Genie Control of Development 337 



diflFerentiating processes are influenced mainly by cytoplasmic prede- 

 termination in the egg. After a certain time, the turning point, sexual 

 differentiation changes into that of the opposite sex. The time of 

 occurrence of the turning point is responsible for the degree of inter- 

 sexuality: late turning point, low-grade intersexuality; earlier turning 

 point, higher degree, extending finally to complete sex reversal. Thus 

 the timing of a developmental, determinative event is proportional 

 to the imbalance produced by wrong dosages. In the presence of two 

 simultaneous and competing chains of reaction, the normal balance 

 (F/M dosage) controls the process whereby either one or the other 

 product of reaction first reaches the threshold of action (i.e., decision 

 of the sex alternative); the wrong balance, or imbalance through non- 

 normal dosages, changes the relative velocities of the two reaction 

 chains, with the result that the wrong one (in regard to chromosomal 

 constitution ) overtakes the right one at the turning point. In the early 

 days of experimentation, the valencies of M and F were assumed to 

 be genie quantities, thus enabling a kinetic relation between dosage of 

 gene and its action. Though we no longer call F and M individual 

 genes, this dosage effect upon the kinetics of genie action still remains. 

 It is obvious that this analysis led, at that time, to the deduction that 

 all genie actions are subject to dosage effects upon the kinetics of that 

 action; which again meant, within the general idea of the classic gene, 

 that mutants should be dosage differences. Thus dosage became a 

 major problem of genie action. 



Within the general sphere of sex determination, the role of dosage 

 could be carried another step farther when actual, not just inferred, 

 dosages became available beyond the 1X-2X relation. Standfuss 

 already had found in pre-Mendelian days that species backcrosses in 

 Lepidoptera produce what I later called intersexes. After Federley 

 ( 1913) discovered the triploidy of such hybrids, and after I had estab- 

 lished the balance theory of sex determination (1912), at that time 

 still believing that in Lymantria the F factors are located in the auto- 

 somes (they are in the Y-chromosome), Standfuss (1914) realized 

 that his intersexes were triploid ones with a disturbed F/M balance, 

 because three sets of autosomes (3F) were confronted by two 

 X-chromosomes (2M) which gives a balance of 3:2 instead of 2:1. 

 Thus a dosage situation for both F and M factors was established. The 

 most elegant example of this type was found later in Drosophila by 

 Bridges ( 1922 ) , when he discovered in this fly triploid intersexes the 

 explanation of which was similar to that of the lepidopteran inter- 

 sexes. The Drosophila technique allowed combinations of many dif- 



