Nucleic Acids:
Introduction:
Discovery of Nucleic acids and development of few concepts and discovery of important biological macromolecules:
Friedrich Miescher 1869.
Found Nuclein from pus cells obtained from bandaged cloths from a hospital. The region of cell that did not digest with the treatment of pepsin was from the nucleus, so the term Nuclein. (1869).
Robert Feulgen 1914:
Feulgen reagent was used in 1927-28 to demonstrate the presence of two types of Nucleic acids, i.e. DNA and RNA. He showed, two types of Nucleic acids by staining, one called Feulgan’s positive called Deoxy Ribo Nucleic Acid (DNA), the second called Feulgan’s negative Nucleic acid called Ribo Nucleic Acid (RNA). Today Feulgen stain (Schiff regent) is added for cytometry for staining chromosomes and quantification of chromosomal DNA.
Frederick Griffith 1928:
Fredrick Griffith used nonvirulent Pneumococcus bacteria (rough strains) and virulent (smooth strain) to transform bacterial cells. Virulent strains, heat killed ones did not grow in mice but the heat killed virulent strains ones injected with live nonvirulent strains, the latter are transformed into virulent ones. This experiment laid Transformation principle (1940).
Erwin Chargaff in the late 1940'-44 analyzed DNA base ratios. The ratios obtained from different species were self- glaring, and Chargaff did not understand importance of it for he was preoccupied?
Oswald Avery, Colin McLeod and Maclyn McCarty 1944:
They used Pneumococcus strains under in vitro conditions, but used purified DNA, RNA and protein for transformation experiments, and found unequivocally, DNA as the transforming biological chemical.
Alfred Hershey and Martha Chase 1952:
Alfred Hershey and Martha Chase-1952, using T2 Bacteriophages, with in-vivo labeled (P32) nucleic acids and (C14) labeled proteins, they showed that DNA as the genetic material, which was a conclusive proof, they were awarded Nobel Prize.
Adolf Mayer 1886, first described the tobacco mosaic disease that could be transferred between plants, similar to bacterial infections. All biologists accepted DNA as the genetic material, come whatever may be the source of organisms, but scientist from Russia (Dimitri Ivanowsky) discovered TMV in 1892, a non-bacterial deadly Tobacco Mosaic Virus as crystals passed through filters (chamberland filters). Later, in 1903, Ivanovsky published a paper describing abnormal crystal intracellular inclusions in the host cells of the affected tobacco plants. Wendell Meredith Stanley, in 1935 also showed that TMV remains active even after crystallization. For his work, he was awarded 1/3 of the Nobel Prize in Chemistry in 1946. In 1955, Heinz Fraenkel-Conrat and Robley C. Williams showed that purified TMV RNA and its capsid (coat) protein assemble by themselves to functional viruses, indicating that this is the most stable structure (the one with the lowest free energy). The crystallographer Rosalind Franklin worked for Stanley for about a month at Berkeley, and later they designed and built a model of TMV for the 1958 World's Fair at Brussels. In 1958, she speculated that the virus was hollow, not solid, and hypothesized that the RNA of TMV is single-stranded. Soon scientists discovered that many viruses contained RNA as the genetic material, among them ex. Rous Sarcoma Virus (RSV), Influenza virus, Picorna virus, Rhabdo viruses, HTLV and HIV, and some bacterial RNA viruses such as. MS2 and Q beta are few bacterial RNA phages and many others.
James Watson, Francis Crick and Wilkins–1952-53, a crowning achievement in proposing a 3-D model of DNA, a double helix. Rosalind Franklin and Maurice Wilkins provided x-ray diffraction data. Jerry Donahue, student of Linus Pauling an office mate and a friend of J.D.Watson provided the clue about the correct base tautomeric states.
1995- Edward B. Lewis, Christiane Nusslein-Volhard and Eric Wieschaus, , Nobel Prize in Medicine and Physiology for their work on genetic control of embryonic development. Watson and Crick acknowledged Donohue; "We are much indebted to Dr. Jerry Donohue for constant advice and criticism, especially on interatomic distances".
John Ken drew, Max F. Perutz, 1962, for their great work on 3-D structure of globular proteins, awarded Nobel Prize in chemistry.
Boyer, Cohen and Paul Berg-1977-78, conducted DNA cloning experiments.
Sanger & Barrel and Maxam & Walter Gilbert (1975-75) devised techniques for DNA sequencing.
Southern-1975; He and his coworkers developed Southern blotting technique.
Richard Dickerson-1974 did x-ray diffraction of synthesized oligos of CGCGAATTTCGCG for –B- DNA; GGCCGGCC, G GTATACC for A-DNA and CGCGCG sequences are used for Z-DNA. The first X-ray diffraction photograph was by Miss Franklin and Dr Wilkins; still the best one of the pictures of synthetic DNA oligos ever taken.
Illert-1967, discovered DNA ligase.
Maramur Dotty-1961 conducted historical DNA-DNA and DNA-RNA hybridization experiments.
Palmitter and Ralph Brienster –1981-82, produced transgenic mice with human growth hormone gene. The author of this website was a witness to this epoch making work, University of Penn, downtown campus.
Beadle, Joshua Lederberg, Edward L.Tatum, 1958, for work on gene expression, in Neurospora, in medicine and Physiology.
Fredric Sanger, 1958, in chemistry for his work on primary structure of proteins; amino acid sequence of Insulin; he also developed dideoxy nucleotide methods for sequencing. DNA sequencing; using this technique he sequenced phiX174 virus in quick time.
Korenberg; 1959, did in vitro synthesis of DNA using DNA polymerase, which is now called DNA polymerase-I.
Severo Ochoa did an excellent job on RNA polymerases; also he worked on in initiation of translation in eukaryotes. Both got Nobel Prize for physiology or Medicine (2006).
F.MacFarlane and Peter B. Medawar, 1960, for their excellent work on clonal selection theory of Antibody formation awarded Nobel Prize in Medicine or physiology.
Melvin Calvin, 1961, Nobel Prize in chemistry for his work on Biochemistry of carbon fixation (photosynthesis),
Arbor –1962, showed evidence for restriction enzymes; Nathan and H. Smith showed that restriction enzymes cut DNA in sequence specific manner; Nobel
Prize in chemistry.
F.C. Crick. J.D.Watson and M.H.F. Wilkins in 1962 awarded Nobel Prize in medicine and Physiology, for their work on 3-D structure of DNA.
John C. Eccles, Alan L. Hodkin and Andrew F. Huxley, 1963, awarded Nobel Prize in medicine and Physiology for their work on ionic basis of nerve membrane potentials.
Dorothy L. Hodkin, 1964, awarded Nobel Prize in Chemistry for their work in structure of complex organic molecules.
Francois Jacob, Andre M. Lwoff, and Jacques Monad, 1965, awarded Nobel Prize in medicine and physiology for their excellent work on bacterial operons, Lac-operon, and mRNAs.
Peyton Rous, 1966, for the discovery of Rous sarcoma virus, awarded Nobel Prize for this pioneering discovery of retroviruses.
H. Gobind Khorana, Marshal W. Nierenberg and Robert W. Holley, 1968, awarded Nobel Prize in Medicine and Physiology, for their path breaking work in elucidating Genetic code and tRNA structure. H. G. Khorana elucidated the genetic code dictionary, using filter paper assays and also responsible for the synthesis of first gene in test tube. M.W Nierenberg was the first to elucidate the meaning of the first codon UUU means Phenylalanine. Robert W. Holley elucidated the structure of ala tRNA and proposed clover leaf model.
Max Delbruck, Alfred D. Hershey, Salvador E. Luria, 1969, awarded Nobel Prize in Medicine and Physiology for their work on genetics and structure of viruses.
Bernard Katz, Ulf S Voneuler, 1970, awarded Nobel Prize in Medicine and Physiology for their extraordinary work on Biochemistry of Nerve impulse propagation and transmission.
F.loir, 1970, awarded Nobel Prize in Chemistry, for his work on the role of nucleotides in carbohydrate synthesis.
Earl. Sutherland, 1971, Nobel Prize in Medicine and physiology for their work on the mechanism of hormone action and cyclic AMP.
Christian B. Anfinsen, 1972, awarded Nobel Prize for his work on relationship between primary and tertiary structures of proteins.
Gerald Edelman, Rodney R. porter, 1972, awarded Nobel Prize in medicine for their work on the structure of Immunoglobulins.
Albert Claude, Christian de Duve, and George E. Palade 1974 awarded Nobel Prize in medicine and physiology, for their work on internal structure of cells.
David Baltimore, Renato Dulbecco and Howard M. Timin, 1975, awarded Nobel Prize for their work on Reverse transcriptase and tumor causing viral activities.
D. Carleton Gajdusek, 1976, awarded Nobel Prize in medicine and physiology for his work on Prion based diseases.
Peter Mitchell, 1978, awarded Nobel Prize for his work on chemiosmotic mechanism in mitochondrial oxidative phosphorylation.
Werner Arber, Daniel Nathan and Hamilton Smith, 1978, awarded Nobel Prize for their work on restriction endonuclease technology.
Baruj Bennacerraf, Jean Dausset, and George D.Snell, 1980, Nobel Prize in Medicine and Physiology, for their work on Major Histocompatibility complex.
Paul Berg, Walter Gilbert, Frederick Sanger, 1980, awarded Nobel Prize in chemistry for their work on Recombinant DNA technology, DNA sequencing.
Aarton Klug, 1982, Nobel Prize in chemistry, for his work on structure of Nucleic acid and Protein complex.
Barbara McClintock, 1983, Nobel Prize in medicine and Physiology for her work on mobile elements in genome especially in corn plants, her work at that time was ahead of her times, a Botanist par excellence.
George Kohler, Cesar Milstein, and Neils K. Jerne, 1984, Nobel Prize in medicine and physiology for their work on monoclonal antibodies.
Michael S. brown and Joseph L.Goldstein, 1985, Nobel Prize in Medicine and Physiology for their work on regulation of cholesterol metabolism and endocytosis.
Mullis et al –1985, conducted first PCR experiments successfully.
Rita Levi-Montalcini and Stanley Cohen, 1986, Nobel Prize in Medicine and Physiology for their work on neuronal growth factors.
Susumu Tonegawa, 1987, Nobel Prize in medicine and physiology for the work on DNA rearrangement responsible for generating diverse antibodies.
Joahan Deisenhofer, Robert Huber and Hartmut Michel, 1988, Nobel Prize in chemistry, for their work on bacterial photosynthetic reaction center.
J. Michael Bishop, Harold Varmus, 1989, Nobel Prize chemistry, for their work on Oncogenes, that is cellular genes causing cancer or causing malignant transformation.
Thomas R. Czech, Sidney Altman, 1989, Nobel Prize in chemistry for their work on RNA as enzymes or work on Ribozymes.
Erwin Neher and Bert Sakmann, 1991, Nobel Prize in Medicine and Physiology for their work on measurement of ion flux by patch and clamp recording.
Edmond Fischer and Edwin Krebs, 1992, Nobel Prize in medicine and physiology for their work on alteration of enzyme activity by phosphorylation and dephosphorylation.
Karry Mullis and Michael Smith, 1993, Nobel Prize in chemistry for their pioneering work on polymerase chain reaction (PCR) experiments and site directed mutagenesis (SDM).
Richer Roberts and Philip Sharp, 1993, Nobel Prize in Medicine and Physiology for their work on split genes and RNA processing or RNA splicing.
Alfred Gilman and Martin Rodbell, 1994, Nobel Prize in Medicine and Physiology for their work on structure and function of GTP-binding (G) proteins.
Jens C.Skou, Paul Boyer and John Walker, 1996, Nobel Prize in Chemistry for their work Na+/K+- ATPase and the mechanism of ATP synthesis.
Rolf M. Zinkernagel and Peter C. Doherty, 1997, Nobel Prize for their work on recognition of viral infected cell by immune system.
Elizabeth H. Blackburn, Carol W. Greider, Jack W. Szostak –telomerase.
@010- Robert G. Edwards; development of in vitro fertilization.
2011- The Nobel Prize in Physiology or Medicine 2011 was divided, one half jointly to Bruce A. Beutler and Jules A. Hoffmann "for their discoveries concerning the activation of innate immunity" and the other half to Ralph M. Steinman "for his discovery of the dendritic cell and its role in adaptive immunity"
2012; Sir Jhn B. Gurdon and Shiny Yamaka; "for the discovery that mature cells can be reprogrammed to become pluripotent"
2012; chemistry; Robert J. Lefkowitz and Brian K. Kobilka, "for studies of G-protein-coupled receptors"
2013; James E. Rothman, Randy W. Schekman, Thomas C. Südhof- "for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells".
Note, there are innumerable Molecular Biologists and Biochemists (including some Biophysists) who have contributed to the knowledge of Molecular Biology and Gene Engineering of what we know today. If I can understand the subject properly and teach my students, is itself is good contribution to ‘Education”. Cellular molecular biological process inside the cell is like “Microcosm” and looking at sky and beyond we call it ‘Macrocosm’; both are mysterious but understanding the details, perhaps is a stupendous task not insurmountable but achievable.