March 3, 1916] 



SCIENCE 



301 



of fibroblasts and blood vessels into the 

 transplanted tissue may, according to Rus- 

 sel and Woglom (in the case of tumors) and 

 Peyton Rous (in the ease of embryonic 

 tissues) be delayed or else diminished in 

 amount. However, even in the latter case 

 the defence of the organism against the 

 foreign tumor cells may principally con- 

 sist in an attack by lymphocytes and other 

 leucocytes (B. E. Tyzzer). 



As the most probable explanation for 

 these phenomena, we have proposed the fol- 

 lowing theory:^ The mutual chemical in- 

 compatibility of the body fluids of one 

 individual and the tissues of another, which 

 we could especially clearly demonstrate 

 after homoiotransplantation of pigmented 

 skin, leads to changes in the metabolism of 

 the tissues, resulting in the production of 

 homoio- and heterotoxins, which if they do 

 not exceed a certain strength, disturb the 

 normal functions of the transplanted 

 tissues to some extent without, however, 

 interfering seriously with their life. But 

 the abnormal products formed attract the 

 lymphocytes and in certain cases also other 

 leucocytes, and alter the reaction of the 

 fibroblasts, which latter are induced to pro- 

 duce dense fibrous tissue. If the poisons 

 become more active, they may directly in- 

 jure tissues to such an extent that growth 

 and life become impossible. 



These conclusions, as we believe, also 

 throw light on so-called chronic inflamma- 

 tory processes of various organs where a 

 changed metabolism of the cells, and per- 

 haps also poisons produced by microorgan- 

 isms, may induce fibroblasts to form fibrous 

 bands and attract lymphocytes, thus lead- 

 ing to processes of cirrhosis. In a similar 

 way, in the case of tumor immunity, which, 



5 Leo Loeb, ' ' The Influence of Changes in the 

 Chemical Environment on the Life and Growth of 

 Tissues," Journal American Medical Association, 

 Vol. 64, February, 1915, p. 726. 



for instance (as Clowes and Gaylord have 

 shown), exists in the case of the retrogres- 

 sion of tumors, substances produced as a 

 result of immunization and which circulate 

 in the body fluids alter the metabolism of 

 the tumor cells, which in turn influence the 

 activity of the lymphocytes and fibroblasts 

 in a way similar to normal tissues in a 

 strange host. This theory correlates the 

 immunity against tumor and tissue growth 

 with the immunity against certain sub- 

 stances and non-growing foreign cells. "We 

 have also in the former case to deal with 

 the production of immune substances, 

 which, however, in the case of homoiotrans- 

 plantation, are usually not such that they 

 directly destroy the foreign tissues, but 

 merely lead to an alteration of their metab- 

 olism and to the production of substances 

 which change the behavior of the host cells. 

 "We no longer need to assume a primary 

 tissue alteration following the homoiotrans- 

 plantation. 



It remains for further investigations to 

 decide to what extent the presence of for- 

 eign tissue leads to the direct production 

 of what we could call primary homoio- and 

 heterotoxins as the result of the interaction 

 between the preformed constituents of the 

 body-fluids and the foreign cells, and to 

 what extent it leads to the production of 

 secondary homoio- and heterotoxins — the 

 immune substances — as the result of im- 

 mune reactions. At present it appears 

 probable that both these substances play a 

 role. In vitro the toxicity of body fluids 

 of foreign species is apparently not very 

 marked, as we, as well as Lambert, found. 

 The toxicity is certainly less than we should 

 expect, considering the fate of tissues after 

 heterotransplantation. "We must, however, 

 take into account the fact that the amount 

 of body fluid and especially of toxin acting 

 on the tissue in vitro, is extremely small as 

 compared with the quantity acting in the 



