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Legacies - Transformation and DNA

Chris Evers

Bacteria can exchange genetic material in a variety of ways, the most amazing being transformation - the transfer of genetic material from one bacterium to another through the liquid in which the bacteria live. Think of it as analogous to a person being able to pick up new genes from someone who has sneezed into the air across the room from them.

This surprising process was discovered in the late 1920's by Fred Griffith, an English medical officer studying the bacteria responsible for a pneumonia epidemic in London. This bacteria, a pneumococcus, occurred in two forms that differed in both appearance and infective properties. One form (S) was smooth and highly infective. The other form (R) was rough and harmless. Griffith knew that both forms could be cultured from patients suffering from pneumonia and wondered if the bacteria could change from one type to the other.

In his famous experiment, Griffith injected mice with harmless living R cells and heat-killed S cells. The mice died, and living cells of both types were found in their bodies. Somehow, some substance from the heat-killed S cells had been picked up by some of the R cells, changing them into virulent S type cells. Griffith coined the term "transformation" to describe this process. Griffith's pioneering work laid the foundation for the experiments that led to the discovery of the molecular basis of heredity and the birth of molecular genetics. Unfortunately, he did not live to see these discoveries - he was killed during a German air raid on London early in World War II.

The experiments that actually revealed that DNA is the material responsible for transformation were carried out during the 1940s in Oswald Avery's laboratory at the Rockefeller Institute in New York. Avery was a specialist in medical bacteriology with a special interest in pneumococcal pneumonia, then the major cause of death in the United States. He knew of Griffith's work, but was skeptical about it until Colin MacLeod, a young Canadian physician working in his lab, repeated and then further refined Griffith's experiments. MacLeod showed that the substance responsible for transformation was heat sensitive - extracts of S cells heated to over 80 degree centigrade couldn't transform R cells, but extracts that had been frozen and defrosted were still active.

In 1941, MacLeod left the Rockefeller Institute, and Avery was joined by Maclyn MacCarthy. Avery and MacCarthy continued to study the transformation process. They knew that the extracts that transformed cells contained protein, RNA, and DNA, but they didn't know which of these substances were essential for transformation. They decided to use the process of elimination - to figure out which part or parts of the extract were important by destroying each one and seeing what the effect on transformation was. Extracts were treated with either proteases (to destroy protein), RNase (to destroy RNA), or DNase (to destroy DNA). The ability of each of the treated extracts to transform R cells was then tested. Neither the proteases nor the RNase had any effect, but the DNase rendered the extracts inactive - proving that transformation was due exclusively to DNA.

Avery published this work in 1943, with MacLeod and MacCarthy as co-authors. However, the importance of its implication - that DNA was the genetic material of all living things - was not fully appreciated for almost 10 years. Just as the importance of Griffith's work was clear only after it was continued by Avery and his colleagues, so their work was fully accepted and understood only in light of the later work by Alfred Hershey and Martha Chase.

In fact, it is unlikely that either Griffith or Avery had any real feeling for how important their work would ultimately become. Instead, each focused only on answering a very specific question. Griffith wondered, "Can bacteria change from one type to another?" and showed that they could. Avery asked, "What substance makes them change?" and found that it was DNA. Yet, by asking simple questions and designing elegant experiments to answer them, Griffith and Avery laid the groundwork for a scientific revolution that neither could have imagined.

Go to next story: Lwoff's Pathways - Viral Replication

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