VARIATION DUE TO CHANGE IN THE INDIVIDUAL GENE

In this remarkably prescient analysis, Muller lays out the

paradoxical nature of the genetic material. It is apparently both

autocatalytic (i.e., directs its own synthesis) and heterocatalytic

(i.e., directs the synthesis of other molecules), yet only the

heterocatalytic function seems subject to mutation. With this, he

defines the key problems that must be solved for a successful

chemical model of the gene.

Muller also anticipated the ultimate development of molecular

genetics:

That two distinct kinds of substances — the d'Hérelle substances

(NOTE: viruses) and the genes — should both possess this most

remarkable property of heritable variation or "mutability," each

working by a totally different mechanism, is quite conceivable,

considering the complexity of protoplasm, yet it would seem a

curious coincidence indeed. It would open up the possibility of two

totally different kinds of life, working by different mechanisms. On

the other hand, if these d'Hérelle bodies were really genes,

fundamentally like our chromosome genes, they would give us an

utterly new angle from which to attack the gene problem. They are

filterable, to some extent isoluble, can be handled in test tubes, and

their properties, as shown by their effects on the bacteria, can then

be studied after treatment. It would be very rash to call these bodies

genes, and yet at present we must confess that there is no

distinction known between the genes and them. Hence we cannot

categorically deny that perhaps we may be able to grind genes in a

mortar and cook them in a beaker after all. Must we geneticists

become bacteriologists, physiological chemists and physicists,

simultaneous-ly with being zoologists and botanists? Let us hope.

I. THE RELATION BETWEEN THE GENES AND THE CHARACTERS OF

THE ORGANISM

The present paper will be concerned rather with problems, and

the possible means of attacking them, than with the details of cases

and data. The opening up of these new problems is due to the

fundamental contribution which genetics has made to cell physiology

within the last decade. This contribution, which has so far scarcely

been assimilated by the general physiologists themselves, consists in

the demonstration that, besides the ordinary proteins, carbohydrates,

lipoids, and extractives, of their several types, there are present within

the cell thousands of distinct substances — the “genes”; these genes

exist as ultramicroscopic particles; their influences nevertheless

permeate the entire cell, and they play a fundamental role in

determining the nature of all cell substances, cell structures, and cell

activities. Through these cell effects, in turn, the genes affect the

entire organism.

It is not mere guesswork to say that the genes are

ultramicroscopic bodies. For the work on Drosophila has not only

proved that the genes are in the chromosomes, in definite positions,

but it has shown that there must be hundreds of such genes within

each of the larger chromosomes, although the length of these

chromosomes is not over a few microns. If, then, we divide the size of the chromosome by the minimum number of its genes, we find that

the latter are particles too small to give a visible image.

The chemical composition of the genes, and the formulae of their

reactions, remain as yet quite unknown. We do know, for example,

that in certain cases a given pair of genes will determine the existence

of a particular enzyme (concerned in pigment production), that

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