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September 1, 1999

Unlicensed Vaccines and Bioweapon Defense in World War II

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JAMA. 1999;282(9):822. doi:10.1001/jama.282.9.822-JMS0901-5-1

Joel Schofer presented well the ethical controversy surrounding use of unapproved agents for chemical and biological warfare defense in Operation Desert Storm.1 Such dilemmas are not new, however, nor the risks purely ethical or medically theoretical. They occurred several times during World War II, the most dramatic and sobering being the yellow fever vaccine incident of 1942.

In January 1942, immediately after Pearl Harbor, the US military decided to vaccinate all active duty personnel with yellow fever vaccine. This decision was based largely on the fear that an enemy power would launch a strategic biologic attack by releasing a virulent virus in areas that harbored the vector. The area at risk included vital areas of the United States: much of the East, Midwest, and South and southern California. It also included essentially all overseas combat areas: China, the Pacific islands, Australia, India, Burma, southern Britain, coastal France, the Mediterranean area, and the southern Soviet Union. The army had since January 1941 already addressed possible accidental transmission of the virus from endemic areas by selective vaccination, fumigation, and quarantine.2

Concern regarding biological attack was well founded. From 1932 to 1945 the Imperial Japanese Army undertook a massive and ethically horrific program to develop biological weapons. The United States became aware of this effort, sought intelligence, and took the threat seriously. The FBI investigated repeated overt and covert attempts by Japan to obtain virulent yellow fever virus in 1939.3

In 1942, all military personnel received typhoid, smallpox, and tetanus vaccines, and soldiers who refused vaccination were subject to court-martials—a military legal principle originating in World War I and continuing to this day.4 However, during World War II, a yellow fever vaccine had not yet been licensed for civilian use in the United States and an FDA-approved vaccine would not be available until 1953. The yellow fever vaccine used in early 1942 contained human serum, and despite earlier published reports of unexplained or "homologous serum" jaundice occurring after its use, the perceived urgency of the biological weapon threat propelled this vaccine into use. Unfortunately, many lots were contaminated by the hepatitis B virus. An epidemic of unexplained hepatitis began in March 1942, and yellow fever vaccination was halted on April 15, 1942. Approximately 51,000 military personnel with symptomatic hepatitis were hospitalized, and subsequent serologic investigation of veterans concluded that approximately 330,000 persons had been infected.5

This is the largest point source outbreak of hepatitis B ever recorded. Although chronic hepatitis following yellow fever vaccination was recognized, the vaccinated soldiers have fared surprisingly well: on follow-up they have an unexpectedly low carrier rate and no increase in death from chronic liver disease. They have, however, a small excess in deaths from liver cancer.6

Of course, in 1942 the principles of the Nuremberg Code (1947) had not yet been formulated, nor had the US military officially adopted them as policy (1953).7,8 Although modern codes of medical ethics did not exist to restrain the use of unlicensed vaccines by the military, the tens of thousands of iatrogenic casualties from the yellow fever vaccine experience may well have had a chilling effect on further use of other experimental vaccines.

In fact, in 1944 an erroneous report of Nazi weapons using botulinum toxin was taken seriously by the US government, and in response a crash program produced enough unlicensed botulinum toxoid to immunize the entire D-day assault force. Despite strong recommendation by the US Army Surgeon General to immunize all personnel before the Normandy invasion, the theatre surgeon, responsible directly to Eisenhower, opted to hold the toxoid in stockpile.9 Ironically, during Desert Storm large-scale administration of this toxoid had to await the formal informed consent process.

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