Microbiology and Immunology

DNA (deoxyribonucleic acid) WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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It was not clear how this relatively simple structure

could assume enough different conformations to “code” for

hundreds of thousands of genetic traits. In comparison, a sin-

gle protein molecule contains various arrangements of twenty

fundamental units (amino acids) making it a much better can-

didate as a carrier of genetic information.

Yet, experimental evidence began to point to a possible

role for nucleic acids in the transmission of hereditary charac-

teristics. That evidence implicated a specific sub-family of the

nucleic acids known as the deoxyribose nucleic acids, or

DNA. DNA is characterized by the presence of the sugar

deoxyribose in the sugar-phosphate backbone of the molecule

and by the presence of adenine, cytosine, guanine, and

thymine, but not uracil.

As far back as the 1890s, the German geneticist

Albrecht Kossel (1853–1927) obtained results that pointed to

the role of DNA in heredity. In fact, historian John Gribbin has

suggested that the evidence was so clear that it “ought to have

been enough alone to show that the hereditary informa-

tion...mustbe carried by the DNA.” Yet, somehow, Kossel

himself did not see this point, nor did most of his colleagues

for half a century.

As more and more experiments showed the connection

between DNA and genetics, a small group of researchers in the

1940s and 1950s began to ask how a DNA molecule could

code for genetic information. The two who finally resolved

this question were James Watson, a 24-year-old American

trained in genetics, and Francis Crick, a 36-year-old

Englishman, trained in physics and self-taught in chemistry.

The two met at the Cavendish Laboratories of Cambridge

University in 1951. They shared the view that the structure of

DNA held the key to understanding how genetic information

is stored in a cell and how it is transmitted from one cell to its

daughter cells.

The key to lay in a technique known as x-ray crystal-

lography. When x rays are directed at a crystal of some mate-

rial, such as DNA, they are reflected and refracted by atoms

that make up the crystal. The refraction pattern thus produced

consists of a collection of spots and arcs. A skilled observer

can determine from the refraction pattern the arrangement of

atoms in the crystal.

Watson and Crick were fortunate in having access to

some of the best x-ray diffraction patterns that then existed.

These “photographs” were the result of work being done by

Maurice Wilkinsand Rosalind Elsie Franklin at King’s College

in London. Although Wilkins and Franklin were also working

on the structure of DNA, they did not recognize the informa-

tion their photographs contained. Indeed, it was only when

Watson accidentally saw one of Franklin’s photographs that he

suddenly saw the solution to the DNA puzzle.

Watson and Crick experimented with tinker-toy-like

models of the DNA molecule, shifting atoms around into var-

ious positions. They were looking for an arrangement that

would give the kind of x-ray photograph that Watson had seen

in Franklin’s laboratory. On March 7, 1953, the two scientists

found the answer. They built a model consisting of two helices

(corkscrew-like spirals), wrapped around each other. Each

helix consisted of a backbone of alternating sugar and phos-

phate groups. To each sugar was attached one of the four nitro-

gen bases, adenine, cytosine, guanine, or thymine. The

sugar-phosphate backbone formed the outside of the DNA

molecule, with the nitrogen bases tucked inside. Each nitrogen

base on one strand of the molecule faced another nitrogen base

on the opposite strand of the molecule. The base pairs were not

arranged at random, however, but in such a way that each ade-

nine was paired with a thymine, and each cytosine with a gua-

nine.

The Watson-Crick model was a remarkable achieve-

ment, for which the two scientists won the 1954 Nobel Prize

in Chemistry. The molecule had exactly the shape and dimen-

sions needed to produce an x-ray photograph like that of

Franklin’s. Furthermore, Watson and Crick immediately saw

how the molecule could “carry” genetic information. The

sequence of nitrogen bases along the molecule, they said,

could act as a genetic code. A sequence, such as A-T-T-C-G-

C-T...etc., might tell a cell to make one kind of protein (such

Computer-generated image of the DNA double helix, showing the

deoxyribose backbone (vertical ribbons) and the linking nucloetides

(horizontal bars).

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