.). In the light of Pasteur’s papers, it became clear that, wherever there was an open wound, the safety of the patient depended on the eradication of germs or on maintaining an aseptic condition. Lister emphasizes this conclusion in the above-cited, 1867 Lancet paper, “Illustrations,” but he reminds practitioners that a balance must be sought since carbolic acid, if used in excess, had irritating qualities:
Admitting, then, the truth of the germ theory, and proceeding in accordance with it, we must when dealing with any case, destroy in the first instance once [and] for all any septic organisms which may exist in the part concerned; and after this has been done, our efforts must be directed to the prevention of the entrance of others into it. And provided that these indications are really fulfilled, the less the antiseptic agent comes in contact with the living tissues the better, so that unnecessary disturbance from the irritating properties may be avoided. [CP, vol. 2, 47-8]
After having replicated a Pasteurian experiment that had been performed in 1861, Lister presented his findings. The results of both experiments further undermined the theory of spontaneous generation. In “On the Causation of Putrefaction and Fermentation” (delivered in the University of Edinburgh, 8 November 1869), Lister explains how Pasteur had prepared a flask in a manner similar to that used in the experiment described above, but there was a significant difference (CP, vol. 2, 477-88). After the yeast had been introduced, the neck of the flask was heated to the point of malleability, drawn into the shape of a narrow tube, and then bent into an S-curve (Dubos , 58). The fluid was boiled, but the end of the neck was left open, allowing air to pass into the flask as the heating lamp was withdrawn. This done, the container was left untouched, to determine what effects, if any, diurnal changes of temperature would have on the decoction. Once again, the alleged contaminative property of atmospheric gas was being tested. The gases in the test flask expanded diurnally and condensed nocturnally. Even though atmospheric air entered and exited the vessel, over an indefinite period of time the decoction did not putrefy. Although this experiment did not explicitly account for the disposition of airborne life, it lent credence to the view that the gases themselves did not generate microbes spontaneously.
Pasteur and others suspected that microbial spores had settled in the angles of the contorted neck (“On the Causation,” CP, vol. 2, 486). The Committee of the French Academy, which adjudicated the proceedings, tested this hypothesis in a simple way. Re-sealing the neck, and once satisfied that the flask was sterile, they inverted and shook it, forcing liquid into the angles of the re-shaped tube, and flushing any microbial spores down into the solution. Once this had been done, they then let the flask sit. In a short period of time, micro-organisms that had adhered to the angles and recesses of the bent tube began to germinate in the fluid. As a result of this test, it became even more difficult to dismiss the possibilities that microscopic growth originated from germs and that microbes were carried by the diurnal influx of air onto the glass surfaces of the angular neck. This intriguing supposition encouraged Lister to continue to think about its clinical importance, but first he needed to convince his colleagues, and to persuade influential opponents, such as Sir James Y. Simpson, who assumed incorrectly, in 1867, that Lister had claimed precedence for the use of carbolic acid as an antiseptic (Godlee 159-61, 199-205). Despite the professional rivalry and confusion surrounding Lister’s claims and intentions, he steadfastly subscribed to Pasteur’s work. For this reason, he was obliged to duplicate the chemist’s experiments, to survey the latter’s work in his own publications, to allude to collateral investigators, and to consider what these findings could mean for his patients.
Lister had to show, beyond doubt, that bacteria were ubiquitous in the operating theaters and recovery rooms. Pasteur’s experimental methods and discoveries inspired Lister to replicate them and, if he were successful, to present the results publicly to satisfy critics. Thus, on 8 November 1869, at Edinburgh, Lister presented his findings. Instead of the yeast decoction that Pasteur had used, Lister used urine as a medium, introducing it into four flasks, each being one-third full. Three of four were heated to the point of malleability. The glass necks were then elongated; and the spout openings, reduced to transverse, diametrical slits. Before the tubes cooled and hardened, Lister, like Pasteur, had bent the necks of three vessels at acute angles. The fourth vessel, its shorter neck elongated and its diameter narrowed more than those of the other three, remained vertical. Lister boiled the four flasks for five minutes until steam issued from the narrow necks; the boiling killed microscopic life. When the burner was removed, air passed into the vessels, displacing the condensed aqueous vapor.
After having recounted his version of the Pasteurian experiment, Lister then demonstrated to the audience at Edinburgh that, after two years, more than one cubic inch of fresh air had entered into each vessel and contacted the liquid (“Causation,” CP, vol. 2, 486-8). In the bent flasks, the air had dried the moisture in the tubes. Despite the entrance of air, however, for two years the urine had remained uncontaminated (CP, vol. 2, 487). Fluid in the vertical-tube flask, however, had changed considerably, exposure to airborne micro-organisms having transformed the yellow transparency of the urine to a muddy brown, filling the solution with sediment and dead fungi; in addition, a strong odor of ammonia was present (CP, vol. 2, 487). Lister had successfully demonstrated his hypothesis: “ . . . no one can say it is impossible, and no other possible explanation presents itself. The experiment proves with certainty that the gases of the air, however abundantly supplied, are of themselves unable to originate the growth of torulae and the other minute organisms which appear in decoction of yeast freely exposed to the atmosphere; and also that the essential source of such development must be suspended particles of germs” (CP, vol. 2, 485-6).
At the six-month mark in the experiment, Lister recalls having examined samples of the bent vessels under the microscope, but he found no organisms. He attributed this aseptic state to his having filtered out the airborne spores: because the necks had been bent, airborne micro-organisms collected in the glass curvatures. The Listerian version of the experiment successfully confirmed Pasteur’s threefold discovery: atmospheric gases themselves were not responsible for putrefaction; organisms did not arise spontaneously from organic solutions; and microbes germinating in the flasks originated from airborne germs and spores. Once exposed to the air, the uncontaminated urine samples from the six-month-old flasks became odorous and full of microscopic life (“Causation,” CP, vol. 2, 487).
1871-1877: A Period of Communication & Exchange
Visiting London, in 1871, Pasteur met the British physicist John Tyndall (1820-1893), who had recently toured Lister’s wards. Tyndall, a committed germ theorist himself, informed Pasteur of Lister’s successes, and this was the “first time Lister had come to Pasteur’s attention” (Fisher 198). As we have seen, from 1864 on, Lister had become well-acquainted with Pasteur’s thinking, was methodically establishing and communicating the validity of the theory, and was exploring ways of applying this knowledge to medicine. Part of this overall strategy, at this time, was to persuade his colleagues as to its merits.
Besides conducting Pasteur’s experiments with precision and care, whenever the opportunity arose for Lister to present the antiseptic system of surgery at a professional forum, he continued to acknowledge his debt to Pasteur’s groundbreaking research of 1857-1863.“The Address in Surgery” (1 August 1871), delivered at Plymouth, is typical of this tendency. In it, Lister reviewed the theoretical basis of his antiseptic treatment, his replication of Pasteur’s experiment on putrefaction (that is, of the boiling of organically-infused liquid in bent flasks), and stressed the fact that airborne germs caused decomposition. Once again, he related that three of the four containers of originally sterilized urine, presented at Edinburgh on November 1869, had not putrefied, even though they had been continually exposed to atmospheric air-that is, to air from which dust and suspended organisms had been filtered. He also reminded his audience that, at the six-month mark in the experiment, he had decanted small amounts of urine from the purportedly-sterile flasks, exposing the samples directly to unfiltered, atmospheric air. As had been predicted, in a short time the samples teemed with organisms and exhibited fungal growth; thus, the urine proved to be a medium chemically favorable to the germination of life (CP, vol. 2, 175-78).
Once the bacterial cause of putrefaction had been proven to Lister’s satisfaction, he turned to surgery, armed with carbolic acid, crude aerosolizing sprayers, and ingenious methods of dressing wounds and of setting broken bones, using saturated putty, rubber, tin and other materials. An inventive stage in Lister’s career had begun, as he devised practical ways of applying such compounds before, during, and after an operation, the intention always being to promote natural healing. In these interventions, Lister consulted colleagues, one of whom, John Tyndall, had been experimenting successfully with cotton-wool filters as a means of arresting germ-laden dust. Lister presented what he learned from Tyndall in the 10 August 1871 “Address on Surgery” (CP, vol. 2, 175-78). The most famous surgery that Lister performed at this time (he had been appointed, in 1871, Surgeon-in-Ordinary to the Queen in Scotland) was to drain an infected abscess in Queen Victoria’s shoulder, using lint strips soaked in an oily solution of carbolic acid, supplemented by antiseptic spray (which, unfortunately, irritated the Queen’s eyes). The operation was a success: the lint worked beautifully to drain the pus while the carbolic acid, however awkwardly applied, prevented infection (Godlee 305).
Lister’s respect for Pasteur’s work is evident in published correspondence of this period. While in London performing dissections and conducting lectures, Lister forwarded a 10 February 1874 letter to Pasteur that included a copy of the October 1873 paper, “A Further Contribution to the Natural History of Bacteria and the Germ Theory of Fermentative Changes” (Letter, Godlee 274-5; “Natural History,” CP, vol. 1, 309-34). Furthermore, Lister invited Pasteur to review the British journals on bacteria and antisepsis and, should he visit Edinburgh, to tour the hospital. Responding in a cordial 27 February 1874 letter, Pasteur explained that he had learned of Lister’s antiseptic system through conversations with Tyndall and with the chief surgeon at the Val de Grâce Hospital in France (Letter, Godlee, 275-77). Although Pasteur had been unacquainted with the details of the research, he was nevertheless genuinely impressed by Lister’s thoroughness and invited him to send along a detailed account of the system.
The exchange of views described above produced important publicity. Just as Lister had found in Pasteur’s biochemical research a promising new approach to the management of hospital infections, Pasteur felt obliged to transmit Lister’s surgical applications to the French medical community. In the interest of humanity, both men felt that the system needed to be widely disseminated. To promote greater cooperation, Pasteur requested from Lister copies of his principal scientific publications on the germ theory. To support Lister’s laboratory research, Pasteur, in turn, offered professional suggestions on safeguarding cultures from contamination.
In a letter of 29 June 1876, Pasteur gratefully accepted two of Lister’s papers and informed him that, although the antiseptic system had not yet been universally accepted in French medical circles, interest in it was increasing. Unknown to Pasteur at that time, a prominent French physician had already been instrumental in introducing Lister’s system to the French medical community. When visiting Glasgow in 1868, Dr. Just Lucas-Championnière was impressed by Lister’s method, and, in 1876, would write the first complete account of it (Letter, Godlee 307-10, 353; Vallery-Radot 239).
Following Lister’s lead, Pasteur began in earnest to investigate the possibility of bacterial infection in surgery. In June 1876, he had witnessed an operation at Necker Hospital, from which no post-surgical sepsis arose (Letter, Godlee 307-10). The satisfactory outcome, Pasteur averred, was attributable to the surgeons having followed Lister’s instructions on the use of carbolic acid. Citing a remark by his colleague, Dr. Charles-Emmanuel Sédillot (1804-1883) (coiner of the word microbe), Pasteur writes that recent successes and failures in surgery “find a rational explanation in the principles upon which the germ theory is based, and that this theory would found a new Surgery-already begun by the celebrated English surgeon, Dr. Lister, who was among the first to understand its fertility” (“The Germ Theory,” 116-17).
The effectiveness of the acid in surgical-wound treatment using Lister’s method encouraged Pasteur to consider the antiseptic properties of diluted boric acid (Letter, Godlee 307-10). Pasteur corroborated Lister’s notion that boric acid was, indeed, a promising germicidal agent, for it, too, had been used in the Necker Hospital operation, and he suggested that Lister experiment with the agent further to derive more data. Thus, both scientists began to work with boric acid, and the interchange of ideas and of findings continued. Pasteur even included in the dispatch a copy of his latest book on the fermentation of beer, in which was reprinted Lister’s 10 February 1874 correspondence to him.
From 1875 to 1878, Lister replicated Pasteur’s bacterial experiments in order to learn more about microbes and, through this knowledge, to be able to manage wounds better. The 1875 article, “A Contribution to the Germ Theory of Putrefaction and other Fermentative Changes, and to the Natural History of Torulae and Bacteria,” exemplifies Lister’s strategy (CP, vol. 1, 275-308, esp. 276). He begins, as expected, with enthusiasm for the “philosophical investigations” of Pasteur that, since 1867, had completely converted him to the germ theory that, in 1875, was a “guiding principle” in his practice (CP, vol. 1, 276). In addition, this principle meant that he had to revise surgical methodology to include chemical and bacteriological components, as evidenced in the 1878 paper, “On the Lactic Fermentation and Its Bearings on Pathology” (CP, vol. 1, 353-85). October 1878 was an important month in Lister’s career as he was appointed to the position of Surgeon-in-Ordinary to Queen Victoria (Godlee 473).
1878-1888: A Decade of Interdisciplinary Research
In the 29 April 1878 paper, “The Germ Theory and Its Applications to Medicine and Surgery,” Pasteur stated to the French Academy of Sciences that chemistry, the emerging discipline of bacteriology and medicine were interdependent sciences that “gain[ed] by mutual support.” Just as Lister recurrently acknowledged his debt to Pasteur, Pasteur acknowledged what he owed to his predecessors, one of whom was the French pathologist and parasitologist, Casimir-Joseph Davaine (1812-1882) (“The Germ Theory and Its Applications,” 110).
To confirm experimentally that microscopic organisms cause disease, Pasteur described in this paper how he cultivated pathogens. Through twelve successive cultivations, each ten cubic centimeters in volume, an original drop of the anthrax bacillus in culture became greatly diluted. Pasteur followed this procedure in sterile liquid a number of times, at each stage in the experiment seeding successive cultures with minute drops from preceding ones. A significant finding was that the final culture in the series remained virulent. Augmenting the work of Davaine, of Dr. Robert Koch, and of others, Pasteur and his colleagues, through this method, acquired further evidence that anthrax was a bacterial disease (“The Germ Theory and Its Applications,” 111). Pasteur reviews the progress of the bacteriological research he and his co-workers had undertaken in 1877, as they searched for definitive proof of the bacterial causation of certain diseases:
Our researches of last year, left the etiology of the putrid disease, septicemia, in a much less advanced condition than that of anthrax. We had demonstrated the probability that septicemia depends upon the presence and growth of a microscopic body, but the absolute proof of this important conclusion was not reached. To demonstrate experimentally that a microscopic organism actually is the cause of a disease and the agent of contagion, I know no other way, in the present state of Science, than to subject the microbe . . . to the method of cultivation out of the body. [“Germ Theory and Its Applications,” 111]
This was a fecund time for bacteriological research. Along with Pasteur’s laboratory work on anthrax, in 1877-1878, Lister delivered the Introductory Address in King’s College, London, on 1 October 1877, entitled “On the Nature of Fermentation (published in the Quarterly Journal of Microscopical Science, April 1878) (CP, vol. 1, 335-52). Dr. Robert Koch was also linking bacteria to medicine, as his concurrent research and publications plainly show. His paper, “The Etiology of Anthrax, Founded on the Course of Development of the Bacillus Anthracis” had appeared in 1876; and “Investigations of the Etiology of Wound Infections,” in 1878 (Essays, 1-17, 20-56, resp.).
Joseph and Agnes Lister visited Paris in June 1878, for the Prince of Wales had appointed him President of the British Commission to the jury on Medicine, Hygiene and Public Relief (Fisher 248). Lister had a wonderful opportunity, at this time, to meet with Pasteur at the home of Dr. Gueneau de Mussy, close friend of Pasteur. After the dinner at de Mussy’s home, Pasteur and Lister met again for lunch on 21 June (248). Unfortunately, there is no record of what transpired. One can reasonably infer, however, that the discussions included disease-causing organisms and post-surgical infection control.
Pasteur congratulated Lister, in a letter of 2 January 1880, on his presentation of surgical methods at the Amsterdam Medical Congress, apprised him of his present work on contagious diseases and bacteria, and hoped that his investigations would uncover “indisputable proof” that microscopic organisms played “a considerable part in . . . infectious disease” (Letter, Godlee 436-7). He was convinced that research of this kind, ranging as it did across disciplines, required a cooperative effort. In the 3 May 1880 paper, “On the Extension of the Germ Theory to the Etiology of Certain Common Diseases,” read before the French Academy of Sciences, Pasteur wrote in just such a multidisciplinary vein (118-30).
“On the Extension” reviews ongoing efforts to connect the germ theory to disease. Its content arose from a fortuitous occurrence. In May 1879, one of Pasteur’s laboratory co-workers had been diagnosed with furuncles, a bacterial infection of hair follicles. With the cooperation of the volunteer, research was conducted from 2 June to 21 July 1879 (“On the Extension,” 118-22). From disparate, suppurating lesions, Pasteur took samples that, hours after being cultured, produced bacterial growth; the same organism was identified in each case. Repeated cultivations in the presence of atmospheric oxygen led him to conclude that furuncles contained “an aerobic microscopic parasite” (121). Thus, the disease had been traced to its probable cause.
Pasteur thought that knowledge about the furuncle germ could illuminate the etiologies of osteomyelitis and of other infectious diseases. Pasteur had also been accumulating observations on puerperal fever, a disorder that Dr. Ignaz Philip Semmelweis (1818-1865) had worked so diligently to cure by requiring obstetric surgeons to wash their hands in chlorinated lime (“Lecture,” 80-2). Pasteur’s initial entry on the subject was based on a visit to a maternity wing under the supervision of Dr. Hervieux (“On the Extension,” 123). Pasteur concluded that “puerperal fever” comprised a group of distinct diseases having in common a single pathogen (128). Infectious organisms spread from traumatized areas to remote sites. Undoubtedly, he deduced from this experience that inhibiting the production of these organisms could improve the patient’s chances of recovery. Confident that Lister’s antiseptic method was the key to treatment, Pasteur suggested that antiseptics, such as carbolic or boric acid, be applied to the patient after delivery and while in recovery (128-9). These clinical experiences illustrated that an understanding of the mechanisms of disease required a broad scope, one encompassing several fields that could work interdependently: one would be called bacteriology (established in Germany in 1884); two others, as we have seen thus far, were chemistry and medicine. Acutely aware that a cooperative effort was involved in this work, Pasteur invited opinions from every circle.
As a chemist, Pasteur realized that, to study the role of germs in post-surgical infections, he needed the guidance of medical professionals. He concludes the paper by underscoring two points: that research in this area must be conducted both scrupulously and collaboratively:
I have detailed the facts as they have appeared to me and I have mentioned interpretations of them; but I do not conceal from myself that, in medical territory, it is difficult to support one’s self wholly on subjective foundations. I do not forget that Medicine and Veterinary practice are foreign to me. I desire judgment and criticism on all my contributions. Little tolerant of frivolous or prejudiced contradiction, contemptuous of the ignorant criticism which doubts on principle, I welcome with open arms the militant attack which has a method in doubting and whose rule of conduct has the motto ‘More Light.’ [“On the Extension,” 129-30]
1880-1896: Fowl-Cholera, the “Jubilee,” and “Interdependence”
In August 1881, Pasteur and Lister met for the second time, in London at the International Medical Congress. At this symposium, and with Pasteur in the audience, Lister delivered, on 5 August 1881, “An Address on the Relations of Minute Organisms to Inflammation” (CP, vol. 1, 399-410). Lister began the Address with a reference to an earlier paper of 12 August 1880, read at the meeting of the British Medical Association at Cambridge. In the earlier paper, he described how he and Pasteur had tried to find a suitable culture medium for the fowl-cholera organism. Because Pasteur valued Lister’s opinion, he had sent to him specimens of chicken-broth cultures. Once they were received, Lister studied the developing bacteria extensively and, as expected, conveyed his observations to colleagues at the Cambridge meeting (CP, vol. 1, 390-1).
The interchange between Pasteur and Lister on the fowl-cholera issue can be traced through five consecutive papers. The first was Pasteur’s 26 October 1880 paper, “The attenuation of the causal agent of fowl cholera” (126-31). Lister’s address followed. More of a summary than a contribution, it was read on 12 August 1880 to the Pathological Section of the British Medical Association (B.M.A.) at Cambridge and was titled, “On the Relations of Micro-Organisms to Disease” (published April 1881) (CP, vol. 1, 387-98). In June 1881, Pasteur’s efforts to develop a vaccine by attenuating the bacillus were publicized in, “On a vaccine for fowl cholera and anthrax” (“vaccine,” 131-2). And an English translation of his “Address on the Germ Theory,” delivered at the International Medical Conference in London on 12 August 1881, was published verbatim in The British Medical Journal on 13 August 1881 as, “An Address on Vaccination in Relation to Chicken Cholera and Splenic Fever” (283-84).
Pasteur’s experiments on fowl-cholera impressed Lister to the extent that the latter described the entire experiment in the 12 August paper, “On the Relations of Micro-Organisms to Disease” (CP, vol. 1, 387-98). Rightly attributing the discovery of the bacillus to Henri Toussaint (1847-1890), a professor at the Lyons’ Veterinary School, Lister concentrates on its symptoms and mode of contagion. Lymphatic swelling, pericarditis and duodenal ulcerations were typical symptoms of this highly-infectious blood disease of chickens. If the blood were mixed with chicken feed, contagion occurred in two-thirds of the animals. Lister was interested in knowing how the bacterial pathogen (misidentified both as “cholera” and as “virus”) entered the circulatory system. According to Toussaint, an abrasion of the oral epithelium was the probable site of infection because the throat and lymph nodes were so affected, and because similar symptoms were produced if chickens were inoculated in the mouth with infected blood or serum. Lister attributed to Toussaint the observation that resistant chickens were not immune to the germ when inoculated orally, suggesting that the previous immunity to the tainted feed was through some “accidental circumstance” (CP, vol. 1, 390).
Lister had firsthand knowledge of how Pasteur cultivated the bacillus in chicken broth. As mentioned above, Pasteur had sent to Lister fowl-cholera cultures in tubes. At the 12 August 1880 B.M.A. meeting, and as his Cambridge University audience looked on, Lister took a drop of Pasteur’s specimens for microscopic examination. He proceeded to describe “a minute form of bacterium, oval-shaped, tending to multiplication by transverse constriction, and very frequently seen in pairs, and occasionally in chains” (CP, vol. 1, 390-1). It resembled the Bacterium lactis in diameter, both microbes ranging from 1/50,000th to 1/25,000th of an inch in length. Pasteur had also been kind enough to send Lister a representation of the organism, a woodcut of a camera-lucida sketch, drawn to scale; to Lister’s knowledge, this was the first time anyone in Britain had ever seen the organism. After a number of successive cultivations, Lister explained, Pasteur claimed that the original virulence remained undiminished; thus, inoculation of the culture or of the blood proved lethal (CP, vol. 1, 390). These findings, Lister believed, increased the probability that the isolated organism was responsible for the disease.
Lister emphasized several of Pasteur’s observations. One was that the pathogen was unlike a putrefactive organism because it did not cause chicken broth to spoil. Another observation that caught Lister’s attention was that the organism reached a threshold of development and then ceased to multiply. The organism, Pasteur was reasonably certain (although subsequently proven wrong), had subsisted on the broth since its volume had diminished over time; furthermore, if another sample of fowl-cholera fluid were introduced into the very same dish, the new specimen did not flourish, which implied that its nutritional content had been depleted. This led Pasteur logically, although incorrectly, to suspect that the broth had been rendered unfit for the further development of the organism. Lister, on the other hand, surmised that the answer lay, not in the medium, but in the organism’s constitution itself: Pasteur had unknowingly “enfeeble[d] the organism,” altering it in some way so that, when the culture was injected into a healthy fowl, only a mild form of the disease occurred (CP, vol. 1, 391-92). If this were true (and perhaps Lister had Jenner in mind), then, through this procedure, the bird had been rendered secure, or (to use a later term) had become immune to, the ordinary form of the disease. The chicken, in effect, had been vaccinated, having received an attenuated form of the pathogen to which it produced an immunological response. Pasteur had taken the trouble of sending an immunized hen along to Lister for demonstration purposes. The chicken, none the worse for the overseas trip and doubtless a source of humor, was “in good health, bright and active, and it both eats and sleeps well” (CP, vol. 1, 392).
Because Pasteur’s method and findings were so significant, Lister outlined both carefully. Pasteur had begun by cultivating the organism, “pure and unmixed in chicken broth”; the culture was then exposed to air but shielded from dust to avoid contamination (CP, vol. 1, 396-98). If the period of cultivation were two months or less, the organism remained unchanged. But, by the third or fourth month, virulence began to decline, and by the eighth month, the organism, though it could cause a mild attack if inoculated into a chicken, was no longer lethal; if the period was sufficiently prolonged, the bacillus was rendered harmless. Although neither Pasteur nor Lister was immediately aware of the fact that the inoculated chickens had developed antibodies to the disease itself, their concerted efforts contributed significantly to the nascent science of immunology.
The reason for the organism’s attenuation was unknown. Lister recounts how Pasteur tested hypotheses on the subject. Speculating that oxygen exposure had degraded the germ, he conducted an experiment. In closed tubes with a minimal oxygen volume, the organism lived until free oxygen was used up; then it sank to the bottom, but, when retrieved, it was reputed to have retained its vitality and virulence if inoculated into healthy chickens (CP, vol. 1, 397). A prominent researcher, whom Lister mentions, subscribed to the theory that the medium attenuated the germ. W.S. Greenfield, M.D., the Brown Professor at the University of London, known for his pioneering work on anthrax and immunity, believed that the colony grew either until nutrients were exhausted or until the broth had undergone chemical changes enfeebling the organism’s progeny. As for the sealed tubes with limited oxygen, Greenfield (according to Lister) suspected that, with the exhaustion of oxygen, the colony ceased to reproduce. Instead of dying out, however, the organisms had simply become inert; and each, “like a vigorous seed” (or spore), remained inherently fecund. Whether the cause of the organism’s diminution lay in the oxygen or in the medium remained a point of interest and of debate.
Eventually, Pasteur, Toussaint, and Greenfield learned that the cause of immunization involved the micro-organism itself and the host’s reaction to it (CP, vol. 1, 398). Lister was certain that Pasteur’s study of chicken cholera, begun in 1878, was leading to extraordinary innovations in the science of vaccination. More definitive explanations were on the horizon. In 1890, Emil von Behring developed a vaccine against tetanus and diphtheria and introduced the concepts of passive immunization and of anti-toxins. The science of serology was inaugurated by the paper, “The mechanism of immunity in animals to diphtheria and tetanus” (1890), co-authored by von Behring and the Japanese bacteriologist, Shibasaburo Kitasato (140), known for his later work on influenza and on plague.
Lister met Pasteur for the third and last time at the latter’s Jubilee celebration, which took place on 27 December 1892. As a representative of the Royal Society of London and of the Royal Society of Edinburgh, Lister delivered an eloquent Address in French (Godlee 518-22). Despite the occasional figurative cliché or superlative phrase, the text reads as a précis of Pasteur’s genuine achievements. Lister writes that Pasteur’s research had changed surgical wound-treatment from an uncertain and often disastrous undertaking to a scientific art. Not only had the chemist’s pioneering efforts helped to remove terrors associated with post-surgical infection, but they had enlarged the capabilities of surgeons who no longer had to hurry through a particular procedure to pre-empt infection.
Uncovering the nature of microbes, Lister states, had made it possible to diagnose the plagues of the human race and also to design prophylactic and curative treatments. He refers to Pasteur’s method of attenuation to create protective vaccines, no more dramatically illustrated than in the campaign against rabies. Because his originality was so striking, many doctors were suspicious of Pasteur. How could a man, they said, who was neither a medical doctor nor a biologist instruct them about a disease, to which the greatest medical minds have applied themselves but in vain? As far as Pasteur’s scientific method was concerned, Lister applauded his colleague’s clarity of thought and scrupulously-formulated inductions. Events justified Lister’s confidence, as the entire world recognized his victory over rabies. The vaccine, painstakingly developed by 1885, had dispelled the anguish of uncertainty that every person exposed to a rabid animal experiences.
One year after Pasteur’s death, Lister presented “On the Interdependence of Science and the Healing Art,” the 1896 Presidential Address to the British Association for the Advancement of Science (CP, vol. 2, 489-514). In this important document, he observes that Pasteur’s fowl-cholera experiments revealed much about immunity. Chickens that had received the weakened microbe had developed immunity to the disease it caused (CP, vol. 2, 504). Lister was certain that Pasteur’s knowledge of the history of medicine and the latter’s conviction that chemistry, biology, and surgery were mutually dependent, had brought him to a decisive phase in the experiment: the inoculation of vaccinated chickens with a virulent strain of the organism. Lister rightly underscores the Jenner-Pasteur connection: “For Pasteur at once saw the analogy between the immunity to fowl-cholera produced by its attenuated virus and the protection afforded against small-pox by vaccination.” On this basis, he attenuated varieties of microbes for prophylactic vaccination against anthrax, swine erysipelas, and rabies (CP, vol. 2, 504).
Lister included in the 1896 “Interdependence” Address an encomium to Pasteur who had died the year before, and this public expression of gratitude and indebtedness helped to define the latter’s position in the history of biology and medicine. Spanning more than three decades, Lister’s Pasteurian commentary, in many ways a professional tribute, includes critical evaluations, replicated experiments, important communications, conferrals with a multidisciplinary scientific community, and adaptations of theory to practice. Pasteur’s statement, in 1878, that the natural sciences and medicine were interdependent disciplines-that they “gain by mutual support”--proved to be quite valid (“The Germ Theory and Its Application,” 110).
Last modified 6 July 2012