Nucleic Acids:

 

Introduction>

 

Discovery of Nucleic acids and development of few concepts and discovery of important biological macromolecules:

 

Friedrich Miescher.

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).

Frederick Grifith-1928 demonstrated genetic transformation principle.

 

 

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 acid 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 Feulgan staining is added for cytometry for quantification of chromosomal DNA.

 

Frederick Griffith 1928:

Used nonvirulent Pneumococcus bacteria (rough strains), and virulent (smooth strain). 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.

 

 

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.

 

All biologists accepted DNA as the genetic material, come whatever may be the source of organisms, but scientist from Russia (Ivanowsky) discovered TMV, a deadly Tobacco Mosaic Virus, contained RNA and it acted as genetic material.   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 an office mate 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.

 

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 firs X-ray diffraction photograph was by Miss Franklin and Dr Wilkins; still the best one of the pictures of DNA 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 is a witness to this epoch making work.

 

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, by 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.

 

2009 - Elizabeth H. Blackburn, Carol W. Greider, Jack W. Szostak (telomerase)

 

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.