Skip to main content
Log in

Different roads to discovery; Prontosil (hence sulfa drugs) and penicillin (hence β-lactams)

  • Review
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

The important chemotherapeutic agents, Prontosil and pentenylpenicillin (penicillin F), were investigated initially by two men, Domagk and Fleming, who had been influenced by the horrendous wound infections of World War I. The very different pathways leading to their development and to that of the successor antibacterials (sulfa drugs, further penicillins, semi-synthetic penicillins), including the role played by patents, are discussed.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Abraham EP, Chain E, Fletcher CM, Florey HW, Gardner AD, Heatley NG, Jennings MA (1941) Further observations on penicillin. Lancet 2:177–189 (issue of August 16)

    Google Scholar 

  2. Anderson S, Homan P (2002) Best for me, best for you––a history of Beecham’s pills. Pharm J 269:921–924

    Google Scholar 

  3. Behr A (1909) Food product and process of making same. US Patent 914,379

  4. Behrens OK, Corse J, Jones RG, Mann MJ, Soper QF, Van Abeele FR, Chiang M-C (1948) Biosynthesis of penicillins I. Biological precursors for benzylpenicillin (penicillin G). J Biol Chem 175:751–764

    PubMed  CAS  Google Scholar 

  5. Bentley R (1991) Holding a mirror to penicillin—a reflection. Biochemist 13:31

    Google Scholar 

  6. Bentley R (2004) The molecular structure of penicillin. J Chem Educ 81:1462–1470

    Article  CAS  Google Scholar 

  7. Bentley R, Bennett JW (2003) What is an antibiotic? Revisited. Adv Appl Microbiol 52:303–331. doi:10.1016/S0065-2164(03)01012-8

    Article  PubMed  CAS  Google Scholar 

  8. Bentley R, Bennett JW (2008) A ferment of fermentations. Reflections on the production of commodity chemicals by microorganisms. Adv Appl Microbiol 63:1–32. doi:10.1016/S0065-2164(07)00001-9

    Article  PubMed  CAS  Google Scholar 

  9. Bickel L (1972) Rise up to life. Angus and Robertson, London

    Google Scholar 

  10. Birkinshaw JH (1972) Harold Raistrick 1890–1971. Biogr Mem Fellows R Soc 18:489–509. doi:10.1098/rsbm.1972.0017

    PubMed  CAS  Google Scholar 

  11. Brown K (2004) Penicillin man. Alexander Fleming and the antibiotic revolution. Sutton Publishing, Thrupp

    Google Scholar 

  12. Bryskier A (2003) Gerhard Johannes Paul Domagk. Chemother J 12:97–105

    Google Scholar 

  13. Bud R (1998) Penicillin and the new Elizabethans. Br J Hist Sci 31:305–333. doi:10.1017/S0007087498003318

    Article  Google Scholar 

  14. Chain E, Florey HW, Gardner AD, Heatley NG, Jennings MA, Orr-Ewing J, Sanders AG (1940) Penicillin as a chemotherapeutic agent. Lancet 2:226–228 (issue of August 24)

    Google Scholar 

  15. Clark RW (1985) The life of Ernst Chain. Penicillin and beyond. Weidenfeld and Nicolson, London

    Google Scholar 

  16. Clarke HT, Johnson JR, Robinson R (1949) The chemistry of penicillin. Princeton University Press, Princeton NJ

    Google Scholar 

  17. Clutterbuck PW, Lovell R, Raistrick H (1932) The formation from glucose by members of the Penicillium chrysogenum series of a pigment, an alkali-soluble protein and penicillin––the antibacterial substance of Fleming. Biochem J 26:1907–1918

    PubMed  CAS  Google Scholar 

  18. Colebrook L (1964) Gerhard Domagk 1895–1964. Biogr Mem Fellows R Soc 10:39–50. doi:10.1098/rsbm.1964.0003

    CAS  Google Scholar 

  19. Colebrook L, Kenny M (1936) Treatment of human puerperal infections, and of experimental infections in mice with Prontosil. Lancet 1279–1286 (issue of June 6)

  20. Demain AL (2004) Pickles, pectin, and penicillin. Annu Rev Microbiol 58:1–42. doi:10.1146/annurev.micro.58.030603.123757

    Article  PubMed  CAS  Google Scholar 

  21. Demain AL, Martin JF, Elander RP (1998) Penicillin biochemistry and genetics. In: Mateles RI (ed) Penicillin: a paradigm for biotechnology. Candida Corp, Chicago, IL, pp 93–114

    Google Scholar 

  22. Domagk G (1935) Ein Beitrag zur Chemotherapie der bakterillen Infektionen. Deutsch Med Wochenschrift 61:250-253 (for English translation see Brock TD Milestones in Microbiology [1961]. American Society for Microbiology, Washington DC)

  23. Domagk G (1936) Chemotherapie der streptokokken-infektionen. Klin Woch 15:1585–1590. Retitled as J Mol Med. doi:10.1007/BF01780820

    Google Scholar 

  24. Domagk D (1957) Twenty-five years of sulfonamide therapy. Ann NY Acad Sci 69:380–384. doi:10.1111/j.1749-6632.1957.tb49674.x

    Article  PubMed  CAS  Google Scholar 

  25. Dunnill M (2000) The Plato of Praed street. The life and times of Almroth Wright. Royal Society of Medicine Press Ltd., London

    Google Scholar 

  26. Du Vigneaud V, Carpenter FH, Holley RW, Livermore AH, Rachele JR (1946) Synthetic penicillin. Science 104:431–433. doi:10.1126/science.104.2706.431

    Article  PubMed  Google Scholar 

  27. Fleming A (1929) On the antibacterial action of cultures of a Penicillium with special reference to their use in the isolation of B. influenzae. Br J Exp Pathol 10:226–236

    CAS  Google Scholar 

  28. Foster JW, McDaniel LE (1943) Process for the production of penicillin. US Patent 2,448,790

  29. Foster JW, McDaniel LE (1946) Production of penicillin in cotton-seed meal medium. US Patent 2,448,791

  30. Hager T (2006) The demon under the microscope. Harmony Books, New York

    Google Scholar 

  31. Hare R (1970) The birth of penicillin and the disarming of microbes. George Allen and Unwin Ltd., London

    Google Scholar 

  32. Henry TA (1952) Obituary notice. Ernest Fourneau 1872–1949. J Chem Soc 261–266. doi:10.1039/jr9520000261

  33. Hobby GL (1985) Penicillin. Meeting the challenge. Yale University Press, New Haven

    Google Scholar 

  34. Kato K (1953) Occurrence of penicillin-nucleus in culture broths. J Antibiot 6:130–136

    PubMed  CAS  Google Scholar 

  35. Lesch J (2007) The first miracle drugs. How the sulfa drugs transformed medicine. Oxford University Press, New York, NY

    Google Scholar 

  36. Macfarlane RG (1979) Howard Florey. The making of a great scientist. Oxford University Press, Oxford

    Google Scholar 

  37. Mateles RI (ed) (1998) Penicillin: A paradigm for biotechnology. Candida Corp, Chicago, IL

    Google Scholar 

  38. Maurois A (1959) The life of Sir Alexander Fleming. EP Sutton & Co In, New York

    Google Scholar 

  39. Mietzsch F, Klarer J (1932) Verfahren zur Herstellung von Azoverbindungen. Reichspatent 607:537

    Google Scholar 

  40. Moyer AJ (1945) Method for production of penicillin. US Patent 2,442,141

  41. Moyer AJ (1945) Method for production of penicillin. US Patent 2,443,989

  42. Moyer AJ (1945) Method for production of penicillin. US Patent 2,476,107

  43. Moyer AJ (1945) Improvements in or relating to methods for producing penicillin. British Patent 618,415

  44. Moyer AJ (1945) Improvements in or relating to methods for producing penicillin. British Patent 618,416

  45. Moyer AJ (1945) Improvements in or relating to methods for producing penicillin. British Patent 624,411

  46. Moyer AJ, Coghill RD (1946) Penicillin VIII. Production of penicillin in surface cultures. J Bacteriol 51:57–78

    PubMed  CAS  Google Scholar 

  47. Moyer AJ, Coghill RD (1947) Penicillin X. The effect of phenylacetic acid on penicillin production. J Bacteriol 53:329–341

    PubMed  CAS  Google Scholar 

  48. Moyer AJ, Umberger EJ, Stubbs JJ (1940) Fermentation of concentrated solutions of glucose to gluconic acid. Improved process. Ind Eng Chem 32:1379–1383. doi:10.1021/ie50370a022

    Article  CAS  Google Scholar 

  49. Rolinson GN, Geddes AM (2007) The 50th anniversary of the discovery of 6-aminopenicillanic acid (6-APA). Int J Antimicrob Agent 29:3–8. doi:10.1016/j.ijantimicag.2006.09.003

    Google Scholar 

  50. Schmidt WH, Moyer AJ (1945) Penicillin I. Methods of assay. J Bacteriol 47:199–208

    Google Scholar 

  51. Scoutaris M (1996) “Moldy Mary” and the Illinois Fruit and Vegetable Company. Pharm Hist 38:175–177

    PubMed  CAS  Google Scholar 

  52. Sheehan JC, Henery-Logan KR (1957) The total synthesis of penicillin V. J Am Chem Soc 79:1262–1263. doi:10.1021/ja01562a063

    Article  CAS  Google Scholar 

  53. Stubbs JJ, Lockwood LB, Roe ET, Tabenkin B, Ward GE (1940) Ketogluconic acids from glucose. Bacterial production. Ind Eng Chem 32:1626–1631. doi:10.1021/ie50372a024

    Article  CAS  Google Scholar 

  54. Swann JP (1983) The search for synthetic penicillin during World War II. Br J Hist Sci 16:154–190. doi:10.1017/S0007087400026789

    Article  PubMed  CAS  Google Scholar 

  55. Tréfouël J, Tréfouël T, Nitti F, Bovet D (1935) Activité du p-amino-phenylsulfamide sur les infections streptococciques experimentales de la souris et du lapin. Compt Rend Soc Biol 120:756–758

    Google Scholar 

  56. Wainwright M, Swan HT (1986) G. C. Paine and the earliest surviving records of penicillin therapy. Med Hist 30:42–56

    PubMed  CAS  Google Scholar 

  57. Wallace CD (1983) Control through disclosure legislation: foreign multinational enterprises in industrialized states. Int Comp Law Q 32:174–1412. doi:10.1093/iclqaj/32.1.141

    Article  Google Scholar 

  58. Wells PA, Lockwood LB, Stubbs JJ, Roe ET, Porges N, Gastrock EA (1939) Sorbose from sorbitol. Semiplant-scale production by Acetobacter suboxydans. Ind Eng Chem 31:1518–1521. doi:10.1021/ie50360a018

    Article  CAS  Google Scholar 

  59. Williams TI (1984) Howard Florey. Penicillin and after. Oxford University Press, Oxford

    Google Scholar 

  60. Wilson D (1976) In search of penicillin. AA Knopf, New York

    Google Scholar 

  61. Woodward RB (1972) Recent advances in the chemistry of natural products. In: Nobel lectures: chemistry 1963–1970. Elsevier, Amsterdam pp 100–121

Download references

Acknowledgments

I thank Philip Eagle of the British Library for information on British and European patents, Ruediger Borstel of Bayer Corporate History and Archives, and Thomas Hager for correspondence concerning Prontosil. Thanks are also due to A. Demain for helpful comments after reading a draft of this paper. A reviewer is thanked for useful suggestions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ronald Bentley.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bentley, R. Different roads to discovery; Prontosil (hence sulfa drugs) and penicillin (hence β-lactams). J Ind Microbiol Biotechnol 36, 775–786 (2009). https://doi.org/10.1007/s10295-009-0553-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-009-0553-8

Keywords

Navigation