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The first step in developing evidence that DNA is the genetic material passed from one generation to the next was the discovery of DNA itself. Around 1870, through experiments on white blood cells, physician-scientist Friedrich Miescher precipitated a substance from the cells' nuclei that he found to be resistant to proteases, lacked sulphur, and contained phosphorous. Not characteristic of protein or lipid, the unknown substance would come to be called nucleic acid. The substance was found to increase markedly (along with protein) in the cells leading up to cell division, and it was posited that this new substance may have a hereditary role.
Around 1880, another physician-scientist, Wilhelm Roux, observed early development of embryos and theorized that the separation of chromosomes (a composite of protein and nucleic acid) between daughter cells was the key to passing on the genetic material.
In 1944, researchers Oswald Avery, Colin MacLeod, and Maclyn McCarty reported the results which built off the findings of Frederick Griffith's 1928 study of transformation between S-strain (virulent) bacteria and R-strain (nonvirulent) bacteria. The Avery–MacLeod–McCarty experiment undertook purification of the material able to be passed from the killed virulent strain into the live nonvirulent bacteria, thereby making it virulent. They found, after precipitating out protein and treating with proteases, a substance with chemical composition consistent with DNA, supporting the idea that it was DNA that was the genetic material conveying virulence.
With this evidence in place, Alfred Hershey and Martha Chase conducted experiments in 1952 to investigate if it was indeed protein, DNA, or both that act as the genetic material. In the Hershey-Chase experiments bacteriophages were observed in their behavior of infecting bacteria, necessarily injecting genetic material in the process. The protein of the bacteriophages (composing the virus's protein coat) was labelled with radioactive sulfur-35, and the DNA was labelled with phosphorus-32. Upon infecting the bacteria, it was found that the protein was detected outside the infected cells, while the DNA was present inside, creating evidence for DNA, not protein, as the important genetic material passed from virus to bacteria.
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