In 1944, Oswald Avery and colleagues published a scientific paper, now considered one of the most important scientific papers of the 20th century, that was foundational to recognizing a link between DNA and heredity. Working with Colin MacLeod and Maclyn McCarty, Avery demonstrated that DNA, not protein or RNA, is the substance responsible for transforming bacteria. Although he is now considered to have been very deserving, Avery never received a Nobel Prize.
The discovery of DNA culminated in the solving of its molecular structure in 1953, published in a famous paper by James Watson and Francis Crick. But prior to their work, many researchers over the first half of the 20th century conducted experiments to demonstrate that DNA was the genetic material responsible for the inheritance of traits. The Avery-MacLeod-McCarty experiment was a key finding in establishing that DNA is the genetic material.
In 1928, Frederick Griffith conducted a now-famous experiment where he discovered the phenomenon of bacterial transformation. When Griffith combined heat-killed virulent bacteria with living nonvirulent bacteria and injected the mixture into mice, he found that the mice died, as they do when injected with living virulent bacteria. This demonstrated that the living bacteria took up genetic material, called the "transforming principle" at the time, from the dead virulent bacteria, and this material transformed them into virulent bacteria. It was not known what that genetic material was, although possible candidates included polysaccharides, DNA and protein.
Oswald Avery, Colin MacLeod and Maclyn McCarty took up where Griffith's experiment left off and began purifying DNA from the other components of the virulent bacteria. By extracting the water-soluble materials from bacteria and precipitating DNA using chloroform, Avery acquired a purified sample of DNA that he could use to transform bacteria. By treating his DNA sample with enzymes that digest protein and another candidate molecule, RNA, Avery was able to demonstrate that DNA was the transforming material. This was further confirmed by the fact that an enzyme that digests DNA destroyed the transforming ability of his sample.
Although the Avery-McCleod-McCarty experiment clearly showed that DNA could transform bacteria, the scientific community did not immediately accept that DNA was the genetic material. Some believed DNA, with only four building blocks, was too simple a material to carry instructions for the many complex traits of living things. It wasn't until 10 years later, when the structure of DNA was solved, that it became clear that the four nucleotides of DNA were the basis of the genetic code of life.
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