po1-7-1 identifying historical facts that can enhance the teaching … · 2018. 8. 14. · 1....

Identifying historical facts that can enhance the teaching of PharmacologySerés E.1*, López-García A.1, Martín-Gonzalvo N.1, Baños J.E.2, Bosch F.1,21Dr. Antoni Esteve Foundation, Barcelona, Catalonia, Spain. *eseres@esteve.org 2Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.

Pharmacology is an important subject in many university undergraduate programmes. Like other disciplines, phar-macology can be taught with different strategies, from lectures to problem-based learning sessions. This study aimed to select some historical facts related to the first antimicrobials that can be used to enhance the teaching of pharmacology*.

We examined articles in scientific journals and materials in pharmacology textbooks related with the first antimi-crobials: arsphenamine, sulphonamides, and streptomycin. Subsequently, we searched The New York Times, The Times of London, and the Spanish newspaper La Vanguardia for news on these drugs published between 1908 and 1979 to identify historical facts and anecdotes that could be attractive for teaching. Finally, we wrote a brief sum-mary of each selected issue and created a card to use for teaching purposes that included a title for the historical fact, a summary, some images, and the selected references.

A review of 50 scientific review articles, 82 books, and 3,004 news articles yielded 26 key historical issues: 13 relat-ed to arsphenamine, 9 to sulphonamides, and 4 to streptomycin. As examples, we included the story of 606, the initial name for arsphenamine (Fig. 3); the controversy surrounding the patent for Prontosil; and sexist discrimina-tion against Elizabeth Bugie in assigning credit for the discovery of the streptomycin. Other selected historical facts addressed issues such as new approaches to administration, drug toxicity, new indications for drugs, patents, commercial interests, and the use of drugs during war.

Reviewing historical information related to drugs makes it possible to identify facts and anecdotes that can enhance the teaching of pharmacology. Interesting anecdotes about arsphenamine, sulphonamides, and streptomycin can serve not only for teaching antimicrobials, but also for teaching pharmacology in a much broader sense.

INTRODUCTION

METHODS

RESULTS

CONCLUSIONS

1900 1910 1920 1930 1940 1950 1960

1908 Paul Ehrlich’s Nobel PrizePaul Gelmo’s sulphanilamide

1909 606 in animals

1912 Arsphenamine in the market

1910 Arsphenamine clinical trial

1914-1918 The Great War

1937 Sulphonamide derivatives1928 Penicillin’sdiscovery

1940 Penicillin synthesis1943 Streptomycin’s discovery

1944 Streptomycin’s first publication1948 Streptomycin’s patent

1952 Selman Waksman’s Nobel Prize

1939 Paul Domagk’s Nobel Prize

1939-1945 World War II

Figure 1: Number of analyzed articles in the study

Figure 2: Context timeline of the drug discoveries and some selected events

Figure 4: Proposed historical key facts cards

Figure 3: Summary of some key historical facts of arsphenamine, sulphanilamide and streptomycin

Poster design by Clara Borràs Eroles @clara.dou

Arsphenamine Paul Ehrlich found out compound number 606 was active against syphilis, later known as arsphenamine. The press made No. 606 famous because of the public’s interest in the new treatment for syphilis.

Alexander Fleming (discoverer of penicillin) was one of the few doctors that could administer Salvarsan by intravenous

injection in London. His practice became so popular that earned him the nickname “Private 606”.

A Lieutenant Colonel of the British Army Medical Corps stated at the 1913’s International Congress of Medicine that the

use of Salvarsan in the British Army, saved as much as keeping an entire battalion of infantry in hospital for 3 months, or

as much as 70,000 to 80,000 days of service.

Movies and TV series have included syphilis and arsphenamine in their plots, such as Out of Africa (1985), Miss Ever’s

Boys (1997), and The Knick (2015, 2nd season). But interestingly in 1940 Warner Bros premiered the film “Dr. Ehrlich’s

Magic Bullet”, where the life of Ehrlich and the discovery of arsphenamine were depicted in great detail.

606, when a number becomes famous

Alexander Fleming aka Private

606

606 and its repercussion in the British

Army

Salvarsan and the movies

1910

1910-11

1913

1940

SulphanilamideOn Christmas Day of 1932, Domagk and his colleagues (through IG Farbenindustrie) patented the first sulphonamide,

Streptozon®, later known as Prontosil®. Part of the molecule was already discovered in 1908. IG Farbenindustrie was

suspected to be trying to reformulate the original molecule to elude its patent protection.

Hildegard Domagk suffered a life-threatening septicemia at the age of 6. After having high fever for a few days, his

father decided to give her an experimental treatment. She recovered and became the first (secret) patient treated with

Prontosil®.

The American company tried to create a similar liquid formula as Prontosil®, but they used dietilenglicol (antifreeze

liquid) as solvent and called it Elixir Sulphanilamide. This elixir caused more than 100 deaths, mostly children. After the

disaster, laws regulating drugs were forced to improve and marked the beginning of the modern FDA.

Sulfa drugs (sulphonamides) were best known as good wound healers, as well as the best way to prevent gaseous gan-

grene. During WWII. Soldier’s 1st aid kits sulphanilamide in powder and pills to help prevent deaths by infected wounds.

The patent game

Domagk’s daughter, the secret first

treated patient

Massengill & Co. disaster

WWII and their “sulfa” 1st aid kit

1932-35

1935

1937

1939

StreptomycinIn 1944 Waksman, Schatz and Bugie published the first article stating the discovery of streptomycin, but Bugie was left

out as discoverer in the streptomycin’s patent. Allegedly Waksman and Schatz told her that she was going to marry soon

and have a family and therefore, she did not need the money, stating a clear example gender discrimination in science.

Merck & Co. (in the USA) was the patent holder of streptomycin and its exclusive manufacturer. During the 1940’s strep-

tomycin was solely produced by Merck and exported overseas. Some years later and due to the demand, Merck

licensed streptomycin’s production to several companies.

There was a legal dispute between Schatz and Waksman due to the distribution of royalties from streptomycin’s patent.

After Schatz got a plaintiff against Waksman and Rutgers University, the later ones agreed to include Schatz and Waks-

man’s former PhD students as recipients of streptomycin’s royalty profits.

The Institute of Microbiology at Rutgers University, led by Waksman, was built with the profits from streptomycin’s

patent. Rutger’s royalties raised over 3 million USD.

Elizabeth Bugie: another example of

gender discrimination in science

Exclusive production of streptomycin in

the USA

Controversies with streptomycin’s

patent and royalties

Creation of The Institute of Microbiolo-

gy at Rutgers University

1944

1945

1950

1954

1932 KL695 (Streptozon®)synthesis & patent

1935 Prontosil® publicationand marketing

ArsphenamineSulphanilamideStreptomycinOther events

Articles after 1st screening

Articles after 2nd screening

Historical facts

Arsphenamine Sulphanilamide Streptomycin

123524,4%

210141.6%

171934%

Number of search results 5055

2799,3%

141747.2%

136843.5%

3004 59,4%

1656,1%

131348.3%

123945.6%

271790,4%

13 9 426

The New York TimesThe Times

La Vanguardia

PubMedScientific literature

Created by Barrizonfrom the Noun Project

Total

132

PO1-7-1

*Preliminary data presented at the 37th SEF National Congress, June 18-21, 2017, Barcelona, Catalonia (Spain).

Poster Session PO1-7-1, 18th World Congress of Basic and Clinical Pharmacology, July 1-6, 2018. Kyoto, Japan.

Serés E., López-García A., Martín-Gonzalvo N., Baños J.E. and Bosch F. declare to have no COI with regards to the presentation.Disclosure of Con�ict of Interest

1. Accepted abstract by the congress organization:

Identifying historical facts that can enhance the teaching of Pharmacology

Elisabet Seres1, Adrian Lopez-Garcia1, Neus Martin-Gonzalvo1, Josep-Eladi Banos2, Felix Bosch1,2 1Esteve Foundation, Catalonia, Spain; 2Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Catalonia, Spain Background. Pharmacology is an important subject in many university undergraduate programmes. Like other disciplines, pharmacology can be taught with different strategies, from lectures to problem-based learning sessions. This study aimed to select some historical facts related to the first antimicrobials that can be used to enhance the teaching of pharmacology. Methods. We examined articles in scientific journals and materials in pharmacology textbooks related with the first antimicrobials: arsphenamine, sulphonamides, and streptomycin. Subsequently, we searched The New York Times, The Times of London, and the Spanish newspaper La Vanguardia for news on these drugs published between 1908 and 1979 to identify historical facts and anecdotes that could be attractive for teaching. Finally, we wrote a brief summary of each selected issue and created a card to use for teaching purposes that included a title for the historical fact, a summary, some images, and the selected references. Results. A review of 50 scientific review articles, 82 books, and 3,078 news articles yielded 26 key historical issues: 13 related to arsphenamine, 9 to sulphonamides, and 4 to streptomycin. As examples, we included the story of 606, the initial name for arsphenamine (Fig. 1); the controversy surrounding the patent for Prontosil; and sexist discrimination against Elizabeth Bugie in assigning credit for the discovery of the streptomycin. Other selected historical facts addressed issues such as new approaches to administration, drug toxicity, new indications for drugs, patents, commercial interests, and the use of drugs during war. Conclusions. Reviewing historical information related to drugs makes it possible to identify facts and anecdotes that can enhance the teaching of pharmacology. Interesting anecdotes about arsphenamine, sulphonamides, and streptomycin can serve not only for teaching antimicrobials, but also for teaching pharmacology in a much broader sense.

2. Links:

Seres E, Lopez-Garcia A, Martin-Gonzalvo N, Banos JE, Bosch F. Identifying historical facts that can enhance the teaching of Pharmacology [Internet]. Abstract accepted at: 18th World Congress of Basic and Clinical Pharmacology; 2018 July 1-6; Kyoto, Japan. Available at: https://www.micenavi.jp/wcp2018/search/detail_program/id:939 Seres E, Lopez-Garcia A, Martin-Gonzalvo N, Banos JE, Bosch F. Identifying historical facts that can enhance the teaching of Pharmacology [Internet]. Poster presented at: 18th World Congress of Basic and Clinical Pharmacology; 2018 July 1-6; Kyoto, Japan. Available at: https://www.esteve.org/libros/poster-kyoto-identifying-historical-facts-that-can-enhance-the-teaching-of-pharmacology/

3. Contact information:

Elisabet Serés, PhD Project Manager eseres@esteve.org, +34 934335322 Dr. Antoni Esteve Foundation Torre Esteve, Passeig de la Zona Franca 109 - 08032 Barcelona, Spain www.esteve.org