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Francis Crick: Co-Discoverer of DNA's Double Helix

francis crick in his office
Francis Crick, shown here in his office is best known for co-discovering, along with James Watson, the structure of the DNA molecule.
Credit: PLoS Biol 2/12/2004: e419. http://dx.doi.org/10.1371/journal.pbio.0020419

Francis Crick was a pioneer molecular biologist who is credited, along with James Watson and Maurice Wilkins, with discovering the double helix structure of the DNA molecule. The trio won the Nobel Prize in Medicine in 1962 for their work.

Early life

Francis Harry Compton Crick was born June 8, 1916. His father, Harry, was manager for a factory producing shoes and boots. His mother, Annie, was a schoolteacher. Francis went to Northampton Grammar School, where he was introduced to basic physics and chemistry. At an early age, he attempted (unsuccessfully) to produce synthetic silk in the laboratory.

As a teenager, he won a scholarship to Mill Hill School, a private boys’ school in North London. He later said that he couldn’t remember himself as being “exceptionally precocious,” but he did recall studying Mendellian Genetics on his own. It interested him, and was not taught in school at the time.

He got a bachelor’s degree in physics from the University of London in 1937 before World War II interrupted his studies. During the war, he worked for the British Admiralty in helping to develop magnetic and acoustic mines.

Gossip test

Continuing his work in physics after the war proved unsatisfying. Crick decided to apply what he called the “gossip test” to decide his future. Crick felt that scientific insight and new discoveries could only come about when a person’s curiosity and dedication were aroused by passionate interest in a topic or question. He reasoned that the subjects a person chooses to talk about most often were the key to identifying that individual’s true interests.

Crick found that his conversations were dominated by two subjects. He loved to talk about the human mind and consciousness, and about a book he had just read. "What is Life? The Physical Aspects of the Living Cell," by Erwin Schrodinger, posed a question that Crick found fascinating: “How can the events of space and time which take place within the living organism be accounted for by physics and chemistry?” Crick decided that his background in physics had prepared him to help answer this question.

Lacking experience in the biological sciences, Crick knew he required training, so he went to work at Strangeways, a tissue culture laboratory affiliated with Cambridge University. He spent the next two years using familiar methods of physical science, such as quantitative analysis and quantum mechanics, to study an unfamiliar subject — the cytoplasm within cells. In 1949, he joined the Medical Research Council unit at the Cavendish Laboratory in London where he began his doctoral research using X-ray diffraction to study the structure of proteins. It was there that he met a young American named James Watson.

At the time, little was understood about the physical and chemical processes of heredity. Hershey and Chase had shown that DNA, a molecule found in the nucleus of living cells, was responsible for transmission of hereditary information during the formation of new cells.  What was not understood was how this process worked. How was the information copied from parent cells to daughter cells? How does a cell use this information to build the proteins and perform the other functions necessary for life? Crick and Watson felt that understanding the three-dimensional structure of the DNA molecule would help answer these questions. They decided to try building a visual model to help understand the molecular geometry DNA.

 It was known that DNA is composed a “backbone” consisting of repeating sugar/phosphate units and four nitrogen bases (adenine, cytosine, thymine and guanine), but how were these arranged? Were there two or three strands making up the molecule? Were the nitrogen bases configured on the outside or inside of the strands? Crick and Watson presented their first model, which used a three-stranded configuration with the bases on the outside. They paired matching nitrogen bases (for example pairing adenine and adenine or thymine and thymine). Visiting scientists, including a young woman named Rosalind Franklin, were harsh in their criticism. The model was unworkable; it answered none of the questions about how DNA could encode or copy genetic information.

Around this time, Crick and Watson came across two vital pieces of information. Jerry Donohue, a chemist visiting from the U.S. pointed out that the configuration for thymine and guanine that they were using in their models was incorrect. When Watson used the correct chemical bonding information to cut out new cardboard models of each nitrogen base, he made an exciting discovery. Using the new shapes it was obvious that the adenine bases would fit perfectly to thymine, and cytosine fit with guanine. Around the same time, Watson was shown Rosalind Franklin’s crystal radiograph of DNA, which he realized showed indications that the DNA molecule was double-stranded and that the nitrogen bases should be placed inside sugar/phosphate backbones, like rungs inside a ladder.

Crick immediately understood the implications of the new model. If the weak hydrogen bonds holding the base pair “rungs” of the ladder were broken then each half of the “ladder” could serve as a template for replicating the information coded by the order of nitrogen bases. The complementary pairing of adenine with thymine and cytosine with guanine explained how accurate information could be replicated each time a cell divides. Pairing the bases also showed how the molecule was twisted into a helix shape. On Feb. 28, 1953, Crick fascinated other scientists gathered for the evening at a local pub by announcing that he and Watson had “found the secret of life.” They presented their findings in the journal Nature, published on May 30, 1953.

Studying RNA

Crick’s most important work during the 1950s and 1960s concerned how the information in DNA is used by the cell to form the thousands of proteins necessary for life. In the mid- to late 1950s, Crick worked with a new team of scientists to discover how information from DNA, which is stored in the nucleus of the cell, could be transmitted to ribosomes in the cytoplasm, where proteins are synthesized. Crick and others suspected that ribosomal RNA (rRNA) was the messenger responsible; an idea that later proved to be incorrect.

Significant amounts of RNA had been found in ribosomes, and some RNA was present in the nucleus, but there were problems. Strands of rRNA were quite short while the strings of amino acids making up different types of proteins could be very long. Secondly, the amount of ribosomal RNA found in the cells of different species was constant, while the amount of DNA differs between species. Crick, working with Sydney Brenner, discovered that a different type of RNA (called messenger RNA) forms a temporary copy of a portion of the DNA template in the nucleus and transports this copy to the ribosome. Ribosomal RNA “reads” the code, and a third type of RNA (transfer RNA) moves through the cell finding the correct amino acids and bringing them to the ribosome to be assembled into proteins.

Crick next turned his attention to discovering how just four nitrogen bases could possibly code for the 20 amino acids that are the building blocks of proteins. It was apparent that groups of bases had to be “read” together to code for each type of amino acid.

The problem was math. Reading the genetic code in groups of two meant there were only 16 possible combinations (4x4.) However, if the ribosome read the code in groups of three bases, there were be 64 possible combinations (4x4x4) and only 20 amino acids. Seymor Benzer coined the term “codon” to mean a group of three bases in the ribosome and “anitcodon” for the corresponding bases on the transfer RNA. 

Crick hypothesized that transfer RNA had a group of bases at one end that would “plug in” to a corresponding group on the ribosome. The transfer RNA would pick up an amino acid on one end and transport it to the ribosome. A group of bases on the other end of the transfer RNA would “plug into” a matching group of three bases on the ribosome. The ribosome would then bond the amino acids into a protein chain.

In 1961, Crick proposed an experiment showing that transfer RNA had to be “read” in groups of three. Together with Brenner and Leslie Barnett, he introduced a mutagen that could either add or delete a base from the messenger RNA copy of the DNA information. Proteins synthesized from the altered code were deformed from the point where the addition or deletion took place.  Altered proteins were generally nonfunctional.

Crick explained that it was like a sentence made up of three letter-words in which a letter was altered. Everything following the alteration would be gibberish.

For example, the following sentence makes sense: The fat cat ate the big rat.

Deleting a letter causes a “phase shift” in all the following words.

The resulting sentence would be unrecognizable: Thf atc ata tet heb igr at

In the 1960s, Crick worked with several research teams. One important project “solved the genetic code,” showing that many amino acids are coded by more than one codon. (For example the amino acid Leucine can be coded by six different codons.) Crick also helped identify the “start” and “stop” codons which inform the ribosome when to stop adding amino acids to a protein chain and begin a new sequence. He became well known for his ability to work with many different people; leading colleagues into forming effective research teams. Others greatly respected the breadth and depth of his knowledge and his ability to correlate information from many sources and formulate workable theories.

In 1966, Crick shifted his research into broader questions. He wanted to know how genes control cell division, cell differentiation and organ growth. Together with the teams of researchers he led, his work helped form the basis of modern developmental biology which is one of the most productive areas of research today.

In the 1970s, Crick’s focus shifted once again. This time he turned to the second of the two passions he had revealed when applying the “gossip test” back at the start of his career. How are the human mind and human consciousness accounted for by the physical and chemical processes within the brain? During this period, Crick read extensively about new discoveries in the field of neurobiology and developed several important theories.

Notably, he is responsible for the idea of “attentional bias.” Attentional bias is how the brain screens sensory input about size, shape, color, movement, etc., allowing formation a concept and label for an object or event while avoiding sensory overload from irrelevant information. Another of Crick’s theories was that REM sleep and dreaming are the brain’s “house cleaning” mechanism to discard irrelevant memory and enhance the retention of functional memory.

Crick continued to work in the field of neurobiology throughout the 1980s and '90s.  He published a book, “Life Itself,” in 1981 about evolution and the possibility that microorganisms responsible for the first life on Earth were “seeded” by intelligence from space. In 1994, another book, "The Astonishing Hypothesis," explained his research in neurobiology and his belief that “our minds — the behavior of our brains — can be wholly explained by the interaction of nerve cells (and other cells) without cause by an outside vital force.”  Although an atheist, he was honest enough to admit that, “I have yet to produce any theory that is both novel and also explains the many disconnected experimental facts (about the human mind) in a convincing way.” He was working on another neurobiology book with Christof Koch up until a few days before his death from colon cancer on July 28, 2004.

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