The Origin of Specific Proteins 103 



This disease leads to blindness and apparently represents a condition 

 in which the gene for tyrosinase was ahnormally provoked to activity. 

 The chick neural retina, which was cultured in vitro, had of course 

 not heen exposed to those stimuli that hring about melanosome for- 

 mation in melanocytes. Nevertheless, pigment granules superficially 

 resembling those of melanocytes, as viewed with the light microscope, 

 were formed. On examination with the electron microscope, however, 

 these granules proved to be quite different in basic structure. Evi- 

 dently the formation of pigmented melanosomes requires the inte- 

 grated activity of several genes in addition to the one for tyrosinase. 

 Any one of these genes functioning at the "wrong" time or in the 

 "wrong" cell would probably lead to abnormal cell differentiation. 

 Perhaps the most instructive inference that can be drawn from these 

 experiments is that inactive genes in cells are not lost and may be 

 abnormally aroused to activity by suitable stimuli that lie outside 

 the normal experience of the cell. 



Chromosomal dWerentiation 



If we are to understand the nature of cell differentiation, in fact, 

 of all embryonic development, it is essential to elucidate the mecha- 

 nism by which primary gene function is controlled. The previous 

 observations on the role of genes in melanocyte differentiation and 

 on the synthesis of tyrosinase have served to emphasize the critical 

 dependence of gene activation on the physical-chemical composition 

 of the cell. In view of the crucial importance of this subject, it is 

 surprising that so few investigators have turned their attention to it. 

 The problem is very difficult, of course, but some promising avenues 

 of investigation have been opened. Before discussing these, it is de- 

 sirable to emphasize that the genes are part of a chromosome in higher 

 organisms — and the chromosomes are the most complicated organelles 

 of the cell. In addition to desoxy ribonucleic acid ( DNA I , the chromo- 

 somes contain protein in at least two general varieties, ribonucleic 

 acid (RNA), polyamines, lipids, and perhaps other substances. From 

 studies of viral genes (Cohen, 1957) we infer that DNA can function 

 even though it is not integrated into complicated structures like 

 chromosomes. What then is the function of these accessory substances 



FIG. 2. Electron micrograph of pigmented retina of pink-eyed black mouse 13 days 

 post partum. Fixed in osmic acid, embedded in EPON-812. stained with uranyl 

 acetate. Note the disorganized arrangement of the fibrils and the irregular shape 

 of the melanosomes. This peculiar melanosome structure is an effect of the gene 

 for pink-eye. (Courtesy of Dr. Frank H. Mover.) 



