365 



is claimed for them. The final responsibility will always be the physician's and 

 cannot be shared. However, it is essential that he be given the best possible in- 

 formation in a reasonable, adult manner.^^ 



It was more than a problem of guarding the patient from individual 

 drugs of potentially dangerous ettects, according to Dr. William Bean, 

 of the School of Medicine, Iowa State University : 



It is in the widespread use of new compounds which may have serious risk of 

 cumulative toxicity, sijecial sensitizing proclivities, or other effects where the 

 problem is serious. Responsible i)ersons in medicine, government, and industry 

 must face these issues together, honestly and courageously, lest there be truth 

 in the statement that the public is now screening new compounds so that phar- 

 macologists in their laboratories know their toxicity before they study them in 

 guinea pigs." 



There were now availfible, he said later, "a tremendous number of 

 very powerful drugs whose therapeutic virtue runs almost in parallel 

 with their danger." These were "chemicals which alter basic functions 

 of the human organisms." As a result, he suggested, "perhaps the mar- 

 gin of safety is smaller." ^" Acute toxicity, he said, could be detected by 

 ordinary clinical trials. But, "where the difficulty arises is when a de- 

 layed reaction, a cumulative reaction, or a sensitivity reaction occurs 

 that could not be predicted." These could not be anticipated "* * * 

 except on a wider trial over a longer period of time." ^^ 



During the Kefauver hearings an illuminating controversy arose 

 between the respective proponents of two alternative oral medications 

 for diabetes. One compound, known generically as tolbutamide, had 

 undergone extensive tests and evaluation since its original discovery 

 in Germany. Brought to the United States for study, late in 1955, it 

 had been tested in 38 major institutions, its effects studied with some 

 20,000 patients, and its therapeutic characteristics reviewed and eval- 

 uated by a succession of national conferences of leading physicians. 

 At one of the final such conferences, under the sponsorship of the 

 New York Academy of Sciences, some 100 physicians and scientists 

 participated. The medication was submitted for review to FDA in 

 March 1957, supported by 23 volumes of data of accumulated ex- 

 perience with it. On June 3, 1957, the drug was released by FDA for 

 general prescription use.^^ 



Before the same hearing. Dr. Henry Dolger, an internal medicine 

 practitioner specializing in diabetes, attached to jNIount Sinai Hos- 

 pital, and past president of the Xew York Diabetes Association, 

 praised the thoroughness of the tolbutamide testing program. How- 

 ever, he said, there had been another sulfonylurea derivative that had 

 been introduced into the United States in 1957 under the generic 

 name of chlorpropamide. He was critical of the developmental plan- 

 ning and testing of this compound. 



In a very limited fashion [he said] the exploration of the effects of this par- 

 ticular agent was explored somewhat fitfully and attempts to arrive at appro- 

 priate dosage were accompanied by pharmacologic studies which revealed hither- 

 to unknown delayed rates of excretion which made decreasing dosage impera- 

 tive. At the time of application to the FDA some 2,000 case reports were sub- 

 mitted and despite the inclusion of 43 deaths and a number of instances of 

 jaundice the drug was passed for public sale in 1958.^ 



16 Ibid., p. 10246. 



w Ibid., p. 10338. 



" Ibid., p. 10340. 



18 Ibid., pp. 10346-10347. 



" Account based on hearings, ibid., pt. 20, pp. 11008-11015. 



20 Ibid., p. 11146. Apparently Dr. Dolger later clarified this statement, explaining that 

 only 8 of the 43 deaths were attributable to the medication referred to. See ibid., pp. 11226- 

 11227. 



