A moral principle in genetic testing is that it should always be done with the consent of the individual. No one wants someone snooping into his DNA.

At lunch Francis [Crick] winged into the Eagle to tell everyone within hearing distance that we had found the secret of life.

Conclusion: Big helix in several chains, phosphates on outside, phosphate-phosphate inter-helical bonds disrupted by water. Phosphate links available to proteins.

DNA neither cares nor knows. DNA just is. And we dance to its music.

DNA was the first three-dimensional Xerox machine.

Finally one should add that in spite of the great complexity of protein synthesis and in spite of the considerable technical difficulties in synthesizing polynucleotides with defined sequences it is not unreasonable to hope that all these points will be clarified in the near future, and that the genetic code will be completely established on a sound experimental basis within a few years.

If the results of the present study on the chemical nature of the transforming principle are confirmed, then nucleic acids must be regarded as possessing biological specificity the chemical basis of which is as yet undetermined.

It is raining DNA outside. On the bank of the Oxford canal at the bottom of my garden is a large willow tree, and it is pumping downy seeds into the air. ... [spreading] DNA whose coded characters spell out specific instructions for building willow trees that will shed a new generation of downy seeds. … It is raining instructions out there; it's raining programs; it's raining tree-growing, fluff-spreading, algorithms. That is not a metaphor, it is the plain truth. It couldn't be any plainer if it were raining floppy discs.

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?

It seems a miracle that young children easily learn the language of any environment into which they were born. The generative approach to grammar, pioneered by Chomsky, argues that this is only explicable if certain deep, universal features of this competence are innate characteristics of the human brain. Biologically speaking, this hypothesis of an inheritable capability to learn any language means that it must somehow be encoded in the DNA of our chromosomes. Should this hypothesis one day be verified, then lingusitics would become a branch of biology.

Leaving aside genetic surgery applied humans, I foresee that the coming century will place in our hands two other forms of biological technology which are less dangerous but still revolutionary enough to transform the conditions of our existence. I count these new technologies as powerful allies in the attack on Bernal's three enemies [the world, the flesh and the devil]. I give them the names 'biological engineering' and 'self-reproducing machinery'. Biological engineering means the artificial synthesis of living organisms designed to fulfil human purposes. Self-reproducing machinery means the imitation of the function and reproduction of a living organism with non-living materials, a computer-program imitating the function of DNA and a miniature factory imitating the functions of protein molecules. After we have attained a complete understanding of the principles of organization and development of a simple multicellular organism, both of these avenues of technological exploitation should be open to us.

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.

One can say, looking at the papers in this symposium, that the elucidation of the genetic code is indeed a great achievement. It is, in a sense, the key to molecular biology because it shows how the great polymer languages, the nucleic acid language and the protein language, are linked together.

Parasites are not only incredibly diverse; they are also incredibly successful. There are parasitic stretches of DNA in your own genes, some of which are called retrotransposons. Many of the parasitic stretches were originally viruses that entered our DNA. Most of them don't do us any harm. They just copy and insert themselves in other parts of our DNA, basically replicating themselves. Sometimes they hop into other species and replicate themselves in a new host. According to one estimate, roughly one-third to one-half of all human DNA is basically parasitic.

Plasma seems to have the kinds of properties one would like for life. It's somewhat like liquid water-—unpredictable and thus able to behave in an enormously complex fashion. It could probably carry as much information as DNA does. It has at least the potential for organizing itself in interesting ways.

Possibly the most pregnant recent development in molecular biology is the realization that the beginnings of life are closely associated with the interactions of proteins and nucleic acids.

The ability of a cell to sense these broken ends, to direct them towards each other, and then to unite them so that the union of the two DNA strands is correctly oriented, is a particularly revealing example of the sensitivity of cells to all that is going on within them. They make wise decisions and act on them.

The capacity to blunder slightly is the real marvel of DNA. Without this special attribute, we would still be anaerobic bacteria and there would be no music.

The inducing substance, on the basis of its chemical and physical properties, appears to be a highly polymerized and viscous form of sodium desoxyribonucleate. On the other hand, the Type m capsular substance, the synthesis of which is evoked by this transforming agent, consists chiefly of a non-nitrogenous polysaccharide constituted of glucose-glucuronic acid units linked in glycosidic union. The presence of the newly formed capsule containing this type-specific polysaccharide confers on the transformed cells all the distinguishing characteristics of Pneumococcus Type III. Thus, it is evident that the inducing substance and the substance produced in turn are chemically distinct and biologically specific in their action and that both are requisite in determining the type of specificity of the cell of which they form a part. The experimental data presented in this paper strongly suggest that nucleic acids, at least those of the desoxyribose type, possess different specificities as evidenced by the selective action of the transforming principle.

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 messages that DNA molecules contain are all but eternal when seen against the time scale of individual lifetimes. The lifetimes of DNA messages (give or take a few mutations) are measured in units ranging from millions of years to hundreds of millions of years; or, in other words, ranging from 10,000 individual lifetimes to a trillion individual lifetimes. Each individual organism should be seen as a temporary vehicle, in which DNA messages spend a tiny fraction of their geological lifetimes.

The possibility that the infective agent may not contain nucleic acid and consist only of a peptide or peptide-polysaccharide complex which has replication properties within susceptible cells is intriguing. If peptides, short-chain proteins, or peptide/fatty-acid/ polysaccharide complexes activate nucleic-acid template activity in the host genes to produce identical infective particles, this would invalidate the accepted dogma of present-day molecular biology in which D.N.A. and R.N.A. templates control all biological activity.

The results serve to disprove the tetranucleotide hypothesis. It is, however, noteworthy—whether this is more than accidental, cannot yet be said—that in all desoxypentose nucleic acids examined thus far the molar ratios of total purines to total pyrimidines, and also of adenine to thymine and of guanine to cytosine, were not far from 1.

The results suggest a helical structure (which must be very closely packed) containing probably 2, 3 or 4 coaxial nucleic acid chains per helical unit and having the phosphate groups near the outside.

We are going to die, and that makes us the lucky ones. Most people are never going to die because they are never going to be born. The potential people who could have been here in my place but who will in fact never see the light of day outnumber the sand grains of Arabia. Certainly those unborn ghosts include greater poets than Keats, scientists greater than Newton. We know this because the set of possible people allowed by our DNA so massively outnumbers the set of actual people. In the teeth of these stupefying odds it is you and I, in our ordinariness, that are here.

We are now witnessing, after the slow fermentation of fifty years, a concentration of technical power aimed at the essential determinants of heredity, development and disease. This concentration is made possible by the common function of nucleic acids as the molecular midwife of all reproductive particles. Indeed it is the nucleic acids which, in spite of their chemical obscurity, are giving to biology a unity which has so far been lacking, a chemical unity.

We wish to discuss a structure for the salt of deoxyribose nucleic acid. (D.N.A.). This structure has novel features which are of considerable biologic interest.

[About the structure of DNA] [T]he whole business was like a child's toy that you could buy at the dime store, all built in this wonderful way that you could explain in Life magazine so that really a five-year-old can understand what's going on...This was the greatest surprise for everyone.