[962 F.H.C. CRICK 



Linear order in which the amino acids are found in the polypeptide chain. 

 Tins seems highly likely, especially .is it has been shown that in several sys- 

 tems mutations affecting the same amino acid are extremely near together 

 on the genetic map. The experimental proof of the co-linearity of a gene 

 and the polypeptide chain it produces may be confidently expected within 

 the next year or so. 



There is one further general question about the genetic code which we 

 can ask at this point. Is the <:odc universal, that is, the same in all organisms? 

 Preliminary evidence suggests that it may well be. For example something 

 very like rabbit haemoglobin can be synthesized using a cell-free system, 

 part of which comes from rabbit reticulocytes and part from Escherichia 

 C('// \ This would not be very probable if the code were very different in these 

 two organisms. 1 low ever as we shall see it is now possible to test the univer- 

 sality of the code by more direct experiments. 



In a cell in which DNA is the genetic material it is not believed that DNA 

 itself controls protein synthesis directly. As Watson has described, it is be- 

 lieved that the base sequence of the DNA - probably of only one of its chains 

 - is eopud onto RNA, and that this special RNA then acts as the genetic 

 messenger and directs the actual process of joining up the amino acids into 

 polypeptide chains. The breakthrough in the coding problem has come 

 from the discovery, made by Nirenberg and Matthaei 6 , that one can use 

 synthetic RNA for this purpose. In particular they found that polyuridylic 

 acid - an RNA in which every base is uracil - will promote the synthesis of 

 polyphenylalanine when added to a cell-free system which was already 

 known to synthesize polypeptide chains. Thus one codon for phenylalanine 

 appears to be the sequence UUU (where U stands for uracil: in the same 

 way we shall use A, G, and C for adenine, guanine, and cytosinc respec- 

 tively). This discovery has opened the way to a rapid although somewhat 

 contused attack on the genetic code. 



It would not be appropriate to review this work in detail here. I have 

 discussed critically the earlier work in the review mentioned previously 1 but 

 such is the pace o{ work 111 this field that more recent experiments have 

 already made it out ot date to some extent. However, some general con- 

 clusions can safely be drawn. 



The technique mainly used so far, both by Nirenberg and his colleagues'' 

 and by Ochoa and his group 7 , has been to synthesize enzymatically « ran- 

 dom 1 polymers of two or three of the four bases. For example, a polynu- 

 cleotide, which I shall call poly (U,C), having about equal amounts of 



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