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Vol. 82, No. 3, 2008
Issue release date: October 2008
Free Access
Pharmacology 2008;82:171–179
(DOI:10.1159/000149583)

The Contributions of Paul Ehrlich to Pharmacology: A Tribute on the Occasion of the Centenary of His Nobel Prize

Bosch F.a, b · Rosich L.a
aEsteve Foundation, and bDepartment of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
email Corresponding Author

Abstract

On the centenary of Paul Ehrlich’s Nobel Prize, this German researcher deserves to be remembered as a pioneer in a large number of scientific disciplines. As a result of his enthusiasm and scientific abilities, dedication, and contacts with other scientists of his time, he was able to make countless contributions in fields as diverse as histology, haematology, immunology, oncology, microbiology and pharmacology, among others. Although the Swedish award was meant to recognize the standardization of the manufacture of antidiphtheria serum, it was the discovery of arsphenamine (Salvarsan) for the treatment of syphilis which won him wider international acclaim. From a pharmacological perspective, Ehrlich’s outstanding contributions include dissemination of the ‘magic bullet’ concept for the synthesis of antibacterials, introduction of concepts such as chemoreceptor and chemotherapy, and linking the chemical structure of compounds to their pharmacological activity. These achievements took place within the framework he established for the transition from experimental pharmacology to therapeutic pharmacology. He introduced a modern research system based on the synthesis of multiple chemical structures for pharmacological screening in animal models of disease states. These contributions were undoubtedly decisive in propitiating the wider development of antibiotics decades later. For these reasons, it is fitting to mark the 100th anniversary of the Nobel Prize awarded to this great scientist by commemorating the importance of his contributions to the advance of pharmacology.


 goto top of outline Key Words

  • Paul Ehrlich
  • Arsenicals
  • Arsphenamine
  • Dyes
  • Animal experimentation
  • Therapeutic pharmacology
  • Chemotherapy
  • Syphilis
  • Side-chain theory

 goto top of outline Abstract

On the centenary of Paul Ehrlich’s Nobel Prize, this German researcher deserves to be remembered as a pioneer in a large number of scientific disciplines. As a result of his enthusiasm and scientific abilities, dedication, and contacts with other scientists of his time, he was able to make countless contributions in fields as diverse as histology, haematology, immunology, oncology, microbiology and pharmacology, among others. Although the Swedish award was meant to recognize the standardization of the manufacture of antidiphtheria serum, it was the discovery of arsphenamine (Salvarsan) for the treatment of syphilis which won him wider international acclaim. From a pharmacological perspective, Ehrlich’s outstanding contributions include dissemination of the ‘magic bullet’ concept for the synthesis of antibacterials, introduction of concepts such as chemoreceptor and chemotherapy, and linking the chemical structure of compounds to their pharmacological activity. These achievements took place within the framework he established for the transition from experimental pharmacology to therapeutic pharmacology. He introduced a modern research system based on the synthesis of multiple chemical structures for pharmacological screening in animal models of disease states. These contributions were undoubtedly decisive in propitiating the wider development of antibiotics decades later. For these reasons, it is fitting to mark the 100th anniversary of the Nobel Prize awarded to this great scientist by commemorating the importance of his contributions to the advance of pharmacology.

Copyright © 2008 S. Karger AG, Basel


 goto top of outline References
  1. Official Website of the Nobel Foundation. Stockholm, 2008. http://nobelprize.org (accessed May 5, 2008).
  2. Rubin RP: A brief history of great discoveries in pharmacology: in celebration of the centennial anniversary of the founding of the American Society of Pharmacology and Experimental Therapeutics. Pharmacol Rev 2007;59:289–359.
  3. Kaufmann SHE: Paul Ehrlich: founder of chemotherapy. Nat Rev Drug Discov 2008;7:373.
  4. Silverman M: Kill the Germs! Lister to Ehrlich to 205. Magic in a Bottle. New York, MacMillan, 1942, pp 134–168.
  5. Mann J: The Elusive Magic Bullet. The Search for the Perfect Drug. New York, Oxford University Press, 1999, pp 1–209.
  6. Kasten FH: Paul Ehrlich: pathfinder in cell biology. 1. Chronicle of his life and accomplishments in immunology, cancer research, and chemotherapy. Biotech Histochem 1996;71:2–37.
  7. Venita J: A portrait of history: Paul Ehrlich. Arch Pathol Lab Med 2001;125:724.

    External Resources

  8. Crivellato E, Beltrami CA, Mallardi F, Ribatti D: Paul Ehrlich’s doctoral thesis: a milestone in the study of mast cells. Br J Haematol 2003;123:19–21.
  9. Riethmiller S: From Atoxyl to Salvarsan: searching for the magic bullet. Chemotherapy 2005;51:234–242.
  10. Paul Ehrlich. Langen, Paul-Ehrlich-Institut. http://www.pei.de/cln_046/nn_162438/EN/institute-en/paul-ehrlich-en/paul-ehrlich-node-en.html?__nnn=true (accessed May 5, 2008).
  11. Parascandola J: The theoretical basis of Paul Ehrlich’s chemotherapy. J Hist Med Allied Sci 1981;36:19–43.
  12. Kristiansen JE: Dyes, antipsychotic drugs, and antimicrobial activity. Fragments of a development, with special reference to the influence of Paul Ehrlich. Dan Med Bull 1989;36:178–185.
  13. Winau F, Westphal O, Winau R: Paul Ehrlich – In search of the magic bullet. Microbes Infect 2004;6:786–789.
  14. Schwartz RS: Paul Ehrlich’s magic bullets. N Engl J Med 2004;350:1079–1080.
  15. Weatheral M: In Search of a Cure. New York, Oxford University Press, 1999.
  16. Witkop B: Paul Ehrlich and his magic bullets – Revisited. Proc Am Philos Soc 1999;143:540–557.
  17. Bennett MR: The concept of transmitter receptors: 100 years on. Neuropharmacology 2000;39:523–546.
  18. Akatsu S, Noguchi H: The drug-fastness of spirochetes to arsenic, mercurial, and iodide compounds in vitro. J Exp Med 1917;25:349–362.
  19. Krantz JC Jr: Paul Ehrlich and ‘The Magic Bullet’, Arsphenamine. Historical Medical Classics Involving New Drugs. Baltimore, Williams & Wilkins, 1974, pp 51–57.
  20. Felsenfeld O: K. Shiga, bacteriologist. Science 1957;126:113.
  21. Sneader W: Drug Discovery: A History. Chichester, Wiley, 2005.
  22. Jolliffe DM: A history of the use of arsenicals in man. J R Soc Med 1993;86:287–289.
  23. Drews J: Paul Ehrlich: magister mundi. Nat Rev Drug Discov 2004;3:797–801.
  24. Gensini GF, Conti AA, Lippi D: The contributions of Paul Ehrlich to infectious disease. J Infect 2007;54:221–224.
  25. Marlow FW Jr: Syphilis then and now. JAMA 1974;230:1320–1321.
  26. Jaouen G, Beck W, McGlinchey MJ: A Novel Field of Research: Bioorganometallic Chemistry, Origins, and Founding Principles. Weinheim, Wiley-VCH, 2006, pp 1–37.
  27. Montes J, Cueva J: Ehrlich, su vida y su obra. Alergia 1967;15:29–42.
  28. Cowley AH, Lasch JG, Norman NC, Pakulski M: Synthesis and structure of a diarsene: the first compound with an unsupported arsenic-arsenic double bond. J Am Chem Soc 1983;105:5506–5507.
  29. Lloyd NC, Morgan H, Nicholson BK, Ronimus RS: The composition of Ehrlich’s salvarsan: resolution of a century-old debate. Angew Chem Int Ed Engl 2005;44:941–944.
  30. Raju TNK: The Nobel chronicles. 1908: Elie Metchnikoff (1845–1916), Paul Ehrlich (1854–1915). Lancet 1998;352:661.
  31. Jacobs MS: Paul Ehrlich and his relation to modern chemotherapy. Bull Hist Med 1940;8:956–964.
  32. Silverstein AM: Paul Ehrlich, archives and the history of immunology. Nat Immunol 2005;6:639.
  33. Cowen DL, Segelman AB: Antibiotics in Historical Perspective. New Jersey, Merck Sharp & Dohme, 1981.

 goto top of outline Author Contacts

Fèlix Bosch
Esteve Foundation
Llobet i Vall-Llosera, 2
ES–08032 Barcelona (Spain)
Tel. +34 934 335 320, Fax +34 934 504 899, E-Mail fbosch@esteve.org


 goto top of outline Article Information

Received: February 29, 2008
Accepted: May 16, 2008
Published online: August 5, 2008
Number of Print Pages : 9
Number of Figures : 3, Number of Tables : 1, Number of References : 33


 goto top of outline Publication Details

Pharmacology (International Journal of Experimental and Clinical Pharmacology)

Vol. 82, No. 3, Year 2008 (Cover Date: October 2008)

Journal Editor: Donnerer J. (Graz), Billingsley M.L. (Hershey, Pa.), Maeyama K. (Matsuyama)
ISSN: 0031–7012 (Print), eISSN: 1423–0313 (Online)

For additional information: http://www.karger.com/PHA


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

On the centenary of Paul Ehrlich’s Nobel Prize, this German researcher deserves to be remembered as a pioneer in a large number of scientific disciplines. As a result of his enthusiasm and scientific abilities, dedication, and contacts with other scientists of his time, he was able to make countless contributions in fields as diverse as histology, haematology, immunology, oncology, microbiology and pharmacology, among others. Although the Swedish award was meant to recognize the standardization of the manufacture of antidiphtheria serum, it was the discovery of arsphenamine (Salvarsan) for the treatment of syphilis which won him wider international acclaim. From a pharmacological perspective, Ehrlich’s outstanding contributions include dissemination of the ‘magic bullet’ concept for the synthesis of antibacterials, introduction of concepts such as chemoreceptor and chemotherapy, and linking the chemical structure of compounds to their pharmacological activity. These achievements took place within the framework he established for the transition from experimental pharmacology to therapeutic pharmacology. He introduced a modern research system based on the synthesis of multiple chemical structures for pharmacological screening in animal models of disease states. These contributions were undoubtedly decisive in propitiating the wider development of antibiotics decades later. For these reasons, it is fitting to mark the 100th anniversary of the Nobel Prize awarded to this great scientist by commemorating the importance of his contributions to the advance of pharmacology.



 goto top of outline Author Contacts

Fèlix Bosch
Esteve Foundation
Llobet i Vall-Llosera, 2
ES–08032 Barcelona (Spain)
Tel. +34 934 335 320, Fax +34 934 504 899, E-Mail fbosch@esteve.org


 goto top of outline Article Information

Received: February 29, 2008
Accepted: May 16, 2008
Published online: August 5, 2008
Number of Print Pages : 9
Number of Figures : 3, Number of Tables : 1, Number of References : 33


 goto top of outline Publication Details

Pharmacology (International Journal of Experimental and Clinical Pharmacology)

Vol. 82, No. 3, Year 2008 (Cover Date: October 2008)

Journal Editor: Donnerer J. (Graz), Billingsley M.L. (Hershey, Pa.), Maeyama K. (Matsuyama)
ISSN: 0031–7012 (Print), eISSN: 1423–0313 (Online)

For additional information: http://www.karger.com/PHA


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Official Website of the Nobel Foundation. Stockholm, 2008. http://nobelprize.org (accessed May 5, 2008).
  2. Rubin RP: A brief history of great discoveries in pharmacology: in celebration of the centennial anniversary of the founding of the American Society of Pharmacology and Experimental Therapeutics. Pharmacol Rev 2007;59:289–359.
  3. Kaufmann SHE: Paul Ehrlich: founder of chemotherapy. Nat Rev Drug Discov 2008;7:373.
  4. Silverman M: Kill the Germs! Lister to Ehrlich to 205. Magic in a Bottle. New York, MacMillan, 1942, pp 134–168.
  5. Mann J: The Elusive Magic Bullet. The Search for the Perfect Drug. New York, Oxford University Press, 1999, pp 1–209.
  6. Kasten FH: Paul Ehrlich: pathfinder in cell biology. 1. Chronicle of his life and accomplishments in immunology, cancer research, and chemotherapy. Biotech Histochem 1996;71:2–37.
  7. Venita J: A portrait of history: Paul Ehrlich. Arch Pathol Lab Med 2001;125:724.

    External Resources

  8. Crivellato E, Beltrami CA, Mallardi F, Ribatti D: Paul Ehrlich’s doctoral thesis: a milestone in the study of mast cells. Br J Haematol 2003;123:19–21.
  9. Riethmiller S: From Atoxyl to Salvarsan: searching for the magic bullet. Chemotherapy 2005;51:234–242.
  10. Paul Ehrlich. Langen, Paul-Ehrlich-Institut. http://www.pei.de/cln_046/nn_162438/EN/institute-en/paul-ehrlich-en/paul-ehrlich-node-en.html?__nnn=true (accessed May 5, 2008).
  11. Parascandola J: The theoretical basis of Paul Ehrlich’s chemotherapy. J Hist Med Allied Sci 1981;36:19–43.
  12. Kristiansen JE: Dyes, antipsychotic drugs, and antimicrobial activity. Fragments of a development, with special reference to the influence of Paul Ehrlich. Dan Med Bull 1989;36:178–185.
  13. Winau F, Westphal O, Winau R: Paul Ehrlich – In search of the magic bullet. Microbes Infect 2004;6:786–789.
  14. Schwartz RS: Paul Ehrlich’s magic bullets. N Engl J Med 2004;350:1079–1080.
  15. Weatheral M: In Search of a Cure. New York, Oxford University Press, 1999.
  16. Witkop B: Paul Ehrlich and his magic bullets – Revisited. Proc Am Philos Soc 1999;143:540–557.
  17. Bennett MR: The concept of transmitter receptors: 100 years on. Neuropharmacology 2000;39:523–546.
  18. Akatsu S, Noguchi H: The drug-fastness of spirochetes to arsenic, mercurial, and iodide compounds in vitro. J Exp Med 1917;25:349–362.
  19. Krantz JC Jr: Paul Ehrlich and ‘The Magic Bullet’, Arsphenamine. Historical Medical Classics Involving New Drugs. Baltimore, Williams & Wilkins, 1974, pp 51–57.
  20. Felsenfeld O: K. Shiga, bacteriologist. Science 1957;126:113.
  21. Sneader W: Drug Discovery: A History. Chichester, Wiley, 2005.
  22. Jolliffe DM: A history of the use of arsenicals in man. J R Soc Med 1993;86:287–289.
  23. Drews J: Paul Ehrlich: magister mundi. Nat Rev Drug Discov 2004;3:797–801.
  24. Gensini GF, Conti AA, Lippi D: The contributions of Paul Ehrlich to infectious disease. J Infect 2007;54:221–224.
  25. Marlow FW Jr: Syphilis then and now. JAMA 1974;230:1320–1321.
  26. Jaouen G, Beck W, McGlinchey MJ: A Novel Field of Research: Bioorganometallic Chemistry, Origins, and Founding Principles. Weinheim, Wiley-VCH, 2006, pp 1–37.
  27. Montes J, Cueva J: Ehrlich, su vida y su obra. Alergia 1967;15:29–42.
  28. Cowley AH, Lasch JG, Norman NC, Pakulski M: Synthesis and structure of a diarsene: the first compound with an unsupported arsenic-arsenic double bond. J Am Chem Soc 1983;105:5506–5507.
  29. Lloyd NC, Morgan H, Nicholson BK, Ronimus RS: The composition of Ehrlich’s salvarsan: resolution of a century-old debate. Angew Chem Int Ed Engl 2005;44:941–944.
  30. Raju TNK: The Nobel chronicles. 1908: Elie Metchnikoff (1845–1916), Paul Ehrlich (1854–1915). Lancet 1998;352:661.
  31. Jacobs MS: Paul Ehrlich and his relation to modern chemotherapy. Bull Hist Med 1940;8:956–964.
  32. Silverstein AM: Paul Ehrlich, archives and the history of immunology. Nat Immunol 2005;6:639.
  33. Cowen DL, Segelman AB: Antibiotics in Historical Perspective. New Jersey, Merck Sharp & Dohme, 1981.