Avery, MacLeod and McCarty
DNA: The Search for the Genetic Material
For the Advanced Science Hobbyist: Repeat Avery's, MacLeod's and McCarty's Experiment

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The Discovery of DNA

Animation of the structure of a section of DNA. The bases lie horizontally between the two spiraling strands.
As early as 1848, Wilhelm Hofmeister, a German botanist, has observed that cell nuclei resolve themselves into small, rodlike bodies during mitosis. Later these structures were found to absorb certain dyes and so came to be called chromosomes (colored bodies).

In 1869, Friedrich Miescher, a Swiss physician, isolated a substance from cell nuclei, that he called nuclein - now known as DNA.

During the early years of the 20th century, cellular studies using ordinary light microscopes clarified the behavior of chromosomes during mitosis and meiosis, which led to the conclusion that chromosomes are the carriers of genes – the basic units of heredity.

The chromosomes of eukaryotes contain a variety of proteins in addition to DNA. Soon the question arose whether the nucleic acids (DNA) or proteins, or both together, are the carriers of the genetic information. Until the early 1950s most biologists were inclined to believe that the proteins were the chief carriers if heredity. Nucleic acids contain only four different unitary building blocks, but proteins are made up of 20 different amino acids. Proteins therefore appeared to have a greater diversity structure, and the diversity of the genes seemed first likely to rest on the diversity of the proteins.

The Contribution of Frederick Griffith

In 1928, Frederick Griffith, an English army doctor, wanted to make a vaccine against a bacteria named Streptococcus pneumoniae, which caused a type of pneumonia. Since the time of Pasteur, about 50 years before, vaccines had been made using killed microorganisms which could be injected into patients to elicit the immune response of live cells without risk of disease. Though he failed in making the vaccine he stumbled on a demonstration of the transmission of genetic instructions by a process we now call the "transformation principle".

Griffith's Experiment from 1928
He found that the bacterium had two forms when grown on agar plates, a smooth (S) and a rough (R) form. The R bacteria were harmless, but the S bacteria were lethal when injected into mice. Heat-killed S cells were also harmless - the same effect seen by Pasteur. However, surprisingly when live R cells were mixed with killed S cells and injected into mice the mice died, and the bacteria rescued from the mice had been "transformed" into the S type.

This experiment strongly implied that genetic material had been transferred from the dead to the live cell. It was hard to be certain of this, or to know what exactly genetic material was transferred and was responsible for the transformation process.

DNA is the Transforming Factor

Sixteen years later, in 1944, the team of Avery, MacLeod and McCarty revisited this experiment and attempted a more definitive experiment. They extracted from Streptococcus pneumoniae S bacteria nucleoid purified DNA, proteins and other materials and mixed R bacteria with these different materials, and only those mixed with DNA were transformed into S bacteria. For their experiments they used a test tube assay instead of mice.

This Experiment strongly implied that DNA is the “transforming factor” and not proteins or other materials and by this was demonstrated what is known to us as the transforming principle - that genes are made of DNA.

Amazingly, not everyone was convinced by the experiments of Avery's, MacLeod's and McCarty's. It was the experiments of Hershey and Chase (1952) that finally proved that DNA was the genetic material and not protein.

While Avery and his team were nominated several times for the Nobel Prize, they never received it. It is a universally recognized omission of the Nobel committee since their work was a blazing discovery that changed everything. For more about this topic see in the link section "The Nobel Prize Omission"

Repeat Avery, MacLeod and McCarty's Experiments

Warning: Before you start, please pay notice that these experiments can be dangerous since you will have to experiment with bacteria that can be infectious and other chemicals, materials and apparatus that can be dangerous for your health.

As a rule: this experiment should be performed under the supervision of professionals familiar with chemical, biomedical and laboratory safety procedures. Among others, it is not so simple to obtain some chemical or bio materials and supplies and use them properly and safely in these experiments. If you are a high school student do not try anything by yourself before you consult your teachers, parents or other knowledgeable adults and experts. Do not try to do this experiment, or any other activity related to it, alone! Notify your parents and school authorities before you begin - wait for their approval.

A few laboratory biological safety links:

After we have clarified the safety issue, a few useful remarks before you begin:
  • These experiments are not as simple as they look, and nevertheless they were performed many years ago they still need some biochemistry and bacteriology extra skills, at least college level. You'll need some professional help.
  • These experiments are somewhat costly and you’ll need some expensive materials and scientific instruments.
  • A school science lab will not suffice for this end, not only for lack of scientific means but also for safety consideration. You’ll have to ask permission to use a university lab or other proper scientific institution – not a simple accomplishment.
  • These experiments are intended mainly for college students or very high motivated and advanced high school students and teachers (for an award winning science fair project).
If you have decided to embark on this challenge, first of all, address the safety concerns mentioned above. Now, ensure that you understand the basic principals of the Avery and coworkers experiment. The following animation is a good place to start and to figure out in a concise manner what is all this about: http://www.dnaftb.org/dnaftb...

The detailed account of Avery, MacLeod and McCarty's Experiments could be found in their paper "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III", published in the February 1944 issue of the Journal of Experimental Medicine, in which Avery and his colleagues suggest that DNA, rather than protein as widely believed at the time, may be the hereditary material of bacteria and could be analogous to genes in higher organisms.
A few links pointing to this article:

Surf the web further and consult scientific libraries, databases and relevant experts, and if you are a high school student, consult also your teachers and other knowledgeable adults and professionals.

Take in account that it's also possible to repeat other related experiments as well. For example: the mentioned above Hershey and Chase (1952).

Further Reading

Griffith's & Avery, MacLeod and McCarty's Experiments
Genetics and Genomics Timeline:1944 - Genome News Network
The Oswald T. Avery Collection - U.S. National Library of Medicine
Avery, Macleod McCarty's Article from 1944 - MicroBiology
Avery-MacLeod-McCarty experiment - Wikipedia
Linus Pauling and the Race for DNA (searchable database) - Oregon State University
The Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types
The Transforming Principal - Maclyn McCarty
The Experiment That Transformed Biology - The Journal of Experimental Medicine
Structures of DNA and RNA - Molecular Biology and Biochemistry
How Can DNA be the Genetic Material? - Jeff Elhai

The Nobel Prize Omission
Maclyn McCarty Dies - The New York Times
How Rhetorical Choices Can Influence the Impact of a Scientific Paper
Prematurity in Scientific Discovery - Ernest B. Hook, Editor

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