DNA

Definition

DNA is a complex, long-chained molecule that contains the genetic blueprint for building and maintaining all living organisms. Found in nearly all cells, DNA carries the instructions needed to create proteins, specific molecules essential to the development and functioning of the body. It also transfers hereditary information between generations.

This vial contains some of the first DNA Friedrich Miescher isolated from salmon sperm. It is in the possession of the University of Turbingen, Germany. Credit: Alfons Renz.

Importance

DNA is central to biotechnology and medicine by virtue of the fact that it not only provides the basic blueprint for all life, it is a fundamental determinant of how the body functions and the disease process. Understanding the structure and function of DNA has helped revolutionise the investigation of disease pathways, assess an individual’s genetic susceptibility to specific diseases, diagnose genetic disorders, and formulate new drugs. It is also critical to the identification of pathogens.

Aside from its medical uses, the fact that DNA is unique to each individual makes it a vital forensic tool identifying criminals, the remains of a missing person, and determining the biological parent of a child. Within agriculture DNA is also used to help improve animal livestock and plants.

Discovery

The discovery of DNA stretches back to 1869, when Friedrich Miescher, a Swiss physician and biologist, began examining leucocytes, a type of white blood cell, he had sourced from pus collected on fresh surgical bandages. This he did while working in the laboratory of Felix Hoppe-Seyler in Tubingen, Germany as part of project to determine the chemical building blocks of cells. On looking through the microscope he observed that a substance separated from the solution of the cells whenever he added an acid and then dissolved again once alkali was added. The compound bore no resemblance to any known protein. Believing the substance to originate from the nuceli of the cell, Miescher nicknamed it 'nuclein'. On investigating further he discovered nuclein to be present in many other tissues. While possessing only simple tools and methods, by 1874 Miescher had come close to working out the genetic role of nuclein. He lacked sufficient communication skills, however, to convey the importance of what he had found to the wider scientific world.

In 1881 Albrecht Kossel, a German biochemist, renamed Miescher's compound deoxyribonucleic acid (DNA) based on the fact that he had discovered it to be a nucleic acid. Following this, he began working out its chemical composition. By 1901 he determined it to be made up of five nitrogen bases: adenine (A), cytosine (C), guanine (G), thymine (T) and uracil (U).

For many decades DNA remained little studied because it was assumed to be an inert substance incapable of carrying genetic material because of its simple structure. Proteins were instead thought to be the carriers of genetic material. In part this was because they had a more complex structure, being made up of 20 different amino acids.

It would not be until the mid 20th century that attitudes towards DNA began to change. This was prompted by the work of Oswald Avery at Rockefeller Institute in New York. From the early 1930s, Avery began to investigate how a type of non-infectious bacteria associated with pneumonia could transform into dangerous virulent forms if mixed with dead cells from the virulent strain and carried this trait into their offspring. The phenomenon had been first observed by Fred Griffith, a British physician, in 1928. By 1944 Avery had demonstrated with the help of his colleagues Colin MacLeod and Maclyn McCarty, that the transformation of the bacteria was linked to a stringy white substance – DNA. While not universally accepted at the time, Avery's finding helped kindle a new interest in DNA. It would take another few years before scientists finally accepted that it was DNA, not proteins, that carried DNA. It was finally agreed following experiments conducted by Alfred Hershey and Martha Hershey at Cold Spring Harbor in 1952.

By the 1950s a number of researchers had begun to investigate the structure of DNA in the hope that this would reveal how the molecule worked. Its structure was finally unveiled in 1953 through the combined efforts of the biophysicists Rosalind Franklin and Maurice Wilkins, based at King's College London, and Francis Crick and James Watson based in the Cavendish Laboratory, Cambridge University. Their work determined DNA to be a long linear molecule made up of two strands coiled around each other in a spiral configuration later known as the 'double helix'. Each strand was made up of four complementary nucleotides, chemical subunits: adenine (A), cytosine (C), guanine (G) and thymine (T). The two strands were oriented in opposite directions so that adenine always joined thymines (A T) and cytosines were linked with guanines (C G). Watson and Crick argued this structure helped each strand to reconstruct the other and facilitate the passing on of hereditary information.

Application

The analysis of DNA is pivotal to understanding both the biological mechanisms of life and diseases that arise when this process goes wrong. Many different applications have been developed to understand this process. Today scientists can analyse the molecule through a range of techniques, including DNA sequencing which helps work out its structure, through to PCR, which rapidly amplifies tiny quantities of DNA into billions of copies. Such techniques underpin all tests carried out today to for example identify a genetic mutation that causes cancer, or to determine whether a person carries a gene for a hereditary disease that can be passed on to their offspring. In addition, scientists have found ways to manipulate and construct new forms of DNA, known as recombinant DNA or gene cloning. Such technology is crucial to the mass production of many drugs, such as interferon, and the development of gene therapy.

DNA: timeline of key events

von Nageli identified string-like bodies in cell nucleus. He did not know they played role in heredity. 1842-01-01T00:00:00+0000Oscar Hertwig, Albrecht von Kolliker, Eduard Strasburger, and August Weismann independently show the cell's nucleus contains the basis for inheritance.1864-01-01T00:00:00+0000Freidrich Miescher, Swiss physician and biologist, performing experiments on the chemical composition of white blood cells (leucocytes) isolates phosphate-rich chemicals from the nuclei of cells. Originally calling this substance nuclein, Miescher's discovery paved the way for the identification of what we today call nucleic acids and the understanding of DNA as the carrier of inheritance. 1869-01-01T00:00:00+0000A Russian-American biochemist, Levene discovered nucleic acids came in two forms: DNA and RNA. He also idenfitied the components of DNA: adenine, guanine, thymine, cytosine, deoxyribose and a phosphate group and showed that these components were linked together by nucleotides, phosphate-sugar base units. 1869-02-25T00:00:00+0000Friedrich Miescher, Felix Hoppe-Seyler, and P. Plosz publish first papers describing nuclein (DNA)1871-01-01T00:00:00+00001872-01-01T00:00:00+0000Albrecht Kossel, German biochemist, shows that the substance called nuclein consists of a protein and non-protein component.1877-01-01T00:00:00+0000Avery was a Canadian-American physician who helped discover the genetic information in genes and chromosomes is made up of DNA.1877-10-21T00:00:00+0000Albrecht Kossel isolates and describes five organic compounds present in nucleic acids as being adenine, cytosine, guanine, thymine, and uracil. 1885-01-01T00:00:00+0000Richard Altmann, German pathologist, renames nuclein as nucleic acid.1889-01-01T00:00:00+0000A Swiss physician and biochemist. Miescher, was the first person to isolate nucleic acids which would subsequently be found to carry the genetic blueprint for life. 1895-08-26T00:00:00+0000William G Ruppel discovered the nucleotide while trying to isolate the bacterial toxin responsible for tuberculosis. 1898-01-01T00:00:00+0000Theodor Boveri, German biologist, and Walter Sutton, American geneticist and physician, independently develop the theory that chromosomes carry genetic material.1902-01-01T00:00:00+0000Wilhelm Johannsen, a Danish botanist and geneticist, introduces the terms phenotype to denote the observable traits of an organism, and genotype to denote the inherited instructions an organism carries within its cells. The terms are published in his paper Om arvelighed i samfund og i rene linie. This lays the foundation for the study of genetics. 1903-01-01T00:00:00+0000A Spanish biochemist, Ochoa helped outline the mechanisms involved in the synthesis of DNA and RNA. This was helped by his discovery of an enzyme in bacteria that allowed him to synthesize ribonucleic acid or RNA.1905-09-24T00:00:00+0000A biochemist, Ochoa shared the 1959 Nobel Prize for Medicine for 'discovery of the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid.'1905-09-24T00:00:00+0000A Scottish biochemist, Todd helped elucidate the structure and synthesis of many of the building blocks of DNA and RNA: nucleotides, nucleosides and their co-enzymes. He also synthesised two important biochemical compounds: adenosine triphosphate (ATP) and flavin adenine dinucleotide (FAD). 1907-10-02T00:00:00+0000Wilhelm Johannsen uses the word gene for the first time to describe units of heredity in his book Elemente der exakten Erblichkeitslehre. The book becomes the founding text of genetics. 1909-01-01T00:00:00+0000Phoebus Levene, a Russian-American biochemist, describes the building blocks of DNA, including four types of bases: adenine (A), cytosine (C), guanine (G), and thymine (T) .1910-01-01T00:00:00+0000Alfred Sturtevant, an American geneticist, experimenting with Drosophila flies, determines that genes are arranged on chromosomes in a linear fashion, like beads on a necklace. 1913-01-01T00:00:00+0000Speigelman developed the nucleic acid hybridization technique that enables specific DNA and RNA strands to be removed from cells and is the foundation of present day recombinant DNA technology. 1914-12-14T00:00:00+0000Crick shared the Nobel Prize for Medicine in 1962 for 'discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.'1916-06-08T00:00:00+0000Wilkins shared the 1962 Nobel Prize for Medicine for work in determining structure of DNA1916-12-15T00:00:00+0000Kornberg shared the 1959 Nobel Prize for Medicine for the discovery of the 'mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid.'1918-03-03T00:00:00+0000Parents Frederick and Cicely Sanger (nee Crewdson)1918-08-13T00:00:00+0000The first to determine the DNA sequence of insulin, Sanger proved proteins have a defined chemical composition. He was also pivotal to the development of the dideoxy chain-termination method for sequencing DNA molecules, known as the Sanger method. This provided a breakthrough in the sequencing of long stretches of DNA in terms of speed and accuracy and laid the foundation for the Human Genome Project. 1918-08-13T00:00:00+0000Franklin was a biophysicist who developed the first x-ray crystalography photograph establishing the double helix structure of DNA. Both Watson and Crick used her photograph to establish their model of DNA for which they won the Nobel Prize. 1920-07-25T00:00:00+0000T.B. Johnson, R.D. Coghill, 'The discovery of 5-methyl-cytosine in tuberculinic acid, the nucleic acid of the Tubercle bacillus', Journal of the American Chemical Society, 47/11 (1925, 2838–44. 1925-11-01T00:00:00+0000Berg helped pioneer recombinant DNA and set up the Asimolar Conference which established guidelines for experiments using the technology.1926-06-30T00:00:00+0000Frederick Griffith, British microbiologist, discovers that a harmless strain of Streptococcus pneumoniae can be made virulent after being exposed to heat-killed virulent strains. On the basis of this he hypothesises that some transforming principle from the heat-killed strain is responsible for making the harmless strain virulent. 1928-01-01T00:00:00+0000Watson shared the 1962 Nobel Prize for Nobel Prize for Medicine helping to determine the double-helix structure of DNA. 1928-04-06T00:00:00+0000Phoebus Levene identifies the building blocks of DNA, including the four bases adenine (A), cytosine (C), guanine (G), and thymine (T) .1929-01-01T00:00:00+0000Werner Arber shared the 1978 Nobel Prize in Medicine for the discovery of 'restriction enzymes and their application to problems in molecular genetics.'1929-06-03T00:00:00+00001932-01-01T00:00:00+0000Michael Smith shared the 1993 Nobel Prize for Chemistry for a technique that enables researchers to introduce specific mutations into genes and, thus, to the proteins that they encode.1932-04-26T00:00:00+0000Cohen helped pioneer recombinant DNA.1935-06-30T00:00:00+0000Studies a combination of chemistry, physics, maths and physiology and specialises in biochemistry in his final year.1936-01-01T00:00:00+0000Initially supervised by Bill Pirie, and then by Albert Neuberger, in the Department of Biochemistry. Thesis: 'On the metabolism of the amino acid lysine in the animal body'. 1940-01-01T00:00:00+0000A Russian-American biochemist, Levene discovered nucleic acids came in two forms: DNA and RNA. He also identified the components of DNA: adenine, guanine, thymine, cytosine, deoxyribose and a phosphate group and showed that these components were linked together by nucleotides, phosphate-sugar base units. 1940-09-06T00:00:00+0000Term first used by A. Jost, a Danish microbiologist, in lecture on sexual reproduction in yeast presented to the Technical Institute in Lwow, Poland 1941-01-01T00:00:00+0000A British molecular biologist, Roberts helped discover, with Philp A Sharp, introns, sections of DNA that do not carry genetic information. 1943-09-06T00:00:00+0000Sanger undertakes the research as part of team working with Albert Chibnall in Department of Biochemistry. His work is initially supported by a Beit Memorial Fellowship from 1944 and then by Medical Research Council from 1951. 1944-01-01T00:00:00+0000The physician-geneticists Oswald Avery, Canadian-born, Colin MacLeod, Canadian-born, and Maclyn McCarty, American-born, announce an experiment demonstrating that a harmless bacteria, Streptococcus pneumoniae, can be made virulent by using DNA isolated from a virulent strain. 1944-02-01T00:00:00+0000An American biochemist, Mullen was jointly awarded 1993 Nobel Prize in Chemistry for development of polymerase chain reaction (PCR) method to quickly make a huge number of copies of specific pieces of DNA.1944-12-28T00:00:00+0000Venter founded Celera Genomics and The Institute for Genomic Research and J Craig Institute which helped sequence the first human genome. It was mostly his genome that was sequenced. 1946-10-14T00:00:00+0000Roger Vendrely, Colette Vendrely and Andre Boivin, French scientists, report that the DNA content of cells is directly related to the chromosomes they contain. Importantly they discover half as much DNA in the nuclei of sex cells as they find in body cells. This provides further evidence for the fact that DNA is genetic material. 1949-01-01T00:00:00+0000Erwin Chargaff, Austro-Hungarian-born American biochemist, shows that the DNA base composition varies between species and that within a species the four DNA bases are always present in fixed ratios: the same number of A’s as T’s and the same number of C’s as G’s. This boosts the belief that DNA is genetic material and provides the foundation for the discovery of the double helix structure. 1949-01-01T00:00:00+0000The American scientists Linus Pauling, Harvey Itano, Seymour Singer and Ibert Wells published an article in Science showing sickle cell anaemia to be a molecular disease caused by a mutation. Sickle cell anaemia was the first disease to be understood at a molecular level. 1949-09-01T00:00:00+0000Maurice Wilkins, New Zealand-born English physicist and molecular biologist, using X-ray analyses indicate DNA has a regularly repeating helical structure. This information together with research then being conducted by Rosalind Franklin inspires James Watson and Francis Crick to start building a molecular model of DNA.1951-11-01T00:00:00+0000Alfred Hershey and Martha Chase, American geneticists, demonstrate that when bacteriophages, which are composed of DNA and protein, infect bacteria, their DNA enters the host bacterial cell, but most of their protein does not. This confirms that DNA is the genetic material, refuting a long-held assumption that proteins carried the information for inheritance.1952-01-01T00:00:00+0000Noted by Salvador Luria and his graduate student Mary Human while conducting experiments into the break-up of DNA in phage-infected bateria.1952-01-01T00:00:00+0000Known as Photo 51, this image was shown, without Franklin's permission, to James Watson, who, together with Francis Crick, used it to develop the double-helix model of DNA.1952-01-03T00:00:00+0000The molecular biologists James Watson, American-born, and Francis Crick, British born, publish in Nature the molecular structure model of DNA: a double helix in which A always pairs with T, and C always with G. This model is inspired by Photo 51 taken by Franklin. Calculations from the photograph provided crucial parameters for the size of the helix and its structure, all of which were critical for the Watson and Crick's molecular modelling work. The final model represents a correction of an earlier model in the light of comments by Franklin the hydrophilic backbones should not go at the centre of the molecule, as Watson and Crick had originally assumed, but go on the outside of the molecule where they could interact with water. 1953-04-01T00:00:00+0000Rosalind Franklin publishes Photo 51 in a joint paper with Raymond Gosling in Nature.1953-04-01T00:00:00+0000Sanger's insulin results establish for the first time that proteins are chemical entities with a defined sequence. The technique Sanger develops for sequencing insulin later becomes known as the degradation or DNP method. It provides the basis for his later development of sequencing tecdhniques for nucleic acids, including RNA and DNA.1955-01-01T00:00:00+0000Avery was a Canadian-American physician who helped discover the genetic information in genes and chromosomes is made up of DNA.1955-02-02T00:00:00+0000The enzyme was discovered in Escherichia Coli. Its isolation paved the way to understanding how DNA is replicated, repaired and transcribed and the development of recombinant DNA. A collective group of scientists made the discovery: Arthur Kornberg, Maurice Bessman, Ernie Simms, I R Lehman.1955-12-01T00:00:00+0000Arthur Kornberg, American biochemist, discovers DNA polymerase, an enzyme that replicates DNA 1956-01-01T00:00:00+0000Ingram shows that the difference between sickle-cell and normal haemoglobulin lies in just one amino acid. 1957-01-01T00:00:00+0000The observation was made by Lazarus Astrachan and Elliot Voilin in an experiment to understand ho hereditary information encoded in DNA is used by living cells to synthesise proteins.1957-01-01T00:00:00+0000Crick presented his theory to the Society for Experimental Biology. He proposed that RNA acted as an intermediary between DNA and proteins, helping to translate information in the DNA into proteins and that three bases in the DNA always specify one amino acid in a protein. 1957-09-19T00:00:00+0000Achieved by Arthur Kornberg, the experiment was published in the Journal of Biological Chemsitry in May 1958.1957-10-01T00:00:00+0000The American molecular biologists Matthew Meselson and Franklin Stahl describe how DNA replicates, arguing that each strand of the DNA serves as a template for the replicated strand. 1958-01-01T00:00:00+0000Prize awarded to Sanger 'for his work on the structure of proteins, especially that of insulin'.1958-01-01T00:00:00+0000Franklin was a British biophysicist who developed the first x-ray crystalography photograph establishing the double helix structure of DNA. Both Watson and Crick used her photograph to establish their model of DNA for which they won the Nobel Prize. 1958-04-16T00:00:00+0000Non-profit institution founded by Robert S Ledley to explore the use of computers in biomedical research. It is eventually located at Georgetown University Medical Center in Washington, D.C.1960-01-01T00:00:00+00001960-01-01T00:00:00+0000Work by Har Gobind Khorana, Indian-born American biochemist on RNA and Robert Holley, American biochemist, on transfer RNA, helps piece together the genetic code. 1961-01-01T00:00:00+0000Experiment conducted by Sydney Brenner, Francois Jacob and Matt Meselson1961-03-31T00:00:00+0000Marshall Nirenberg, American biochemist, and Heinrich Matthaei, German biochemist, discover the coding mechanism for DNA.1961-05-01T00:00:00+0000Werner Arber, Swiss microbiologist and geneticist, and his doctoral student Daisy Dussoix propose bacteria produce restriction and modification enzymes to counter invading viruses. 1962-01-01T00:00:00+0000Sanger now has close contact with protein crystallographers, molecular geneticists and protein chemists1962-01-01T00:00:00+00001962-10-18T00:00:00+0000Robert Holley and colleagues sequence Escherichia coli alanine transfer RNA, laying the foundation for DNA sequencing. 1965-01-01T00:00:00+0000W. Arber, 'Host-controlled modification of bacteriophage', Annual Review Microbiology 19 (1965), 365-78.1965-01-01T00:00:00+0000Book contains all protein sequences known to-date. It is the result of a collective effort to co-ordinate the ever-growing amount of information about protein sequences and their biochemical function. 1965-01-01T00:00:00+0000900 page monograph provides the first introduction to the application of digital computing in biology and medicine. 1965-01-01T00:00:00+0000Tested on ribosomal RNA1965-01-01T00:00:00+0000The sequencer was developed by Pehr Victor Edman with Geoffrey Begg1967-01-01T00:00:00+0000Discovery lays foundation for recombinant DNA and DNA sequencing.1968-01-01T00:00:00+0000Ray Wu and A.D. Kaiser report on the partial sequence of bacteriophage lambda DNA in the Journal of Molecular Biology, 35/3 (1968), 523-37. 1968-01-01T00:00:00+00001968-01-01T00:00:00+0000Kjell Kleppe, a Norwegian scientist working in H. Gobind Khorana's Institute for Enzyme Research at University of Wisconsin publishes papers describing the principles of PCR.1969-01-01T00:00:00+0000Called Thermus aquaticus (Taq) this enzyme becomes a standard source of enzymes because it can withstand higher temperatures than those from E Coli. Taq is later important in the PCR technique. 1969-01-01T00:00:00+0000This was developed by Peter Lobhan, a graduate student of Dale Kaiser at Stanford University.1969-01-01T00:00:00+0000W. Arber, S.Linn, 'DNA modification and restriction', Annual Review Biochemistry, 38 (1969), 467-500.1969-07-01T00:00:00+0000Achived by Har Gobind Khorana at the University of Wisconsin-Madison1970-01-01T00:00:00+0000Hamilton O Smith, Kent W Wilcox, Journal of Molecular Biology 51/2 (1970), 379-91. 1970-07-01T00:00:00+0000K. Kleppe, E Ohtsuka, R Kleppe, I Molineux, HG Khorana, "Studies on polynucleotides *1, *2XCVI. Repair replication of short synthetic DNA's as catalyzed by DNA polymerases", Journal of Molecular Biology, 56/2 (1971), 341-61. The method provides an artificial system of primers and templates that allows DNA polymerase to copy segments of the gene being synthesised. 1971-01-01T00:00:00+0000This was done in Dale Kaiser's laboratory by Douglas Berg together with Janet Mertz and David Jackson1971-01-01T00:00:00+0000The 12 base sequence of bacteriophage lambda DNA is published by Ray Wu and Ellen Taylor in the Journal of Molecular Biology, 57 (1971) 0, 491-511. 1971-05-01T00:00:00+0000Robert Pollack contacted Paul Berg to raise concerns about the potential biohazards of experiments his doctoral research plans to do involving the introduction of genes from the oncovirus SV40 in the human gut bacteria, E-Coli. Following this Berg self-imposed a moratorium on experiments in his laboratory involving the cloning of SV40 in E-Coli. 1971-06-01T00:00:00+0000Kathleen Danna and Daniel Nathans, PNAS, 68/12 (1971), 2913-17.1971-12-01T00:00:00+0000This took place during an unscheduled extra session held at a three-day EMBO workshop on DNA restriction and modification. The session was chaired by Norton Zinder.1972-09-26T00:00:00+0000D A Jackson, R H Symons, P Berg, 'Biochemical Method for Inserting New Genetic Information into DNA of Simian Virus 40: Circular SV40 DNA Molecules Containing Lambda Phage Genes and the Galactose Operon of Escherichia coli', PNAS USA, 69/10 (1972), 2904-09.1972-10-01T00:00:00+0000Janet Mertz and Ronald Davis publish an easy-to-use technique for constructing recombinant DNA. 1972-11-01T00:00:00+0000This was prompted by the publication of the recombinant DNA experpiments published by Berg, Jackson and Symons1972-11-01T00:00:00+0000Stanley Cohen and Herbert Boyer publish genetic engineering techniques to cut and paste DNA (using restriction enzymes and ligases) and reproduce the new DNA in bacteria1973-01-01T00:00:00+0000This is achieved by Walter Gilbert and Allan Maxam at Harvard University using a method known as wandering-spot analysis.1973-01-01T00:00:00+0000The National Institutes of Health forms a Recombinant DNA Advisory Committee to oversee recombinant genetic research.1974-01-01T00:00:00+0000Berg, P, Baltimore, D, Boyer, J W, Cohen, S N, et al, 'Biohazards of Recombinant DNA,' Science, 185 (1974): 3034.1974-07-05T00:00:00+0000Asilomar Conference in California declares moratorium on genetic engineering research in order to have time to estimate the biohazard risks of recombinant DNA research and develop guidelines.1975-01-01T00:00:00+0000The method enables 80 nucleotides to be sequenced in one go. Represents radical new approach which allows direct visual scanning of a sequence. 1975-01-01T00:00:00+0000A.D. Riggs, 'X inactivation, differentiation, and DNA methylation', Cytogenet Cell Genet, 14 (1975), 9–25; R. Sager, R. Kitchin, 'Selective silencing of eukaryotic DNA', Science, 189/4201 (1975), 426-33. 1975-01-01T00:00:00+0000R. Holliday, J.E. Pugh, 'DNA modification mechanisms and gene activity during development', Science, 187 (1975), 226–32.1975-01-01T00:00:00+0000Yeast genes expressed in E. coli bacteria for the first time1976-01-01T00:00:00+0000Robert Swanson, venture capitalist and Herbert Boyer, American biochemist, establish Genentech in San Francisco. It is the first biotechnology company established specifically dedicated to commercialising recombinant DNA. Its founding marks the start of what is to become a burgeoning biotechnology industry. 1976-04-01T00:00:00+0000Genetically engineered bacteria are used to synthesize human growth protein.1977-01-01T00:00:00+0000This is found to contain 5,385 nucleotides. It is the first DNA based organism to have its complete genome sequenced. Sanger and his team use the plus and minus technique to determine the sequence. 1977-01-01T00:00:00+0000Duncan McCallum, a business computer programmer in Cambridge writes the first computer programme for DNA sequencing. This is used by Sanger's sequencing group at the MRC Laboratory of Molecular Biology. 1977-01-01T00:00:00+0000Two separate teams, one led by Fred Sanger at the MRC Laboratory of Molecular Biology, Cambridge, UK, and one composed of Allan Maxam, and Walter Gilbert at Harvard University publish two different methods for sequencing DNA. The first, known as the Sanger Method, or dideoxy sequencing, involves the breaking down and then building up of DNA sequences. The second, the Maxam-Gilbert method, involves the partial chemical modification of nucleotides in DNA. 1977-02-01T00:00:00+0000Genentech scientists succeed in genetically engineering human insulin in E-Coli.1978-01-01T00:00:00+0000Awarded to Werner Arber, Daniel Nathans and Hamilton O Smith.1978-10-01T00:00:00+0000US Supreme Court, in the landmark case Diamond v. Chakrabarty, approves the principle of patenting genetically engineered life forms1980-01-01T00:00:00+0000The American scientists Stanley Cohen and Herbet Boyer are awarded the first US patent for gene cloning.1980-01-01T00:00:00+0000Milstein suggests at a Wellcome Foundation lecture that by using genetic engineering scientists might be able to design tailor-made monoclonal antibodies that mimic antibodies made by the human body. This would free them up from a dependence on rodents for producing monoclonal antibodies. He publishes the idea in C. Milstein, 'Monoclonal antibodies from hybrid myelomas: Wellcome Foundation Lecture 1980', Proceedings Royal Society of London, 211 (1981), 393-412.1980-01-01T00:00:00+0000Prize shared with Walter Gilbert. Awarded on the basis of their 'contributions concerning the determination of base sequences in nucleic acids.' 1980-01-01T00:00:00+0000The aim is to establish a centralised sequence computerised database tha is available free of charge. 1980-01-01T00:00:00+0000Gordon, J W, Scangos, G A, Plotkin, D J, Barbosa, J A, Ruddle, F H, 'Genetic transformation of mouse embryos by microinjection of purified DNA', PNAS USA 77 (1980), 7380–4.1980-09-01T00:00:00+0000The database was developed by Margaret Dayhoff, an American physical chemist, for storing nucleic acid sequences. It was a sophisticated on-line computer database that was accessible by telephone to outside users.1980-09-01T00:00:00+0000Database was started by Margaret Dayhoff at the NBRF in the mid 1960s and comprised over 200,000 residues. Within a month of its operation more than 100 scientists had requested access to the database. The database was funded with contributions from m Genex, Merck, Eli Lilly, DuPont, Hoffman–La Roche, and Upjohn, and computer time donated by Pfizer Medical Systems.1980-09-01T00:00:00+0000First genetically-engineered plant is reported1981-01-01T00:00:00+0000First mice genetically cloned1981-01-01T00:00:00+0000S.J. Compere, R.D. Palmiter, 'DNA methylation controls the inducibility of the mouse metallothionein-I gene lymphoid cells', Cell, 25 (1981), 233–240. 1981-07-01T00:00:00+0000In this method genomic DNA is randomly fragmented and cloned to produce a random library in E Coli. The clones are then sequenced at random and the results assembled by computer which compares all of the sequence reads and aligns the matching sequences to produce the complete genome sequence. 1982-01-01T00:00:00+00001982-01-01T00:00:00+0000Funding secured for the setting up of GenBank, to be located at Los Alamos National Laboratory. It was to serve as a repository for newly determined sequences, as a tool for sequencers assembling genomes and for bioinformatic researchers. 1982-06-01T00:00:00+0000The first drug (human insulin), based on recombinant DNA, is marketed. 1982-10-01T00:00:00+00001983-01-01T00:00:00+0000A.P. Feinberg, B. Vogelstein, 'Hypomethylation distinguishes genes of some human cancers from their normal counterparts', Nature, 301/5895 (1983), 89-92.1983-01-06T00:00:00+0000Speigelman developed the nucleic acid hybridization technique that enables specific DNA and RNA strands to be removed from cells and is the foundation of present day recombinant DNA technology. 1983-01-20T00:00:00+0000Kary Mullis, an American biochemist based at Cetus, proposed an alternative method to Sanger's DNA sequencing method to analyse Sickle cell Anaemia mutation which laid the foundation for the development of the PCR technique. 1983-05-01T00:00:00+0000Mullis reports on his production of olgionucleotides and some results from his experiments with PCR to Cetus Corporation's annual meeting but few show any interest. 1984-06-01T00:00:00+0000Two teams of scientists publish methods for the generation of chimeric monoclonal antibodies, that is antibodies possessing genes that are half-human and half mouse. Each team had developed their techniques separate from each other. The first team was lead by Michael Neuberger together with Terence Rabbitts and other colleagues at the Laboratory of Molecular Biology, Cambridge. The second team consisted of Sherie Morrison and colleagues at Stanford University together with Gabrielle Boulianne and others at the University of Toronto. 1984-12-01T00:00:00+0000A. Bird, M. Taggart, M. Frommer, O.J. Miller, D. Macleod, ‘A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA’, Cell, 40/1 (1985 Jan;40(1):91-9. 1985-01-01T00:00:00+0000The application establishes polymerase chain reaction (PCR) as a method for amplifying DNA in vitro. PCR uses heat and enzymes to make unlimited copies of genes and gene fragments. The application is broad and is based on analysis of Sickle Cell Anaemia mutation via PCR and Oligomer restriction. 1985-03-01T00:00:00+0000Alec Jeffreys published hypervariable minisatellite regions in human DNA, which paved the way to DNA fingerprinting.1985-03-07T00:00:00+0000The technique enabled the amplification of small fragments of DNA on a large scale. It was published in RK Saiki et al, Enzymatic Amplification of beta-globin Genomic Sequences and Restriction Site Analysis for Diagnosis of Sickle Cell Anemia, Science, 230 (1985), 1350-54.1985-12-20T00:00:00+0000Leroy Hood and colleagues at the California Institute of Technology together with a team including Lloyd Smith and Michael and Tim Hunkapiller, develop the first automated DNA sequencing machine. The machine is commercialised by Applied Biosystems. 1986-01-01T00:00:00+0000 First meeting on genome mapping and sequencing takes place at Cold Spring Harbor.1986-04-30T00:00:00+0000Greg Winter together with other colleagues from the Laboratory Molecular Biology demonstrate the feasibility of building a new more human-like monoclonal antibody by grafting on to the humab antibody portions of a variable region from a mouse antibody. This reduced the mouse component of the monoclonal antibody to just 5%, making the monoclonal antibody safer and more effective for use in humans. The technique was published in PT Jones, PH Dear, J Foote, MS Neuberger, G Winter, 'Replacing the complementarity-determining regions in a mouse antibody with those from a mouse', Nature, 321 (29 May 1986), 522-5.1986-05-01T00:00:00+0000Hoffmann-LaRoche and Schering-Plough gain FDA permission to market genetically engineered alpha interferon for use as treatment hairy cell leukaemia. The development of interferon rested on the application of both genetic cloning and monoclonal antibodies. 1986-06-04T00:00:00+0000FDA grants a BLA to Merck & Co. for Recombivax HB, the first recombinant vaccine for hepatitis B. It is seen as a breakthrough because it carries no risk of infecting healthy people,1986-07-23T00:00:00+0000Campath-1G is humanised, resulting in Campath-1H. It is accomplished with technology developed by Greg Winter.1988-01-01T00:00:00+0000Funding secured for precursor of the Human Genome Project. US$10.7 million provided by Department of Energery and US$17.2 million by National Institutes of Health.1988-01-01T00:00:00+0000This method, called FASTA, is published by William R Pearson and David J Lipman in Proc Natl Acad Sci USA, 85/8 (April 1988), 2444-8. This is now a common tool for bioinformatics. It allos for the comparison and aligning of sequences. 1988-04-01T00:00:00+0000T. Bestor, A. Laudano, R. Mattaliano, V. Ingram, 'Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells', Journal Molecular Biology, 203 (1988), 971–83. 1988-10-20T00:00:00+0000V. Greger, E. Passarge, W. Hopping, E. Messmer, B. Horsthemke, 'Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma', Human Genetics, 83 (1989), 155–58. 1989-09-01T00:00:00+0000Joint working group of the US Department of Energy and the National Institututes of Health present plan Understanding Our Genetic Inheritance: The US Human Genome Project.1990-02-01T00:00:00+0000International scientific collaboration, initiated by the US Department of Energy, begun to determine the sequence of chemical base pairs which make up DNA, and to identify and map approximately 20,000 to 25,000 genes of the human genome. 1990-10-01T00:00:00+00001992-01-01T00:00:00+0000M. Frommer, L.E. McDonald, D.S. Millar, C.M. Collis, F. Watt, G.W. Grigg, P.L. Molloy, C.L. Paul, 'A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands', PNAS, 89/5 (1992), 1827-31.1992-03-01T00:00:00+0000W.F. Zapisek, G.M. Cronin, B.D. Lyn-Cook, L.A. Poirier, 'The onset of oncogene hypomethylation in the livers of rats fed methyl-deficient, amino acid-defined diets', Carcinogenesis, 13/10 (1992), 1869-72.1992-10-01T00:00:00+0000A Spanish biochemist, Ochoa helped outline the mechanisms involved in the synthesis of DNA and RNA. This was helped by his discovery of an enzyme in bacteria that allowed him to synthesize ribonucleic acid or RNA.1993-11-01T00:00:00+0000The drug, a genetically engineered enzyme, was developed by the Genentech researcher Steven Shak. It was the first new treatment for cystic fibrosis in 30 years. The enzyme was engineered to dissolve mucus plugs in the lungs of cystic fibrosis patients.1993-12-30T00:00:00+0000Abciximab (ReoPro) approved by the FDA and European regulatory authorities to prevent blot clots during coronary artery procedures like angioplasty. The monoclonal antibody was originally developed by Barry Coller at State University of New York and commercially developed by Centocor. The drug showed for the first time that monoclonal antibodies could be used for the treatment of acute disease conditions. 1994-12-01T00:00:00+0000P.W. Laird, L. Jackson-Grusby, A. Fazeli, S. L. Dickinson, W. E. Jung, E. Li, R.A. Weinberg, R. Jaenisch, 'Suppression of intestinal neoplasia by DNA hypomethylation', Cell, 81 (1995),197-205, April 21, 1995,1995-04-21T00:00:00+00001995-07-28T00:00:00+00001996-01-01T00:00:00+0000Mostafa Ronaghi and Pal Nyren at the Royal Institute of Technology in Stockholm develop pyrosequencing which allows for shotgun sequencing without cloning in E coli or any host cell. The marchinery and reagents involved in the method was first commercialised by Pyrosequencing AB.1996-01-01T00:00:00+0000Lord Todd won the 1957 Nobel Prize for Chemistry 'for work on nucleotides and nucleotide co-enzymes.'1997-01-10T00:00:00+0000Daclizumab was approved by the FDA for the preventition of acute rejection of kidney transplants. The monoclonal antibody was developed by Protein Design Labs using a humanising method devised by Cary Queen and marketed together with F. Hoffmann-La Roche. 1997-12-01T00:00:00+0000Celera Corporation launches a parallel effort to sequence the human genome to the Human Genome Project. Celera's entry into the field pose policy concerns about open access to gene sequencing data and accelerates the sequencing process in the Human Genome Project. 1998-05-01T00:00:00+0000The full 97 Mbp genome of Caenorhabditis elegans is found to have more than 19,000 genes.1998-12-11T00:00:00+0000Sequence of the first human chromosome (22) is published. 1999-01-01T00:00:00+0000M. Toyota, N. Ahuja, M. Ohe-Toyota, J.G. Herman, S.B. Baylin, J-P.J. Issa, 'CpG island methylator phenotype in colorectal cancer', PNAS, 96/15 (1999), 8681–86.1999-07-20T00:00:00+0000Nathans was an American molecular biologist who co-discovered restriction enzymes and their applications to break DNA molecules. 1999-11-16T00:00:00+00002000-01-01T00:00:00+0000U.S. President Bill Clinton and the British Prime Minister Tony Blair announced the completion of a rough draft of the human genome. 2000-06-26T00:00:00+0000A Canadian biochemist, Michael Smith helped develop site-direct mutagenesis, a technique that allows for a mutation to be created at a specific defined site in a DNA molecule. This technique is pivotal to genetic and protein research and engineering. 2000-10-04T00:00:00+0000Map published for the genome of the flowering plant Arabidopsis thaliana. The sequenced genome contains 25,498 genes encoding proteins from 11,000 families.2000-12-14T00:00:00+0000A consortium including scientists from Celera Genomics and 13 other organizations publishes the first consensus sequence of human genome. It is shown to have a 2.91 billioon base pair sequence. 2001-02-16T00:00:00+00002002-01-01T00:00:00+0000Researchers at the State University of New York report the creation of a full-genome complementary DNA from published sequences of poliovirus, and its reverse transcription into viral RNA2002-07-11T00:00:00+0000Genomic sequence completed for Plasmodium falciparum, the malaria parasite, which carries some 5,300 genes (Celera Genomics) and for malaria Anopheles gambiae, mosquito's principal vector (TIGR and Sanger Centre). 2002-10-03T00:00:00+0000The Human Genome Project was completed, two years ahead of schedule and at a cost of US$2.7 billion. Most of the government-sponsored sequencing was performed in universities and research centres from the United States, the United Kingdom, Japan, France, Germany. 2003-04-14T00:00:00+00002004-01-01T00:00:00+0000Crick shared the Nobel Prize for Medicine in 1962 for 'discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.'2004-07-28T00:00:00+0000A New Zealand biophysicist, Wikins helped develop x-ray diffraction techniques to determine the structure of DNA. 2004-10-05T00:00:00+0000US FDA approved Roche AmpliChip Cytochrome P450 Genotyping Test. The first DNA microarray system approved for clinical applications, AmpliChip is designed to match patients with their most effective drug and determine appropriate drug doses. 2004-12-23T00:00:00+0000Study conducted by team led by Shelley Berger published in Molecular Cell.2005-02-17T00:00:00+0000Drug made by MGI Pharma. approved for treatment of myelodysplastic syndromes, bone marrow disorders2006-01-01T00:00:00+0000 Germ-line cell experiments remain off-limit. Sequence of the last chromosome in the Human Genome Project is published in Nature.2006-05-01T00:00:00+0000Kornberg shared the 1959 Nobel Prize for Medicine for the discovery of the 'mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid.'2007-10-26T00:00:00+0000Achieved by Emmanuel Skordalakes2008-01-01T00:00:00+00002011-01-01T00:00:00+0000Sharon Peacock and Julian Parkhill together with other researchers from the University of Cambridge and the Wellcome Trust Sanger Institute used whole genome sequencing to trace the spread of an outbreak of meticillin resistant Staphylococcus aureus (MRSA) in Rosie Hospital's special care baby unit. Prospective sequencing then led them to screen staff and identify the potential source of infection. The researchers reported that the cost of DNA sequencing for the infection was half of the 10,000 pounds spent by the hospital to combat the outbreak of MRSA.2012-06-01T00:00:00+0000Undertaken at the University of California's Rady Children's Hospital in San Diego, the study involves the sequencing of all the genes of individuals in 118 families with a neurodevelopment problem. 2012-12-01T00:00:00+00002013-11-19T00:00:00+0000Twelve patients with HIV treated between 2009 and 2014 report benefits from genetically engineered virus with a rare mutatiuon known to protect against HIV (CCR5 deficiency).2014-03-01T00:00:00+0000Awarded to the Swedish scientist, Tomas Lindahl, American scientist, Paul Modrich and Turkish-American scientist, Aziz Sancar.2015-10-07T00:00:00+0000
Date Event People Places
1842First observation of chromosomes by Swiss botanist Karl von NageliNageli
1864 - 1865Nucleus shown to contain genetic substanceHertwig, von Kolliker, Strasburger, Weismann University of Munich, University of Wurzburg, University of Freiburg
1869Discovery of DNAMiescher University of Tubingen
25 Feb 1869Phoebus Levene was bornLevene 
1871Papers describe DNA for first timeMiescher, Hoppe-Seyler, PloszUniversity of Tubingen
1872Walther Flemming, German biologist, describes chromosomes and examines their behaviour during cell division. FlemmingUniversity of Kiel
1877 - 1880Nucleic acid shown to have protein and non-protein componentsKosselUniversity of Tubingen
21 Oct 1877 Oswald Theodore Avery was born in Halifax, CanadaAveryRockefeller University
1885 - 1901Nucleic acids structure determinedKosselInstitute of Physiology, University of Berlin, University of Marburg
1889Richard Altmann, German pathologist, renames nuclein as nucleic acidAltmannLeipzig University
26 Aug 1895Johann Friedrich Miescher diedMiescher 
1898A nucelotide called tuberculinic acid found to bind to the protein tuberculin. It is now regarded as the precursor to the discovery of DNA methylationRuppelPhilipps University of Marburg
1902Chromosomes linked with inheritanceBoveri, GarrodZoological-Zootomical Institute, Columbia University
1903The notion genetics is introducedJohannsenRoyal Veterinary University
24 Sep 1905Severo Ochoa was born in Luarca, SpainOchoaNew York University
24 Sep 1905Severo Ochoa was born in Luarca, SpainOchoaNew York University
2 Oct 1907Alexander R Todd was born in Glasgow, ScotlandToddUniversity of Manchester
1909The term gene is first usedJohannsenUniversity of Copenhagen
1910First description of the building blocks of DNALeveneRockefeller University
1913First mapping of a chromosomeSturtevantColumbia University
14 Dec 1914Solomon Spiegelman was born in Brooklyn, NY, USASpiegelmanUniversity of Minnesota
8 Jun 1916Francis H C Crick was born in Northampton, United KingdomCrickLaboratory of Molecular Biology
15 Dec 1916Maurice H F Wilkins was born in Pongaroa, New ZealandWilkinsKing's College London
3 Mar 1918Arthur Kornberg was born in Brooklyn NY, USAKornbergStanford University
13 Aug 1918Frederick Sanger, twice Nobel Prize winner, born in Rendcombe, United KingdomSangerRendcomb, Gloucestershire
13 Aug 1918Frederick Sanger, twice Nobel Prize winner, bornSangerRendcomb, Gloucestershire, United Kingdom
25 Jul 1920Rosalind E Franklin was born in London, United KingdomFranklinKings College London
November 1925T.B. Johnson and R.D. Coghill reported detecting a minor amount of methylated cytosine derivative as byproduct of hyrdrolysis of tuberculinic acid with sulfuric acid but other scientists struggled to replicate their results. Johnson, CoghillYale University
30 Jun 1926Paul Berg was born in New York NY, USABergStanford University
1928Bacteria shown capable of transformationGriffithPathological Laboratory of the Ministry of Health
6 Apr 1928James D Watson was born in Chicago IL, USAWatsonLaboratory of Molecular Biology
1929DNA nucleobases identifiedLeveneRockefeller University
3 Jun 1929Werner Arber was born in Granichen, SwitzerlandArberUniversity of Geneva
1932Sanger attends Bryanston School, Dorset, as boarderSanger 
26 Apr 1932Michael Smith was born in Blackpool, United KingdomSmithUniversity of British Columbia
30 Jun 1935Stanley Norman Cohen was born in Perth Amboy, NJ, USACohenStanford University
1936 - 1940Sanger takes degree in Natural Sciences at Cambridge UniversitySangerCambridge University
1940 - 1943Sanger studies for a doctorate at Cambridge UniversitySangerCambridge University
6 Sep 1940Phoebus Levene diedLevene 
1941Term 'genetic engineering' first coinedJost 
6 Sep 1943Richard J Roberts was bornRoberts 
1944Sanger starts working on amino acid composition of insulinSangerCambridge University
1 Feb 1944DNA identified as a heritary agentAveryRockefeller University
December 1944Kary Banks Mullis was bornCetus Corporation
14 Oct 1946J Craig Venter was born in Salt Lake City, UtahSalt Lake City, Utah
1949DNA content of a cells linked to a cell's number of chromosomesVendrely, BoivinPasteur Institute, Strasbourg School of Medicine
1949 - 1950DNA four base ratio shown to be always consistentCargraffColumbia University
September 1949Sickle cell shown to be caused by genetic mutationPaulingCalifornia Institute of Technology
November 1951Purified DNA and DNA in cells shown to have helical structureWilkinsKings College London
1952Bacteriophage experiments show DNA and not proteins to be genetic materialHershey, ChaseCarnegie Institution for Science
1952First observation of the modification of viruses by bacteriaLuria, HumanUniversity of Illinois
January 1952X-ray diffraction image, produced by Rosalind Franklin, shows DNA to have regularly repeating helical structureFranklinKings College London
April 1953DNA double-helix structure announcedCrick, WatsonCavendish Laboratory
April 1953Franklin's x-ray image of DNA publishedFranklinKings College London
1955Sanger completes the full sequence of amino acids in insulinSangerCambridge University
2 Feb 1955Oswald Theodore Avery diedAveryRockefeller University
December 1955First discovery of the enzyme DNA polymeraseKornberg, Bessman, Simms, LehmanWashington University in St. Louis
1956DNA polymerase discovered to replicate DNAKornberg Washington University in St. Louis
1957Victor Ingram breaks the genetic code behind sickle-cell anaemia using Sanger's sequencing techniqueIngram, SangerCambridge University
1957First observation of messenger RNAAstrachan, VolkinOak Ridge National Laboratory
19 Sep 1957Francis Crick presented what is now known as the 'central dogma' in molecular biology which argues that the main function of genetic material is to control the synthesis of proteinsCrickCavendish Laboratory
October 1957First synthesis of DNA in a test tubeKornbergWashington University in St. Louis
1958DNA replication explainedMeselson, StahlCalifornia Institute of Technology
1958Sanger awarded his first Nobel Prize in ChemistrySangerCambridge University
16 Apr 1958Rosalind E Franklin diedFranklinKings College London
1960National Biomedical Research Foundation establishedLedleyGeorgetown University
1960Sanger begins to devise ways to sequence nucleic acids, starting with RNASangerCambridge University
1961 - 1966Genetic code cracked for the first timeKhorana, HolleyUniversity of Wisconsin, Cornell University
31 Mar 1961Experiments reveal a type of RNA (messenger RNA) transports genetic information from the nucleus to the protein-making machinery in a cellBrenner, Crick, Jacob 
May 1961Coding mechanism for DNA discoveredNirenberg, MatthaeiNational Institute for Health
1962Concept of restriction and modification enzymes bornArber, DussoixUniversity of Geneva
1962Sanger moves to the newly created Laboratory of Molecular Biology in CambridgeSangerLaboratory of Molecular Biololgy
18 Oct 1962Watson, Crick and Wilkins won the Nobel Prize for Medicine for their work in determining the structure of DNAWatson, Crick, WilkinsLaboratory of Molecular Biology
1965Transfer RNA is the first nucleic acid molecule to be sequencedHolleyCornell University
1965Werner Arber predicts restriction enzymes could be used as a labortory tool to cleave DNAArberUniversity of Geneva
1965Atlas of Protein Sequence and Structure publishedDayhoffNational Biomedical Research Foundation
1965Ledley publishes Uses of Computers in Biology and MedicineLedleyNational Biomedical Research Foundation
1965Sanger and colleagues publish two-dimension partition sequencing methodSanger, Brownlee, BarrellLaboratory of Molecular Biology
1967First automatic protein sequencer developedEdman, BeggSt Vincent's School of Medical Research
1968 - 1970Restriction enzymes found to act as chemical knives to cut DNASmith, NathansUniversity of Geneva, University of California in Berkeley, Johns Hopkins University
1968The first partial sequence of a viral DNA is reportedWu, KaiserCornell University, Stanford University Medical School
1968Paul Berg started experiments to generate recombinant DNA moleculesBergStanford University
1969First principles for PCR publishedKhorana, KleppeUniversity of Wisconsin-Madison
1969New species of bacterium is isolated from hot spring in Yellowstone National Park by Thomas BrockBrockCase Western Reserve University
1969New idea for generating recombinant DNA conceivedLobhanStanford University
July 1969Discovery of methylase, an enzyme, found to add protective methyl groups to DNAArber, LinnUniversity of Geneva
1970First complete gene synthesised KhoranaUniversity of Wisconsin
July 1970First restriction enzyme isolated and characterisedSmith, WilcoxJohns Hopkins University
1971Process called repair replication for synthesising short DNA duplexes and single-stranded DNA by polymerases is publishedKhorana, KleppeMIT
1971First plasmid bacterial cloning vector constructedBerg, Mertz, JacksonStanford University
May 1971Complete sequence of bacteriophage lambda DNA reportedWu, TaylorCornell University
June 1971First time potential biohazards of recombinant DNA raisedMertz, Berg, PollackStanford University
December 1971First experiments published demonstrating the use of restriction enzymes to cut DNADanna, NathansJohns Hopkins University
September 1972 - Sep 1972First time possible biohazards of recombinant DNA technology publicly discussedZinder 
October 1972First paper published on generating recombinant DNABerg, Jackson, SymonsStanford University
November 1972First easy-to-use technique published for constucting recombinant DNA. J. Mertz, R. Davis, Proceedings of the National Academy of Science, USA 69/11, pp. 2270-74.Berg, MertzStanford University Medical School
1 Nov 1972Nature editorial voiced concern about generating recombinant DNABerg, Jackson, SymonsStanford University
1973Recombinant DNA produced in bacteriaCohen, BoyerStanford University Medical School, University of California San Francisco
1973The sequencing of 24 basepairs is reportedGilbert, MaxamHarvard University
1974Regulation begins for recombinant genetic research 
July 1974First concerns about potential biohazards of recombinant DNA publishedBerg, Baltimore, Boyer, Cohen 
1975Temporary moratorium on genetic engineeringBerg 
1975Sanger and Coulson publish their plus minus method for DNA sequencingSanger, CoulsonLaboratory of Molecular Biology
1975DNA methylation suggested as mechanism behind X-chomosome silencing in embryosRiggs, Sager, KitchenCity of Hope National Medical Center, Harvard University
1975DNA methylation proposed as important mechanism for the control of gene expression in higher organismsHoilliday, PughNational Institute for Medical Research
1976 
April 1976Genentech foundedSwanson, BoyerGenentech Inc
1977Human growth hormone genetically engineered 
1977Complete sequence of bacteriophage phi X174 DNA determinedSangerLaboratory of Molecular Biology
1977First computer programme written to help with the compilation and analysis of DNA sequence dataMcCallumLaboratory of Molecular Biology
February 1977Two different DNA sequencing methods published that allow for the rapid sequencing of long stretches of DNASanger, Maxam, GilbertHarvard University, Laboratory of Molecular Biology
1978Human insulin produced in E-coliGenentech
October 1978Nobel Prize for discovery and understanding of restriction enzymesArber, Nathans, SmithJohns Hopkins University, University of Geneva
1980Genetic engineering recognised for patenting 
1980First patent awarded for gene cloningCohen, BoyerStanford University Medical School
1980Cesar Milstein proposed the use of recombinant DNA to improve monoclonal antibodiesMilsteinLaboratory of Molecular Biology
1980Sanger awarded his second Nobel Prize in ChemistrySanger, GilbertHarvard University, Laboratory of Molecular Biology
January 1980European Molecular Biology Laboratory convenes meeting on Computing and DNA SequencesEMBL
September 1980First transgenic mice made with recombinant DNA announced Barbosa, Gordon, Plotkin, Ruddle, ScangosYale University
September 1980First DNA sequence database createdDayhoffNational Biomedical Research Foundation
1980Largest nucleic acid sequence database in the world made available free over telephone networkDayhoffNational Biomedical Research Foundation
1981First genetically-engineered plant reported 
1981First genetically cloned mice 
July 1981First evidence provided to show that DNA methylation involved in silencing X-chromosomeCompere, PalmitterHoward Hughes Medical Institute
1982Whole genome sequencing method is introduced for DNA sequencing 
1982 - 1985Studies reveal azacitidine, a cytoxic agent developed by Upjohn, inhibits DNA methylation 
June 1982NIH agrees to provide US$3.2 million over 5 years to establish and maintain a nucleic sequence database 
October 1982First recombinant DNA based drug approvedGenentech Inc
1983Sanger retiresSangerLaboratory of Molecular Biology
6 Jan 1983Widespread loss of DNA methylation found on cytosine-guanine (CpG) islands in tumour samplesFeinberg, VogelsteinJohns Hopkins University
20 Jan 1983Solomon Spiegelman diedSpiegelmanUniversity of Minnesota
1983Polymerase chain reaction (PCR) starts to be developed as a technique to amplify DNAMullisCetus Corporation
June 1984Results from PCR experiments start being reportedMullisCetus Corporation
1984First chimeric monoclonal antibodies developed which lays foundation for safer and more effective monoclonal antibody therapeuticsNeuberger, Rabbitts, Morrison, Oi, Herzenberg, Boulianne, Schulman, HozumiLaboratory of Molecular Biology, Stanford Univerity Medical School
January 1985DNA methylation found to occur on specific DNA segments called CpG islandsBird, Taggart, Fromer, Miller, MacleodEdinburgh University, Kanematsu Laboratories, Columbia University
March 1985Mullis and Cetus Corporation filed patent for the PCR techniqueMullisCetus Corporation
March 1985DNA fingerprinting principle laid outJeffreysUniversity of Leicester
20 Dec 1985The Polymerase Chain Reaction technique was publishedMullisCetus Corporation
1986First machine developed for automating DNA sequencingHood, Smith, HunkapillerCalifornia Institute of Technology, Applied Biosystems
30 Apr 1986Human Genome Organization founded 
May 1986First humanised monoclonal antibody createdDear, Foote, Jones, Neuberger, WinterLaboratory of Molecular Biology
June 1986Interferon approved for treating hairy cell leukaemia 
23 Jul 1986First recombinant vaccine licensedMerck & Co
1988Campath-1H is created - the first clinically useful humanised monoclonal antibody.Winter, Waldmann, Reichmann, ClarkCambridge University, Laboratory of Molecular Biology
1988US Congress funds genome sequencing 
April 1988Development of first rapid search computer programme to identify genes in a new sequencePearson, Lipman 
20 Oct 1988Cloning of first mammalian enzyme (DNA methyltransferase, DNMT) that catalyses transfer of methyl group to DNA Bestor, Laudano, Mattaliano, IngramMassachusetts Institute of Technology
September 1989DNA methylation suggested to inactivate tumour suppressor genesGreger, Passarge, Hopping, Messmer, HorsthemkeInstitute of Human Genetics
1 Feb 1990First pitch for US Human Genome Project 
October 1990Human Genome Project formally launched 
1992GenBank is integrated into the NIH National Center for Biotechnology Information 
1 Mar 1992Method devised to isolate methylated cytosine residues in individual DNA strands providing avenue to undertake DNA methylation genomic sequencing 
1 Oct 1992First experimental evidence showing links between diet and DNA methylation and its relationship with cancerZapisek, Cronin, Lyn-Cook, PoirierFDA, National Center for Toxicological Research
1 Nov 1993Severo Ochoa diedOchoaNew York University
December 1993Recombinant human deoxyribonuclease approved by FDA for cystic fibrosisGenentech
1994First chimeric monoclonal antibody therapeutic approved for marketCollerCentocor, State University of New York
21 Apr 1995First evidence published to demonstrate reduced DNA methylation contributes to formation of tumoursLaird, Jackson-Grusby, Fazeli, Dickinson, Jung, Li, Weinberg, JaenischMassachusetts Institute of Technology, Massachusetts General Hospital
July 1995Craig Venter's team at The Institute of Genomics Research (TIGR) published the first complete sequence of the 1.8 Mbp genome of a free-living organism (the bacterium Haemophilus influenzae)VenterThe Institute for Genomic Research
1996Complete genome sequence of the first eukaryotic organism, the yeast S. cerevisiae, is published  
1996Pyrosequencing is introduced for DNA sequencingRonaghi, NyrenRoyal Institute of Technology
10 Jan 1997Alexander R Todd diedToddUniversity of Manchester
December 1997First humanised monoclonal antibody approved for marketQueenProtein Design Labs, Roche
May 1998Commercial Human Genome Project launchedVenterCelera Genomics
December 1998Complete genome sequence of the first multicellular organism, the nematode worm Caenorhabditis elegans, is publishedSanger Institute, Washington University
1999First human chromosome sequence published 
20 Jul 1999DNA methylation of CpG islands shown to be linked to colorectal cancerToyota, Ahuja, Ohe-Toyota, Herman, Baylin, IssaJohns Hopkins University
16 Nov 1999Daniel Nathans diedNathans Johns Hopkins University
2000Complete sequences of the genomes of the fruit fly Drosophila and the first plant, Arabidopsis, are published 
June 2000Human genome draft sequence announced 
4 Oct 2000Michael Smith diedUniversity of British Columbia
December 2000First plant DNA sequenced 
February 2001First consensus sequence of human genome publishedCelera
2002Complete genome sequence of the first mammalian model organism, the mouse, is published  
July 2002Poliovirus synthesisedStony Brook University
October 2002Genomic sequence of the principal malaria parasite and vector reported 
April 2003The sequence of the first human genome was published 
2004FDA approved first DNA methylation inhibitor drug, azacitidine (Vidaza®), for treatment of rare bone marrow disorder 
28 Jul 2004Francis H C Crick diedCrickLaboratory of Molecular Biology
5 Oct 2004Maurice H F Wilkins diedWilkinsKing's College London
23 Dec 2004First DNA microarray diagnostic device approved 
February 2005Enzyme Ubp10 demonstrated to protect the genome from potential destabilising molecular eventsBerger, EmreWistar Institute
2006FDA approved second DNA methylation inhibitior, decatabine (Dacogen) 
May 2006Last human chromosome is sequenced 
26 Oct 2007Arthur Kornberg diedKornbergStanford University
2008Structure of telomerase, an enzyme that conserves the ends of chomosomes, was decodedWistar Institute
January 2011DNA sequencing proves useful to documenting the rapid evolution of Streptococcus penumoniae in response to the application of vaccinesWellcome Trust Sanger Institute
June 2012DNA sequencing helps identify the source of an MRSA outbreak in a neornatal intensive care unitPeacock, ParkhillCambridge University, Wellcome Trust Sanger Institute
December 2012DNA sequencing utilised for identifying neurological disease conditions different from those given in the original diagnosisUniversity of California San Diego
19 Nov 2013Sanger, the inventor of DNA sequencing, died at the age of 95SangerCambridge
March 2014Promising results announced from trial conducted with HIV patients 
7 Oct 2015Nobel Prize in Chemistry awarded to scientists for understanding the process of DNA repairLindahl, Modrich, SancarFrancis Crick Institute, Howard Hughes Medical Institute, University of North Carolina

1842

First observation of chromosomes by Swiss botanist Karl von Nageli

1864 - 1865

Nucleus shown to contain genetic substance

1869

Discovery of DNA

25 Feb 1869

Phoebus Levene was born

1871

Papers describe DNA for first time

1872

Walther Flemming, German biologist, describes chromosomes and examines their behaviour during cell division.

1877 - 1880

Nucleic acid shown to have protein and non-protein components

21 Oct 1877

Oswald Theodore Avery was born in Halifax, Canada

1885 - 1901

Nucleic acids structure determined

1889

Richard Altmann, German pathologist, renames nuclein as nucleic acid

26 Aug 1895

Johann Friedrich Miescher died

1898

A nucelotide called tuberculinic acid found to bind to the protein tuberculin. It is now regarded as the precursor to the discovery of DNA methylation

1902

Chromosomes linked with inheritance

1903

The notion genetics is introduced

24 Sep 1905

Severo Ochoa was born in Luarca, Spain

24 Sep 1905

Severo Ochoa was born in Luarca, Spain

2 Oct 1907

Alexander R Todd was born in Glasgow, Scotland

1909

The term gene is first used

1910

First description of the building blocks of DNA

1913

First mapping of a chromosome

14 Dec 1914

Solomon Spiegelman was born in Brooklyn, NY, USA

8 Jun 1916

Francis H C Crick was born in Northampton, United Kingdom

15 Dec 1916

Maurice H F Wilkins was born in Pongaroa, New Zealand

3 Mar 1918

Arthur Kornberg was born in Brooklyn NY, USA

13 Aug 1918

Frederick Sanger, twice Nobel Prize winner, born in Rendcombe, United Kingdom

13 Aug 1918

Frederick Sanger, twice Nobel Prize winner, born

25 Jul 1920

Rosalind E Franklin was born in London, United Kingdom

Nov 1925

T.B. Johnson and R.D. Coghill reported detecting a minor amount of methylated cytosine derivative as byproduct of hyrdrolysis of tuberculinic acid with sulfuric acid but other scientists struggled to replicate their results.

30 Jun 1926

Paul Berg was born in New York NY, USA

1928

Bacteria shown capable of transformation

6 Apr 1928

James D Watson was born in Chicago IL, USA

1929

DNA nucleobases identified

3 Jun 1929

Werner Arber was born in Granichen, Switzerland

1932

Sanger attends Bryanston School, Dorset, as boarder

26 Apr 1932

Michael Smith was born in Blackpool, United Kingdom

30 Jun 1935

Stanley Norman Cohen was born in Perth Amboy, NJ, USA

1936 - 1940

Sanger takes degree in Natural Sciences at Cambridge University

1940 - 1943

Sanger studies for a doctorate at Cambridge University

6 Sep 1940

Phoebus Levene died

1941

Term 'genetic engineering' first coined

6 Sep 1943

Richard J Roberts was born

1944

Sanger starts working on amino acid composition of insulin

1 Feb 1944

DNA identified as a heritary agent

Dec 1944

Kary Banks Mullis was born

14 Oct 1946

J Craig Venter was born in Salt Lake City, Utah

1949

DNA content of a cells linked to a cell's number of chromosomes

1949 - 1950

DNA four base ratio shown to be always consistent

Sep 1949

Sickle cell shown to be caused by genetic mutation

Nov 1951

Purified DNA and DNA in cells shown to have helical structure

1952

Bacteriophage experiments show DNA and not proteins to be genetic material

1952

First observation of the modification of viruses by bacteria

Jan 1952

X-ray diffraction image, produced by Rosalind Franklin, shows DNA to have regularly repeating helical structure

Apr 1953

DNA double-helix structure announced

Apr 1953

Franklin's x-ray image of DNA published

1955

Sanger completes the full sequence of amino acids in insulin

2 Feb 1955

Oswald Theodore Avery died

Dec 1955

First discovery of the enzyme DNA polymerase

1956

DNA polymerase discovered to replicate DNA

1957

Victor Ingram breaks the genetic code behind sickle-cell anaemia using Sanger's sequencing technique

1957

First observation of messenger RNA

19 Sep 1957

Francis Crick presented what is now known as the 'central dogma' in molecular biology which argues that the main function of genetic material is to control the synthesis of proteins

Oct 1957

First synthesis of DNA in a test tube

1958

DNA replication explained

1958

Sanger awarded his first Nobel Prize in Chemistry

16 Apr 1958

Rosalind E Franklin died

1960

National Biomedical Research Foundation established

1960

Sanger begins to devise ways to sequence nucleic acids, starting with RNA

1961 - 1966

Genetic code cracked for the first time

31 Mar 1961

Experiments reveal a type of RNA (messenger RNA) transports genetic information from the nucleus to the protein-making machinery in a cell

May 1961

Coding mechanism for DNA discovered

1962

Concept of restriction and modification enzymes born

1962

Sanger moves to the newly created Laboratory of Molecular Biology in Cambridge

18 Oct 1962

Watson, Crick and Wilkins won the Nobel Prize for Medicine for their work in determining the structure of DNA

1965

Transfer RNA is the first nucleic acid molecule to be sequenced

1965

Werner Arber predicts restriction enzymes could be used as a labortory tool to cleave DNA

1965

Atlas of Protein Sequence and Structure published

1965

Ledley publishes Uses of Computers in Biology and Medicine

1965

Sanger and colleagues publish two-dimension partition sequencing method

1967

First automatic protein sequencer developed

1968 - 1970

Restriction enzymes found to act as chemical knives to cut DNA

1968

The first partial sequence of a viral DNA is reported

1968

Paul Berg started experiments to generate recombinant DNA molecules

1969

First principles for PCR published

1969

New species of bacterium is isolated from hot spring in Yellowstone National Park by Thomas Brock

1969

New idea for generating recombinant DNA conceived

Jul 1969

Discovery of methylase, an enzyme, found to add protective methyl groups to DNA

1970

First complete gene synthesised

Jul 1970

First restriction enzyme isolated and characterised

1971

Process called repair replication for synthesising short DNA duplexes and single-stranded DNA by polymerases is published

1971

First plasmid bacterial cloning vector constructed

May 1971

Complete sequence of bacteriophage lambda DNA reported

Jun 1971

First time potential biohazards of recombinant DNA raised

Dec 1971

First experiments published demonstrating the use of restriction enzymes to cut DNA

Sep 1972 - Sep 1972

First time possible biohazards of recombinant DNA technology publicly discussed

Oct 1972

First paper published on generating recombinant DNA

Nov 1972

First easy-to-use technique published for constucting recombinant DNA. J. Mertz, R. Davis, Proceedings of the National Academy of Science, USA 69/11, pp. 2270-74.

1 Nov 1972

Nature editorial voiced concern about generating recombinant DNA

1973

Recombinant DNA produced in bacteria

1973

The sequencing of 24 basepairs is reported

1974

Regulation begins for recombinant genetic research

Jul 1974

First concerns about potential biohazards of recombinant DNA published

1975

Temporary moratorium on genetic engineering

1975

Sanger and Coulson publish their plus minus method for DNA sequencing

1975

DNA methylation suggested as mechanism behind X-chomosome silencing in embryos

1975

DNA methylation proposed as important mechanism for the control of gene expression in higher organisms

1976

Apr 1976

Genentech founded

1977

Human growth hormone genetically engineered

1977

Complete sequence of bacteriophage phi X174 DNA determined

1977

First computer programme written to help with the compilation and analysis of DNA sequence data

Feb 1977

Two different DNA sequencing methods published that allow for the rapid sequencing of long stretches of DNA

1978

Human insulin produced in E-coli

Oct 1978

Nobel Prize for discovery and understanding of restriction enzymes

1980

Genetic engineering recognised for patenting

1980

First patent awarded for gene cloning

1980

Cesar Milstein proposed the use of recombinant DNA to improve monoclonal antibodies

1980

Sanger awarded his second Nobel Prize in Chemistry

Jan 1980

European Molecular Biology Laboratory convenes meeting on Computing and DNA Sequences

Sep 1980

First transgenic mice made with recombinant DNA announced

Sep 1980

First DNA sequence database created

1980

Largest nucleic acid sequence database in the world made available free over telephone network

1981

First genetically-engineered plant reported

1981

First genetically cloned mice

Jul 1981

First evidence provided to show that DNA methylation involved in silencing X-chromosome

1982

Whole genome sequencing method is introduced for DNA sequencing

1982 - 1985

Studies reveal azacitidine, a cytoxic agent developed by Upjohn, inhibits DNA methylation

Jun 1982

NIH agrees to provide US$3.2 million over 5 years to establish and maintain a nucleic sequence database

Oct 1982

First recombinant DNA based drug approved

1983

Sanger retires

6 Jan 1983

Widespread loss of DNA methylation found on cytosine-guanine (CpG) islands in tumour samples

20 Jan 1983

Solomon Spiegelman died

1983

Polymerase chain reaction (PCR) starts to be developed as a technique to amplify DNA

Jun 1984

Results from PCR experiments start being reported

1984

First chimeric monoclonal antibodies developed which lays foundation for safer and more effective monoclonal antibody therapeutics

Jan 1985

DNA methylation found to occur on specific DNA segments called CpG islands

Mar 1985

Mullis and Cetus Corporation filed patent for the PCR technique

Mar 1985

DNA fingerprinting principle laid out

20 Dec 1985

The Polymerase Chain Reaction technique was published

1986

First machine developed for automating DNA sequencing

1986

Human Genome Organization founded

May 1986

First humanised monoclonal antibody created

Jun 1986

Interferon approved for treating hairy cell leukaemia

Jun 1986

First recombinant vaccine licensed

1988

Campath-1H is created - the first clinically useful humanised monoclonal antibody.

1988

US Congress funds genome sequencing

Apr 1988

Development of first rapid search computer programme to identify genes in a new sequence

20 Oct 1988

Cloning of first mammalian enzyme (DNA methyltransferase, DNMT) that catalyses transfer of methyl group to DNA

Sep 1989

DNA methylation suggested to inactivate tumour suppressor genes

Sep 1989

First pitch for US Human Genome Project

Oct 1990

Human Genome Project formally launched

1992

GenBank is integrated into the NIH National Center for Biotechnology Information

1 Mar 1992

Method devised to isolate methylated cytosine residues in individual DNA strands providing avenue to undertake DNA methylation genomic sequencing

1 Oct 1992

First experimental evidence showing links between diet and DNA methylation and its relationship with cancer

1 Nov 1993

Severo Ochoa died

Dec 1993

Recombinant human deoxyribonuclease approved by FDA for cystic fibrosis

1994

First chimeric monoclonal antibody therapeutic approved for market

21 Apr 1995

First evidence published to demonstrate reduced DNA methylation contributes to formation of tumours

Jul 1995

Craig Venter's team at The Institute of Genomics Research (TIGR) published the first complete sequence of the 1.8 Mbp genome of a free-living organism (the bacterium Haemophilus influenzae)

1996

Complete genome sequence of the first eukaryotic organism, the yeast S. cerevisiae, is published

1996

Pyrosequencing is introduced for DNA sequencing

10 Jan 1997

Alexander R Todd died

Dec 1997

First humanised monoclonal antibody approved for market

May 1998

Commercial Human Genome Project launched

Dec 1998

Complete genome sequence of the first multicellular organism, the nematode worm Caenorhabditis elegans, is published

1999

First human chromosome sequence published

20 Jul 1999

DNA methylation of CpG islands shown to be linked to colorectal cancer

16 Nov 1999

Daniel Nathans died

2000

Complete sequences of the genomes of the fruit fly Drosophila and the first plant, Arabidopsis, are published

Jun 2000

Human genome draft sequence announced

4 Oct 2000

Michael Smith died

Dec 2000

First plant DNA sequenced

Feb 2001

First consensus sequence of human genome published

2002

Complete genome sequence of the first mammalian model organism, the mouse, is published

Jul 2002

Poliovirus synthesised

Oct 2002

Genomic sequence of the principal malaria parasite and vector reported

Apr 2003

The sequence of the first human genome was published

2004

FDA approved first DNA methylation inhibitor drug, azacitidine (Vidaza®), for treatment of rare bone marrow disorder

28 Jul 2004

Francis H C Crick died

5 Oct 2004

Maurice H F Wilkins died

5 Oct 2004

First DNA microarray diagnostic device approved

Feb 2005

Enzyme Ubp10 demonstrated to protect the genome from potential destabilising molecular events

2006

FDA approved second DNA methylation inhibitior, decatabine (Dacogen)

May 2006

Last human chromosome is sequenced

26 Oct 2007

Arthur Kornberg died

2008

Structure of telomerase, an enzyme that conserves the ends of chomosomes, was decoded

Jan 2011

DNA sequencing proves useful to documenting the rapid evolution of Streptococcus penumoniae in response to the application of vaccines

Jun 2012

DNA sequencing helps identify the source of an MRSA outbreak in a neornatal intensive care unit

Dec 2012

DNA sequencing utilised for identifying neurological disease conditions different from those given in the original diagnosis

19 Nov 2013

Sanger, the inventor of DNA sequencing, died at the age of 95

Mar 2014

Promising results announced from trial conducted with HIV patients

7 Oct 2015

Nobel Prize in Chemistry awarded to scientists for understanding the process of DNA repair