Alexander Fleming: a second look.

In 1928, Alexander Fleming (1881-1955) identified penicillin, the world's first antibiotic. It was a chance discovery that could have easily been missed had Fleming not taken a second look at a contaminated Petri dish. The discovery of penicillin marked a profound turning point in history as it was the first time deadly infections such as bacterial pneumonia, sepsis, diphtheria, meningitis, and puerperal fever after childbirth could be cured, and it paved the way for the development of additional antibiotics. The Alexander Fleming Laboratory Museum, one of several London Museums of Health and Medicine, is a reconstruction of Fleming's laboratory in its original location at St. Mary's Hospital. As if stepping back in time, visitors gain a glimpse into the man, his bacteriology work, and the events surrounding this important finding. For those unable to travel to London, this article provides a brief narrative of the fascinating story.

Premios Nobel Chain y Schatz evalúan la producción de penicilina en Chile en los años sesenta / Nobel Prize winners Chain and Schwartz evaluate the production of penicillin in Chile in the sixties

En los años sesenta el antiguo Instituto Bacteriológico de Chile obtuvo de la Universidad de Chile la ayuda de Albert Schatz, descubridor de la estreptomicina, para mejorar su producción de penicilina. Esta asesoría no fue aprovechada y la situación empeoró, hasta la llegada de Mario Miranda como Director, quien trajo a Sir Ernst Chain, Premio Nobel por el desarrollo de la penicilina, para que hiciese una evaluación de la planta de producción antes de decidir su cierre. El autor de estas líneas, quien puso fin a la producción en 1973, relata las visitas y las conclusiones de ambos asesores.

In the sixties the ancient Bacteriological Institute of Chile obtained from the University of Chile the transfer of Albert Schatz, discoverer of streptomycin, to improve its penicillin production. This advisory was wasted and the situation worsened until the arrival of Mario Miranda as the new Director, who brought Sir Ernst Chain, Nobel Prize for the development of penicillin, to make an evaluation of the production plant before deciding to continue or close it. The author of these lines, who ended production in 1973, recounts the visits and the conclusions of both advisors.

Penicillin: promise, problems and practice in wartime Edinburgh.

While medical historians have paid ample attention to the introduction of antibiotics and their impact on hospital-based practice during and after the Second World War, the multiple issues surrounding their use in Scottish hospitalsare sorely lacking in current discussions. Drawing on an extensive yet underused range of materials including patient treatment records, oral histories and medical correspondence, this paper explores the introduction of penicillin for civilian treatment at the Royal Infirmary of Edinburgh during the closing stages of the War. It highlights the success of the drug in clinical treatment as well as its shortcomings, offering an alternative view of its initial impact on surgical practice.

Sífilis por "exposição normal" e inoculação: um médico da equipe do estudo tuskegee na guatemala, 1946-1948 / Syphilis from "normal exposure" and inoculation: a physician on the tuskegee study team in guatemala, 1946-1948 / La syphilis par 'exposition normale' et par inoculation: un médecin de l'équipe d'étude tuskegee au guatemala, 1946-1948 / Sífilis por 'exposición normal' e inoculación: un médico del equipo de la investigación tuskegee en guatemala, 1946-1948

Entre 1946 e 1948, o Serviço de Saúde Pública dos Estados Unidos (PHS) e a Oficina Sanitária Panamericana, com a colaboração de funcionários de saúde pública do governo da Guatemala, realizaram um estudo sobre o uso da penicilina como possível profilaxia para a sífilis, gonorreia e cancro. Os "sujeitos" do estudo - prisioneiros, doentes mentais e soldados gualtematecos foram inoculados com essas doenças e também pelo contato com prostitutas infectadas. A fraude foi parte do estudo e os abusos éticos foram discutidos no PHS. Os resultados do estudo não foram publicados.

Between 1946 and 1948, the United States Public Health Service and the PanAmerican Sanitary Office, in cooperation with public health officials of the Guatemalan government, conducted a study on the use of penicillin as a possible prophylaxis for syphilis, gonorrhea and cancer. The "subjects" of the study (prisoners, mental patients and Guatemalan soldiers) were inoculated with these diseases and also acquired them through contact with infected prostitutes. The fraud was part of the study and ethical abuses were discussed at the US Public Health service. The study results were not published.

Entre 1946 et 1948, le Public Health Service des États-Unis (PHS) et l'Oficina Sanitaria Panamericana, en collaboration avec les responsables de la santé publique du gouvernement guatémaltèque, ont mené une étude sur l'utilisation de la pénicilline à titre préventif contre la syphilis, la gonorrhée et le cancer. Les sujets de l'étude - des prisonniers, des malades mentaux et des soldats guatémaltèques - ont été inoculés directement avec ces maladies, ainsi que par contact avec des prostituées infectées. Cette fraude était partie intégrale de l'étude, dont les abus éthiques ont été discutés par le PHS. Les résultats de l'étude n'ont jamais été publiés.

Entre 1948 y 1948, El Servicio de Salud Pública de los Estados Unidos (PHS) y la Oficina Sanitaria Panamericana, con la colaboración de funcionarios de la salud pública del gobierno de Guatemala realizaron un estudio sobre el uso de la penicilina como una profilaxis posible para el sífilis, gonorrea y cancro. Los "sujetos" del estudio - prisioneros, enfermos mentales y soldados guatemaltecos, fueron inoculados con esas enfermedades y también a través del contacto con prostitutas infectadas. El fraude fue parte del estudio y los abusos éticos fueron discutidos en el PHS. Los resultados del estudio no fueron publicados.

History of antibiotics. From salvarsan to cephalosporins.

Infections have represented for a long time the leading cause of death in humans. During the 19th century, pneumonia, tuberculosis, diarrhea and diphtheria were considered the main causes of death in children and adults. Only in the late 19th century did it become possible to correlate the existence of microscopic pathogens with the development of various diseases. Within a few years the introduction of antiseptic procedures had begun to reduce mortality due to postsurgical infections. Sanitation and hygiene played a significant role in the reduction of the mortality due to several infectious diseases. The introduction of the first compounds with antimicrobial activity succeeded in conquering many diseases. In this review we analyzed, from a historical perspective, the development of antibiotics and the circumstances that led to their discovery. The first compound with antimicrobial activity was introduced in 1911 by Erlich. He focused his research activity on the discovery of a "magic bullet" to treat syphilis. Afterwards, Foley and colleagues brought penicillin to the forefront. Streptomycin represents the first drug discovered for the treatment of tuberculosis, and its development included the first use of clinical trials. Finally, with the development of cephalosporins, the introduction of new antimicrobial compounds with broad activity against gram-positive and also some gram-negative bacteria began.

Penicillin: the medicine with the greatest impact on therapeutic outcomes.

The principal point of this paper is that the discovery of penicillin and the development of the supporting technologies in microbiology and chemical engineering leading to its commercial scale production represent it as the medicine with the greatest impact on therapeutic outcomes. Our nomination of penicillin for the top therapeutic molecule rests on two lines of evidence concerning the impact of this event: (1) the magnitude of the therapeutic outcomes resulting from the clinical application of penicillin and the subsequent widespread use of antibiotics and (2) the technologies developed for production of penicillin, including both microbial strain selection and improvement plus chemical engineering methods responsible for successful submerged fermentation production. These became the basis for production of all subsequent antibiotics in use today. These same technologies became the model for the development and production of new types of bioproducts (i.e., anticancer agents, monoclonal antibodies, and industrial enzymes). The clinical impact of penicillin was large and immediate. By ushering in the widespread clinical use of antibiotics, penicillin was responsible for enabling the control of many infectious diseases that had previously burdened mankind, with subsequent impact on global population demographics. Moreover, the large cumulative public effect of the many new antibiotics and new bioproducts that were developed and commercialized on the basis of the science and technology after penicillin demonstrates that penicillin had the greatest therapeutic impact event of all times.

Penicilina: oitenta anos / Penicillin: eighty years

Há oitenta anos, Alexander Fleming descobriu a penicilina. O trabalho enfatiza o contexto no qual foi descoberto a penicilina e suas repercussões na prática clínica e na epidemiologia...

Eighty years ago, Alexander Fleming discovered the penicillin. This paper stress the context in which the penicillin was discovered and its repercussions on clinical practice and epidemiology...

O papel da penicilina da medicina moderna / The role of penicillin in modern medicine

A penicilina foi o primeiro antibiótico descrito na literatura na década de 1940 e ainda tem o seu papel na medicina moderna. O uso deste medicamento ampliou-se desde sua descrição e atualmente continua a ser a indicação de escolha para algumas doenças. Este trabalho tem como objetivo descrever a importância da penicilina no contexto atual, além de explicitar o mecanismo imunológico de reação adversa às drogas incluindo a alergia à penicilina, mostrando que a reação anafilática é uma situação incomum e freqüentemente diagnosticada pelos médicos e profissionais da área da saúde de forma equivocada. Tal erro leva a uma substituição desta droga, que, apesar de antiga, continua relevante para o tratamento da sífilis.

Penicillin was the first antibiotic described in the literature in the 1940?s, and it still has a role in the modern medicine. The use of this drug has beenamplified since its description, and nowadays, it continues to be the treatment of choice in some diseases. This paper has the objective to describe the importance of penicillin on the actual context, and further, explain the immune mechanisms of adverse reaction to drugs, including penicillin allergy. It is also presented that the anaphylactic reaction is uncommon and it is frequently mistaken diagnosed by doctors and health staff. Such mistake leads to the substitution of this drug, that even described long time ago continues relevant to the treatment of syphilis.

Gonorrhea and the beginnings of clinical research ethics.

Research on ocular inflammation associated with gonorrhea began in conjunction with the entry of trachoma into Europe during the Napoleonic wars. The initial questions involved the cause of the contagiousness of gonorrhea and how the contagion spreads from the genitalia to other sites. Because efforts to infect animals with gonorrheal matter were unsuccessful, all experiments were conducted on human subjects. Once these two causes of blindness were tentatively differentiated, attempts to restore vision in an eye that had been blinded by a trachomatous membrane over the cornea by instilling gonorrheal pus began to be practiced. In 1841, Joseph Piringer described his use of this method to determine infectiousness decades before the discovery of pathogenic bacteria, as well as ethical concerns about the associated endangerment of patients. Beginning in the 1880s, research focused on the identification of the gonococcus and assessment of its pathogenicity. The ethical dilemma of inducing a disease with an unpredictable outcome persisted until the 1940s, when gonorrhea could be reliably cured by penicillin.

Champ Lyons: an incomplete life.

The life of Champ Lyons, MD, is presented, with emphasis on his tenure as Chairman of the Department of Surgery of the Medical College of Alabama (University of Alabama in Birmingham School of Medicine) from 1950 until 1965. Before becoming chairman Dr. Lyons, as an esteemed microbiologist, participated in the early use of penicillin in wounded servicemen during World War II. Later in his career, he made many contributions to the emerging disciplines of vascular and cardiac surgery. After a brief illness in 1965, Dr. Lyons expired due to a brain tumor. His relatively brief career and his unanticipated sudden demise have lessened the fame of Dr. Lyons to which he is justly entitled. It is the purpose of this presentation to reawaken the surgical community to the importance of this giant of American surgery.

Sir Edward Abraham's contribution to the development of the cephalosporins: a reassessment.

This paper is based on an invited lecture given at the 21st International Congress of Chemotherapy in July 1999, as part of a Symposium entitled '50 years of cephalosporins: their use the next 50 years', (Hamilton-Miller JMT, Cephalosporins: from mould to drug. Sardinia to Oxford and beyond, J Antimicr Chemother 1999;44(A):26). Celebration of this Golden Anniversary was made more poignant by the death of the last major participant, Sir Edward Abraham, in May 1999. This history has been told before, but mainly by Sir Edward, who being a very modest man (to which his obituaries graphically attest) consistently underplayed the role that he and Newton had in the discovery of cephalosporin C, that led to all the cephalosporins now in use. I had the privilege of working at the Dunn School from 1967 to 1970, with Abraham and Newton, where I met Brotzu, Florey and Dorothy Hodgkin, all of whom had important roles in this story. Other workers at the Dunn School at that time, e.g. Heatley, Sanders and Jennings (who became Lady Florey), helped develop penicillin. Such a galaxy of stars of the antibiotic firmament will never again be assembled. "Let us now praise famous men... these were honoured in their generation, and were the glory of their times" - Ecclesiasticus XLIV. vv 1.7.