"In other words we think we have found the basic copying mechanism by which life comes from life..."
"Twice, especially, since 1900, scientists and their ideas have generated a transformation so broad and so deep that it touches everyone's most intimate sense of the nature of things. The first of these transformations was in physics, the second in biology. Between the two, we are most of us spontaneously more interested in the science of life..." (Horace Freeland Judson, The Eighth Day of Creation).
CRICK, Francis Harry Compton (1916-2004). Autograph Letter Signed ("Daddy") to his son Michael, outlining the revolutionary discovery of the structure and function of DNA. Cambridge, 19 March 1953. 7 pages, 4to, on Basildon bond blue writing paper, watermarked ...written on rectos and versos (each sheet with two small hole-punches, otherwise very fine).
MORE THAN ONE MONTH BEFORE THE FIRST PUBLISHED ANNOUNCEMENT, FRANCIS CRICK, THE CO-DISCOVERER OF THE STRUCTURE AND FUNCTION OF DNA, DETAILS ONE OF THE MOST IMPORTANT SCIENTIFIC DISCOVERIES OF THE 20TH CENTURY--THE 'SECRET OF LIFE'--TO HIS SON
"We have discovered the secret of life," Francis Crick announced to the patrons of the Eagle Pub in Cambridge on that historic afternoon of February 1953. According to his co-discoverer James D. Watson: "As was normal for a Saturday morning, I got to work at Cambridge University's Cavendish Laboratory earlier than Francis Crick on February 28, 1953. I had good reason for being up early. I knew that we were close--though I had no idea just how close--to figuring out the structure of a then little-known molecule called deoxyribonucleic acid: DNA. This was not any old molecule: DNA, as Crick and I appreciated, holds the very key to the nature of living things. It stores the hereditary information that is passed on from one generation to the next, and it orchestrates the incredibly complex world of the cell. Figuring out its three-dimensional structure--the architecture by which the molecule is put together--would, we hoped, provide a glimpse of what Crick referred to only half-jokingly as 'the secret of life'" (James Watson, DNA: The Secret of Life, NY, 2003, preface).
Francis Crick was born in Northampton, England in 1916, to a family which ran a successful shoemaking firm. Crick's grandfather was a shoemaker and an amateur scientist; his father's brother Walter was also science-minded, and he and Francis conducted chemical experiments together when he was young. Crick studied physics at University College in London, but his studies were interrupted by service in World War II.
During the war he worked as a scientist for the British Admiralty, where he contributed important work in connection with magnetic and acoustic mines. After the War, Crick left the Admiralty in 1947 to study biological research at the Strangeways Laboratory in Cambridge. Although the research did not excite him, from there he was able to keep up on developments in the fields of genetics and bacteriology, and in 1949, he transferred to the Cavendish Laboratory, headed by Nobel Laureate Sir Lawrence Bragg. There he would join the new unit established by the Medical Research Council (MRC) to study protein structure using X-rays working alongside future Nobel laureates Max Perutz and John Kendrew.
Crick was 33 years old and still a graduate student when the young American, James D. Watson arrived at the Cavendish. Twelve years Crick's junior, Watson had already completed his Ph.D in 1950, and was determined to pursue the nature of the gene and its chemical basis. He and Crick were assigned an office together and quickly began to share their ideas on the physical nature of the gene and how to determine the structure of DNA. Unlike the experimentalists Maurice Wilkins and Rosalind Franklin, they believed the structure could be determined through a combination of data and theory, and model-building to see which structures made the most sense. Watson's carefully constructed models showing the base pairs were critical, while the data they worked with included crucial information from Franklin's X-ray research, which determined that DNA was helical among other characteristics.
The Race for the Discovery of the Structure of DNA
The knowledge of the existence of DNA was reported as early as 1868, when the Swiss physician Fritz Miescher first discovered its presence in the nuclei of cells. During the decades following Miescher's discovery, other scientists--notably, Phoebus Levene and Erwin Chargaff--carried out a series of research efforts that revealed additional details about the DNA molecule, including its primary chemical components and the ways in which they joined with one another. In 1943, the American medical researcher Oswald Avery had proven that DNA was the molecule responsible for carrying genetic information. But prior to Watson and Crick's study of the structure of DNA (which led to the discovery of its function), proteins were primarily thought to be the carriers of genetic material. Although the chemical composition of DNA was known and understood, scientists were unable to make conclusions about its function.
By the 1950s, three groups made it their goal to determine the structure of DNA. Led by Maurice Wilkins, the first group to start was at King's College London, and was later joined by Rosalind Franklin. At King's they were focused on the examination of X-ray diffraction patterns of DNA fibers. Crick and Watson were at Cambridge building physical models using metal rods and balls, in which they incorporated the known chemical structures of the nucleotides, as well as the known position of the linkages joining one nucleotide to the next along the polymer. A third group, at Caltech, was led by Linus Pauling. Of the three groups, only the London team was able to produce good quality diffraction patterns and thus produce adequate quantitative data about the molecule's structure.
Crick and Watson's collaboration to discover the structure of DNA became a race with the obvious progress the chemist Linus Pauling was making in California. Pauling had previously published the structure of an important structural component of proteins known as the alpha helix in 1951, and while Watson and Crick were working on their model he published an incorrect triple model of DNA.
On that fateful last day in February 1953, Watson recounted: "When I got to our still empty office the following morning, I quickly cleared away the papers from my desk top so that I would have a large, flat surface on which to form pairs of bases held together by hydrogen bonds. Though I initially went back to my like-with-like prejudices, I saw all too well that they led nowhere. When Jerry [Donahue] came in I looked up, saw that it was not Francis, and began shifting the bases in and out of various other pairing possibilities. Suddenly I became aware that an adenine-thymine pair held together by two hydrogen bonds was identical in shape to a guanine-cytosine pair held together by at least two hydrogen bonds. All the hydrogen bonds seemed to form naturally; no fudging was required to make the two types of base pairs identical in shape Upon his arrival Francis did not get more than halfway through the door before I let loose that the answer to everything was in our hands. However, we both knew that we should not be home until a complete model was built in which all the stereo-chemical contacts were satisfactory. There was the obvious fact that the implications of its existence were far too important to risk crying wolf. Thus I felt slightly queasy when at lunch Francis winged into the Eagle to tell everyone within hearing distance that we had found the secret of life" (Watson, The Double Helix, pp. 194-197).
"Those early days of March raced by as they attached and detached skeletal metal representations of the atoms using cylindrical collars, such as those familiar to construction kit enthusiasts. It took them several days to measure the positions of all the atoms with a plumb line and ruler. Crick would beat Watson to the lab in the morning, where he could be seen tightening the clamps holding the skeletal model and checking and recording the positions of each atom. Every now and then, a visitor would arrive from the Cavendish to see what all the fuss was about. As physicists upstairs commented, 'steam' was rising from the floor below-excited voices, laughter, and Crick's voice as he delivered yet another 'buoyant and booming' lecture to the next visitor. This went on all week, ending Saturday morning 'by which time,' said Crick, 'I was so tired, I just went straight home and to bed.'" (Olby, p. 169).
As soon as they made their discovery, they immediately set about preparing it for publication, and on April 2nd it was submitted to the journal Nature. To avoid any embarrassment such as they had had on one of their earlier failed attempts at a structure, the two scientists checked and re-checked their model and began showing it to their colleagues at the Cavendish, before announcing it to their rivals at King's College and Caltech.
"Confirmation that Watson and Crick were over the first hurdle came after they had given Wilkins a copy of the paper intended for Nature that they had been drafting and redrafting. Wilkins responded in a letter dated 18 March that begins 'I think you're a couple of old rogues but you may well have something. I like the idea'" (Olby, p. 171).
"The final version was ready to be typed on the last weekend of March. Our Cavendish typist was not on hand, and the brief job was given to my sister. There was no problem persuading her to spend a Saturday afternoon this way, for we told her that she was participating in perhaps the most famous event in biology since Darwin's book. Francis and I stood over her as she typed the nine-hundred-word article that began, '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.' On Tuesday the manuscript was sent up to Bragg's office and on Wednesday, April 2, went off to the editors of Nature" (James Watson, The Double Helix, p. 222).
The 'Secret of Life' Letter
It was during this period, while successive drafts of their first paper were going back and forth between Cambridge and London, that Francis Crick wrote a remarkable letter outlining their discovery to his twelve-year old son, Michael, who was at the time convalescing while away at boarding school. Michael F.C. Crick was Francis Crick's son from his first marriage (1940-47) to Ruth Doreen Dodd. In the same understated voice that would become familiar in their published announcement, Crick writes on March 19th:
Jim Watson and I have probably made a most important discovery. We have built a model for the structure of des-oxy-ribose-nucleic-acid (read it carefully) called D.N.A. You may remember that the genes of the chromosomes - which carry the hereditary factors - are made up of protein and D.N.A. Our structure is very beautiful"
He goes on to describe the structure in detail including its helical shape with his hand drawn diagram: "Now we have two of these chains winding round each other - each one is a helix - and the chain, made up of sugar and phosphorus, is on the outside, and the bases are all on the inside. I can't draw it very well, but it looks like this" Crick lays out the fixed base pairings which he describes as being like a code: "If you are given one set of letters you can write down the others.
"Now we believe that the D.N.A. is a code. That is, the order of the bases (the letters) makes one gene different from another gene (just as one page of print is different from another). You can now see how Nature makes copies of the genes. Because if the two chains unwind into two separate chains, and if each chain then makes another chain come together on it, then because A always goes with T, and G with C, we shall get two copies where we had one before."
After a series of diagrams of the base pairings, he modestly continues: "In other words we think we have found the basic copying mechanism by which life comes from life." Referring to publication of the discovery, Crick informs he son: "You can understand that we are very excited. We have to have a letter off to Nature in a day or so" and instructs him "Read this carefully so that you understand it. When you come home we will show you the model.
Lots of love, Daddy."
This letter was referred to by Crick as the "Secret of Life Letter," and has been cited often in the accounts of the discovery, including those of Horace Freeland Judson, and Robert Olby. This is due to its remarkable content, apart from the touching personal aspect of the transmission of his most recent discovery to his young son. In essence, it provides a concise illustrated summary of the first two important papers written by Watson and Crick that appeared in Nature in April and May of 1953, respectively. Beyond describing the double-helix structure and base pair combinations of the first paper, the letter summarizes their ideas about genetic replication that would appear in their important second article for Nature, published on May 30, 1953.
Although recognized today as one of the seminal scientific papers of the twentieth century, Watson and Crick's original article in Nature was not frequently cited at first. Its true significance became apparent, and its circulation widened, only towards the end of the 1950s, when the structure of DNA they had proposed was shown to provide a mechanism for controlling protein synthesis, and when their conclusions were confirmed in the laboratory by Matthew Meselson, Arthur Kornberg, and others.
Watson and Crick collaborated on three papers on DNA in 1953, and one the following year. Their second Nature article, which appeared in May 1953, entitled "Genetical Implications of the Structure of Deoxyribonucleic Acid," is considered by some scientists to be more important in some ways than the first, because it describes a mechanism for duplication, and for the first time a diagram of the two base pairs, and describes their replication--these critical aspects are all included in Crick's remarkable letter to his son, well in advance of formal publication.
"Watson and Crick's second paper begins with a sweeping declamatory statement typical of both authors: 'The importance of deoxyribonucleic acid (DNA) within living cells is undisputed.' Then follow three very carefully worded sentences, probably written by Crick, that neatly express the main reason for the widespread reluctance at the time to accept DNA as the genetic material. 'Many lines of evidence indicate that it is the carrier of a part of (if not all) the genetic specificity of the chromosomes and thus of the gene itself. Until now, however, no evidence has been presented to show how it might carry out the essential operation required of a genetic material, that of exact duplication.'Then follows the important inference that 'it therefore seems likely that the precise sequence of the bases is the code which carries the genetical information.' That word 'code,' speaking of a secret to be discovered, expressed their hopes for the future" (Olby, p. 186).
In 1962, Crick, Watson and Maurice Wilkins received the Nobel Prize in medicine for their work at the Cavendish Laboratory and at the University of Cambridge. Rosalind Franklin, who also worked on the research, died in 1958 before the Nobel was awarded. It is not awarded posthumously.
Watson and Crick continued their investigations into the secrets of life, and eventually would go their separate ways in their search, but it was their discovery in early 1953 of the double helical structure of deoxyribonucleic acid (DNA), which led to their worldwide recognition--as well as the development of the field of molecular biology. It marked a milestone in the history of science and gave rise to modern molecular biology, which is largely concerned with understanding how genes control the chemical processes within cells. Their discovery yielded ground-breaking insights into the genetic code and protein synthesis. During the 1970s and 1980s, it helped to produce new and powerful scientific techniques, specifically recombinant DNA research, genetic engineering, rapid gene sequencing, and monoclonal antibodies, techniques on which today's multi-billion dollar biotechnology industry is founded. Major current advances in science, such as genetic fingerprinting and modern forensics, the mapping of the human genome, and the future promise of gene therapy, all have their origins in Watson and Crick's inspired work.
In 1968, Watson became director of the molecular-biology lab at Cold Spring Harbor, New York and in 1988 became head of the United States Human Genome Project. In 1977, Crick became professor at the Salk Institute for Biological Studies in La Jolla, California, where he did brain research. Francis Crick died in 2004 at the age of 88. Most of his scientific papers are at The Wellcome Library for the History and Understanding of Medicine in London, and therefore ANY MANUSCRIPT MATERIAL FROM THE TIME OF THEIR DISCOVERY IS UNLIKELY TO APPEAR ON THE MARKET.
Watson reflected fifty years after the discovery: "Crick's brag in the Eagle...that we had indeed discovered that 'secret of life,' struck me as somewhat immodest, especially in a country like England, where understatement is a way of life. Crick, however, was right. Our discovery put an end to a debate as old as the human species: Does life have some magical, mystical essence, or is it, like any chemical reaction carried out in a science class, the product of normal physical and chemical processes? Is there something divine at the heart of [a] cell that brings it to life? The double helix answered that question with a definitive No" (DNA: The Secret of Life, preface).
Crick's work with Watson on the double helix structure, and his subsequent work laying down the foundations of molecular biology, made him a seminal figure in the field of science. Their findings, as expressed by Crick in this remarkable early letter, constitute one of the most important scientific discoveries of the 20th century, the recognition of the double helix structure of DNA as the blueprint of life-the "Secret of Life."