5IO W. F. LOOMIS 



and his colleagues have shown that insulin has the structure given in 

 Fig. 2. A glance at this structure shows that the "one gene, one enzyme" 

 theory must include the incredible fact that " one gene " can contain the 

 10'" or so "bits" of information needed to synthesize such a protein 

 from an amino acid pool. The striking fact is that this insulin-synthesiz- 

 ing gene is present but unused in all the other cells within the body. 

 What is it then that selects which genes are activated where ? What are 

 the activating agents ? Whence do they come, and how do they reflect 

 the embryo-as-a-whole with all its nearly magical powers of self- 

 regulation ? 



Even single-celled animals are capable of demonstrating selective gene 

 activation, for Sonneborn [i] has shown that paramecia possess eight 

 different sets of flagellal-protein-synthesizing genes, but the expression of 

 one set automatically inhibits the expression of the remaining seven. It is 

 as if a Paramecium were a player piano with eight different tunes stored 

 on rolls within the piano stool. The selection of any one tune for conversion 

 from genotype to phenotype automatically prevents the expression of the 

 other seven rolls. 



Most of the gene-activating agents we know today come under the cate- 

 gory of maturation hormones, chemicals that activate long-dormant 

 genes during metamorphosis or adolescence. This paper will not consider 

 the various steroid, amino acid and protein hormones that fall into this 

 category, for clearly they are not responsible for the beginnings of develop- 

 ment when the complex glands responsible for their manufacture are not 

 yet present. Simple animals such as hydra contain no endocrine glands 

 and indeed no circulatory system, yet they demonstrate cellular dif- 

 ferentiation and produce seven different types of adult cells from their 

 original zygote. Clearly there is a chemical progression to development, a 

 series of causes where early effects produce later results almost auto- 

 matically as envisioned long ago by Aristotle in his famous passage from 

 De Generatione Aniwalium: 



"It is possible, then, that A should move B, and B move C: that in 

 fact the case should be the same as with automatic machines shown as 

 curiosities. For the parts of such machines while at rest have a sort of 

 potentiality of motion in them, and when any external force puts the first 

 of them in motion, immediately the next is moved in actuality." 



What then is "A" in Aristotle's list, the agent that operates even in the 

 blastula and gastrula ? How can the ecto-, endo-, and mesoderm differ so 

 much from each other at such an early date when they were all descended 

 from the zygote just a few cell generations before ? My purpose in this 

 lecture is to propose the hypothesis that Artistotle's "A" is in fact carbon 

 dioxide, and that carbon dioxide tension — pCOo — is the first self-produced 

 regulator in embryological development. 



