The Aftermath of Penicillin

Size: px

Start display at page:

Download "The Aftermath of Penicillin"

Lionel Conley
5 years ago
Views:

The Aftermath of Penicillin Introduction After the discovery of penicillin, a great deal of effort was begun to find other antibiotics. Thousands would be discovered.

1 The Aftermath of Penicillin Introduction After the discovery of penicillin, a great deal of effort was begun to find other antibiotics. Thousands would be discovered. Most would be bacterial (Actinomycete) metabolites. Most well known would be Story is very similar to penicillin, but with different outcome. Like penicillin, discovery required joint effort and story complex. Main players. Selman Waksman, soil microbiologist at Rutgers during discovery of streptomycin and at that time already internationally known. Albert Schatz, graduate student under Waksman who isolated streptomycin and demonstrated its effectiveness against a number of disease causing organisms. Main players. William Feldman & Corwin Hinshaw of the Mayo Clinic, in Minnesota. Doctors who were working on anti-metabolites for Mycobacterium tuberculosis. Nobel Prize Committee of 1952 had a more minor, but very significant role in the life of Albert Schatz. Compare this story with that of Florey, Chain & Fleming. Until 1988, the discovery of streptomycin was solely attributed to Waksman. No mention of Albert Schatz was ever made in his autobiography. When mentioned comments made often not very flattering. During late 1930s, when Waksman first decided to work on antibiotics, he was already an internationally known microbiologist. Albert Schatz and Selman Waksman 1

2 Waksman screened for antibiotic activity against bacteria in culture. Actual work carried out by graduate students. Waksman believed he made intellectual contribution, directed research, got funding deserved all credit for research in his lab. Students that he hired to do research were fully compensated by employment. Waksman screened for antibiotic activity against bacteria in culture. Actual work carried out by graduate students. Not all his graduate students agree on this point. Schatz was one who did not agree. Schatz began his graduate work at Rutgers, in June Research at that time unrelated to Drafted into army, in November Became interested in finding antibiotics that were useful against diseases resistant to penicillin. Stay in army was short due to congenital back problem. Returned to Rutgers and began research in screening for new antibiotics for a variety of disease causing bacteria, resistant to penicillin. Visit from Feldman and Hinshaw occurred at about same time. Wanted to collaborate with Waksman in testing clavacin against Mycobacterium tuberculosis. Cause of what is known as TB, consumption or the white plague. Killed millions each year, at this time. Some antibiotics, including clavacin, discovered by Waksman were toxic. Waksman added M. tuberculosis to list of organisms Schatz would test. Schatz selected strain of M. tuberculosis that was particularly virulent. Prompted Waksman to remove Schatz from main lab and isolated him in basement. Waksman never visited Schatz. Schatz was fortunate in finding antibiotic that was effective against all his disease bacteria in short period of time. Schatz would receive his Ph.D. under Waksman. Also published Streptomycin: A substance exhibiting antibiotic activity against gram positive and gram negative bacteria. Authors were Schatz, Bugie and Waksman, in that order. What about testing streptomycin on laboratory animals and people? Not done by Schatz and Waksman 2

3 After Schatz demonstrated effectiveness against bacteria, Waksman contacted Feldman and Hinshaw. They were the ones who tested streptomycin in guinea pigs and human subjects. They demonstrated actual practical use of Should Feldman and Hinshaw share in the credit for streptomycin? Question as to who should receive credit came later. Schatz and Waksman both awarded patent for streptomycin, in Schatz and Waksman agreed that all royalties to streptomycin would go to Rutgers. Relationship was amicable at this time. Waksman looked upon by Schatz as a father figure. Schatz leaves Rutgers for Hopkins Marine Station, in California. Still communicated with Waksman in letters, frequently. Waksman sent number of documents for Schatz to sign. At some point Schatz realized the documents signed meant that he had given up all rights and credits to streptomycin Schatz leaves Rutgers for Hopkins Marine Station, in California. Schatz confronts Waksman with documents and questioned if anyone, other than Rutgers Foundation, was benefiting financially from streptomycin royalties. Schatz discovered Waksman getting 20% of royalties for streptomycin, $350,000 was already received by this time and $35,000 from Merck. Schatz leaves Rutgers for Hopkins Marine Station, in California. Numerous letters of exchanged followed that were not so friendly. Schatz eventually sued Waksman and Rutgers Foundation for recognition and royalties for Caused considerable embarrassment to Waksman, Rutgers and scientific establishment. The case went to trial but would not be decided in open court. Judge rendered decision behind closed doors. Schatz was given credit as codiscoverer of streptomycin and 3% of royalties. Another 7% went to students and researchers. 3

4 Schatz won case, but lost a great deal more. About 40% of settlement was paid to his lawyer. His court action led to him being essentially black balled by scientific community for a number of years. He was perceived by the scientific community as resentful and jealous because of the lawsuit. Nobel Prize, in 1952, was awarded to Waksman, only, for the discovery of 1952 Nobel Prize in Medicine The Nobel Prize in Physiology or Medicine 1952 "for his discovery of streptomycin, the first antibiotic effective against tuberculosis" Selman Abraham Waksman USA Rutgers University New Brunswick, NJ, USA b (in Priluka, Ukraine, Russia) d Titles, data and places given above refer to the time of the award. Photos: Copyright The Nobel Foundation Nobel Prize, in 1952, was awarded to Waksman, only, for the discovery of This would be the most devastating moment in Schatz life. Wrote to Nobel Committee, and other Nobel Prize Winners asked them to intercede, but there would be no changes in the award! Nobel Prize, in 1952, was awarded to Waksman, only, for the discovery of Hinshaw and Feldman considered, but also not awarded Nobel Prize. Nobel Committee indicated that they did not even know anything about Albert Schatz s contribution. Schatz s role in the discovery of streptomycin would virtually remain unknown for years to come. It would not be until 1988 that the injustice that was done to him and his role in the discovery of streptomycin was recognized. Milton Wainwright, lecturer in microbiology, at University of Sheffield wrote a short article, Selman A. Waksman and the streptomycin controversy. Was doing research on history of antibiotics at that time. 4

5 It would not be until 1988 that the injustice that was done to him and his role in the discovery of streptomycin was recognized. Schatz s cause was more recently championed by Ross M. Tucker, of Mayo Clinic. In 1994, Rutgers University awarded Schatz the Rutgers Medal, for his achievement as co-discoverer of Impact on Albert Schatz Schatz was very bitter after the award of the Nobel Prize to Waksman and spent most of his life trying to get the recognition he deserved. He would make some contribution to science, but bitterness he must have felt in seeing Waksman get all of the credit for streptomycin surely bothered him. Impact on Albert Schatz With the recognition he is now getting, he is now feeling better, but still the Nobel Prize would have been nice to have. Should he have been given credit all along? Other Antibiotics Actinomycetes would be where most of the useful antibiotics would be isolated. Some topical ones, such as Bacitracin and Neosporin are even sold over the counter. Actinomycetes would account for 4600 antibiotics by 1998 Fungi would account for 1600 and other bacteria would account for another 950 and 3000 from lichens algae, animals and plants. Not committed enough, however, that they were funding travels for samples. Chas. Pfizer & Co. became largest drug manufacturers, with more than 20,000 cultures. Most obtained through contributions. Each sample tested for antibacterial activity. If present, testing with animals would be next. Most antibiotics tested were harmful and even lethal to lab animals. 5

Same antibiotics began to be found. New antibiotics was de-emphasized. Filter pads with antibiotics inhibiting bacterial growth Emphasis made to alter existing antibiotics.

6 Same antibiotics began to be found. New antibiotics was de-emphasized. Filter pads with antibiotics inhibiting bacterial growth Emphasis made to alter existing antibiotics. A number of antibiotics were created in this way. However, approximately 300 new antibiotics are discovered each year. For a number of years, Greg Paterson, researcher in Chemistry, looked for antibiotic in bacteria. Economic Aspects 100,000 tons of antibiotics produced annually, gross $4.2 billion, in United States alone gross about $1 billion. Most of sales involve cephalosporins, ampicillin and tetracyclines. Less than 3% of the antibiotics developed are useful. Each antibiotic developed cost between $10-20 million and 8-10 years of time and resources. Economic Aspects Pharmaceutical Co. now market only ones that will be of therapeutic value. Why continue to spend more money on finding new antibiotics? Many antibiotics have side effects, not very effective or somewhat toxic. Many diseases for which there are no antibiotic treatment. Economic Aspects Economics and not humanitarian purposes play a large role in development. Eastern European countries played no role in early history of antibiotics. However, now a great deal of research is being carried out. Capitalistic system stimulates development of antibiotics? Resistance of bacteria to currently used antibiotics. 6

7 Application of Antibiotics Chemotherapeutic Antibiotics: Treatment of diseases, the ones most familiar to you. Broad-spectrum antibiotics: useful against a wide varieties of diseases. Narrow-spectrum antibiotics: useful against only a restricted number of diseases. Application of Antibiotics Antibiotics for Plant Pathology Prior to antibiotics, plant diseases were treated with chemicals. At first used same antibiotics as those used by people, but this only increased resistance of bacteria to bacteria. Antibiotics now developed specifically for plant diseases. Application of Antibiotics Antibiotics for Food Preservatives Antibiotics as Growth Promoter in Animals: Alters bacterial in digestive sys Antitumor antibiotics Used to stop or retard tumors. Many are toxic, but with controlled dosage still effective against certain tumors. Does not treat bacteria in this case. Examples Derived From Fungi Cephalosporins: Isolated from Cephalosprium, Emericellopsis and Paecilomyces. Very important! Griseofulvin: Isolated from Penicillium griseofulvum and used against fungi. Is fungistatic. Side effects include nausea and/or diarrhea and occasionally headaches. Fusidic Acid: Isolated from Fusidium coccineum used in Staphylococus that are resistant to penicillin. 7

Pharm 262: Antibiotics. 1 Pharmaceutical Microbiology II DR. C. AGYARE

Pharm 262: Antibiotics. 1 Pharmaceutical Microbiology II DR. C. AGYARE Pharm 262: 1 Pharmaceutical Microbiology II Antibiotics DR. C. AGYARE Reference Books 2 HUGO, W.B., RUSSELL, A.D. Pharmaceutical Microbiology. 6 th Ed. Malden, MA: Blackwell Science, 1998. WALSH, G. Biopharmaceuticals: