A Brief History of Creation (33 page)

Joshua Lederberg would one day call the experiment “the historical platform of modern DNA research,” but it took a great deal of time for most scientists to accept its full significance. Everybody knew about Avery's findings, but too many great minds had invested themselves in the centrality of protein. The idea of DNA as the carrier of genetic information represented a fundamental paradigm shift in the understanding of biochemistry and the working of cells. There was a great deal of resistance in the scientific community, even within the Rockefeller Institute. As late as 1951, in an essay marking the half-century anniversary of the rediscovery of Mendel, the great geneticist Hermann Muller—the first to realize that genes were subject to mutations—would write, “We have as yet no actual knowledge of the mechanism underlying that unique property which makes a gene a gene—its ability to cause the synthesis of another structure like itself.”

For a growing number of scientists, however, the implication of Avery's experiment was clear: DNA was indeed the central agent of genetics. Crick
counted himself cautiously among this group. By the time he and James Watson met, though, Watson was outright convinced. A blunt American with a crew cut that stood out like a sore thumb at the Cavendish, Watson had been sure of the primacy of DNA since his undergraduate days at the University of Chicago. He was angered by the reluctance of more established scientists to recognize DNA's importance. Later, in
The Double Helix
, he railed against the resistance he had faced from “cantankerous fools who unfailingly backed the wrong horses,” adding for good measure that “a goodly number of scientists were not only narrow-minded and dull, but also just stupid.”

After Watson arrived in 1950, he and Crick were drawn together by a crystallographer named Maurice Wilkins, who had produced some of the first X-ray diffraction images of DNA. Wilkins soon recruited both men to help him make sense of his raw data.

At the time, prominent labs around the world were racing to discover the structures of proteins. Protein research made up the bulk of the crystallography work being done at the Cavendish. As for solving the structure of DNA, the most serious competition Watson and Crick faced was from a team led by Linus Pauling at Caltech, but Pauling was handicapped by his lack of access to the state-of-the-art X-ray data being produced in Cambridge. By 1953, Watson and Crick were accessing increasingly detailed data provided by a researcher who had taken over the lead role in much of the Cavendish's DNA work: Rosalind Franklin, a chemist and the niece of former home secretary Herbert Samuel. Drawing upon the raw data provided by Franklin's increasingly sophisticated crystallographic work, Crick and Watson were finally able to deduce the structure of DNA.
^§

It became one of the most recognizable and beautiful images in science: the twisting double helix of DNA, two long strands of nucleotides wrapped around each other like a tiny caduceus. It was a structure that might have been envisioned by Salvador Dali. Most critically, it had all the attributes that scientists expected to find in the carrier of genes. As early as 1927, the Soviet scientist Nikolai Koltsov had proposed that genes were passed along by a hereditary molecule consisting of “two mirror strands that would replicate.”
^¶
In 1934, Haldane had guessed that genes copied themselves by means of complementary templates. By the time Crick and Watson set out to find proof that DNA was indeed the carrier of genetic information, they knew they were looking for complementary strands that could serve as a template. The structure of the DNA double helix fit like a glove.

In May of 1953, three complementary papers announcing the discovery of the double-helix structure of DNA appeared in
Nature
—one authored by Crick and Watson, one by Maurice Wilkins, and a final paper by Franklin. The structure, Watson and Crick wrote, “suggests a possible copying mechanism for DNA.” The articles appeared just a few weeks before Miller published the results of his own experiment in
Science
. Yet in contrast to the barrage of stories that trumpeted the discovery of the generation of amino acids from inorganic elements, the discovery of DNA's structure received almost no notice in the popular press. A short article entitled “Form of ‘Life Unit' in Cell Is Scanned” had been slated to run in the
New York Times
, but it was pulled at the last minute, presumably because the editors thought it insignificant.
^#

Despite having just made one of the most important discoveries of the century, Crick was put back to work on the structure of hemoglobin. The idea that proteins still played a significant role in inheritance did not die quickly. Many scientists persisted in the belief that DNA and proteins had
a kind of symbiotic relationship in controlling the flow of genetic information, that while DNA shared information with proteins, proteins also shared information with DNA, making them cocarriers of genetic inheritance. Crick gradually won support for what he had at first controversially called the “central dogma” of biology: that genetic information can be passed from nucleic acid to protein, but not vice versa. Acceptance of DNA as the sole carrier of genetic information would come only after Crick spent the next thirteen years deciphering the intricate language that organisms have used to speak to each other for billions of years, the genetic code.

An iconic 1953 image of Watson and Crick with a DNA double helix model.

T
HE GENETIC CODE IS
the oldest language we know of. It is as old, or at least nearly as old, as biology itself. For billions of years, it has been “spoken” by every cell of every living thing. It has only four letters, each recorded by the presence of a specific chemical. It is typically translated as A, C, G, and T, the letters corresponding, respectively, to the chemicals adenine, cytosine, guanine, and thymine, which are the bases of nucleotides, all arranged in long strings composed of three-letter words.

It should have come as no surprise that the code's eventual unraveling began in Great Britain, the nation where Alan Turing and his Bletchley Park colleagues had turned their skills to breaking German ciphers during the war and constructed one of the world's first computers. With the help of several scientists, including the Russian-émigré physicist George Gamow, most noted for his advancement of the Big Bang theory, Crick and colleagues managed to crack the basic underlying structure of biology's genetic language. By 1966, three years after Crick received a Nobel Prize for his role in establishing the structure of DNA, the code had been deciphered in its entirety, showing how each three-letter sequence, known as a codon, translated into corresponding positions in proteins. With this discovery, human beings could read the cellular language of living things.

As Crick worked on breaking the code, he also confronted the question of
how
exactly DNA communicates with proteins. A language that could not be understood was useless on its own. DNA had to be able to direct proteins to facilitate the sequential arrangement of amino acids. There had to be some kind of messenger between the two. Since the 1940s, some scientists had suspected that large molecules of a nucleic acid called ribonucleic acid, or RNA, played a role in the creation of proteins within cells. By 1958, Crick and others had largely worked out RNA's role in passing genetic information from DNA to proteins. Crick also noticed that RNA played a versatile role in the cell, that it resembled in some ways both DNA and proteins, the agents of replication and metabolism. Though it carried genetic information, he wrote, some RNA must have
once been capable of doing “the job of a protein.” He even speculated that the first living organism might have “consisted entirely of RNA.” His remark would eventually come to be seen as prophetic by many in the field of origin-of-life research.

A
S THE CENTRALITY
of nucleic acids in genetics began to be established in biology, it started to transform the way scientists looked at the origin of life. If, as it seemed, a particular subcomponent of a cell preceded the others, then either metabolism or genetics had to have developed first. One school of thought, which would come to be called “metabolism first,” saw the protein or something like it as the earliest key component of life. In contrast, other scientists, including Stanley Miller, thought that work on proteins was barking up the wrong tree, and that the development of DNA and of genetic machinery was the likely first step. Once replicating, mutable molecules existed, all else would follow through evolution. A protein bereft of a gene, they thought, could lead nowhere.

Sidney Fox always remained firmly in the metabolism-first camp. As most scientists in the field began to tilt heavily to replication or some combination of the two, he started to complain bitterly about what he called the “nucleic acid monopoly.” But the biggest problem Fox faced wasn't so much his insistence on the protein-first model for the earliest life. Rather, it was his dogged insistence that he had largely solved the problem of abiogenesis through his experiments on proteinoid microspheres. During the 1970s, Fox became fixated on the existence of differential electric charge that he found on the membranes of the microspheres, which to his mind was not unlike that which exists in living cells. As late as 1988, in his book
The Emergence of Life
, Fox went so far as to claim that these microspheres showed signs of a “rudimentary consciousness.”

The claim was met with incredulity and, in some cases, even ridicule in the origin-of-life circles in which Fox had once been so prominent. But he never lost the high esteem of administrators at NASA, and he continued to receive generous funding into the twilight of his career. And although he was an atheist, Fox even managed to secure an official position as an
occasional adviser to Pope John Paul II on the subject of the origin of life. By the time of his death in 1998, Fox was mostly ignored by his origin-of-life colleagues, and his unique ability to promote his own work among the organs of power stirred up more than a little jealous resentment.

The true legacy of Sidney Fox's work is more mixed. Fox's skills as an institution builder were instrumental in turning the study of the origin of life into a mainstream academic discipline. When many scientists were leaning toward the idea that the origin of life was a random, unique event, Fox stayed true to Oparin's vision of life's beginnings being part of an inevitable evolutionary progression. And though few scientists still view proteinoid microspheres as significant, the idea of the importance of some type of preprotein, a polymer of amino acids, has never been fully dismissed and would form the basis of many later theories as to how the first organism may have come into being.

L
IKE SIDNEY FOX
, Francis Crick would, in his later years, face many strains on his reputation. Some stemmed from his outspoken stance on controversial subjects; others, to his penchant for broad, daring hypothesizing. When correct, these ideas reinforced his reputation for genius. When wrong, they could make him appear a bit of a crackpot. He embraced the spirit of the late 1960s, wearing sideburns and colorful shirts and experimenting with LSD. He lent his name to a campaign to legalize marijuana in Britain. He also made several ill-advised comments in support of euthanasia and eugenics, which he came to regret.

Religion was another controversial topic that Crick did not shy away from. After his work on elaborating the nature of genetics, he had been named a founding fellow of Churchill College. It was a prestigious appointment. Named in honor of Winston Churchill, the college was meant to become a kind of British counterpart to American scientific universities like Caltech and MIT. But Crick soon resigned in protest of the building of an exclusively Christian chapel rather than, as Crick preferred, a nondenominational meditation room that could be used by people of all faiths. Crick was not fond of religion in general or Christianity in particular,
which, he once joked, “may be OK between consenting adults in private but should not be taught to young children.”

Crick moved on to the Salk Institute in California, named for the discoverer of the polio vaccine. There Crick turned his focus more thoroughly to the question of the origin of life. Joined by an old friend from Cambridge, Leslie Orgel, a leading authority in the origin-of-life field, Crick began to contemplate an early stage in the history of life in which amino acids were ordered into primitive proteins using a simple code that might have then evolved into the genetic code used in all modern organisms. He became fixated on the reasons why alternative codes had not arisen, spawning competing lines of descent.

Frustrated with his inability to make headway into the problem of the origin of life, Crick began exploring the idea that life might have originated elsewhere in the universe. In a 1973 article entitled “Directed Panspermia” in the planetary science journal
Icarus
, he and Orgel presented a theory that the Earth had been deliberately seeded with bacterium-like life-forms by an intelligent species from another solar system. Orgel treated the subject almost as a joke. Crick was not entirely unserious, though he knew it was wild speculation. They had based much of their argument on the puzzling abundance of molybdenum in cells. Since molybdenum is extremely rare in the Earth's crust, maybe, they argued, our ancestors emerged on a molybdenum-rich planet. Most scientists were quick to point out that pushing the problem of the origin of life off Earth did little to solve the problem, and quite a bit to complicate it.