The double helix

Crime scene evidence. Paternity Testing. Designer babies.

Today, it is well-known that DNA is the molecule containing our genetic code.
Whether on crime programmes, tabloid talk shows, or in your daily newspaper,
DNA will be mentioned without need for an explanation. But what is DNA and
how long have we known about it? And who really deserves the credit for our
current knowledge? To begin to study Genomics, we must look at the history of
how we came to learn about and understand DNA.

It all started way back in the late 19th century, when a German biochemist
discovered that the nucleic acids, DNA and RNA, consisted of long chains of
subunits known as nucleotides. Each nucleotide is made up of a base, a sugar
and a phosphate. DNA has deoxyribose as its sugar and the bases can be
adenine (A), guanine (G), cytosine (C), or thymine (T).

However, it wasnt until 1943 that an unassuming American scientist, Oswald

Avery, proved that DNA carried genetic information. He was pooh-poohed at
first most people thought that it was proteins that carried genetic information,
and that DNA was just a boring collection of bases.

Oswald T Avery Rockefeller Archive Center

However, soon, despite the fact that much of the world was still at war, his
discovery was accepted. The scientific spotlight turned to DNA.

Still, DNAs exact structure remained a mystery.

During the war, an Austrian biochemist named Erwin Chargaff fled the Nazis to
America. Chargaff read Averys work and immediately focused the work of his
laboratory toward the study of DNA. In 1950, Chargaff discovered that the
bases A and T and C and G always occurred in a 1:1 ratio, suggesting that they
were paired in some way. But this finding remained largely unknown.

By the early 1950s, the race was on to determine the structure of DNA. The
American team was led by Linus Pauling at Caltech, and was widely tipped to

be the favourite to find the structure first. In the meantime, two British teams,
one based at Kings College London, and another, at Cambridge, worked hard
to find the answer.

The Cambridge team was led by two young scientists, American research
fellow, James Watson and graduate student Francis Crick. They tried to pinpoint
the structure by making physical models to narrow down the possibilities. On
the Kings team were Maurice Wilkins and Rosalind Franklin, two scientists who
had a notoriously difficult relationship. The Kings team were taking a more
experimental approach than the Cambridge scientists, looking at X-Ray
diffraction images of DNA obtained by Franklin. X-ray diffraction was a tool that
allowed scientists to determine the structure of crystalline molecules by the
way they scattered X-Ray beams. Franklin was a world expert in
crystallography and pioneered the use of this technique to look at complex
crystallised solids. She determined that there were two forms of DNA; the
crystalline form and the wet form, dissolved in water.

In 1951, Watson took a day trip to London to attend a lecture of Franklins, in

which she presented her initial findings on her photographs of DNA.

He raced back to Cambridge and relayed what he remembered of the lecture to

Crick. The pair then used this information to build a new model of DNA; a triple
helix, with the bases on the outside of the molecule. Excited, they invited
Franklin and Wilkins to their laboratory to test the structure against Franklins
pictures.

X-ray of Double Helix Kings College London

It was wrong. Embarrassing and wrong. Their head of lab told the humiliated
pair to stop DNA research. Was DNA as a helix dead?

Maybe not. Over in California, Pauling was building his own models. He asked to
see Franklins pictures but Wilkins, keen not to hand them over to a competitor
in the race, told him they were not ready to share. Nonetheless, in early 1953,
Pauling announced that he had discovered the structure of DNA.

Watson panicked. Pauling was his closest rival. Had he got there first?

He studied Paulings structure. It was also a triple helix. Watson knew this was
wrong and breathed a sigh of relief. But they still couldnt relax. Pauling would
find out his mistake soon enough. Watson and Crick would still have to hurry if
they wanted to beat him.

Back in London, Franklin continued to study her X-Ray diffraction pictures. By

January 1953, her preliminary findings were that DNA in its wet form did show
the characteristics of a helix. However, in her typically cautious style, she was
not ready to share these findings. She wanted to confirm them first. Before she
could, and apparently without her knowledge or consent, Wilkins, growing
frustrated and impatient, showed her results to Watson.

From there, Watson and Crick took a big conceptual step. They suggested that
the DNA molecule was made up of two chains of nucleotides, each in a helix, as
Franklin found, but with one chain that went up and another that went down.
This is what we now call the double helix. They used Chargaffs finding about
the 1:1 base ratios to add to the model, determining that matching base pairs
A and T and C and G interlocked in the centre of the double helix, keeping a
constant distance between the chains.

They went on to show that each strand of DNA was a template for the other, so
that DNA can replicate without changing its structure. This explained one of
lifes great mysteries: how genetic information can be inherited. The double
helix structure of DNA fit the experimental data perfectly and the scientific
community accepted it almost immediately. It was probably the most important
biological work of the last century and it forms the basis for the evolving field
of genetics and genomics.

In 1962, Watson and Crick won the Nobel Prize for physiology/medicine, sharing
it with Wilkins. By then, Franklin had sadly died of ovarian cancer, possibly as a
result of her work with X-Rays. Now, few people know her name. She, along
with others such as Chargaff and Avery who contributed much to the discovery
of the double helix, died without recognition.