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1999 Third Place Research Paper
Racing Through a Five-Billion-Year-Old Mystery: The Secret of DNA
Early 1953. Three labs, two in England and one in California, raced to discover the structure of deoxyribose
nucleic acid. At Cal Tech in Pasadena, California, Linus Pauling had recently discovered the alpha-helix. Now
he was turning his attention to DNA. At King's College in the University of London, Maurice Wilkins and
Rosalind Franklin, although hampered by their inability to get along with one another, had taken actual pictures
of DNA using x-rays and were hot on the trail. The most unlikely pair in the race, a 24-year-old American
biologist and a 36-year-old English physicist, were also close to identifying the elusive molecule, although they
were forbidden from directly working on it. And so the race intensified for the secret of life itself.
Get Ready, Get Set...
Mendel and Pea Plants
The events leading up to this race actually began with an Austrian monk named Johann Gregor Mendel.
Although in reality Mendel wanted to be a high school teacher, he failed the mandatory examination three
times and decided to become a monk to pursue his studies in the peace of a monastery (Asimov, Genes 11).
Interested in the inheritance of characteristics, he began working with pea plants in 1857. He crossed true-bred
plants and then their offspring and recorded the results. From these results he established general rules or laws
for inheritance. He worked for eight years and with over ten thousand different plants (Arnold 20). Looking for
a sponsor for his work, Mendel sent his paper to noted botanist Wilhelm von Nageli. Nageli sent it back after
barely glancing at it (Nageli died in 1891 and would be remembered, not for his own vast scientific work, but
for his failure to pay attention to Mendel) (Asimov, Genes 19-20). Mendel finally did publish his results in the
magazine of the National History Society of Brunn in 1866 (Arnold 7). Other botanists paid little or no attention
to his work, and his ideas about inheritance became lost for thirty-four years. Mendel became the abbot of his
monastery in 1868 and was too busy and discouraged to continue his experiments. He died in 1884, never
knowing that he would be touted as the "father of modern genetics."
The Early Work on DNA
In 1869, just after Mendel had quit working with plants, a 25-year-old Swiss chemist, Johann Friedrich
Miescher, discovered a substance called nuclein inside cells. This substance was later found to be attached to a
protein which was named "histone" from the Greek word meaning "cell." The combination of nuclein and this
protein, histone, was called a nucleoprotein and was held together because nuclein was an acid and histone was
a base. Nuclein then became known as nucleic acid.
Structure
A Russian-American chemist, Phoebus Aaron Theodore Levene, discovered one of the components of
nucleic acid in 1909. It was an altered ribose sugar that he called a deoxyribose--adding the "deoxy" which
means "minus the oxygen" in Latin (Asimov, DNA 18). The other two components of this nucleic acid were
found to be a phosphate group with phosphorus as its central atom and one of four groups of atoms called
nitrogenous bases. Two of these nitrogenous bases were made of double rings. One ring had six atoms and the
other five--two atoms were part of both rings for a total of nine atoms. Four of these nine atoms were nitrogen
and five were carbon. These two bases were classified in a group called purines. Scientists found that these two
purines had side chains which distinguished them from other purines. One of these two new purines was named
adenine, the other guanine. The other two nitrogenous bases were formed with one ring of six atoms--two
nitrogen and four carbon atoms. These were in the pyrimidine group. Side chains formed the pyrimidines
cytosine and thymine. One molecule of this nucleic acid, consisting of a phosphate group, a deoxyribose
sugar, and one of the four nitrogenous bases was called a nucleotide. This particular type of nucleic acid was
called deoxyribonucleic acid or DNA.
Mendel's "Traits" Become "Genes"
In the first decade of the nineteenth century, new discoveries helped give Mendel's ideas about heredity a
physical basis in the cell. These discoveries included:
Dutch botanist Hugo de Vries, German botanist Karl Erich Correns, and Austrian botanist Erich Tschermak von
Seysenegg each independently did experiments similar to Mendel's, and in preparing to publish their papers,
rediscovered Mendel's work in 1900.
An American biologist, W. S. Sutton, then related Mendel's inheritance of traits to a structure found in the
nucleus of the cell, the chromosome.
In 1909, Wilhelm Ludvig Johannsen, a Danish botanist, suggested the name of "gene," from a Greek word
meaning "to give birth to," for each portion of a chromosome relating to a physical characteristic (Asimov,
Genes 40).
Scientists now had a concrete substance to search for which described why children look like their parents.
Furthermore, they knew where to begin looking--in the nucleus of the cell.
The Transforming Principal
In 1928, Frederick Griffith, Jr., an American biologist, worked with the bacterium pneumococcus, which causes
pneumonia. He proved that there was a "transforming principal" that transferred genes from one bacteria to
another.
The Protein Paradigm
Although both DNA and protein were found in the chromosome of the cell, protein was thought to be the
substance that transferred information from one generation to the next. Scientists believed that this
"transforming factor"must be able to make many different combinations to account for the diversity of life.
Proteins were huge molecules made up of any combination of twenty amino acids and from hundreds to
hundreds of thousands of atoms. This resulted in possibly trillions of different arrangements of number and
order within each protein. DNA, by contrast, was only made of four different nitrogenous bases and was, at the
time, thought to be a fairly small molecule.
Paradigm Shift
This paradigm, that protein carried genetic material, shifted somewhat in 1944, when Canadian-American
biologist Oswald Theodore Avery and two co-workers, Colin Munro MacLeod and Maclyn McCarty, purified
Griffith's "transforming principal." They found that the substance that carried genetic material contained only
DNA--no protein. Some scientists refuted their results, claiming that Avery's samples were not totally free of
protein. Many still favored a protein or nucleoprotein combination for the transforming factor, despite the new
evidence.
Further evidence for DNA as the transforming factor came in 1952 from Alfred Day Hershey and Martha
Chase, working in Cold Springs Harbor Laboratory on Long Island, New York. They found that when a virus
invaded a cell, only the DNA entered the cell. This DNA then made more DNA and protein. Since only DNA
had entered the cell, this DNA must be the transforming factor that transferred the genetic material.
Hidden Pieces of the Puzzle
Along with Avery's transforming principal experiment in 1944, a new method of analyzing mixtures called
paper chromatography helped Austrian-American biochemist Erwin Chargraff find equal numbers of the
purines--adenine and guanine--and the pyrimidines--cytosine and thymine--in DNA. (Watson and Crick would
later use this clue to figure out how the bases paired with each other.)
In 1951 American chemist Linus Pauling, working at Caltech in California, discovered an alpha-helix, a chain
of amino-acids (which make up proteins) twisted into a helix like a spiral staircase. A few scientists
hypothesized that DNA might also be a helix similar to the one Pauling had discovered.
And so the stage was set for the race to the structure of DNA.
...Go!
The Contenders
The lab at King's College, the closest of the three labs to discovering the structure of DNA, was headed by New
Zealand-born Maurice Hugh Wilkins and his "assistant" Rosalind Elise Franklin, but their inability to work
together slowed their progress. Wilkins had brought Franklin to King's college to take x-ray pictures of DNA
using a method developed in 1912 in which molecules were bombarded with x-rays. The x-rays would hit the
atoms and bounce back onto film, but pass through the empty space. This created x-ray diffraction pictures and
was called x-ray crystallography. Despite Franklin's talent in taking x-ray pictures, "almost from the
moment she arrived in Maurice's lab, they had began to upset each other" (Watson 20). Franklin took over
the work on DNA as her own and would often not even share her pictures with Wilkins. Wilkins was not so
tight with these pictures, showing one of them to colleague James Watson when Watson visited his lab. Watson
and his partner, Francis Crick, were convinced that the image suggested a helical structure similar to the one
Pauling had discovered two years earlier in alpha-helix, but Franklin wouldn't hear of it.
The second contender in the race was Linus Pauling, one of the most noted chemists in the world. He had
recently been working on the super-coiling of his new molecule, the alpha-helix, in hair protein, but was now
turning his attention to DNA. As with the alpha-helix, he used very little experimentation and relied on
principals of chemistry to build models of what the molecules should look like. His son, Peter, happened to be
studying at Cambridge and shared an office with Watson and Crick. He kept them advised of his father's work.
Pauling proposed a structure for DNA in February 1953, but the molecule was incredibly off. Pauling had not
even represented DNA as an acid. In his autobiographical book, James Watson stated that, "if a student had
made a similar mistake, he would be thought unfit to benefit from Cal Tech's chemistry faculty" (103). Despite
this blunder, Pauling soon learned about his mistake and was immediately back in the race.
The third team, Englishman Francis Harry Compton Crick and American James Dewey Watson began
working in the same lab in 1951. They enjoyed talking about theory and especially DNA. Upon forming a
three chain structure of DNA in 1951, they were sharply and quickly made aware of their mistakes by Wilkins
and Franklin. The director of their lab, Sir Lawrence Bragg, told them to stop working on DNA and encouraged
Crick to finish his doctoral thesis. (Bragg didn't really like the loud, obnoxious Crick and felt he could not get
rid of him until he had at least finished his doctorate.) While Watson worked with the Tobacco Mosaic Virus
and bacteria sex, Crick did his doctoral work--investigating ways that hemoglobin crystals shrink when they are
placed in salt. But they continued to talk DNA at lunch and on afternoon walks (Watson 68).
The Finish Line
Amid the exciting new work, Watson and Crick again became engrossed in DNA. They used both Pauling's
model building techniques and the photographs of Franklin and soon came up with a model that paired like
nitrogenous bases to themselves (i.e. adenine with adenine, thymine with thymine, etc.). Within a day, Jerry
Donobue, an American crystallographer who shared the office, informed them that this structure would not
work (Watson 120). They lost no time and began manipulating the nitrogenous bases. They soon had a
molecule that met the requirements of the photograph of DNA and the laws of chemistry. They had beat
Pauling, Wilkins, and Franklin in their own game. The array of atoms connected to form molecules and
twisted into a double helix in their office contained the secret of life. Watson and Crick had unraveled a five
billion year old mystery.
The Prize
The structure Watson and Crick had worked out was a double helix with the nitrogenous bases on the
inside and the deoxyribose and phosphate on the outside. The nitrogenous bases were connected with
hydrogen bonds. Adenine always bonded with thymine and guanine always bonded to cytosine. This structure
could unzip like a zipper to be copied and replicated, automatically explaining how it worked in creating new
cells. Watson and Crick's paper was published in "Nature" on April 25, 1953, forever changing our perceptions
of our own selves. Crick's wife Odile, an artist, drew up the picture of the molecule. Crick later said that "it's her
best-known work, she normally draws nudes" (Hall 1533). In "one of the great understatements in literature,"
the paper only modestly hinted at the profound importance of the structure in explaining how genes worked,
stating, "it has not escaped our notice that the specific pairing we have postulated immediately suggests a
possible copying mechanism for the genetic material" (Hall 1532). The paper, along with a second one by
Watson and Crick further expounding their theory, created a new science--giving molecular biology its "charter
molecule" (Hall 1532). At the time he helped create this new science, Watson was only 24 years old. "It's sort of
taken 40 years to feel that I'm almost justified finding the double helix," said a 65 year old James Watson in
1993 of the discovery that shall cause him to live immortally in history books (Hall 1532).
Impact
From the early experiments, beginning with Mendel, to the "blaze of understanding" of Watson and Crick,
DNA has had tremendous impact on the scientific world. It brought with it a new science--molecular
biology--that has pervaded everything "from evolution and microbiology, through physiology, embryology,
neurobiology, psychology to medicine, nutrition, pharmacology, and agriculture" (Stent 22). Today,
manipulation and translation of this powerful molecule--that determines to a large part who we are and what we
look like--has become one of the fastest expanding fields in science. This scientific revolution was begun by
two scientists in a lab in early 1953 who won a race to DNA's structure. Although the molecule Watson and
Crick discovered has been instrumental to life for billions of years, it is significant that a creature has finally
arisen that can understand and manipulate the DNA that created it. And so life comes full circle with the created
becoming the creator and the creator becoming the created. DNA--the molecule that directs the physical
creation of all life on Earth--has become the "watershed of life sciences in the twentieth century" (Stent 22).
Works Cited
Arnold, Caroline. Genetics From Mendel to Gene Splicing. New York: Franklin Watts, 1986.
Asimov, Isaac. How Did We Find Out About DNA? New York: Walker Publishing Company, Inc., 1985.
----------. How Did We Find Out About Genes? New York: Walker Publishing Company, Inc., 1983.
Hall, Stephen S. "Old School Ties: Watson, Crick, and 40 Years of DNA." Science 12 Mar. 1993: 1532-1533.
Stent, Gunther. "DNA's Stroke of Genius." New Scientist 24 Apr. 1993: 21-23.
Watson, James D. The Double Helix. New York: The New American Library, Inc., 1968.
Works Consulted
Lederberg, Joshua, Ph.D. "The Transformation of Genetics by DNA: An Anniversary Celebration of Avery,
MacLeod, and McCarty (1944)." Genetics Feb. 1994: 423-426.
--------. "What the Double Helix (1953) Has Meant for Basic Biomedical Science." JAMA (Journal of the
American Medical Association) 21 Apr. 1993: 1981-1985.