The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapyrevolution has arrived, but many of the principles and limitations of chemotherapy discovered by the early researchers still apply.
Beginnings
The beginnings of the modern era of cancer chemotherapy can be traced directly to the German introduction of chemical warfare during World War I. Among the chemical agents used, mustard gas was particularly devastating. Although banned by the Geneva Protocol in 1925, the advent of World War II caused concerns over the possible re-introduction of chemical warfare. Such concerns led to the discovery of nitrogen mustard, a chemical warfare agent, as an effective treatment for some types of cancer. Two pharmacologists from the Yale School of Medicine, Louis S. Goodman and Alfred Gilman, were recruited by the US Department of Defense to investigate potential therapeutic applications of chemical warfare agents. Goodman and Gilman observed that mustard gas was too volatile an agent to be suitable for laboratory experiments. They exchanged a nitrogen molecule for sulfur and had a more stable compound in nitrogen mustard.[1] A year into the start of their research, a German air raid in Bari, Italy led to the exposure of more than 1000 people to the SS John Harvey’s secret cargo composed of mustard gasbombs. Dr. Stewart Francis Alexander, a lieutenant colonel who was an expert in chemical warfare, was subsequently deployed to investigate the aftermath. Autopsies of the victims suggested that profound lymphoid and myeloid suppression had occurred after exposure. In his report, Dr. Alexander theorized that since mustard gas all but ceased the division of certain types of somatic cells whose nature was to divide fast, it could also potentially be put to use in helping to suppress the division of certain types of cancerous cells.[2]
Using that information, Goodman and Gilman reasoned that this agent could be used to treat lymphoma, a tumor of lymphoid cells. They first set up an animal model by establishing lymphomas in mice and demonstrated they could treat them with mustard agents. Next, in collaboration with a thoracic surgeon, Gustaf Lindskog, they injected a related agent, mustine(the prototype nitrogen mustard anticancer chemotherapeutic), into a patient with non-Hodgkin’s lymphoma.[3] The patient, a Polish immigrant to Connecticut known in literature only as JD, received his first injections on August 27, 1942 at 10 a.m.[4] The doctors observed a dramatic reduction in the patient’s tumor masses.[5][6] Although the effect lasted only a few weeks, and the patient had to return for another set of treatment, that was the first step to the realization that cancer could be treated by pharmacological agents.[3] The patient ultimately died of cancer on December 1, 1942, 96 days after his first dose.[4]Publication of the first clinical trials was reported in 1946 in The New York Times.[7]
https://en.m.wikipedia.org/wiki/History_of_cancer_chemotherapy
Paul Ehrlich: founder of chemotherapy
https://www.nature.com/articles/nrd2582
Ehrlich, P. Chemotherapy (Pergamon Press, London, 1960).
Paul Ehrlich’s Collected Papers
The Collected Papers of Paul Ehrlich
Compiled and edited by Dr. F. Himmelweit, with the assistance of the late Martha Marquardt. Under the editorial direction of Sir Henry Dale. Vol. 2: Immunology and Cancer Research. Pp. viii + 562 + 9 plates. Vol. 3: Chemotherapy. Pp. viii + 615 + 6 plates. (London and New York: Pergamon Press, 1960.) 160s. net each.
The Collected Papers of Paul Ehrlich. In four volumes. Volume 1 Histology, Bio- chemistry and Pathology. Edited by F. Himmelweit, M.D., Ph.D., F.R.C.P.Ed. (Pp.vi+ 653; ilustrated. Volume 1-£12.) London and New York: Pergamon Press. 1956.
This work may, without exaggeration, be described as one of the most ambitious and important contributions made to medical literature and medical history this century, and doctors, scientists, historians, and librarians owe an enormous debt of gratitude to the editor, Dr. Himmelweit, to the late Martha Marquardt, to Sir Henry Dale, to the Pergamon Press, and to the Wellcome Trust for the part they have played in translating what might well have remained a pious dream into the realm of reality. The first volume contains a scholarly and enlightening introduction by Sir Henry Dale and 55 of Ehrlich’s papers which are arranged in the following sections: Practice and theory of staining in histology; Cytology of the blood in health and disease; Staining of bacteria and its application to diagnosis; „The requirement of the organism for oxygen“ and allied biochemical studies; Pharmacology, therapeutics, and toxicology; The diazobenzenesulphonic acid and dimethylaminobenzaldehydere actions. The earliest paper is dated 1877 and the last 1904. The great majority of the articles a rein German. Two previously unpublished ones are also translated into English: Ehrlich’s inaugural dissertation (Leipzig, 1878), entitled „Contributions to the theory and practice of histological staining“,and his Habilitationsschrift (thesis for recognition as university teacher), „The requirement of the organism for oxygen: an analytical study with the aid of dyes“(1885). There are five coloured plates and a front is piece showing Ehrlich aged about 40.
Having enjoyed the literary feast provided by this unique and fascinating volume, it may be greedy and ungrateful to ask for more, but to the reviewer it seems a great pity that a few lines of comment did not accompany each article, explaining its historical significance and its value to-day.
Chemotherapy of cancer
SK Carter, M Bakowski, K Hellman
[en] This is a convenient reference to anti-cancer drugs commonly used in the US and Europe. It provides up-to-date information on recommended dosage, toxicity, administration, and mechanism of action. The book is divided into a reference guide to specific anticancer drugs, treatment of solid tumors and hematologic malignancies, and new approaches, experimental drugs, and future directions in cancer therapy. A section on nursing considerations, contributed by a nurse oncologist, is also provided
META
Chemotherapy of cancer, 3rd ed
Carter, S.K.; Bakowski, M.; Hellman, K.1987
[en] This is a convenient reference to anti-cancer drugs commonly used in the U.S. and Europe. It provides up-to-date information on recommended dosage, toxicity, administration, and mechanism of action. The book is divided into a reference guide to specific anticancer drugs, treatment of solid tumors and hematologic malignancies, and new approaches, experimental drugs, and future directions in cancer therapy. A section on nursing considerations, contributed by a nurse oncologist, is also provided
Primary Subject
RADIOLOGY AND NUCLEAR MEDICINE (C6400)
Source
1987; 320 p; John Wiley and Sons Inc; New York, NY (USA); ISBN 0-471-85266-X;
Record Type
Book
Country of publication
Descriptors (DEI)
CHEMOTHERAPY, DRUGS, FORECASTING, NEOPLASMS, PATIENTS, REVIEWS
Descriptors (DEC)
DISEASES, DOCUMENT TYPES, MEDICINE, THERAPY
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