PROBLEMS OF MEASUREMENT OF MUTATION RATES 11 



any age dependence; there will just be a constant proportion of mutants 

 added. But the mutations occurring in the stem lines themselves will 

 give a linear dependence on age, just as mutants accumulate in the 

 chemostat. The stem line is the natural chemotsat. It is a turbidostat, 

 in fact, because we are not clear what is regulating it. 



Novick: Is the maturing of a spermatogonium a random process, or 

 is it nonrandom? 



Lederberg: It is very nonrandom. 



Atwood: Yes. 



Lederberg: There has to be another term to this formula, because 

 this takes account only of the mutations in the stem cells. These are 

 the mutations that occur during the growth, the original laying down 

 of the stem cell population. These are mutations that occurred dur- 

 ing the subsequent multiplication of the stem cells. But, if you then 

 have an additional element, you are quite right that there are stem cell 

 progeny, which, however, have only limited extent, and once they are 

 formed, they then disappear, but mutations may occur there, so you 

 have to add another term, which is a constant term, which is the size 

 of the progeny, which will be the 4. 



Stem: Would you clarify this question of randomness versus non- 

 randomness of the spermatogonia producing sperm which was just 

 discussed? 



Atwood: As I understand it, the question was just how regular is 

 the cell lineage in the production of sperm from gonial cells. 



Novick: I thought you told me it was random, that is, the progeny 

 of a given cell might all become mature sperm, and that little line 

 dies out. 



Atwood: The way it is usually visualized is that one daughter cell 

 stays as a gonial cell, and the other one goes on to make four spenn. 



Lederberg: Yes. The one that stays gonial is the one 2 over X, and 

 then, in addition, you need a term for the addition of sperm from 

 that gonial cell. They have no further future but mutations could 

 occur there, and that is the term, 1 "log" 4. 



Goldstein: With advancing age, it is easy to show that the only 

 ones of importance are the mutations in the germ cell line. 



Stern: May I ask, Dr. Russell, didn't Oakberg find that this is really 

 much more complicated, that the stem cell divides several times and 

 that some of the resulting cells return to the state of stem cells? 



Russell: In the rat, Cleremont and LeBlond (7) estimated that 

 when a stem cell differentiates it produces 64 spermatozoa. Oakberg 

 (26) estimates that, in the mouse, a differentiating stem cell produces. 



