28 JOHN H. NORTHROP 



whereas influenza virus grown on mouse lung does not. The mouse-lung 

 virus, on the other hand, reacts with normal mouse antiserum but not 

 with normal chicken antiserum. After a single passage through chicken 

 embryos the mouse virus reacts with normal chicken protein antiserum. 



The results of Gye and Purdy with Fujinama tumor virus from dif- 

 ferent hosts are very similar to those found by Knight for influenza 

 virus. In both cases the results agree with the predictions based on the 

 analogy between the formation of viruses and normal proteins. 



It is not necessary to assume that any appreciable amount of pre- 

 cursor is present at any one time since it would serve its purpose as a 

 link between the synthetic and specific part of the reaction even though 

 it were only present in traces as an intermediate product. 



Luria, Delbriick, and Anderson (1943) were unable to find any large 

 molecules, comparable to those of the virus, in uninfected cells. They 

 consider that this result proves that no precursor exists. There is no 

 necessity, however, for the precursor to be of the same molecular weight 

 as the virus since association of proteins to larger molecules is known to 

 occur readily. This step is quite different from the synthesis of the 

 primary bonds in the smaller units (Northrop, 1938). 



Adaptation of Viruses.* In certain cases inoculation of a different 

 host results in the production of a different virus after a longer or 

 shorter time (equine encephalitis, yellow fever). This result may also 

 be accounted for on the basis of a precursor. Assume that Host i con- 

 tains Precursor Pi and that Host 2 contains a slightly different precur- 

 sor, P2. The original virus forms more of itself by reaction with Pre- 

 cursor Fi but forms more or less of a slightly different virus, V2, as well 

 as more of itself, by reaction with Precursor Pg- The reaction in Host 

 I is Pi + ^1 -* Vx. In Host 2 three reactions occur, P2 + ^1 -» ^1 ; 

 P2 + ^1 ~^ ^2 ; also P2 + f^2 -^ V2. If the production of Fi and V2 pro- 

 ceeds at exactly the same rate, both will be formed indefinitely. It is 

 extremely improbable that two such reactions have exactly the same 

 rates. If the rates differ, that reaction with the higher rate will eventu- 



* Sudden changes in the properties of a virus are usually referred to as "mutations" 

 of the virus. As far as the writer is aware, there is no evidence to indicate whether the 

 mutation occurs in the virus or in the host cell. The experiments show that a different 

 virus appears as a result of some reaction in the host-virus system, but whether this is 

 due to a mutation in the host cell which then produces a different virus, or a mutation 

 in the virus itself, cannot be determined. If the mutation occurred first in the virus, it 

 would be expected that a chemically modified virus would reproduce itself, but as dis- 

 cussed above, it does not. Attempts to cause mutation by irradiating tobacco mosaic 

 virus were also unsuccessful, whereas mutations did arise if infected leaves were ir- 

 radiated (Kausche and Stube, 1939). 



