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History of Microbiology Milton Wainwright University of Sheffield Joshua Lederbergl The Rockefeller University I. Observations without Application ness of the nature and etiology of disease, with the II. The Spontaneous Generation Controversy result that the majority of the traditional killer dis- III. Tools of the Trade eases have now been conquered. Similar strides IV. Microorganisms as Causal Agents of have been made in the use of microorganisms in Disease industry. and more recently attempts are being made V. Chemotherapy and Antibiosis to apply our knowledge of microbial ecology and VI. Microbial Metabolism and Applied physiology to help solve environmental problems. A Microbiology dramatic development and broadening of the subject VII. Nutrition, Comparative Biochemistry, and of microbiology has taken place since World War II. Other Aspects of Metabolism Microbial genetics, molecular biology, and bio- VIII. Microbial Genetics technology in particular have blossomed. It is to be IX. Viruses and Lysogeny: The Plasmid hoped that these developments are sufficiently op- Concept portune to enable us to conquer the latest specter of X. Virology disease facing us, namely AIDS. Any account of the XI. Mycology and Protozoology, history of a discipline is. by its very nature, a per- Microbiology’s Cinderellas sonal view: hopefully, what follows includes all the XII. Modern Period major highlights in the development of our science. The period approximating 1930-1950 was a ‘vi- cennium” of extraordinary transformation of micro- Glossary biology, just prior to the landmark publication on the structure of DNA by Watson and Crick in 1953. Antibiotics Antimicrobial agents produced b) We have important milestones for the vicennium: living organisms Jordan and Falk (1928) and “System of Bacteriol- Bacterial genetics Study of genetic elements and ogy” (1930) at its start are magisterial reviews of hereditary in bacteria prior knowledge and thought. Dubos (1945) and Chemotherapy Systemic use of chemical agents Burner (1945) anticipate the modern era. and Werk- to treat microbial infections man and Wilson (1951) and Gunsalus and Stanier Molecular biology Science concerned with DNA (1962) document its early and continued progress in and protein synthesis of living organisms monographic detail. The AnnunI Review of Micru- Monoclonal antibodies Specific antibodies pro- biology, starting in 1947 (and several other Annual duced by in vitro clones of B cells hybridized Reviews), and Bacteriological Reviews. starting in with cancerous cells 1937, offer invaluable snapshots of the contempo- rary state of the art. These works can be consulted for many of the pertinent bibliographic citations, and they will be explicitly repeated here only when ALTHOUGH MICROORGANISMS were first ob- important for the argument. served using primitive microscopes as early as the This account will center on the fundamental biol- late 16OOs, the science of microbiology is barely 150 ogy of microbes and give scant attention to continu- years old. In this time, major developments have ing advances in the isolation of etiological agents of been made in our understanding of microbial physi- disease and of vaccines and immunodiagnostic pro- olog),. ecology, and systematics. This knowledge cedures. Most of the agents of common bacterial has been successfuly applied to broaden our aware- infections had been characterized by ” 1930,” but IFor the period from 1930. Encyclopedia of Microbiology, Volume 2 419 Copyright C 1992 by Academic Press. Inc. All rights of reproduction in any form reserlred 420 History of Microbiology the vicennium was distinguished b! important work croscopes (Fig. 2) to examine microorganisms in on the classification of enteric (diarrhea]) bacteria rainwater. well water. and seawater as well as water and, above all. by the isolation and nev,’ stud! of infused u ith peppercorns. His observations 1%ere viruses and rickettsia with methods such as culti- forwarded to the Royal Society in London on Octo- vation virus in the chick embr),o (Kilbourne. 1987). ber 1676 and were later published in the Society’s Philosopi~icr~l T~~rr~strc~rious.In 1683. van Leeuwen- hoek contributed a second letter to the Society de- scribing his various microscopical investigations. in- I. Observations without cluding novel obser\,ations on bacteria present in the Application scurf of teeth. Published in 1683. these observations include the first dra\+ ings of bacteria ever to appear. Macroscopic manifestations of microbial gro\\ th These drawings are >til extant and cleal-ly show that such as bacterial and algal 4limes ha\.e been recag- van Leeuwenhoek observed bacilli. streptococci. nized since antiquity. However. it \\as the Dutch and man\; other characteristic forms of bacteria. microscopist van Leeuljenhoek (Fig. I ) \+ ho pro- van Leeuu,enhoek’s meticulous drawings also she\\, vided the first observations of bacteria at the micro- protozoa such as Vo~ric,c~llr/, VO/UO.\-, and C‘//gl~)/~tr. scopic level. van Leeuisenhoek. a draper in Delft. At about the hame time, Huygens also reported ob- Holland. ground his own lense\ lo make micro- servations on a number of free-living protozoa. in- scopes \+zith short-focal length lenses gi\,ing magni- cluding species of P~i/,rr/llc,c,i,l/rl. Van Leeuwcnhoek fications of betw.een x.30 and x266. Dr\carte\ had also gains credit for describing the first parasitic earlier described a similar crude form of micro- protozoan. when in 1681 he observed his ou’n fecal scope. but the quality of his lenbe\ did not allo\\ stools during a bout of diarrhea and described large for magnifications sufficient to bee bacteria. \‘an populations of what later became known ;is Gir,rtlitr Leeuwenhoek. in contrast. used his homemade mi- I~it~lblitr. History of Microbiology 421 Although van Leeuwenhoek also observed yeast moved by Pouchet’s work to offer a prize to anyone cells in beer, the first illustrations of filamentous who could settle the controversy once and for all. microscopic fungi were provided by Robert Hooke, Despite discouragement from his friends who cau- again in a letter to the Royal Society. this time in tioned against becoming embroiled in the con- 1667. However. the most important early work on troversy, Louis Pasteur (Fig. 3) realized that if mi- molds appeared in the following century when the crobiology was to advance as a rational science the Tuscan botanist. Pietro Antonio hlicheli described idea that microorganisms arose spontaneously some 900 species. including important genera such would need to be experimentally defeated. as Asper-gillrrs and Marco,-. It is also worth noting Pasteur’s studies were published in memoir in that molds have been used from ancient times to 1861 and effortlessly took the prize offered by the treat infections, an approach termed mold therapy, Academy. He first of all showed that when air is which was based on folk medicine rather than on any filtered through cotton wool, large numbers of scientific rationale. microorganisms are held back. Pasteur then suc- Because the connection between microorganisms cessfully repeated Schwann’s work, but his most and fermentation or disease was never made during famous and successful experiments involved the this period. observations made by the first microsco- use of swan-necked flasks, with which he showed pists had surprisingly little impact on human affairs. that heat-sterilized infusions could be kept sterile Despite this. Cicero and the Renaissance scholar in an open flask as long as the open part was tor- Fracastorius had previously suggested that fevers tuous enough to allow any microorganism to set- might be caused by minute animals. collectively de- tle on the sides of the tubes before reaching the scribed as conragium vivum, but it was to be many liquid. centuries before the role of microorganisms in dis- It is often assumed that Pasteur’s experiments ease became recognized, eventually to replace the view that disease resulted from odors or other invisi- ble “miasmas.” II. The Spontaneous Generation Controversy The view that life arises tie t~oco from inanimate objects was widely held from the hliddle Ages until remarkably recent times: Van Helmont even pro- vides us with a recipe for the production of mice. The tenacity with which spontaneous generation lin- gered on is highlighted by the fact that H. Charlton Bastian. one of the concept’s chief proponents, died in 1915, still totally convinced of its merit. Although a scientific rationale was apparently provided to ac- count for spontaneous generation by Needham and Buffon as early as 1745. these ideas were quickly dismissed by Spallanzani in the following year. Fur- ther developments then had to await the work of Schwann. who in 1837 showed that “air which had been heated then cooled left unchanged a meat broth which had been boiled.” Yet by the middle of the seventeenth century, the concept of spontaneous generation held on tenaciously. Then, in 1858,Pou- chet published a paper entitled “Proto-organisms . Borne Spontaneously in Artificial Air and Oxy- gen Gas.” The French Academy, of Sciences was Figure 3 Louis Pasteur (1822-1895). 422 History of Microbiology immediately brought about the defeat of the theory alization of microorganisms to occur. The staining of of spontaneous generation, but this is far from true. histolo$cal specimens was first carried out by the Pouchet. for one, remained convinced that Pasteur’s German botanist Ferdinand Cohn in 1849, his work experiments did not defeat the concept. The con- being based on vegetable dyes such as carmine and troversy continued over the next quarter of a decade hematoxylin. By 1877. Robert Koch (Fig. 4) was or so. Proponents of Pasteur’s views included Brit- using methylene blue to stain bacteria. a process in ish scientists such as Huxley, William Roberts. John which he developed the standard techniques of pre- Tyndall, and the American Jeffries Wyman. The paring dried films. and with the aid of coverslips was main counter-arguments were provided by the last preparing permanent preparations.

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