I should like to compare this rearrangement which the proteins undergo in the animal or vegetable organism to the making up of a railroad train. In their passage through the body parts of the whole may be left behind, and here and there new parts added on. In order to understand fully the change we must remember that the proteins are composed of Bausteine united in very different ways. Some of them contain Bausteine of many kinds. The multiplicity of the proteins is determined by many causes, first through the differences in the nature of the constituent Bausteine; and secondly, through differences in the arrangement of them. The number of Bausteine which may take part in the formation of the proteins is about as large as the number of letters in the alphabet. When we consider that through the combination of letters an infinitely large number of thoughts may be expressed, we can understand how vast a number of the properties of the organism may be recorded in the small space which is occupied by the protein molecules. It enables us to understand how it is possible for the proteins of the sex-cells to contain, to a certain extent, a complete description of the species and even of the individual. We may also comprehend how great and important the task is to determine the structure of the proteins, and why the biochemist has devoted himself with so much industry to their analysis.

In describing a protein it is now common to distinguish the primary, secondary and tertiary structures. The primary structure is simply the order, or sequence, of the amino-acid residues along the polypeptide chains. This was first determined by Sanger using chemical techniques for the protein insulin, and has since been elucidated for a number of peptides and, in part, for one or two other small proteins. The secondary structure is the type of folding, coiling or puckering adopted by the polypeptide chain: the a-helix structure and the pleated sheet are examples. Secondary structure has been assigned in broad outline to a number of librous proteins such as silk, keratin and collagen; but we are ignorant of the nature of the secondary structure of any globular protein. True, there is suggestive evidence, though as yet no proof, that a-helices occur in globular proteins, to an extent which is difficult to gauge quantitatively in any particular case. The tertiary structure is the way in which the folded or coiled polypeptide chains are disposed to form the protein molecule as a three-dimensional object, in space. The chemical and physical properties of a protein cannot be fully interpreted until all three levels of structure are understood, for these properties depend on the spatial relationships between the amino-acids, and these in turn depend on the tertiary and secondary structures as much as on the primary. Only X-ray diffraction methods seem capable, even in principle, of unravelling the tertiary and secondary structures.
Co-author with G. Bodo, H. M. Dintzis, R. G. Parrish, H. Wyckoff, and D. C. Phillips

It is, I believe, justifiable to make the generalization that anything an organic chemist can synthesize can be made without him. All he does is increase the probability that given reactions will 'go.' So it is quite reasonable to assume that given sufficient time and proper conditions, nucleotides, amino acids, proteins, and nucleic acids will arise by reactions that, though less probable, are as inevitable as those by which the organic chemist fulfills his predictions. So why not self-duplicating virus-like systems capable of further evolution?

Knowing what we know from X-ray and related studies of the fibrous proteins, how they are built from long polypeptide chains with linear patterns drawn to a grand scale, how these chains can contract and take up different configurations by intramolecular folding, how the chain- groups are penetrated by, and their sidechains react with, smaller co-operating molecules, and finally how they can combine so readily with nucleic acid molecules and still maintain the fibrous configuration, it is but natural to assume, as a first working hypothesis at least, that they form the long scroll on which is written the pattern of life. No other molecules satisfy so many requirements.

Life goes faster on protein.

My own thinking (and that of many of my colleagues) is based on two general principles, which I shall call the Sequence Hypothesis and the Central Dogma. The direct evidence for both of them is negligible, but I have found them to be of great help in getting to grips with these very complex problems. I present them here in the hope that others can make similar use of them. Their speculative nature is emphasized by their names. It is an instructive exercise to attempt to build a useful theory without using them. One generally ends in the wilderness.
The Sequence Hypothesis
This has already been referred to a number of times. In its simplest form it assumes that the specificity of a piece of nucleic acid is expressed solely by the sequence of its bases, and that this sequence is a (simple) code for the amino acid sequence of a particular protein...
The Central Dogma
This states that once 'information' has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein. This is by no means universally held—Sir Macfarlane Burnet, for example, does not subscribe to it—but many workers now think along these lines. As far as I know it has not been explicitly stated before.

On the whole, at least in the author's experience, the preparation of species-specific antiserum fractions and the differentiation of closely related species with precipitin sera for serum proteins does not succeed so regularly as with agglutinins and lysins for blood cells. This may be due to the fact that in the evolutional scale the proteins undergo continuous variations whereas cell antigens are subject to sudden changes not linked by intermediary stages.

Protein synthesis is a central problem for the whole of biology, and that it is in all probability closely related to gene action.

Since many cases are known in which the specificities of antigens and enzymes appear to bear a direct relation to gene specificities, it seems reasonable to suppose that the gene's primary and possibly sole function is in directing the final configurations of protein molecules.
Assuming that each specific protein of the organism has its unique configuration copied from that of a gene, it follows that every enzyme whose specificity depends on a protein should be subject to modification or inactivation through gene mutation. This would, of course, mean that the reaction normally catalyzed by the enzyme in question would either have its rate or products modified or be blocked entirely.
Such a view does not mean that genes directly 'make' proteins. Regardless of precisely how proteins are synthesized, and from what component parts, these parts must themselves be synthesized by reactions which are enzymatically catalyzed and which in turn depend on the functioning of many genes. Thus in the synthesis of a single protein molecule, probably at least several hundred different genes contribute. But the final molecule corresponds to only one of them and this is the gene we visualize as being in primary control.

The initiation of the fermentation process does not require so complicated an apparatus as is represented by the living cell. The agent responsible for the fermenting action of the press juice is rather to be regarded as a dissolved substance, doubtless a protein; this will be denoted zymase.

The language of the genes has a simple alphabet, not with twenty-six letters, but just four. These are the four different DNA bases—adenine, guanine, cytosine and thymine (A, G, C and T for short). The bases are arranged in words of three letters such as CGA or TGG. Most of the words code for different amino acids, which themselves are joined together to make proteins, the building blocks of the body.

The serum, when subjected to heat, coagulates and hardens like egg. This property is one of its striking characteristics; it is attributed to a particular substance which is thereby readily recognizable, and which is called albumine, because it is the one present in egg white, termed albumen.

There is no existing ‘standard of protein intake’ that is based on the sure ground of experimental evidence. ... Between the two extremes of a very high and a very low protein intake it is difficult to prove that one level of intake is preferable to another. ... Physiologists, in drawing up dietary standards, are largely influenced by the dietary habits of their time and country.