192 R. A. McCance and E. M. Widdowson 



matter, however, is not quite so simple as that, for the evidence 

 is that our httle pig, who was certainly undernourished, had 

 larger liver cells than those of her big sister or of an adult pig. 

 These contained more protein and "ribonucleic acid and pre- 

 sumably therefore more cytoplasm. The percentage of fat 

 was lower than it was in the cells of the well nourished pig. 

 We have therefore been led to suppose that the lethal factor 

 is not so much the size of the cell as the nature of the material 

 enlarging it. Too much reserve material inside the cell is the 

 trouble, or perhaps too much inside it for too long. This in 

 itself is no "explanation" but it is possible to get a little 

 further by venturing into the modern world of cellular 

 organisation and enzyme chemistry. If the metabolism of 

 the cell is directed more to the handling of reserve materials 

 than to the synthesis of protein and nuclear substances, 

 adaptation and increase of all the enzymes required for the 

 former may be expected to take place (Liener and Schultze, 

 1950; Davies and Yudkin, 1952), as happens if a bacterial 

 colony is subjected to a change of substrate or to some growth 

 inhibitor. This reorganisation must affect both the deoxy- 

 and ribonucleic acids in the nucleus and cytoplasm respec- 

 tively (Brachet, 1954; Gale and Folkes, 1954) and may 

 displace or reduce some of those enzymes within or without 

 the nucleus responsible for processes essential for growth and 

 reproduction. When now the stimulus for reproduction comes 

 the organisation of the cell is not ready for it and readaptation 

 may take some time. This would lead to a slow initial repro- 

 duction rate (as of the large coloured cysts of Hcematococcus 

 pluvialis) and would also explain the possibility of a return 

 to full reproductive activity. The higher organisms are 

 naturally more complicated and all the cells do not succumb 

 equally readily to overnutrition. Some may be protected in 

 various ways. Overnutrition in the higher animals may cause 

 death from its mechanical effects and also from humoral 

 causes (Editorial, 1954) but there must be some reason at 

 cell level why overnutrition kills. One would expect highly 

 specialized cells like those of the pancreatic islets to go first, 



