V GROWTH IN TIME OF THE TOTAL ORGANISM 211 



largement of embryonic chick spleen and liver after implant of grafts of the homologous 

 organ; [3. Increase of mitotic activity of the kidney by injection of kidney brei, and decrease 

 by liver brei; y. Specific transfer of radioactivity from the graft (chicken spleen) to the 

 homologous host tissue, and lack of this transfer to non-homologous tissue (chicken kidney 

 — » chicken spleen) and tissue of different species (mouse spleen —> chicken spleen) ; S. Since 

 embryo extract contains cell debris of all organs, promotion of growth of any explanted 

 tissue in it is to be expected and is generally found. Using extract in which a certain organ 

 was omitted gave the following results. In full embryo extract, the frequency of differentia- 

 tion of tubules of embryonic kidney was greatly reduced as compared to cultures in extract 

 without kidney tissue. Similarly, in full extract, only two of 333 heart fragments showed 

 pulsation (indicative of differentiation of myofibrils) after the fourth day, compared to 

 129 among 349 when heart extract was omitted from the medium. Because of the general 

 antagonism between proliferation and differentiation, inhibition of the latter is interpreted 

 as stimulation of growth by the homologous extract. 



Thus, there appear to be specific influences on growth and differentiation issuing from 

 homologous tissues and active by way of chemical communication. However, the inter- 

 pretation of this evidence is not unequivocal, and explanation in terms of cell-bound 

 "templates" and freely circulating "antitemplates" (as was emphasized by Weiss, 1955b) 

 is to be considered as a working hypothesis. The extrapolation that an antagonism between 

 self-multiplying and growth-inhibiting compounds is a basic and general principle in 

 growth is not proved experimentally. 



5. For these reasons, also assumption (5) is not experimentally proved. 



6. The omission of catabolic loss of generative mass in the model and consequent growth 

 equations appear not to correspond with isotope experiments (p. 148), other physiological 

 determinations of protein turnover (Table 11, p. 200), cell turnover (Table 4, p. 164), 

 etc., which show that this factor is by no means negligible. 



//. The laws governing the rate of the processes summarized in Fig. 19 are unknown. 

 Hence, even if these are taken for granted as growth-regulating factors, any particular 

 function expressing these terms is necessarily arbitrary. 



From the rather elaborate system of equations of the Weiss-Kavanau model, 

 two experimentally verifiable consequences were derived, namely 



J. A calculation of the growth in chickens; — 2. The qualitative prediction 

 that after experimental or pathological disturbances there will be a spurt of 

 growth, and later on restitution of the equilibrium by an oscillatory process 

 with first overshooting the steady-state level. 



With regard to i, Weiss and Kavanau justly emphasize that calculation of one 

 growth curve is no proof for the underlying model, but fitting can be achieved by 

 different equations if a sufficient number of arbitrary parameters is permitted. 



With regard to 2, overshoot phenomena (if these can be found experimentally 

 in compensatory growth) are a general characteristic of reestablishment of steady 

 states under certain mathematical conditions (p. 146). Hence, overshoot is not 

 a consequence of the particular model and equations, but will appear in any 

 open-system model provided these mathematical conditions are fulfilled. 



The value of the Weiss-Kavanati model (as its authors emphasize) is in calling 

 attention to certain possible mechanisms in the intricate process of growth by mathe- 

 matically formulating them. Thus, malignant growth may be interpreted by a 

 loss of control of cell multiplication exerted by cellular feedback (Weiss) and/or 

 "higher" regulatory centers (Druckrey, 1959). Further experimentation suggested 

 by the model may lead to more detailed analysis of the overall process of growth. 



Lileralure p. 253 



