Health and Disease 
I would like to ask Dr. Koprowski his opinion of the relevance 
of our newer knowledge of polymorphism to the problem of 
resistance to infectious disease. It is a most important discovery 
that all large molecules—polypeptides, polysaccharides, and of 
course polynucleotides—exist in chemically and structurally 
variant forms in different individuals and these variant forms 
are not merely rare freaks maintained by mutation, but are 
present in the population in frequencies far higher than could 
possibly be maintained by mutation. According to genetical 
theory, which Haldane or Huxley may be able to uphold, all 
these variants are of medical significance, and if that is so, it 
must be one of the tasks of medicine to find out what that sig- 
nificance is. For example, the existence of these variants may 
make it virtually impossible for any one infective agent to 
overcome every member of the human population; there will 
always be a residue of individuals resistant to infection, no 
matter what the infective agent is. This indeed may be, as I 
think Haldane first suggested, the main reason for the existence 
of this genetical diversity. 
Pincus: ‘There is an ancient theory of ageing which should 
be mentioned, which dates back to certain ideas about rejuve- 
nation. Essentially, it is dependent on the fact that a decline in 
secretory capacity of certain endocrine glands is accompanied 
by signs of infirmity. For some years we have been trying to 
find out about the situation in these glands. Among the steroid 
hormones, there is only one group, the 11-deoxy-17-ketosteroids, 
that tends to decline markedly with advancing age in the human 
species, both male and female. It is very interesting that these 
particular compounds appear to derive biogenetically from just 
one substance, 17-hydroxy-pregn-5-enolone. This is a key 
substance so far as hormones in ageing are concerned, because 
the rate of conversion of this substance to the 11-deoxy-17-keto- 
steroids declines with advancing age. We might try to find a 
method of keeping up this rate of conversion. I am inclined 
to think that this among others offers a chance for what 
Medawar calls replacement therapy—a replacement therapy of 
a very interesting nature. 
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