Journal of the History of Biology

, Volume 49, Issue 1, pp 3–36 | Cite as

The Bacterial Cell Wall in the Antibiotic Era: An Ontology in Transit Between Morphology and Metabolism, 1940s–1960s



This essay details a historical crossroad in biochemistry and microbiology in which penicillin was a co-agent. I narrate the trajectory of the bacterial cell wall as the precise target for antibiotic action. As a strategic object of research, the bacterial cell wall remained at the core of experimental practices, scientific narratives and research funding appeals throughout the antibiotic era. The research laboratory was dedicated to the search for new antibiotics while remaining the site at which the mode of action of this new substance was investigated. This combination of circumstances made the bacterial wall an ontology in transit. As invisible as the bacterial wall was for clinical purposes, in the biological laboratory, cellular meaning in regard to the action of penicillin made the bacterial wall visible within both microbiology and biochemistry. As a border to be crossed, some components of the bacterial cell wall and the biochemical destruction produced by penicillin became known during the 1950s and 1960s. The cell wall was constructed piece by piece in a transatlantic circulation of methods, names, and images of the shape of the wall itself. From 1955 onwards, microbiologists and biochemists mobilized new names and associated conceptual meanings. The composition of this thin and rigid layer would account for its shape, growth and destruction. This paper presents a history of biochemical morphology: a chemistry of shape – the shape of bacteria, as provided by its wall – that accounted for biology, for life itself. While penicillin was being established as an industrially-manufactured object, it remained a scientific tool within the research laboratory, contributing to the circulation of further scientific objects.


Biochemistry Microbiology Penicillin Antibiotic screening Spheroplasts History 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bechtel, William. 2006. Discovering Cell Mechanisms: The Creation of Modern Cell Biology. Cambridge: Cambridge University Press.Google Scholar
  2. Bing, Frederick. 1971. “The History of the Word ‘Metabolism.” Journal of the History of Medicine and Allied Sciences 26: 158–180. doi: 10.1093/jhmas/XXVI.2.158.CrossRefGoogle Scholar
  3. Brandt, Christina. 2004. Metapher und Experiment: von der Virusforschung zum genetischen Code. Göttingen: Wallstein Verlag.Google Scholar
  4. Brenner, S., Dark, F.A., Gerhardt, P., Jeynes, M.H., Kandler, O., Kellenberg, E., Klieneberger-Nobel, E., McQuillen, K., Rubio-Huertos, M., Salton, M.R.J., Strange, R.E., Tomsik, J., and Weibull, C. 1958. “Bacterial Protoplasts.” Nature 181: 1713–1715.CrossRefGoogle Scholar
  5. Bud, Robert. 2007a. Penicillin: Triumph and Tragedy. Oxford/New York: Oxford University Press.Google Scholar
  6. Bud, Robert. 2007b. “From Germfobia to Carefree Life and Back Again. The Lifecycle of the Antibiotic Brand.” A. Tone and E.S. Watkins (eds.), Medicating Modern America: Prescription Drugs in History. New York: New York University Press, pp. 17–41.Google Scholar
  7. Butenandt, Adolf, Weidel, Wolfhard, and Becker, Erich. 1940. “Kynurenin als Augenpigmentbildung auslosendes Agens bei Insekten.” Die Narturwissenschaften 28: 63–64.CrossRefGoogle Scholar
  8. Coyette, Jacques, Frère, Jean-Marie, and Reynolds, Peter. 2005. “Jean-Marie Ghuysen.” Molecular Microbiology 57: 871–873.CrossRefGoogle Scholar
  9. Creager, Angela N. 2002. The Life of a Virus: Tobacco Mosaic Virus as an Experimental Model, 1930–1965. Chicago: University of Chicago Press.Google Scholar
  10. Creager, Angela N. 2007. “Adaptation or Selection? Old Issues and New Stakes in the Postwar Debates over Bacterial Drug Resistance.” Studies in History and Philosophy of Biological and Biomedical Sciences 38: 159–190.CrossRefGoogle Scholar
  11. Deichmann, Utte. 2002a. “Chemists and Biochemists During the National Socialist Era.” Angewandte Chemie International Edition 41: 1310–1328.CrossRefGoogle Scholar
  12. Deichmann, Utte. 2002b. “Emigration, Isolation and the Slow Start of Molecular Biology in Germany.” Studies in History and Philosophy of Biological and Biomedical Sciences 33: 449–471.CrossRefGoogle Scholar
  13. Gadebusch, Hans H., Stapley, Edward O., and Zimmerman, Sheldon B. 1992. “The Discovery of Cell Wall Active Antibacterial Antibiotics.” Critical Reviews in Biotechnology 12: 225–243.CrossRefGoogle Scholar
  14. Gardner, A.D. 1940. “Morphological Effects of Penicillin on Bacteria.” Nature 146: 837.CrossRefGoogle Scholar
  15. Gaudillière, Jean-Paul. 2002. Inventer la biomédecine: la France, l’Amérique et la production des savoirs du vivant, 1945–1965. Paris: La découverte.Google Scholar
  16. Gaudillière, Jean-Paul. 2008. “Professional or Industrial Order? Patents, Biological Drugs, and Pharmaceutical Capitalism in Early Twentieth Century Germany.” History and Technology 24: 107–133.CrossRefGoogle Scholar
  17. Geison, Gerald L. 1969. “The Protoplasmic Theory of Life and the Vitalist-Mechanist Debate.” Isis 60: 273–292.CrossRefGoogle Scholar
  18. Ghuysen, Jean-Marie. 1960. “Acetylhexosamine Compounds Enzymically Released from Micrococcus lysodeikticus Cell Walls: II. Enzymic Sensitivity of Purified Acetylhexosamine and Acetylhexosamine-Peptide Complexes.” Biochimica et Biophysica Acta 40: 473–480.CrossRefGoogle Scholar
  19. Ghuysen, Jean-Marie. 1961. “Précisions sur la structure des complexes disaccharide-peptide libérés des parois de Micrococcus lysodeikticus sous l’action des β (I → 4) N-acetyl-hexosaminidases.” Biochimica et Biophysica Acta 47: 561–568.CrossRefGoogle Scholar
  20. Ghuysen, Jean-Marie. 1968. “Use of Bacteriolytic Enzymes in Determination of Wall Structure and Their Role in Cell Metabolism.” Bacteriological reviews 32(4): 425–464.Google Scholar
  21. Ghuysen, Jean-Marie. 1977. “The Concept of the Penicillin Target from 1965 Until Today: The Thirteenth Marjory Stephenson Memorial Lecture.” Journal of General Microbiology 101: 13–33.CrossRefGoogle Scholar
  22. Ghuysen, Jean-Marie and Salton, Milton R.J. 1960. “Acetylhexosamine Compounds Enzymically Released from Micrococcus lysodeikticus Cell Walls: I. Isolation and Composition of Acetylhexosamine and Acetylhexosamine-Peptide Complexes.” Biochimica et Biophysica Acta 40: 462–472.CrossRefGoogle Scholar
  23. Ghuysen, Jean-Marie and Strominger, Jack L. 1963. “Structure of the Cell Wall of Staphylococcus aureus, Strain Copenhagen. II. Separation and Structure of Disaccharides.” Biochemistry 2: 1119–1125.CrossRefGoogle Scholar
  24. Gradmann, Christoph. 2011. “Magic Bullets and Moving Targets: Antibiotic Resistance and Experimental Chemotherapy.” Dynamis 31: 305–321.CrossRefGoogle Scholar
  25. Gradmann, Christoph. 2013. “Sensitive Matters: The World Health Organisation and Antibiotic Resistance Testing, 1945–1975.” Social History of Medicine 26: 555–574.CrossRefGoogle Scholar
  26. Grote, Mathias. 2010. “Surfaces of Action: Cells and Membranes in Electrochemistry and the Life Sciences.” Studies in History and Philosophy of Biological and Biomedical Sciences 41: 183–193.CrossRefGoogle Scholar
  27. Grote, Mathias. 2013. “Purple Matter, Membranes and ‘Molecular Pumps’ in Rhodopsin Research (1960s–1980s).” Journal of the History of Biology 46: 331–368.CrossRefGoogle Scholar
  28. Grote, Mathias and O’Malley, Maureen A. 2011. “Enlightening the Life Sciences: The History of Halobacterial and Microbial Rhodopsin Research.” FEMS Microbiology Reviews 35: 1082–1099.CrossRefGoogle Scholar
  29. Hendlin, D., Stapley, E.O., Jackson, M., Wallick, H., Miller, A.K., Wolf, F.J., Miller, T.W., Chaiet, L., Kahan, F.M., Foltz, E.L., Woodruff, H.B., Mata, J.M., Hernández, S., and Mochales, S. 1969. “Phosphonomycin, A New Antibiotic Produced by Strains of Streptomyces.” Science 166: 122–123.CrossRefGoogle Scholar
  30. Hobby, Gladys. 1985. Penicillin. Meeting the Challenge. New Haven/London: Yale University Press.Google Scholar
  31. Holmes, Frederic L. 1992. Between Biology and Medicine: The Formation of Intermediary Metabolism. Berkeley: University of California, Office for the History of Science.Google Scholar
  32. Hüntelmann, Axel C. 2012. “Priority, Property and Trust: Patent Laws and Pharmaceuticals in the German Empire.” Interdisciplines 2: 194–226.Google Scholar
  33. Kay, Lily E. 1985. “Conceptual Models and Analytical Tools: The Biology of Physicist Max Delbrück.” Journal of the History of Biology 18: 207–246.CrossRefGoogle Scholar
  34. Kay, Lily E. 1996. The Molecular Vision of Life: Caltech, the Rockefeller Foundation, and the Rise of the New Biology. Oxford/New York: Oxford University Press.Google Scholar
  35. Keating, Peter, Cambrosio, Albert. 2003. Biomedical Platforms: Realigning the Normal and the Pathological in Late-Twentieth-Century Medicine. Cambridge, MA: MIT Press.Google Scholar
  36. Kohler, Robert E. 1973. “The Enzyme Theory and the Origin of Biochemistry.” Isis 64: 181–196.CrossRefGoogle Scholar
  37. Kohler, Robert E. 1982. From Medical Chemistry to Biochemistry: The Making of a Biomedical Discipline. Cambridge: Cambridge University Press.CrossRefGoogle Scholar
  38. Landecker, Hannah. 2013. “Postindustrial Metabolism: Fat Knowledge.” Public Culture 25: 495–522.CrossRefGoogle Scholar
  39. Lederberg, Joshua. 1956. “Bacterial Protoplasts Induced by Penicillin.” Proceedings of the National Academy of Sciences of the United States of America 42: 574–578.CrossRefGoogle Scholar
  40. Lederberg, Joshua. 1957. “Mechanism of Action of Penicillin.” Journal of Bacteriology 73: 144.Google Scholar
  41. Lederberg, Joshua. 1958. Nobel Lecture: A View of Genetics. Nobel Media at Accessed 24 February 2015.
  42. Lederberg, Joshua and St. Clair, Jacqueline. 1958. “Protoplasts and L-type Growth of Escherichia coli.” Journal of Bacteriology 75: 143–160.Google Scholar
  43. Lesch, John. 2007. The First Miracle Drugs. How Sulfa Drugs Transformed Medicine. Oxford/New York: Oxford University Press.Google Scholar
  44. Lie, Anne Kveim. 2014. “Producing Standards, Producing the Nordic Region: Antibiotic Susceptibility Testing, from 1950–1970.” Science in Context 27: 215–248. doi: 10.1017/S0269889714000052.CrossRefGoogle Scholar
  45. Löwy, Ilana. 1996. Between Bench and Bedside: Science, Healing, and Interleukin-2 in a Cancer Ward. Cambridge, MA: Harvard University Press.Google Scholar
  46. Marks, Harry. 1997. The Progress of Experiment: Science and Therapeutic Reform in the United States, 1900–1990. Cambridge: Cambridge University Press.Google Scholar
  47. Martin, H.H. 1963. “Bacterial Protoplasts – A Review.” Journal of Theoretical Biology 5: 1–34.CrossRefGoogle Scholar
  48. McQuillen, Kenneth. 1955. “Bacterial Protoplasts: Growth and Division of Protoplasts of Bacillus megaterium.” Biochimica et Biophysica Acta 18: 458–461.CrossRefGoogle Scholar
  49. McQuillen, Kenneth. 1960. “Bacterial protoplasts.” I.C. Gunsalus and R.Y. Stanier (eds.), The Bacteria: A treatise on Structure and Function. New York/London: Academic Press, pp. 249–359.Google Scholar
  50. McQuillen, Kenneth and Salton, Milton R.J. 1955. “Synthetic Media for Maintenance and Induction of Lysogenic Bacillus megaterium.” Biochimica et Biophysica Acta 16: 596–597.CrossRefGoogle Scholar
  51. Melchers, Georg. 1964. “Wolfhard Weidel.” Mitteilungen aus der Max-Planck-Gessellschaft, Heft 5(6): 226–233.Google Scholar
  52. Mickle, H. 1948. “II. —Tissue Disintegrator”. Journal of the Royal Microscopical Society 68(1–4): 10–12Google Scholar
  53. Nathenson, Stanley G. and Strominger, Jack L. 1961. “Effects of Penicillin on the Biosynthesis of the Cell Walls of Escherichia coli and Staphylococcus aureus.” Journal of Pharmacology and Experimental Therapeutics 131: 1–6.Google Scholar
  54. Nyhart, L.K. 1995. Biology Takes Form: Animal Morphology and the German Universities, 1800–1900. Chicago: University of Chicago Press.Google Scholar
  55. Park, James T. 1952a. “Uridine-5′-pyrophosphate Derivatives. I. Isolation from Staphylococcus aureus.” Journal of Biological Chemistry 194: 877–884.Google Scholar
  56. Park, James T. 1952b. “Uridine-5′-pyrophosphate Derivatives. II. Isolation from Staphylococcus aureus.” Journal of Biological Chemistry 194: 855–895.Google Scholar
  57. Park, James T. 1952c. “Uridine-5′-pyrophosphate Derivatives. III. Amino acid-Containing Derivatives.” Journal of Biological Chemistry 194: 897–904.Google Scholar
  58. Park, James T. and Johnson, Marvin J. 1949. “Accumulation of Labile Phosphate in Staphylococcus aureus Grown in the Presence of Penicillin.” Journal of Biological Chemistry 179: 585–592.Google Scholar
  59. Park, James T. and Strominger, Jack L. 1957. “Mode of Action of Penicillin.” Science 125: 99–101.CrossRefGoogle Scholar
  60. Perkins, H.R. and Nieto, M. 1974. “The Chemical Basis for the Action of the Vancomycin Group of Antibiotics.” Annals of the New York Academy of Sciences 235(1): 348–363.CrossRefGoogle Scholar
  61. Podolsky, Scott H. 2010. “Antibiotics and the Social History of the Controlled Clinical Trial.” Journal for the History of Medicine and Allied Sciences 65: 327–367.CrossRefGoogle Scholar
  62. Podolsky, Scott H. 2014. The Antibiotic Era: Reform, Resistance, and the Pursuit of a Rational Therapeutics. Baltimore: Johns Hopkins University Press.Google Scholar
  63. Rasmussen, Nicolas. 1997. Picture Control: The Electron Microscope and the Transformation of Biology in America, 1940–1960. Stanford:Stanford University Press.Google Scholar
  64. Reissig, José L., Strominger, Jack L., and Leloir, Luis F. 1955. “A Modified Colorimetric Method for the Estimation of N-acetylamino Sugars.” Journal of Biological Chemistry 217: 959–966.Google Scholar
  65. Rheinberger, Hans-Jörg. 1996. “Comparing Experimental Systems: Protein Synthesis in Microbes and in Animal Tissue at Cambridge (Ernest F. Gale) and at the Massachusetts General Hospital (Paul C. Zamecnik), 1945–1960.” Journal of the History of Biology 29: 387–416.CrossRefGoogle Scholar
  66. Rheinberger, Hans-Jörg. 2000. “Ephestia: The Experimental Design of Alfred Kühn’s Physiological Developmental Genetics.” Journal of the History of Biology 33: 535–576.CrossRefGoogle Scholar
  67. Romero de Pablos, Ana. 2011. “Regulation and the Circulation of Knowledge: Penicillin Patents in Spain.” Dynamis 31: 87–107.CrossRefGoogle Scholar
  68. Romero de Pablos, Ana. 2014. “Patents, Antibiotics, and Autarky in Spain.” Medicina nei Secoli 26(2): 423–449.Google Scholar
  69. Salton, M.R.J. 1957. “The Properties of Lysozyme and Its Action on Microorganisms.” Bacteriological Reviews 21: 82–99.Google Scholar
  70. Salton, Milton R. 1952. “Cell Wall of Micrococcus lysodeikticus as the Substrate of Lysozyme.” Nature 170: 746.CrossRefGoogle Scholar
  71. Salton, Milton R.J. 1953. “Cell Structure and the Enzymic Lysis of Bacteria.” Journal of General Microbiology 9: 512–523.CrossRefGoogle Scholar
  72. Salton, Milton R.J. 1960. Microbial Cell Walls. New York/London:Wiley.CrossRefGoogle Scholar
  73. Salton, Milton R.J. and Ghuysen, Jean-Marie. 1960. “Acetylhexosamine Compounds Enzymically Released from Micrococcus lysodeikticus Cell Walls: III. The Structure of Di-and tetra-saccharides Released from Cell Walls by Lysozyme and Streptomyces F1 Enzyme.” Biochimica et Biophysica Acta 45: 355–363.CrossRefGoogle Scholar
  74. Salton, Milton R.J. and McQuillen, Kenneth. 1955. “Bacterial Protoplasts: II. Bacteriophage Multiplication in Protoplasts of Sensitive and Lysogenic Strains of Bacillus megaterium.” Biochimica et Biophysica Acta 17: 465–472.CrossRefGoogle Scholar
  75. Salton, Milton R. and Horne, R.W. 1951. “Studies of the Bacterial Cell Wall II. Methods of Preparation and Some Properties of Cell Walls.” Biochimica et Biophysica Acta 7: 177–197.CrossRefGoogle Scholar
  76. Santesmases, María Jesús. 2002. “Enzymology at the Core: Primers and Templates in Severo Ochoa’s Transition from Biochemistry to Molecular Biology.” History and Philosophy of the Life Sciences 24: 193–218.CrossRefGoogle Scholar
  77. Santesmases, María Jesús. 2011a. “Screening Antibiotics: Industrial Research by CEPA and Merck in the 1950s.” Dynamis 31: 407–427.CrossRefGoogle Scholar
  78. Santesmases, María Jesús. 2011b. “Circulación postcolonial de autoridad entre Argentina y España: Viajes y tránsitos de la fisiología y la bioquímica, 1936–1981.” M. Albornoz and J. Sebastián (eds.), Trayectorias de las políticas científicas y universitarias en Argentina y España. Madrid: CSIC, pp. 39–66.Google Scholar
  79. Santesmases, María Jesús. 2014. “Gender in Research and Industry: Women in Antibiotic Factories in 1950s Spain.” Teresa Ortiz-Gómez and María Jesús Santesmases (eds.), Gendered Drugs and Medicine: Historical and Socio-cultural Perspective. Farham: Ashgate, pp. 61–84.Google Scholar
  80. Santesmases, María Jesús and Gradmann, Christoph. 2011. “Circulation of Antibiotics: An Introduction.” Dynamis 31: 293–303.CrossRefGoogle Scholar
  81. Santesmases, María Jesús and Suárez-Díaz, Edna. 2015. “A Cell-Based Epistemology: Human Genetics in the Era of Biomedicine.” Historical Studies in the Natural Sciences 45: 1–13.CrossRefGoogle Scholar
  82. Silver, Lynn L. 2012. “Rational Approaches to Antibacterial Discovery: Pre-genomic Directed and Phenotypic Screening.” T.J. Dougherty and M.J. Pucci (eds.), Antibiotic Discovery and Development. New York: Springer, pp. 33–75.CrossRefGoogle Scholar
  83. Smith, L.D. and Hay, T. 1942. “The Effect of Penicillin on the Growth and Morphology of Staphylococcus aureus.” Journal of the Franklin Institute 233: 598–602.CrossRefGoogle Scholar
  84. Strominger, Jack L. 1957. “Microbial Uridine-5′-pyrophosphate N-acetylamino sugar Compounds. I. Biology of the Penicillin-Induced Accumulation.” Journal of Biological Chemistry 224: 509–523.Google Scholar
  85. Strominger, Jack L. 2006. “The Tortuous Journey of a Biochemist to Immunoland and What He Found There.” Annual Review of Immunology 24: 1–31.CrossRefGoogle Scholar
  86. Strominger, Jack L. 2007. “Bacterial Cell Walls, Innate Immunity and Immunoadjuvants.” Nature Immunology 8: 1269–1271.CrossRefGoogle Scholar
  87. Strominger, Jack L. and Ghuysen, Jean-Marie. 1967. “Mechanisms of Enzymatic Bacteriaolysis.” Science 156: 213–221.CrossRefGoogle Scholar
  88. Strominger, Jack L., Park, James T., and Thompson, Richard E. 1959. “Composition of the Cell Wall of Staphylococcus aureus: Its Relation to the Mechanism of Action of Penicillin.” Journal of Biological Chemistry 234: 3263–3268.Google Scholar
  89. Waksman, Selman. 1947. “What is an Antibiotic or Antibiotic Substance?’ Mycologia 39: 565–569.CrossRefGoogle Scholar
  90. Weidel, Wolfhard. 1950. “Supplementary Information on Receptor Spots.” Max Delbrück (ed.), Viruses 1950: Conference on the Similarities and Dissimilarities Between Viruses Attacking Animals, Plants and Bacteria. Pasadena: California Institute of Technology, pp. 119–121.Google Scholar
  91. Weidel, Wolfhard. 1953. Phage Receptor Systems of E. coli B. Cold Spring Harbor Symposia on Quantitative Biology 18: 155–157.Google Scholar
  92. Weidel, Wolfhard. 1957. Virus; die Geschichte vom geborgten Leben. Heidelberg: Springer.Google Scholar
  93. Weidel, Wolfhard. 1959. Virus. Translated by Lotte Streisinger. Ann Arbor: University of Michigan Press.Google Scholar
  94. Weidel, Wolfhard. 1964. Virus und Molekularbiologie; eine elementare Einführung. Heidelberg: Springer.CrossRefGoogle Scholar
  95. Weidel, Wolfhard and Kellenberger, Edward. 1955. “The E. coli B-receptor for the Phage T 5. II. Electron Microscopic Studies.” Biochimica et Biophysica Acta 17: 1–9.CrossRefGoogle Scholar
  96. Weidel, Wolfhard and Primosigh, J. 1958. “Biochemical Parallels Between Lysis by Virulent Phage and Lysis by Penicillin.” Journal of General Microbiology 18: 513–517.CrossRefGoogle Scholar
  97. Weidel, Wolfhard and Pelzer, H. 1964. “Bag-Shaped Macromolecules. A New Outlook on Bacterial Cell Walls.” Advances in Enzymology 26: 193–232.Google Scholar
  98. Weidel, Wolfhard, Frank, H., and Martin, H.H. 1960. “The Rigid Layer of the Cell Wall of Escherichia coli Strain B.” Journal of General Microbiology 22: 158–166.CrossRefGoogle Scholar
  99. Yi, Doogab. 2009. “The Scientific Commons in the Marketplace: The Industrialization of Biomedical Materials at the New England Enzyme Center, 1963–1980.” History and Technology 25: 69–87.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Instituto de FilosofíaCCHS, Consejo Superior de Investigaciobnes CientíficasMadridSpain

Personalised recommendations