The discovery of DNA as the genetic material was one of the landmark events in the field of biology. By confirming DNA as the genetic material scientists made a huge leap that has advanced the cause of medical science to a great degree. While discussing the discovery of DNA as the genetic material, we mostly speak of Friedrich Miescher (1871), the man who discovered DNA. After the discovery of DNA a significant number of studies were conducted that proved DNA as the genetic material. Then Griffith, (1928) conducted studies on bacterial transformation and indicated that genetic information can be transferred from one individual to the next. Another experiment conducted by Avery, MacLeod, & McCarty, (1944) characterized the nature of DNA and established it as the genetic material. Alfred Hershey and Martha Chase(1952)also conducted experiments on labeled bacteriophages and proved that genetic information was carried in the form of nucleic acids and not protein. Finally, Watson & Crick, (1953) along with that of Maurice Wilkins and Rosalind Franklin furnished vital information about the structure of the genetic material. All the above-mentioned experiments extended the vista of human knowledge about genetics and inheritance. Twentieth century biology has made exponential progress due to the results published by these experiments. In the following section we will try to see how DNA was established as the genetic material, and how its functional structure was determined.
Discovery of DNA as the genetic Material
The story of DNA as a genetic material started in 1869, when a young physician by the name of Friedrich Miescher, started studying the proteins in leucocytes. Friedrich Miescher was born in the town of Basel in Switzerland. Friedrich was close to his uncle Wilhelm Miescher, who was one of the best physician and professor of anatomy. From a very early age, miescher developed a keen interests in biology. Miescher joined Hoppe-Seyler’s laboratory in 1868, which was situated in Tubingen Castle. Miescher wanted to understand the chemical composition of cells to understand the fundamental principles of life of cells. On Hoppe-Seyler’s suggestion, Miescher chose Leucocytes obtained from pus in fresh surgical bandages as the study material. At first Miescher focused on different types of proteins that made up the Leucocyte cells. Through his initial experiments, Miescher showed that cells were mostly composed of lipids and proteins. However, Miescher observed that during experiments he found that a substance precipitated from the solution when acid was added and again went back to solution when alkali was added. Miescher suspected that this material had its origins in the nucleus and started examining the nucleus more closely. Miescher developed protocols to isolate the mysterious substance. First, he would wash the pus obtained from bandages in warm alcohol, then he would use the acid extract from pig’s stomach to dissolve cell membranes, and he was left with a gray paste of the mysterious substance. In order to understand the elementary composition of the substance, Miescher subjected it to charring, he found that apart from containing Carbon Hydrogen and Oxygen the paste also contained around 3 percent phosphorus. Miescher was convinced that this substance was unique and named it “Nuclein”. Despite protests from Hoppe-Seyler that the tests were wrong and needed to be redone, Miescher published his works in 1871. Miescher laid the groundwork for molecular studies on the composition of genetic material.
In 1928, Frederick Griffith conducted an experiment to show that bacteria (Pneumococcus) was capable of transferring genetic information through a process of transformation. Griffith called this material the “transforming principle”. Griffith’s experiment was the first of its kind to suggest the transference of the genetic material. In this experiment Griffith used two strains of Streptococcus pneumonia; a type-IIIS strain (smooth surface) and a type II-R strain (rough) strain. The II-R strain is devoid of the protective coating and the III-S strain has a polysaccharide coating that protects it from the host’s immune system. In this classic experiment, Griffith killed the smooth coated bacteria with heat. Then Griffith went on to inject three types of solutions a. Heat killed III-S strain, b. living II-R strain, and c. a combination of a and c. Griffith discovered that mice treated with option ‘a’ and ‘b’ were not affected but those treated by the combination of heat killed III-S strain and the II-R strain were infected. Griffith deduced that the remains of the heat-killed III-S strain must have contained a “transforming principle” that changed the II-R strain. This experiment was the guiding principle for future work by Avery, MacLeod, & McCarty, (1944).
Oswald Avery, Colin MacLeod and Maclyn McCarty in 1944 set out to prove that DNA was the substance responsible for bacterial transformation. The team would later disprove existing misconception that genetic material was composed of proteins. In this experiment, Avery first killed the bacteria III-S strain and extracted the component of the cell that were saline soluble. In the next step, the protein of the remaining solution was precipitated using chloroform and the polysaccharide capsule of the III-S strain was hydrolyzed and the resulting solution was precipitated using alcohol fractionation. The resulting material was confirmed as Griffith’s “transforming principle”. Avery and associates then went on to prove that the material obtained was immune to the action of ribonuclease, trypsin or chymotrypsin. The material broke down and lost its transforming capabilities under the action of a crude extract of “deoxyribonucleodepolymerase”. This study clearly proved the DNA was the genetic material and is considered one of the landmark studies that changed the course of biological sciences. Initially, this experiment initially went unnoticed but later was give the due appreciation by the scientific community.
Structure of DNA
The quest to understand the structure of DNA was partaken by various scientists that included Alfred Hershey and Martha Chase (Hershey & Chase, 1952). Erwin Chargaff, an Austrian Chemist also provided some great insights into the chemical composition of DNA and its constitution. However Chargaff is pivotal for the “Chargaff’s rule”, which claimed that in natural DNA, the number of Guanine units equal the number of Cytosine units, while the number of Adenine units corresponded to that of Thymine. This discovery further aided Watson and Crick to come up with the actual double helical model of DNA(Chargaff & Vischer, 1948).
Now the only step that was needed to understand the actual structure of DNA was the X-Ray Crystallography images. Rosalind Franklin and Maurice Wilkins worked at the King’s college X-ray crystallography lab. Although Franklin and Wilkins were both working on the X-ray crystallography of DNA, they never really collaborated due to personal differences. At the same time, James Watson and Francis Crick from the Cavendish Laboratory were working to solve the structure of DNA. Rosalind Franklin and her student Raymond Gosaling compared two X-ray Crystallography pictures of two strands DNA, one more hydrated than the other and proposed that DNA had a helical structure with phosphates on the outside. Meanwhile at the Cavendish laboratory, Francis and Crick were trying construct a model of the DNA using metal plates. Watson and Crick had trouble figuring out whether to build the model of DNA with the phosphates inside or outside. Wilkins showed Watson and Crick an X-ray Crystallography images of hydrated DNA molecules which showed a beautiful helical structure, as was initially proposed by Franklin. American Chemist, Jerry Donohue suggested that hydrogen bonding may allow adenosine to bind with Thymine and Guanine to bind with Cytosine. Therefore, Watson and Crick concluded that the phosphates should be outside with nucleotides inside forming the double helical structure of DNA. Based on the findings of their respective studies, all three teams published their findings in Nature. According to Watson & Crick, (1953), DNA had a double-stranded helical structure with base pairing between adenosine and Thymine and Guanine and Cytosine. Both the strands could unwind from each other and make exact copies of each other to be passed on to the next generations. Wilkins, Stokes, & Wilson, (1953) and Franklin & Gosling, (1953) also published their findings on the double helical structure of DNA on the same issue of Nature. The year 1953, can be considered one of the biggest years for biological sciences as this was the end for all speculation regarding the genetic material and its composition. All these studies created the platform for scientists from where they could understand the genetic basis of diseases and develop other techniques to understand and help the society.
References
Avery, O., MacLeod, C., & McCarty, M. (1944). Studies on the chemical nature of the substance inducing transformation of Pneumococcal types. The Journal of Experimental Medicine, 79(2), 137–158. Retrieved from http://www.springerlink.com/index/g345284417660444.pdf
Chargaff, E., & Vischer, E. (1948). The separation and quantitative estimation of purines and pyrimidines in minute amounts. J. Biol. Chem, 176, 703–714. Retrieved from http://www.biomonsters.com/uploads/8/5/4/6/8546703/j._biol._chem.-1948-vischer-703-14-chagraff.pdf
Franklin, R. E., & Gosling, R. G. (1953). Evidence for 2-chain helix in crystalline structure of sodium deoxyribonucleate. Nature, 172, 156–157.
Griffith, F. (1928). The significance of pneumococcal types. Journal of Hygiene, (13), 129–176. Retrieved from http://journals.cambridge.org/abstract_S0022172400031879
Hershey, A., & Chase, M. (1952). Independent functions of viral protein and nucleic acid in growth of bacteriophage. The Journal of General Physiology, 39–56. Retrieved from http://jgp.rupress.org/content/36/1/39.short
Miescher-Rüsch, F. (1871). Ueber die chemische Zusammensetzung der Eiterzellen.
Watson, J. D., & Crick, F. H. C. (1953). Molecular structure of nucleic acids. Nature, 171(4356), 737–738.
Wilkins, M. H. F., Stokes, A. R., & Wilson, H. R. (1953). Molecular structure of nucleic acids: molecular structure of deoxypentose nucleic acids. Nature, 171(4356), 738–740.
