Ill XENO-INDUCTIONS 447 



either in "active" human serum, or in the same serum inactivated by heating it 

 thirty minutes at 65". In the first case, the cell-material, fixed by ethanol, shows a 

 predominating notogenic eflfect, in the second, the acrogenic inductions become 

 predominant. The difference could be due to a notogenic agent present in the 

 active serum and adsorbed on the HeLa cells, so that a maskage would occur. The 

 Finnish authors have a tendency' to equate the two main groups of inductions 

 to a mesodermal and a neural inductor, but there is no firm basis in favour of 

 this oversimplification. It is by far preferable to maintain the concept of the two 

 main types of induction, with the complexity inherent to them, which does not 

 exclude that the corresponding agents can be relatively simple. 



What do we know concerning the biochemical nature of the agents responsible 

 for xeno-inductions? It is certainly a noteworthy achievement to have discovered 

 that they are so far uniformly proteins, but, it is scarcely necessary to stress the 

 vagueness of this conclusion. We are ignoring whether or not the agent contained in 

 different organs, and causing the same type of induction is the same protein, 

 whether the efBciency is bound to some definite amino acids, or to sulfhydril 

 groups, whether some structural property is linked with the type of induction. In 

 addition, the relation with nucleic acids remains puzzling. It is certainly of con- 

 sequence that several remarkable inductors can be obtained as (ribo)nucleo- 

 proteins, even if a further fractionation turns in favor of the proteic moiety. There 

 is also the possibility that one agent would be more complex than the other. This 

 eventuality, as seen above, is not excluded by Tiedemann. For Vahs (19573), the 

 notogenic complex is fundamentally represented by proteins — a contention also 

 admitted by Yamada (1958a, b) — but is possibly associated with enzymes or RNA. 

 He also assumes that the acrogenic agent is a most ubiquitous ribonucleoprotein 

 which would be primary in the egg, although often masked by the notogenic 

 complex. What it may be, we do not know whether the active macromolecules 

 originate from the epithelial cells of the organ, or from its connective tissue and 

 vascular epithelia, whether they are related to the differentiated structures of 

 some cells, or whether they work in these as metabolites or as enzymes. 



In presence of these and other persisting difficulties, it is probably not an idle 

 task to push the discussion in the direction of the relation to normal mechanisms of 

 induction. The first question to consider is that of a possible identity or relation- 

 ship between the substances extracted from organs and the normal agents of 

 induction. Such an assumption cannot be accepted without caution. It is of course 

 a possibility that the normal inductors subsist in the cells of most tissues, either in 

 their primitive form, or modified, and even that they play during the whole life some 

 unknown but important role. But it is also possible that the xeno-inductors simply 



' This point of view is definitely expressed in a still more recent contribution of Saxen and 

 Toivonen (1958) concerning a further analysis of the inductive power of HeLa cells. They 

 insist that the M-principle, mesodermalizing, is dependent on external factors, i.e., in their 

 experiment, on the nature of the human serum used for cultivation, while the N-principle, 

 neuralizing, is "more stable". It is implicite in their conviction that the inductive agents 

 present in various xeno-inductors and exerting the same effect are necessarily of the same 

 nature, an assumption which, in my opinion, cannot be granted fsee below). 



Lileralure p. 483 



