In just over 75 years, DNA – deoxyribonucleic acid – has risen in public and scientific status from being “an obscure molecule with presumed accessory or structural functions inside the nucleus, to the icon of modern bioscience”.
So wrote Ralf Dahm, Director of Scientific Management at Germany’s Institute of Molecular Biology, in the journal Developmental Biology in 2005.
The DNA story may appear to begin in 1944, Rahm adds, with crucial discoveries by researchers Oswald Avery, Colin MacLeod and Maclyn McCarty. But it really began back in 1869, with the young Swiss physician Johann Friedrich Miescher.
McCarty, an American, and Canadians Avery and MacLeod were working at Rockefeller University in New York when they discovered that DNA, not proteins, had the ability to transform the properties of cells.
An article published by the US National Human Genome Research Institute says biochemists had previously “assumed that deoxyribonucleic acid was a relatively unimportant, structural chemical in chromosomes and that proteins, with their greater chemical complexity, transmitted genetic traits”.
Avery, MacLeod and McCarty were studying Streptococcus pneumoniae – bacteria that can cause pneumonia. They wanted to discover how a non-virulent strain could be “transformed” into a virulent form and to “understand its chemical nature”.
In 1944 they identified and isolated DNA as the “transforming principle”. “This was the agent that could produce an enduring, heritable change in an organism.”
Within 10 years of these experiments, Dahm says, “James Watson and Francis Crick deciphered its structure and, yet another decade on, the genetic code was cracked”.
But it would not have been possible without Miescher.
Born in Basel on 13 August 1844, he studied medicine, like his father and an uncle before him, receiving his qualification in 1868. But severe ear infections left him with impaired hearing and, believing this would hinder his ability to work as a doctor, he turned to a career in chemistry and medical research.
He went to work at the University of Tubingen in Germany, in a newly established faculty of natural science, tasked with researching the chemical composition of leukocytes, or white blood cells.
To obtain material, he would collect freshly used surgical bandages from a nearby hospital, wash off the pus and filter out the leukocytes.
Dahm, writing in the journal Human Genetics, says that in his experiments Miescher “noticed a precipitate of an unknown substance, which he characterised further.
“Analyses of its elementary composition revealed that, unlike proteins, it contained large amounts of phosphorous and lacked sulphur. Miescher recognised that he had discovered a novel molecule.”
Because he had isolated it from the cells’ nuclei, he named it nuclein, “a name preserved in today’s designation deoxyribonucleic acid”.
Dahm says that in subsequent work “Miescher showed that nuclein was a characteristic component of all nuclei and hypothesised that it would prove to be inextricably linked to the function of this organelle. He suggested that its abundance in tissues might be related to their physiological status with increases in ‘nuclear substances’ preceding cell division. Miescher even speculated that it might have a role in the transmission of hereditary traits, but subsequently rejected the idea.”
Dahm believes Miescher’s discovery was a matter of “serendipity and the prepared mind”.
“He had set out to characterise proteins and discovered DNA, which he recognised as being very worthy of further investigation. However, the breakthrough in thought that his discovery deserved only occurred half a century after his death, when the data necessary to fully grasp the significance of DNA’s function were emerging. In many ways, Miescher’s discovery was well ahead of its time.”
Miescher died of tuberculosis on 26 August 1895.
Jeff Glorfeld is a former senior editor of The Age newspaper in Australia, and is now a freelance journalist based in California, US.
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