DNA: The Long Journey to Discovering the Blueprint of Life

For many years, scientists believed that proteins—with their complexity and variety—were the likely candidates for carrying genetic information. The idea that DNA, a seemingly simple molecule, could serve such a fundamental role in heredity faced skepticism across the scientific community.

That skepticism slowly began to fade, thanks to the visionary work of scientists across continents and decades.

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Early Insights: Koltsov’s Vision of a Hereditary Molecule

In 1927, Russian biologist Nikolai Koltsov proposed a groundbreaking idea: that hereditary traits were passed through a “giant hereditary molecule” composed of two strands capable of self-replication. Each strand, he suggested, could serve as a template for creating its counterpart—a concept strikingly similar to what we now know about DNA’s double helix.

Tragically, Koltsov never saw his theory validated. He died in 1940 under Soviet repression. Yet, his vision was finally confirmed a quarter-century later when James Watson and Francis Crick unveiled the double-helix structure of DNA in 1953—a discovery that changed biology forever.

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Griffith’s Pioneering Experiment in Bacterial Transformation

While Koltsov was theorizing in Russia, Frederick Griffith, a British bacteriologist, was making discoveries of his own. In the 1920s, while studying pneumonia-causing bacteria (pneumococci), Griffith identified two strains:

• A smooth (S) strain, which was virulent and caused death in mice.
• A rough (R) strain, which was non-virulent and did not cause illness.

In a key experiment, Griffith injected mice with a mixture of heat-killed S-strain bacteria and live R-strain bacteria. Surprisingly, the mice developed pneumonia and died. The dead mice's tissues contained live S-strain bacteria. Griffith concluded that some "transforming factor" had turned the harmless R-strain into a deadly form—though he did not yet know what that factor was.

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Avery, MacLeod, and McCarty: Identifying DNA as the Genetic Material

In the 1930s and early 1940s, Oswald Avery, a leading expert on pneumococcus at Rockefeller University, set out to identify Griffith’s mysterious transforming factor. Along with Colin MacLeod and Maclyn McCarty, Avery recreated and refined Griffith’s experiment.

Rather than using heat to kill the S-strain bacteria, they applied chemical treatments to selectively destroy key biological molecules—proteins, lipids, carbohydrates, and RNA. Yet the transformation still occurred.

Only when they added deoxyribonuclease (DNase)—an enzyme that breaks down DNA—did the transformation stop. This critical finding, published in 1944, provided the first solid evidence that DNA is the molecule responsible for carrying genetic information.

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Key Points to Remember

• DNA was not immediately accepted as the hereditary material—proteins were long thought to be more likely candidates due to their complexity.
• Nikolai Koltsov envisioned a double-stranded hereditary molecule decades before DNA’s structure was discovered.
• Frederick Griffith’s bacterial experiments laid the foundation for understanding transformation, even before DNA was identified.
• Avery, MacLeod, and McCarty’s work pinpointed DNA as the “transforming factor,” marking a turning point in molecular biology.
• This discovery paved the way for Watson and Crick’s breakthrough, forever changing our understanding of life at the molecular level.

In the 1940s, the groundbreaking Avery-MacLeod-McCarty experiment delivered decisive proof that DNA, not protein, is the true carrier of genetic information.