VIRUSES, CANCER, GENES, AND LIFE — STANLEY 369 



possess, coded within its 1,000 or so nucleotides, not only all the 

 information that is necessary to bring about in the host cell the 

 production of more of this same nucleic acid, but also apparently 

 the de novo synthesis of its own characteristic and highly specific 

 protein with which it eventually coats itself. This work provides 

 wonderful evidence for a direct relationship between specific nucleic 

 acid and specific protein synthesis and makes it possible to consider 

 virus and gene action, including their relationships to cancer and to the 

 nature of life, in terms, not of nucleoprotein structure, but of nucleic 

 acid structure. We see, most importantly, that viruses, cancer, genes, 

 and life are all directly dependent upon the structure of nucleic acid. 



It may be calculated that a thousand-unit polynucleotide linear 

 chain consisting of a coded repeat of only four different components, 

 adenine, guanine, cytosine, and uracil, in the same ratio as exists 

 in tobacco mosaic virus nucleic acid, could form about 10 590 different 

 arrangements. This number is so large that it is incomprehensible. 

 Even a hundred-unit polynucleotide chain of this composition could 

 exist in about 10 57 different arrangements and this number is vastly 

 larger than the total of all living things on earth and in the oceans. 

 We have, therefore, in this structure consisting of the four chemicals, 

 adenine, guanine, cytosine, and uracil (thymine in the case of de- 

 oxyribonucleic acid), repeated many times over in unique fashion, 

 the code for every bit of life on earth and in the sea. When a normal 

 cell becomes a cancer cell there is undoubtedly a change in this 

 structure within the cell. It is of interest to note that many anti- 

 cancer compounds are antimetabolites for these chemical components 

 of nucleic acids. And in our laboratory Litman and Pardee made 

 the very important observation that the incorporation of 5-bromouracil 

 into a bacterial virus in place of thymine resulted in the production 

 of the highest percentage of mutants ever recorded. Certainly all 

 this information plus the discovery that virus activity can be a 

 property of nucleic acid and our knowledge of relationships between 

 viruses, cancer, genes, and life now make it obvious that the common 

 thread upon which all of these depend is specific nucleic acid structure. 

 Therefore, this declaration of dependence revolves around nucleic acid. 



I believe that the elucidation of the structure of nucleic acid in all its 

 aspects is the most important scientific problem we face today. It 

 is vastly more important than any of the problems associated with 

 the structure of the atom, for in nucleic acid structure we are dealing 

 with life itself and with a unique approach for bettering the lot 

 of mankind on earth. It is possible that the solution of this scientific 

 problem could lead eventually to the solution of major political and 

 economic problems. Never before has it been possible to realize 

 so fully our utter dependence upon the structure of nucleic acid. 



