Charles M. Grossman

The First Use of Penicillin in the United States

The first dose of penicillin given in the United States was administered at YaleNew Haven Hospital on 12 March 1942 to a patient dying of septicemia. As a young Yale house officer, I found myself involved in what few of us then realized was a very profound sequence of events. It was my ninth month of service, and I was an acting assistant resident. On the private floor of the YaleNew Haven Isolation Building, a very ill 33-year-old patient had -hemolytic streptococcal sepsis. She had run a steady temperature of 103 F to 106 F for 4 weeks (Figure [1]). Her private physician, Dr. John Bumstead, persuaded Dr. John F. Fulton, another ill patient of his with a severe pulmonary infection, to try to obtain a new drugpenicillin. The drug was not yet available in the United States. Dr. Howard Florey had reported on the use of penicillin in England in 1941, and Dr. Fulton was aware of Floreys studies (2). Since their Oxford days together, Fulton and Florey had remained friends. In fact, Dr. Floreys children were living with the Fultons in New Haven, Connecticut, to escape the German bombs falling on London in 1941. Figure. First clinical trial of penicillin in the United States: penicillin therapy of -hemolytic streptococcal septicemia. Reprinted with permission from reference 1. Dr. Fulton, a National Research Council (NRC) Committee on Aviation Medicine member and Sterling Professor of Physiology, and Dr. Francis G. Blake, Sterling Professor of Medicine and a leading member of the National Academy of Science Chemotherapy Committee, used their considerable influence to complete the tortuous route required to release the small amount of penicillin available in the United States. Dr. Florey and his associate, Dr. Norman Heatley, had come to the United States in an effort to increase penicillin production, because England was so busy with the war with Germany. The first vial was mailed to Dr. Bumstead in New Haven from Merck & Co. in Rahway, New Jersey, and it arrived on Saturday, 12 March 1942. Dr. Bumstead and I took the vial to Dr. Morris Tager, Associate Professor of Bacteriology and Immunology. We discussed what to do with the pungent, brown-red powder. We decided to dissolve it in saline and pass it through an E.K. Seitz [asbestos] filter pad to sterilize it, wrote Dr. Tager in 1976 (3). We then returned to the patient, and I injected 5000 U into the intravenous tubing. Rocko Fasanella, a medical student (later a professor of ophthalmology at Yale), gave subsequent doses every 4 hours. By Monday morning, the patient was eating hearty meals, the intravenous treatment was stopped, and she subsequently received 5000 U intravenously every 4 hours. On Monday morning rounds, Dr. Wilder Tileston, a senior consultant, looking at the temperature chart (Figure), muttered to those of us close enough to hear, black magic. My fellow intern, Dr. Herbert Tabor (later the editor of the Journal of Biological Chemistry for many years), saved all of the patients urine because Dr. Heatley had informed us that more penicillin could be purified from it than could be produced by cultivation. Probably up to 95% of each intravenous dose was excreted unchanged. When Dr. Heatley delivered a subsequent vial, some of which had come from the patients urine, he carted the gallons of urine back to Rahway. The patient survived and later died of other causes at the age of 90 years. Four hundred million units of penicillin were produced in the first 5 months of 1943. In the next 7 months, 20.5 billion units were producedan increase of more than 500 times. By August 1945, 650 billion units were distributed each month. The subsurface liquid culture technique produced so well that when the structures of penicillin F and G were later established, it was decided that producing penicillin by culture rather than by any chemical synthetic method would be far less costly. Production costs changed so that the cost of an ampoule of 100 000 units was scarcely more than the cost of material and labour to put it into an ampoule (4). If any one person is to be credited with the development of penicillin in the United States, it should be Dr. John F. Fulton. The literature does indeed tell about his significant role (37). His telephone calls from his own hospital bed demonstrated his persistence, perspicacity, patience (when needed), propriety, and personal influence. He recognized a need and a possible fulfillment of this need, and he effectively pushed for the sequence of events that transpired. Fleming, Florey, and Chain received the Nobel Prize in Medicine in 1945 for their contributions. Fulton deserves credit together with Dr. Francis G. Blake for proving the enormous value of penicillin and effecting the birth of the antibiotic era.

MUSHROOM POISONING: A REVIEW OF THE LITERATURE AND REPORT OF TWO CASES CAUSED BY A PREVIOUSLY UNDESCRIBED SPECIES

Excerpt Little information is available in the British and American literature on mushroom poisoning. Smith1described a wide variety of poisonous and allegedly poisonous mushrooms in a recent text....

Hypothyroidism and Spontaneous Abortions among Hanford, Washington, Downwinders

Spontaneous abortions occurred more than twice as frequently in hypothyroid women, compared with nonhypothyroid women. Both groups of women had lived in the same environment during the same period of time. The high incidence of hypothyroidism in a cohort of several hundred women who lived downwind of the Hanford, Washington, nuclear installation was likely associated with environmental contamination from deliberate releases of radioactive iodine from the facility.

Cancers among Residents Downwind of the Hanford, Washington, Plutonium Production Site

A community-based health survey for the time period between 1944 and 1995 was collected from 801 individuals who had lived downwind of the U.S. plutonium production facility located in Hanford, Washington. The results of the survey revealed high incidences of all cancers, including thyroid cancer. There were greater than expected numbers of central nervous system tumors and cancers that invaded the female reproductive system (e.g., cancers of the uterus, ovary, cervix, and breast). The authors argue that the greater-than-expected numbers found cannot be accounted for by selection bias alone. Comparisons of crude incidence rates, as well as of occurrence ratios between pairs of cancer types among Downwinders and reasonably similar populations, suggested that the excess neoplasms may be associated with radioactive contamination of food, water, soil, and/or air. In addition, a synergistic effect may exist with agricultural toxins. Previously neglected biophysical and physiological properties of internally lodged, long-lived 129I may be a significant etiological factor in the development of thyroid diseases, including cancer, and other malignancies in exposed populations.

Community-Based Participatory Health Survey of Hanford, WA, Downwinders: A Model for Citizen Empowerment

Residents around the Hanford, WA, plutonium production facility have long suspected damage to their health due to radioactive releases from the plant. From 1944 to 1986 the government denied environmental contamination, let alone any health impact. An alliance of residents (Downwinders), physicians, scientists, and social justice activists designed, distributed, collected, and analyzed a health survey concerning persons who had been at risk for exposure to internally lodged radioisotopes. This community-participatory health study suggests an excess of illnesses among Hanford Downwinders. These findings cast doubts on conclusions drawn from a widely publicized government study: that radioactive emissions from Hanford did not lead to increases in thyroid disease. The described collaborative grass-roots project may serve as a model for identifying health effects among other populations exposed to radioactive fallout or other environmental contaminants. Concomitantly, a community-participatory survey can provide a sense of validation and empowerment by affording affected populations valuable data in support of their demands for large-scale epidemiological studies of environmental links to their health problems, followed by remedial actions.

Reproductive outcomes after radiation exposure.

Reproductive Outcomes after Radiation Exposure Charles Grossman;William Morton;Rudi Nussbaum; Epidemiology

Human Aortic Valve Calcification

To the Editor: Rajamannan et al1 addressed the problem of bone formation in calcified aortic valves, quoting the publication of actual bone formation by Mohler et al.2 Mohler et al had indicated that ossification in calcified aortic valves was relatively common, finding evidence of valve ossification in 36 of 323 patients. Of historical interest, I reported ossification in the left ventricular wall of a patient who had died 3 years after a myocardial infarction.3 I could find no other example of human “myocarditis ossificans” in a literature search. In 1967, however, Selye et al4 reported on …

Mortality Rate of Community-acquired Pneumonia: 1944 and Today

Excerpt To the Editors:Some old data seem to have been overlooked in the literature. In their article, Farr and colleagues (1) discussed pneumonia mortality, quoting the usual rates of 6% to 24%. I...

Cholesterol screening and coronary artery heart disease.

Excerpt To the Editor:The recent article by Garber and colleagues (1) on serum cholesterol as a cardiac risk factor was very comprehensive and well documented. Is it fair, however, to add more weig...