This lesson will discuss the life and scientific contributions of Francis Crick, a prominent English physicist and biochemist who was part of the team responsible for the discovery of the structure of the DNA molecule.

Francis Crick
Francis Crick

Introduction

One of the most remarkable and important events in modern biology was the discovery of the structure of the DNA molecule. This structure is called a double helix. While efforts were being made in both England and the United States to make this discovery, it was a pair of scientists from the Cavendish Laboratory at Cambridge University in London who were able to describe what the molecule looked like and be the first to publish their findings. Francis Crick, an English biochemist, was part of that team. But, as remarkable as this discovery was, it was not Crick’s only work.

The Life of Francis Crick

Francis Harry Compton Crick was born on June 8, 1916 in Northampton, England. He was the older son of Harry Crick, the manager of a shoe factory, and Annie Wilkins, a schoolteacher. Francis attended Northampton Grammar and Mill Hill schools in London and then went on to study physics at University College in London. He graduated with honors with his B.Sc. degree in 1937.

Crick Starts His Career

Crick pursued his graduate degree at University College, but the outbreak of World War II interrupted his studies in 1939 (in fact, it was a bomb hitting his laboratory that took him from his work). He left college and worked for the British Admiralty during the war, designing acoustic and magnetic mines that were used by the British Navy.

Crick stayed in this position until 1947, when he left the Admiralty and took a position at the Strangeways Research Laboratory, located at Cambridge University in London, working on the behavior of fibroblasts (a fibroblast is a type of cell that makes fibers, such as collagen, in the body). This gave Crick the biology knowledge he would need for his next position.

After two years at Strangeways, Crick moved over to the Medical Research Council (MRC) Unit of the Cavendish Laboratory at Cambridge, working on x-ray crystallography of proteins. The MRC had the primary responsibility for promoting all of the biomedical research happening in England. With this move, Crick joined a group of other former physicists who had made the transition into molecular biology.

Scientists such as Max Delbruck and Maurice Wilkins made this shift to molecular biology because they wanted to apply the ideas that were essential to physics (such as quantum mechanics and 3-D model building) to biology, which they saw as being less structured. Crick’s ideas and values fit right in with this frame of thinking. While working at the MRC, he enrolled as a graduate student, completing his thesis investigating the x-ray crystallography of protein structure in 1953.

Also in 1953, Crick and an American scientist named James Watson made what was probably the biggest discovery of their careers, which was the structure of the DNA molecule. This effort led both men (along with Maurice Wilkins and Rosalind Franklin) to the Nobel Prize in Physiology or Medicine in 1962.

After the Nobel Prize

After his graduation and discovery of the structure of the double helix, Crick spent the next year working at the Polytechnic Institute in Brooklyn, New York. He returned to the MRC the following year, and would spend the next 22 years of his career there. He rejoined Watson in 1955 and the two developed ideas about viruses and their molecular structure. He also worked with other visiting scientists on projects pertaining to the structure of proteins and other biological molecules. In the mid-1960s, Crick changed his focus and began trying to understand how genes cause the growth of certain organs.

While he never taught or advised students, Crick was very much in demand on the lecture circuit. Partly due to his fame with the double helix, and partly due to his vast fund of knowledge about genetics and developmental biology, many universities all over the world called upon him to give talks and present his research.

In 1976, Crick got a year’s research fellowship at the Salk Institute for Biological Studies in La Jolla, California, and in 1977 took a permanent position there. He took this opportunity to refocus his research once again, this time towards neurobiology. He studied the eyes and how humans see, and also how nervous impulses were able to trigger memories and other thought processes. He spent the rest of his career (and life) at the Salk Institute.

Francis Crick died from colon cancer on July 28, 2004. He left behind his wife, Odile, a son from his first marriage, and two daughters from his second marriage.

Crick, Watson, and the ‘Race’

In 1951, Crick met an American biochemist named James Watson, who would turn out to be one of his longest and most valued friends in his professional career. Although Watson was 11 years younger than Crick, the two men got along splendidly, although they did argue quite a bit. Their skills were quite complementary to each other as well. Crick had the knowledge of x-ray diffraction and protein structure, while Watson was versed in phage and bacterial genetics. They felt they needed to know how the DNA molecule looked or else the concepts of heredity and reproduction could never be fully understood. They set out to find its structure in the fall of 1951.

Background of DNA

DNA had been known since 1869 and was widely thought to be the factor that carried traits from parent to offspring. It was known that it was made up of nucleotides (the small molecules containing a sugar, a phosphate group, and a nitrogen base that make up nucleic acids), but it was unclear how these pieces fit together to form the structure of DNA.

Previous research on the subject of DNA indicated that there were four nitrogen bases: adenine, thymine, cytosine, and guanine (A, T, C, and G), and that there were equal amounts of A and T and C and G. It was also known that these nitrogen bases were complementary, meaning each one only fit together with one other based on its shape. This knowledge came from the work of Erwin Chargaff in 1950. He surmised that, based on their shape, A could only pair with T and C could only pair with G. This came to be known as Chargaff’s Rule and was very helpful in Crick and Watson’s work.

The ‘Race for the Double Helix,’ as it has been called, is a story about how scientists, no matter how intelligent they are or how many discoveries they have made, can be petty, deceitful, and act in very underhanded ways when trying to make a big discovery. The scientists involved knew that whoever made the discovery first would secure their place in the annals of scientific history. As a result, it has been alleged that there were many episodes of betrayal, lying, and scheming while the hunt was on for the structure of DNA.

The Discovery

Crick and Watson were working with Maurice Wilkins and Rosalind Franklin from King’s College on this discovery. Wilkins and Franklin were x-ray crystallographers, meaning people who use x-rays to take pictures of macromolecules. These pictures were an essential part of Crick and Watson’s research because they would take the pictures and then build 3-D models of what they saw.

One of the anecdotes about how the discovery of the double helix was made includes a picture called Photograph 51 (taken by Franklin) that had been put in a drawer in Wilkins’ lab and forgotten about. One day after Franklin had left his employ, Wilkins was going through some old papers and came across that picture. He immediately recognized it as a DNA molecule and raced across town to Cavendish to show it to Crick and Watson. It was at this point they knew they had found what they were looking for. They constructed a model using metal wires and balls, and on April 25, 1953 announced to the world that they had discovered the structure of the DNA molecule. They called it the double helix.

The double helix looks very much like a ladder that has been twisted at both ends. The sides of the ladder are made of the sugar deoxyribose and alternating phosphate groups, while the rungs of the ladder are the nitrogen bases (A, T, C, G). The nitrogen bases are held together with hydrogen bonds (hydrogen bonds are the attraction between a hydrogen atom with a positive charge and another atom with a negative charge – a fact that would become very important in later work on how DNA replicated itself during cell division).

As a result of their work, Crick, Watson, and Wilkins were awarded the Nobel Prize in Physiology or Medicine in 1962. Franklin had died a few years earlier and was awarded her Prize posthumously.

Crick’s Other Work

While his work with Watson and the discovery of the double helix was probably the most important of his career, Crick was also involved in many other types of research, ranging from the genetic code (the sequence of nitrogen bases on a DNA molecule) to how humans create consciousness. Knowing the structure of the double helix and how the nitrogen bases fit together made Crick wonder if there was any importance to the sequence of those bases. His research led him to the conclusion that it was, in fact, the order of the nitrogen bases that controlled the synthesis of proteins. It was these proteins that caused the expression of traits in an organism.

The Central Dogma

Crick discovered that the long chains of nitrogen bases found within the DNA molecule were the blueprint for the creation of 20 common amino acids, which could then be reformed and condensed into proteins. Once he had determined this, the hard part was figuring out which sequence of nitrogen bases could be used to make an amino acid (something that would later be accomplished by Watson and the Human Genome Project in the 1990s). He made the assumption that once the sequence had been passed on from the DNA (probably to the RNA, although he did not know for certain), it was used to put together the amino acid chains.

Crick called this sequence hypothesis the ‘Central Dogma,’ an idea that has become a cornerstone of molecular biology. The idea is that DNA codes for a sequence of RNA, then undergoes some change in form in order to assemble the amino acids, which in turn bend and fold to make proteins.

The biggest problem with this idea was to figure out how many of the nitrogen bases coded for the 20 amino acids. Crick figured that the code could not have two bases in it because that would only mean a possible 16 amino acids (4×4). However, he suggested that if there were three bases in each code, that would provide 64 possible combinations (4x4x4), but that was far too many to code for just 20 amino acids.

Crick proposed that, in order for there to be a triplet used to code for each amino acid, there would have to be some form of mutation to the DNA that would alter one of the three nitrogen bases. He tested this hypothesis in 1954 and found that, in fact, no mutation appeared, so was unable to finish his work. He did, however, establish that the genetic code was universal to all higher life forms and that acquired changes in proteins could not be passed on from parent to offspring (an idea that was central to Darwin’s ideas of evolution).

Another Change in Research Topics

In 1966, Crick changed the focus of his research to how organogenesis (the formation of organs during development), cell division, and cell differentiation were controlled by genes. He was able to merge his knowledge of DNA with embryology and study how these things happened in higher organisms (since up to this point, much of the accumulated knowledge was from studies on bacteria and viruses). He felt that an understanding of this would build the understanding of how life worked and also give insight into certain genetic diseases.

Crick continued his work in developmental biology until the mid-1970s, when he traveled across the Atlantic to the Salk Institute. It was here that Crick abandoned his previous work and started his new career as a neurobiologist, one that he would have for the rest of his life. He wanted to study the pathways and connections in the brain, because only then would it be possible to determine how behavior and emotions were created. While it took him a while to get started in this field (because many other scientists constantly relied upon him for his genetics knowledge), he turned out to be more of an ‘idea man’ than a researcher. He proposed many new ideas and experiments for others to investigate.

Crick was editing a paper on the human brain when he died in 2004.

Conclusion and Thoughts

Francis Crick was a scholar, author, and lecturer, world-renowned for his work in genetics and his co-discovery of the double helix. Like many others of the time, Crick had several areas of interest over the years, ranging from genetics and molecular biology to brain science. He always invested everything he had into his work and was able to depend upon his previous experiences to work through current problems.

Crick was the author of four textbooks and over 130 scientific papers and articles. In addition to the Nobel Prize, he was also the recipient of several distinguished honors (although he was never knighted). He was a Fellow of the Royal Society and a member of the U.S. National Academy of Sciences, the French Academy of Sciences, and the Irish Academy of Sciences. He also won the Lasker Award, along with Watson and Wilkins, which is often called the ‘American Nobel Prize.’

Francis Crick was one of the most influential scientists of the 20th century. His work on the discovery of the double helix, along with his research in genetics and developmental biology has led to many important discoveries about human development and the origins of many genetic diseases.

Learning Outcomes

When you are finished, you should be able to:

  • Recall who Francis Crick was
  • Summarize Crick’s career
  • Detail how the structure of DNA was discovered
  • Explain the ‘Race for the Double Helix’
  • Summarize some of Crick’s other work
  • State the Central Dogma