CHEMICAL PATHWAYS 125 



the formation in vitro of the complete virulent virus by spontaneous 

 association of some 3000 molecules of protein and one RNA chain into the 

 well-known structure. 



The association of proteins with lipids and other substances into micro- 

 scopical structures like membranes, fibres, lamellae, mitochondria, etc. . . . will 

 raise other problems which have practically not been touched at the mole- 

 cular level so far. These organelles do not seem to arise de novo, they 

 develop from similar or related pre-existing structures, as if they could only 

 grow by accretion of new material on to structures which insure the cor- 

 rect arrangement of the building blocks. 



The thiol-disulphide equilibrium seems to be determining in the forma- 

 tion of structures. Embryologists have reported on many occasions striking 

 inhibitions of morphogenesis by sulphydril reagents like iodoacetamide 

 (see Brachet, 1946, 1960). Certain of these effects are due to the inhibition 

 of some common SH enzymes, or to the inhibition of mitosis. But more 

 subtle changes in morphogenesis caused by various thiols or disulphide 

 containing compounds certainly reflect processes of a completely diff"erent 

 nature. As a rule, free thiols disturb morphogenesis; on the contrary 

 disulphide substances improve it, if anything. This was observed in widely 

 different morphogenetic processes: development of amphibian embryos, 

 regeneration of the tail in amphibian tadpoles, regeneration of the head of 

 planarians, and cap formation in Acetabularia mediterranea (Brachet, 1959). 

 This last-mentioned case is especially interesting, for the alga consists of a 

 single cell (see p. 50) and the morphogenetic processes here do not depend 

 on cell division or cell migration. Growth continues in the presence of 

 thiols, synthesis of new material is not prevented, but the newly made 

 material does not form the normal macroscopic structure. Instead of a well- 

 shaped hat, the alga develops a swollen club-like structure. It would seem 

 that the thiol-disulphide equilibrium is of great importance for the relative 

 positions in space that the substances synthesized during growth come to 

 occupy. This strongly suggests that when the formation of disulphide 

 bridges is interfered with, proteins cannot associate correctly into structures, 

 either because the folding of the structure proteins themselves is not right, 

 or because disulphide bridges play a fundamental part in the association of 

 constituents — proteins or otherwise — into microscopic structures. 



A new field of study will soon develop here, for the progress of electron- 

 microscopy, X-ray diffraction analysis and light microscopy will certainly 

 make it possible to bridge the gap between biochemistry and morphology, 

 and eventually give the first molecular interpretation of form. 



