Ontogeny of Immunological Properties 



569 



autolyzed suspensions of liver, kidney or 

 pectoral muscle of adult chickens. Upon 

 examination at 20 days of incubation the 

 total weights of the injected embryos were 

 found to average considerably less than 

 those of the controls. However, the organ 

 corresponding to the antiserum employed 

 showed rather marked relative increase in 

 size. Thus the liver weights averaged 10 per 

 cent above the normal controls and 29 per 

 cent more than the livers of embryos that 

 had been injected with anti-kidney serum. 

 Kidney size in the embryos treated with 

 anti-kidney serum was found to average 28 

 per cent higher than in the embryos treated 

 with anti-liver serum. Experiments by Ebert 

 ('51, '54) on the enlargement of host-embryo 

 spleen by chorioallantoic grafting of adult 

 spleen can be related to this, as he suggests, 

 on the assumption of a release from the 

 graft of certain of the complementary sub- 

 stances which then become incorporated in 

 the host spleen and serve as templates for 

 the synthesis of further splenic substance. 

 There is, then, some evidence of a specific 

 stimulating effect of antibodies. This en- 

 courages further examination of the pos- 

 sibility that specific morphological alterations 

 may be induced in cells by means of anti- 

 bodies. In the above cited experiments of 

 Weiss no alteration of cell type seems to be 

 involved, and in no experiments of others 

 does this possibility seem to have been 

 directly tested. Perhaps the nearest approach 

 to this is the work on changes in morpho- 

 logical and antigenic structure in micro- 

 organisms. It is well known (see Dubos, '46, 

 for references) that certain transformations, 

 such as the smooth to rough change, can 

 be brought about in many kinds of bacteria 

 by growth in immune serum. Cultures of 

 encapsulated organisms, such as the pneumo- 

 cocci or Friedlander's bacilli, growing in 

 media containing the homologous, specific 

 anticapsular antibody, transform to a non- 

 specific, non-encapsulated type. The reverse 

 transformation can also be obtained by 

 growth in an antiserum directed against the 

 non-encapsulated organisms. Motile variants 

 of B. subtilis can be transformed to non- 

 motile, and vice versa, by growth in the 

 corresponding antisera. Reversible changes 

 described as phase variation, as for example 

 in the specificity of the flagellar antigens of 

 various Salmonella species, can be induced 

 by means of homologous antisera. Changes 

 in antigenic specificity have been described 

 also in Paramecium (Sonneborn, '48). The 

 manner in which the antibodies act has not. 



as yet, been fully elucidated in any of these 

 experiments. The various changes also occur, 

 although generally more slowly, in response 

 to other environmental changes or sometimes 

 spontaneously in the absence of controlled 

 or readily detectable environmental change. 

 In the bacteria it is often uncertain to what 

 extent the antibodies act by selectively in- 

 hibiting the types with which they react 

 and thus permit a more rapid growth of 

 the variants in the culture. 



Selective action of this type does not appear 

 to be involved in the experiments on directed 

 transformation of pneumococcal types (see 

 McCarty, Taylor and Avery, '46). This 

 tranformation consists in the conversion of 

 a non-encapsulated (R) variant derived from 

 one specific serological type into a serolog- 

 ically different encapsulated (S) type. The 

 conditions for transformation involve sev- 

 eral factors, including anti-R serum and 

 desoxyribonucleic acid derived from organ- 

 isms of the type into which the change is to 

 be directed. The latter is evidently the direc- 

 tive agent in this transformation. The R- 

 antibodies can be replaced by other agents, 

 such as normal serum and agar semisolid 

 medium, that cause a colonial type of growth 

 of the R organisms. The action of the R- 

 antibodies is interpreted as inducing a type 

 of growth in which local conditions sur- 

 rounding the organisms so modify the cells 

 as to permit absorption or entrance and 

 action of the specific desoxyribonucleic acid. 



There is, then, evidence that antibodies 

 can induce changes in cells, but as far as 

 present evidence is concerned, they do not 

 appear to be directive agents. If the antigen- 

 antibody type of reaction is involved in the 

 phenomena of embryonic induction it could 

 conceivably operate in some manner such as 

 is indicated in the experiments on the trans- 

 formation of pneumococcal types. It is of 

 interest to note, in this connection, that nu- 

 cleic acids, as Brachet ('47) has emphasized, 

 can act as inductors. This might mean that 

 certain specific nucleic acids are liberated 

 from the surface of living cells having spe- 

 cific inductive action in the embryo. This 

 possibility has not, as yet, been examined, 

 but seems worth investigating. On the other 

 hand, the present status of experimentation 

 along this line does not exclude the possibil- 

 ity that natural auto-antibodies may act 

 rather directly as inductive agents, and var- 

 ious schemes could be devised whereby this 

 would entail inactivation of different sets of 

 genes in cells of different tissues. This be- 

 comes similar to the proposals of Sturtevant 



