oswald avery macleod mccarty experiment

Microbe Notes

DNA Experiments (Griffith & Avery, McCarty, MacLeod & Hershey, Chase)

DNA, deoxyribonucleic acid, is the carrier of all genetic information. It codes genetic information passed on from one generation to another and determines individual attributes like eye color, facial features, etc. Although DNA was first isolated in 1869 by a Swiss scientist, Friedrich Miescher, from nuclei of pus-rich white blood cells (which he called nuclein ), its role in the inheritance of traits wasn’t realized until 1943. Miescher thought that the nuclein, which was slightly acidic and contained a high percentage of phosphorus, lacked the variability to account for its hereditary significance for diversity among organisms. Most of the scientists of his period were convinced by the idea that proteins could be promising candidates for heredity as they were abundant, diverse, and complex molecules, while DNA was supposed to be a boring, repetitive polymer. This notion was put forward as the scientists were aware that genetic information was contained within organic molecules.

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Griffith’s Transformation Experiment

In 1928, a young scientist Frederick Griffith discovered the transforming principle. In 1918, millions of people were killed by the terrible Spanish influenza epidemic, and pneumococcal infections were a common cause of death among influenza-infected patients. This triggered him to study the bacteria Streptococcus pneumoniae and work on designing a vaccine against it . It became evident that bacterial pneumonia was caused by multiple strains of S. pneumoniae, and patients developed antibodies against the particular strain with which they were infected. Hence, serum samples and bacterial isolates used in experiments helped to identify DNA as the hereditary material. 

He used two related strains of S. pneumoniae and mice and conducted a series of experiments using them. 

• When type II R-strain bacteria were grown on a culture plate, they produced rough colonies. They were non-virulent as they lacked an outer polysaccharide coat. Thus, when RII strain bacteria were injected into a mouse, they did not cause any disease and survived.
• When type I S-strain bacteria were grown on a culture plate, they produced smooth, glistening, and white colonies. The smooth appearance was apparent due to a polysaccharide coat around them that provided resistance to the host’s immune system. It was virulent and thus, when injected into a mouse, resulted in pneumonia and death. 
• In 1929, Griffith experimented by injecting mice with heat-killed SI strain (i.e., SI strain bacteria exposed to high temperature ensuing their death). But, this failed to harm the mice, and they survived.
• Surprisingly, when he mixed heat-treated SI cells with live RII cells and injected the mixture into the mice, the mice died because of pneumonia. Additionally, when he collected a blood sample from the dead mouse, he found that sample to contain live S-strain bacteria.

Conclusion of Griffith’s Transformation Experiment

Based on the above results, he inferred that something must have been transferred from the heat-treated S strain into non-virulent R strain bacteria that transformed them into smooth coated and virulent bacteria. Thus, the material was referred to as the transforming principle.

Following this, he continued with his research through the 1930s, although he couldn’t make much progress. In 1941, he was hit by a German bomb, and he died.

Avery, McCarty, and MacLeod Experiment

During World War II, in 1943, Oswald Avery, Maclyn McCarty, and Colin MacLeod working at Rockefeller University in New York, dedicated themselves to continuing the work of Griffith in order to determine the biochemical nature of Griffith’s transforming principle in an in vitro system. They used the phenotype of S. pneumoniae cells expressed on blood agar in order to figure out whether transformation had taken place or not, rather than working with mice. The transforming principle was partially purified from the cell extract (i.e., cell-free extract of heat-killed type III S cells) to determine which macromolecule of S cell transformed type II R-strain into the type III S-strain. They demonstrated DNA to be that particular transforming principle.

• Initially, type III S cells were heat-killed, and lipids and carbohydrates were removed from the solution.
• Secondly, they treated heat-killed S cells with digestive enzymes such as RNases and proteases to degrade RNA and proteins. Subsequently, they also treated it with DNases to digest DNA, each added separately in different tubes.
• Eventually, they introduced living type IIR cells mixed with heat-killed IIIS cells onto the culture medium containing antibodies for IIR cells. Antibodies for IIR cells were used to inactivate some IIR cells such that their number doesn’t exceed the count of IIIS cells. that help to provide the distinct phenotypic differences in culture media that contained transformed S strain bacteria.

Observation of Avery, McCarty, and MacLeod Experiment

The culture treated with DNase did not yield transformed type III S strain bacteria which indicated that DNA was the hereditary material responsible for transformation. 

Conclusion of Avery, McCarty, and MacLeod Experiment

DNA was found to be the genetic material that was being transferred between cells, not proteins.

Hershey and Chase Experiment

Although Avery and his fellows found that DNA was the hereditary material, the scientists were reluctant to accept the finding. But, not that long afterward, eight years after in 1952, Alfred Hershey and Martha Chase concluded that DNA is the genetic material. Their experimental tool was bacteriophages-viruses that attack bacteria which specifically involved the infection of Escherichia coli with T2 bacteriophage.

T2 virus depends on the host body for its reproduction process. When they find bacteria as a host cell, they adhere to its surface and inject its genetic material into the bacteria. The injected hereditary material hijacks the host’s machinery such that a large number of viral particles are released from them. T2 phage consists of only proteins (on the outer protein coat) and DNA (core) that could be potential genetic material to instruct E. coli to develop its progeny. They experimented to determine whether protein or DNA from the virus entered into the bacteria.

• Bacteriophage was allowed to grow on two of the medium: one containing a radioactive isotope of phosphorus( 32 P) and the other containing a radioactive isotope of sulfur ( 35 S).
• Phages grown on radioactive phosphorus( 32 P) contained radioactive P labeled DNA (not radioactive protein) as DNA contains phosphorus but not sulfur.
• Similarly, the viruses grown in the medium containing radioactive sulfur ( 35 S) contained radioactive 35 S labeled protein (but not radioactive DNA) because sulfur is found in many proteins but is absent from DNA.
• E. coli were introduced to be infected by the radioactive phages.
• After the progression of infection, the blender was used to remove the remains of phage and phage parts from the outside of the bacteria, followed by centrifugation in order to separate the bacteria from the phage debris.
• Centrifugation results in the settling down of heavier particles like bacteria in the form of pellet while those light particles such as medium, phage, and phage parts, etc., float near the top of the tube, called supernatant.

Observation of Hershey and Chase Experiment

On measuring radioactivity in the pellet and supernatant in both media, 32 P was found in large amount in the pellet while 35 S in the supernatant that is pellet contained radioactively P labeled infected bacterial cells and supernatant was enriched with radioactively S labeled phage and phage parts.

Conclusion of Hershey and Chase Experiment

Hershey and Chase deduced that it was DNA, not protein which got injected into host cells, and thus, DNA is the hereditary material that is passed from virus to bacteria.

• Fry, M. (2016). Landmark Experiments in Molecular Biology. Academic Press.
• https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Introductory_Biology_(CK-12)/04%3A_Molecular_Biology/4.02%3A_DNA_the_Genetic_Material
• https://byjus.com/biology/dna-genetic-material/
• https://bio.libretexts.org/Bookshelves/Genetics/Book%3A_Online_Open_Genetics_(Nickle_and_Barrette-Ng)/01%3A_Overview_DNA_and_Genes/1.02%3A_DNA_is_the_Genetic_Material
• https://www.toppr.com/guides/biology/the-molecular-basis-of-inheritance/the-genetic-material/
• https://www.nature.com/scitable/topicpage/discovery-of-dna-as-the-hereditary-material-340/
• https://www.biologydiscussion.com/genetics/dna-as-a-genetic-material-biology/56216
• https://www.nature.com/scitable/topicpage/discovery-of-the-function-of-dna-resulted-6494318/
• https://www.ndsu.edu/pubweb/~mcclean/plsc411/DNA%20replication%20sequencing%20revision%202017.pdf
• https://www.britannica.com/biography/Frederick-Griffith
• https://ib.bioninja.com.au/higher-level/topic-7-nucleic-acids/71-dna-structure-and-replic/dna-experiments.html
• https://biolearnspot.blogspot.com/2017/11/experiments-of-avery-macleod-and.html
• https://www.khanacademy.org/science/biology/dna-as-the-genetic-material/dna-discovery-and-structure/a/classic-experiments-dna-as-the-genetic-material

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1944: DNA is \"Transforming Principle\"

1944: dna is "transforming principle".

Avery, MacLeod and McCarty identified DNA as the "transforming principle" while studying Streptococcus pneumoniae , bacteria that can cause pneumonia. The bacteriologists were interested in the difference between two strains of Streptococci that Frederick Griffith had identified in 1923: 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. In their blood, Griffith found live bacteria of the deadly S type. The S strain extract somehow had "transformed" the R strain bacteria to S form. Avery and members of his lab studied transformation in fits and starts over the next 15 years. In the early 1940s, they began a concerted effort to purify the "transforming principle" and understand its chemical nature.

Bacteriologists suspected the transforming factor was some kind of protein. The transforming principle could be precipitated with alcohol, which showed that it was not a carbohydrate like the polysaccharide coat itself. But Avery and McCarty observed that proteases - enzymes that degrade proteins - did not destroy the transforming principle. Neither did lipases - enzymes that digest lipids. They found that the transforming substance was rich in nucleic acids, but ribonuclease, which digests RNA, did not inactivate the substance. They also found that the transforming principle had a high molecular weight. They had isolated DNA. This was the agent that could produce an enduring, heritable change in an organism.

Until then, biochemists had assumed that deoxyribonucleic acid was a relatively unimportant, structural chemical in chromosomes and that proteins, with their greater chemical complexity, transmitted genetic traits.

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Last updated: April 23, 2013

Oswald Avery and the Avery-McLeod-McCarthy Experiment

Oswald Avery and his colleagues showed that DNA was the key component of Griffith’s experiment , in which mice are injected with dead bacteria of one strain and live bacteria of another, and develop an infection of the dead strain’s type

On February 1 , 1944 , physician and medical researcher Oswald Avery together with his colleagues Colin MacLeod and Maclyn McCarty announced that DNA is the hereditary agent in a virus that would transform a virus from a harmless to a pathogenic version. This study was a key work in modern bacteriology .

Prelude – The Griffith Experiment

The achievement by the scientists Avery, MacLeod, and McCarty were based on Frederick Griffith’s studies on bacteria, believing that bacteria types were not changeable from one to another generation. His also famous attempt is called the Griffith experiment, and was published in 1928. In it, the medical officer Griffith identified a principle in pneumococcal bacteria, in which they could transform from one to another type. After several years of research on the disease pneumonia , he found out that types changed into another rather than multiple types being present at the same time. His later research proved, that the transformation occurred, when dead bacteria of a virulent and live bacteria of a non-virulent type were injected in mice, they would suffer an infection and die shortly after. The other case proved, that the injected virulent bacteria was to be isolated from an infected mouse, depicted in the picture above. The German bacteriologist Fred Neufeld was the first to prove Griffith’s findings right and soon, renowned institutes, like the Koch Institute or the Rockefeller Institute took over the case, doing further research on Griffith’s great accomplishments.

Oswald Avery (1877-1955)

The Avery-MacLeod-McCarty Experiment

Avery and his collaborators Colin MacLeod and Maclyn McCarty at Rockefeller University (then Rockefeller Institute) in New York wanted to elucidate the chemical nature of the transforming substance. They refined the purification process until the result was a cell extract whose amounts of carbon, hydrogen, nitrogen and phosphorus corresponded to those of DNA.[ 4 ] To ensure that the transformation was not induced by residues of RNA or proteins, they treated the cell extract with different enzymes prior to the transformation. One of these enzymes had a deoxyribonucleode polymerase activity described by Greenstein in 1940. Only this neutralized the transformation activity of the extract, while trypsin, chymotrypsin (two protein cleaving enzymes), ribonuclease, protein phosphatases and esterase had no effect on transformation activity. They were also able to show that all offspring inherited the S-properties and that the repetition of the experiment with extracts from these offspring led to the same results.

This experiment shows that the genetic information must lie on the DNA, since the R-cells needed information from the S-cells to form a mucus capsule, i. e. to become S-cells. And only the DNA made it possible to transform R cells into S cells. In the counterexample with an enzyme, it became even clearer that the genetic information must lie in the DNA, since only R cells develop when a DNAse is added, because the DNA was broken down by the enzyme.

The achievements of the Avery-MacLeod-McCarty experiment quickly spread out into the scientific community and it was proven right just as fast. However, only very few scientists would accept the thought that genetics were to be applied to bacteria, but as Joshua Lederberg , himself an American molecular biologist suggested, the three scientists paved the early way for molecular genetics. The experiment opened up new possibilities and research fields for following biologists. Avery was awarded the Copley Medal for his bacterial transformations, but neglected by many scientists and organizations for his work.

References and Further Reading:

• [1] Lederberg J (February 1994). “The transformation of genetics by DNA: an anniversary celebration of Avery, MacLeod and McCarty (1944)” . Genetics 136 (2): 423–6
• [2] History of DNA Researc h Timeline
• [3] Isolating Hereditary Material: Frederick Griffith, Oswald Avery, Alfred Hershey, and Martha Chase at Nature
• [4] Crick and Watson Decipher the DNA , SciHi Blog, February 28, 2013
• [4] Louis Pasteur – The Father of Medical Microbiology , SciHi Blog, December 27, 2012
• [5] National Academy of Sciences Biographical Memoir
• [6]  Oswald T. Avery Collection (1912-2005)  – National Library of Medicine finding aid
• [7]  DNA: The Search for the Genetic Material  Avery, MacLeod and McCarty’s Experiment for the Advanced Science Hobbyist.
• [8] Oswald T. Avery at Wikidata
• [9]  How 3 Scientists Found that DNA is the Molecule of Heredity – Avery, MacLeod, and McCarty , 2020, YourekaScience @ youtube
• [10] Timeline of famous Biology Experiments , via DBpedia and Wikidata

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Discovery of DNA as the Hereditary Material using Streptococcus pneumoniae

No one could have predicted that experiments designed to understand bacterial pneumonia would lead to the discovery of DNA as the hereditary material. In the early part of the twentieth century, before the advent of antibiotics, pneumococcal infections claimed many more lives than they do today. Researchers on both sides of the Atlantic were thus actively engaged in studying Streptococcus pneumoniae , the bacterium responsible for clinical infections. Early on, it became apparent that multiple strains of S. pneumoniae were responsible for causing bacterial pnuemonia. Researchers also noted that patients developed antibodies to the particular strain, or serotype, with which they were infected, but these antisera were not universally reactive against pneumococcal strains. However, the bacterial isolates and serum samples from these clinical studies provided the critical reagents for the experiments that ultimately led to the identification of DNA as the hereditary material.

Pneumococcal Research Provides Critical Tools in DNA Research

Although numerous scientists engaged in pneumococcal research during the first half of the twentieth century, two of these researchers played an especially important role in the course of events that led to the discovery of DNA as the hereditary material . One of these individuals was Oswald Avery . Avery joined the Rockefeller Institute for Medical Research, now the Rockefeller University, in 1913 as part of a team seeking to develop a therapeutic serum for treating lobular pneumonia. Avery believed that knowledge of the chemical composition of the pneumococcus bacterium was essential for understanding and treating the disease . He perfected his biochemical technique by focusing on the chemical composition of the capsule that surrounded virulent S strains of pneumococci. In his early work, Avery helped establish that polysaccharides were a major component of the pneumococcal capsule and that capsules from different serotypes of pneumococci had distinctive polysaccharide compositions. Avery also concerned himself with the role of capsules in pathogenicity, as capsules were notably absent from the surface of nonvirulent R forms of streptococci. Defying the conventional wisdom of the time, Avery hypothesized that the polysaccharides in the capsules were the actual antigens stimulating the production of antibodies in infected patients (Avery & Goebel, 1933).

Purification of the Active Transforming Principle

When Avery first became aware of Griffith's results, he treated them with skepticism. Other researchers and laboratories, however, were quick to reproduce and build upon Griffith's data. Within a few years, Sia and Dawson (1931) showed that transformation could be carried out in liquid cultures of pneumococci as well as in mice, allowing more precise control of environmental variables in transformation experiments. In 1932, Alloway further demonstrated that the active transforming principle was present in sterile, cell-free extracts prepared from heat-treated pneumococci by filtration. These additional findings convinced Avery that the transforming principle could be identified, and he applied his considerable biochemical expertise to its purification from pneumococcal extracts (Avery et al. , 1944).

A critical aspect of any biochemical purification is the development of an assay, or a way to measure the activity of interest. For their experiments, Avery and his colleagues developed conditions under which R cells could be reliably transformed into S cells using extracts of heat-killed Type III S cells. These same conditions could then be used to measure transforming activity in fractions obtained at different steps in the purification process. To quantify the actual amount of transforming principle in a fraction, each sample was tested at a series of increasing dilutions. These data represent four identical experiments in which Avery and his colleagues tested the ability of the purified factor, designated preparation 44, to transform Type II R cells into Type III S cells. The transforming activity was very concentrated in the extract, since it could be diluted ten-thousand-fold without losing its transforming ability. Fractions that maintained transforming activity at the highest dilutions were deemed to possess the highest concentration of transforming activity. Specifically, when at least 0.01μg of the extract was added to cells, transformation was observed. When any less than 0.01μg was added, the transformation was inconsistent (comparing samples 1 and 3 with 2 and 4) (Figure 2).

Physical Characterization of the Transforming Principle

Avery and his colleagues submitted the purified transforming principle to rigorous physical characterization in order to demonstrate that it possessed the properties expected of DNA (Avery et al. , 1944). The elemental composition of the purified transforming compound was close to the theoretical values for DNA (last row, sodium desoxyribonucleate) (Figure 3). Significantly, the purified principle had a high phosphorous content, which is characteristic of DNA, but not of proteins.

Consistent with these results, the factor gave positive reactions in chemical tests for DNA, but negative or weakly positive reactions in tests for proteins and RNA . Other tests indicated that the transforming principle was a very large molecule that absorbed the same spectrum of ultraviolet light as DNA. However, the most definitive proof that the transforming principle was DNA was its sensitivity to specific enzymes, called DNAses, that specifically degrade different kinds of DNA. Avery and his colleagues were able to show that transforming activity was not destroyed by enzymes that degrade proteins or RNA. At the time, Avery could not obtain samples of pure DNAse. Instead, Avery and his colleagues used crude preparations from animal tissues that were known to contain DNAse activity. They then measured the ability of these various crude preparations to destroy the transforming principle in parallel with measurements of phosphatase, esterase, and DNAse activities in the same extracts. In all cases, the ability of the crude extracts to destroy the transforming principle was proportional to their DNAse activity, measured with pure calf thymus DNA as substrate (Figure 4).

DNA Has the Properties Expected of Genes

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How Did Scientists Prove That DNA Is Our Genetic Material?

Griffith experiment, avery, macleod and mccarty experiment, hershey and chase experiment.

Three seminal experiments proved, without doubt, that DNA was the genetic material, and not proteins. These experiments were the Griffith experiment, Avery, MacLeod, and McCarthy Experiment, and finally the Hershey-Chase Experiment.

DNA is the fundamental component of our being. The human body is merely the carrier for this genetic material, passing it down from generation to generation. Our purpose is to ensure the survival of the species. Humans are to DNA like a fruit is to a seed. We are just an outer covering to ensure the safe passage and protection of the source code of our existence through time. Makes you feel pretty useless, doesn’t it?

However, that’s not what I want you to focus on. The main focus is, how did we discover that DNA is the carrier of information? How did we determine that it wasn’t something else, like proteins? After all, proteins are also present in every cell.

For a long time this debate had been going on. Even after Gregor Mendel formed the 3 laws of inheritance , it wasn’t accepted by the scientific community for 45 years. The reason? There was no concept of DNA or genes being the information carriers! The whole debate was finally put to rest by 3 main experiments carried out by independent researchers, which formed the basis of all our evolutionary and molecular biology studies.

Recommended Video for you:

The first step was taken by Frederick Griffith in the year 1928. He was a bacteriologist who focused on epidemiology.  Griffith was studying how Streptococcus pneumoniae caused an infection. He was working with 2 strains of the bacteria called the S and R strains. S strain organisms, when cultured in the lab, gave rise to bacterial colonies with a smooth appearance. This was due to a shiny, polysaccharide coat, which is supposed to be their virulence factor. A virulence factor is any quality or factor of a pathogen that helps it in achieving its goal – causing a disease! The other strain was the R strain. This strain gave rise to colonies that didn’t possess the polysaccharide coat, and therefore had a ‘rough’ appearance. Therefore, the S strain was virulent and the R strain was avirulent.

Griffith took 4 mice and injected them with different solutions. The first one was injected with the S strain organisms; the second one was injected with the R strain organisms; the third mouse was injected with heat-killed S strain organisms; and the last one was injected with a mixture of heat-killed S strain and live R strain organisms. The result? The first and fourth mice died due to the infection, while the second and third mice survived. When he extracted the infectious agent from the dead mice, in both cases, he found S strain organisms.

Let’s break it down. The first 2 mice showed that S strain is the virulent strain, while the R strain is avirulent. The third mouse proved that heat-killed S strain organisms cannot cause an infection. Now here is where it gets interesting. The death of the 4 th mouse, and the retrieval of live S strain organisms showed that, somehow, the heat-killed S strain organisms had caused the transformation of live R strain organisms to live S strain organisms.

This was called the transformation experiment… not particularly creative in the naming department.

Also Read: Does Human DNA Change With Time?

While Griffith’s experiment had provided a surprising result, it wasn’t clear as to what component of the dead S strain bacteria were responsible for the transformation. 16 years later, in 1944, Oswald Avery, Colin Macleod and MacLynn McCarty solved this puzzle.

They worked with a batch of heat-killed S strain bacteria. They divided it into 5 batches. In the first batch, they destroyed the polysaccharide coat of the bacteria; in the second batch they destroyed its lipid content; they destroyed the RNA of the bacteria in the third batch; with the fourth batch, they destroyed the proteins; and in the last batch, they destroyed the DNA. Each of these batches was individually mixed with live R strain bacteria and injected into individual mice.

From all 5 mice, all of them died except the last mouse. From all the dead mice, live S strain bacteria was retrieved. This experiment clearly proved that when the DNA of the S strain bacteria were destroyed, they lost the ability to transform the R strain bacteria into live S strain ones. When other components, such as the polysaccharide coat, lipid, RNA or protein were destroyed, transformation still took place. Although the polysaccharide coat was a virulent factor, it wasn’t responsible for the transfer of the genetic matter.

Even after the compelling evidence provided by the Avery, Macleod and McCarty experiment, there were still a few skeptics out there who weren’t convinced. The debate still raged between proteins and DNA. However, the Hershey – Chase experiment permanently put an end to this long-standing debate.

Alfred Hershey and Martha Chase in 1952, performed an experiment that proved, without a doubt, that DNA was the carrier of information. For their experiment, they employed the use of the bacteriophage T2. A bacteriophage is a virus that only infects bacteria. This particular virus infects Escherichia coli . T2 had a simple structure that consisted of just 2 components – an outer protein casing and the inner DNA. Hershey and Chase took 2 different samples of T2. They grew one sample with 32 P, which is the radioactive isotope of phosphorus, and the other sample was grown with 35 S, the radioactive isotope of sulphur!

The protein coat has sulphur and no phosphorus, while the DNA material has phosphorus but no sulphur. Thus, the 2 samples were labelled with 2 different radioactive isotopes.

The viruses were then allowed to infect the E. coli . Once the infection was done, the experimental solution was subjected to blending and centrifugation. The former removed the ghost shells, or empty shells of the virus from the body of the bacteria. The latter separated the bacteria from everything else. The bacterial solution and the supernatant were then checked for their radioactivity .

In the first sample, where 32 P was used, the bacterial solution showed radioactivity, whereas the supernatant barely had any radioactivity. In the sample where 35 S was used, the bacterial solution didn’t show any radioactivity, but the supernatant did.

This experiment clearly showed that DNA was transferred from the phage to the bacteria, thus establishing its place as the fundamental carrier of genetic information.

Until the final experiment performed by Hershey and Chase, DNA was thought to be a rather simple and boring molecule. It wasn’t considered structured enough to perform such a complicated and extremely important function. However, after this experiment, scientists started paying much more attention to DNA, leading us to where we are in research today!

Also Read: A History Of DNA: Who Discovered DNA?

• How was DNA shown to be the genetic material?. The University of Texas at Austin
• The Genetic Material - DNA - CSUN. California State University, Northridge
• Home - Books - NCBI. National Center for Biotechnology Information

Mahak Jalan has a BSc degree in Zoology from Mumbai University in India. She loves animals, books and biology. She has a general assumption that everyone shares her enthusiasm about the human body! An introvert by nature, she finds solace in music and writing.

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Oswald Avery: the professor, DNA, and the Nobel Prize that eluded him

Affiliation.

• 1 Professor Emeritus of Pathology, Dalhousie University.
• PMID: 15202433
• DOI: 10.3138/cbmh.21.1.135

In 1944, two Canadians, Oswald Avery and Colin MacLeod, and an American, MacLyn McCarty, published a paper in The Journal of Experimental Medicine that demonstrated genes to be the chemical, deoxyribonucleic acid (DNA). Even though this paper is now regarded as the single mos important publication in biology of the 20th century, Avery was not awarded the Nobel Prize. This raises the question as to why his work did not earn him the Prize. These are several possible reasons: the discovery may have been ahead of tis time; all three authors were physician-scientists ans not recognized chemists or geneticists; and Avery, the principal author, had reached an advanced age and characteristically took an extremely cautious and low-key approach to his work. Discussion of these reasons in turn raises other issues surrounding the recognition of the work of celebrated scientist, from Galileo and Copernicus onwards.

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Concept 17 A gene is made of DNA.

It's hard to imagine now the impact that Avery's experiments must have had. Until Avery's experiments, scientists weren't even sure that bacteria had genes.

Avery's experiments showed that DNA is the tranforming principle, but he didn't try to figure out how transformation works. How do you think transformation works?

Funded by --> The Josiah Macy, Jr. Foundation © 2002 - 2011, DNA Learning Center , Cold Spring Harbor Laboratory . All rights reserved.

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

The Avery-MacLeod-McCarty Experiment was presented by Oswald Avery, Colin MacLeod, and Maclyn McCarty in 1944. During the 1930s and early 1940s, Avery and MacLeod performed this experiment at Rockefeller Institute for Medical Research, after the departure of MacLeoirulency (measure of deadly potency). This experiment would allow them to determine if rough bacteria could be transformed into smooth bacteria, hence passing along the genetic information causing the transformation. By isolating and purifying this chemical component, they could deduce if it had characteristics of a protein or DNA molecule.

The purpose behind this experiment was to better understand the chemical component that carries the genetic information and transforms one molecule to the next.

Bacteria grown in petri dishes can grow spots or colonies inside the dish multiplying under certain conditions. Virulent (deadly) colonies look smooth or like tiny droplets, where as non-deadly bacteria formed rigid, uneven edges, basically rough colonies. While analyzing a certain kind of pneumonia caused by bacteria in mice, they were able to isolate a "variant" (mutant) strain that did not kill the mice. During the experiments, Avery and MacLeod injected a mouse simultaneously with "boiled" or dead smooth bacteria and live rough bacteria. Thereafter a short while they were surprised to see that the mouse died. When they took samples from the dead mice, and cultured the samples in a petri dish, Avery and MacLeod found that what grew inside the culture was in fact the smooth deadly bacteria. This suggested that something from the "dead" bacteria somehow converted the rough bacteria into smooth bacteria. The rough bacteria had been permanently converted or transformed into the smooth dangerous bacteria. They had confirmed that they could not grow smooth bacteria from the boiled culture and cause disease if the dead smooth bacteria were injected alone. This all implied that a chemical component in the smooth bacteria survived and transformed the rough bacteria into smooth. Isolating and purifying that chemical component had shown that is was DNA, NOT proteins that transferred the genetic code from the smooth to the rough.

Simpler Experimental

Here is a simpler demonstration for this experiment by Oswald Avery, Colin MacLeod, and Maclyn McCarty. There are two sets of bacteria – one is smooth (virulent), one is rough (nonvirulent).

1) They first inject deadly encapsulated bacteria into the mouse – the mouse dies at the end.

2) They then inject non-encapsulated, nonvirulent bacteria into the mouse – the mouse lives.

3) Next, they heated the virulent bacteria at a temperature that kills them and injected these bacteria into the mouse – the mouse lives.

4) After that, they then have the denatured fatal bacteria mix into the living non-encapsulated, nonfatal bacteria. The mixture was then injected into the mouse – the mouse dies.

5) Finally, they mix the live, non-encapsulated harmless bacteria with the DNA that was extracted from the heated, lethal bacteria. These “harmless” bacteria injected to the mouse after being mixed – the mouse dies.

From these experiments, Avery and his group showed that nonvirulent bacteria become deadly after mixing with the DNA of the virulent bacteria . Such a demonstration shows that nonvirulent bacteria became virulent because of the genetic information that originally came from the virulent bacteria. The protein from the virulent bacteria was already denatured during Step 3. Thus, it was DNA and not protein that transferred the genetic information to the nonvirulent bacteria.

Griffith Experiment

In 1928, Frederick Griffith performed a DNA experiment using pneumonia bacteria and mice. This experiment provided evidence that some particular chemical within cells is genetic material. The objective of the experiment was to find the material within the cells responsible for the genetic codes.

For the experiment, Griffith used Streptococcus pneumoniae , known as pneumonia. Pneumonia contains two strains - a smooth and a rough strain. The smooth strain causes pneumonia and contains a polysaccharide coating around it. The rough strain does not cause pneumonia and also lacks a polysaccharide coating. For his first experiment, Griffith took the S strain (smooth strain) and injected it into the mice. He found that the mice contracted pneumonia and ended up dying. He then took the R strain (rough strain) and injected it into the mice and found that they did not contract the pneumonia illness and survived the insertion of the strain. Through these first two experiments Griffith concluded that the polysaccharide coating on the bacteria somehow caused the pneumonia illness, so he used heat to kill the bacteria (polysaccharides are prone to heat) of the S strain and injected the dead bacteria into the mice. He found that the mice lived, which indicated that the polysaccharide coating was not what caused the disease, but rather something living inside the cell. Then he hypothesized that the heat used to kill the bacteria denatured a protein within the living cells, which caused the disease. He then injected the mice with a heat killed S strain and a live R strain, which resulted in the mice dying.

Griffith performed a necropsy on the dead mice and isolated the S strain bacteria from the corpses. He concluded that the live R strain bacteria must have absorbed the genetic material from the dead S strain bacteria, which is called transformation, a process where one strain of a bacterium absorbs genetic material from another strain of bacteria and turns into the type of bacterium whose genetic material it absorbed. Since heat denatures proteins, the protein in the bacterial chromosomes was not the genetic material. However, evidence pointed to DNA. This experiment that Griffith performed was a precursor to the Avery experiment. Avery, Macleod and McCarty followed up on the experiment because they wanted a more definitive experiment and answer.

Avery, MacLeod and McCarty used heat to kill the virulent Streptococcus pneumonia bacteria and extracted RNA, DNA, carbohydrates, lipids and proteins - which were considered possible candidates for the carriers of genetic information - from the dead cells. Each molecule was added to a culture of live non-virulent bacteria to determine which was responsible for changing them into virulent bacteria. DNA was the only molecule that turned the non-virulent cells into virulent cells, which they concluded was the genetic material within cells.

Lockshin, Richard A., The Joy of Science 2007.

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Oswald Avery (c.1930)

• Description

In a very simple experiment, Oswald Avery's group showed that DNA was the "transforming principle." When isolated from one strain of bacteria, DNA was able to transform another strain and confer characteristics onto that second strain. DNA was carrying hereditary information. With DNA as the hereditary molecule, the stage was set for one of the most exciting periods in DNA science: understanding DNA structure and function.

oswald avery,dna structure and function,dna science,strain of bacteria,structure of dna,transforming principle,structure and function,molecule,periods

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