78 Essays in Biochemistry 



Pirie's recent contribution and definition with gratitude. The phe- 

 nomena which I shall discuss seem best described by the term "death." 

 This is to be understood as signifying the situation which occurs when 

 cells have lost one or more of the attributes included in the minimal 

 definition of life or living presented above. More particularly, I shall 

 then refer to cells as "dead" when they have lost the power to multiply. 



Of course according to this definition the brain of a man is dead 

 from the moment of birth. I would refer to Pirie all quibblers who 

 have this type of example and argument to offer. On the other hand, 

 it will be recognized that in the field of microbiology this definition is 

 actually in common use. For example, one distinguishes between the 

 bacteriostatic action of the sulfonamides and the bactericidal action of 

 penicillin on the basis of what happens to the ability of the treated 

 cells to form colonies. One speaks of the killing and lethal action of 

 ultraviolet irradiation despite the now-well-known gamut of restoring 

 treatments which bring the dead cells to life, i.e., restore the ability 

 to multiply. I shall use the words "death" and "dead" in this way, 

 even though such a use leads to some curious formulations. 



Several years ago it was discovered by Wyatt and myself that a 

 group of bacterial viruses, the T2, T4, and T6 bacteriophages, con- 

 tained a new pyrimidine, 5-hydroxymethylcytosine. 2 This substance 

 was not present in detectable amounts in the host cell, Escherichia coli, 

 and it therefore appeared that we were dealing with the first instance 

 of a building block unique unto a virus. A study of the metabolic 

 relations of the pyrimidine was then begun. 3 Among other questions, 

 we wished to see if 5-hydroxymethyl derivatives of cytosine and uracil 

 could be converted to the 5-methyluracil, thymine. A thymine-requir- 

 ing strain of E. coli, called 15 T -, was obtained and was tested for the 

 ability to use the hydroxymethylpyrimidines. It was found that the 

 mutant organism was incapable of this conversion. 



Ordinarily the thymineless mutant might have been dropped at this 

 point. However, we routinely infect our bacteria under various con- 

 ditions, and we attempted to do this with strain 15 T -, using the bacterial 

 virus, T2. To the surprise of my collaborator, Miss Hazel Barner, and 

 myself, infection of 15 T - in the absence of exogenous thymine led to 

 the synthesis of virus and virus deoxyribonucleic acid (DNA). Indeed, 

 it was found that, in the absence of thymine in the medium, infected 

 cells synthesized and accumulated only thymine and hydroxymethyl- 

 cytosine, and were in the interesting position of making only those 

 pyrimidines which the bacterium appeared unable to make before 

 infection. 4 This result has led us to a closer scrutiny of the properties 



