MUTAGENS OF POTENTIAL SIGNIFICANCE 209 



coffee or tea at all; another one-fifth drinks five or more, and some- 

 times up to ten cups a day. The bulk of the people drink one, two, 

 or three cups a day. 



If we accept 300 mg/day as the mean intake, we find this would 

 establish 6 mg/1 in body water, with a half-life of 3.5 hours. Integrating 

 the exponential decay curve, we find a mean level of something like 

 1.3 mg/1, considered to apply over the whole 24-hour period. We may 

 say, then, that the exposure of the population is as though all the 

 human germ plasm of this country were constantly bathed in caffeine at 

 a concentration of about 1 mg/1. 



More realistically, we note that about one-fifth of the adult popula- 

 tion is not exposed to caffeine at all. The majority drink between one 

 and five cups daily, achieving a mean tissue level around 1 mg/1. An- 

 other one-fifth are heavy coffee-drinkers, who may be exposed to 

 mean levels as high as 5 mg/1. These people are "addicted" to caffeine, 

 in the sense that they clearly take caffeine for its psychic effects, they 

 crave it strongly, and they display distinct withdrawal symptoms, 

 such as headache (21) , if it cannot be had. 



We believe that coffee-drinking patterns are quite consistent for 

 individuals; they remain stable over long periods of time, and we 

 think they may in some respects be genetically determined. We have 

 been interested for some time in the general belief that some people 

 are kept awake by coffee and some people are not. When you talk 

 to people about it, you get the impression that if they are correct 

 about their own reactions to caffeine, there must be very great differ- 

 ences in the sensitivities to caffeine within the population. 



We have been making studies, using large numbers of medical 

 students as subjects, to try to get more information about these 

 differences. The first question was whether it really is true that some 

 people are consistent reactors and some people are consistent non- 

 reactors to the psychic stimulation of coffee. We can now say with 

 some confidence that this is certainly true. The criteria that we used 

 were rather crude, because there is still no adequate objective test for 

 psychic stimulation by a drug. But what we used — ■ 



Glass: You are probably not familiar with the little study, but I 

 developed a test for the effect of caffeine on individuals, using a 

 muscular and visual precision test, and applied it to two monozygotic 

 twins, in a series of studies (27). They showed almost identical re- 

 actions when they were tested, and tested without knowing the other's 

 reaction, in separate rooms, with placebos for the control and so on. 



