The reception of penicillin in Portugal during World War II: cooperation with Brazil and the United States of America

The discovery of penicillin in 1928 and its introduction as therapeutic agent in the 1940’s significantly altered the prognosis of infectious diseases and represented the starting point for research that led to the discovery of other antibiotics. Portugal was one of the first European countries, non-participant in the II World War, to obtain penicillin for civilian use. World production of the antibiotic was scarce and military forces and Versão integral disponível em digitalis.uc.pt

1 The present study results of the doctoral research project (Doctoral fellowship SFRH/BD/62391/2009) from Fundação para a Ciência e a Tecnologia -FCT.Group of History and Sociology of Science and Technology Interdisciplinary Studies Center of the twentieth century the University of Coimbra -CEIS20 / Grupo de História e Sociologia da Ciência e da Tecnologia do Centro de Estudos Interdisciplinares do Século XX da Universidade de Coimbra -CEIS20 (UID/HIS/00460/2013). Acknowledgements: Fundação para a Ciência e a Tecnologia -FCT; Cruz Vermelha Portuguesa (Lisboa).
In Portugal, even before it was available, patients in life threatening situations due to the severity of their illness regarded penicillin as 'the last hope of salvation' 4 .
Family members and patient physicians sent innumerous appeals to the Portuguese Red Cross requesting penicillin 5 .In response to these requests, the acquisition of penicillin for Portugal became a priority for the Portuguese humanitarian institution 6 .In hope of obtaining penicillin, the Portuguese Red Cross contacted Brazil, the United States of America and Great Britain 7 .Great Britain acknowledged the request but was unable to assist 8 the United States were also incapable to satisfy this request 9 .Brazil, after some insistence from the Portuguese Red Cross, complied and sent twelve vials of penicillin to Portugal 10 .The first vials of penicillin arrived in our country on the May 24, 1944, offered by the Brazilian Red Cross 11 .
As production of penicillin increased, civilian distribution of the therapeutic agent became possible 12 .However, as the existing supplies were limited, Controlling Committees became necessary to oversee the distribution of the antibiotic 13 .
To our knowledge, the Civilian Penicillin Distribution Unit 14  Although the main goal of the controlling committees was to supervise allocation and distribution of the scarce amount of penicillin available for civilian use, the procedures implemented in each country were different.
The reception of penicillin in Portugal, the countries and the institutions involved must be perceived in the context of World War II and in the political context associated with the dictatorship of António Oliveira Salazar.Portugal officially assumed a neutral position in World War II.However, in spite of this fact, Portugal became a country of substantial spy activity.It was also a country where intense diplomatic relations were developed.Portugal was a passing point for numerous war fugitives, some of which took up residency in this country.According to Luís Reis Torgal, after WWII, the Portuguese president António Oliveira Salazar tried to explain that the neutral position assumed by Portugal was in fact a "neutral collaboration" with the allied countries (after 1942-1943) even though he admitted some comprehension toward the German situation 16 .
It seems important to refer that several science historians have studied the discovery of penicillin, its industrial production and its reception in different countries 17 .The study presented derived from a larger project concerning the reception 15   antibiotic to other hospitals in their vicinity.The location the hospital, the number of existing beds, the rate of admission and the population served, were some of the major factors that determined the amount of penicillin consigned monthly to each healthcare unit 22 .The WPB informed all US hospitals of the required procedures to attain penicillin and the location of the assigned depository hospitals.In order to avoid

Controlling Committees in Europe: Spain and France
As penicillin production increased and larger amounts of the therapeutic agent became available, the USA began to export the antibiotic to friendly and neutral countries.In order to supervise penicillin distribution, the US Foreign Economic Administration obliged the requisitioning countries to establish controlling committees 27 .From June 1944 to August 1945, the USA exported over 750 billion units of penicillin to these countries 28 . 22Ibid. 23

Spain -Comité Nacional de la Penicilina
In September 1944, Spanish government negotiated with its American counterpart a regular supply of penicillin for Spain.The Spanish Consejo Nacional de Sanidad nominated a technical committee, the Comité Nacional de la Penicilina, to control penicillin import, distribution and use in Spain.Four members composed the appointed committee, a physician, Carlos Jimenez Diaz, a pharmacist, Nazario Diaz Lopez, a bacteriologist, Gerardo Clavero del Campo and a dermatologist, Enrique Alvarez Sainz 31 .The Comité Nacional de la Penicilina determined to allocate penicillin supplies to previous appointed pharmacies -farmácias depositarias.The committee devised directives for patients and physicians who wished to requisition penicillin.The requisitioning parties had to provide the committee with a complete medical history of the patient.Appointed physicians by the Comité Nacional de la Penicilina analysed the patients file and if approved the requisitioning party received a voucher that enabled him to acquire a designated amount of penicillin form a "farmácia depositária" 32

Junta Consultiva para a Distribuição de Penicilina em Portugal
In May 1944, the Brazilian government offered Portugal 12 vials of penicillin.
Even though the amount of antibiotic provided by the Brazilian government sufficed to save a life, the meagre amount supplied could not fulfill Portugal's needs.The Portuguese Red Cross knew that a regular supply of penicillin was required in order to satisfy the innumerous requests received.Acting on this intent, they once more appealed to the United States of America 33 .On May 5, the United States Red Cross delegate informed the Portuguese institution that it might be possible to supply Portugal with penicillin 34 and on July 1 requested a meeting to discuss the matter 35 .The American government requested that the Portuguese Red Cross establish a controlling committee to analyse requests and oversee the distribution of penicillin in Portugal 36 .
In order to fulfill the request entailed by the United States government, the Portuguese Red Cross established the Junta Consultiva para a Distribuição da Penicilina em Portugal (Consultive Committee for the Distribution of Penicillin in Portugal) 37 .
This committee was composed of five medical doctors, Professor Doutor Francisco Gentil (presidente), Dr. Luís António Xavier Júnior (secretary), Professor Doutor Fernando da Fonseca, Professor Doutor João Maia Loureiro and Dr. Ernesto Galeão Roma.Francisco Gentil was a well renowned physician that played a key role in the establishment of the Portuguese Institute of Oncology founded in 1923.The first meeting of the Junta Consultiva took place on the July 26, 1944 at the Portuguese Red Cross headquarters in Lisbon.The Vice-President of the Portuguese Red Cross and members of the American Red Cross attended the meeting.The attending members discussed the best procedures to allocate, distribute and store penicillin.They also discussed and agreed upon the need to create a questionnaire to requisition of penicillin.
The Junta determined that the antibiotic should be stored in the Instituto Português de Oncologia (Portuguese Institute of Oncology) and that physicians who wished to request penicillin would have to fill in the questionnaire and provide their patient's clinical details.Furthermore, the attending members decide that physicians should be provided with information regarding the correct use of penicillin and that no information be released to the press, at present.Negotiations with the American government were successful and on September 2, 1944, the American Red Cross Delegate informed the Portuguese Red Cross that the first allotment of penicillin should arrive soon 38 .On September 8, 700 vials, containing 100 000 units of penicillin, arrived at Lisbon airport, transported by Pan American Airways 39 .The initial monthly quota of penicillin allocated to Portugal was 700 vials, in January 1945 the allotment was increased to 1000 vials 40  -Carta da Legação dos Estados Unidos da América de 19 de Abril de 1944 -Número de ordem de entrada 1445.

Introduction
Industrial production of penicillin 1 began in 1942 2 .During 1943 and the beginning of 1944 overall production of the antibiotic was scarce and the military forces absorbed most of the available quantities 3 .
established in the USA, on May 1, 1944, was the first installed controlling committee.Later, European countries such as France, Spain and Portugal established equivalent committees to supervise penicillin distribution.Portugal established, the Junta Consultiva para a Distribuição da Penicilina em Portugal in Portugal, in July 1944 15 , Spain established, The Comité de la penicilina, in September 1944, and in January 1945, France established, The Comité de distribuição da penicilina.
incorrect use and enlighten physicians on the most efficient way to use penicillin, Dr. Chester Keefer 23 , of the Committee on Medical Research of Office of Scientific Research and Development, prepared "The Use, Indications, Contraindications, and Mode of Administration of Penicillin" 24 .This elaborate report, informed physicians of the infectious diseases susceptible to penicillin treatment, advised them on the best route of administration for the antibiotic as well as the possible side effects that may occur.The WPB distributed copies of Dr. Keefer's report to hospitals and private physicians 25 .Between May 1, 1944 and March 15, 1945 (when terminated) the Civilian Penicillin Distribution Unit distributed over 250 billion units of penicillin to 8000 hospitals and other healthcare units in the United States, Alaska, Puerto Rico, Hawaii, and the Virgin Islands 26 .

France-
Commission de la Pénicilline: After liberation from German occupation, in 1944, France negotiated with the USA a regular supply of penicillin for civilian use.The first allotment of 500 vials of the antibiotic arrived in France in January 1945 29 .In order to ensure the equitable distribution of the antibiotic and in accordance with the recommended therapeutic indications, the French Ministère de la Santé Public (French Ministry of Health) constituted the Commission de la Pénicilline.The committee decided to allocate the amount of penicillin supplied to previous selected hospitals that would function as "therapeutic centers".Patients diagnosed with pathologies susceptible to the antibiotic were transported to the designated centers to receive treatment.With this measure, the commission ensured an even distribution of penicillin among patients.It also guaranteed the correct use of the therapeutic agent and minimized transportation difficulties.In February 1945, six therapeutic centers functioned in France, three in Paris and three in the province.By February 1946, 600 centers operated in the country and in April 1946, every hospital in France treated patients with penicillin 30 .

ARQUIVO DA CRUZ VERMELHA PORTUGUESA -'Carta Enviada À Delegação Da Cruz Vermelha Portuguesa de Estremoz Em 20 de Setembro 1944 -Número de Ordem 4524', Livro de
Chester Scott Keefer, M.D., D.Sc.(1897-1972).During World War II, Dr. Chester Keefer was appointed Chairman of the National Research Council's Committee on Chemotherapeutics and Other Agents and Medical Administrative Officer of the Committee on Medical Research of the Office of Scientific Research and Development.One of Dr. Keefer´s main assigned duties was to supervise and control distribution and allocation of penicillin for civilian use in the United States during World War II. 24'Penicilina Em Portugal' -Jornal Do Médico, 4, 93 (1944), p. 709.