Letters to the Editor

LETTERS TO THE EDITOR Dear Sir: The article, "Penicillins and Staphylococci: A Historical Interaction," in the Summer 1992 issue states that "The first patient to receive parenterally administered penicillin was a woman dying of breast cancer, in whom it was hoped to demonstrate the safety of the drug." This reference to the "first patient" is correct only if it refers to the work carried out by Florey's group at Oxford. Following the publication of the landmark paper [1] by the Oxford group, penicillin preparations were made at the College of Physicians and Surgeons, Columbia University. The driving force was the physician Henry Dawson, who hoped penicillin could be used against subacute bacterial endocarditis. He enlisted the biochemist Karl Meyer and the microbiologist Gladys Hobby and was able to obtain a culture of Fleming's organism from Roger Reid at Pennsylvania State University. In a remarkable achievement, this group quickly duplicated the procedure of the Oxford team. Dawson injected crude penicillin preparations intracutaneously into his first two patients, Aaron Alston and Charles Aronson, on October 15, 1940. A Mr. Conant received penicillin intravenously beginning on January 18, 1941 [2, p. 72]. The Oxford cancer patient was injected intravenously nine days later—on January 27, 1941 [3]. Although too little material was available to Dawson in his early experiments, positive results in treatment of subacute bacterial endocarditis were obtained by him with several patients from 1942 to 1944 [2, p. 163]. Florey's early work had also suffered from the same limitation in penicillin supplies. Unhappily, Dawson had been afflicted with myasthenia gravis early in 1941; he died in 1945. In an astonishing lapse, the penicillin injection in the Oxford cancer patient was not recorded in the woman's case notes, and Florey kept no record of her name. Later examination of hospital records for a cancer patient showing a "spike" in the temperature chart, indicates that she was probably Mrs. Elva Akers [5]. The penicillin treatment of the Oxford policeman, Albert Alexander, was begun on February 12, 1941, and constitutes the first recorded parenteral administration of penicillin at Oxford. Florey had previously attempted direct introduction of penicillin into the duodenum of a patient, Edward Reynolds, who was suffering from osteomyelitis. No penicillin could be detected in the blood or urine, and this case was discounted as a record of treatment [4]. In the five decades that have passed since these early investigations, there have been profound changes in the evaluation of new drugs for human use. In his search for a potential subject for toxicity testing, Florey had used the "old Permission to reprint a letter printed in this section may be obtained only from the author. 472 Letters to the Editor boy network" by consulting a friend, Professor Hugh Cairns. Cairns, a neurosurgeon , has been described as "a power in the organization of the Radcliffe Infirmary " [4]. He referred Florey to the Professor of Medicine, L. J. Witt. As Witt and Florey talked, Dr. C. M. Fletcher, a Nuffield Research Fellow, appeared with a question for Witt. Fletcher was immediately enlisted to find a suitable, terminally ill patient on whom penicillin could be tested for toxicity—ethically. Fletcher approached the patient directly, saying the proposed injection would be of no avail in the treatment of cancer. She agreed to the proposal and received an intravenous injection of 100 mg of Florey's material. As previously noted, no records of any kind were kept, and the agreement to the injection was only made verbally. Although Fletcher was initially somewhat unenthusiastic about his role, he subsequently became an acknowledged expert in the use of penicillin. The toxic reaction stunned the Florey team, especially since a second patient also showed the same result. Fortunately, further purification of the crude preparations removed the pyrogenic impurity. Florey's determined approach with a poorly characterized material and with very limited animal testing is in stark contrast to the immense quantity of paperwork and prior experimentation that would be required today. Penicillin was actually used clinically (but not parenterally) before the epic work of Dawson and Florey. Fleming himself described a number of cases in the period 1929—1932, unfortunately providing little information [5, 6]. Moreover...