381 



letter to the editor in the Journal of IMedicine, issue of Dec. 31, 1960) , 

 Dr. Kelsey was even more concerned. It is probable that one 

 factor in her initial consideration of tlie case was the fact that the 

 drug was used to deal with minor disorders, but which would involve 

 the i)rospect of enormous usage. Such a drug, if it had any inherent 

 possibility of hazard, would unbalance the risk/benefit calculation, in 

 terms of the potential range of unwanted consequences versus tlie rela- 

 tive unimportance of the desirable consequences. Moreover, there were 

 already a number of drugs of proved effect on the market to deal with 

 these same minor disorders. However, when the side effect of peripheral 

 neuritis became known, her apprehensions seem to have been sharpened. 

 According to one account. Dr. Kelsey had discovered in the course 

 of her World War II research on the effects of quinine on rabbits, that 

 drugs that irritate the nerves of adults sometimes operate so as to de- 

 form and stunt a fetus when absorbed into the system of a pregnant 

 female.*'* The first entry in Dr. Kelsey's FDA record of thalidomide 

 transactions with the Merrell Co. that raises this possibility was for 

 May 11, 1961. The entry reads in part : 



* * * regarding neurological toxicity * * *. We discussed certain points as 

 being ones on which more information was necessary. These included both 

 animal studies and clinical information. It was at this conference that we speci- 

 fied a need for evidence that the drug would be safe during pregnancy. [Hand- 

 written note on original reads : This was based on peripheral neuritis symptoms 

 in adults.] At this time our concern was only on theoretical grounds.^ 



The impression that thalidomide was associated with phocomelia be- 

 came general at the end of November 1961. The last entry in the FDA 

 record on thalidomide before this time was a memorandum of a tele- 

 phone interview by Ealph G. Smith, M.D., Dr. Kelsey's superior, with 

 a medical representative of the Merrell Co., dictated September 6, 1961. 

 It read in part : "After checking with Dr. Kelsey I informed him [the 

 company representative] that other changes in labeling were required 

 in connection with exclusion of use in pregnant women * * *.'' ^ 



Some criticism has been expressed because of timelags from the 

 point at which the serious effects of thalidomide on tlie fetus were 

 discovered and thalidomide was withdrawn from the German and 

 British markets (Xov. 26 and Dec. 3, 1961) to the time at which it was 

 withdrawn from the Canadian market (3.1arch 2) and to the time that 

 the U.S. new drug application was withdrawn (March 8). There was 

 also criticism, in Canada, of the slowness and incompleteness of the 

 action — governmental and private — to halt sale of thalidomide (known 

 there as Kevadon or Talimol). A feature article in MacLean's maga- 

 zine, for example, indicated that the drug was still being sold — and 

 even prescribed — as late as April 10, 1962."' 



The thalidomide testing fro grain in the United States 



The concept and criteria of the conduct of experimental trials of new 

 drugs was described to a Senate subcommittee by George P. Larrick, 

 Commissioner of the FDA, on August 1, 1962, in a general congres- 

 sional review of the process by which a new drug is introduced into the 

 United States. Commissioner Larrick explained : 



8* Richard Harris. The Real Voice. Op. clt.. p. 185. 

 «s Humphrey hearings, op. cit., pt. 1, pp. 78-79. 

 •« Ibid., p. 96. 



8^ MacLean's. (May 19, 1962). Article reproduced in Humphrey hearings, op. clt pt 1 

 p. 277. 



