192 CELLS, TISSUES, AND ORGANISMS 



tions, fetiiin, has properties of particular interest. It exercises a highly 

 specific effect on mammalian cells in causing them to attach to glass 

 and stretch out to assume the characteristic morphology which is a 

 prelude to reproduction under the conditions of study. This interesting 

 protein fraction fetuin, which is necessary for the growth of isolated 

 mammalian cells under these conditions, is present in particularly high 

 concentration in calf fetal serum, and it has been studied intensively 

 with respect to its physico-chemical properties. So far it has not been 

 possible to fractionate this material into any components with activity 

 equal to or greater than .the original material. \Vhile the electrophoretic 

 and ultracentrifugal characteristics of this protein fraction reveal a high 

 degree of homogeneity with respect to these characteristics, it cannot 

 yet be excluded with certainty that the observed biological activity is 

 due to a relatively minor constituent. Analysis of the molecular nature 

 of this activity has shown that an enzyme such as neuraminidase, which 

 hydrolyzes sialac acid from glycoproteins like fetuin, causes complete 

 loss of fetuin's biological activity. Recently the amino-acid composition 

 of fetuin has been determined (Fisher and Puck, 1960); it is shown 

 in Table I. 



All of the physical, chemical, and biological properties of fetuin so 

 far studied are consistent with the thesis that the alpha-globulin frac- 

 tion of adult mammalian serum contains an appreciable amount of the 

 same material. It has been observed that processes such as extensive 

 wound-healing, which require an appreciable increase in cell division, 

 are accompanied by a rise in the alpha-globulin content of mammalian 

 serum. On the basis of the foregoing discussion concerning the effect of 

 ionizing radiation in inhibiting the reproduction of somatic mammalian 

 cells, one might have expected that whole-body radiation would also 

 cause the body to respond with an increase in alpha-globulin, so as to 

 maximize reproduction of the cell survivors. Just such an increase has 

 now been reported in experiments carried out on mice. 



While early experiments on mammalian cell nutrition disappoint- 

 ingly emphasized the apparent sameness of the nutritional requirements 

 of cells from diverse animal species ( Eagle, 1955 ) and normal or malig- 

 nant tissues, studies with single-cell techniques have uncovered a highly 

 variegated spectrum of nutritional differences (Puck, Cieciura, and 

 Fisher, 1957; Fisher, Ham, and Puck, 1960). In general, hyperploid 

 cells such as the malignant S3 HeLa strain are much more nutritionally 

 self-sufficient than those of normal diploid cells— a fact which may well 

 be associated with the malignancy of the former. Normal human cells 

 are readily differentiated nutritionally from strains of the Chinese ham- 

 ster. Mutants of both Chinese hamster and HeLa cells with altered 

 nutritional characteristics are isolable with ease. An absorbing field of 

 biochemical genetic study of mammalian cells in vitro appears to be 

 available for intensive study. 



