Who Discovered Dna Is The Genetic Material

DNA, or deoxyribonucleic acid, is universally recognized as the molecule carrying genetic information in all known living organisms and many viruses. But the path to understanding that DNA is the genetic material was not a straightforward one. It involved a series of experiments spanning several decades and the contributions of numerous scientists.

The Initial Understanding: Proteins as the Primary Suspects

In the late 19th and early 20th centuries, scientists generally believed that proteins, not DNA, were the carriers of genetic information. There were several reasons for this belief:

• Complexity: Proteins are composed of 20 different amino acids, allowing for a vast number of possible combinations and complex structures. In contrast, DNA is composed of only four nucleotides. It seemed logical to scientists that the molecule carrying the complex information needed for heredity would be more complex itself.
• Abundance: Proteins were known to perform a wide variety of functions in the cell, indicating their importance and prevalence. DNA's role, on the other hand, was largely unknown.

Given these factors, the scientific community initially favored proteins as the likely candidates for genetic material.

Friedrich Miescher: The Discovery of Nuclein

The story of DNA's discovery begins with Friedrich Miescher, a Swiss physician and biologist. In 1869, while working in the laboratory of Felix Hoppe-Seyler in Tübingen, Germany, Miescher was studying the composition of leukocytes (white blood cells). He obtained these cells from pus-soaked bandages discarded by local hospitals.

Miescher developed a process to isolate the nuclei of these cells. From the nuclei, he extracted a phosphorus-rich substance that was unlike any protein or lipid he had previously encountered. He named this substance "nuclein," recognizing that it came from the cell's nucleus.

Key points about Miescher's discovery:

• Isolation of Nuclein: Miescher's work was the first to isolate DNA, albeit in a crude form mixed with proteins.
• Unique Properties: Nuclein's high phosphorus content and acidic properties set it apart from known cellular components.
• Unrecognized Significance: While Miescher recognized the unique nature of nuclein, he did not realize its potential role as the genetic material. He believed it might be involved in the cell's acidic processes.

Miescher's findings were initially met with skepticism. Hoppe-Seyler, Miescher's mentor, took a long time to verify and publish Miescher's results. The scientific community was hesitant to accept the existence of a novel substance with such unusual properties.

Albrecht Kossel: Dissecting Nuclein

Albrecht Kossel, a German biochemist, further characterized nuclein in the late 19th century. Kossel isolated and identified the five nitrogenous bases that are the building blocks of nucleic acids: adenine (A), guanine (G), cytosine (C), thymine (T), and uracil (U). While uracil is primarily found in RNA, Kossel's work laid the foundation for understanding the composition of both DNA and RNA.

Key contributions of Kossel:

• Identification of Nitrogenous Bases: Kossel discovered that nuclein contained the bases adenine, guanine, cytosine, and thymine (in DNA).
• Recognition of Nucleic Acid Components: He correctly identified the key components of nucleic acids, paving the way for future research into their structure and function.
• Nobel Prize: Kossel was awarded the Nobel Prize in Physiology or Medicine in 1910 for his work on the chemical composition of nucleic acids.

Despite Kossel's significant contributions, the function of nucleic acids remained a mystery. Scientists still believed that the relatively simple composition of DNA could not account for the complexity of heredity.

Phoebus Levene: The Tetranucleotide Hypothesis

Phoebus Levene, a Russian-American biochemist, made significant contributions to our understanding of nucleic acids in the early 20th century. He determined that DNA is composed of nucleotides, each containing a sugar (deoxyribose), a phosphate group, and a nitrogenous base.

Levene proposed the "tetranucleotide hypothesis," which suggested that DNA consisted of a repeating sequence of the four nucleotides (A, G, C, T) in a fixed order. This hypothesis, while ultimately incorrect, had a profound impact on the field:

• Identification of Nucleotides: Levene correctly identified the components of a nucleotide: a sugar, a phosphate group, and a nitrogenous base.
• Tetranucleotide Hypothesis: Levene's hypothesis proposed a simple, repeating structure for DNA, which led many scientists to believe that DNA could not carry complex genetic information. If the nucleotides were always present in the same order, DNA would lack the variability needed to encode the diversity of life.
• Reinforcing the Protein Belief: The tetranucleotide hypothesis reinforced the prevailing belief that proteins were the genetic material, as proteins offered the complexity that DNA seemed to lack.

The tetranucleotide hypothesis was widely accepted for many years, hindering progress in understanding DNA's true role.

Frederick Griffith: Transformation in Bacteria

The first experimental evidence suggesting that DNA might be the genetic material came from Frederick Griffith, a British bacteriologist. In 1928, Griffith was studying Streptococcus pneumoniae, a bacterium that causes pneumonia. He was trying to develop a vaccine against this deadly disease.

Griffith worked with two strains of S. pneumoniae:

• Virulent (S) Strain: This strain had a smooth capsule and caused pneumonia in mice.
• Non-Virulent (R) Strain: This strain lacked a capsule and did not cause pneumonia.

Griffith conducted a series of experiments:

1. Injection of S Strain: Mice injected with the S strain died.
2. Injection of R Strain: Mice injected with the R strain lived.
3. Injection of Heat-Killed S Strain: Mice injected with heat-killed S strain lived. The heat killed the bacteria, rendering it harmless.
4. Injection of Heat-Killed S Strain + R Strain: Mice injected with a mixture of heat-killed S strain and live R strain died. When Griffith examined the dead mice, he found live S strain bacteria.

Griffith concluded that the live R strain bacteria had been "transformed" into the virulent S strain by some "transforming principle" from the heat-killed S strain. He didn't know what this transforming principle was, but he hypothesized that it was a molecule that carried genetic information.

Key implications of Griffith's experiment:

• Transformation: Griffith's experiment demonstrated that genetic material could be transferred between bacteria, changing their characteristics.
• Identification of a "Transforming Principle": The existence of a transforming principle suggested that a specific molecule was responsible for carrying genetic information.
• A Shift in Thinking: Griffith's work challenged the prevailing view that genetic traits were fixed and unchangeable.

Griffith's experiment was a groundbreaking discovery, but he was unable to identify the transforming principle. His findings sparked further research to identify the molecule responsible for this transformation.

Oswald Avery, Colin MacLeod, and Maclyn McCarty: DNA as the Transforming Principle

The definitive experiment that identified DNA as the genetic material was conducted by Oswald Avery, Colin MacLeod, and Maclyn McCarty at the Rockefeller Institute for Medical Research in New York City. In 1944, they published a landmark paper that provided strong evidence that DNA, not protein, was the transforming principle in Griffith's experiment.

Avery, MacLeod, and McCarty meticulously purified various components from the heat-killed S strain bacteria, including DNA, RNA, proteins, lipids, and carbohydrates. They then tested each component separately to see if it could transform the R strain bacteria into the S strain.

Their experimental approach:

1. Preparation of S Strain Extract: They prepared an extract from heat-killed S strain bacteria.
2. Separation of Components: They separated the extract into its major components: DNA, RNA, proteins, lipids, and carbohydrates.
3. Transformation Assays: They treated the R strain bacteria with each purified component separately.
4. Enzyme Degradation: To confirm their results, they used specific enzymes to degrade each component before adding it to the R strain bacteria. For example, they used DNase to degrade DNA, RNase to degrade RNA, and proteases to degrade proteins.

Their results were conclusive:

• DNA as the Transforming Principle: Only the DNA fraction was able to transform the R strain bacteria into the S strain.
• Enzyme Degradation Confirms DNA's Role: When the DNA fraction was treated with DNase, it lost its ability to transform the bacteria. However, treatment with RNase or proteases did not affect its transforming ability.

Avery, MacLeod, and McCarty concluded that DNA was the molecule responsible for carrying genetic information. Their results provided the first direct evidence that genes are made of DNA.

Key implications of the Avery-MacLeod-McCarty experiment:

• Definitive Identification of DNA: The experiment provided strong evidence that DNA, not protein, is the genetic material.
• Transformation Mechanism: The experiment clarified the mechanism of transformation, showing that DNA could directly alter the genetic makeup of bacteria.
• Paradigm Shift: The results challenged the long-held belief that proteins were the carriers of genetic information and paved the way for a new era in molecular biology.

Despite the strength of their evidence, the Avery-MacLeod-McCarty experiment was not immediately accepted by all scientists. Some researchers remained skeptical, partly because the concept of DNA as the genetic material was so different from the prevailing view. Additionally, some questioned whether the results obtained in bacteria could be extrapolated to other organisms.

Alfred Hershey and Martha Chase: The Blender Experiment

Further support for DNA as the genetic material came from the work of Alfred Hershey and Martha Chase in 1952. They conducted a series of experiments using bacteriophages, viruses that infect bacteria. Their experiments, often referred to as the "Waring blender experiment," provided elegant and compelling evidence that DNA, not protein, is the genetic material of bacteriophages.

Hershey and Chase used bacteriophage T2, which consists of a protein coat surrounding a DNA core. They devised a way to selectively label either the protein coat or the DNA with radioactive isotopes:

• Radioactive Sulfur (35S) to Label Proteins: Sulfur is present in proteins but not in DNA.
• Radioactive Phosphorus (32P) to Label DNA: Phosphorus is present in DNA but not in proteins.

Their experimental procedure:

1. Infection: They allowed the labeled bacteriophages to infect E. coli bacteria.
2. Blending: After infection, they agitated the mixture in a Waring blender to separate the phage coats from the bacterial cells.
3. Centrifugation: They centrifuged the mixture to separate the heavier bacterial cells from the lighter phage coats.
4. Measurement of Radioactivity: They measured the radioactivity in both the bacterial cells and the supernatant (the liquid containing the phage coats).

Their results were clear:

• Radioactive Phosphorus (32P) in Bacteria: Most of the radioactive phosphorus (32P), which labeled DNA, was found inside the bacterial cells.
• Radioactive Sulfur (35S) in Supernatant: Most of the radioactive sulfur (35S), which labeled proteins, was found in the supernatant containing the phage coats.

Hershey and Chase concluded that DNA, not protein, enters the bacterial cells during infection and carries the genetic information needed to produce more bacteriophages.

Key implications of the Hershey-Chase experiment:

• Confirmation of DNA's Role: The experiment provided strong and independent confirmation that DNA is the genetic material.
• Mechanism of Viral Infection: The experiment elucidated the mechanism of viral infection, showing that viruses inject their DNA into cells to replicate.
• Widespread Acceptance: The Hershey-Chase experiment was widely accepted by the scientific community and helped to solidify the central dogma of molecular biology.

Erwin Chargaff: Chargaff's Rules

Erwin Chargaff, an Austrian-American biochemist, made important contributions to our understanding of DNA's structure. In the late 1940s and early 1950s, Chargaff analyzed the base composition of DNA from various organisms. He discovered that the amount of adenine (A) was always equal to the amount of thymine (T), and the amount of guanine (G) was always equal to the amount of cytosine (C). These relationships are known as Chargaff's rules:

• A = T: The amount of adenine is equal to the amount of thymine.
• G = C: The amount of guanine is equal to the amount of cytosine.

Chargaff's rules provided crucial clues for understanding the structure of DNA. While he did not propose the double helix structure himself, his findings were essential for Watson and Crick's model.

Key implications of Chargaff's rules:

• Base Pairing: Chargaff's rules suggested that adenine and thymine, and guanine and cytosine, were paired together in some way.
• Structural Clues: The rules provided important constraints for any proposed structure of DNA.
• Foundation for Watson and Crick: Chargaff's rules played a crucial role in Watson and Crick's discovery of the double helix structure of DNA.

James Watson and Francis Crick: The Double Helix

The final piece of the puzzle was the discovery of the double helix structure of DNA by James Watson and Francis Crick in 1953. Using X-ray diffraction data obtained by Rosalind Franklin and Maurice Wilkins, as well as Chargaff's rules, Watson and Crick built a model of DNA as a double helix.

Their model:

• Double Helix: DNA consists of two strands wound around each other in a helical structure.
• Sugar-Phosphate Backbone: The sugar-phosphate backbone forms the outside of the helix.
• Base Pairing: The nitrogenous bases are located on the inside of the helix, with adenine (A) paired with thymine (T), and guanine (G) paired with cytosine (C).
• Hydrogen Bonds: The base pairs are held together by hydrogen bonds.

The Watson-Crick model of DNA provided a clear and elegant explanation for how DNA could carry genetic information and how it could be replicated. The double helix structure allowed for the faithful transmission of genetic information from one generation to the next.

Key implications of the Watson-Crick model:

• Structure and Function: The model revealed the structure of DNA and explained how it could function as the genetic material.
• Replication Mechanism: The model suggested a mechanism for DNA replication, with each strand serving as a template for the synthesis of a new strand.
• Genetic Code: The model opened the door to understanding the genetic code, the set of rules by which information encoded in DNA is translated into proteins.
• Nobel Prize: Watson and Crick, along with Maurice Wilkins, were awarded the Nobel Prize in Physiology or Medicine in 1962 for their discovery of the structure of DNA. (Rosalind Franklin had passed away in 1958 and was not eligible for the prize.)

Conclusion

The discovery that DNA is the genetic material was a long and complex process involving the contributions of many scientists. From Friedrich Miescher's initial isolation of nuclein to Watson and Crick's discovery of the double helix structure, each step built upon the previous one.

The key milestones in this journey include:

• Friedrich Miescher: Discovery of nuclein.
• Albrecht Kossel: Identification of nitrogenous bases.
• Phoebus Levene: Identification of nucleotides and the tetranucleotide hypothesis.
• Frederick Griffith: Discovery of transformation in bacteria.
• Oswald Avery, Colin MacLeod, and Maclyn McCarty: Identification of DNA as the transforming principle.
• Alfred Hershey and Martha Chase: Confirmation of DNA as the genetic material in bacteriophages.
• Erwin Chargaff: Discovery of Chargaff's rules.
• James Watson and Francis Crick: Discovery of the double helix structure of DNA.

The identification of DNA as the genetic material revolutionized biology and medicine. It paved the way for advancements in genetics, molecular biology, biotechnology, and medicine. Today, our understanding of DNA is fundamental to fields ranging from personalized medicine to gene editing, offering unprecedented opportunities to improve human health and understand the nature of life itself.