66 Inside the Living Cell 



Fig. 14) and then to grow it in the presence of this compound. Quite 

 a large number of such mutants have been produced, all of which 

 lack the enzyme which is required to make the missing substance. 



It is inferred from this that in each case one gene has been damaged 

 by X-rays and this gene controls the formation of one enzyme. Occa- 

 sionally strains of the fungus are produced where two or more sub- 

 stances must be added to the basal medium to enable them to grow. 

 But it can be shown by cross-breeding experiments that the genes are 

 distinct and it is only a matter of chance that two have been damaged 

 in the same spore. A gene that has been lost can be replaced by cross- 

 breeding with a strain which possesses it. This is the clearest evidence 

 we have for a close, and probably a one-to-one, relation between 

 genes and enzymes. According to this the gene essentially contains 

 the pattern which guides the formation of the enzyme. It is probable 

 that it carries this pattern as a sequence of bases in dna, as described 

 in Chapter V. If this is so, it is evident that damage to the pattern of 

 bases in dna will clearly interfere with the ability of this material to 

 pass on its message. The damage might be only damage to the bases 

 at one or two critical points which would interfere with the code; or 

 it might be a break of the dna thread which would prevent an intact 

 protein being formed. Many of the stages by which genes bring about 

 their effects still remain to be worked out. It has been sometimes pos- 

 sible in micro-organisms to track down the whole chain of reactions 

 by which a particular chemical substance is formed, in a number of 

 stages, each of which require a special enzyme. It is found that each 

 step is controlled by a separate gene. If this gene is damaged by 

 X-rays, the progeny of this individual is unable to perform the cor- 

 responding process, so that the whole sequence of reactions is broken 

 at this point. If the substance which the organism is now unable to 

 make is added artificially, growth will proceed normally; but other- 

 wise the substance which is formed as an intermediate, just before the 

 break in the sequence, accumulates because the organism is unable 

 to make use of it. By experiments of this kind, many complex 

 sequences of reactions have been worked out. 



Another example of the control of protein synthesis by genes has 

 been found in connection with *sickle cell anaemia', a human disease 

 which is inherited according to the Mendelean rules and is therefore 

 under genie control. It has been found by V. M. Ingram that the 

 haemoglobin extracted from sickle cells differs from normal human 

 haemoglobin in a single amino acid only out of the 300 present in the 

 molecule — one glutamic acid group in the normal haemoglobin being 

 replaced by valine. 

 1 Nature 180, 326, 1957. 



