212 MUTATIONS 



It occurred to us that these were matters that could be approached 

 experimentally — the matter of access to the human gonads and to the 

 human fetus. Unfortunately, I do not yet have more than one piece 

 of incomplete data to present, but we are going to go on with these 

 studies, as the opportunity presents itself. 



With regard to the fetus, what is required is a therapeutic abortion 

 being performed early in pregnancy, by a transabdominal incision so 

 the fetus would not be macerated. Caffeine must be given before the 

 operation to establish a high plasma level. 



With regard to the gonads, we have two approaches. There are cases 

 in which there is surgical indication for removal of both ovaries. In 

 those cases, we propose to have one ovary removed first, to use as a 

 tissue blank, then to make an intravenous infusion of caffeine before 

 removing the second ovary. In the male, we have a similar possibility, 

 when there is metastatic cancer of the prostate, and the surgical indi- 

 cation is for removal of both testes. 



We carried out such an experiment in one patient, an 82-year-old 

 man with prostatic cancer.* One would have liked to do the experi- 

 ment in a patient in the reproductive age group, where there would be 

 much less atrophy and fibrous replacement of the testicular tissue. 

 With patience, we will eventually find such a patient. In the present 

 instance, under spinal anesthesia, the control testis was removed and 

 then an intravenous infusion of 500 mg of caffeine was given. This is 

 a normal therapeutic dose if one were using caffeine as a respiratory 

 stimulant. It is equivalent to about four cups of coffee. Higher doses 

 could safely be given. 



After a period of ten minutes for equilibration, the remaining testis 

 was removed. The blood supply of the second testis was not disturbed 

 during removal of the first. Our analyses showed that the plasma level 

 established was about 19 mg/1. The equilibrium level at complete 

 distribution in the body water should have been approximately 13 

 mg/1, from which we deduce that complete equilibration with the body 

 water of all organs had not yet taken place in the ten-minute period. 

 This is borne out by the fact that in the tissue water we found a 

 lower concentration than in plasma. Slow equilibration is to be expected 

 on the basis of the blood supply of the testis. Tissues with the most 

 abundant blood supply obviously equilibrate first, other tissues more 

 slowly. The testis, compared with many other body tissues, has a rela- 

 tively poor blood supply. 



*I am indebted to Drs. Roy Cohn and Joseph Hart for their co-operation. 



