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156 The emergence of chloroquine as the first-line drug for malaria prophylaxis and treatment was the great medical accomplishment of the antimalarial program ’s later years. Chloroquine’s path from a failed drug in the Bayer interwar program to a wonder drug of the postwar world merits attention in its own right and also illustrates the networks of relationships that evolved during the U.S. antimalarial program. For U.S. soldiers and marines, chloroquine would emerge from testing programs too late to impact combat operations. With chloroquine and the insecticide DDT, another wartime development, in hand, the old Ross-Koch public health debate about whether mosquitoes or parasites were the proper target for disease intervention entered a new era: these chemicals were deadly weapons against both. DDT and chloroquine would later founder in the face of resistance—pesticide resistance and drug resistance, respectively. But for millions of people living in malarious areas, cheap, effective chloroquine would be a lifesaver. Chloroquine rose just as the sun was setting on the CMR program itself. Recall sontochin from chapter 3. A chemical cousin of chloroquine developed by Bayer, it appeared more than once early in the U.S. antimalarial program and showed good activity in avian screens.1 It was one of number of compounds provided to the program by the Winthrop Chemical Company. W. Mansfield Clark’s staff gave it Survey Number SN-183, indicating that it was one of the first compounds that they processed. Later in the war, sontochin was thrust into the spotlight when it was captured with an enemy prisoner of war in North Africa. Sontochin, however, had been in the possession of Chapter 7 Chloroquine, Wonder Drug Chloroquine, Wonder Drug 157 the program even before the formation of the Survey Office. In 1940, Justus B. Rice, vice president for medical research at the Winthrop Chemical Company, had given the compound to Lowell Coggeshall, then still working at the Rockefeller Institute. Though they had the Winthrop compound in 1940, the Rockefeller team did not test it until John Maier picked it up in January 1941. Maier found the compound active against his avian malaria, P. cathemerium. In due course, Winthrop released Maier’s testing data to the Survey in December 1942, where it rested in the Survey’s open files until its North African appearance . Testing by chemists at the Rockefeller Institute in New York revealed that the German sontochin was identical with SN-183. For security reasons, the Survey issued the compound a new survey number, SN-6911. After testing at Hopkins and Chicago, E. K. Marshall reported sontochin to be four to eight times as active as quinine against the duck malaria, P. lophurae.2 The Subcommittee on Coordination of Malarial Studies was especially keen to move forward on sontochin as they already had in their possession a report by a French military doctor in Tunis on field trials of sontochin in the French army, a report they had received courtesy of the U.S. Army Surgeon General’s Office.3 By the spring of 1944, sontochin was moving on in toxicology trials in humans.4 Sontochin pointed back to chloroquine. As soon as sontochin had reemerged from the Survey and the North African desert, the CMR solicited all of Winthrop’s records on sontochin and related compounds. The program began a reexamination of these 4-aminoquinolines. Readers will recall the sontochin differed from chloroquine by only a methyl group (fig. 3.13). NRC interest in chloroquine originally derived from its inclusion in Bayer antimalarial patents—specifically U.S. Patent 2,233,970—assigned to Winthrop Chemical.5 Apparently, the company had never produced the compound before Clark and Kenneth Blanchard of the Survey Office requested them to do so in November 1943. With no regard for their prewar ties to Bayer, Winthrop was consistently helpful and compliant with government requests. They assisted with chloroquine voluntarily and under contract, and worked on other wartime chemical problems. In July 1944, the War Production Board received from Winthrop Chemical Company its plasmochin pilot plant.6 By July 1944, Marshall and others were convinced that chloroquine, SN-7618, was the drug they had been looking for: Marshall wrote that the board “had as its primary objective the discovery of a drug that is a true causal prophylactic in both falciparum and vivax malaria or a drug which consistently cures both of these infections.” He went on to express the recom- [3.138.105...

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