Francis Crick's Discovery of the Structure of DNA Transformed 20th Century Biologic Sciences 


Get Permission

Courtesy of the Salk Institute for Biological Studies.

He is a giant. It’s fair to say Francis Crick defined the discipline of theoretical biology, and so far no other practitioners of that art have come up to that standard.

—Francis S. Collins, MD, PhD

“My Dear Michael, 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, called DNA for short.… In other words we think we have found the basic copying mechanism by which life comes from life,” wrote Francis Crick, PhD, on March 19, 1953, to his 12-year-old son Michael, who was a student at Bedales, a British boarding school. The 7-page handwritten letter, signed “Lots of love, Daddy,” just fetched $6 million at Christie’s auction house. Half of the money will go to Michael, now 72, and the other half to the Salk Institute for Biological Studies in California, where Francis Crick worked until his death from colon cancer on July 28, 2004, at the age of 88.

The letter was sent to Michael just weeks before Dr. Crick and his scientific collaborator James D. Watson, PhD, published their findings on the double-helix structure for DNA in the British scientific weekly Nature.In the paper, the authors described how pairs of bases on the inside of the two DNA backbones—adenine (purine) with thymine (pyrimidine), and guanine (purine) with cytosine (pyrimidine), or A-T and C-G—bond together in the middle of the double helix, suggesting a copying mechanism for the genetic material.

In a follow-up article in Nature the next month, the two described the mechanism for DNA self-duplication.2 “We feel that the proposed structure for deoxyribonucleic acid may help to solve one of the fundamental biological problems—the molecular basis of the template needed for genetic replication. The hypothesis we are suggesting is that the template is the pattern of bases formed by one chain of the deoxyribonucleic acid and that the gene contains a complementary pair of such templates,” wrote Dr. Crick and Dr. Watson.

The Gossip Test

Born Francis Harry Compton Crick on June 8, 1916, in Northampton, England, during the middle of World War I, Dr. Crick’s interest in science was evident from the time he was a young child. In his autobiography, What Mad Pursuit: A Personal View of Scientific Discovery (Basic Books, 1990), Dr. Crick describes how his constant questions about the world forced his parents to buy him the complete set of The Children’s Encyclopedia. Although he writes that he read all the sections on art, science, history, mythology, and literature “avidly,” it was the sections about science that captured his interest the most.

Dr. Crick earned a Bachelor of Science degree in physics from University College in London and planned to stay to work on a graduate degree in physics, when World War II erupted, altering his plans. He took a civilian job at the British Admiralty Research Laboratory developing radar and magnetic mines for naval warfare and helped design a new mine that was effective against German minesweepers. After the war, feeling intellectually restless, unsatisfied in his chosen field of physics, and unsure about what he wanted to do, he decided to change careers.

While still a member of the scientific staff at the Admiralty, Dr. Crick recounts in What Mad Pursuit, his conversations with naval officers about recent advances in antibiotics, including penicillin, led him to realize his interest wasn’t really in physics after all but in the life sciences. “I had discovered the gossip test—what you are really interested in is what you gossip about. Without hesitation, I applied it to my recent conversations. Quickly I narrowed down my interests to two main areas: the borderline between the living and the nonliving, and the workings of the brain,” wrote Dr. Crick.

Race to Discover DNA

In 1947, Dr. Crick took a position at Strangeways Research Laboratory in Cambridge, studying the physical properties of cytoplasm in cultured fibroblast cells. Two years later, he joined the staff of the Medical Research Council Unit at Cavendish Laboratory, where a scientific team led by molecular biologist Max Perutz was using x-ray crystallography to study the structure of proteins, a subject that became the focus of Dr. Crick’s doctoral thesis.

It was while working at Cavendish Laboratory that Dr. Crick began his friendship—and scientific collaboration—with American-born biologist James Watson, who joined the lab in 1951. By the time the two met, the race to discover the structure of DNA had already been going on for several years, and the experimental findings from those earlier efforts eventually led the two men to develop a theory of genetic transfer.

In 1948, Linus Pauling had discovered the single-stranded alpha helix, the structure found in many proteins, which prompted biologists to think of helical forms. It was Dr. Pauling’s method of model building in chemistry that Dr. Crick and Dr. Watson used to uncover the structure of DNA.

But perhaps the greatest boost to their DNA discovery came from the work of British molecular biologist Rosalind Franklin, who along with New Zealand–born physicist Maurice Wilkins, was studying DNA at King’s College in London the year Drs. Crick and Watson met. Dr. Franklin, an authority in the field of x-ray crystallography, was investigating x-ray diffraction images of DNA to understand the physical structure of the DNA molecule. She found that DNA can exist in two forms, depending on the humidity in the surrounding air. Her x-ray diffractions showed that the “wet” form of DNA had all the characteristics of a helix, and she suspected that all DNA was helical.

In January 1953, Dr. Wilkins showed Dr. Crick one of Dr. Franklin’s crystallographic portraits of DNA— reportedly without her knowledge—which enabled Drs. Crick and Watson to take the next conceptual step, suggesting that the molecule was made of two chains of nucleotides, each in a helix as Dr. Franklin had found but with one chain going up and the other down. In the spring of that year, Drs. Crick and Watson published their findings in Nature, acknowledging Drs. Franklin and Wilkins for their “unpublished experimental results.”

In 1962, Drs. Crick, Watson, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their discovery of the structure of DNA. Because the Nobel Prize is given only to the living, Dr. Franklin, who had died of ovarian cancer 4 years earlier, could not be considered for the award.

Discovery That Altered Science

Throughout the 1950s and 1960s, Dr. Crick investigated the relationship between DNA and genetic coding and explored other fields of study, including developmental biology and how genes control the growth and specialization of organs. In 1977, Dr. Crick changed the focus of his work again, this time to neurobiology and the neural underpinnings of consciousness. Also that year, he accepted an appointment as J.W. Kieckhefer Research Professor at the Salk Institute for Biological Studies.

Understanding the structure of DNA has led to the unraveling of how genetic instructions are passed on from one generation to the next and paved the way for the Human Genome Project. In an obituary of Francis Crick published in TheWashington Post in 2004, then Director of the National Human Genome Research Institute, Francis S. Collins, MD, PhD, said, “He is a giant. It’s fair to say Francis Crick defined the discipline of theoretical biology, and so far no other practitioners of that art have come up to that standard.”

In What Mad Pursuit, Dr. Crick was more circumspect of his and Dr. Watson’s accomplishment. “We both believed that DNA was important though I don’t think we realized just how important it would turn out to be.” ■

References

1. Watson JD, Crick FHC: Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid. Nature 171:737-738, 1953.

2. Watson JD, Crick FHC: Genetical implications of the structure of deoxyribonucleic acid. Nature 171:964-967, 1953.



Advertisement

Advertisement



Advertisement