Who first identified the process of oligonucleotide synthesis?
Oligonucleotide synthesis
In the 1960s, groups led by R. Letsinger and C. Reese developed a phosphotriester approach. The defining difference from the phosphodiester approach was the protection of the phosphate moiety in the building block 1 (Scheme 4) and in the product 3 with 2-cyanoethyl group. This precluded the formation of oligonucleotides branched at the internucleosidic phosphate. The higher selectivity of the method allowed the use of more efficient coupling agents and catalysts, which dramatically reduced the length of the synthesis. The method, initially developed for the solution-phase synthesis, was also implemented on low-cross-linked "popcorn" polystyrene, and later on controlled pore glass (CPG, see "Solid support material" below), which initiated a massive research effort in solid-phase synthesis of oligonucleotides and eventually led to the automation of the oligonucleotide chain assembly.
Emile Zuckerkandl
During the succeeding years, Zuckerkandl worked to refine the molecular clock. In 1963, he and Pauling invented the term "semantides" for biological sequences—DNA, RNA, and polypeptides—that have evolutionary information and argued that such sequences could be the basis for constructing molecular phylogenies, suggesting that the "molecular clock" method might be useful for other semantides besides proteins. Emanuel Margoliash's first publication of sequence data for cytochrome c allowed comparison of the rates of molecular evolution for different proteins (cytochrome c seemed to evolve faster than hemoglobin), which Zuckerkandl discussed at a 1964 conference in Bruges. Zuckerkandl also adjusted the mathematics of the "clock" to account for the observation that some positions in an amino acid sequence were more stable than others, and the likelihood of multiple substitutions at the same position. In September 1964, he attended the important Evolving Genes and Proteins symposium, where he and Pauling presented their most influential paper ("Evolutionary Divergence and Convergence in Proteins", published in the conference proceedings the next year). The paper, primarily Zuckerkandl's work, named the "evolutionary clock" and presented a derivation of its basic mathematical form. Though Zuckerkandl and Pauling saw the clock as compatible with natural selection, it would later become the basis of the neutral theory of molecular evolution, in which genetic drift rather than selection is the driving force of evolution at the molecular level.
Systematic evolution of ligands by exponential enrichment
The first step of SELEX involves the synthesis of fully or partially randomized oligonucleotide sequences of some length flanked by defined regions which allow PCR amplification of those randomized regions and, in the case of RNA SELEX, in vitro transcription of the randomized sequence. While Ellington and Szostak demonstrated that chemical synthesis is capable of generating ~10 unique sequences for oligonucleotide libraries in their 1990 paper on in vitro selection, they found that amplification of these synthesized oligonucleotides led to significant loss of pool diversity due to PCR bias and defects in synthesized fragments. The oligonucleotide pool is amplified and a sufficient amount of the initial library is added to the reaction so that there are numerous copies of each individual sequence to minimize the loss of potential binding sequences due to stochastic events. Before the library is introduced to target for incubation and selective retention, the sequence library must be converted to single stranded oligonucleotides to achieve structural conformations with target binding properties.
Oswald Avery
Oswald Theodore Avery Jr. (October 21, 1877 – February 20, 1955) was a Canadian-American physician and medical researcher. The major part of his career was spent at the Rockefeller University Hospital in New York City. Avery was one of the first molecular biologists and a pioneer in immunochemistry, but he is best known for the experiment (published in 1944 with his co-workers Colin MacLeod and Maclyn McCarty) that isolated DNA as the material of which genes and chromosomes are made.
Oganesson
The first genuine decay of atoms of oganesson was observed in 2002 at the Joint Institute for Nuclear Research (JINR) in Dubna, Russia, by a joint team of Russian and American scientists. Headed by Yuri Oganessian, a Russian nuclear physicist of Armenian ethnicity, the team included American scientists of the Lawrence Livermore National Laboratory, California. The discovery was not announced immediately, because the decay energy of Og matched that of Po, a common impurity produced in fusion reactions aimed at producing superheavy elements, and thus announcement was delayed until after a 2005 confirmatory experiment aimed at producing more oganesson atoms. On 9 October 2006, the researchers announced that they had indirectly detected a total of three (possibly four) nuclei of oganesson-294 (one or two in 2002 and two more in 2005) produced via collisions of californium-249 atoms and calcium-48 ions.
Lawrencium
The first important work on element 103 was carried out at Berkeley by the nuclear-physics team of Albert Ghiorso, Torbjørn Sikkeland, Almon Larsh, Robert M. Latimer, and their co-workers on February 14, 1961. The first atoms of lawrencium were reportedly produced by bombarding a three-milligram target consisting of three isotopes of the element californium with boron-10 and boron-11 nuclei from the Heavy Ion Linear Accelerator (HILAC). The Berkeley team reported that the isotope 103 was detected in this manner, and that it decayed by emitting an 8.6 MeV alpha particle with a half-life of . This identification was later corrected to be 103, as later work proved that Lr did not have the properties detected, but Lr did. This was considered at the time to be convincing proof of the synthesis of element 103: while the mass assignment was less certain and proved to be mistaken, it did not affect the arguments in favor of element 103 having been synthesized. Scientists at the Joint Institute for Nuclear Research in Dubna (then in the Soviet Union) raised several criticisms: all but one were answered adequately. The exception was that Cf was the most common isotope in the target, and in the reactions with B, Lr could only have been produced by emitting four neutrons, and emitting three neutrons was expected to be much less likely than emitting four or five. This would lead to a narrow yield curve, not the broad one reported by the Berkeley team. A possible explanation was that there was a low number of events attributed to element 103. This was an important intermediate step to the unquestioned discovery of element 103, although the evidence was not completely convincing. The Berkeley team proposed the name "lawrencium" with symbol "Lw", after Ernest Orlando Lawrence, inventor of the cyclotron. The IUPAC Commission on Nomenclature of Inorganic Chemistry accepted the name, but changed the symbol to "Lr". This acceptance of the discovery was later characterized as being hasty by the Dubna team.
Gerd Jürgens
During his postdoctoral years in the 1980s he worked with Nobel prize winners Christiane Nüsslein-Volhard and Eric Wieschaus at the European Molecular Biology Laboratory (EMBL) in Heidelberg on the topic of "Drosophila melanogaster" embryogenesis.
At the age of 37 he made the switch from animal to plant research and became one of the first researchers to work on what was later to become the model plant organism: "Arabidopsis thaliana".
He was responsible for pioneering research in the genetic dissection of plant embryogenesis. Using the genetically-tractable plant "Arabidopsis thaliana" he conducted the first forward genetic screen (using mutagenesis with 0.3% ethyl methane sulfonate(EMS)) looking for embryonic defects.
His laboratory discovered and characterized the protein KNOLLE, which is required for cytokinesis and was the first protein known to exclusively target the cell plate in plant cells. 
Prof Gerd Jürgens also worked extensively on the ARF-GEF GNOM. Both "knolle" and "gnom" were first discovered in his embryonic mutant screens.
N,N-Dimethyltryptamine
DMT was first synthesized in 1931 by chemist Richard Helmuth Fredrick Manske (born 1901 in Berlin, Germany – 1977). In general, its discovery as a natural product is credited to Brazilian chemist and microbiologist Oswaldo Gonçalves de Lima (1908–1989) who, in 1946, isolated an alkaloid he named "nigerina" (nigerine) from the root bark of "jurema preta", that is, "Mimosa tenuiflora". However, in a careful review of the case Jonathan Ott shows that the empirical formula for nigerine determined by Gonçalves de Lima, which notably contains an atom of oxygen, can match only a partial, "impure" or "contaminated" form of DMT. It was only in 1959, when Gonçalves de Lima provided American chemists a sample of "Mimosa tenuiflora" roots, that DMT was unequivocally identified in this plant material. Less ambiguous is the case of isolation and formal identification of DMT in 1955 in seeds and pods of "Anadenanthera peregrina" by a team of American chemists led by Evan Horning (1916–1993). Since 1955, DMT has been found in a host of organisms: in at least fifty plant species belonging to ten families, and in at least four animal species, including one gorgonian and three mammalian species.
Richard Müller (chemist)
Richard Gustav Müller (17 July 1903 – 7 July 1999) was a German chemist. He and Eugene G. Rochow independently discovered the direct process of organosilicon compounds in 1941. That synthesis, also known as the "Müller-Rochow process" is the copper-catalysed reaction of chloromethane with silicon. Müller was awarded the National Prize of East Germany in 1952 for his work.
Shell higher olefin process
The first step in this process is the ethylene oligomerization to a mixture of even-numbered α-olefins at 80 to 120 °C and 70 to 140 bar (7 to 14 MPa) catalyzed by a nickel-phosphine complex. Such catalysts are typically prepared from diarylphosphino carboxylic acids, such as (CH)PCHCOH. The process and its mechanism was elucidated by the group of Wilhelm Keim, first at Shell and later at the RWTH Aachen.
Auguste André Thomas Cahours
August André Thomas Cahours (1813-1891) was a chemist and scientist whose contribution to organic chemistry was one of the greatest in history. He discovered, among other things, the processes of synthesis of several chemical molecules, including toluene, xylene, several organo-magnesiums, and derivatives of phosphine and arsine.
John Shine
Professor John Shine (born 3 July 1946) is an Australian biochemist and molecular biologist. Shine discovered the nucleotide sequence, called the Shine-Dalgarno sequence, necessary for the initiation and termination of protein synthesis. He directed the Garvan Institute of Medical Research in Sydney from 1990 to 2011. In May 2018 Shine was elected President of the Australian Academy of Science.
The brother of scientist, Richard Shine, John Shine was born in Brisbane in 1946 and completed his university studies at the Australian National University (ANU) in Canberra, graduating with a bachelor of science with honours in 1972 and completing his PhD in 1975. During the course of his studies he discovered the RNA sequence necessary for ribosome binding and the initiation of protein synthesis in the bacterium "Escherichia coli". The sequence was named the Shine-Dalgarno sequence. This was a key discovery allowing further development of molecular biology, especially genetic engineering, and was an important discovery towards understanding gene expression and regulation.
Elmer McCollum
McCollum and Davis, who ultimately received credit for the discovery, submitted their paper for publication three weeks before Osborne and Mendel. Both papers appeared in the same issue of the "Journal of Biological Chemistry" in 1913. This turned out to be a very close call given that learning about vitaminA took scientists about 130 years, beginning with François Magendie in 1816 through its synthesis in 1947.
Otto Kandler
So, in 1950, he was the first to present experimental evidence for the light-dependent formation of ATP (photophosphorylation) "in vivo" in intact "Chlorella" cells.
In 1954, Daniel I. Arnon discovered photophosphorylation "in vitro" using isolated chloroplasts and mentioned Kandler's pioneering work. Kandler's early publications on light-dependent formation of ATP led the Rockefeller Foundation to offer him a one-year research fellowship in the USA. So in 1956-1957 he worked for 6 months with Martin Gibbs at the Brookhaven National Laboratory and then for another 6 months with Melvin Calvin (1961 Nobel Prize in Chemistry) at the University of California, Berkeley on central questions of photosynthesis (e.g. the path of carbon in photosynthesis, today called the Calvin-Benson-Bassham Cycle).
Cell-free protein synthesis
The first elucidation of a codon was done by Marshall Nirenberg and Heinrich J. Matthaei in 1961 at the National Institutes of Health. They used a cell-free system to translate a poly-uracil RNA sequence (or UUUUU... in biochemical terms) and discovered that the polypeptide they had synthesized consisted of only the amino acid phenylalanine. They thereby deduced from this poly-phenylalanine that the codon UUU specified the amino-acid phenylalanine. Extending this work, Nirenberg and his coworkers were able to determine the nucleotide makeup of each codon.
Synthetic genomics
Polymerase cycling assembly (PCA) uses a series of oligonucleotides (or oligos), approximately 40 to 60 nucleotides long, that altogether constitute both strands of the DNA being synthesized. These oligos are designed such that a single oligo from one strand contains a length of approximately 20 nucleotides at each end that is complementary to sequences of two different oligos on the opposite strand, thereby creating regions of overlap. The entire set is processed through cycles of: (a) hybridization at 60 °C; (b) elongation via Taq polymerase and a standard ligase; and (c) denaturation at 95 °C, forming progressively longer contiguous strands and ultimately resulting in the final genome. PCA was used to generate the first synthetic genome in history, that of the Phi X 174 virus.
Oncogene
The resultant protein encoded by an oncogene is termed oncoprotein. Oncogenes play an important role in the regulation or synthesis of proteins linked to tumorigenic cell growth. Some oncoproteins are accepted and used as tumor markers. The Spanish biochemist Mariano Barbacid isolated the first oncogene. His discovery was published in the prestigious journal Nature in 1982 in an article titled "A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder-carcinoma oncogene". He spent the following months extending his research, eventually discovering that such oncogene was the mutation of an allele of the Ras subfamily, as well as its activation mechanism.
Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid
Linus Pauling was a chemist who was very influential in developing an understanding of the structure of biological molecules. In 1951, Pauling published the structure of the alpha helix, a fundamentally important structural component of proteins. In early 1953, Pauling published a triple helix model of DNA, which subsequently turned out to be incorrect. Both Crick, and particularly Watson, thought that they were racing against Pauling to discover the structure of DNA.
History of electrophoresis
The history of electrophoresis began with the work of Arne Tiselius in 1931, while new separation processes and chemical analysis techniques based on electrophoresis continue to be developed in the 21st century. Tiselius, with support from the Rockefeller Foundation, developed the "Tiselius apparatus" for moving boundary electrophoresis, which was described in 1937 in the well-known paper "A New Apparatus for Electrophoretic Analysis of Colloidal Mixtures". The method spread slowly until the advent of effective zone electrophoresis methods in the 1940s and 1950s, which used filter paper or gels as supporting media. By the 1960s, increasingly sophisticated gel electrophoresis methods made it possible to separate biological molecules based on minute physical and chemical differences, helping to drive the rise of molecular biology. Gel electrophoresis and related techniques became the basis for a wide range of biochemical methods, such as protein fingerprinting, Southern blot, other blotting procedures, DNA sequencing, and many more.
Kelvin Ogilvie
His scientific achievements include the development of an automated process for the manufacture of RNA, and the invention of the drug ganciclovir.
Oligonucleotide synthesis
In contrast to organic solid-phase synthesis and peptide synthesis, the synthesis of oligonucleotides proceeds best on non-swellable or low-swellable solid supports. The two most often used solid-phase materials are controlled pore glass (CPG) and macroporous polystyrene (MPPS).To make the solid support material suitable for oligonucleotide synthesis, non-nucleosidic linkers or nucleoside succinates are covalently attached to the reactive amino groups in aminopropyl CPG, LCAA CPG, or aminomethyl MPPS. The remaining unreacted amino groups are capped with acetic anhydride. Typically, three conceptually different groups of solid supports are used.
Oxygenase
Oxygenases were discovered in 1955 simultaneously by two groups, Osamu Hayaishi from Japan and Howard S. Mason from the US. Hayaishi was awarded the 1986 Wolf Prize in Medicine "for the discovery of the oxygenase enzymes and elucidation of their structure and biological importance."
Brin process
The reaction was discovered by Joseph-Louis Gay-Lussac and Louis-Jacques Thenard in 1811 and Jean-Baptiste Boussingault tried to use this reaction to establish a process to produce oxygen in 1852. The process worked only for a few cycles and then became inefficient. Two students of Boussingault, Quentin and Arthur Leon Brin, discovered that traces of carbon dioxide formed barium carbonate. Removing the carbon dioxide with sodium hydroxide solved this problem. In 1884 they opened a factory producing oxygen by their improved process. In the commercial process, oxygen capture and release was controlled by pressure rather than temperature, with oxygen being captured at high pressure and released at low pressure. This allowed a faster change between the capture and release phases, which would last one to two hours.
Eugene G. Rochow
Eugene George Rochow (October 4, 1909 – March 21, 2002) was an American inorganic chemist. Rochow worked on organosilicon chemistry; in the 1940s, he described the direct process, also known as the Rochow process or Müller-Rochow process.
Michael Smith (chemist)
Michael Smith (April 26, 1932 – October 4, 2000) was a British-born Canadian biochemist and businessman. He shared the 1993 Nobel Prize in Chemistry with Kary Mullis for his work in developing site-directed mutagenesis. Following a PhD in 1956 from the University of Manchester, he undertook postdoctoral research with Har Gobind Khorana (himself a Nobel Prize winner) at the British Columbia Research Council in Vancouver, British Columbia, Canada. Subsequently, Smith worked at the Fisheries Research Board of Canada Laboratory in Vancouver before being appointed a professor of biochemistry in the UBC Faculty of Medicine in 1966. Smith's career included roles as the founding director of the UBC Biotechnology Laboratory (1987 to 1995) and the founding scientific leader of the Protein Engineering Network of Centres of Excellence (PENCE). In 1996 he was named Peter Wall Distinguished Professor of Biotechnology. Subsequently he became the founding director of the Genome Sequencing Centre (now called the Genome Sciences Centre) at the BC Cancer Research Centre.
History of Syracuse, New York
The first Solvay Process Company plant in the United States was erected on the southeastern shore of Onondaga lake in 1884 and the village was given the name Solvay, New York, to commemorate its inventor, Ernest Solvay. In 1861 he developed the ammonia-soda process for the manufacture of soda ash (anhydrous sodium carbonate—a rare chemical called natrite, to distinguish it from natural natron of antiquity) The process used sodium chloride (from brine wells dug in the southern end of the Tully valley) and limestone (as a source of calcium carbonate). The process was an improvement on the earlier Leblanc process. The Syracuse Solvay plant was the incubator for a large chemical industry complex owned by Allied Signal in Syracuse. This plant, though, made Onondaga Lake the most polluted in the nation.
Molecular Biology Core Facilities
The MBCF at DFCI was first started in 1984 to supply small oligonucleotides to researchers. Marvin H. Caruthers at the University of Colorado determined how to synthesize small oligonucleotides by solid-phase synthesis using the phosphoramidite method. Caruthers and Leroy Hood at the California Institute of Technology constructed the first automated DNA Synthesizer which the MBCF successfully tested after discussions with Don Taylor.
Nicotinamide adenine dinucleotide
The coenzyme NAD was first discovered by the British biochemists Arthur Harden and William John Young in 1906. They noticed that adding boiled and filtered yeast extract greatly accelerated alcoholic fermentation in unboiled yeast extracts. They called the unidentified factor responsible for this effect a "coferment". Through a long and difficult purification from yeast extracts, this heat-stable factor was identified as a nucleotide sugar phosphate by Hans von Euler-Chelpin. In 1936, the German scientist Otto Heinrich Warburg showed the function of the nucleotide coenzyme in hydride transfer and identified the nicotinamide portion as the site of redox reactions.
Robert Bruce Merrifield
In the mid-60s Dr. Merrifield's laboratory first synthesized bradykinin, angiotensin, desamino-oxytocin and insulin. In 1969, he and his colleague Bernd Gutte announced the first synthesis of the enzyme, ribonuclease A. This work proved the chemical nature of enzymes.
Dr. Merrifield's method greatly stimulated progress in biochemistry, pharmacology and medicine, making possible the systematic exploration of the structural basis of the activities of enzymes, hormones and antibodies. The development and applications of the technique continued to occupy his laboratory, where he remained active at the bench until recently. In 1993, he published his autobiography, "Life during a Golden Age of Peptide Chemistry." He received the Association of Biomolecular Resource Facilities Award for outstanding contributions to Biomolecular Technologies in 1998.
Oxygen
Oxygen was isolated by Michael Sendivogius before 1604, but it is commonly believed that the element was discovered independently by Carl Wilhelm Scheele, in Uppsala, in 1773 or earlier, and Joseph Priestley in Wiltshire, in 1774. Priority is often given for Priestley because his work was published first. Priestley, however, called oxygen "dephlogisticated air", and did not recognize it as a chemical element. The name "oxygen" was coined in 1777 by Antoine Lavoisier, who first recognized oxygen as a chemical element and correctly characterized the role it plays in combustion.
Syracuse, New York
The first Solvay Process Company plant in the United States was erected on the southwestern shore of Onondaga Lake in 1884. The village was called Solvay to commemorate the inventor, Ernest Solvay. In 1861, he developed the ammonia-soda process for the manufacture of soda ash (anhydrous sodium carbonate, a rare chemical called natrite, to distinguish it from natural natron of antiquity) from brine wells dug in the southern end of Tully valley (as a source of sodium chloride) and limestone (as a source of calcium carbonate). The process was an improvement over the earlier Leblanc process. The Syracuse Solvay plant was the incubator for a large chemical industry complex owned by Allied Signal in Syracuse. While this industry stimulated development and provided many jobs in Syracuse, it left Onondaga Lake as the most polluted in the nation.
Elias Anton Cappelen Smith
Elias Anton Cappelen Smith (6 November 1873 – 25 June 1949) was a Norwegian American chemical engineer, civil engineer and metallurgist. He pioneered copper production in the early 20th century. Among his achievements were the and the Guggenheim process.
Cappelen Smith was born at Trondheim in Sør-Trøndelag, Norway. He was the son of Elias Anton Smith (1842–1912), founder of E.A. Smith AS and Ingeborg Anna Røvig (1846–1923). His middle name Cappelen is from the family of his paternal grandmother, Marie Severine Cappelen (died 1900) married to Peder Høegh Smith (died 1881). He grew up as the eldest son among nine children and attended the Trondheim Cathedral School.
He was educated as a chemist at , now the Norwegian University of Science and Technology, taking his final exam in 1893. The same year he emigrated to the United States.
Nitrogen fixation
The possibility that atmospheric nitrogen reacts with certain chemicals was first observed by Desfosses in 1828. He observed that mixtures of alkali metal oxides and carbon react at high temperatures with nitrogen. With the use of barium carbonate as starting material the first commercially used process became available in the 1860s developed by Margueritte and Sourdeval. The resulting barium cyanide could be reacted with steam yielding ammonia. In 1898 Adolph Frank and Nikodem Caro decoupled the process and first produced calcium carbide and in a subsequent step reacted it with nitrogen to calcium cyanamide. The Ostwald process for the production of nitric acid was discovered in 1902. Frank-Caro process and Ostwald process dominated the industrial fixation of nitrogen until the discovery of the Haber process in 1909. 
Prior to 1900, Nikola Tesla also experimented with the industrial fixation of nitrogen "by using currents of extremely high frequency or rate of vibration".
Robert Feulgen
Joachim Wilhelm Robert Feulgen (2 September 1884 – 24 October 1955) was a German physician and chemist who, in 1914, developed a method for staining DNA (now known as the Feulgen stain) and who also discovered plant and animal nuclear DNA (""thymonucleic acid"") congeniality.
Synthetic genomes
Polymerase cycling assembly (PCA) uses a series of oligonucleotides (or oligos), approximately 40 to 60 nucleotides long, that altogether constitute both strands of the DNA being synthesized. These oligos are designed such that a single oligo from one strand contains a length of approximately 20 nucleotides at each end that is complementary to sequences of two different oligos on the opposite strand, thereby creating regions of overlap. The entire set is processed through cycles of: (a) hybridization at 60 °C; (b) elongation via Taq polymerase and a standard ligase; and (c) denaturation at 95 °C, forming progressively longer contiguous strands and ultimately resulting in the final genome. PCA was used to generate the first synthetic genome in history, that of the Phi X 174 virus.
Citric acid cycle
Several of the components and reactions of the citric acid cycle were established in the 1930s by the research of Albert Szent-Györgyi, who received the Nobel Prize in Physiology or Medicine in 1937 specifically for his discoveries pertaining to fumaric acid, a key component of the cycle. He was able to make this discovery successful with the help of pigeon breast muscle. Because this tissue maintains its oxidative capacity well after breaking down in the "Latapie" mill and releasing in aqueous solutions breast muscle of the pigeon was very well qualified for the study of oxidative reactions. The citric acid cycle itself was finally identified in 1937 by Hans Adolf Krebs and William Arthur Johnson while at the University of Sheffield, for which the former received the Nobel Prize for Physiology or Medicine in 1953, and for whom the cycle is sometimes named (Krebs cycle).
Oligonucleotide synthesis
Oligonucleotide synthesis is the chemical synthesis of relatively short fragments of nucleic acids with defined chemical structure (sequence). The technique is extremely useful in current laboratory practice because it provides a rapid and inexpensive access to custom-made oligonucleotides of the desired sequence. Whereas enzymes synthesize DNA and RNA only in a 5' to 3' direction, chemical oligonucleotide synthesis does not have this limitation, although it is, most often, carried out in the opposite, 3' to 5' direction. Currently, the process is implemented as solid-phase synthesis using phosphoramidite method and phosphoramidite building blocks derived from protected 2'-deoxynucleosides (dA, dC, dG, and T), ribonucleosides (A, C, G, and U), or chemically modified nucleosides, e.g. LNA or BNA.
Leslie Orgel
Together with Sydney Brenner, Jack Dunitz, Dorothy Hodgkin, and Beryl M. Oughton he was one of the first people in April 1953 to see the model of the structure of DNA, constructed by Francis Crick and James Watson, at the time he and the other scientists were working at Oxford University's Chemistry Department. According to the late Dr. Beryl Oughton, later Rimmer, they all travelled together in two cars once Dorothy Hodgkin announced to them that they were off to Cambridge to see the model of the structure of DNA. All were impressed by the new DNA model, especially Brenner who subsequently worked with Crick; Orgel himself also worked with Crick at the Salk Institute for Biological Studies.
Paul D. Boyer
Paul Delos Boyer (July 31, 1918 – June 2, 2018) was an American biochemist, analytical chemist, and a professor of chemistry at University of California Los Angeles (UCLA). He shared the 1997 Nobel Prize in Chemistry for research on the "enzymatic mechanism underlying the biosynthesis of adenosine triphosphate (ATP)" (ATP synthase) with John E. Walker, making Boyer the first Utah-born Nobel laureate; the remainder of the Prize in that year was awarded to Danish chemist Jens Christian Skou for his discovery of the Na+/K+-ATPase.
RNA
Research on RNA has led to many important biological discoveries and numerous Nobel Prizes. Nucleic acids were discovered in 1868 by Friedrich Miescher, who called the material 'nuclein' since it was found in the nucleus. It was later discovered that prokaryotic cells, which do not have a nucleus, also contain nucleic acids. The role of RNA in protein synthesis was suspected already in 1939. Severo Ochoa won the 1959 Nobel Prize in Medicine (shared with Arthur Kornberg) after he discovered an enzyme that can synthesize RNA in the laboratory. However, the enzyme discovered by Ochoa (polynucleotide phosphorylase) was later shown to be responsible for RNA degradation, not RNA synthesis. In 1956 Alex Rich and David Davies hybridized two separate strands of RNA to form the first crystal of RNA whose structure could be determined by X-ray crystallography.
Ribonucleotide
Prior to James Watson and Francis Crick's landmark paper that detailed the structure of DNA from Rosalind Franklin's X-ray crystallography image, there were several historical scientists that also contributed to its discovery. Friedrich Miescher, a Swiss physician, who, in 1869, was first to isolate and identify nucleic substance from the nuclei of white blood cells he later called “nuclein”, paving the way for the discovery of DNA. Following Mieschers work, was the German biochemist, Albrecht Kossel, who, in 1878, isolated the non-protein components of “nuclein”, and discovered the five nucleobases present in nucleic acids: adenine, cytosine, guanine, thymine and uracil. Although some fundamental facts were known about nucleic acids due to these early discoveries, its structure and function remained a mystery.
Stanford Moore
In 1958 he and William H. Stein developed the first automated amino acid analyzer, which facilitated the determination of protein sequences. In 1959 Moore and Stein announced the first determination of the complete amino acid sequence of an enzyme, ribonuclease, work which was cited in the Nobel award. He never married.
History of biochemistry
One of the most prolific of these modern biochemists was Hans Krebs who made huge contributions to the study of metabolism. Krebs was a student of extremely important Otto Warburg, and wrote a biography of Warburg by that title in which he presents Warburg as being educated to do for biological chemistry what Fischer did for organic chemistry. Which he did. Krebs discovered the urea cycle and later, working with Hans Kornberg, the citric acid cycle and the glyoxylate cycle. These discoveries led to Krebs being awarded the Nobel Prize in physiology in 1953, which was shared with the German biochemist Fritz Albert Lipmann who also codiscovered the essential cofactor coenzyme A.
Aaron Novick
Aaron Novick (June 24, 1919 – December 21, 2000) is considered one of the founders of molecular biology. He started the University of Oregon's Institute of Molecular Biology, believed to be the first of its kind in the world, in 1959.
DnaG
DnaG is a bacterial DNA primase and is encoded by the "dnaG" gene. The enzyme DnaG, and any other DNA primase, synthesizes short strands of RNA known as oligonucleotides during DNA replication. These oligonucleotides are known as primers because they act as a starting point for DNA synthesis. DnaG catalyzes the synthesis of oligonucleotides that are 10 to 60 nucleotides (the fundamental unit of DNA and RNA) long, however most of the oligonucleotides synthesized are 11 nucleotides. These RNA oligonucleotides serve as primers, or starting points, for DNA synthesis by bacterial DNA polymerase III (Pol III). DnaG is important in bacterial DNA replication because DNA polymerase cannot initiate the synthesis of a DNA strand, but can only add nucleotides to a preexisting strand. DnaG synthesizes a single RNA primer at the origin of replication. This primer serves to prime leading strand DNA synthesis. For the other parental strand, the lagging strand, DnaG synthesizes an RNA primer every few kilobases (kb). These primers serve as substrates for the synthesis of Okazaki fragments.
Lund University
Per Georg Scheutz (1785–1873) was a Swedish lawyer, publicist and inventor who created the first working programmable difference engine with a printing unit. Martin Wiberg (1826–1905) was a prolific inventor who, among many things, created the first difference engine the size of a sewing machine that could calculate and print logarithmic tables. Johannes Rydberg (1854–1919) was a renowned physicist famous for the Rydberg formula and the Rydberg constant. Carl Charlier (1862–1934) was an internationally acclaimed astronomer who made important contributions to astronomy as well as statistics and was awarded the James Craig Watson Medal in 1924 and the Bruce Medal in 1933. Manne Siegbahn (1886–1978), a student of Rydberg, was awarded the Nobel Prize in Physics 1924 for his discoveries and research in the field of X-ray spectroscopy. Oskar Klein (1894–1977) was an internationally renowned theoretical physicist famous for the Klein-Kaluza theory, the Klein-Gordon equation, and the Klein-Nishina formula. Pehr Edman (1916–1977) was a renowned biochemist who developed a method for sequencing proteins, known as the Edman degradation, and has been called the father of modern biochemistry. Hellmuth Hertz (1920–1990) developed the echocardiography together with Inge Edler (see above), and was also the first to develop the ink jet technology of printing. Lars Hörmander (1931–2012) is sometimes considered the foremost contributor to the modern theory of linear partial differential equations and received the Fields Medal in 1962 for his early work on equations with constant coefficients. Karl Johan Åström (1934–) is a notable control theorist, who in 1993 was awarded the IEEE Medal of Honor for "fundamental contributions to theory and applications of adaptive control technology". Sven Mattisson (1955–) is an electrical engineer who was one of the developers of the Bluetooth technology.
Coenzyme Q10
CoQ was first discovered by Fredrick L. Crane and colleagues at the University of Wisconsin–Madison Enzyme Institute in 1957. In 1958, its chemical structure was reported by Karl Folkers and coworkers at Merck. In the early 1970s, Gian Paolo Littarru and Karl Folkers observed that a deficiency of CoQ was associated with human heart disease. The 1980s witnessed a steep rise in the number of clinical trials due to the availability of large quantities of pure CoQ and methods to measure plasma and blood CoQ concentrations. The redox functions of CoQ in cellular energy production and antioxidant protection are based on the ability to exchange two electrons in a redox cycle between ubiquinol (reduced CoQ) and ubiquinone (oxidized CoQ). The antioxidant role of the molecule as a free-radical scavenger was widely studied by Lars Ernster. Numerous scientists around the globe started studies on this molecule since then in relation to various diseases including cardiovascular diseases and cancer.
Denis Jordan
Whilst at Nottingham 'Doj' Jordan was a key member of the team whose research made important contributions to the eventual decoding of DNA in 1953. Jordan worked with John Masson Gulland, Michael Creeth and others on a series of experiments in 1947 which firstly created high quality DNA, then measured its viscocity, and finally demonstrated the hydrogen bonds within the molecule. Their discoveries were ultimately acknowledged by James Watson as critical contributions even if he did at first dismiss them incorrectly: "...a rereading of J. M. Gulland's and D. O. Jordan's papers...made me finally realize the strength of their conclusion that a large fraction, if not all, of the bases formed hydrogen bonds to other bases.” Gulland and Jordan's work was also acknowledged in the first papers concerning the decoding of DNA by Rosalind Franklin and Raymond Gosling. It has however been argued that the work of the Nottingham team was subsequently overlooked until commemorations were held in 2010 and 2017
J. Robert Oppenheimer
Julius Robert Oppenheimer (; April 22, 1904 – February 18, 1967) was an American theoretical physicist and professor of physics at the University of California, Berkeley. Oppenheimer was the wartime head of the Los Alamos Laboratory and is among those who are credited with being the "father of the atomic bomb" for their role in the Manhattan Project, the World War II undertaking that developed the first nuclear weapons used in the atomic bombings of Hiroshima and Nagasaki. The first atomic bomb was detonated on July 16, 1945, in the Trinity test in New Mexico; Oppenheimer later remarked that it brought to mind words from the "Bhagavad Gita": "Now I am become Death, the destroyer of worlds."
Monsanto
In the mid‑1960s, William Standish Knowles and his team invented a way to selectively synthesize enantiomers via asymmetric hydrogenation. This was the first method for the catalytic production of pure chiral compounds. Knowles' team designed the "first industrial process to chirally synthesize an important compound"—L‑dopa, which is used to treat Parkinson's disease. In 2001, Knowles and Ryōji Noyori won the Nobel Prize in Chemistry. In the mid-1960s, chemists at Monsanto developed the Monsanto process for making acetic acid, which until 2000 was the most widely used production method. In 1964, Monsanto chemists invented AstroTurf (initially ChemGrass).
Otto Hahn
In February 1921, Otto Hahn published the first report on his discovery of uranium Z (later known as Pa ), the first example of nuclear isomerism. Gerlach remarked that this was "a discovery that was not understood at the time but later became highly significant for nuclear physics". Not until 1936 did Carl Friedrich von Weizsäcker provide a theoretical explanation of the phenomenon of nuclear isomerism. For this discovery, whose full significance was recognized by very few, Hahn was again proposed, from 1923 till 1929, for the Nobel Prize in Chemistry by Naunyn, Goldschmidt, and Max Planck.
Synthetic biology
Driven by dramatic decreases in costs of oligonucleotide ("oligos") synthesis, the sizes of DNA constructions from oligos have increased to the genomic level. In 2000, researchers reported synthesis of the 9.6 kbp (kilo bp) Hepatitis C virus genome from chemically synthesized 60 to 80-mers. In 2002 researchers at SUNY Stony Brook succeeded in synthesizing the 7741 bp poliovirus genome from its published sequence, producing the second synthetic genome, spanning two years. In 2003 the 5386 bp genome of the bacteriophage Phi X 174 was assembled in about two weeks. In 2006, the same team, at the J. Craig Venter Institute, constructed and patented a synthetic genome of a novel minimal bacterium, "Mycoplasma laboratorium" and were working on getting it functioning in a living cell.
Patterns in nature
The American photographer Wilson Bentley took the first micrograph of a snowflake in 1885.
In 1952, Alan Turing (1912–1954), better known for his work on computing and codebreaking, wrote "The Chemical Basis of Morphogenesis", an analysis of the mechanisms that would be needed to create patterns in living organisms, in the process called morphogenesis. He predicted oscillating chemical reactions, in particular the Belousov–Zhabotinsky reaction. These activator-inhibitor mechanisms can, Turing suggested, generate patterns (dubbed "Turing patterns") of stripes and spots in animals, and contribute to the spiral patterns seen in plant phyllotaxis.
Gustav Embden
Embden conducted studies on carbohydrate metabolism and muscle contraction, and he was the first to discover and link together all the steps involved in the conversion of glycogen to lactic acid. In 1918, Otto Fritz Meyerhof's work on cellular metabolism showed that the process involved the breakdown of glucose to lactic acid. Embden is known for having worked out the precise steps involved in this breakdown. Henceforth, this cellular metabolic sequence from glycogen to lactic acid became known as the Embden–Meyerhof pathway.
Mysore A. Viswamitra
Mysore Ananthamurthy Viswamitra (1932–2001) was an Indian molecular biophysicist and crystallographer, known for his pioneering work on the X-Ray structural studies of DNA fragments and nucleotide coenzyme molecules. His work is reported to have assisted in the development of the concept of sequence-dependent oligonucleotide conformation. He was an INSA senior scientist and an MSIL chair professor of physics at the Indian Institute of Science and a visiting professor at the University of Cambridge.
Atomic Age
The concept of a nuclear chain reaction was hypothesized in 1933, shortly after Chadwick's discovery of the neutron. Only a few years later, in December 1938 nuclear fission was discovered by Otto Hahn and his assistant Fritz Strassmann, and proved with Hahn's radiochemical methods. The first artificial self-sustaining nuclear chain reaction (Chicago Pile-1, or CP-1) took place in December 1942 under the leadership of Enrico Fermi.
Otto Kandler
Otto Kandler was very interested in plant growth processes, photosynthesis, metabolism, especially of carbohydrates. 
As the first in Germany he started to grow isolated plant tissue cultures (e.g. of stems, roots, sprouts, embryos) "in vitro"
to study metabolism and the effect of auxins under defined "in vitro" conditions. As mentioned above, this formed the subject of his dissertation (summa cum laude) in 1949.
In his contribution „Historical perspectives on queries concerning photophosphorylation” Kandler describes the beginnings of photophosphorylation research and how he became interested: In 1948, he was inspired by a lecture on the phosphate metabolism of yeast by Feodor Lynen (1964 Nobel Prize in Physiology or Medicine). In these years, in the aftermath of World War II, the original Chemical Institute of the Ludwig Maximilian University of Munich was still in ruins and Feodor Lynen and his assistant Helmut Holzer were working temporarily as guests in the Botanical Institute just next door to the laboratory where Kandler was engaged in his thesis in botany. Kandler was impressed by the experimental methods in Lynen’s laboratory and got acquainted with them; Holzer and Kandler became close friends. At that time, Holzer was able to present the first evidence for ATP formation in yeast oxidizing butanol to butyric acid. Kandler then decided to transfer their techniques to measuring phosphorylation rates "in vivo" to photosynthesis studies in "Chlorella".
Site-directed mutagenesis
In 1971, Clyde Hutchison and Marshall Edgell showed that it is possible to produce mutants with small fragments of phage ϕX174 and restriction nucleases. Hutchison later produced with his collaborator Michael Smith in 1978 a more flexible approach to site-directed mutagenesis by using oligonucleotides in a primer extension method with DNA polymerase. For his part in the development of this process, Michael Smith later shared the Nobel Prize in Chemistry in October 1993 with Kary B. Mullis, who invented polymerase chain reaction.
Alex Stokes
Alexander (Alec) Rawson Stokes (27 June 1919 – 5 February 2003) was a co-author of the second of the three papers published sequentially in "Nature" on 25 April 1953 announcing the presumed molecular structure of DNA. The first was authored by Francis Crick and James Watson, and the third by Rosalind Franklin and Raymond Gosling. The Nobel Prize in Physiology or Medicine was awarded in 1962 to Crick, Watson, and Wilkins for this work.
Colin Munro MacLeod
Colin Munro MacLeod (January 28, 1909 – February 11, 1972) was a Canadian-American geneticist. He was one of a trio of scientists who discovered that deoxyribonucleic acid, or DNA is responsible for the transformation of the physical characteristics of bacteria, which subsequently led to its identification as the molecule responsible for heredity.
Ubiquitin
Ubiquitin (originally, ubiquitous immunopoietic polypeptide) was first identified in 1975 as an 8.6 kDa protein of unknown function expressed in all eukaryotic cells. The basic functions of ubiquitin and the components of the ubiquitination pathway were elucidated in the early 1980s at the Technion by Aaron Ciechanover, Avram Hershko, and Irwin Rose for which the Nobel Prize in Chemistry was awarded in 2004.
Genomics
In addition to his seminal work on the amino acid sequence of insulin, Frederick Sanger and his colleagues played a key role in the development of DNA sequencing techniques that enabled the establishment of comprehensive genome sequencing projects. In 1975, he and Alan Coulson published a sequencing procedure using DNA polymerase with radiolabelled nucleotides that he called the "Plus and Minus technique". This involved two closely related methods that generated short oligonucleotides with defined 3' termini. These could be fractionated by electrophoresis on a polyacrylamide gel (called polyacrylamide gel electrophoresis) and visualised using autoradiography. The procedure could sequence up to 80 nucleotides in one go and was a big improvement, but was still very laborious. Nevertheless, in 1977 his group was able to sequence most of the 5,386 nucleotides of the single-stranded bacteriophage φX174, completing the first fully sequenced DNA-based genome. The refinement of the "Plus and Minus" method resulted in the chain-termination, or Sanger method (see below), which formed the basis of the techniques of DNA sequencing, genome mapping, data storage, and bioinformatic analysis most widely used in the following quarter-century of research. In the same year Walter Gilbert and Allan Maxam of Harvard University independently developed the Maxam-Gilbert method (also known as the "chemical method") of DNA sequencing, involving the preferential cleavage of DNA at known bases, a less efficient method. For their groundbreaking work in the sequencing of nucleic acids, Gilbert and Sanger shared half the 1980 Nobel Prize in chemistry with Paul Berg (recombinant DNA).
CpG Oligodeoxynucleotide
One of the first Class A ODN, ODN 2216, was described in 2001 by Krug et al. This class of ODN was distinctly different from the previously described Class B ODN (i.e., ODN 2006) in that it stimulated the production of large amounts of Type I interferons, the most important one being IFNα, and induced the maturation of plasmacytoid dendritic cells. Class A ODN are also strong activators of NK cells through indirect cytokine signaling.
Oliver Patterson Watts
Oliver Patterson Watts (1865–1953) was a professor of chemical engineering and applied electrochemistry at the University of Wisconsin–Madison. Born in Thomaston, Maine, Watts received his bachelor's degree from Bowdoin College. He was the first person to be awarded a Ph.D. in the field of chemical engineering at the University of Wisconsin, where he served as a professor until 1937. Watts is famously known for his development of the hot nickel plating bath known as the "Watts Bath" which he first described in a paper published in the year 1915.
Andrew R. Barron
Following from his work on the chalcogenides, Barron was the first person to crystallographically characterise an alumoxane in 1993. These structures were spectroscopically consistent with methylalumoxane and he showed that despite being octet molecules they had significant Lewis acidity, he termed this as “Latent Lewis acidity”, and showed that this mechanism applied to a number of MAO style polymerization systems. Barron’s model has been evolved by others but is essentially the same as now widely accepted.
Alloxan
The compound was discovered by Justus von Liebig and Friedrich Wöhler. It is one of the oldest named organic compounds. It was originally prepared in 1818 by Brugnatelli (1761-1818) and was named in 1838 by Wöhler and Liebig. The name "Alloxan" emerged from an amalgamation of the words "allantoin" and "Oxalsäure" (oxalic acid). The alloxan model of diabetes was first described in rabbits by Dunn, Sheehan and McLetchie in 1943. The name is derived from allantoin, a product of uric acid excreted by the fetus into the allantois, and oxaluric acid derived from oxalic acid and urea, found in urine.
Oligonucleotide
Oligonucleotides are characterized by the sequence of nucleotide residues that make up the entire molecule. The length of the oligonucleotide is usually denoted by "-mer" (from Greek "meros", "part"). For example, an oligonucleotide of six nucleotides (nt) is a hexamer, while one of 25 nt would usually be called a "25-mer". Oligonucleotides readily bind, in a sequence-specific manner, to their respective complementary oligonucleotides, DNA, or RNA to form duplexes or, less often, hybrids of a higher order. This basic property serves as a foundation for the use of oligonucleotides as probes for detecting DNA or RNA. Examples of procedures that use oligonucleotides include DNA microarrays, Southern blots, ASO analysis, fluorescent in situ hybridization (FISH), PCR, and the synthesis of artificial genes. Oligonucleotides are also indispensable elements in antisense therapy.
Biomolecular engineering
Site-directed mutagenesis is a technique that has been around since the 1970s. The early days of research in this field yielded discoveries about the potential of certain chemicals such as bisulfite and aminopurine to change certain bases in a gene. This research continued, and other processes were developed to create certain nucleotide sequences on a gene, such as the use of restriction enzymes to fragment certain viral strands and use them as primers for bacterial plasmids. The modern method, developed by Michael Smith in 1978, uses an oligonucleotide that is complementary to a bacterial plasmid with a single base pair mismatch or a series of mismatches.
Hans Adolf Krebs
While working at the Medical Clinic of the University of Freiburg, Krebs met Kurt Henseleit, with whom he investigated the chemical process of urea formation. In 1904, two Germans A. Kossel and H. D. Dakin had shown that arginine could be hydrolysed by the enzyme arginase to form ornithine and urea in inorganic reaction. Based on this reaction, Krebs and Henseleit postulated that in living cells, similar reaction could occur, and that ornithine and citrulline could be the intermediate reactions. Krebs started working on the possible method for the synthesis of arginine. Using his Warburg manometer, he mixed a slice of liver with purified ornithine and citrulline. He found that citrulline acted as a catalyst in the metabolic reactions of urea from ammonia and carbon dioxide. He and Henseleit published their discovery in 1932. Thus the urea cycle (or "ornithine cycle") was established, and it was the first metabolic cycle to be discovered.
Oxygen
It is also commonly claimed that oxygen was first discovered by Swedish pharmacist Carl Wilhelm Scheele. He had produced oxygen gas by heating mercuric oxide and various nitrates in 1771–2. Scheele called the gas "fire air" because it was then the only known agent to support combustion. He wrote an account of this discovery in a manuscript titled "Treatise on Air and Fire", which he sent to his publisher in 1775. That document was published in 1777.
Mahlon Hoagland
By the time Hoagland had joined Huntington Laboratories, his colleagues there were well known for their work in protein synthesis. In the early 1950s Hoagland and his associates were able to show that polypeptide synthesis occurs on ribosomes. They did this by giving a rat injections of radioactive amino acids, waiting for a defined period of time, extracting the liver, and examining sub-cellular fractions for radioactivity. He found that after longer periods of times (hours, days) radioactively labeled proteins were present in all subcellular fractions. However, if they allowed less time to pass, radioactivity was found in only certain particles, which they deemed the sites of proteins synthesis. These particles were named ribosomes.
Charles Frédéric Kuhlmann
Charles Frédéric Kuhlmann (22 May 1803 – 27 January 1881) was a French chemist who patented the reaction for converting ammonia to nitric acid, which was later used in the Ostwald process.
Nitrophosphate process
The nitrophosphate process (also known as the Odda process) was a method for the industrial production of nitrogen fertilizers invented by Erling Johnson in the municipality of Odda, Norway around 1927.
Organoaluminium chemistry
The first organoaluminium compound (CH)AlI was discovered in 1859. Organoaluminium compounds were, however, little known until the 1950s when Karl Ziegler and colleagues discovered the direct synthesis of trialkylaluminium compounds and applied these compounds to catalytic olefin polymerization. This line of research ultimately resulted in the Nobel Prize to Ziegler.
Oppenheimer security hearing
Still, Oppenheimer was not well known before the war, and certainly not as renowned as his friend and colleague Ernest O. Lawrence, who was awarded the Nobel Prize in Physics in 1939 for his invention of the cyclotron. But as an experimental physicist, Lawrence had come to rely on Oppenheimer, and it was Lawrence who brought Oppenheimer into the effort to develop an atomic bomb, which became known as the Manhattan Project. Brigadier General Leslie R. Groves, Jr., who became director of the Manhattan Project on September 8, 1942, met Oppenheimer at Berkeley, where Oppenheimer briefed Groves on his work on the "Super" (thermonuclear) bomb. Oppenheimer told Groves on October 8 that the Manhattan Project needed a dedicated weapons development laboratory. Groves agreed, and after a second meeting with Oppenheimer on a train on October 15, decided that Oppenheimer was the man he needed to head what became the Los Alamos Laboratory, despite Oppenheimer's lack of a Nobel Prize or administrative experience.
Oligomer restriction
The Oligomer Restriction technique was developed as a variation of the Restriction Fragment Length Polymorphism (RFLP) assay method, with the hope of avoiding the laborious Southern blotting step used in RFLP analysis. OR was conceived by Randall Saiki and Henry Erlich in the early 1980s, working at Cetus Corporation in Emeryville, California. It was patented in 1984 and published in 1985, having been applied to the genomic mutation responsible for Sickle Cell Anemia. OR was soon replaced by the more general technique of Allele Specific Oligonucleotide (ASO) probes.
Woeseian revolution
This reorganization caused for an initial push back, being accepted nearly a decade after its publication. Possible factors that led to the initial criticism of the discovery include Woese’s oligonucleotide cataloging of which he was one of “only two or three people in the world” to be able to execute this method let alone read the films. Also, Woese’s background was in physics whereas most of the research was being done in the realm of microbiologists.
Nucleoside phosphoramidite
Nucleoside phosphoramidites are derivatives of natural or synthetic nucleosides. They are used to synthesize oligonucleotides, relatively short fragments of nucleic acid and their analogs. Nucleoside phosphoramidites were first introduced in 1981 by Beaucage and Caruthers. To avoid undesired side reactions, reactive hydroxy and exocyclic amino groups present in natural or synthetic nucleosides are appropriately protected. As long as a nucleoside analog contains at least one hydroxy group, the use of the appropriate protecting strategy allows one to convert that to the respective phosphoramidite and to incorporate the latter into synthetic nucleic acids. To be incorporated in the middle of an oligonucleotide chain using phosphoramidite strategy, the nucleoside analog must possess two hydroxy groups or, less often, a hydroxy group and another nucleophilic group (amino or mercapto). Examples include, but are not limited to, alternative nucleotides, LNA, morpholino, nucleosides modified at the 2'-position (OMe, protected NH, F), nucleosides containing non-canonical bases (hypoxanthine and xanthine contained in natural nucleosides inosine and xanthosine, respectively, tricyclic bases such as G-clamp, etc.) or bases derivatized with a fluorescent group or a linker arm.
History of molecular biology
Using X-ray diffraction, as well as other data from Rosalind Franklin and her information that the bases were paired, James Watson and Francis Crick arrived at the first accurate model of DNA's molecular structure in 1953, which was accepted through inspection by Rosalind Franklin. The discovery was announced on February 28, 1953; the first Watson/Crick paper appeared in "Nature" on April 25, 1953. Sir Lawrence Bragg, the director of the Cavendish Laboratory, where Watson and Crick worked, gave a talk at Guy's Hospital Medical School in London on Thursday, May 14, 1953 which resulted in an article by Ritchie Calder in the "News Chronicle" of London, on Friday, May 15, 1953, entitled "Why You Are You. Nearer Secret of Life." The news reached readers of "The New York Times" the next day; Victor K. McElheny, in researching his biography, "Watson and DNA: Making a Scientific Revolution", found a clipping of a six-paragraph "New York Times" article written from London and dated May 16, 1953 with the headline "Form of `Life Unit' in Cell Is Scanned." The article ran in an early edition and was then pulled to make space for news deemed more important. ("The New York Times" subsequently ran a longer article on June 12, 1953). The Cambridge University undergraduate newspaper also ran its own short article on the discovery on Saturday, May 30, 1953. Bragg's original announcement at a Solvay Conference on proteins in Belgium on 8 April 1953 went unreported by the press. In 1962 Watson, Crick, and Maurice Wilkins jointly received the Nobel Prize in Physiology or Medicine for their determination of the structure of DNA.
Exopolyphosphatase
PPX was discovered by the lab of Nobel laureate Arthur Kornberg in 1993 and is part of the polyphosphate operon along with polyphosphate kinase, the enzyme which synthesizes polyphosphate. The Kornberg lab was very interested in polyphosphate and published a series of papers elucidating the metabolism and roles of polyphosphate "in vivo". Their interest in polyphosphate led them to identify and characterize the polyphosphate operon (which includes polyphosphate kinase [PPK] and PPX) and develop a wide variety of assays and techniques for quantification of polyphosphate production and degradation, "in vitro" and "in vivo". The results of these studies of polyphosphate by the Kornberg lab led Kornberg to speculate that due to its high energy and phosphate content and the degree to which it is conserved across species, polyphosphate may have been the precursor to RNA, DNA, and proteins.
Har Gobind Khorana
Their Nobel lecture was delivered on 12 December 1968. Khorana was the first scientist to chemically synthesize oligonucleotides. This achievement, in the 1970s, was also the world's first synthetic gene; in later years, the process has become widespread. Subsequent scientists referred to his research while advancing genome editing with the CRISPR/Cas9 system.
Otto Hahn
Otto Hahn (8 March 1879 – 28 July 1968) was a German chemist and pioneer in the fields of radioactivity and radiochemistry. Otto Hahn discovered nuclear fission in 1938. He is referred to as the father of nuclear chemistry. He was awarded the Nobel Prize in Chemistry in 1944 for the discovery and the radiochemical proof of nuclear fission. This process is exploited by nuclear reactors and is one of the basics of nuclear weapons that were developed in the U.S. during World War II.
George Cowan
Cowan was born in Worcester, Massachusetts. In 1941, at the age of twenty one, after graduating from Worcester Polytechnic Institute in chemistry, he worked on the cyclotron project at Princeton University with the intention of taking graduate courses in physics. He worked there with future Nobel Prize Laureate Eugene Wigner, who would design the first uranium chain reactor. In 1941, George participated in taking measurements essential to determining whether the chain reaction in uranium could be achieved. His knowledge of chemistry and nuclear physics experience provided expertise on a number of things necessary to the Manhattan Project. In 1942, Wigner, Cowan, and several others transferred to the Metallurgy Lab at the University of Chicago where the first atomic pile was being developed under Enrico Fermi. Starting as a junior member, Cowan became a jack-of-all-trades, capable of such skills as machining graphite blocks used for control of the pile's reaction rate and in casting uranium metal. In 1942, the Chicago Pile 1 (CP-1) generated the first controlled nuclear reaction. This controlled release of energy from the nucleus of the atom enabled development of a method to obtain nuclear fuel for the first atomic weapons. His experience made him one of the experts on the chemistry of radioactive elements in the field of applied nuclear fission. Since he was single and in possession of high expertise, project managers transferred him around the nation to help resolve bottlenecks. He was one of the select group with knowledge of the separate components of the project, kept separate for security reasons. He received a draft deferment from the president of the United States for possessing skills uniquely useful to the war effort.
Deoxyribozyme
The first known deoxyribozyme was a ribonuclease, discovered in 1994 by Ronald Breaker while a postdoctoral fellow in the laboratory of Gerald Joyce at the Scripps Research Institute.
This deoxyribozyme, later named GR-5,
catalyzes the Pb-dependent cleavage of a single ribonucleotide phosphoester at a rate that is more than 100-fold compared to the uncatalyzed reaction. Subsequently, additional RNA-cleaving deoxyribozymes that incorporate different metal cofactors were developed, including the Mg-dependent E2 deoxyribozyme
and the Ca-dependent Mg5 deoxyribozyme.
These first deoxyribozymes were unable to catalyze a full RNA substrate strand, but by incorporating the full RNA substrate strand into the selection process, deoxyribozymes which functioned with substrates consisting of either full RNA or full DNA with a single RNA base were both able to be utilized.
The first of these more versatile deoxyribozymes, 8-17 and 10-23, are currently the most widely studied deoxyribozymes. In fact, many subsequently discovered deoxyribozymes were found to contain the same catalytic core motif as 8-17, including the previously discovered Mg5, suggesting that this motif represents the "simplest solution for the RNA cleavage problem".
The 10-23 DNAzyme contains a 15-nucleotide catalytic core that is flanked by two substrate recognition domains. This DNAzyme cleaves complementary RNAs efficiently in a sequence specific manner between an unpaired purine and a paired pyrimidine. DNAzymes targeting AU or GU vs. GC or AC are more effective. Furthermore, the RNA cleavage rates have been shown to increase after the introduction of intercalators or the substitution of deoxyguanine with deoxyinosine at the junction of the catalytic loop. Specifically, the addition of 2’-O-methyl modifications to the catalytic proved to significantly increase the cleavage rate both in vitro and in vivo.
Robert Burns Woodward
In the early 1960s, Woodward began work on what was the most complex natural product synthesized to date—vitamin B. In a remarkable collaboration with his colleague Albert Eschenmoser in Zurich, a team of almost one hundred students and postdoctoral workers worked for many years on the synthesis of this molecule. The work was finally published in 1973, and it marked a landmark in the history of organic chemistry. The synthesis included almost a hundred steps, and involved the characteristic rigorous planning and analyses that had always characterised Woodward's work. This work, more than any other, convinced organic chemists that the synthesis of any complex substance was possible, given enough time and planning (see also palytoxin, synthesized by the research group of Yoshito Kishi, one of Woodward's postdoctoral students). As of 2016, no other total synthesis of Vitamin B has been published.
Mariano Barbacid
Mariano Barbacid (born 4 October 1949 in Madrid) is a Spanish molecular biochemist who discovered the first oncogene. His discovery was published in the prestigious journal Nature in 1982 in an article titled "A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder-carcinoma oncogene". He spent the following months extending his research, eventually discovering that such oncogene was the mutation of an allele of the Ras subfamily, as well as its activation mechanism.
Theodore Nicolas Gobley
Theodore (Nicolas) Gobley (), who first isolated, and ultimately determined the chemical structure of lecithin, the first identified and characterized member of the phospholipids class, and a pioneer researcher in the study and analysis of the chemical components of brain tissues, was born in Paris on 11 May 1811 and died in Bagneres-de-Luchon (a small city in central Pyrenees famous in the second half of the 19th century for its thermal waters) on 1 September 1876.
Jacques Masquelier
Jack Masquelier was a French scientist. In July 1948 he published his doctoral thesis based on his successful isolation and chemical description of the phytonutrient we know today as oligomeric proanthocyanidins or OPCs. That same year he filed a patent for the industrial method of producing the first botanical product based on OPCs.
Derek George Smyth
Derek Smyth was Head of the Laboratory of Peptide Chemistry at the National Institute for Medical Research (NIMR) from 1972-1992. He had worked previously with Professor Joseph Fruton at Yale University where he gained experience in protein and peptide chemistry (1-3) and in 1960 transferred to Rockefeller University in New York City where in the laboratory of Stanford Moore and William Stein he reinvestigated and established the definitive amino acid sequence of pancreatic ribonuclease (4-9), the first enzyme to have its primary structure determined. On moving to NIMR in 1963, Derek Smyth prepared two novel derivatives of oxytocin, N-carbamylcystine-1-oxytocin and N-carbamyl cystine-1-O-carbamyltyrosine-2-oxytocin, and in a collaborative study with Gordon Bisset it was shown that while the monocarbamyl hormone retained weak biological activity (10), the dicarbamyl derivative proved to be a specific inhibitor of oxytocin devoid of intrinsic activity (11,12), demonstrating that the action of the hormone takes place in consecutive stages that could be studied independently (13). Maintaining his interest in protein structure (14-16), Derek Smyth together with Sayaki Utsumi unravelled the structure of the ‘hinge region’ of rabbit 7S gamma globulin, juxtaposing the FAB and (FAB)2 fragments of the 4-chain IgG molecule, locating the bridge that links the two half molecules and revealing a new oligosaccharide chain (17-21). He followed this by sequencing the connecting peptide (C-peptide) of proinsulin (22-25), modelling its contribution to the 3 dimensional structure of the prohormone (25) and building on the crystallographic studies of insulin by Tom Blundell and his colleagues. The enzymatic processing of prohormones to release their biologically active constituents was a dominant lifetime interest. His major contribution came from studies of β-lipotropin (61), now recognised as a component of the pro-opiomelanocortin locus. In a classic series of papers from 1975-1982, he and his collaborators* (26-34) showed that the C-terminal fragment of lipotropin, first isolated in his laboratory from pituitary (35-37), was an endogenously expressed opiate (38). They showed that this 31 amino acid peptide, now known to all as β-endorphin, is a neurohormone with potent analgesic activity (39-43) and producing profound behavioural effects in the brain (40, 44, 45). Later, with Alan Bradbury, he elucidated the mechanism of peptide amidation, a post-translational modification essential for the activity of many peptide hormones (46-49) and more recently he and his colleagues have isolated a series of pyroglutamyl peptide amides that may play an important role in the regulation of hormone activity (50-54). After retiring from NIMR, he continued his research at the Institute for Molecular Biology in Salzburg (55, 56) and then in the Pharmacology Department of the University of Murcia, Spain (57-59). For several years (1977-1982) he assisted the Nobel Committee in their nomination of candidates for the Nobel Prize in Physiology or Medicine and in 1997 he was elected as an honorary member (Excmo) of the Royal Academy of Medicine and Surgery in Murcia (60).
Eckard Wimmer
Using the nucleotide sequence of the genome deciphered in 1981, Wimmer followed up on the work published in 1991 by synthesizing chemically the genome in the form of double stranded DNA (“cDNA”), which was then transcribed enzymatically into genome RNA and “booted to life” in the cell free system. This work, published in 2002 by Cello, Paul and Wimmer, was the first test-tube synthesis of an organism in the absence of a natural template achieved outside living cells. The poliovirus synthesis caught global attention, high praise, ridicule and fierce condemnation. Several years later, Wimmer published an essay in EMBO Reports reflecting on hotly debated issues that this new kind of research generated (ethical matters, questions about the global eradication of poliovirus, concerns of “dual use research”). Apart from providing a ‘proof of principle,’ the experiment heralded the total synthesis of organisms with computers as parents, a strategy that allows investigating the structure and function of an organism’s biology to an extent hitherto impossible. Meanwhile, synthetic biology has led to a new kind of RNA virus genetics and has been used to develop rapid methods for computer-aided chemical synthesis of viral recoded genomes. This strategy allows for the generation of new vaccines in a very short time.
Superoxide dismutase
Irwin Fridovich and Joe McCord at Duke University discovered the enzymatic activity of superoxide dismutase in 1968. SODs were previously known as a group of metalloproteins with unknown function; for example, CuZnSOD was known as erythrocuprein (or hemocuprein, or cytocuprein) or as the veterinary anti-inflammatory drug "Orgotein". Likewise, Brewer (1967) identified a protein that later became known as superoxide dismutase as an indophenol oxidase by protein analysis of starch gels using the phenazine-tetrazolium technique.
Pharmacogenomics
Pharmacogenomics was first recognized by Pythagoras around 510 BC when he made a connection between the dangers of fava bean ingestion with hemolytic anemia and oxidative stress. This identification was later validated and attributed to deficiency of G6PD in the 1950s and called favism. Although the first official publication dates back to 1961, circa 1950s marked the unofficial beginnings of this science. Reports of prolonged paralysis and fatal reactions linked to genetic variants in patients who lacked butyryl-cholinesterase (‘pseudocholinesterase’) following administration of succinylcholine injection during anesthesia were first reported in 1956. The term pharmacogenetic was first coined in 1959 by Friedrich Vogel of Heidelberg, Germany (although some papers suggest it was 1957 or 1958). In the late 1960s, twin studies supported the inference of genetic involvement in drug metabolism, with identical twins sharing remarkable similarities to drug response compared to fraternal twins. The term pharmacogenomics first began appearing around the 1990s.
Michael Smith (chemist)
Smith's particular area of interest remained the synthesis of olgonucleotides and the characterization of their properties. A sabbatical at the University of Cambridge in England with Fred Sanger placed Smith at the forefront of research into the organization of genes and genomes and methods of sequencing large DNA molecules. He returned from England as one of the world's leading molecular biologists.
Solid-phase synthesis
Relatively short fragments of DNA, RNA, and modified oligonucleotides are also synthesised by the solid-phase method. Although oligonucleotides can be synthesised in a flask, they are almost always synthesised on solid phase using a DNA/RNA synthesizer. For a more comprehensive review, see oligonucleotide synthesis. The method of choice is generally phosphoramidite chemistry, developed in the 1980s.
Oligonucleotide
Oligonucleotides composed of 2'-deoxyribonucleotides (oligodeoxyribonucleotides) are fragments of DNA and are often used in the polymerase chain reaction, a procedure that can greatly amplify almost any small amount of DNA. There, the oligonucleotide is referred to as a primer, allowing DNA polymerase to extend the oligonucleotide and replicate the complementary strand.
Ribonucleotide
It wasn’t until the discovery of nucleotides in 1919 by Phoebus Levene, a Russian-Lithuanian biochemist that re-opened the gates of the DNA discovery. Levene first identified the carbohydrate component present in yeast RNA was in fact ribose. However, it was not until his discovery that the carbohydrate component in thymus nucleic acid was also a sugar but lacked one oxygen atom, termed deoxyribose, that his discovery was widely appreciated by the scientific community. Eventually, Levene was able to identify the correct order of which the components of RNA and DNA are put together, a phosphate-sugar-base unit, in which he later called a nucleotide. Although the order of nucleotide components were well understood by Levene, the structure of nucleotide arrangement in space and its genetic code still remained a mystery during the early years of his career.
Gilbert Stork
Gilbert Stork (December 31, 1921 – October 21, 2017) was an organic chemist. For a quarter of a century he was the Eugene Higgins Professor of Chemistry Emeritus at Columbia University. He is known for making significant contributions to the total synthesis of natural products, including a life-long fascination with the synthesis of quinine. In so doing he also made a number of contributions to mechanistic understanding of reactions, and performed pioneering work on enamine chemistry, leading to development of the Stork enamine alkylation.
It is believed he was responsible for the first planned stereocontrolled synthesis as well as the first natural product to be synthesised with high stereoselectivity.
James Watson
James Dewey Watson (born April 6, 1928) is an American molecular biologist, geneticist and zoologist. In 1953, he co-authored with Francis Crick the academic paper proposing the double helix structure of the DNA molecule. Watson, Crick, and Maurice Wilkins were awarded the 1962 Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".
Kary Mullis
Kary Banks Mullis (born December 28, 1944) is a Nobel Prize-winning American biochemist. In recognition of his invention of the polymerase chain reaction (PCR) technique, he shared the 1993 Nobel Prize in Chemistry with Michael Smith and earned the Japan Prize in the same year. The process was first described by Kjell Kleppe and 1968 Nobel laureate Har Gobind Khorana, and allows the amplification of specific DNA sequences. The invention made by Mullis allowed PCR to become a central technique in biochemistry and molecular biology, described by "The New York Times" as "highly original and significant, virtually dividing biology into the two epochs of before P.C.R. and after P.C.R."
Wöhler synthesis
It is argued that organic chemistry did not actually start with this discovery in 1828 but 4 years earlier with the synthesis of oxalic acid in 1824 also by Wöhler and also from the inorganic precursor cyanogen. It is also argued that vitalism was not put to bed either in 1828. His contemporaries Liebig and Pasteur never abandoned vitalism and it took until 1845 when Kolbe repeated an inorganic – organic conversion of carbon disulfide to acetic acid before vitalism started to lose supporters in serious numbers.
Phase-change memory
In the 1960s, Stanford R. Ovshinsky of Energy Conversion Devices first explored the properties of chalcogenide glasses as a potential memory technology. In 1969, Charles Sie published a dissertation, at Iowa State University that both described and demonstrated the feasibility of a phase-change-memory device by integrating chalcogenide film with a diode array. A cinematographic study in 1970 established that the phase-change-memory mechanism in chalcogenide glass involves electric-field-induced crystalline filament growth. In the September 1970 issue of "Electronics", Gordon Moore, co-founder of Intel, published an article on the technology. However, material quality and power consumption issues prevented commercialization of the technology. More recently, interest and research have resumed as flash and DRAM memory technologies are expected to encounter scaling difficulties as chip lithography shrinks.