Friedrich Miescher's Experiments on the Nuclei

In the year 1869, a Swiss physiological chemist named Friedrich Miescher identified a substance called nuclein which he found inside the nuclei of human white cells. He was the first to identify such a substance from leukocytes also called white blood cells. Miescher’s intention was not to isolate the nuclein from the white blood cells but rather to isolate the components of the protein in the white blood cell. Because of this, he arranged for a local surgical clinic to send him used pus-coated bandages from patients on receiving the pus-coated bandages, he washed them and filtered out the leukocytes, then he extracted and tried to identify the various protein within the leukocytes. But in the process, He came across an unfamiliar substance from the cell’s nuclei that had chemical properties unlike the protein. Some of the unfamiliar properties were that it had a much higher phosphorous content and also resistant to protein digestion, so he realized he had discovered a new substance but not so certain about his finding but sensing its importance he wrote “it seems probable to me that a whole family of such slightly varying phosphorous-containing substance will appear, as a group of nucleins equivalent to proteins ”

Now after DNA has being discovered, it was left with people to understand the essence of it. Many scientists tried to understand the importance of DNA in the organisms by examining its structure and function by the use of experiments. Scientist could not tell the exact role a DNA plays in the life of organisms but one scientist called Gregor Mendel brought to bear some issues that lead to the role or understanding of DNA. In 1860,s, he studied several different traits in pea plants and by conducting an appropriate crossing. He realized that traits are inherited in an unaltered way. Implying that living organisms contain a genetic material that governs an individual traits. He finally came out with four properties that the genetic material must meet to fulfill its role

1. The genetic material must contain the information necessary to construct an entire organism.
2. During reproduction, the genetic material must usually pass unaltered from parent to offspring.
3. Since a parent can produce many offspring’s, the genetic material must be copied.
4. Within any species a significant amount of phenotypic variation occurs.

After his experiment other scientists did other experiments that helped understand as the role of DNA. A scientist who was an army medical office named Frederick Griffith studied a type of bacterium known then as pneumococci now classified as Diplococcus pneumoniae. During his experiment he realized that certain strains of D. pneumonia secrets a polysaccharide capsule while other strains do not. When streaked on a petri plates containing solid growth media, capsule-secreting strains gave a smooth colony morphology where as those strains unable to secret gave a rough appearance. He designated the strains S and R respectively. Now from here he carried out an experiment that involved the injection of live and/or heat-killed bacteria into mice to observe whether or not the bacteria caused any lethal infection.

1. The laboratory mice were injected with live R-strain cells and it was observed that the R- strain was harmless.
2. Mice were injected with live S- strain cells. The mice died meaning the S- strain was pathogenic.
3. S cells were killed by exposure to high temperature and was injected into the mice.the mice did not die.
4. Live R- strain cells were mixed with heat killed S- strain cells and injected it into the mice and the mice died.

Now the question was what was going on in the fourth experiment? The simplest explanation was that the heat did kill the cells but could not destroy their hereditary material. Somehow that material had being transferred from the dead S-strain cell to the living R-strain cell which caused the mice to die. However, Griffith did not know what the transforming substance was but after him came Oswald Avery, Colin Maclead and Maclyn McCarthy who realized that Griffiths experiment could be used as an experimental strategy to identify the genetic material and their question was “what substance was transferred from the heat killed S- strain cell to the live R- strain cell? Now during this time DNA, RNA and protein had being discovered to be the major constituents of living cells. To understand things better they had to separate these components by using a biochemical purification procedures. In their experiment they prepared from the dead bacteria, that is, the heat –killed S-strain “an extracted that was responsible for making the live R- strain virulent. They used the term transformation principle. The extract contained a purified preparation of DNA. When the extract was mixed with live R- strain cell some of the bacteria were converted to heat killed S- strain bacteria. However if no extract was added no S- strain bacterial colonies were observed on the petri plate. Now it was argued that the DNA extract may have been contaminated by some portion of RNA or proteins. To verify their points that DNA was actually what caused the transformation, they treated samples of the DNA extract with enzymes that digest DNA, RNA and protein. Now when the DNA extract sample was treated with RNase and protase it was still realized that the life R-strain was converted into heated-killed S-strain but when it was treated with DNase its ability to transform was lost. And so this confirmed that DNA was a genetic material. Now understanding the importance and role of DNA in an organism its structure was then to be studied to understand actually how it and worked. As years passed, other scientists continued to research into what Miescher has discovered especially its chemical nature. One of these scientists is Phoebus Levene, a Russian Biochemist. He worked using Hydrolysis to break down the nucleic acid of yeasts for analysis after analyzing the nucleic acid of the yeast he realized that the nucleic acid was composed of a series of nucleotides and each nucleotides was in turn composed of just one of four nitrogen-containing basis, a sugar molecule and a phosphate group and this is the polynucleotide structure of the categories of the nitrogenous base that is,

1. the purines which consists of adenine[A] and guanide[G]
2. The purimidines which is composed of cytosine[C] and thymine [T].

With the purines each has two fused rings and purimidines each with a single ring. All the four types of nucleotides in DNA have their component parts joined together in much same way. He also proposed what is called the tetranucleotide structure which deals with the fact that nucleotides are always arranged in the same order (G-C-T-A-G-C-T-A).The nucleotides are linked together to form a strand of DNA.The linear sequence of nucleotide within a strand is called primary structure of DNA.From his, many new facts and new evidence soon emerged and caused little alterations in Levene’s proposal. Another scientist, Erwin Chargaff also came to strengthen the foundation by bringing forth additional details from the structure of DNA.