by Livio, Mario
The April 25, 1953, issue of Nature contained three papers on the structure of DNA. First, there was the landmark paper by Watson and Crick describing the double helix structure. The paper was just a little more than one page long, but what a page that was. Watson and Crick started by acknowledging, “A structure for nucleic acid has already been proposed by Pauling and Corey. They kindly made their manuscript available to us in advance of publication.” However, they immediately added, “In our opinion, this structure is unsatisfactory.” They then concisely explained their “radically different structure,” consisting of “two helical chains each coiled around the same axis,” and, in particular, the “novel feature” of the structure, which is “the manner in which the two chains are held together by the purine and pyrimidine bases.”
Watson and Crick’s model immediately suggested a solution both to how the coding of genetic information is achieved and to the puzzle of how the molecule manages to copy itself. The details were presented in a second paper, published just five weeks after the first, in which Watson and Crick proposed the mechanism underlying the genetic code: “The phosphate-sugar backbone of our model is completely regular, but any sequence of the pairs of bases can fit into the structure. It follows that in a long molecule many different permutations are possible, and it therefore seems likely that the precise sequence of the bases is the code which carries the genetical information [emphasis added].” The message was clear: The coding of the genetic instructions that are needed to create, say, an amino acid, is contained in the specific sequence of bases in the rungs. For instance, the sequence C-G followed by G-C and then by T-A codes for forming the amino acid arginine, while G-C followed by C-G and then by T-A codes for alanine. The copying is done (precisely as anticipated abstractly by Pauling in 1948) by “unzipping” the double helix ladder at its center, producing two halves, each containing a leg and one-half of each one of the rungs. Because the sequence of bases in one chain automatically determines the sequence of the bases in the other (since the partner of T is always A, and that of G is always C), it is clear that one-half of the molecule contains all the information needed for constructing the whole molecule. For instance, if the sequence of bases along one chain of DNA is TAGCA, then the complementary sequence in the other chain must be ATCGT. This way, two new complete ladders can be generated from the original one and, hence, copying of the DNA molecule is accomplished.
In their first paper, Watson and Crick did not spell out the copying mechanism, but they remarked laconically, “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copy mechanism for the genetic material.” Crick explained later that this enigmatically economical sentence (which has been labeled “coy” by some historians of science) was, in fact, a compromise between his own desire to discuss the genetic implications in the first paper and Watson’s concern that the structure might still be wrong. The statement was, therefore, a simple claim to priority. The fact that Watson did still harbor doubts about the model is well documented in his contemporary letters.
As I have noted, two other papers in Nature accompanied the first paper by Watson and Crick. One was by Wilkins, Alexander Stokes, and Herbert Wilson, in which they analyzed some of the X-ray crystallographic data and also presented evidence that the helical structure exists not just in isolated fibers but also in intact biological systems. In the years that followed, Wilkins and his colleagues, and also Matthew Meselson, Arthur Kornberg, and others, did much work to confirm in detail the Watson and Crick model and their conclusions.
The third paper in the April 25, 1953, issue of Nature was by Franklin and Gosling. It contained the famous X-ray photograph of structure B. True to Franklin’s general attitude to science, the manuscript was formulated cautiously to read:
While we do not attempt to offer a complete interpretation of the fibre-diagram of structure B, we may state the following conclusions. The structure is probably helical. The phosphate groups lie on the outside of the structural unit, on a helix of diameter about 20 Angstroms. The structural unit probably consists of two coaxial molecules which are not equally spaced along the fibre axis . . . Thus our general ideas are not inconsistent with the model proposed by Watson and Crick in the preceding communication.
Few would disagree with the statement that Franklin’s exquisite X-ray diffraction photographs provided crucial information concerning DNA’s overall structure and specific dimensions. Sadly, Rosalind Franklin died from cancer in 1958 at the age of thirty-seven. It is conceivable that the disease was brought on by overexposure to those same X-rays that helped uncover the structure of DNA. Four years later, Watson, Crick, and Wilkins shared the Nobel Prize in Physiology or Medicine for discovering the molecular structure of DNA and its significance for information transfer in living material. Since the Nobel Prize is not awarded posthumously and cannot be shared by more than three people (in a given category in a given year), we shall never know what would have happened had Franklin survived until 1962.
In 2009 the famous photograph 51 became the title of a successful play by Anna Ziegler. As its title implies, the fictionalized account in the play concentrated on Rosalind Franklin and her rocky relationship with Maurice Wilkins. When asked to comment on the play, Watson remarked that the character of Maurice Wilkins “talked too much,” while the actor who played Crick did not do justice to the real Crick, since the play imparted him with a “used-car-salesman” vibe.
No one likes to admit defeat, and scientists are no exception. In a letter Pauling wrote to Peter on March 27, 1953, he first “casually” noted:
It might be good for you to get in touch with Miss Franklin, if you decide that this is a good plan, and arrange for us to see her also. If the King’s College people (Miss Franklin has left King’s College, and is with Bernal at Birkbeck) express an interest in having me visit their place, perhaps this could be worked in on the same day. I am not planning, however, to approach them on the matter.
Then, after another paragraph in which he described his precise travel plans, Pauling continued:
I have received a letter from Watson and Crick, describing their structure briefly—a copy of their letter to Nature is enclosed. The structure seems to me to be a very interesting one, and I have no strong argument against it. I do not think that their arguments against our structure are strong ones either.
Later in the letter, Pauling recognized that the water content of the molecule could be very important: “We give an argument . . . to support the assignment of three nucleotide residues . . . However, if the specimen of reasonably dry nucleic acid contained about 30% water . . . there would be only two residues on this length.” He concluded, “I think that the Wilkins photographs should settle the question definitely.”
I asked Alex Rich if Pauling truly thought that he could hold on to his triple helix model, and that the double helix was uncertain. Rich’s answer was fairly categorical: “Of course Pauling knew that the double helix was the correct model,” he said. “All this talk about it being uncertain was just bravado.” Indeed, Pauling came to Cambridge the first week in April (figure 17 shows him in 1953), and after seeing Watson and Crick’s wired model and Franklin’s X-ray photo, and having listened to Crick’s explanation, he acknowledged graciously that the structure appeared to be correct. A couple of days later, Pauling and Bragg left for the Solvay Conference in Brussels, Belgium. At that meeting of the world’s top researchers, Bragg first announced the double helix. With great style, Pauling admitted during the discussion that followed, “Although it is only two months since Professor Corey and I published our proposed structure for nucleic acid, I think that we must admit that it is probably wrong.”
Figure 17
One could certainly argue that there was nothing particularly “brilliant” in Pauling’s blunder—after all, his model was built inside out and with the wrong number of chains. But it was Pauling’s method, way of thinking, and previous incredible success with
complex protein molecules that inspired and informed Watson and Crick. In a short article published on March 21, 1999, Watson wrote about Pauling, “Failure hovers uncomfortably close to greatness. What matters now are his perfections, not his past imperfections. I most remember Pauling from 50 years ago, when he proclaimed that no vital forces, only chemical bonds, underlie life. Without that message, Crick and I might never have succeeded.”
The discovery of the structure of DNA had flung open the doors to a limitless range of research that to date culminated in April 2003 with the formal completion of the Human Genome Project—the decoding of the complete DNA of a human (although analysis of all the data will continue for many years). Along the way came many surprises. For instance, prior to the year 2000, biologists believed that the human genome contained about one hundred thousand protein-coding genes. Findings from the International Human Genome Sequencing Consortium published in October 2004 reduced the estimate to fewer than twenty-five thousand—only a little more than the gene count of the simple roundworm C. elegans! Cheaper and faster genetic sequencing technology has recently helped scientists to draw a new picture of human origins. The new view that emerges from the genetic analysis of the tip of a girl’s forty-thousand-year-old pinky finger found in a Siberian cave, is that modern humans did not simply march out of Africa. Rather, they probably encountered and bred with at least two other groups of ancient, now-extinct humans.
The discovery of the structure and function of DNA has also shed light on evolution by clarifying the nature of the hereditary variations on which natural selection can operate. Pauling’s proclamation that life processes are the consequence of the laws of chemistry and physics became verifiable through an understanding of the forces that shape and can vary DNA patterns. (Figure 18, a picture of some of the participants in the Pasadena Conference on the Structure of Proteins that took place in September 1953, shows many of the major players in the discovery of the alpha-helix and the double helix.)
Figure 18
We cannot even imagine what opportunities our comprehension of DNA and our ability to modify the molecule will present in the distant future. Possibilities range from significant lengthening of the human life expectancy to the creation of new life-forms. Deciphering the DNA structure has already led to an understanding of the genetic basis of diseases, which has revolutionized the search for treatments. The genome era has heralded previously unimaginable achievements in forensic science. For instance, following the deaths of five people from anthrax-laced letters in 2001, the US Federal Bureau of Investigation decided to sequence the entire microbial genome of the strain used in the attacks (5.2 million base pairs). That effort eventually led investigators to an army lab that was the most likely source of the strain. At the same time, with the exposition of the structure of DNA and of proteins, the question of the origin of life has become even more intriguing and potentially answerable. But the inquiries have penetrated to an even more fundamental level than the purely biological: Where did the building blocks of life, those information-carrying, replicating molecules, come from? And on the physics side, going back to earlier origins yet, how did the hydrogen atom, which was so crucial to Pauling’s hydrogen bond, appear in the universe? And what about the heavier elements that are so essential for life, such as carbon, oxygen, nitrogen, and phosphorus?
The Russian-born physicist George Gamow participated in the early attempts to understand how the four bases in DNA could control the synthesis of proteins from amino acids. Gamow was shown a copy of the paper by Watson and Crick on the genetic implications of their model while visiting the Radiation Laboratory at Berkeley. Excited, he started thinking about it as soon as he returned to his department at George Washington University, swiftly dispatching a letter to Watson and Crick. He started apologetically—“Dear Drs. Watson and Crick, I am a physicist, not a biologist”—but soon came to his main point: Could the relationship between the four letters corresponding to the bases in DNA, and the twenty amino acids in proteins, be solved as a problem in pure numerical cryptoanalysis? While Gamow’s mathematical solutions eventually turned out to be wrong, they did help in framing the questions of biology in the language of information.
About five years earlier, Gamow was involved in solving an even more fundamental problem: the cosmic origin of hydrogen and helium. His solution was truly brilliant. It did not explain, however, the existence of all the elements heavier than helium. This formidable task was left to another astrophysicist and cosmologist: Fred Hoyle. On one hand, Hoyle concerned himself with the evolution of the universe as a whole, and on the other, with the emergence of life within it. He was at the same time one of the most distinguished and one of the most controversial scientists of the twentieth century.
CHAPTER 8
B FOR BIG BANG
The philosophy which is so important in each of us is not a technical matter; it is our more or less dumb sense of what life honestly and deeply means. It is only partly got from books; it is our individual way of just seeing and feeling the total push and pressure of the cosmos.
—WILLIAM JAMES
On March 28, 1949, at six thirty in the evening, astrophysicist Fred Hoyle gave one of his authoritative radio lectures on the BBC’s The Third Programme, a cultural broadcast that featured such intellectuals as philosopher Bertrand Russell and playwright Samuel Beckett. At one point, as he was trying to contrast his own scenario—one of continuous creation of matter in the universe—with the opposing theory, which claimed that the universe had a distinct and definite beginning, Hoyle made what was to become a controversial statement:
We now come to the question of applying the observational tests to earlier theories. These theories were based on the hypothesis that all the matter in the universe was created in one big bang at a particular time in the remote past [emphasis added]. It now turns out that in some respect or other all such theories are in conflict with the observational requirements.
This lecture marked the birth of the term “big bang,” which has since been inextricably attached to the initial event from which our universe sprouted. Contrary to popular belief, Hoyle did not use the term in a derogatory manner. Rather, he was simply attempting to create a mental picture for his listeners. Ironically, a scientist who always opposed the idea behind this model coined and popularized the term big bang. The name has even survived a public referendum. In 1993 Sky & Telescope magazine solicited suggestions from readers for a better name—an act generally viewed as an attempt at cosmic political correctness. After three judges (including Carl Sagan, the famous astronomer and popularizer of science) sifted through the 13,099 entries, however, they found no worthy replacement. The title of this chapter (“B for Big Bang”) was fashioned after the title of a British television science-fiction drama, A for Andromeda, written by Hoyle and TV producer John Elliot. The seven-part series aired in 1961, and it featured actress Julie Christie in her first major role.
Fred Hoyle was born on June 24, 1915, in Gilstead, a village near the town of Bingley in West Yorkshire, England. His father was a wool and textiles merchant who was drafted into the Machine Gun Corps and dispatched to France during World War I. His mother studied music, and for a while played the piano in a local cinema, to accompany silent films. Fred Hoyle, who originally planned to be a chemist, studied mathematics at Cambridge, and he demonstrated such talent and accomplishments that he was elected fellow of St. John’s College in Cambridge in 1939. In 1958 he earned the prestigious Chair of Plumian Professor of Astronomy and Experimental Philosophy at Cambridge. Incidentally, George Darwin, Charles Darwin’s son, had held this chair between 1883 and 1912.
Signs of Hoyle’s relish for independence and sometimes dissension were apparent from an early age. He later recalled: “Between the ages of five and nine, I was almost perpetually at war with the education system . . . As soon as I learned from my mother that there was a place called school that I must attend willy nilly—a place where you were obliged to think about matters pre
scribed by a ‘teacher,’ not about matters decided by yourself—I was appalled.” His disdain for convention continued into his university years. In 1939 he decided to forgo a PhD degree for the “earthy motive,” in his words, of having to pay less income tax!
Not surprisingly, this curiosity-driven independent thinker matured to become a brilliant scientist. In terms of contributions to astrophysics and cosmology, Hoyle was probably the leading figure for at least a quarter century. At the same time, he never shied away from controversy. “To achieve anything really worthwhile in research,” he once wrote, “it is necessary to go against the opinions of one’s fellows. To do so successfully, not merely becoming a crackpot, requires fine judgment, especially on long-term issues that cannot be settled quickly.” We shall soon discover that Hoyle followed his own advice to a fault.
Even without World War II, 1939 was a critical year for Hoyle. It so happened that one after another, two of his research supervisors left Cambridge for appointments elsewhere. His third advisor was the great physicist Paul Dirac, one of the founders of quantum mechanics—the revolutionary new view of the subatomic microworld. Following the wealth of novel ideas of the 1920s, science of the late 1930s looked dull by comparison. Hoyle later wrote that Dirac told him one day in 1939, “In 1926 it was possible for people who were not very good to solve important problems, but now people who are very good cannot find important problems to solve.” Hoyle took this warning to heart and shifted his focus from pure, theoretical nuclear physics to the stars.