[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.

[Our work on the structure of DNA] was fairly fast, but you know, we were lucky. One must remember, it was based on the X-ray work done here in London started off by Morris Wilkins and carried on by Rosalind Franklin, and we wouldn’t have got to the stage of at least having a molecular model, if it hadn't been for their work.

[Professor Pauling] confesses that he had harboured the feeling that sooner or later he would be the one to get the DNA structure; and although he was pleased with the double-helix, he ‘rather wished the idea had been his’.

A DNA sequence for the genome of bacteriophage ΦX174 of approximately 5,375 nucleotides has been determined using the rapid and simple “plus and minus” method. The sequence identifies many of the features responsible for the production of the proteins of the nine known genes of the organism, including initiation and termination sites for the proteins and RNAs. Two pairs of genes are coded by the same region of DNA using different reading frames.
[Paper co-author]

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.

All living things need their instruction manual (even nonliving things like viruses) and that is all they need, carried in one very small suitcase.

All of today’s DNA, strung through all the cells of the earth, is simply an extension and elaboration of [the] first molecule.

And now the announcement of Watson and Crick about DNA. This is for me the real proof of the existence of God.

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 that used to have some function way back in evolution but currently does not (and might possibly be revived if, say, an ancient parasite reappeared), DNA that controls how genes switch their protein manufacturing on and off, DNA that controls those, and so on. Some may actually be genuine junk. And some (so the joke goes) may encode a message like ‘It was me, I’m God, I existed all along, ha ha.’

DNA was the first three-dimensional Xerox machine.

Earlier this week … scientists announced the completion of a task that once seemed unimaginable; and that is, the deciphering of the entire DNA sequence of the human genetic code. This amazing accomplishment is likely to affect the 21st century as profoundly as the invention of the computer or the splitting of the atom affected the 20th century. I believe that the 21st century will be the century of life sciences, and nothing makes that point more clearly than this momentous discovery. It will revolutionize medicine as we know it today.

Every book is a quotation; and every house is a quotation out of all forests and mines and stone-quarries; and every man is a quotation from all his ancestors.

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.

Genetics as a whole is the great over-hyped science, and geneticists know that even if they don't say it. All that genetics really is is anatomy plus an enormous research group grant. It's what anatomists did in the fifteenth century-looking at the heart and seeing how it worked. Now, we are doing the same with DNA

I am terribly proud of—I was born in Cambridge in 1952 and my initials are DNA!

I think she [Rosalind Franklin] was a good experimentalist but certainly not of the first rank. She was simply not in the same class as Eigen or Bragg or Pauling, nor was she as good as Dorothy Hodgkin. She did not even select DNA to study. It was given to her. Her theoretical crystallography was very average.

I think that the formation of [DNA's] structure by Watson and Crick may turn out to be the greatest developments in the field of molecular genetics in recent years.

If the double helix was so important, how come you didn’t work on it?

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.

If Watson and I had not discovered the [DNA] structure, instead of being revealed with a flourish it would have trickled out and that its impact would have been far less. For this sort of reason Stent had argued that a scientific discovery is more akin to a work of art than is generally admitted. Style, he argues, is as important as content. I am not completely convinced by this argument, at least in this case.

In a purely technical sense, each species of higher organism—beetle, moss, and so forth, is richer in information than a Caravaggio painting, Mozart symphony, or any other great work of art. Consider the typical case of the house mouse, Mus musculus. Each of its cells contains four strings of DNA, each of which comprises about a billion nucleotide pairs organized into a hundred thousand structural nucleotide pairs, organized into a hundred thousand structural genes. … The full information therein, if translated into ordinary-sized printed letters, would just about fill all 15 editions of the Encyclopaedia Britannica published since 1768.

In Cairo, I secured a few grains of wheat that had slumbered for more than thirty centuries in an Egyptian tomb. As I looked at them this thought came into my mind: If one of those grains had been planted on the banks of the Nile the year after it grew, and all its lineal descendants had been planted and replanted from that time until now, its progeny would to-day be sufficiently numerous to feed the teeming millions of the world. An unbroken chain of life connects the earliest grains of wheat with the grains that we sow and reap. There is in the grain of wheat an invisible something which has power to discard the body that we see, and from earth and air fashion a new body so much like the old one that we cannot tell the one from the other.…This invisible germ of life can thus pass through three thousand resurrections.

It has been found experimentally that the ratio of the amounts of adenine to thymine, and the ratio of guanine to cytosine, are always very close to unity for deoxyribose nucleic acid.
[Co-author with Francis Crick]

It has been stated that the research should be discontinued because it involved “meddling with evolution.” Homo sapiens has been meddling with evolution in many ways and for a long time. We started in a big way when we domesticated plants and animals. We continue every time we alter the environment. In general, recombinant DNA research docs not seem to represent a significant increase in the risks associated with such meddling—although it may significantly increase the rate at which we meddle.

It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.
[Concluding remark in the paper by Watson and Crick announcing discovery of the structure of DNA.]

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 just so happens that during the 1950s, the first great age of molecular biology, the English schools of Oxford and particularly of Cambridge produced more than a score of graduates of quite outstanding ability—much more brilliant, inventive, articulate and dialectically skillful than most young scientists; right up in the Jim Watson class. But Watson had one towering advantage over all of them: in addition to being extremely clever he had something important to be clever about.

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. 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.

Natural selection based on the differential multiplication of variant types cannot exist before there is material capable of replicating itself and its own variations, that is, before the origination of specifically genetic material or gene-material.

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.

Rather than believe that Watson and Crick made the DNA structure, I would rather stress that the structure made Watson and Crick.

Recently, we’ve reported that we have made all five bases, the compounds that spell out the instructions for all life and are a part of the nucleic acids, RNA and DNA. Not only did we make all five bases but we found them in a meteorite! So that these two things coming together really assure us that the molecules necessary for life can be found in the absence of life. This was the biggest stumbling block.

Rosalind Franklin made X-rays dance,
Getting DNA’s first inner glance.
  No Nobel arrived,
  After she died;
Science history honors her advance.

Science is beautiful when it makes simple explanations of phenomena or connections between different observations. Examples include the double helix in biology, and the fundamental equations of physics.
[Answer to question: What are the things you find most beautiful in science?]

Science is in a literal sense constructive of new facts. It has no fixed body of facts passively awaiting explanation, for successful theories allow the construction of new instruments—electron microscopes and deep space probes—and the exploration of phenomena that were beyond description—the behavior of transistors, recombinant DNA, and elementary particles, for example. This is a key point in the progressive nature of science—not only are there more elegant or accurate analyses of phenomena already known, but there is also extension of the range of phenomena that exist to be described and explained.
Co-author with Michael A. Arbib, English-born professor of computer science and biomedical engineering (1940-)

The … publicity is always the same; only the blanks need to be filled in: “It was announced today by scientists at [Harvard, Vanderbilt, Stanford] Medical School that a gene responsible for [some, many, a common form of] [schizophrenia, Alzheimer’s, arterio-sclerosis, prostate cancer] has been located and its DNA sequence determined. This exciting research, say scientists, is the first step in what may eventually turn out to be a possible cure for this disease.”

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 blueprints for the construction of one human being requires only a meter of DNA and one tiny cell. … even Mozart started out this way.

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 Continuity of the Germ-plasm.

The discovery that DNA is the stuff of genes can be traced to Oswald Avery, a practitioner who wanted to learn how bacteria cause pneumonia.

The essential molecule of reproduction, DNA, … is composed of only four nitrogen bases (adenine, thymine, guanine, and cytosine), the sugar deoxyribose, and a phosphate. DNA’s intermediary, RNA, differs only by the substitution of the sugar ribose for deoxyribose and the nitrogen base uracil for thymine. The proteins of living organisms are made with a mere 20 amino acids, all arranged in a “left-handed” configuration. Taking into account all 28 building blocks, or “letters” (20 amino acids, five bases, two sugars, and one phosphate), the message is clear: With such a limited alphabet, all life must have had a common chemical origin.

The fundamental biological variant is DNA. That is why Mendel's definition of the gene as the unvarying bearer of hereditary traits, its chemical identification by Avery (confirmed by Hershey), and the elucidation by Watson and Crick of the structural basis of its replicative invariance, are without any doubt the most important discoveries ever made in biology. To this must be added the theory of natural selection, whose certainty and full significance were established only by those later theories.

The greatest single achievement of nature to date was surely the invention of the molecule DNA.

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 information reported in this section [about the two different forms, A and B, of DNA] was very kindly reported to us prior to its publication by Drs Wilkins and Franklin. We are most heavily indebted in this respect to the Kings College Group, and we wish to point out that without this data the formation of the picture would have been most unlikely, if not impossible.
[Co-author with Francis Crick]

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 nitrogen in our DNA, the calcium in our teeth, the iron in our blood, the carbon in our apple pies were made in the interiors of collapsing stars. We are made of starstuff.

The notion that individualism came first runs against the very grain of cosmic history. … grouping has been inherent in evolution since the first quarks joined to form neutrons and protons. Similarly, replicators—RNA, DNA, and genes—have always worked in teams… The bacteria of 3.5 billion years ago were creatures of the crowd. So were the trilobites and echinoderms of the Cambrian age.

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 realization of the role played by DNA has had absolutely no consequence for either therapy or prevention…. Treatments for cancer remain today what they were before molecular biology was ever thought of: cut it out, burn it out, or poison it.

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.

These results demonstrate that there is a new polymerase inside the virions of RNA tumour viruses. It is not present in supernatents of normal cells but is present in virions of avian sarcoma and leukemia RNA tumour viruses. The polymerase seems to catalyse the incorporation of deoxyrinonucleotide triphosphates into DNA from an RNA template. Work is being performed to characterize further the reaction and the product. If the present results and Baltimore's results with Rauscher leukemia virus are upheld, they will constitute strong evidence that the DNA proviruses have a DNA genome when they are in virions. This result would have strong implications for theories of viral carcinogenesis and, possibly, for theories of information transfer in other biological systems. [Co-author with American virologist Satoshi Mizutani]

We are going through the body-snatching phase right now, and there are all these Burke and Hare attitudes towards geneticists-that they are playing God and that DNA is sacred. No, it’s not. It’s no more sacred than your toenails. Basically, we are not going to make long-term medical progress without understanding how the genes work.
[Referring to the similarity of fears and superstitions in genetics as once were associated with anatomy ]

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 machines built by DNA whose purpose is to make more copies of the same DNA. ... This is exactly what we are for. We are machines for propagating DNA, and the propagation of DNA is a self-sustaining process. It is every living object's sole reason for living.

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 cannot cheat on DNA. We cannot get round photosynthesis. We cannot say I am not going to give a damn about phytoplankton. All these tiny mechanisms provide the preconditions of our planetary life. To say we do not care is to say in the most literal sense that “we choose death.”

We have come a long way on that old molecule [DNA].

We knew that DNA was important. We knew it was an important molecule. And we knew that its shape was likely to be important. But we didn’t realise I think just how important it would be. Put in other words, we didn’t realise that the shape would give us a clue to the replication mechanism. And this turned out to be really an unexpected dividend from finding out what the shape was.

We must infer that a plant or animal of any species, is made up of special units, in all of which there dwells the intrinsic aptitude to aggregate into the form of that species: just as in the atoms of a salt, there dwells the intrinsic aptitude to crystallize in a particular way.

We should first look at the evidence that DNA itself is not the direct template that orders amino acid sequences. Instead, the genetic information of DNA is transferred to another class of molecules which then serve as the protein templates. These intermediate templates are molecules of ribonucleic acid (RNA), large polymeric molecules chemically very similar to DNA. Their relation to DNA and protein is usually summarized by the central dogma, a How scheme for genetic information first proposed some twenty years ago.

We should like to propose instead that the specificity of DNA self replication is accomplished without recourse to specific protein synthesis and that each of our complementary DNA chains serves as a template or mould for the formation onto itself of a new companion chain.
[Co-author with Francis Crick]

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 biological interest. [Co-author with Francis Crick]

We wish to put forward a radically different structure for the salt of deoxyribose nucleic acid. This structure has two helical chains each coiled round the same axis (see diagram).
[Co-author with Francis Crick]

We wish to suggest a structure for the salt of deoxyribose nucleic acid (DNA). This structure has novel features which are of considerable biological interest.
[Opening remark in the paper by Watson and Crick announcing discovery of the structure of DNA.]

While DNA could be claimed to be both simple and elegant, it must be remembered that DNA almost certainly originated fairly close to the origin of life when things were necessarily simple or they would not have got going.

While the biological properties of deoxypentose nucleic acid suggest a molecular structure containing great complexity, X-ray diffraction studies described here … show the basic molecular configuration has great simplicity. [Co-author with A.R. Stokes, H.R. Wilson. Thanks include to “… our colleagues R.E. Franklin, R.G. Gosling … for discussion.”]

You know something I could really do without? The Space Shuttle. … It’s irresponsible. The last thing we should be doing is sending our grotesquely distorted DNA out into space.

You too can win Nobel Prizes. Study diligently. Respect DNA. Don't smoke. Don't drink. Avoid women and politics. That's my formula.