In 1918 Sir Ronald Fisher published "" marking the beginning of the modern evolutionary synthesis, or neo-Darwinism - generally denoting the integration of 's theory of the of by , 's theory of as the basis for biological inheritance, random genetic mutation as the source of variation, and mathematical . At this point in scientific history theories were combining to piece together the fundamentals of living organisms. (4) (5)
The next two decades saw experimentation in order to further understanding of genetics, including the first case of transformation as Frederick Griffith showed the uptake and expression of foreign DNA in bacteria in 1928. This was perhaps the first example of the manipulation of genes that would later progress to genetic engineering. Although the presence of DNA in chromosomes and RNA in cytoplasm could be observed, DNA was not yet fully understood and it was still popular belief that proteins rather than DNA carried a cell’s genetic instructions. (3)
This was the case until 1944 when Canadian-born scientist Oswald Avery, with his co-workers and discovered that is the material of which and are made. Their experiment involved removing various organic compounds from a bacteria cell, if the remaining compounds were still able to cause another strain of bacteria to transform then the substances removed could not be the carrier of genes. Proteases were used to remove proteins, thought to carry genetic instruction, and the other bacteria strain was able to transform – showing that although the protein had been removed – genetic instructions were still present. Therefore, DNA was then removed using a enzyme and it was found the other strain of bacteria did not transform – proving that DNA was the carrier of genes in cells. (6) (7)
This work was further proved by and with the . Two T2 phages were used, one containing radioactive labelled protein, one containing radioactive labelled DNA, to infect bacteria. The bacteria and phage coat were then separated by blending and centrifugation and the radioactive DNA was found to be transferred to the bacteria, whereas the protein stayed in the phage coat. This showed that it is indeed DNA which is the genetic material of a phage, and not proteins. (8) (10i)
The recognised importance of DNA led to a race to understand its structure. British scientist Rosalind Franklin, working at King’s College, London, made great advances towards this goal using the technique of X-ray crystallography in which X-rays are passed through DNA crystals and are diffracted by the atoms in the molecule The diffraction pattern produced revealed that the components of the DNA molecule fitted together in a helical shape. Meanwhile in Cambridge, American Biologist James Watson, and British Physicist Francis Crick were attempting to build 3-dimentional models of the DNA. This, they were struggling to achieve until Franklin’s estranged senior colleagues showed them her diffraction photographs, without her knowledge and after previously refusing to show Watson. It was said, although, that the photograph was not marked confidential and had already been shown at a lecture which Watson had attended anyway. (6)
After this it was possible for a team of scientists to “crack” the genetic code using the language of bases, in order to decipher the codons which coded for specific amino acids. They proved the code to be degenerate and include start and stop codons. Scientists, by this time, had also shown that DNA undergoes semi-conservative replication by labelling strands of DNA using nitrogen isotopes. (10ii) It was also discovered that humans have 46 chromosomes. The workings of DNA were largely understood. (3)
This understanding led to the possibility of changing and manipulating DNA, with the discovery of restriction enzymes in bacterium that could be used to “cut and paste” DNA sequences. In 1983 Kary Mullis, an American Biochemist, developed the Polymerase Chain Reaction technique of amplifying small amounts of DNA; although the main principles of were described in 1971 by Kjell Kleppe, a Norwegian scientist. PCR is now used in many genetic techniques requiring the amplification of DNA, including genetic fingerprinting, paternity testing, sequencing, the detection of genetic diseases and the analysis of ancient DNA. Research progressed from the initial aim of understanding to the ways in which knowledge of genetics can be successfully exploited through the second half of the 20th century. This saw the introduction of gene therapy, genetically modified crops, cloning and use of stem cells. (9)
Also in the late 20th century the task became to sequence particular genes (for example the gene in which defects cause Cystic Fibrosis) and map the genomes of increasingly complex organisms. The Human Genome Project was completed in 2003.
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Book: Genes and DNA, Richard Walker
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Book: Life, Beck, Liem, Simpson, page 361(i), 375(ii)