Skip navigation. In , Oswald Avery, Colin MacLeod, and Maclyn McCarty published an article in which they concluded that genes , or molecules that dictate how organisms develop, are made of deoxyribonucleic acid, or DNA. In the early s, many scientists supported the idea that genes were made of protein. Scientists had verified that genes were heritable, meaning that genes could be passed from cell to cell, and from parent to offspring.

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Skip navigation. In , Oswald Avery, Colin MacLeod, and Maclyn McCarty published an article in which they concluded that genes , or molecules that dictate how organisms develop, are made of deoxyribonucleic acid, or DNA. In the early s, many scientists supported the idea that genes were made of protein. Scientists had verified that genes were heritable, meaning that genes could be passed from cell to cell, and from parent to offspring.

They had also identified the different chemical constituents, or building blocks, of DNA and proteins. In contrast, scientists thought that the building blocks of protein could adopt many different structures. With those ideas, many researchers argued that genes could not be made of DNA because DNA could not possess the necessary complexity to account for genetic variation, or the amount of genetic differences between individual organisms.

Bacterial transformation is the process by which bacteria can ingest and use new genetic material from its surroundings.

In , Frederick Griffith, a scientist at the British Ministry of Health in London, United Kingdom, reported that he observed bacterial transformation. He studied Streptococcus pneumoniae , also called pneumococcus, which is a species of bacteria that causes pneumonia, a lung disease in humans and other animals. There are two types of pneumococcus, smooth and rough, which scientists label S and R, respectively. The living S form of pneumococcus causes disease, and the R form does not.

When Griffith injected mice with a large amount of dead S form bacteria and a small amount of living R form bacteria, the mice still died. When Griffith analyzed the blood of those mice, he found living S form bacteria that continued to reproduce and make more S form bacteria.

Griffith concluded that the dead S form bacteria must have exchanged some genetic material with the living R form bacteria, so the R form bacteria transformed into living S form. Griffith did not determine whether the living S form took up a genetic element, also called the transforming principle, made of protein or made of DNA. In the early s, Avery started researching bacterial transformation in pneumococcus to develop treatments for pneumonia. They explain that transformation in pneumococcus, or pneumonia-causing bacteria, is an example of how scientists could cause specific heritable changes in bacteria.

Finally, Avery, MacLeod, and McCarty state that the purpose of their research is to identify the chemical nature of the transforming principle that causes transformation in bacteria.

That discussion includes details about the type of R form pneumococcus the researchers used and how they prepared that bacteria. Avery, MacLeod, and McCarty explain why they chose to use certain materials in their experiment and why they carried out experimental procedures in the ways that they did. In other words, the authors describe a method by which they could determine whether R form bacteria transformed into S form bacteria and the extent to which that transformation occurred.

Without successfully inducing transformation in R form bacteria, the researchers would not be able to identify the transforming principle. The researchers emphasize that their procedure preserves the material of interest, or the transforming principle.

According to the authors, they prepared pneumococcus in a broth where R form and S form bacteria position themselves differently in the test tube. The authors state that in that broth, R form bacteria accumulates at the bottom of the test tube and leaves a clear liquid above.

In contrast, the S form bacteria does not accumulate at the bottom, but instead disperses throughout the broth, making it cloudy. The authors conclude that they will know if transformation occurs when the clear liquid above the R form bacteria turns cloudy.

Next, the authors explain how they extract and purify the transforming principle. After they verify that transformation occurred, the researchers extract the heat-killed S form bacteria. They remove and purify the transforming principle from the bacteria so they can analyze it further.

The authors document the temperature at which they conducted their experiment and the amount of time each step took.

Avery, MacLeod, and McCarty state that the extracted transforming principle was a fibrous substance. First, they describe the physical and chemical properties of the extracted substance. They describe the effects that light, dissolving in water, and heating had on the transforming principle and its activity, or the extent to which bacteria transformed in the presence of the principle. In addition to observing the physical properties of the transforming principle, Avery, MacLeod, and McCarty describe how they performed various chemical tests.

According to the authors, both the physical and chemical tests showed that the transforming principle was DNA, and not protein. For example, Avery, MacLeod, and McCarty state that they performed a test which revealed that the elements present in their sample were carbon, hydrogen, nitrogen, and phosphorus and how much of each element was present.

According to the authors, the experimental ratios of those four elements supported the idea that the transforming principle was DNA, and not in protein. Enzymes are molecules that facilitate chemical reactions in cells by interacting with the substances that participate in the chemical reaction.

Enzymes are specific, meaning that a certain enzyme can only interact with certain substances. The authors state that enzymes that degrade ribonucleic acid, or RNA, a molecular similar to DNA, and enzymes that degrade protein had no effect on the transforming principle. However, Avery, MacLeod, and McCarty write that when they exposed the transforming principle to an enzyme that degrades DNA, the enzyme broke down the transforming principle. The authors summarize their results of the enzyme tests in a table.

The authors conclude that the results of their enzyme tests are further proof that the transforming principle is DNA. They state that the transforming principle sample did not contain any pneumococcal protein, the disease-causing substance of pneumococcus, and therefore the transforming principle must be structurally different from the pneumococcal protein.

The researchers also state that they used an analytical ultracentrifuge, a centrifuge that spins substances rapidly and can separate different components in a mixture, to see whether the transforming principle was a mixture of different types of substances.

After centrifugation, Avery, MacLeod, and McCarty found that no parts of the transforming principle separated. Instead, it was consistent throughout, which, according to the authors, meant that the transforming principle likely only contained one kind of substance. The authors identify that substance as DNA. Avery, MacLeod, and McCarty also write that the transforming principle absorbed the same type of light as DNA, an indication that the substances are likely the same.

In that section, the authors interpret their experimental findings and conclude that the transforming principle was likely to be DNA. Avery, MacLeod, and McCarty state that, in their study, they successfully induced transformation in R form pneumococcus and that they extracted and purified DNA from the bacteria that caused R form bacteria to become S form bacteria.

They explicitly state that the DNA sample, containing no protein, could induce transformation in bacteria. The researchers also note when the bacteria transformed, they generated a capsule, or a protective outer layer made of sugar molecules. The authors discuss that capsule generation seemed to be related to the transforming principle even though the capsule substance was made of different chemicals than the transforming principle.

The authors state that for a substance to induce transformation in bacteria, it must have a high degree of biological specificity. Biological specificity is the idea that certain characteristics of organisms, like behaviors or biochemicals, vary depending on the species. According to Avery, MacLeod, and McCarty, scientists had not explained how the DNA molecule, which had little structural variability when compared with proteins, could allow for biological specificity.

For that reason, the authors do not claim that DNA is indisputably the cause of bacterial transformation. However, the researchers state that if other experiments support their findings, DNA must facilitate transformation in bacteria.

In their paper, Avery, MacLeod, and McCarty did not completely rule out the possibility of some substance other than DNA causing the genetic changes required for bacterial transformation.

Historians have noted that, privately, Avery was more confident that DNA facilitated bacterial transformation. In what scientists later called the Hershey-Chase experiments, Hershey and Chase demonstrated that bacteriophages injected DNA into bacteria during infection, and that the phage DNA was the genetic element that replicated and created new bacteriophage particles inside the bacteria.

Fry, Michael. Academic Press, Hershey, Alfred D. Holmes, Frederic L. Judson, Horace Freeland. The Eighth Day of Creation. Mahadevan, S. Morange, Michel. A History of Molecular Biology. Cambridge: Harvard University Press , Olby, Robert Cecil. Seattle: University of Washington Press, Printer-friendly version PDF version.


Structural Biochemistry/Nucleic Acid/DNA/Avery-MacLeod-McCarty Experiment

The bacteriologists were interested in the difference between two strains of Streptococci that Frederick Griffith had identified in one, the S smooth strain, has a polysaccharide coat and produces smooth, shiny colonies on a lab plate; the other, the R rough strain, lacks the coat and produces colonies that look rough and irregular. The relatively harmless R strain lacks an enzyme needed to make the capsule found in the virulent S strain. Griffith had discovered that he could convert the R strain into the virulent S strain. After he injected mice with R strain cells and, simultaneously, with heat-killed cells of the S strain, the mice developed pneumonia and died.


Avery–MacLeod–McCarty experiment

The Avery—MacLeod—McCarty experiment was an experimental demonstration, reported in by Oswald Avery , Colin MacLeod , and Maclyn McCarty , that DNA is the substance that causes bacterial transformation , in an era when it had been widely believed that it was proteins that served the function of carrying genetic information with the very word protein itself coined to indicate a belief that its function was primary. It was the culmination of research in the s and early 20th century at the Rockefeller Institute for Medical Research to purify and characterize the "transforming principle" responsible for the transformation phenomenon first described in Griffith's experiment of killed Streptococcus pneumoniae of the virulent strain type III-S, when injected along with living but non-virulent type II-R pneumococci, resulted in a deadly infection of type III-S pneumococci. With the development of serological typing , medical researchers were able to sort bacteria into different strains , or types. When a person or test animal e. Blood serum containing the antibodies can then be extracted and applied to cultured bacteria.





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