230 MUTATIONS 



used in the sample census of employment has, or can have, data which 

 permit it to obtain information on socio-economical conditions of the 

 people belonging to the sample. It covers the economic situation, em- 

 ployment, and so on. It is a complete census questionnaire, and every 

 question can be put in the calculating machine, so you can do any- 

 thing you want. 



Lederberg: Would I be permitted to raise another but related issue? 

 It may cut across caffeine. 



Neel: Have you finished now. Dr. Goldstein? 



Goldstein: I have extracted everything there is, I think. I will add 

 just one point. Many pharmacologists are concerned about the in- 

 discriminate use of drugs in the population, with respect to many 

 potential toxic actions of drugs. I think it worth while to point out 

 that although we still know very little about this, we could take what 

 we do know as a further indication against the indiscriminate use of 

 drugs on the ground that some of them might be potential genetic 

 hazards. 



Lederberg: I wanted to bring up a related point. There is a good 

 deal of interest in this in view of the etiology of mongohsm, and I 

 think it may be apropos to indicate that there are a number of alka- 

 loids — I don't remember whether caffeine is included among them — 

 that have effects on the spindle of dividing cells. Indeed, if one were 

 to calculate how one should experimentally produce mongolism in man, 

 it would be by the administration of colchicine or other similar spindle 

 inhibitors, presumably quite possibly immediately after impregnation, 

 at the time of reduction division. I don't know at what time this 

 applies in man. Do you know. Dr. Russell, just when reduction 

 division takes place in the human egg? 



Russell: In the mouse and, I believe, in man, sperm entry occurs 

 when the egg is in metaphase of the second meiotic division. Thus, 

 treatment after impregnation would presumably be too late to cause 

 meiotic nondisjunction. However, important chromosomal disturbances 

 can be induced during cleavage. Mrs. Russell (52) has been able to 

 induce XO mice by irradiation between sperm entry and the first 

 cleavage. She is also getting some evidence, although it is too early to 

 say for sure, that XO can be induced by irradiation of sperm prior to 

 entry. 



Lederberg: Since there is the age dependence with respect to the 

 mother in mongolism in man, an adult woman is presumably a target 

 for such agents. Colchicine is used therapeutically; in fact, not so 

 very rarely it is a specific for gout. It is one of the earliest specific 



