Smallpox has long been a germ of choice among biowarriors. In the 15th century, Pizarro is reported to have presented South American natives with variola-contaminated clothing. The English apparently did the same during the French and Indian War in 1754-67. According to the medical journal article, Sir Jeffrey Amherst, commander of the British forces in North America, suggested that smallpox be used to reduce American Indian tribes hostile to Britain, and on June 24, 1763, Captain Ecuyer, one of Amherst's aides, gave blankets and a handkerchief from the smallpox hospital to the Indians.

''I hope it will have the desired effect,'' he noted in his journal. It apparently did, though the scientists argue that cause and effect are uncertain since smallpox epidemics had been occurring among Indians for more than 200 years after initial contacts with Europeans.

The 19th-century discoveries of modern microbiology led to technological breakthroughs in biowarfare, especially the ability to isolate and produce stocks of specific pathogens, or deadly germs. World War I provided ample opportunities to use them.

There is substantial evidence, say the scientists in the journal article, that Germany developed an ambitious biological warfare program and that German agents inoculated horses and cattle with glanders in the United States before the animals were shipped to France. The Bucharest Institute of Bacteriology and Pathology identified germ cultures that were confiscated from the German Legation in Romania in 1916 as B. anthracis and B. mallei. And German agents operating allegedly used Burkholderia mallei in Mesopotamia to inoculate 4,500 mules and in France to infect the French cavalry's horses.

The use of chemical and biological weapons in World War I caused public revulsion and helped bring about the 1925 Geneva Protocol, which prohibited the use of germ or chemical weapons in warfare. But the protocol did not ban basic research, production or possession of such agents, and many countries that signed the accord specifically preserved the right to retaliate if they were attacked.

While Germany tried to develop biological weapons in World War II, the only known German use of them then was ''the pollution of a reservoir in northwestern Bohemia with sewage in May 1945,'' according to the Fort Detrick scientists. Japan, however, used a series of germ weapons on a vast scale, especially against prisoners in Manchuria from 1932 until the end of World War II. Thousands of prisoners died after being infected with B. anthracis, meningitidis, shigella and yersinia pestis, to name but a few. Japan also dropped germ-filled bombs, feathers and cotton wadding from its fighter planes, infecting thousands more in at least 11 Chinese cities.