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Veterans at Risk: The Health Effects of Mustard Gas and Lewisite (1993)
Institute of Medicine (IOM)

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. "3 History and Analysis of Mustard Agent and Lewisite Research Programs in the United States." Veterans at Risk: The Health Effects of Mustard Gas and Lewisite. Washington, DC: The National Academies Press, 1993.

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Veterans at Risk: The Health Effects of Mustard Gas and Lewisite

U.S.S. Bistera, well outside the harbor and undamaged by the raid, had pulled 30 men from the water in a rescue effort. By the next day, the officers and crew of the Bistera were blinded from the effects of the sulfur mustard carried onto the ship by those rescued. Bari was overloaded with casualties by then, and the Bistera and its crew struggled to nearby Taranto for treatment. Soon the U.S. command had no choice but to confirm the cause of these injuries. With the assistance of Colonel Stewart Alexander, a military physician with extensive knowledge of mustard poisoning, better precautions and treatment were begun. By the end of the disaster, over 600 victims of mustard poisoning were treated from the harbor area alone; of these, 83 died (Alexander, 1947). Close to 1,000 civilians from the town also died (Harris and Paxman, 1982). Unfortunately, no long-term medical follow-up of survivors of the Bari harbor disaster has been reported.

Medical Applications of Chemical Warfare Research

As history has repeatedly shown, the experience of medical personnel and researchers in wartime can lead to major innovations in medical treatment practices. Such was the case with chemical warfare research in WWII. Numerous advances were made in the treatment of metal poisoning, development of antibiotics, treatment of burn injuries, and other areas. Many of these advances were reviewed soon after the war in a two-volume summary Advances in Military medicine (Andrus et al., 1948). The story of the use of nitrogen mustard as a cancer chemotherapy agent is especially relevant to the present report.

Nitrogen mustards were first synthesized in the 1930s. These compounds were modifications of sulfur mustard and were found to have greater systemic toxicity than sulfur mustard (Gilman and Philips, 1946; OSRD, 1946). Particularly potent was the effect of nitrogen mustard on cells that are actively proliferating, including the lymphoid tissue, bone marrow, and certain cells lining the gastrointestinal tract. During WWII, the Committee on the Treatment of Gas Casualties authorized a contract between the Office of Scientific Research and Development and Yale University (Andrus et al., 1948). Under this contract, Louis C. Goodman headed a group that was responsible for the study of the pharmacologic effects of nitrogen mustards. The group, including Alfred Gilman, Frederick Philips, and Roberta Allen, focused its efforts on the study of the cytotoxic properties of nitrogen mustard. Enlisting the help of anatomist Thomas Dougherty, the group expanded its work to examine the effect of nitrogen mustard on experimental tumor cells in mice. It was found, but not published until later, that systemic administration of nitrogen mustard caused dramatic regression of these mouse tumors. These data formed the experimental basis of the first clinical trials of

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Front Matter (R1-R20)
Executive Summary (1-8)
1 Introduction (9-13)
2 Methods of Literature Collection and Survey (14-20)
3 History and Analysis of Mustard Agent and Lewisite Research Programs in the United States (21-60)
4 Findings from the Public Hearing Process (61-70)
5 Chemistry of Sulfur Mustard and Lewisite (71-80)
6 Relationship of Mustard Agent and Lewisite Exposure to Carcinogenesis (81-111)
7 Nonmalignant Respiratory Effects of Mustard Agents and Lewisite (112-130)
8 Ocular Effects of Mustard Agents and Lewisite (131-147)
9 Dermatological Effects of Mustard Agents and Lewisite (148-178)
10 Other Physiological Effects of Mustard Agents and Lewisite (179-198)
11 Relationship of Mustard Agent and Lewisite Exposure to Psychological Dysfunction (199-213)
12 Summary of Findings and Recommendations (214-226)
Bibliography (227-330)
A. Scientific and Background Presentations Made to the Committee (331-334)
B. Excerpt from The Residual Effects of Warfare Gases (335-337)
C. Involvement of the National Academy of Sciences Complex in World War II Research Programs: A Summary (338-339)
D. Excerpts from Chamber Tests with Human Subjects I, II, and IX. Naval Research Laboratory Reports Nos. P-2208 and P-2579 (340-369)
E. Interim Report and Addendum: Feasibility of Developing a Cohort of Veterans Exposed to Mustard Gas During WWII Testing Programs (370-377)
F. Summary of the Department of the Army Report: Use of Volunteers in Chemical Agent Research (378-381)
G. Public Hearing Announcement (382-385)
H. Letter from Dr. Jay Katz to Dr. David P. Rall (386-389)
I. Risk Assessment Considerations for Sulfur Mustard (390-398)
J. Examination of the Effects of Certain Acute Environmental Exposures on Future Respiratory Health Consequences (399-416)
List of Acronyms and Abbreviations (417-420)
Index (421-428)