Skip to main content
SpringerLink
Log in
SpringerLink
Log in

The Early History of Antibiotic Discovery: Empiricism Ruled

  • Chapter
  • First Online:
Antibiotic Discovery and Development

Abstract

The history of the discovery of agents used in the treatment of bacterial infections is reviewed. Starting from the early work of Ehrlich that led to Salvarsan, the approach used to discover novel antibiotics is described. The antibiotics discussed are of synthetic, semi synthetic, or natural origin. Research is this area was initially driven by the chemical efforts of the dye industry; however, with the discovery of penicillin and streptomycin, natural products, made by soil microbes for many years, assumed a predominant role. More recently, as the productivity of soil screening programs has diminished, chemistry-driven efforts have come to play an important role again. The incredible structural diversity of the antibiotics discovered has resulted from a largely empirical approach, which has been based on the large scale screening of soil microbes as potential producers of antibacterial activity without the benefit of any knowledge as to the mechanism of action and basis for selective toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Abraham EP, Newton GG (1961) The structure of cephalosporin C. Biochem J 79:377–393

    PubMed  CAS  Google Scholar 

  2. Abraham EP, Newton GG, Crawford K, Burton HS, Hale CW (1953) Cephalosporin N: a new type of penicillin. Nature 171:343

    Article  PubMed  CAS  Google Scholar 

  3. Batts DH, Koleff MH, Lipsky BA, Nicolau DP, Weigelt JA (eds) (2004) Creation of a novel class: the oxazolidinone antibiotics. Innova Institute for Medical Education, Tampa

    Google Scholar 

  4. Bérdy J (1980) CRC handbook of antibiotic compounds. CRC Press, Boca Raton

    Google Scholar 

  5. Bernheim F (1940) The effect of salicylate on the oxygen uptake of the tubercle bacillus. Science 92:204

    Article  PubMed  CAS  Google Scholar 

  6. Boothe JH, Morton J, Petisi JP, Wilkinson RG, Williams JH (1953) Tetracycline. J Am Chem Soc 75:4621

    Article  CAS  Google Scholar 

  7. Brotzu G (1948) Ricerche su di un nouvo antibiotico. Lavori Dell’Instituto D’Igiene du Cagliari, pp 1–11

    Google Scholar 

  8. Bryskier A (2005) Antimicrobial agents: antibacterials and antifungals. ASM Press, Washington, DC

    Google Scholar 

  9. Bunch RL, McGuire JM (1952) Erythromycin, its salts and method of preparation. Eli Lilly, USA, pp 1–12

    Google Scholar 

  10. Burton HS, Abraham EP (1951) Isolation of antibiotics from a species of cephalosporium; cephalosporins P1, P2, P3, P4, and P5. Biochem J 50:168–174

    PubMed  CAS  Google Scholar 

  11. Bycroft BW, Higton AA, Roberts AD (1988) Dictionary of antibiotics and related substances. Chapman and Hall, London

    Google Scholar 

  12. Clark RW (1985) The life of Ernst chain: penicillin and beyond. St. Martin’s Press, New York

    Google Scholar 

  13. Cocito C (1979) Antibiotics of the virginiamycin family, inhibitors which contain synergistic components. Microbiol Rev 43:145–192

    PubMed  CAS  Google Scholar 

  14. Conover LH, Moreland WT, English AR, Stephens CR, Pilgrim FJ (1953) Terramycin. XI. Tetracycline. J Am Chem Soc 75:4622–4623

    Article  CAS  Google Scholar 

  15. Controulis J, Rebstock MC, Crooks HM (1949) Chloramphenicol (chloromycetin). IV. Synthesis. J Am Chem Soc 71:24563–22468

    Article  Google Scholar 

  16. Cosar C, Julou L (1959) The activity of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole (R. P. 8823) against experimental Trichomonas vaginalis infections. Ann Inst Pasteur 96:238–241 (Paris)

    CAS  Google Scholar 

  17. Debono M et al (1987) A21978C, a complex of new acidic peptide antibiotics: isolation, chemistry, and mass spectral structure elucidation. J Antibiot 40:761–777 (Tokyo)

    PubMed  CAS  Google Scholar 

  18. Domagk G (1935) Ein beitrag zur chemotherapieder bakteriellen infektionem. Deut Med Wochenschr 61:250–258

    Article  CAS  Google Scholar 

  19. Dubos R (1939) Bactericidal effect of an extract of a soil bacillus on gram-positive bacteria. Proc Soc Exp Biol Med 40:311–312

    CAS  Google Scholar 

  20. Duggar BM (1948) Aureomycin; a product of the continuing search for new antibiotics. Ann N Y Acad Sci 51:177–181

    Article  PubMed  CAS  Google Scholar 

  21. Ehrlich J, Bartz QR, Smith RM, Joslyn DA, Burkholder PR (1947) Chloromycetin, a new antibiotic from a soil actinomycete. Science 106:417

    Article  PubMed  CAS  Google Scholar 

  22. Eliopoulos GM, Willey S, Reiszner E, Spitzer PG et al (1986) In vitro and in vivo activity of LY 146032, a new cyclic lipopeptide antibiotic. Antimicrob Agents Chemother 30:532–535

    PubMed  CAS  Google Scholar 

  23. Emmerson AM, Jones AM (2003) The quinolones: decades of development and use. J Antimicrob Chemother 51(Suppl S1):13–30

    Article  PubMed  CAS  Google Scholar 

  24. Finlay AC, Hobby GL et al (1950) Terramycin, a new antibiotic. Science 111:85

    Article  PubMed  CAS  Google Scholar 

  25. Fleming A (1929) Cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Brit J Exp Path 10:226–236

    CAS  Google Scholar 

  26. Fox HH (1953) The chemical attack on tuberculosis. Trans N Y Acad Sci 15:234–242

    PubMed  CAS  Google Scholar 

  27. Gerzon K, Flynn EH, Sigal MV, Wiley PF, Monahan R, Quarck UC (1956) Erythromycin. VIII. Structure of dihydroerythronolide. J Am Chem Soc 78:6396–6408

    Article  CAS  Google Scholar 

  28. Godtfredsen W, Roholt K, Tybring L (1962) Fucidin: a new orally active antibiotic. Lancet 1:928–931

    Article  PubMed  CAS  Google Scholar 

  29. Godtfredsen WO, Jahnsen S, Lorck H, Roholt K, Tybring L (1962) Fusidic acid: a new antibiotic. Nature 193:987

    Article  PubMed  CAS  Google Scholar 

  30. Harris DA, Reagan MA, Ruger M, Wallick H, Woodruff HB (1955) Discovery and antimicrobial properties of cathomycin, a new antibiotic produced by Streptomyces spheroides n. sp. Antibiot Annu 3:909–917

    PubMed  Google Scholar 

  31. Hopwood DA (2007) Streptomyces in nature and medicine: the antibiotic makers. Oxford University Press, Oxford

    Google Scholar 

  32. Iwai Y, Omura S (1982) Culture conditions for screening of new antibiotics. J Antibiot 35:123–141 (Tokyo)

    PubMed  CAS  Google Scholar 

  33. Johnson BA, Anker H, Meleney FL (1945) Bacitracin: a new antibiotic produced by a member of the B. subtilis group. Science 102:376–377

    Article  PubMed  CAS  Google Scholar 

  34. Katz E, Demain AL (1977) The peptide antibiotics of bacillus: chemistry, biogenesis, and possible functions. Bacteriol Rev 41:449–474

    PubMed  CAS  Google Scholar 

  35. Kucers A (1997) The use of antibiotics: a clinical review of antibacterial, antifungal, and antiviral drugs, 5th edn. Butterworth-Heinemann, Boston/Oxford

    Google Scholar 

  36. Kushner S et al (1952) Experimental chemotherapy of tuberculosis. II. The synthesis of pyrazinamides and related compounds. J Am Chem Soc 74:3617–3621

    Article  CAS  Google Scholar 

  37. Lawrence P (2002) Rank injustice. Nature 415:835–836

    Article  PubMed  CAS  Google Scholar 

  38. Lazzarini A, Cavaletti L, Toppo G, Marinelli F (2000) Rare genera of actinomycetes as potential producers of new antibiotics. Antonie Van Leeuwenhoek 78:399–405

    Article  PubMed  CAS  Google Scholar 

  39. Lesher GY, Froelich EJ, Gruett MD, Bailey JH, Brundage RP (1962) 1, 8-naphthyridine derivatives. A new class of chemotherapeutic agents. J Med Pharm Chem 91:1063–1065

    Article  PubMed  CAS  Google Scholar 

  40. Levine DP (2006) Vancomycin: a history. Clin Infect Dis 42(Suppl 1):S5–S12

    Article  PubMed  CAS  Google Scholar 

  41. Lloyd NC, Morgan HW, Nicholson BK, Ronimus RS (2005) The composition of Ehrlich’s salvarsan: resolution of a century-old debate. Angew Chem Int Ed Engl 44:941–944

    Article  PubMed  CAS  Google Scholar 

  42. Locci R (2005) La discuvierte dai antibiotics. Gentamicine: L’antibiotic che al a riscjat l’abort. Gjournal Furlan des siencis 6:129–137

    Google Scholar 

  43. Luedemann G (1991) Free spirit of enquiry: the uncommon common man in research and discovery. The Gentamicin story. The International Centre for Theoretical and Applied Ecology, Gorizia

    Google Scholar 

  44. Maeda K, Osato T, Umezawa H (1953) A new antibiotic, azomycin. J Antibiot 6:182 (Tokyo)

    PubMed  CAS  Google Scholar 

  45. Maggi N, Pasqualucci CR, Ballotta R, Sensi P (1966) Rifampicin: a new orally active rifamycin. Chemotherapy 11:285–292

    Article  PubMed  CAS  Google Scholar 

  46. Mason DJ, Dietz A, Smith RM (1961) Actinospectacin, a new antibiotic. I. Discovery and biological properties. Antibiot Chemother 11:118–122

    PubMed  CAS  Google Scholar 

  47. Mason DJ, Dietz A, Deboer C (1962) Lincomycin, a new antibiotic. I. Discovery and biological properties. It was an annual volume at that stage only later were there monthly issues. Antimicrob Agents Chemother :554–559

    Google Scholar 

  48. McCormick MH, McGuire JM, Pittenger GE, Pittenger GC et al (1955) Vancomycin, a new antibiotic. I. Chemical and biological properties. Antibiot Annu 1955–56:606–611

    Google Scholar 

  49. McOsker CC, Fitzpatrick PM (1994) Nitrofurantoin: mechanism of action and implications for resistance development in common uropathogens. J Antimicrob Chemother 33(Suppl A):23–30

    PubMed  CAS  Google Scholar 

  50. Mikusova K, Slayden RA, Besra GS, Brennan PJ (1995) Biogenesis of the mycobacterial cell wall and the site of action of ethambutol. Antimicrob Agents Chemother 39:2484–2489

    PubMed  CAS  Google Scholar 

  51. Moberg CL, Cohn Z (1990) Launching the antibiotic era: personal accounts of the discovery and use of the first antibiotics. Rockefeller University Press, New York

    Google Scholar 

  52. Nakamura S (1955) Structure of azomycin, a new antibiotic. Pharm Bull 3:379–383

    PubMed  CAS  Google Scholar 

  53. Oppolzer W, Prelog V, Sensi P (1964) The composition of rifamycin B and related rifamycins. Experientia 20:336–339

    Article  PubMed  CAS  Google Scholar 

  54. Preud’Homme J, Tarridec P, Belloc A (1968) Isolement de la pristinamycine et etude de ses principales proprietes physico-chimiques. Revue de Medecine 9:619–620

    Google Scholar 

  55. Rahman A-U, Ahmad VU (1990) Handbook of natural products data. Distributors for the U.S. and Canada, Elsevier Science, Amsterdam/New York

    Google Scholar 

  56. Rohlfing SR, Gerster JR, Kvam DC (1976) Bioevaluation of the antibacterial flumequine for urinary tract use. Antimicrob Agents Chemother 10:20–24

    PubMed  CAS  Google Scholar 

  57. Ryan F (1993) The forgotten plague: how the battle against tuberculosis was won–and lost. Little, Brown/Boston, 1st American edn

    Google Scholar 

  58. Sensi P, Margalith P, Timbal MT (1959) Rifomycin, a new antibiotic; preliminary report. Farmaco (Sci) 14:146–147

    CAS  Google Scholar 

  59. Shinn DLS (1962) Metronidazole in acute ulcerative gingivitis. Lancet 279:1191

    Article  Google Scholar 

  60. Smee AM et al (1987) Oxazolidinones, a new class of synthetic antibacterial agents: in vitro and in vivo activities of DuP 105 and DuP 721. Antimicrob Agents Chemother 31: 1791–1797

    Google Scholar 

  61. Smith CG, Dietz A, Sokolski WT, Savage GM (1956) Streptonivicin, a new antibiotic. I. Discovery and biological studies. Antibiot Chemother 6:135–142

    CAS  Google Scholar 

  62. Sneader W (2005) Drug discovery: a history. Wiley, Hoboken

    Book  Google Scholar 

  63. Stansly PG, Schlosser ME (1947) Studies on polymyxin: isolation and identification of Bacillus polymyxa and differentiation of polymyxin from certain known antibiotics. J Bacteriol 54:549–556

    CAS  Google Scholar 

  64. Stephens CH, Conover LH, Hochstein FA, Regna PP et al (1952) Terramycin. VIII. Structure of aureomycin and terramycin. J Am Chem Soc 74:4976–4977

    Article  CAS  Google Scholar 

  65. Surrey AR, Hammer HF (1946) Some 7-substituted 4-aminoquinoline derivatives. J Am Chem Soc 68:113–116

    Article  PubMed  CAS  Google Scholar 

  66. Taylor FS (1971) The conquest of bacteria, from salvarsan to sulphapyridine. Books for Libraries Press, Freeport

    Google Scholar 

  67. Thomas JP, Baughn CO, Wilkinson RG, Shepherd RG (1961) A new synthetic compound with antituberculous activity in mice: ethambutol (dextro-2,2’-(ethylenediimino)-di-l-butanol). Am Rev Respir Dis 83:891–893

    PubMed  CAS  Google Scholar 

  68. Umezawa H et al (1957) Production and isolation of a new antibiotic: kanamycin. J Antibiot 10:181–188 (Tokyo)

    PubMed  CAS  Google Scholar 

  69. Wagman GH, Weinstein MJ (1980) Antibiotics from micromonospora. Annu Rev Microbiol 34:537–557

    Article  PubMed  CAS  Google Scholar 

  70. Waksman SA, Lechevalier HA (1949) Neomycin, a new antibiotic active against streptomycin-resistant bacteria, including tuberculosis organisms. Science 109:305–307

    Article  PubMed  CAS  Google Scholar 

  71. Weinstein MJ et al (1963) Gentamicin, a new antibiotic complex from micromonospora. J Med Chem 6:463–464

    Article  PubMed  CAS  Google Scholar 

  72. Wilkinson S, Lowe LA (1963) Identities of the fatty acids derived from the polymyxins and colistin. Nature 200:1008–1009

    Article  PubMed  CAS  Google Scholar 

  73. Woods D (1940) The relation of p-aminobenzoic acid to the mechanism of action of sulphanilamide. Brit J Exp Pathol 21:74–90

    CAS  Google Scholar 

  74. Zimhony O, Cox JS, Welch JT, Vilcheze C, Jacobs WR Jr (2000) Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med 6:1043–1047

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. HMB Biotechnology Consulting, 132 Spyglass Lane, Half Moon Bay, CA, 94019, USA

    Richard J. White D. Phil., B. Sc

Authors
  1. Richard J. White D. Phil., B. Sc
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard J. White D. Phil., B. Sc .

Editor information

Editors and Affiliations

  1. , Senior Principal Scientist, AstraZeneca Pharmaceuticals LP, Gatehouse Dr. 35, Waltham, 02451, Massachusetts, USA

    Thomas J. Dougherty

  2. Achillion Pharmaceuticals, Inc., George St. 300, New Haven, 06511, Connecticut, USA

    Michael J. Pucci

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

White, R.J. (2012). The Early History of Antibiotic Discovery: Empiricism Ruled. In: Dougherty, T., Pucci, M. (eds) Antibiotic Discovery and Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1400-1_1

Download citation

Publish with us

Policies and ethics

Search

Navigation