History of DNA as the Genetic Material

Until early in the nineteenth century, it was believed that living matter was quite different from inanimate matter and was not subject to the normal laws of chemistry. In other words, organisms were thought to be made from chemical components unique to living creatures. Furthermore, there was supposedly a special vital force that mysteriously energized living creatures. Then, in 1828, Friedrich Wohler demonstrated the conversion in a test tube of ammonium cyanate, a laboratory chemical, to urea, a "living" molecule also generated by animals. This was the first demonstration that there was nothing magical about the chemistry of living matter.

Further experiments showed that the molecules found in living organisms were often very large and complex. Consequently, their complete chemical analysis was time consuming and is indeed, still continuing today. The de-mystification of life chemistry reached its peak in the 1930s when the Russian biochemist Alexander Oparin wrote a book outlining his proposal for the chemical origin of life. Although the nature of the genetic material was still unknown, Oparin put forward the idea that life, with its complex molecular composition, evolved from small molecules in the primeval ocean as a result of standard physical and chemical forces (see Ch. 20).

Until the time of World War II, the chemical nature of the inherited genetic information remained very vague and elusive. DNA was actually discovered in 1869 by Frederich Miescher, who extracted it from the pus from infected wounds! However, it was nearly a century before its true significance was revealed by Oswald Avery. In 1944, Avery found that the virulent nature of some strains of bacteria that caused pneumonia could be transmitted to related harmless strains by a chemical extract. Avery purified the essential molecule and demonstrated that it was DNA, although he did not use the name "DNA," since its structure was then uncharacterized. When DNA from virulent strains was added to harmless strains, some took up the DNA and were "transformed" into virulent strains (see Ch. 18 for the mechanism of transformation). Avery concluded that the genes were made of DNA and that somehow genetic information was encoded in this molecule. Since DNA was known to have only half a dozen components, it had not been a leading competitor for the role of genetic material; it was viewed as too simple to encode the information for a living creature!

The question of how DNA, with only half a dozen components, could act as the genetic information was answered by James Watson and Francis Crick in 1953. Their now famous double helix provided a chemical basis for the genetic code and suggested

FIGURE 4.01 Watson and Crick in the 1950s

James Watson (b.1928) at left and Francis Crick (b.1916), with their model of part of a DNA molecule in 1953. Courtesy of: A. Barrington Brown, Science Photo Library.

History of DNA as the Genetic Material 77

X-ray diffraction showed that two strands of DNA are twisted together forming a double helix.

a mechanism for DNA replication. In 1950 Maurice Wilkins and his assistant Raymond Gosling took the first images of DNA using X-ray diffraction. Gosling's work was continued by Rosalind Franklin who joined Wilkins' group the following year. Watson and Crick used a X-ray diffraction picture taken by Rosalind Franklin and Raymond Gosling in 1952 as the basis for their structural model. Rosalind Franklin died in 1958 of cancer aged 37, probably due to the effects of the X-rays. Unraveling the chemical basis for inheritance won Watson, Crick and Wilkins the Nobel Prize in Physiology or Medicine for 1962 "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".

This central finding underlies our whole understanding of how living cells operate and what life means. Since the discovery of the double helix, the genetic code has been worked out, and starting in 1995 with the bacterium Haemophilus influenzae, the DNA of a variety of organisms has been totally sequenced. As the third millennium begins, the human genome has been sequenced, but researchers are still working to assemble the data into complete contiguous sequences for each chromosome. This chapter will discuss how much genetic information is needed to operate a living cell and how that information is arranged on the DNA. Much of the information about these processes comes from studying bacteria, but the information frequently applies also to eukaryotes.

The Double Helix by James D. Watson Published in 1968 by Atheneum, New York

This book gives a personal account of the greatest biological advance of the 20th century—the unraveling of the structure of the DNA double helix by James Watson and Francis Crick. Like the bases of DNA, Watson and Crick formed a complementary pair. Crick, a physicist with an annoying laugh, was supposed to be working towards a Ph.D. on protein X-ray crystallography. Watson was a homeless American biologist, wandering around Europe with a postdoctoral fellowship, looking for something to do.

Despite spending much time carousing, the intrepid heroes, Crick and Watson, beat their elders to the finish line. Watson describes with relish how the great American chemist, Linus Pauling, placed the phosphate backbone of DNA down the middle, so failing to solve the structure. The data proving the phosphate backbone was on the outside of the double helix came from Rosalind Franklin, an X-ray crystallographer at London University. Of her Watson says, "... the best home for a feminist was in another person's lab."

The Director of the Cavendish Laboratory at Cambridge was Sir William Bragg, the august inventor of X-ray crystallography. Despite being depicted as a stuffy has-been who nearly threw Crick out for loud-mouthed insubordination, Bragg wrote the foreword to the book. After all, when younger scientists under your direction make the greatest discovery of the century, it is no time to bear a grudge!

The biographies of great scientists are usually exceedingly dull. Who cares, after all, what Darwin liked for breakfast or what size shoes Mendel wore? It is their discoveries, and how they changed the world, that are fascinating. "The Double Helix" is different. Biographers are generally minor figures, understandably hesitant to criticize major achievers. Watson, himself a big name, happily lacks such respect, and cheerfully castigates other top scientists. It is this honest portrayal of the flaws and fantasies of those involved in unraveling the DNA double helix that keeps the readers attention.

If your stomach can't stand any more sagas about caring investigators who work on into the early hours hoping that their discoveries will help sick children, this book is for you. Like most candid scientists, Watson and Crick did not work for the betterment of mankind; they did it for fun.

The simplest living cell probably needs around 200-300 genes.

Most bacteria have a few thousand genes.

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