The antibiotic discovery era

240 Pages·2013·2.03 MB·English

AN ABSTRACT OF THE THESIS OF
DONALD J. McGRAW for the degree of DOCTOR OF PHILOSOPHY
in BIOLOGICAL SCIENCE presented on May 3, 1974
Title: THE ANTIBIOTIC DISCOVERY ERA (1940-1960):
VANCOMYCIN AS AN EXAMPLE OF THE ERA
Redacted for Privacy
Abstract Approved:
Paul L. Farber
An examination of the technical and historical literature
concerning the discovery and development of antibiotics suggests the
possible existence of an era of discovery. This era appears to have
a well-defined beginning (about 1940) and a well-defined close (about
It is the purpose of this dissertation to examine the various
1960).
strands of evidence that support the thesis that a definable antibiotic
discovery era does indeed exist. An examination of several antibio-
tics discovered and developed during the period 1940-1960 support
the thesis. One antibiotic in particular, vancomycin, discussed in
depth is shown to be exemplary of the trends established about 1940
and which ceased to function about 1960. In concluding, a definition
for the discovery era is proposed.
0
1976
DONALD JESSE McGRAW
ALL RIGHTS RESERVED
The Antibiotic Discovery Era (1940-1960):
Vancomycin as an Example of the Era
by
Donald J. McGraw
A THESIS
submitted to
Oregon State University
in partial fulfillment of
the requirements for the
degree of
Doctor of Philosophy
Completed December 1975
Commencement June 1976
APPROVEID:
Redacted for Privacy
A ssistanlProfessor of the History of Science
in charge of major
Redacted for Privacy
Chairman of Department of General Science
Redacted for Privacy
Dean of Graduate School
Date thesis is presented May 3, 1974
Typed by Clover Redfern for Donald J. McGraw
DEDICATED
TO
ELI LILLY
WHOSE MUSE
IS CLIO
ACKNOWLEDGMENTS
Not unlike the team effort which brought vancomycin into
existence, this history was dependent upon the assistance of a great
many people. Foremost among them was Mr. Eli Lilly to whom this
history is dedicated. The Eli Lilly Company, discoverers and devel-
opers of vancomycin, have supported and encouraged this research.
To them the author is most grateful. Special thanks are accorded to
Dr. Earl B. Herr, Jr. , President of Lilly Research Laboratories,
for his guidance and assistance. Many others at the Lilly Company
deserve special mention and thanks for their help. They include:
Miss Libby Bland, Mrs. Lee Ann Bertram, Dr. Albert Drum ley,
Mr. Lee G. Crawford, Mrs. Louise B. Randall, Mrs. Helen
Davidson, Mrs. Peg Evans, Mr. Ralph Ernesberger, Miss Gloria
Gruber, Dr. Richard S. Griffith, Miss Adele Hoskins, Mr. Donald W.
Hollings, Mr. Marvin M. Hoehn, Dr. Harvey M. Higgings, Mr.
Robert Higgs, Mr. William C. Herman, Miss Jane Johnson, Dr.
Edmund C. Kornfeld, Dr. Kenneth G. Kohlsteadt (retired), Mrs.
Louise C. Lage, Mrs. Bernadine Kinder, Mrs. Lynda McBee, Dr.
Mack H. McCormick, Dr. Henry K. Nelis, Dr. C. W. Pettinga,
Mr. James H. Pearcy, Mr. Richard A. Porter, Mrs. Bernice L.
Roberts, Mrs. Hendretta Reagen, Dr. W. Max Stark, Dr. Robert W.
Squires, Mr. James L. Shaver, Mrs. Judy A. Stenger, Miss Phyllis
Wente, Dr. Robert H. Williams, and Mr. Frederick G. Winters.
Also special thanks go to Dr. W. Brooks Fortune (retired) who helped
begin the project and to Mr. Robert T. Doerr for such a great variety
of things. Mr. Gene E. McCormick was inspirational in extenso, and
that has been acutely appreciated. Others whose help is acknowledged
include the Library Staff of the Indiana University School of Medicine
(Indianapolis) and Mr. Arni Shareski of the Christian and Missionary
Alliance (New York City). I wish to thank Dr. Paul Farber, my major
professor, and Drs. Robert Becker, Daniel Jones, Richard Morita,
and David Willis, from whom I have learned so much. The extensive
aid given by Dr. Harry Phinney is especially appreciated. The
foundation laid by Drs. Edward Towne Roche, Jerome E. Dimitman,
and Ralph W. Ames remains as warmly appreciated as it always has.
Thanks are also accorded Mrs. Clover Redfern for her typing ofthe
final manuscript. A proper completion of the work would have been
impossible without the devotion and labors of wife Laura and daughters
Adrienne and Holly who deserve the greatest thanks of all.
Though the phrase is oft repeated, its importance does not
diminish- -any mistakes in this history are my own.
TABLE OF CONTENTS
Chapter Page
1. THE ANTIBIOTIC DISCOVERY ERA 1
1.1. Statement of the Problem
1
1.2. Dating the Discovery Era
3
1.3. Format of the History and Methods of Research 12
Z. PENICILLIN- -THE PRECEDENT 16
3. REPRESENTATIVE ANTIBIOTICS OF 1940-1960 26
3.1 Choice of the Representative Antibiotics 26
3.2. Streptomycin
28
3.3. Aureomycin
33
3.4. Terramycin
34
3.5. V ancomyc in 36
4. STAPHYLOCOCCUS AUREUS AND ANTIBIOTIC
MEDICINE 38
4.1. The Use and Misuse of Antibiotics 38
4.2. Ogston of Aberdeen 41
4.3. Microbial Resistence
44
4.4. Penicillin and Staphylococcus aureus
53
4.5. The Search for Alternatives
60
4.6. Antibiotics in Combination
69
5. THE DEVELOPMENT OF VANCOMYCIN 78
5.1. The Soils of Borneo
78
5. 2. Screening for New Antibiotics 81
5.3. The Nutrition of Streptomyces orientalis
90
5.4. The Diary of 1955
94
5.5. News of a New Antibiotic
115
5.6. Microbial Strains and Antibiotic Factors 125
5.7. The Problem of Pyrogens
134
5.8. Recent History
146
6. VANCOMYCIN AND STAPHYLOCOCCUS AUREUS 153
6. 1. Trials of a New Antibiotic
153
6.2. Vancomyc in and Other Antibiotics -A Comparison
177
6.3. Bacterial Endocarditis
185
6.4. The Question of Ototoxicity
191
Chapter Page
7. CONCLUSIONS 197
7. I. Questions Examined and Suggested by the
Dissertation 197
7.2. The Antibiotic Discovery Era- -A Proposed
Definition 205
BIBLIOGRAPHY 208
CRITICAL BIBLIOGRAPHY 209
GENERAL BIBLIOGRAPHY 218
LIST OF FIGURES
Figure Page
1. The chromatogram of vancomyc in. 86