MOLECULAR BIOLOGY-HISTORICAL BACKGROUND

Molecular biology is a very young biological discipline and has a very short history. Some notable accomplishments of molecular biologists can be summarized as follows :

1928 F. Grifth discovered the phenomenon of transformation in bacteria.

1934 M. Schlesinger demonstrated that the bacteriophages are composed of DNA and protein.

1941 G.W. Beadle and E.L.Tatum published their classical study on the biochemical genetics of
Neurospora.

1944 O.T. Avery, C.M. MacLeod and M. McCarthy recognized the DNA nature of transforming principle of pneumococcus bacteria. The fact suggested that it is DNA and not protein which is the hereditary chemical.

1948 A. Boivin, R.Vendrely and C. Vendrely showed that in the different cells of an organism the quantity of DNA for each haploid set of chromosome is constant.

1950 E. Chargaff demonstrated that in DNA the numbers of adenine and thymine groups are always

equal and so are the numbers of guanine and cytosine groups.

1952 A.D. Hershey and M. Chase demonstrated that only the DNA of T2 bacteriophage enters the host, the bacterium Escherichia coli, whereas the protein remains behind.

1953 J. D. Watson and F.H.C. Crick proposed a model for DNA comprising of two helically
intertwined chains tied together by hydrogen bonds between the purines and pyrimidines.

1956 A. Gierer and G. Schramm demonstrated that RNA is the genetic material of tobacco mosaic virus (TMV).

1957 H. Fraenkel-Contrat and B.Singer separated RNA from the protein of TMV viruses, produced hybrid RNA viruses andconfirmed the view that RNA is the genetic material of some viruses.

Mathew Meselson and Franklin W. Stahl performed a density-gradient experiment (using heavy isotope of nitrogen, 15N) in bacteria to confirm the Watson and Crick’s semiconservative theory of DNA replication.

1958 G. Beadle and E. Tatum received Nobe Prize for their contribution in biochemical genetics of fungus.
J. Laderberg got Nobel Prize for the discovery of bacterial recombination.

1959 R.L. Sinsheimer isolated singlestranded
DNA from a small virus φ-X-174 which attacks Escherichia coli.
S. Ochoa ; A. Kornberg received Nobel Prize for artificial synthesis of nucleic acids.

1961 M.W. Nirenberg and J.H. Matthaei cracked the messenger RNA code.F.H.C.Crick and his colleagues showed that the genetic language is made up of three-letter words (i.e., triplet codons). F.Jacob and J. Monod put forward the operon concept.

1962 J. Watson and F. Crick ; M. Wilkens got Nobel Prize for the
discovery of molecular nature of DNA.

1963 J.P. Waller reported that nearly one-half of all proteins in E.coli
cells have the amino acid methionine in the N-terminal position.

1964 K.A. Marcker and F. Sanger discovered a peculiar aminoacyltRNAin E.coli, called N-formyl- methionyl - tRNA and
suggested that this molecule may play a role in the special
mechanism of chain elongation.R.W. Holley and his colleagues gave detailed structure of alanyl tRNA (tRNA ala) from yeast. Holley died in 1993.

1965 F.H.C. Crick proposed the wobble hypothesis for anticodons
 of tRNA and explained how several codons meant for same
 amino acid are recognized by same tRNA.H. Wallace and M.L. Birnstiel isolated ribosomal RNA genes in Xenopus. F. Jacob., A. Lwoff, and J. Monod received Nobel Prize for the discovery of protein synthesis mechanism in virus.

1968 R.W. Holley ; H.G. Khorana and M.W. Nirenberg got Nobel
Prize for deciphering the genetic code.

1969 A.D. Hershey, M. Delbruck and S.E. Luria shared Nobel Prize
in medicine for their contribution to replication and recombination
in viruses (bacteriophages).

Britten and Davidson proposed the gene-battery model for
 regulation of protein synthesis in eukaryotes.1970 Howard Temin and David Baltimore demonstrated the synthesis of DNA on
 RNA template tumour viruses. Both were
 awarded Nobel Prize in 1975 for the discovery of an enzyme called RNA directed DNA polymerase (or reverse transcriptase)
which is present in the core of virus particle (rous sarcoma virus).
Biotechnology emerged as a new discipline due to marriage of biological science with technology (see Dubey, 1995).Knippers ; Kornberg and Gefter ; Moses and Richardson isolated DNA-polymerase-II enzyme.

1972 Mertz and Davis in 1972 demonstrated that cohesive termini of cleaved DNA molecule could be covalently sealed with E.coli DNA ligase and were able to produce recombinant DNA molecules.Cohen et al., for the first time reported the cloning of DNA by using plasmid as vector.R. Porter; G.M. Edelman received Nobel Prize (physiology and medicine) for the discovery of chemical structure of antibodies.
C.B. Anfinsen; S. Moore and W.H. Stein got Nobel Prize (chemistry) for the discovery of chemical structure and activity of the enzyme ribonuclease.

1973 S.H. Kim suggested three dimensional structure, i.e., L-shaped model, of tRNA.

1975 E.M. Southern developed a method, called Southern blotting technique for analysing the related genes in a DNA restriction fragment. D. Pribnow discovered Pribnow box or minus ten sequence in E. coli genome.

1977 P.A. Sharp and R.J. Roberts discovered split genes of adenovirus.D.S. Hogness, I.B. David and N. Davidson studied split genes for 28 S rRNA in Drosophila.P. Chambon, P. Leder and R.A. Flavell studied split genes of B'globin, ovalbumin and tRNA.Itakura et al., first of all produced human insulin (humulin) by means of recombinant technology.

1978-79 W. Gilbert first of all used the terms exon and intron (for split genes).

1978 Hinnen et al., first of all described the transformation of yeast
(Saccharomyces cervisae) by the help of plasmid of E.coli.

1979 Khorana reported completion of the total synthesis of a biologically functional gene.Alwine et al., developed northern blotting technique in which mRNA bands are blot transferred from the gel onto chemically reactive paper. Towbin et al., developed the western blotting technique to find out the newly encoded protein by a transformed cell.

1980 Fredrick Sanger got the second Nobel Prize for discovering
complete sequence of 5400 nucleotides of single stranded DNA of
φ × 174 bacteriophage.

1982 A. Klug was awarded Nobel Prize in chemistry for providing three-dimensional structure of tRNAs. Rubin and Spradling for the first time introduced Drosophila gene of xanthine dehydrogenase
into a P-element (= parental element) which then was microinjected into embryo deficient forthis gene. R.D. Palmiter and R.L. Brinter produced transgenic mice by genetic engineering.

1983 Marilyn Kozak proposed the scanning hypothesis for initiation of translation by eukaryotic ribosomes.

1984 Robert Tijan identified a DNA-binding protein called SP1
which is involved in eukaryotic gene regulation.

1985 Karry Mullis discovered polymerase chain reaction (PCR)which is widely exploited in gene cloning for genetic engineering.
He made use of a thermostable enzyme (acts best on 720 C
temperature), called Taq DNA polymerase, isolated from
Thermus aquaticus.

1984,86 Alec Jeffreys discovered the technique of DNA fingerprinting.

1987 S. Tonegawa was awarded Nobel Prize for discovering the mode of rearrangements of DNA sequences of mammalian immunoglobulin genes to produce a large variety of antibodies Stanford and coworkers developed the particle bombardment
gun which shooted foreign DNA into plant cells or tissues at a very high speed.

1988 J.W. Black, G.B. Elion and G.H. Hitchings were awarded Nobel Prize for formulating drugs such as 6- mercaptopurine and thioguanine, which lead to inhibition of DNA synthesis and of cell division. This proved effective in cancer chemotherapy. They also designed drugs for treating gout, malaria and viral infections such as herpes.

1989 T. Cech and S. Altman awarded Nobel Prize for showing
enzymatic role of some RNA molecules, called ribozymes.

1991 Dr. Lalji Singh at CCMB, Hyderabad has developed a new
technique of DNA fingerprinting by using BKM-DNA probe
(BKM = banded krait minor satellite). He discovered this probe
while he was working on sex determination in snake, the banded
krait (Bungarus fasciatus) for his Ph.D. work.

1992 Edwin G. Krebs and Edmond H. Fisher were awarded Nobel
Prize for the pioneering work on “reversible protein phosphorylation
as a biological regulator mechanism.” Phosphorylation of
proteins is shown to affect transcription, translation, cell division
and many other cellular processes.Prof. Asis Dutta of JNU, New Delhi, was selected for the BirlaAward for Science and Technology for cloning and characterizationof two novel genes–gene for oxalate decarboxylase from Lathyrus sativus (in 1991) and
 gene for a seed specific nutritionally balanced protein from Amaranthus (in 1992).

1993 M.J. Chamberlain proposed the inchworm model for elongation of transcript of DNA template.This year’s Nobel Prize in chemistry was shared by Kary Mullis (for the discovery of PCR) with
Michael Smith (for site directed mutagenesis)