Longevity of Man and his Tissues 
moment, though some would locate the cause of Simmonds’ 
disease, which has some characters of a reversible senescence, in 
the pituitary hypothalamic system, nobody has apparently 
ever produced ageing effects by giving a nerve cell poison or by 
experimental injury to the brain. It may be that the effects of 
these are too local or too widespread. And there for the moment 
the matter must rest. 
Somatic mutation is today a more popular theory than mere 
loss of cells. My colleague Mr. Maynard Smith has attributed 
its popularity—rightly I think—to three things: the fact that 
mutation in clonally-dividing cells would eventually produce 
ageing if nothing else did, the fact that a theory which is cousin 
to cancer research and radiobiology is a sure grant-winner, and 
the fact that it lends itself to the construction of elaborate 
mathematical models by non-biologists. If we widen the field 
to include not only point mutation but all possible copying 
errors, including deletions, aneuploidy, cross-linking and 
chromosome anomalies, then this group of theories might now 
secure a majority vote. The majority is not always right, 
however. In favour of the faulty-copying hypothesis are the 
apparent age-accelerating effect of low doses of radiation, the 
recent finding that some but not all chemical mutagens shorten 
life in much the same way, and the appearance of several papers 
suggesting that aneuploidy in somatic cells increases with age. 
Against the hypothesis are the huge somatic mutation rate 
which would be required to account for the observed rate of 
ageing, and the fact that if point mutation were the sole process 
involved, the life of a haploid should be vastly inferior to that of 
a diploid. In amphibia this is true, but haploid amphibia are 
poor things, and in the gall wasp Habrobracon haploid and 
diploid males have the same order of lifespan, though the 
former are far more radiosensitive. 
If generalized mutagenesis were the main cause of our ageing, 
I would feel unoptimistic about the possibility of interference 
with it. It need not, however, be generalized in order to be a 
timekeeping mechanism—if the important error were confined 
to one system it might well be possible to gain a few years 
223 
