Historia de la Genética

Genómica
Farmacogenómica
Ramón Cacabelos, M.D., Ph.D., D.M.Sci.
Catedrático de Medicina Genómica
Centro Internacional de Neurociencias y Medicina Genómica
15165-Bergondo, Coruña, España
Cátedra de Medicina Genómica
Universidad Continental, Facultad de Medicina, Huancayo, Perú
Toda Historia es subjetiva y
se ajusta más a los intereses
y/o capacidad del Historiador
que a la realidad pasada
La interpretación de la
Historia depende de la
Documentación disponible y
de la Ideología del
Observador
Ramón Cacabelos
Charles Robert Darwin
(1809-1882)
Gregor Mendel
(1822-1884)
Mendel’s Contributions
-The existence of Genes
-Genes are in pairs
-The Principle of Segregation
-Gametic Content
-Random Fertilization
Date Event People Places Sciences
1 Oct 1744 Jean-Baptiste Lamarck was Lamarck French Academy of Sciences Genetics

Historia
born in Bazentin, Picardy,
France
5 Apr 1804 Matthias J Schleiden was Schleiden University of Jena Cell, Genetics
born
16 Feb 1822 Francis Galton was born in Galton University College London Genetics

20 Jul 1822
Birmingham, UK
Gregor Johann Mendel was
born in Hyncice, Czech
Republic
Mendel Hyncice, Czech Republic Genetics Genética
18 Dec 1829 Jean-Baptiste Lamarck died Lamarck French Academy of Sciences Epigenetics, Genetics
1842 First observation of Nageli Genetics, DNA
chromosomes by Swiss
botanist Karl von Nageli
21 Apr 1843 Walther Flemming was Flemming University of Kiel Cell, Genetics
born in Schwerin, Germany
5 Mar 1846 Edouard van Beneden was van Beneden University of Liege Cell, Genetics, DNA
born in Leuven, Belgian
21 Apr 1849 Oskar Hertwig was born in Hertwig Friedberg, Germany Reproduction, Genetics
Friedberg, Germany
16 Sep 1853 Albrecht Kossel was born in Kossel University of Heidelberg Genetics
Rostock, Mecklenburg
(now Germany)
7 Jul 1861 Nettie Maria Stevens was Stevens Carnegie Institute, Bryn Mawr Genetics
born in Cavendish, College
Vermon, USA
11 Aug 1861 James Bryan Herrick was Herrick Rush Medical College Genetics
born in Oak Park, Illinois,
USA
1864 - 1865 Nucleus shown to contain Hertwig, von University of Munich, University Genetics, DNA
genetic substance Kolliker, Strasburger, of Wurzburg, University of
Weismann Freiburg
1865 Laws of inheritance Mendel Abbey of St Thomas, Brno, Genetics
established Austro-Hungarian Empire
1866 Theory that cell's nucleus Haeckel University of Jena Cell, Genetics
contains genetic substance
25 Sep 1866 Thomas Hunt Morgan was Morgan Columbia University, California Genetics
born in Lexington KY, USA Institute of Technology
5 Apr 1870 Clarence E McClung was McClung University of Pennsylvania Genetics
born in Clayton, California,
USA
5 Apr 1877 Walter Sutton born in Utica, Sutton Columbia University Genetics
New York, USA
1878 Chromosomes and the Flemming University of Kiel DNA, Genetics
process of mitiotic cell
division first discovered
1878 Chromosome first Flemming DNA, genetics
discovered
Date Event People Places Sciences
1883 The term 'Eugenics' is Galton Genetics
coined by Francis Galton to
denote the science of
improving stock by
judicious mating
6 Jan 1884 Gregor Johann Mendel Mendel Genetics
died
1889 Richard Altmann, German Altmann Leipzig University Genetics, DNA
pathologist, renames
nuclein as nucleic acid
17 Feb 1890 Ronald Aylmer Fisher was Fisher Rothamsted Experimental Genetics
born in London, United Station
Kingdom
21 Dec 1890 Hermann J Muller was Muller Indiana University Genetics
born in New York, USA
5 Nov 1892 John BS Haldane born in JBS Haldane University of Cambridge, Genetics, Biology, Physiology
Oxford, UK University of California
Berkeley, University of London
1898 A nucelotide called Ruppel Philipps University of Marburg DNA methylation, Epigenetics
tuberculinic acid found to
bind to the protein
tuberculin. It is now
regarded as the precursor
to the discovery of DNA
methylation
29 Sep 1898 Trofim D Lysenko as born Lyscheno Lenin All-Union Academy of Evolution, Genetics
in Karlivka, Poltava Agricultural Sciences
Governorate, Russian
Empire
28 Feb 1901 Linus C Pauling was born Pauling California Institute of Genetics, DNA
in Portland OR, USA Technology
1902 Chromosomes linked with Boveri, Garrod Zoological-Zootomical Institute, Genetics, DNA
inheritance Columbia University
1902 - 1908 Metabolic disease Garrod Oxford University Genetics
explained by genetic
defects
16 Jun 1902 Barbara McClintock was McClintock University of Missouri Genetics
born in Hartford CT, USA
22 Oct 1903 George Wells Beadle was Beadle California Institute of Genetics
born in Wahoo, Nebraska, Technology, Stanford
USA University
19 Dec 1903 George D Snell was born Snell Jackson Laboratory Genetics, Immunology,
in Bradford MA, USA Transplantation
4 Aug 1905 Walther Flemming died Flemming University of Kiel Cell, Genetics
24 Sep 1905 Severo Ochoa was born in Ochoa New York University Genetics, DNA, RNA
Luarca, Spain
1906 Term 'genetics' coined Bateson Genetics

4 Sep 1906 Max Delbruck was born in Delbruck California Institute of Genetics, Virology
Berlin, Germany Technology
22 Aug 1907 Cyril A Clarke was born in Cyril Clarke Liverpool University Genetics
Leicester, UK
4 Dec 1908 Alfred D Hershey was born Hershey Carnegie Institution of Genetics, Virology
in Owosso, MI, USA Washington
14 Dec 1909 Edward L Tatum was born in Tatum Stanford University, Yale University Genetics
Boulder CO, USA
1910 Chromosomes linked with Morgan Columbia University Genetics
hereditary traits
28 Apr 1910 Edouard van Beneden died van Beneden University of Liege Cell, Genetics, DNA
29 Jul 1910 Heinz Ludwig Fraenkel-Conrat Fraenkel- University of California Berkeley Genetics, Virology
was born in Breslau, German Conrat
Empire (now Wroclaw, Poland)
17 Jan 1911 Francis Galton died Galton University College London Genetics
4 May 1912 Nettie Maria Stevens died Stevens Bryn Mawr College, Carnegie Institute Genetics
13 Aug 1912 Salvador E Luria was born in Luria Massachusetts Institute of Technology Genetics, Virology
Torino, Italy
18 Dec 1912 Daniel Mazia was born Mazia University of California Berkeley Cell, Genetics, Reproduction
Scranton, PA, USA
22 Feb 1914 Renato Dulbecco was born in Dulbecco Imperial Cancer Research Fund Genetics, Virology, Oncology
Catanzaro, Italy Laboratory
8 Jun 1916 Francis H C Crick was born in Crick Laboratory of Molecular Biology DNA, Genetics
Northampton, UK
10 Nov 1916 Walter S Sutton died Sutton Columbia University Genetics
15 Dec 1916 Maurice H F Wilkins was born Wilkins King's College London DNA, Genetics
in Pongaroa, New Zealand
7 Feb 1918 Ruth Sager was born in Sager Rockefeller University Genetics, Oncology
Brookline, Massachusetts, USA
3 Mar 1918 Arthur Kornberg was born in Kornberg Stanford University Genetics, DNA, RNA
Brooklyn NY, USA
20 May 1918 Edward B Lewis was born in Lewis California Institute of Technology Genetics, Embryology
Wilkes-Barre, PA, USA
7 Jun 1920 Jacques Monod was born in Monod Pasteur Institute Genetics, mRNA
Nancy, France
17 Jun 1920 Francois Jacob was born in Jacob Pasteur Institute Genetics
Nancy, France
9 Mar 1921 Evelyn Witkin was born in New Witkin New York City DNA, Genetics
York City, USA
15 Oct 1921 Seymour Benzer was born in Benzer Purdue University, California Institute of DNA, genetics
Brooklyn, NY, USA Technology
9 Jan 1922 Har Gobind Khorana was born Khorana University of Wisconsin-Madison, DNA, Genetics, PCR
in Raipur, India Massachusetts Institute of Technology
28 Jan 1922 Robert W Holley was born in Holley Cornell University Genetics, RNA
Urbana IL, USA
25 Oct 1922 Oskar Hertwig died Hertwig Reproduction, Genetics
18 Dec 1922 Esther Lederberg was born in Esther Wisconsin University Genetics, Antimicrobial resistance,
Bronx, New York, USA Lederberg Bacteriophages, Lambda phage
8 Dec 1924 John D Smith was born in John D Smith California Institute of Genetics, DNA, RNA
Southampton, UK Technology, Laboratory of Molecular
Biology
23 May 1925 Joshua Lederberg was born in Joshua University of Wisconsin Genetics, Plasmids, Recombinant DNA
Montclair, NJ, USA Lederberg
23 Jun 1925 Oliver Smithies was born in Smithes University of Washington, University of Genetics, Transgenic animals
Halifax, United Kingdom North Carolina
Nov 1925 T.B. Johnson and R.D. Coghill Johnson, Coghill Yale University DNA methylation, Epigenetics
reported detecting a minor
amount of methylated cytosine
derivative as byproduct of
hyrdrolysis of tuberculinic acid
with sulfuric acid but other
scientists struggled to replicate
their results.
13 Jun 1926 Jérôme-Jean-Louis-Marie Lejeune Paris School of Medicine Genetics
Lejeune was born in
Montrouge, France
13 Jun 1926 Jérôme-Jean-Louis-Marie Lejeune Paris School of Medicine Genetics
Lejeune was born in
Montrouge, France
13 Jan 1927 Sydney Brenner was born in Brenner Laboratory of Molecular Biology Genetics
Germiston, South Africa
10 Apr 1927 Marshall W Nirenberg was Nirenberg National Institutes of Health Genetics, DNA
born in New York NY, USA
5 Jul 1927 Albrecht Kossel died Kossel University of Heidelberg Genetics
6 Apr 1928 James D Watson was born in Watson Laboratory of Molecular Biology DNA, Genetics
Chicago, IL, USA
7 Nov 1928 Norton D Zinder was born New Zinder Rockefeller University Genetics
York City, USA
1929 Jackson Memorial Laboratories Jackson Memorial Laboratoroies Genetics, Immunology,
established to develop inbred Oncology, Transgenic animals
strains of mice to study the
genetics of cancer and other
diseases
19 Aug 1929 Frank Ruddle was born in Ruddle Yale University Genetics, Transgenic animals, Cloning
West New York, New Jersey
23 Jan 1930 Beverly Griffin was born in Griffin Imperial College DNA sequencing, genetics, oncology,
Delhi, Louisiana, USA virology
Aug 1931 Barbara McClintock and Harriet McClintock, Cornell University Genetics, DNA
Creighton, her graduate Creighton
student, provided first
experimental proof that genes
are positioned on
chromosomes
26 Apr 1932 Michael Smith was born in Michael Smith University of British Columbia Gene editing, Genetics, Monoclonal
Blackpool, United Kingdom antibodies
10 Dec 1934 Howard M Temin was born in Temin University of Wisconsin Genetics, Virology, Oncology
Philadelphia, PA, USA
7 May 1939 Sidney Altman was born in Altman Harvard University, Laboratory of RNA, genetics
Montreal, Canada Molecular Biology, Yale University
30 Oct 1939 Leland H Hartwell was born Hartwell Fred Hutchinson Cancer Research Cell, Genetics
in Los Angeles, CA, USA Center
1940 The first cogenic line of Snell Jackson Laboratory Genetics, Immunology
inbred mouse strains were
developed, which helped
determine the major
histocompatibility complex, a
set of genes that code for
proteins found on the
surfaces of cells which help
the immune system
recognise foreign
substances.
1940 Inbred strains of mice bred at Barrett Jackson Memorial Laboratoroies Genetics, Immunology, Oncology
Jackson Memorial
Laboratory showed that
resistance to transplanted
tumours were due to body's
resistance to genetically
different tissue
1941 Genes shown to regulate Beadle, Tatum Stanford University Medical School Genetics
biochemical events within
cells
1 Jan 1941 Martin J Evans was born in Evans Cardiff University Genetics
Stroud, United Kingdom
1942 'Epigenetics' coined as a Waddngton Cambridge University Epigenetics
term to describe how genes
interact with the environment
to produce the physical traits
of an organism
27 Mar 1942 John E Sulston born in
Cambridge, UK
20 Oct 1942 Christiane Nusslein-Volhard
was born in Magdeburg,
Germany
15 May 1943 Oswald claimed DNA to be
the 'transforming factor' and
the material of genes
1944 Evelyn Witkin discovered
radiation resistance in
bactiera
6 Jun 1944 Phillip A Sharp was born in
Falmouth, Kentucky, USA
4 Dec 1945 Thomas Hunt Morgan died
17 Jan 1946 Clarence E McClung died
24 Apr 1947 Roger D Kornberg was born
in St. Louis, MO, USA
8 May 1947 H Robert Horvitz was born in
Chicago IL, USA
8 Jun 1947 Eric F Wieschaus was born Wieschaus
in South Bend, Indiana, USA
1948 - 1950 McClintock developed her McClintock
theory of genetic
transposition
Mar 1948 Hotchkiss discovered the first Hotchkiss
naturally modifed DNA
nucleotide, cytosine, in a
chromatography of calf
thymus DNA
Sulston Laboratory of Molecular Biology Cell, Genetics, DNA sequencing
Nusslein- Max-Planck-Institute for Embyology, Genetics
Volhard Developmental Biology
Avery Rockefeller University DNA, genetics
Witkin Cold Spring Harbor Laboratory Genetics, DNA
Sharp Massachusetts Institute of RNA, genetics
Technology, Biogen, Alynylam
Pharmaceuticals, Magen
Biosciences
Morgan Columbia University, California Genetics
Institute of Technology
McClung University of Pennsylvania Genetics
Kornberg Stanford University Genetics, RNA
Horvitz Laboratory of Molecular Biology, Genetics
Massachusetts Institute of
Technology
European Molecular Biology Genetics, Embryology
Laboratory, Princeton University
Cold Spring Harbor Laboratory Genetics
Rockefeller Institute Epigenetics
25 Jan 1949 Paul M Nurse was born in Nurse Imperial Cancer Research Fund, Cell, Genetics, Oncology
Norwich, United Kingdom Francis Crick Institute
5 Jun 1949 Susan Lindquist was born in Linquist Massachusetts Institute of Genetics, Proteomics
Chicago, Illiniois, USA Technology
Jan 1950 Esther Lederberg discovered Esther University of Wisconsin Bacteriophages, Genetics, Recombinant
the lambda phage Lederberg DNA
9 Jan 1950 Alec Jeffreys was born in Jeffreys University of Leicester Genetics
Oxford, UK
10 May 1950 Hattie E Alexander and Grace Alexander, Columbia University Genetics
Leidy reported success using Leidy
DNA to alter the hereditary
characteristics of Hemophilus
influenzae
May 1951 5-methcytosine isolated in Wyatt Epigenetics
nucleic acids for the first time
9 Nov 1952 Jack Szostak was born in Szotak Harvard University Genetics, RNA
London, United Kingdom
7 Mar 1954 James Bryan Herrick died Herrick Rush Medical College Genetics
31 Oct 1954 Linus Pauling was awarded the Pauling California Institute of Technology Genetics, DNA
Nobel Prize
2 Feb 1955 Oswald T Avery died Avery Rockefeller University DNA, Genetics
1956 First observation of messenger Astrachan, Oak Ridge National Laboratory DNA, RNA, genetics, mRNA
RNA, or mRNA Volkin
1957 Conrad Waddington develops Waddngton Cambridge University Epigenetics, Embryology
model of epigenetic landscape
to show the process of cellular
decision-making during
biological development
1 Nov 1959 New technique published for Benzer Purdue University, California Institute of DNA, genetics
mapping the gene shows Technology
genes are linear and cannot be
divided
1961 'Jumping genes', transposable McLintock Cold Spring Harbor Laboratory DNA, Genetics
elements, discovered by
Barbara McClintock
15 Apr 1961 Carol W Greider was born in Greider Johns Hopkins University Genetics
San Diego CA, USA
22 Apr 1961 Genes linked to X-chromosome Lyon Cambridge University Epigenetics, Embyology
inactivation in female mice
embyos
13 May 1961 Experiment confirms existence Brenner, Jacob, University of Cambridge, Pasteur DNA, RNA, genetics, mRNA
of mRNA Meselson Institute, California Institute of
Technology
Dec 1961 Normal cell population Hayflick Wistar Institute Cell culture, Genetics, Oncology
discovered to only be able to
divide a limited number of times
before it stops
23 Jan 1962 Idea of restriction and Arber, Dussoix University of Geneva Restriction enzymes, Recombinant
modification enzymes born DNA, DNA Sequencing, Epigenetics
29 Jul 1962 Ronald Aylmer Fisher died Fisher Rothamsted Experimental Station Genetics
1 Dec 1964 JBS Haldane died JBS Haldane University of Cambridge, University of Genetics, Biology, Physiology
California Berkeley, University of
London
18 Jan 1965 First summary of the genetic Nirenberg, National Institutes of Health DNA, Gene
code was completed Mathaei, Ochoa
7 Aug 1965 Mouse and human cells Harris, Watkins, Oxford University Cell, Genetics
successfully fused Campbell, Evans,
Ford
15 Apr 1967 Hermann J Muller died Muller Indiana University Genetics
Sep 1967 Chromosome with a Weiss, Green New York University DNA, Genetics, Genomics
specific gene isolated from
hybrid cells produced from
fused mouse and human
cells
Jul 1969 Discovery of methylase, Arber, Linn University of Geneva DNA methylation, Epigenetics
an enzyme, found to add
protective methyl groups
to DNA
Jun 1970 First method published for Casperson, Zech, Karolinska Institute DNA, Genetics
staining human or other Johansson, Modest
mammalian chromosomes
27 Jul 1970 Reverse transcriptase first Baltimore, Temin, Massachusetts Institute of Genetics, Virology, Recombinant DNA
isolated Mizutani Technology, University of
Wisconsin
7 Feb 1972 Immune response genes McDevitt, Deak, Stanford University, University Genetics, Immunology
discovered Shreffler, Klein, of Michigan, Jackson
Stimpfling, Snell Laboratory
10 Jun 1973 - 13 Jun First international Ruddle DNA, Genetics, Geonomics
1973 workshop on human gene
mapping held
1975 DNA methylation Riggs, Sager, City of Hope National Medical DNA methylation, Epigenetics,
suggested as mechanism Kitchen Center, Harvard University Embryology
behind X-chomosome
silencing in embryos
1975 DNA methylation proposed Hoilliday, Pugh National Institute for Medical DNA methylation, Epigenetics
as important mechanism Research
for the control of gene
expression in higher
organisms
5 Nov 1975 Edward L Tatum died Tatum Stanford University, Yale Genetics
University
11 Mar 1976 Proto-oncogenes Bishop, Varmus, University of California San DNA, Genetics, Oncology
suggested to be part of the Stehelin, Vogt Francisco
genetic machinery of
normal cells and play
important function in the
developing cell
31 May 1976 Jacques Monod died Monod Pasteur Institute Genetics, mRNA
20 Nov 1976 Trofim Denisovich Lysenko Lenin All-Union Academy of Evolution, Genetics
Lysenko died Agricultural Sciences
1977 First method developed for Mertz, Gurdon, De Laboratory of Molecular Biology Genetics
studying gene regulation in Robertis
a higher organism
9 Mar 1981 Max Delbruck died Delbruck California Institute of Genetics, Virology
Technology
Jul 1981 First evidence provided to Compere, Palmitter Howard Hughes Medical DNA methylation, Epigenetics
show that DNA Institute
methylation involved in
silencing X-chromosome
1982 - 1985 Studies reveal azacitidine, DNA methylation, Epigenetics
a cytoxic agent developed
by Upjohn, inhibits DNA
methylation
1982 Azacitidine fails to win Epigenetics, Oncology
FDA approval for
treatment of acute
myelogenous leukaemia
due to lack of controlled
studies showing clinical
benefit
6 Jan 1983 Widespread loss of DNA Feinberg, Johns Hopkins University DNA methylation, Epigenetics
methylation found on Vogelstein
cytosine-guanine (CpG)
islands in tumour samples
10 Sep 1984 First genetic fingerprint Jeffreys University of Leicester DNA sequencing, genetics, PCR
revealed
Jan 1985 DNA methylation found to Bird, Taggart, Edinburgh University, Kanematsu DNA methylation, Epigenetics
occur on specific DNA Fromer, Miller, Laboratories, Columbia University
segments called CpG islands Macleod
7 Mar 1985 DNA fingerprinting principle Jeffreys University of Leicester DNA sequencing, genetics, PCR
laid out
17 May 1985 1st legal case resolved using Jeffreys University of Leicester DNA sequencing, genetics
DNA fingerprinting
20 Oct 1988 Cloning of first mammalian Bestor, Laudano, Massachusetts Institute of DNA methylation, Epigenetics
enzyme (DNA Mattaliano, Technology
methyltransferase, DNMT) that Ingram
catalyses transfer of methyl
group to DNA
9 Jun 1989 George Wells Beadle died Beadle California Institute of Technology, Genetics
Stanford University
Sep 1989 DNA methylation suggested to Greger, Institute of Human Genetics DNA methylation, Epigenetics, Oncology
inactivate tumour suppressor Passarge,
genes Hopping,
Messmer,
Horsthemke
Dec 1990 BRCA1, a single gene on King, Lee, University of California Berkeley Genetics, DNA sequencing
chromosome 17, shown to be Newman,
responsible for many breast Morrow,
and ovarian cancers Anderson, Huey
6 Feb 1991 Salvador E Luria died Luria Massachusetts Institute of Genetics, Virology
Technology
1 Mar 1992 Method devised to isolate DNA methylation, Epigenetics,DNA
methylated cytosine residues sequencing
in individual DNA strands
providing avenue to undertake
DNA methylation genomic
sequencing
12 Jun 1992 First transgenic mouse model Li, Bestor, Whitehead Institute for Biomedical Epigenetics, Transgenic animals
created for studying link Jaenisch Research
between DNA methylation and
disease
2 Sep 1992 Barbara McClintock died McClintock University of Missouri Genetics
1 Oct 1992 First experimental evidence Zapisek, Cronin, FDA, National Center for DNA methylation, Epigenetics, Oncology
showing links between diet and Lyn-Cook, Poirier Toxicological Research
1 Nov 1993 Severo Ochoa died
9 Feb 1994 Howard M Temin died
3 Apr 1994 Jérôme-Jean-Louis-Marie
Lejeune died
19 Aug 1994 Linus C Pauling died
1995 Christiane Nüsslein-Volhard,
Eric Wieschaus and Edward B
Lewis jointly awarded Nobel
Prize in Physiology or
Medicine for illuminating the
genetic control of embryonic
development
21 Apr 1995 First evidence published to
demonstrate reduced DNA
methylation contributes to
formation of tumours
6 Jun 1996 George D Snell died
9 Jun 1996 Daniel Mazia died
29 Mar 1997 Ruth Sager died
22 May 1997 Alfred D Hershey died
Feb 1998 Double stranded RNA
demonstrated to be potent
mechanism for silencing genes Kostas, Driver,
10 Apr 1999 Heinz Ludwig Fraenkel-Conrat Fraenkel-Conrat
died
20 Jul 1999 DNA methylation of CpG
islands shown to be linked to Ohe-Toyota,
colorectal cancer
Ochoa New York University Genetics, DNA
Temin University of Wisconsin Genetics, Virology, Oncology
Lejeune Paris School of Medicine Genetics
Pauling California Institute of Technology Genetics, DNA
Nusslein- Genetics, Embryology
Volhard,
Wieschaus,
Lewis
Laird, Jackson- Massachusetts Institute of DNA methylation, Epigenetics, Oncology
Grusby, Fazeli, Technology, Massachusetts General
Dickinson, Jung, Hospital
Li, Weinberg,
Jaenisch
Snell Jackson Laboratory Genetics, Immunology, Transplantation
Mazia University of California Berkeley Cell, Genetics, Reproduction
Sager Rockefeller University Genetics, Oncology
Hershey Carnegie Institution of Washington Genetics, Virology
Fire, Mello, Xu, Carnegie Institution of Washington, RNA interference, Genetics
Montgomery, Johns Hopkins University, University of
Massachusetts Cancer Center
University of California Berkeley Genetics, Virology
Toyota, Ahuja, Johns Hopkins University DNA methylation, Epigenetics,
Oncology
Herman, Baylin,
Issa
Nov 1999 First evidence from mammals Morgan, University of Sydney Epigenetics
that epigenetic changes can be Sutherland, Martin,
passed down generations Whitelaw
4 Oct 2000 Michael Smith died Michael Smith University of British Columbia Gene editing, Genetics, Monoclonal
antibodies
21 Nov 2000 Cyril A Clarke died Clarke Liverpool University Genetics
2001 Pharmion licenses azacitidine Epigenetics
from Pharmacia and Upjohn to
Pharmacia's azacityidine
technology, patents and
clinical data
Apr 2002 Identification of new enzyme Rauscher Wistar Institute Genetics
for silencing certain genes,
opening new avenues for
cancer treatments
20 Aug 2002 Link identified between genes Shiekhattar Wistar Institute Neuroscience, Genetics
responsible for
neurofibromatosis, a common
neurological disorder, and a
protein thought to play role in
Alzheimer's disease
22 Nov 2003 John D Smith died John D Smith California Institute of Genetics, DNA, RNA
Technology, Laboratory of Molecular
Biology
2004 FDA approved first DNA DNA methylation, Epigenetics
methylation inhibitor drug,
azacitidine (Vidaza®), for
treatment of rare bone marrow
disorder
21 Jul 2004 Edward B Lewis died Lewis California Institute of Technology Genetics, Embryology
28 Jul 2004 Francis H C Crick died Crick Laboratory of Molecular Biology DNA, Genetics
5 Oct 2004 Maurice H F Wilkins died Wilkins King's College London DNA, Genetics
Feb 2005 Enzyme Ubp10 demonstrated Berger, Emre Wistar Institute DNA, Genetics
to protect the genome from
potential destabilising
molecular events
2006 FDA approved second DNA DNA methylation, Epigenetics
methylation inhibitior,
decatabine (Dacogen)
6 Oct 2006 FDA approved first histone Epigenetics, Oncology
deacetylase inhibitor,
Vorinostat (Zolinza), for
cutaneous T-cell lymphoma
11 Nov Esther Lederberg died Esther Wisconsin University Genetics, Antimicrobial resistance, Bacteriophages,
2006 Lederberg Lambda phage
26 Oct Arthur Kornberg died Kornberg Stanford University Genetics, DNA, RNA
2007
30 Nov Seymour Benzer died Benzer Purdue University, California DNA, genetics
2007 Institute of Technology
2008 Structure of telomerase, an Wistar Institute DNA, genetics
enzyme that conserves the
ends of chomosomes, was
decoded
2 Feb 2008 Joshua Lederberg died Joshua University of Wisconsin Genetics, Plasmids, Recombinant DNA
Lederberg
Nov 2009 FDA approved second Epigenetics, Oncology
histone deactylase inhibitor,
Romidepsin (Istodax), for
cutaneous T-cell lymphoma
15 Jan Marshall W Nirenberg died Nirenberg National Institutes of Health Genetics
2010
9 Nov 2011 Har Gobind Khorana died Khorana University of Wisconsin- DNA, Genetics, PCR
Madison, Massachusetts
Institute of Technology
6 Oct 2006 FDA approved first histone Epigenetics, Oncology
deacetylase inhibitor,
Vorinostat (Zolinza), for
cutaneous T-cell lymphoma
11 Nov Esther Lederberg died Esther Wisconsin University Genetics, Antimicrobial resistance, Bacteriophages,
2006 Lederberg Lambda phage
26 Oct Arthur Kornberg died Kornberg Stanford University Genetics, DNA, RNA
2007
30 Nov Seymour Benzer died Benzer Purdue University, California DNA, genetics
2007 Institute of Technology
2008 Structure of telomerase, an Wistar Institute DNA, genetics
enzyme that conserves the
ends of chomosomes, was
decoded
2 Feb 2008 Joshua Lederberg died Joshua University of Wisconsin Genetics, Plasmids, Recombinant DNA
Lederberg
Nov 2009 FDA approved second Epigenetics, Oncology
histone deactylase inhibitor,
Romidepsin (Istodax), for
cutaneous T-cell lymphoma
15 Jan Marshall W Nirenberg died Nirenberg National Institutes of Health Genetics
2010
9 Nov 2011 Har Gobind Khorana died Khorana University of Wisconsin- DNA, Genetics, PCR
Madison, Massachusetts
Institute of Technology
3 Feb 2012 Norton David Zinder died Zinder Rockefeller University Genetics, Antimicrobial resistance
19 Feb Renato Dulbecco died Dulbecco Imperial Cancer Research Fund Genetics, Virology, Oncology
2012 Laboratory
2012 European approval of Epigenetics, Oncology
decatabine (Dacogen) for
treatment of acute myeloid
leukaemia
3 Feb 2012 Norton David Zinder died
19 Feb Renato Dulbecco died
2012
2012 European approval of
decatabine (Dacogen) for
treatment of acute myeloid
leukaemia
10 Mar Frank Ruddle died in New Ruddle
2013 Haven, Connecticut
Apr 2015 Chinese regulatory
authorities approved
Chidamide, a histone
deactylase inhibitor, for
peripheral T cell lymphoma
27 Aug Experiments with mice
2015 showed that azacytidine
treatment enhanced the
responsiveness of tumors to
anti–CTLA-4 therapy
13 Jun Beverly Griffin died Griffin
2016
27 Oct Susan Lindquist died
2016
10 Jan Oliver Smithies died
2017
15 Nov Rare mutation of gene
2017 called Serpine 1 discovered
to protect against biological
ageing process
Zinder Rockefeller University Genetics, Antimicrobial resistance
Dulbecco Imperial Cancer Research Fund Genetics, Virology, Oncology
Laboratory
Epigenetics, Oncology
Yale University Genetics, Transgenic animals, Cloning
Epigenetics, Oncology
Cancer immunotherapy, Epigenetics, Immune
checkpoint inhibitors, Oncology
Imperial College DNA sequencing, genetics, oncology, virology
Linquist Massachusetts Institute of Genetics, Proteomics
Technology
Smithies University of Washington, Genetics, Transgenic animals
University of North Carolina
Khan, Shah, Northwestern University, DNA sequencing, Genetics, Genomics
Klyachko, University of British Columbia,
Baldridge, New Jersey Medical School,
Eren, Place, Tohoku University,
Aviv,
Puterman,
Lloyd-Jones,
Heiman,
23 Jan 2019 CRISPR-Cas9 used to control Grunwald, University of California San Diego CRISPR-Cas9, Genetics, Transgenic
genetic inheritance in mice Gntz, animals
Poplawski, Xu,
Bier, Cooper
5 Apr 2019 Sydney Brenner died Brenner Laboratory of Molecular Biology Genetics
Oct 2019 NHS introduced new fast-track South West Genomic Laboratory Hub DNA Sequencing, Genomics, Genetics
DNA test to scan for rare
diseases in babies and children
5 Apr 2022 Sidney Altman died Altman Harvard University, Laboratory of RNA, genetics
Molecular Biology, Yale University

https://www.whatisbiotechnology.org/index.php/timeline/science/genetics/200
Date Event People Places
1842

13 Aug 1844
First observation of chromosomes by Swiss botanist Nageli
Karl von Nageli
Johann Friedrich Miescher was born in Basel,
Switzerland
Miescher University of Tubingen
Historia
ADN
5 Mar 1846 Edouard van Beneden was born in Leuven, Belgian van Beneden University of Liege
1864 - 1865 Nucleus shown to contain genetic substance Hertwig, von Kolliker, Strasburger,University of Munich, University of
Weismann Wurzburg, University of Freiburg
1869 Discovery of DNA Miescher University of Tubingen
25 Feb 1869 Phoebus Levene was born in Sagor, Russia (now Levene Rockefeller University
Zagare, Lithuania)
1877 - 1880 Nucleic acid shown to have protein and non-protein Kossel University of Tubingen
components
21 Oct 1877 Oswald T Avery was born in Halifax, Canada Avery Rockefeller University
1878 Chromosomes and the process of mitiotic cell divisionFlemming University of Kiel
first discovered
1878 Chromosome first discovered Flemming
1885 - 1901 Nucleic acids structure determined Kossel Institute of Physiology, University of Berlin,
University of Marburg
1889 Richard Altmann, German pathologist, renames Altmann Leipzig University
nuclein as nucleic acid
26 Aug 1895 Johann Friedrich Miescher died Miescher University of Tubingen
1898 A nucelotide called tuberculinic acid found to bind to Ruppel Philipps University of Marburg
the protein tuberculin. It is now regarded as the
precursor to the discovery of DNA methylation
28 Feb 1901 Linus C Pauling was born in Portland OR, USA Pauling California Institute of Technology
1902 Chromosomes linked with inheritance Boveri, Garrod Zoological-Zootomical Institute, Columbia
University
1903 The notion genetics is introduced Johannsen Royal Veterinary University
24 Sep 1905 Severo Ochoa was born in Luarca, Spain Ochoa New York University
2 Oct 1907 Alexander R Todd was born in Glasgow, Scotland Todd University of Manchester
1909 The term gene is first used Johannsen University of Copenhagen
1910 First description of the building blocks of DNA Levene Rockefeller University
28 Apr 1910 Edouard van Beneden died van Beneden University of Liege
22 Nov 1912 Paul Zamecnik was born in Cleveland, Ohio, USA Zamecnik Massachusetts General Hospital
1913 First mapping of a chromosome Sturtevant Columbia University
14 Dec 1914 Solomon Spiegelman was born in Brooklyn, NY, USA Spiegelman University of Minnesota
8 Jun 1916 Francis H C Crick was born in Northampton, UK Crick Laboratory of Molecular Biology
15 Dec 1916 Maurice H F Wilkins was born in Pongaroa, New Wilkins King's College London
Zealand
3 Mar 1918 Arthur Kornberg was born in Brooklyn NY, USA Kornberg Stanford University
13 Aug 1918 Frederick Sanger, twice Nobel Prize winner, born Sanger Laboratory of Molecular Biology
25 Jul 1920 Rosalind E Franklin was born in London, UK Franklin Kings College London
9 Mar 1921 Evelyn Witkin was born in New York City, USA Witkin New York City
15 Oct 1921 Seymour Benzer was born in Brooklyn, NY, USA Benzer Purdue University, California Institute of
Technology
9 Jan 1922 Har Gobind Khorana was born in Raipur, India Khorana University of Wisconsin-Madison,
Massachusetts Institute of Technology
8 Dec 1924 John D Smith was born in Southampton, UK John D Smith California Institute of
Technology, Laboratory of Molecular Biology
23 May 1925 Joshua Lederberg was born in Montclair, NJ, USA Joshua Lederberg University of Wisconsin
November 1925 T.B. Johnson and R.D. Coghill reported detecting a Johnson, Coghill Yale University
minor amount of methylated cytosine derivative as
byproduct of hyrdrolysis of tuberculinic acid with
sulfuric acid but other scientists struggled to replicate
their results.
30 Jun 1926 Paul Berg was born in New York NY, USA Berg Stanford University
10 Apr 1927 Marshall W Nirenberg was born in New York NY, USA Nirenberg National Institutes of Health
1928 Bacteria shown capable of transformation Griffith Pathological Laboratory of the Ministry of
Health
6 Apr 1928 James D Watson was born in Chicago, IL, USA Watson Laboratory of Molecular Biology
14 Aug 1928 Ray Wu was born in Beijing, China Wu Cornell University
30 Oct 1928 Daniel Nathans was born in Wilmington, Delaware, Nathans Johns Hopkins University
USA
3 Jun 1929 Werner Arber was born in Granichen, Switzerland Arber University of Geneva
8 Oct 1929 Franklin W Stahl was born in Boston, Massachusetts, Stahl California Institute of Technology, University
USA of Missouri, University of Oregon
23 Jan 1930 Beverly Griffin was born in Delhi, Louisiana, USA Griffin Imperial College
August 1931 Barbara McClintock and Harriet Creighton, her McClintock, Creighton Cornell University
graduate student, provided first experimental proof
that genes are positioned on chromosomes
23 Aug 1931 Hamilton O Smith was born in New York City, USA Smith Johns Hopkins University, Celera
1932 Sanger attends Bryanston School, Dorset, as boarder Sanger
21 Mar 1932 Walter Gilbert was born in Boston MA, USA Gilbert Harvard University, Biogen
30 Jun 1935 Stanley Norman Cohen was born in Perth Amboy, NJ, Cohen Stanford University
USA
1936 - 1940 Sanger takes degree in Natural Sciences at Cambridge Sanger Cambridge University
University
10 Jul 1936 Herbert Boyer was born in Derry, Pennsylvania, USA Boyer University of California San Francisco,
Genentech
7 Mar 1938 David Baltimore was born in New York City Baltimore New York City
1940 - 1943 Sanger studies for a doctorate at Cambridge Sanger Cambridge University
University
6 Sep 1940 Phoebus Levene died Levene Rockefeller University
1941 Term 'genetic engineering' first coined Jost
27 Mar 1942 John E Sulston born in Cambridge, UK Sulston Laboratory of Molecular Biology
26 Feb 1943 Erwin Schrodinger proposed that life was passed on Shrodinger
from generation to generation in a molecular code.
15 May 1943 Oswald claimed DNA to be the 'transforming factor' Avery Rockefeller University
and the material of genes
6 Sep 1943 Richard J Roberts was born in Derby, United Kingdom Roberts
1944 Sanger starts working on amino acid composition of Sanger Cambridge University
insulin
1944 Evelyn Witkin discovered radiation resistance in Witkin Cold Spring Harbor Laboratory
bactiera
1 Feb 1944 DNA identified as a hereditary agent Avery, MacLeod, McCarty Rockefeller University
14 Oct 1946 J Craig Venter was born in Salt Lake City, Utah Venter Salt Lake City, Utah
29 Nov 1947 Robert Swanson was born in Florida, USA Swanson Genentech
1949 DNA content of a cells linked to a cell's number of Vendrely, Boivin Pasteur Institute, Strasbourg School of
chromosomes Medicine
1949 - 1950 DNA four base ratio shown to be always consistent Cargraff Columbia University
September 1949 Sickle cell shown to be caused by genetic mutation Pauling California Institute of Technology
January 1950 Esther Lederberg discovered the lambda phage Esther Lederberg University of Wisconsin
November 1951 Purified DNA and DNA in cells shown to have helical Wilkins Kings College London
structure
1952 First observation of the modification of viruses by Luria, Human University of Illinois
bacteria
28 Sep 1952 Experiments proved DNA, and not proteins, hold the Hershey, Chase Carnegie Institution of Washington
genetic code
2 Apr 1953 Nature published Crick and Watson's letter on Watson,Crick Cambridge
Molecular Structure of Nucleic Acids
25 Apr 1953 Nature published three papers showing the Franklin, Gosling, Crick, Watson, Birkbeck College, Kings College London,
molecular structure of DNA to be a double helix Wilkins. Stokes, Wilson Cambridge University
31 Oct 1954 Linus Pauling was awarded the Nobel Prize Pauling California Institute of Technology
1955 Sanger completes the full sequence of amino acids in Sanger Cambridge University
insulin
2 Feb 1955 Oswald T Avery died Avery Rockefeller University
15 Oct 1955 Virus dismantled and put back together to Fraenkel-Conrat University of California Berkley
reconstitute a live virus
1956 Transfer RNA (tRNA) discovered Zamecnik, Hoagland, Stephenson, Harvard University
1956 First observation of messenger RNA, or mRNA Astrachan, Volkin Oak Ridge National Laboratory
16 Apr 1956 DNA polymerase isolated and purified and shown to Kornberg, Bessman, Simms, Washington University in St. Louis
replicate DNA Lehman
1957 Victor Ingram breaks the genetic code behind sickle- Ingram, Sanger Cambridge University
cell anaemia using Sanger's sequencing technique
19 Sep 1957 Francis Crick presented the theory that the main Crick Cavendish Laboratory
function of genetic material is to control the
synthesis of proteins
October 1957 First synthesis of DNA in a test tube Kornberg Washington University in St. Louis
1958 Sanger awarded his first Nobel Prize in Chemistry Sanger Cambridge University
16 Apr 1958 Rosalind E Franklin died Franklin Kings College London
15 Jul 1958 DNA replication explained Meselson, Stahl California Institute of Technology
16 Mar 1959 Existence of gene regulation established Pardee, Jacob, Monod Pasteur Institute, University of California
Berkley
May 1959 Steps in protein synthesis outlined Zamecnik
1 Nov 1959 New technique published for mapping the gene Benzer Purdue University, California Institute of
shows genes are linear and cannot be divided Technology
1960 National Biomedical Research Foundation established Ledley Georgetown University
1960 Sanger begins to devise ways to sequence nucleic Sanger Cambridge University
acids, starting with RNA
1961 - 1966 Genetic code cracked for the first time Khorana, Holley University of Wisconsin, Cornell University
1961 'Jumping genes', transposable elements, discovered McLintock Cold Spring Harbor Laboratory
by Barbara McClintock
13 May 1961 Experiment confirms existence of mRNA Brenner, Jacob, Meselson University of Cambridge, Pasteur Institute,
California Institute of Technology
15 May 1961 Coding mechanism for DNA cracked Nirenberg, Mathaei National Institute for Health
1962 Sanger moves to the newly created Laboratory of Sanger Laboratory of Molecular Biololgy
Molecular Biology in Cambridge
23 Jan 1962 Idea of restriction and modification enzymes born Arber, Dussoix University of Geneva
18 Oct 1962 Nobel Prize for Physiology or Medicine awarded for Watson, Crick, Wilkins Laboratory of Molecular Biology
determining the structure of DNA
19 Oct 1962 Nobel Prize awarded for uncovering the structure of Watson, Crick, Wilkins, Franklin, University of Cambridge, King's College
DNA Gosling London, Birkbeck College
May 1964 Evelyn Witkin discovered that UV mutagenesis in E. Witkin Cold Spring Harbor Laboratory
coli could be reversed through dark exposure
1965 Transfer RNA is the first nucleic acid molecule to be Holley Cornell University
sequenced
1965 First comprehensive protein sequence and structure Dayhoff, Ledley, Eck National Biomedical Research Foundation,
computer data published as 'Atlas of Protein Georgetown University
Sequence and Structure'
1965 Ledley publishes Uses of Computers in Biology and Ledley National Biomedical Research Foundation
Medicine
1965 Sanger and colleagues publish two-dimension Sanger, Brownlee, Barrell Laboratory of Molecular Biology
partition sequencing method
18 Jan 1965 First summary of the genetic code was completed Nirenberg, Mathaei, Ochoa National Institutes of Health
1 Oct 1965 Werner Arber predicted restriction enzymes could be Arber University of Geneva
used as a labortory tool to cleave DNA
1966 Discovery ligase, an enzyme that facilitates the Gellert, Lehman, Richardson,
joining of DNA strands Hurwitz
1967 First automatic protein sequencer developed Edman, Begg St Vincent's School of Medical Research
September 1967 Chromosome with a specific gene isolated from Weiss, Green New York University
hybrid cells produced from fused mouse and human
cells
14 Dec 1967 Functional, 5,000-nucleotide-long bacteriophage Goulian, Kornberg Stanford University, Chicao University
genome assembled
1968 The first partial sequence of a viral DNA is reported Wu, Kaiser Cornell University, Stanford University
Medical School
1968 Paul Berg started experiments to generate Berg Stanford University
recombinant DNA molecules
1969 First principles for PCR published Khorana, Kleppe University of Wisconsin-Madison
1969 New species of bacterium is isolated from hot spring Brock Case Western Reserve University
in Yellowstone National Park by Thomas Brock
1969 New idea for generating recombinant DNA conceived Lobhan Stanford University
July 1969 Discovery of methylase, an enzyme, found to add Arber, Linn University of Geneva
protective methyl groups to DNA
1970 First complete gene synthesised Khorana University of Wisconsin
June 1970 First method published for staining human or other Casperson, Zech, Johansson, Karolinska Institute
mammalian chromosomes Modest
July 1970 First restriction enzyme isolated and characterised Smith, Wilcox Johns Hopkins University
27 Jul 1970 Reverse transcriptase first isolated Baltimore, Temin, Mizutani Massachusetts Institute of Technology,
University of Wisconsin
September 1970 Mertz started her doctorate in biochemistry at Mertz, Berg
Stanford University under Paul Berg
1971 Process called repair replication for synthesising shortKhorana, Kleppe MIT
DNA duplexes and single-stranded DNA by
polymerases is published
1971 First plasmid bacterial cloning vector constructed Berg, Mertz, Jackson Stanford University
May 1971 Complete sequence of bacteriophage lambda DNA Wu, Taylor Cornell University
reported
June 1971 Janet Mertz forced to halt experiment to clone Mertz, Berg, Pollack Stanford University
recombinant DNA in bacteria after safety concerns
raised
December 1971 First experiments published demonstrating the use of Danna, Nathans Johns Hopkins University
restriction enzymes to cut DNA
26 Sep 1972 - 4 First time possible biohazards of recombinant DNA Zinder EMBO
Sep 1972 technology publicly discussed
1 Oct 1972 First recombinant DNA generated Berg, Jackson, Symons Stanford University
November 1972 Janet Mertz and Ronald Davis published first easy-to- Mertz, Davis Stanford University
use technique for constructing recombinant DNA
showed that when DNA is cleaved with EcoRI, a
restriction enzyme, it has sticky ends
1973 The sequencing of 24 basepairs is reported Gilbert, Maxam Harvard University
1973 - 1976 Discovery of DNA repair mechanism in bacteria - the Witkin, Radman Cold Spring Harbor Laboratory, Free
SOS response University of Brussels
1 Mar 1973 Ames test developed that identifies chemicals that Ames, Lee, Durston University of California Berkeley
damage DNA
10 Jun 1973 - 13 First international workshop on human gene mapping Ruddle
Jun 1973 held
1 Nov 1973 First time DNA was successfully transferred from one Cohen, Chang, Boyer Stanford University, University of California
life form to another San Francisco
1974 Regulation begins for recombinant genetic research
1 May 1974 Recombinant DNA successfuly reproduced in Marrow, Cohen, Chang, Boyer, Stanford University, University of California
Escherichia coli Goodman, Helling San Francisco
July 1974 Temporary moratorium called for on genetic Berg, Baltimore, Boyer, Cohen
engineering until measures taken to deal with
potential biohazards
January 1975 Mertz completed her doctorate Mertz Stanford University
1975 Sanger and Coulson publish their plus minus method Sanger, Coulson Laboratory of Molecular Biology
for DNA sequencing
1975 DNA methylation suggested as mechanism behind X- Riggs, Sager, Kitchen City of Hope National Medical Center,
chomosome silencing in embryos Harvard University
1975 DNA methylation proposed as important mechanism Hoilliday, Pugh National Institute for Medical Research
for the control of gene expression in higher
organisms
February 1975 Asilomar Conference called for voluntary moratorium Berg
on genetic engineering research
1976 Yeast genes expressed in E. coli bacteria for the first
time
11 Mar 1976 Proto-oncogenes suggested to be part of the genetic Bishop, Varmus, Stehelin, Vogt University of California San Francisco
machinery of normal cells and play important
function in the developing cell
April 1976 Genentech founded Swanson, Boyer Genentech Inc
23 Jun 1976 NIH released first guidelines for recombinant DNA
experimentation
1977 Human growth hormone genetically engineered
1977 Complete sequence of bacteriophage phi X174 DNA Sanger Laboratory of Molecular Biology
determined
1977 First computer programme written to help with the McCallum Laboratory of Molecular Biology
compilation and analysis of DNA sequence data
February 1977 Two different DNA sequencing methods published Sanger, Maxam, Gilbert Harvard University, Laboratory of Molecular
that allow for the rapid sequencing of long stretches Biology
of DNA
1978 Human insulin produced in E-coli Genentech
October 1978 Nobel Prize given in recognition of discovery of Arber, Nathans, Smith Johns Hopkins University, University of
restriction enzymes and their application to the Geneva
problems of molecular genetics
December 1978 Biogen filed preliminary UK patent for technique to Kenneth Murray Biogen, University of Edinburgh
clone hepatitis B DNA and antigens
1979 First DNA fragments of Epstein Barr Virus cloned Griffin, Lindahl Imperial Cancer Research Fund Laboratories,
University of Gothenberg
February 1979 University of Edinburgh scientists published the Burrell, Mackay, Greenaway, University of Edinburgh, Microbiological
successful isolation and cloning DNA fragments of the Hofschneider, K Murray Research Establishment, Biogen
hepatitis B virus in Escherichia coli
May 1979 - Oct Pasteur Institute scientists reported successful Galibert, Mandart, Fitoussi, Pasteur Institute
1979 cloning of hepatitis B DNA in Escherichia coli Tiollais, Charnay, Hampe
30 Aug 1979 UCSF scientists announced the successful cloning and Valenzuela, Gray, Quiroga, University of California San Francisco, Merck
expression of HBsAg in Escherichia coli Zaldivar, Goodman, Rutter
21 Dec 1979 Biogen applied for European patent to clone Murray Biogen
fragment of DNA displaying hepatitis B antigen
specificity
1980 Genetic engineering recognised for patenting
1980 First patent awarded for gene cloning Cohen, Boyer Stanford University Medical School
1980 Cesar Milstein proposed the use of recombinant DNA Milstein Laboratory of Molecular Biology
to improve monoclonal antibodies
1980 Sanger awarded his second Nobel Prize in Chemistry Sanger, Gilbert Harvard University, Laboratory of Molecular
Biology
January 1980 European Molecular Biology Laboratory convenes EMBL
meeting on Computing and DNA Sequences
1980 Polyoma virus DNA sequenced Griffin, Soeda, Arrand, Walsh Imperial Cancer Research Fund Laboratories
31 Jul 1980 UCSF scientists published method to culture HBsAg Edman, Gray, Valenzuela, Rall, University of California San Francisco
antigens in cancer cells Rutter
September 1980 Scientists reported the first successful development Barbosa, Gordon, Plotkin, Ruddle, Yale University
of transgenic mice Scangos
15 Sep 1980 Largest nucleic acid sequence database in the world Dayhoff National Biomedical Research Foundation,
made available free over telephone network Georgetown University
1981 First genetically-engineered plant reported
1981 First genetically cloned mice
July 1981 First evidence provided to show that DNA Compere, Palmitter Howard Hughes Medical Institute
methylation involved in silencing X-chromosome
July 1981 UCSF and Merck filed patent to synthesise HBsAg in Rutter University of California San Francisco, Merck
recombinant yeast
10 Jul 1981 Complete library of overlapping DNA fragments of Griffin, Arrand, Walsh, Bjorck, Imperial Cancer Research Fund Laboratories,
Epstein Barr Virus cloned Rymo University of Gothenberg
1982 Whole genome sequencing method is introduced for
DNA sequencing
1982 - 1985 Studies reveal azacitidine, a cytoxic agent developed
by Upjohn, inhibits DNA methylation
June 1982 NIH agrees to provide US$3.2 million over 5 years to
establish and maintain a nucleic sequence database
October 1982 First recombinant DNA based drug approved Genentech Inc
1983 Sanger retires Sanger Laboratory of Molecular Biology
6 Jan 1983 Widespread loss of DNA methylation found on Feinberg, Vogelstein Johns Hopkins University
cytosine-guanine (CpG) islands in tumour samples
20 Jan 1983 Solomon Spiegelman died Spiegelman University of Minnesota
1983 Polymerase chain reaction (PCR) starts to be Mullis Cetus Corporation
developed as a technique to amplify DNA
June 1984 Results from PCR experiments start being reported Mullis Cetus Corporation
1 Jun 1984 Genetically engineered vaccine against hepatitis B Scolnick, McLean, West, McAleer ,Merck, University California San Francisco
reported to have positive trial results Miller, Buynak
10 Sep 1984 First genetic fingerprint revealed Jeffreys University of Leicester
1984 First chimeric monoclonal antibodies developed, Neuberger, Rabbitts, Morrison, Laboratory of Molecular Biology, Stanford
laying foundation for safer and more effective Oi, Herzenberg, Boulianne, Univerity Medical School
monoclonal antibody therapeutics Schulman, Hozumi
December 1984 Carol Greider and Elizabeth Blackburn announced the Blackburn, Greider University of California Berkeley
discovery of telomerase, an enzyme that adds extra
DNA bases to the ends of chromosomes
January 1985 DNA methylation found to occur on specific DNA Bird, Taggart, Fromer, Miller, Edinburgh University, Kanematsu
segments called CpG islands Macleod Laboratories, Columbia University
March 1985 Mullis and Cetus Corporation filed patent for the PCR Mullis Cetus Corporation
technique
7 Mar 1985 DNA fingerprinting principle laid out Jeffreys University of Leicester
17 May 1985 1st legal case resolved using DNA fingerprinting Jeffreys University of Leicester
20 Dec 1985 The Polymerase Chain Reaction (PCR) technique was Mullis Cetus Corporation
published
1986 First machine developed for automating DNA Hood, Smith, Hunkapiller California Institute of Technology, Applied
sequencing Biosystems
30 Apr 1986 Plans for sequencing human genome first laid out Gilbert, Watson, Berg
May 1986 First humanised monoclonal antibody created Dear, Foote, Jones, Neuberger, Laboratory of Molecular Biology
Winter
1986 First genetically engineered vaccine against hepatitis Scolnick Merck
B approved
June 1986 Interferon approved for treating hairy cell leukaemia
December 1986 Genetically engineered hepatitis B vaccine, Engerix-B, SmithKline Biologicals
approved in Belgium
18 Dec 1986 Results released from first small-scale clinical trial of Hoofnagle, Mullen, Jones, Rustgi, National Institutes of Health
recombinant interferon-alpha therapy for post- Di Bisceglie, Peters, Waggoner,
transfusion chronic hepatitis B Park
1987 mRNA encapsulated into liposome made with Malone, Felgner, Verna Salk Institute for Biological Sciences, Syntex
cationic lipids injected into mouse cells shown to
produce proteins
1988 Campath-1H is created - the first clinically useful Winter, Waldmann, Reichmann, Cambridge University, Laboratory of
humanised monoclonal antibody. Clark Molecular Biology
1988 US Congress funds genome sequencing
April 1988 Development of first rapid search computer Pearson, Lipman
programme to identify genes in a new sequence
12 Apr 1988 OncoMouse patent granted Leder, Stewart Harvard University
20 Oct 1988 Cloning of first mammalian enzyme (DNA Bestor, Laudano, Mattaliano, Massachusetts Institute of Technology
methyltransferase, DNMT) that catalyses transfer of Ingram
methyl group to DNA
January 1989 Genetically engineered hepatitis B vaccine, Engerix-B, SmithKline Biologicals
approved in US
May 1989 Genetically engineered hepatitis B vaccine, Pasteur Vaccins
GenHevac, approved in France
25 May 1989 David Deamer draws the first sketch to use a
biological pore to sequence DNA
September 1989 DNA methylation suggested to inactivate tumour Greger, Passarge, Hopping, Institute of Human Genetics
suppressor genes Messmer, Horsthemke
1 Feb 1990 First pitch for US Human Genome Project
1 Oct 1990 Human Genome Project formally launched
December 1990 BRCA1, a single gene on chromosome 17, shown to King, Lee, Newman, Morrow, University of California Berkeley
be responsible for many breast and ovarian cancers Anderson, Huey
21 Dec 1990 BRCA1 gene linked with inherited predisposition to King University of California Berkley
cancer
1992 GenBank is integrated into the NIH National Center
for Biotechnology Information
1 Mar 1992 Method devised to isolate methylated cytosine
residues in individual DNA strands providing avenue
to undertake DNA methylation genomic sequencing
13 Jul 1992 FDA approved the use of genetically engineered Schering-Plough
interferon-alpha, Intron A, for the treatment of
hepatitis B
1 Oct 1992 First experimental evidence showing links between Zapisek, Cronin, Lyn-Cook, Poirier FDA, National Center for Toxicological
diet and DNA methylation and its relationship with Research
cancer
13 Oct 1993 Cetus Corporation was sold to Chiron and its patent Cape, Farley, Glaser Mullis Cetus Corporation, Chiron, Hoffman-La
rights sold for US$300 million to Hoffman-La Roche Roche
1 Nov 1993 Severo Ochoa died Ochoa New York University
30 Dec 1993 FDA appproved genetically engineered enzyme drug Snak Genentech
for cystic fibrosis
19 Aug 1994 Linus C Pauling died Pauling California Institute of Technology
22 Dec 1994 First chimeric monoclonal antibody therapeutic Coller, Schoemaker Centocor, State University of New York
approved for market
21 Apr 1995 First evidence published to demonstrate reduced Laird, Jackson-Grusby, Fazeli, Massachusetts Institute of Technology,
DNA methylation contributes to formation of Dickinson, Jung, Li, Weinberg, Massachusetts General Hospital
tumours Jaenisch
28 Jul 1995 First complete genome sequence published for a self- Venter, Fleischmann, Adams, The Institute for Genomic Research, Johns
replicating free-living organism White, Clayton, Kirkness, Bult, Hopkins
Tomb, Dougherty, Merrick
1996 Complete genome sequence of the first eukaryotic
organism, the yeast S. cerevisiae, is published
1996 Pyrosequencing is introduced for DNA sequencing Ronaghi, Nyren Royal Institute of Technology
10 Jan 1997 Alexander R Todd died Todd University of Manchester
December 1997 First humanised monoclonal antibody approved for Queen Protein Design Labs, Roche
market
May 1998 Commercial Human Genome Project launched Venter Celera Genomics
11 Jun 1998 Complete genome sequence of bacteria that causes Cole, Brosch, Parkhill, Garnier,Wellcome Trust Sanger Institute, National
tuberculosis published Churcher, Harris, Gordon Institutes of Health, Technical University of
Denmark
17 Jul 1998 Genome map published for Treponema pallidum, Fraser, Norris, Weinstock, White, Institute for Genomic Research, University
bacteria that causes syphilis Sutton of Texas Health Centre
11 Dec 1998 Publication of complete genome sequence of the first Sanger Institute, Washington University
multicellular organism, the nematode worm
Caenorhabditis elegans
1999 First human chromosome sequence published
20 Jul 1999 DNA methylation of CpG islands shown to be linked Toyota, Ahuja, Ohe-Toyota, Johns Hopkins University
to colorectal cancer Herman, Baylin, Issa
16 Nov 1999 Daniel Nathans died Nathans Johns Hopkins University
December 1999 Term 'nanopore' used for first time in a publication Akeson, Branton, Kasianowicz, Harvard University, University of California
Brandin, Deamer Santa Cruz, National Institute of Science and
Technology
6 Dec 1999 Robert Swanson died Swanson Genentech
2000 Complete sequences of the genomes of the fruit fly
Drosophila and the first plant, Arabidopsis, are
published
26 Jun 2000 Human genome draft sequence announced
14 Dec 2000 First complete plant genome sequenced
February 2001 First consensus sequence of human genome Sanger, Arber, Wu Laboratory of Molecular Biology, Celera,
published Sanger Institute
2002 Complete genome sequence of the first mammalian
model organism, the mouse, is published
12 Jul 2002 Polio: First ever virus synthesised from chemicals Cello, Paul, Wimmer Stony Brook University
alone
3 Oct 2002 Genomic sequence of the principal malaria parasite Celera Genomics, TIGR, Sanger Centre
and vector completed
April 2003 The sequence of the first human genome was
published
22 Nov 2003 John D Smith died John D Smith California Institute of
Technology, Laboratory of Molecular Biology
2004 FDA approved first DNA methylation inhibitor drug,
azacitidine (Vidaza®), for treatment of rare bone
marrow disorder
28 Jul 2004 Francis H C Crick died Crick Laboratory of Molecular Biology
5 Oct 2004 Maurice H F Wilkins died Wilkins King's College London
23 Dec 2004 FDA approved first DNA microarray diagnostic device Roche
February 2005 Enzyme Ubp10 demonstrated to protect the genome Berger, Emre Wistar Institute
from potential destabilising molecular events
December 2005 Oxford Nanopore Technology secured two rounds of Oxford Nanopore Technology
seed funding from IP Group Plc
2006 FDA approved second DNA methylation inhibitior,
decatabine (Dacogen)
May 2006 Last human chromosome is sequenced
2007 - 2016 Human Microbiome Project (HMP) carried out
May 2007 Oxford Nanopore Technology decides to focus its Oxford Nanopore Technology
resources on developing nanopore sequencing for
DNA sequencing
26 Oct 2007 Arthur Kornberg died Kornberg Stanford University
30 Nov 2007 Seymour Benzer died Benzer Purdue University, California Institute of
Technology
2008 Structure of telomerase, an enzyme that conserves Wistar Institute
the ends of chomosomes, was decoded
2008 - 2012 METAgenomics of the Human Intestinal Tract
(MetaHIT) project carried out
2 Feb 2008 Joshua Lederberg died Joshua Lederberg University of Wisconsin
10 Feb 2008 Ray Wu died in Ithaca, USA Wu Cornell University
27 Dec 2009 Paul Zamecnik died Zamecnik Massachusetts General Hospital
January 2011 DNA sequencing proves useful to documenting the Wellcome Trust Sanger Institute
rapid evolution of Streptococcus pneumococci in
response to the application of vaccines
March 2011 Hand-held DNA sequencer (MinION) successfully Clive Brown Oxford Nanopore Technology
used to sequence first piece of DNA
9 Nov 2011 Har Gobind Khorana died Khorana University of Wisconsin-Madison,
Massachusetts Institute of Technology
15 Feb 2012 - 18 MinION presented in public for first time Clive Brown Oxford Nanopore Technology
Feb 2012
June 2012 DNA sequencing helps identify the source of an MRSA Peacock, Parkhill Cambridge University, Wellcome Trust
outbreak in a neornatal intensive care unit Sanger Institute
December 2012 DNA sequencing utilised for identifying neurological University of California San Diego
disease conditions different from those given in the
original diagnosis
19 Nov 2013 Fred Sanger, the inventor of DNA sequencing, died at Sanger Cambridge
the age of 95
March 2014 Promising results announced from trial conducted
with HIV patients
April 2014 Oxford Nanopore Technology released its palm-sized Oxford Nanopore Technology
DNA sequencer to researchers through its MinION
Access Programme
7 Oct 2015 Nobel Prize in Chemistry was awarded to scientists Lindahl, Modrich, Sancar Francis Crick Institute, Howard Hughes
for understanding the process of DNA repair Medical Institute, University of North
Carolina
13 Jun 2016 Beverly Griffin died Griffin Imperial College
3 Nov 2017 Research showed simple blood test can identify Lee, Gremel, Marshall, Myers, University of Manchester
patients at most risk of skin cancer returning Fisher, Dunn, Dhomen, Corrie,
Middleton, Lorigan, Marais
15 Nov 2017 Rare mutation of gene called Serpine 1 discovered to Khan, Shah, Klyachko, Baldridge, Northwestern University, University of
protect against biological ageing process Eren, Place, Aviv, Puterman, British Columbia, New Jersey Medical
Lloyd-Jones, Heiman, Miyata, School, Tohoku University,
Gupta, Shapiro, Vaughan
29 Jan 2018 MinION shown to be promising tool for sequencing Loman, Quick, Jain, Koren, Miga, University of Birmingham, University of
human genome Rand, Sasani, Tyson, Beggs, Nottingham, University of Utah, University
Dilthey, Fiddes, Malla, Marriot, of British Columbia, University of East
Nieto, O'Grady, Olsen, Pedersen, Anglia, Ontario Institute for Cancer
Rhie, Richardson, Quinlan, Research, University of California Santa Cruz,
Snutch, Tee, Paten, Philippy, National Human Genome Research Institute
Simpson, Loose
9 Mar 2018 John E Sulson died Sulston Laboratory of Molecular Biology, Sanger
Institute
12 Jul 2018 Genetic test shown to accurately predict which Sparano Genomic Health
women benefit from chemotherapy
5 Dec 2018 Genomics England completed sequencing 100,000 Caulfield Sanger Institute, Illumina
whole genomes
October 2019 NHS introduced new fast-track DNA test to scan for South West Genomic Laboratory Hub
rare diseases in babies and children

https://www.whatisbiotechnology.org/index.php/science/summary/dna

James Watson y Francis Crick en 1953

Human Genome Sequence
 Historia del Genoma Humano
Aunque la historia de la genómica tendría que empezar con los estudios pioneros de Gregor Medel (1822-1884) en su
jardín del convento de Brno, Moravia, al norte de la República Checa, publicados en 1985-1986, y el trabajo que
condujo a James Watson (1928-), Francis Crick (1916-2004), Maurice Wilkins (1916-2004) y Rosalind Franklin (1920-
1958) a descubrir el ADN en 1953, por rigor histórico, según la Web oficial del gobierno norteamericano
(www.ornl.gov/techresources/Human_Genome/project/timeline.shtml) la idea de entender las bases del Genoma
Humano (GH) comenzó en realidad en 1983 cuando el LANL (Los Alamos National Laboratory) y el LLNL (Lawrence
Livermore National Laboratory) iniciaron la producción de librerías de cDNA (ADN cósmido) que representaban
cromosomas simples. Obviamente, estos trabajos se basaban en los estudios pioneros de la década de los años
cincuenta, cuando Watson, Crick, Wilkins y Franklin descubrieron el ADN, lo que les valió el Premio Nobel de Medicina
en 1962 a los tres primeros (Rosalind Franklin murió de cáncer a los 37 años).

En 1984, la OHER (Office of Health and Environmental Research) del DOE (Department of Energy) y la ICPEMC
(International Commission for Protection Against Environmental Mutagens and Carcinogens) cofinanciaron la
Conferencia de Alta, en Utah, en la que se planteó el papel relevante de las tecnologías del ADN recombinante.
En 1985, Robert Sinsheimer organizó el meeting sobre la secuenciación del GH en la Universidad de California, en Santa
Cruz; y Charles DeLisi y Davis A. Smith fueron los comisarios de la reunión de Santa Fe para evaluar la viabilidad de la
iniciativa del GH (Human Genome Initiative).
En 1986, el DOE anunció la Human Genome Initiative y dotó al proyecto piloto con un presupuesto de $3.5 millones. La
reunión de Santa Fe se realizó el 3-4 de marzo de 1986. El Genome Sequencing Workshop organizado por M.W. Bitensky,
de Los Alamos National Laboratory, contó con la participación de Norman Anderson, Ben Bernhart, George Bell, Mark
Bitensky, Fred Blattner, Albert Branscomb, Sidney Brenner, Christian Burks, Charles Cantor, Anthony Carrano, Thomas
Caskey, George Chruch, David Comings, Scott Cram, Joseph D’Anna, Larry Deaven, James Fickett, Richard Gelinas, Walter
Gilbert, Walter Goad, Gerald Guralnik, Joyce Hamlin, John Hearst, Elaine Heron, Ed Hildebrand, Maurice Kashdan, Hans
Lehrach, Sankar Mitra, Jane Moores, Robert Moyzis, Ted Puck, Richard Roberts, Francis Ruddle, David Smith, Hamilton
Smith, Gary Stein, Janet Stein, F. William Studier, Eldon Sutton, Robert Wagner, David Ward, Ronald Walters, and Sherman
Weissman. En un escrito del 15 de octubre de la revista Nature, Charles DeLisi definía a esta reunión como el “Meeting”
que cambió el mundo.
En 1987, un comité del DOE ordenado por el Congreso de los Estados Unidos, el HERAC (Health and Environmental
Research Advisory Committe), recomendó un proyecto a 15 años para secuenciar el genoma, y el DOE designó diversos
centros multidisciplinares para llevarlo a cabo. Este mismo año, el NIGMS (National Institute of General Medical Science)
de los NIH (National Institutes of Health) comenzó la financiación del Proyecto GH.
En 1988, los comités de la OTA (Office of Technological Assessment) y la NAS (National Academy of Sciences) del NRC
(National Research Council) recomendaron la creación de un programa concertado para realizar el PGH. El mundo
científico creó la HUGO (Human Genome Organization). El Cold Spring Harbor Laboratory celebró el primer meeting sobre
secuenciación y cartografía del GH. El DOE y los NIH firmaron un MOU (Memorandum of Understanding) para la
cooperación en la investigación del genoma. En el LANL se secuenció el telómero de los cromosomas y se descubrió su
importancia en el envejecimiento y el cáncer.
En 1989, el DNA STS (sequence tagged site) recomendó correlacionar diversos clones de ADN. El DOE y los NIH establecieron
el Joint ELSI (Ethical, Legal, and Social issues) Working Group. Se celebró el primer DOE Human Genome Contractor/Grantee
Workshop el 3-4 de noviembre de 1989 en el Hotel Hilton de Santa Fe.
En 1990, el DOE y los NIH presentaron al Congreso de los Estados Unidos el Plan del HGP (Human Genome Project) y el HGP
comenzó formalmente como un proyecto a 15 años. El HGP se inició marcando genes en los cromosomas como lugares de
expresión de RNA; y se desarrollaron los instrumentos necesarios para producir eficientemente large-insert BACs (Bacterial
Artificial Chromosomes).
En 1991 se estableció la base de datos GDB (Genome Database), en la que se recogía toda la información sobre el genoma
generada en los centros asignados a su investigación.
En 1992 de publicó el primer mapa de ligamiento genético de baja resolución, y se establecieron las bases del DOE y los NIH
para compartir datos y poder acceder libremente a la información sobre el genoma.
En 1993 se estableció el Consorcio Internacional IMAGE (Integrated Molecular Analysis of Gene Expression), presentado el
17 de febrero 1993 en The Scientist y cuyos resultados se hicieron públicos en 1996 en la revista Genomics, en un artículo
firmado por G. Lennon, C. Auffray, M. Polymeropoulos y M.B. Soares. En 1993, la Task Force on Genetic and Insurance
Information del DOE-NIH ELSI Working Group publicó las recomendaciones para el uso de la información genética y revisó la
evolución del proyecto y la consecución de objetivos a 5 años. French Généthon aportó mega-YACs (Yeast Artificial
Chromosomes) a la comunidad científica del genoma. El IOM (Institute for Medicine) hizo público el U.S. HGP-funded report
sobre “Assessing Genetic Risks”. El LBNL (Lawrence Berkeley National Laboratory) implementó un sistema de secuenciación
cromosómica mediada por transposones. El servicio GRAIL (Gene Recognition and Analysis Internet Link) para interpretación
de secuencias facilitó el acceso por internet al ORNL (Oak Ridge National Laboratory).
En 1994 se consiguieron los objetivos marcados para los primeros 5 años del proyecto, un año por delante de lo previsto.
Los laboratorios LLNL y LBNL completaron la segunda generación de librerías de clones de ADN correspondientes a cada
cromosoma humano; se hizo efectiva la Genetic Privacy Act, primer producto legislativo del U.S. HGP, propuesto para
regular la colección, análisis, almacenamiento y uso de muestras de ADN e información genética obtenida a partir de
esas muestras, a propuesta del ELSI Working Group; se inauguró el DOE MGP (Microbial Genome Project), primer spin-off
del HGP; el LLNL comercializó chromosome paints; el ANL (Argonne National Laboratory) también comercializó las
tecnologías SBH (Sequencing by Hybridization); y se activó la Information Web site del HGP para acceso público.

En 1995, los LANL y LLNL anunciaron un mapa físico en alta resolución de los cromosomas 16 y 19, y se publicaron
mapas de resolución media de los cromosomas 3, 11, 12 y 22, así como un mapa físico con más de 15.000 marcadores
STS; en el 95th Meeting de la American Society of Microbiology, celebrado el 21-25 de mayo en Washington DC, Craig
Venter, del Institute for Genomic Research, y Hamilton Smith, de la Johns Hopkins University, anunciaron la secuenciación
completa de los genomas de la bacteria Haemophilus influenze, y de la bacteria más pequeña, Mycoplasma genitalium;
y aparecieron las Guidelines de la EEOC (Equal Employment Opportunity Commission) y la ADA (American with Disabilities
Act) para cubrir la discriminación basada en información genética relativa a enfermedades u otras condiciones
personales.
En 1996 el grupo liderado por Carol Bult secuenció el genoma del microbio productor de metano, Methanococcus jannaschii
(1.7 Mb), confirmando la existencia de la tercera rama de la vida sobre la tierra; el DOE inició 6 proyectos piloto sobre BAC
end sequencing; la Health Care Portability and Accountability Act estableció la prohibición del uso de información genética en
aquellos casos que pudieran condicionar decisiones en seguros de salud; en la Conferencia de las Bermudas se acordó
adoptar una serie de medidas para regular la liberación de datos sobre secuenciación; el DOE y el NCHGR (National Center
for Human Genome Research) establecieron las reglas para el uso de personas en proyectos de secuenciación genómica; el
consorcio internacional completó la secuenciación de la levadura Saccharomyces cerevisiae; se completó la secuencia del
receptor de las células T humanas; y la Wellcome Trust financió una reunión sobre estrategias de secuenciación a gran escala
para la coordinación internacional de la secuenciación del GH.

En 1997, el NIH NCHGR se convirtió en el National Human Genome Research Institute (NHGRI); un grupo de científicos
liderado por Frederick Blattner, de la Universidad de Wisconsin, Madison, completó la secuenciación del genoma de
Escherichia coli (4.6 Mb); se celebró en las Bermudas la segunda reunión sobre estrategias de secuenciación a gran escala; se
completaron los mapas físicos en alta resolución de los cromosomas X y 7; la Task Force on Genetic Testing del DOE-NIH hizo
públicas las recomendaciones para la realización de test genéticos; el DOE creó el Joint Genome Institute para la
implementación de actividades high-throughput en secuenciación y genómica funcional; y la UNESCO adoptó la Universal
Declaration on the Human Genome and Human Rights.
En 1998, el Hospital for Sick Children de Toronto, Ontario, se incorporó a la colección de datos para la GDB; un grupo
internacional liderado por Robert Waterston de la Washington University School of Medicine, St. Louis, y John Sulston, del
Sanger Centre, en Cambridge, Inglaterra, completaron la secuenciación de los 97 millones de bases que constituyen el
genoma del gusano Caenorhabditis elegans; el DOE y los NIH revelaron los planes para los próximos 5 años, anticipando
que el proyecto estaría completado en 2003; el JGI (Joint Genome Institute) del Departamento de Energía, en Walnut
Creek, California, superó las expectativas, secuenciando unos 20 Mb en 1998; se liberó el GeneMap’98, con 30.000
marcadores; Incyte Pharmaceuticals reveló planes para secuenciar el GH en 2 años; la Wellcome Trust Pathogen Genome
Unit del Sanger Centre publicó la secuencia del genoma de Mycobacterium tuberculosis (4.4 Mb); y el Human Genome
News anunció que el Microbial Genome Program (MGP) del DOE estaba secuenciando los genomas de Psedomonas
putida (5.0 Mb), Thiobacillus ferroxidans (2.9 Mb), Desulfovibrio vulgaris (1.7 Mb), Caulobacter crescentus (3.8 Mb),
Chlorobium tepidum (2.1 Mb) y Dehalococcoides ethenogenes; se constituyó Celera Genomics para secuenciar el GH
usando recursos generados por el HGP; el DOE financió nuevos proyectos para BAC end sequencing; más de 800
científicos asistieron al meeting del Largest-ever ELSI financiado por el DOE, el Whitehead Institute y la American Society
of Law, Medicine, and Ethics; y el HGP traspasó su ecuador temporal.
En 1999, el 1 de diciembre, científicos del Sanger Centre, de la Universidad de Oklahoma en Norman, de la
Universidad de Washinton en St. Louis, y de la Universidad Keio en Japón, anunciaron la secuenciación completa del
primer cromosoma humano, el cromosoma 22, con 33.5 millones de bases; se inauguró el Joint Genome Institute en
Walnut Creek, California; un grupo de firmas farmacéuticas anuncian la creación de un consorcio liderado por Arthur
L. Holden para crear un mapa de 300.000 SNPs, con un presupuesto de $30 millones aportado por Bayer, Bristol-
Myers Squibb, Glaxo Wellcome, Hoescht Marion Roussel, Monsanto, Novartis, Pfizer, Roche, SmithKline Beecham y
Zeneca, con una participación adicional de $14 millones aportada por la Wellcome Trust; el 23 de noviembre se
conmemoró la The Billion Base Celebration, con Bruce Alberts como Presidente de la Academy of Sciences y
planificador del proyecto, Francis Collins, como director del NHGRI, Donna Shalala, como Secretaria del HHS, y Bill
Richardson, como Secretario del DOE; y el HGP anunció el objetivo de conseguir un primer borrador del genoma
entre 2000 y 2001.
En 2000, el 25 de junio, los líderes del HGP y el Presidente Clinton anunciaron la consecución del primer borrador del GH
completo, como un gran hito histórico. Las estrellas del evento, aparte del Presidente de los Estados Unidos y el Primer
Ministro inglés, Tony Blair, fueron Ari Patrinos, Director del Human Genome Program, Craig Venter, Director de Celera
Genomics, y Francis Collins, Director del National Human Genome Research Institute de los NIH. Este mismo año, el
Consorcio International presentó la secuencia completa del cromosoma 21, el segundo cromosoma humano secuenciado y
el más pequeño del genoma. Investigadores del DOE, encabezados por Elbert Branscomb, Director del Joint Genome
Institute, y Trevor Hawkins, Director de Secuenciación del mismo instituto, anunciaron la secuenciación completa de los
cromosomas 5, 16 y 19. El 24 de marzo de 2000, la revista Science publicó una serie de artículos de cientos de científicos
distribuidos por más de 20 instituciones públicas y privadas, dirigidos por Gerald Rubin de la Universidad de California en
Berkeley y del Howard Hughes Medical Institute, y Craig Venter de Celera Genomics en Rockville, Maryland, en el que se
descifraban los 250 millones de bases del genoma de la mosca de la fruta, Drosophila melanogaster. Ese mismo año, muy
prolífico para el HGP, el Presidente Clinton firmó la orden ejecutiva por la que se prohibía a las agencias y departamentos
federales usar información genética para la contratación o promoción de los trabajadores públicos.
En 2001 se completó la secuenciación del cromosoma 20, el tercero de la saga humana, en el Wellcome Trust Sanger
Centre. El 15 de febrero en Nature y el 16 de febrero en Science se publicaron los trabajos que descifraban la secuencia del
primer borrador del GH, bajo el liderazgo de Venter y Collins. En el mismo número de Science se publicó un artículo sobre
“Functional Annotation of Mouse Genome Sequences”. Por esa época, Pieter de Jong lideraba un gran equipo de científicos
que se encargaba de proveer las librerías BAC empleadas en la secuenciación del genoma humano y los genomas de otras
especies.
En 2002, el 5 de diciembre, Nature publicó la secuencia del genoma del ratón (Mus musculus), con 2.500 millones de pares
de bases, que comparten un 99% de similitud con el genoma humano, según Jane Rogers del Wellcome Trust Sanger
Centre; y científicos del Consorcio Internacional, liderados por el Joint Genome Institute, hicieron pública la secuencia del
genoma del pez japonés Fugu rubripes, temible por la letal neurotoxina que fabrican sus vísceras.
En 2003 se produjeron dos acontecimientos relevantes: el 50 aniversario del descubrimiento de la doble hélice del ADN, y la
consecución de la secuencia completa del genoma humano (periodo 1990-2003). El 14 de abril se declaró completo el HGP,
compuesto por 3.000 millones de pares de bases, dos años antes de lo previsto, con gran despliegue mediático. El 24 de abril
de 2003, la revista Nature sacó un número especial dedicado al 50 aniversario del ADN, conmemorando la hazaña de James
Watson (primer director del HGP, defenestrado en 1992 por desavenencias sobre la patente de genes con Bernardine Healey,
Directora de los NIH; sustituido en abril de 1993 por Francis Collins), Maurice Wilkins, Rosalind Franklin y Francis Crick en
1953, y una serie de trabajos que culminaban el esfuerzo heroico realizado para secuenciar el GH en un tiempo record. Entre
los trabajos publicados destacaban "A Vision for the Future of Genomics Research" de Francis S. Collins, Eric D. Green, Alan E.
Guttmacher, y Mark S. Guyer, (Nature Apr 24: 835, 2003), "Genetics and the Making of Homo sapiens" de Sean B. Carroll
(Nature Apr 24: 849, 2003), y "Genome Sequencing: Revelations from a Bread Mould" de Jonathan Arnold y Nelson Hilton
(Nature Apr 24: 821, 2003). Simultáneamente, el 11 de abril, la revista Science publicó un número especial (Building on the
DNA Revolution), con trabajos de Francis S. Collins, Michael Morgan, and Aristides Patrinos ("The Human Genome Project:
Lessons from Large-Scale Biology", Science 300: 286, 2003) y de Marvin E. Frazier, Gary M. Johnson, David G. Thomassen,
Carl E. Oliver, y Aristides Patrinos ("Realizing the Potential of the Genome Revolution: The Genomes to Life Program", Science
300:290, 2003). También en abril se celebró el symposium From Double Helix to Human Sequence - and Beyond. En enero, se
había completado la secuencia de 87 millones de pares de bases del cromosoma 14. En junio se hizo pública la secuencia del
cromosoma Y, y Helen Skaletsky lideró el trabajo publicado el 19 de junio en Nature (423, 825-837, 2003;
doi:10.1038/nature01722). El 10 de Julio, Nature publicó la secuencia del cromosoma 7, completada por el equipo
de Ladeana W. Hillier; y en octubre se completó la secuencia del cromosoma 6.
El 2004 no fue un año menos prolífico que el anterior. La producción científica sobre GH se multiplicó, impulsada por el
impacto generado por la secuenciación completa del genoma, aunque muchos creían, con toda lógica, que todavía estaba
cargada de lagunas e imperfecciones que se fueron puliendo en años sucesivos. En marzo de 2004 se completaron las
secuencias de los cromosomas 13, 19 (1500 genes, 55.8 millones de bases, 2% del genoma) y 18 (Chad Nusbaum y Eric S.
Lander publicaron la secuencia en Nature 437, 551 – 555, 2005); en mayo, las de los cromosomas 9 y 10; el 27 de mayo,
Nature publicó un trabajo de Jeremy Schmutz del Stanford Human Genome Center sobre Human genome: Quality
assessment of the human genome sequence (Nature 429, 365-368 | doi:10.1038/nature02390); en septiembre se completó
la secuencia del cromosoma 5; en octubre se hizo una nueva estimación del número posible de genes en el genoma
humano, estimando la existencia de unos 25.000 genes funcionales; el 21 de octubre, F .S. Collins, E. S. Lander, J. Rogers y R.
H. Waterston lideraban un trabajo del International Human Genome Sequencing Consortium (Nature 431, 931-
945|doi:10.1038/nature03001) sobre la conclusión de la secuencia eucromática del genoma humano; y en diciembre se
completó la secuencia del cromosoma 16. En el trabajo del Consorcio se establecía que el GH tenía unos 2.850 millones de
nucleótidos, con 341 gaps, cubriendo un 99% del genoma eucariótico con una tasa de error de un evento por cada 100.000
bases, sobre un número de 20.000-25.000 genes.
En marzo de 2005 se completó la secuencia del cromosoma X (Ross et al. Nature 434, 325 - 337); y en abril de 2005, se
completaron los cromosomas 2 y 4. En 2005, el Chimpanzee Sequencing and Analysis Consortium adelantó un análisis
comparativo entre el genoma del chimpancé y el humano (Nature 437, 69 – 87); K. Lindblad Toh y colaboradores
presentaron la secuencia del genoma del perro (Nature 438, 803 – 819). En enero de 2006 se completó la secuencia del
cromosoma 8 (Chad Nusbaum et al; Nature, 439|doi:10.1038/nature04406) ; en marzo se completaron las secuencias de los
cromosomas 11 (Todd D. Taylor et al; Nature, 440|doi:10.1038/nature04632) , 12 (Steven E. Scherer et al; Nature,
440|doi:10.1038/nature04569), y 15 (Michael C. Zody et al; Nature, 440|doi:10.1038/nature04601); en abril los
cromosomas 3 (Donna M. Muzny et al; Nature, 440|doi:10.1038/nature04728) y 17 (Michael C. Zody et al; Nature,
440|doi:10.1038/nature04689); y en mayo se completó la secuencia del cromosoma 1 (S. G. Gregory et al; Nature,
441|doi:10.1038/nature04727).
2007 no fue un año muy productivo en publicaciones relevantes, según la Web oficial del HGP, y en 2008 se convirtió en ley
la GINA (Genetic Information Nondiscrimination Act). El 1 de mayo, apareció en Nature la última publicación oficial del HGP
(Mapping and sequencing of structural variation from eight human genomes)(Nature 453, 56-64| doi:10.1038/nature06862).
Este trabajo, liderado por Jeffrey Kidd, de la Universidad de Washington en Seattle, revelaba la existencia de unas 1695
variantes genómicas, así como la existencia de múltiples alteraciones en la estructura del genoma.
La última gran aportación oficial del HGP es el ENCODE (the ENCyclopedia Of DNA Elements)(Guidebook to the Human
Genome), una serie de artículos editados por Nature el 6 de septiembre de 2012, con financiación de Illumina, Inc., y la labor
editorial de Magdalena Skipper, Ritu Dhand y Philip Campbell.
Venter JC, The sequence of the human genome. Science. 2001 Feb
16;291(5507):1304-51. doi: 10.1126/science.1058040. Erratum in:
Science 2001 Jun 5;292(5523):1838. PMID: 11181995.
Nurk S et al. The complete sequence of a human genome. Science. 2022 Apr;376(6588):44-53.
doi: 10.1126/science.abj6987. Epub 2022 Mar 31. PMID: 35357919; PMCID: PMC9186530.

Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome,
leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-
Telomere (T2T) Consortium presents a complete 3.055 billion-base pair sequence of a human genome, T2T-CHM13, that
includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly
200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The
completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five
acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies.
Antonarakis SE. Short arms of human acrocentric chromosomes and the completion of the human genome sequence.
Genome Res. 2022 Apr;32(4):599-607. doi: 10.1101/gr.275350.121. Epub 2022 Mar 31. PMID: 35361624; PMCID:
PMC8997349.
The complete, ungapped sequence of the short arms of human acrocentric chromosomes (SAACs) is still unknown almost
20 years after the near completion of the Human Genome Project. Yet these short arms of Chromosomes 13, 14, 15, 21, and
22 contain the ribosomal DNA (rDNA) genes, which are of paramount importance for human biology. The sequences of
SAACs show an extensive variation in the copy number of the various repetitive elements, the full extent of which is
currently unknown. In addition, the full spectrum of repeated sequences, their organization, and the low copy number
functional elements are also unknown. The Telomere-to-Telomere (T2T) Project using mainly long-read sequence
technology has recently completed the assembly of the genome from a hydatidiform mole, CHM13, and has thus
established a baseline reference for further studies on the organization, variation, functional annotation, and impact in
human disorders of all the previously unknown genomic segments, including the SAACs. The publication of the initial results
of the T2T Project will update and improve the reference genome for a better understanding of the evolution and function
of the human genome.
Jarvis, E.D., Formenti, G., Rhie, A. et al. Semi-automated assembly of high-quality diploid human reference
genomes. Nature 611, 519–531 (2022). https://doi.org/10.1038/s41586-022-05325-5

The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly,
which has benefitted society. However, it still has many gaps and errors, and does not represent a biological genome as
it is a blend of multiple individuals. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated
with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous
genome. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating
high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic
diversity. Here, in our first scientific report, we determined which combination of current genome sequencing and
assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation.
Approaches that used highly accurate long reads and parent–child data with graph-based haplotype phasing during
assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated
our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average,
with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous
amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a
foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global
genetic variation from single nucleotides to structural rearrangements.
Sequencing Genomes-I
Sequencing Genomes-II
Comparative Genomics
Cariotipo Humano
Cromosomas del Genoma Humano
Mitochondrial Heteroplasmy

Mitochondrial Genome
Evolutionary Tree
Tracing Human Origins
 Caenorhabditis elegans genome

Chromosome 1 Chromosome 2 Chromosome 3

 Drosophila melanogaster genome

Chromosome 4 Chromosome X
Drosophila melanogaster genome

Mitochondrial Genome
 Mouse Genome

Chromosome 1 Chromosome 2 Chromosome 3 Chromosome 4 Chromosome 5

Transgénicos
Date Event People Places
23 Jun 1925 Oliver Smithies was born in Halifax, United Kingdom Smithes University of Washington, University of
North Carolina
1929 Jackson Memorial Laboratories established to Jackson Memorial Laboratoroies
develop inbred strains of mice to study the genetics of
cancer and other diseases
19 Aug 1929 Frank Ruddle was born in West New York, New Ruddle Yale University
Jersey
18 Sep 1951 Anthony J Clark was born in Blackpool, UK Anthony Clark Roslin Institute
1974 First publication on inserting foreign DNA into mice Jaenisch, Mintz Salk Institute, Fox Chase Institute for
Cancer Research
September 1980 Scientists reported the first successful development Barbosa, Gordon, Yale University
of transgenic mice Plotkin, Ruddle, Scangos
November 1980 Technique published using fine glass micropipettes to Capecchi University of Utah
inject DNA directly into the nuclei of cultured
mammalian cells. High efficiency of the method
enables investigators to generate transgenic mice
containing random insertions of exogenous DNA.
5 Nov 1981 First successful transmission of foreign DNA into Constantini, Lacy Oxford University, Yale University
laboratory mice
December 1982 Giant mice made with the injection of rat growth Brinster, Palmiter University of Pennsylvania, University of
hormone Washington Seattle
1983 Course started in the molecular embyology of mice Costantini, Hogan, Lacy Cold Spring Harbour Laboratory, NIMR,
Sloan Kettering Cancer Research Center,
Columbia University
1985 First transgenic mice created with with genes coding Kohler, Rusconi Max-Planck Institute
for both the heavy and light chain domains in an
antibody.
6 Nov 1987 Publication of gene targeting technique for targetting Thomas, Capecchi University of Utah
mutations in any gene
1988 Patent application filed for a method to create Bruggeman, Caskey, Laboratory of Molecular Biology, Babraham
transgenic mice for the production of human Neuberger, Surani, Institute, Cambridge University
antibodies Teale, Waldmann, Williams
12 Apr 1988 OncoMouse patent granted Leder, Stewart Harvard University
12 Jun 1992 First transgenic mouse model created for studying Li, Bestor, Jaenisch Whitehead Institute for Biomedical Research
link between DNA methylation and disease
1994 First transgenic mice strains reported for producing Bruggemann, S.Green, Cell Genesys, GenPharm, Laboratory of
human monoclonal antibodies Lonsberg, Neuberger Molecular Biology
5 Jul 1996 Dolly the sheep, the first cloned mammal, was born Wilmut, Campbell Roslin Institute
9 Jul 1997 Birth of first sheep cloned with human genes Schnieke, Kind, Ritchie, PPL Therapeutics, Roslin Institute
Mycock, Scott, Wilmutt,
Colman, Campbell
14 Feb 2003 Dolly the sheep, the first cloned mammal, died Wilmut Roslin Institute
12 Aug 2004 Anthony J Clark died Anthony Clark Roslin Institute
September 2006 First fully human monoclonal antibody drug approved Agensys, Amgen
2007 Nobel Prize for Physiology for Medicine awarded for Capecchi, Evans, Smithies University of North Carolina, University of
discoveries enabling germline gene modification in Utah
mice using embryonic stem cells
10 Mar 2013 Frank Ruddle died in New Haven, Connecticut Ruddle Yale University
26 Oct 2013 Michael Neuberger died Neuberger Laboratory of Molecular Biology
23 Sep 2015 Beijing Genomics Institute announced the sale of the Beijing Genomics Institute
first micropigs created with the help of the TALENs
gene-editing technique
5 Oct 2015 CRISPR/Cas9 modified 60 genes in pig embryos in Church Harvard University
first step to create organs suitable for human
transplants
10 Jan 2017 Oliver Smithies died Smithies University of Washington, University of
North Carolina
20 Apr 2017 Diabetes research using transgenic mice shows the Menzies University of Edinburgh, University College
protein P2X7R plays important role in inflammation London, Imperial College
and immune system offering new avenue for treating
kidney disease
23 Jan 2019 CRISPR-Cas9 used to control genetic inheritance in Grunwald, Gntz, Poplawski, University of California San Diego
mice Xu, Bier, Cooper
25 Sep 2021 First genetically engineered pig kidney successfully Robert Montgomery New York University
transplanted into a brain-dead human patient
11 Jan 2022 First pig-to-human heart transplant Mohiuddin University of Maryland
https://www.whatisbiotechnology.org/index.php/science/summary/transgenic
PCR
Date Event People Places
9 Jan 1922 Har Gobind Khorana was born in Raipur, India Khorana University of Wisconsin-Madison,
Massachusetts Institute of Technology
28 Dec 1944 Kary B Mullis was born in Lenoir, North Carolina, USA Mullis Cetus Corporation
1969 First principles for PCR published Khorana, Kleppe University of Wisconsin-Madison
1969 New species of bacterium is isolated from hot spring in Brock Case Western Reserve University
Yellowstone National Park by Thomas Brock
1971 Process called repair replication for synthesising short Khorana, Kleppe MIT
DNA duplexes and single-stranded DNA by polymerases
is published
1983 Polymerase chain reaction (PCR) starts to be developed Mullis Cetus Corporation
as a technique to amplify DNA
June 1984 Results from PCR experiments start being reported Mullis Cetus Corporation
10 Sep 1984 First genetic fingerprint revealed Jeffreys University of Leicester
January 1985 - Cetus developed PCR for measuring amount of HIV Cetus Corporation
May 1987 circulating in blood
March 1985 Mullis and Cetus Corporation filed patent for the PCR Mullis Cetus Corporation
technique
7 Mar 1985 DNA fingerprinting principle laid out Jeffreys University of Leicester
December 1985 Cetus Corporation and Perkin-Elmer partnered to Cetus Corporation
develop instruments and reagents for PCR
20 Dec 1985 The Polymerase Chain Reaction (PCR) technique was Mullis Cetus Corporation
published
November 1988 Patent application filed for the the use of PCR to create Gussow, Jones, Olandi, Laboratory of Molecular Biology, Istituto
a library of antibody fragments Winter Nazionale dei Tumori
January 1989 PCR technique starts being used for DNA finger printing
tests
13 Oct 1993 Cetus Corporation was sold to Chiron and its patent Cape, Farley, Glaser Mullis Cetus Corporation, Chiron, Hoffman-La Roche
rights sold for US$300 million to Hoffman-La Roche
15 Jun 2000 New simpler and cheaper PCR method published Nogtomi, Okayama, University of Tokyo, Osaka University, Eiken
opening possibility for use in middle to low-income Masubuchi, Yonekawa, Chemical Co
countries Wantabe, Amino
9 Nov 2011 Har Gobind Khorana died Khorana University of Wisconsin-Madison,
Massachusetts Institute of Technology
https://www.whatisbiotechnology.org/index.php/science/summary/pcr
Epigenetica
Hans Selye (1907-1982) Conrad Waddington (1905-1975)
General Adaptation Syndrome Epigenetics-Transgenerational Inheritance
Genome Epigenome Environment
Biochemical Language for Communication
Between Genome and Environment

Trangenerational Inheritance of phenotypes

without structural changes in DNA

Transcriptional and post-transcriptional

Regulation of gene expression

Reversibility of epigenetic marks

by exogenous intervention
Pharmacological
Nutritional
Physico-Chemical
Developmental Origins of Health and Disease
 DNA Methylation

Chromatin Remodeling

Acetylation
Deacetylation
Methylation EpiGenomics
Phosphorylation
Sumoylation

Histone Modification

miRNA Regulation
18 Dec 1829 Jean-Baptiste Lamarck died Lamarck French Academy of Sciences
1898 A nucelotide called tuberculinic acid found to bind to Ruppel Philipps University of Marburg
the protein tuberculin. It is now regarded as the
precursor to the discovery of DNA methylation
November 1925 T.B. Johnson and R.D. Coghill reported detecting a Johnson, Coghill Yale University
minor amount of methylated cytosine derivative as
byproduct of hyrdrolysis of tuberculinic acid with
sulfuric acid but other scientists struggled to replicate
their results.
1942 'Epigenetics' coined as a term to describe how genes Waddngton Cambridge University
interact with the environment to produce the physical
traits of an organism
March 1948 Hotchkiss discovered the first naturally modifed DNA Hotchkiss Rockefeller Institute
nucleotide, cytosine, in a chromatography of calf
thymus DNA
May 1951 5-methcytosine isolated in nucleic acids for the first Wyatt
time
1957 Conrad Waddington develops model of epigenetic Waddngton Cambridge University
landscape to show the process of cellular decision-
making during biological development
22 Apr 1961 Genes linked to X-chromosome inactivation in female Lyon Cambridge University
mice embyos
23 Jan 1962 Idea of restriction and modification enzymes born Arber, Dussoix University of Geneva
July 1969 Discovery of methylase, an enzyme, found to add Arber, Linn University of Geneva
protective methyl groups to DNA
1975 DNA methylation suggested as mechanism behind X- Riggs, Sager, Kitchen City of Hope National Medical Center,
chomosome silencing in embryos Harvard University
1975 DNA methylation proposed as important mechanism Hoilliday, Pugh National Institute for Medical Research
for the control of gene expression in higher organisms
July 1981 First evidence provided to show that DNA methylation Compere, Palmitter Howard Hughes Medical Institute
involved in silencing X-chromosome
1982 - 1985 Studies reveal azacitidine, a cytoxic agent developed
by Upjohn, inhibits DNA methylation
1982 Azacitidine fails to win FDA approval for treatment of
acute myelogenous leukaemia due to lack of controlled
studies showing clinical benefit
6 Jan 1983 Widespread loss of DNA methylation found on Feinberg, Vogelstein Johns Hopkins University
cytosine-guanine (CpG) islands in tumour samples
January 1985 DNA methylation found to occur on specific DNA Bird, Taggart, Fromer, Edinburgh University, Kanematsu
segments called CpG islands Miller, Macleod Laboratories, Columbia University
20 Oct 1988 Cloning of first mammalian enzyme (DNA Bestor, Laudano, Massachusetts Institute of Technology
methyltransferase, DNMT) that catalyses transfer of Mattaliano, Ingram
methyl group to DNA
September 1989 DNA methylation suggested to inactivate tumour Greger, Passarge, Institute of Human Genetics
suppressor genes Hopping, Messmer,
Horsthemke
1 Mar 1992 Method devised to isolate methylated cytosine
residues in individual DNA strands providing avenue to
undertake DNA methylation genomic sequencing
12 Jun 1992 First transgenic mouse model created for studying link Li, Bestor, Jaenisch Whitehead Institute for Biomedical Research
between DNA methylation and disease
1 Oct 1992 First experimental evidence showing links between diet Zapisek, Cronin, Lyn- FDA, National Center for Toxicological
and DNA methylation and its relationship with cancer Cook, Poirier Research
21 Apr 1995 First evidence published to demonstrate reduced DNA Laird, Jackson-Grusby, Massachusetts Institute of Technology,
methylation contributes to formation of tumours Fazeli, Dickinson, Jung, Massachusetts General Hospital
Li, Weinberg, Jaenisch
20 Jul 1999 DNA methylation of CpG islands shown to be linked to Toyota, Ahuja, Ohe- Johns Hopkins University
colorectal cancer Toyota, Herman, Baylin,
Issa
November 1999 First evidence from mammals that epigenetic changes Morgan, Sutherland, University of Sydney
can be passed down generations Martin, Whitelaw
2001 Pharmion licenses azacitidine from Pharmacia and
Upjohn to Pharmacia's azacityidine technology,
patents and clinical data
2004 FDA approved first DNA methylation inhibitor drug,
azacitidine (Vidaza®), for treatment of rare bone
marrow disorder
2006 FDA approved second DNA methylation inhibitior,
decatabine (Dacogen)
6 Oct 2006 FDA approved first histone deacetylase inhibitor,
Vorinostat (Zolinza), for cutaneous T-cell lymphoma
November 2009 FDA approved second histone deactylase inhibitor,
Romidepsin (Istodax), for cutaneous T-cell lymphoma
2012 European approval of decatabine (Dacogen) for
treatment of acute myeloid leukaemia
April 2015 Chinese regulatory authorities approved Chidamide, a
histone deactylase inhibitor, for peripheral T cell
lymphoma
27 Aug 2015 Experiments with mice showed that azacytidine
treatment enhanced the responsiveness of tumors to
anti–CTLA-4 therapy
https://www.whatisbiotechnology.org/index.php/science/summary/epigenetics
CRISPR
Date Event People Places
December 1987 The CRISPR mechanism first published Amemura, Ishino, Makino, Osaka University
Nakata, Shinagawa, Takase,
Wachi
18 Jan 2000 More clustered repeats of DNA identified in other Mojica, Diez-Villasenor, Soria, University of Alicante, University Miguel
bacteria and archaea, termed Short Regularly Juez Hernandez
Spaced Repeats (SRSR)
March 2002 Term CRISPR-Cas9 published for first time Mojica, Jansen, Embden, Utrecht University
Gaastra, Schouls
2005 Jennifer Doudna and Jillian Banfield started Doudna, Banfield University of California Berkeley
investigating CRISPR
1 Aug 2005 French scientists suggested CRISPR spacer Bolotin, Quinquis, Sorokin, Institut National de la Recherche
sequences can provide cell immunity against phage Ehrlich Agronomique
infection and degrade DNA
11 Nov 2005 American researchers identified new familes of Cas Haft, Selengut, Mongodin, The Institute for Genomic Research
genes which appeared to help in protecting bacteria Nelson
against invading viruses
23 Mar 2007 Experiments demonstrate for the first time the role of Barrangou, Horvath, Fremaux, Danisco USA Inc
CRISPR together with Cas9 genes in protecting Deveau,
bacteria against viruses
2008 DNA, not RNA, demonstrated to be the molecular
target of most CRISPR-Cas systems
February 2008 Scientists coin the term 'protospacer' to denote viral
sequence that corresponds to a 'spacer' in the
CRISPR-Cas9 system
August 2008 Scientists characterised the RNA processing Wageningen University, University of
pathway in CRISPR system Sheffield, National Institutes of Health
December 2008 Scientists published the RNA gene silencing pathway Carte, Wang, Li, Terns University of Georgia, Florida State
involved in the CRISPR-Cas mechanism University
2011 Classification of the CRISPR-Cas system is
proposed
March 2011 Emmanuelle Charpentier and Jennifer Doudna joined Doudna, Charpentier, Hinek, University of California Berkeley, Umea
forces to investigate Cas9 enzyme Hauser University
April 2012 First commercialisation of CRISPR-Cas 9 technology Dupont
May 2012 First patent application submitted for CRISPR-Cas 9 Doudna, Charpentier University of California Berkeley, University
technology of Vienna
17 Aug 2012 Publication of radically new gene editing method that Jinek, Chylinski, Fonfara, University of California Berkeley
harnesses the CRISPR-Cas9 system Hauer, Doudna, Charpentier
25 Sep 2012 Scientists at the Vilnius University published paper Siksnys, Gasiunas, Vilunius University
elucidating the potential of CRSIPR/Cas9 to edit Barrangou, Horvath
DNA
12 Dec 2012 Fast track application for CRISPR-Cas 9 technology Zhang Broad Institute, Massachusetts Institute of
submitted to US patent office. Technology
January 2013 CRISPR-Cas is used in human genome editing
January 2013 CRISPR-Cas is used to edit the genome of a
zebrafish
February 2013 CRISPR-Cas shown to programme repression and Bikard, Murrafini Rockefeller University
activation of gene transcription
March 2013 CRISPR-Cas is used in genome editing of
Saccharomyces cerevisiae, a yeast species used in
wine making, baking and brewing
1 Apr 2013 CRISPR-Cas mediated gene regulation shown to Sampson, Weiss Emory University
help regulation of endogenous bacterial genes
August 2013 CRISPR-Cas used to engineer a rat's genome
August 2013 CRISPR-Cas used to engineer plant genomes
including rice, wheat, Arabidopsis, tobacco and
Sorghum
August 2013 Improvements made to the specificity of CRISPR-
Cas system
March 2015 Scientists suggest CRISPR/Cas9 used with stem Feng, Dai, Mou, Cooper, Shi, Shenzhen University, University of
cells could provide human organs from transgenic Cai Pittsburgh Medical Center, Guangxi
pigs University
26 Mar 2015 US scientists call for a voluntary worldwide Lamphier, Urnov
moratorium on the use of genome editing tools to
modify human reproductive cells
15 Apr 2015 National Institutes of Health declared it will not fund
any use of genome editing technologies in human
embryos
22 Apr 2015 UK Nuffield Council on Bioethics launched a new
working group to look into institutional, national and
international policies and provisions relevant to
genome editing
1 May 2015 First report of genes edited in human embryos Huang, Liang, Xu, Zhang Sun Yat-sen University
ignited global ethical debate about gene edting
technology
2 Sep 2015 Leading UK research councils, including the MRC,
declared support for using CRISPR-Cas9 and other
genome editing techniques in preclinical research
11 Sep 2015 Hinxton Group issues a statement indicating that
most of the ethical and moral questions raised about
CRISPR and gene editing have been debated before
11 Sep 2015 Hinxton Group issues a statement indicating that
most of the ethical and moral questions raised about
CRISPR and gene editing have been debated before
15 Sep 2015 UK Nuffield Council on Bioethics held its first
workshop to identify and define ethical questions
relating to developments in genome editing research
18 Sep 2015 UK scientists sought license to genetically modify Naikan Crick Institute
human embryos to study the role played by genes in
the first few days of human fertilisation
25 Sep 2015 New protein, Cpf1, found, offering means to simplify Zhang, Zetsche, Gootenberg, Broad Institute, Massachusetts Institute of
gene editing. Abudayyeh, Slaymaker Technology
5 Oct 2015 CRISPR/Cas9 modified 60 genes in pig embryos in Church Harvard University
first step to create organs suitable for human
transplants
6 Oct 2015 UNESCO’s International Bioethic Committee called
for ban on genetic editing of human germline
16 Nov 2015 US scientists published a technique for overwriting DiCarlo, Chavez, Dietz, Harvard University, Swiss Federal Institute
changes made by CRISPR/Cas 9 Esvelt, Church of Technology in Zurich
23 Nov 2015 US scientists genetically modified mosquitos using Gantz, Jasinskiene, University California San Diego, University
CRISPR/Cas9 to prevent them carrying malaria Tatarenkova, Fazekas, of California Irvine
parasite Macias, Bier, James
1 Dec 2015 International Summit on Human Gene Editing met to Baltimore, Doudna, Church, US National Academies of Science,
discuss the scientific, medical, ethical, and Zhang Engineering and Medicine, US National
governance issues associated with recent advances Academy of Medicine, Chinese Academy of
in human gene-editing research Sciences, Royal Society
31 Dec 2015 Gene editiing tool, CRISPR, successfully used to Nelson, Gersbach, Hakim, Duke University, University of Missouri,
improve muscle function in mouse model of Ousterout, Thakore University of North Carolina, Massachusetts
Duchenne muscular dystrophy Institute of Technology, Harvard University
6 Jan 2016 US scientists published improved version of Kleinstiver, Pattanayak, Prew, Harvard University
CRISPR/Cas 9 with less risk of off-target DNA Tsai, Nguyen, Zheng, Joung
breaks
1 Feb 2016 UK scientists authorised to genetically modify human Niakan Crick Institute
embryos using CRISPR-Cas 9
16 May 2016 US scientists publish new base editing technique Komor, Kim, Packer, Zuris, Harvard University
offering means to alter genome without needing to Liu
cleave double-stranded DNA or for a donor DNA
template
21 Jun 2016 2016: NIH gives green light for first clinical trial using June University of Pennsylvania
gene editing tool CRISPR/Cas 9 to treat patients
February 2017 US National Academies of Science and Medicine
gave green light to proceed with CRISPR in germ-
line experiments
13 Apr 2017 CRISPR shown to be sensitive diagnostic tool for Abudayyeh, Bhattacharyya, Broad Institute, Massachusetts Institute of
detecting single target of DNA or RNA molecule Collins, Daringe, Donghia, Dy, Technology, Harvard University, Howard
Essletzbichler, Freije, Hung, Hughes Medical Institute
Joung, Koonin, Lee, Livny,
Myhrvold, Regev, Sabeti,
Gootenberg, Verdine, Zhang
13 May 2017 Research published demonstrating how CRISPR- Yin, Zhang, Qu, Chang, Temple University, University of Pittsburgh,
CAS9 can be used to eliminate HIV in infected mice. Putatunda, Xiao, Li, Zhao, Sichuan University
Dhai, Qin, Mo, Young, Khalili,
Hu
2 Aug 2017 Research published demonstrating possibility of Hong, Marti-Gutierrez, Park, Oregon Health & Science University, Salk
editing gene defect in pre-implanted human embryos Mitalipov, Kaul, Kim, Amato, Institute, Center for Genome Engineering,
for preventing inherited heart disease Belmonte Seoul National University, China National
GeneBank,
September 2017 DNA of human embryos edited using CRISPR-Cas9 Fogarty, McCarthy, Snijders, Francis Crick Instiitute, Cambridge
to study cause of infertility Powell, Kubikova, Blakeley, University, Oxford University, Seoul
Lea, Elder, Wamaitha, Kim, National University
Maciulyte, Kleinjung, Kim,
Wells, Vallier, Bertero, Turner,
Niakan
23 Sep 2017 Chinese researchers report correction of gene linked Liang, Ching, Sun, Xie, Xu, Sun Yat-sen University, Baylor College of
to beta thalassaemia, inherited blood disorder, in Zhang, Xhiong, Ma, Liu, Medicine
human embryos using base editing technique Wang, Fang, Songyang,
Zhou, Huang
25 Oct 2017 New CRISPR technique published for editing RNA Zhang, Cox, Gootenberg, Massachusetts Institute of Technology,
Abudayyeh, B Franklin, University of Minnesota
Kellner, Essletzbichler,
Verdine, Joung, Lander,
Belanto, Voytas, Regev
25 Oct 2017 Base editing improvements announced for CRISPR Gaudelli, Komor, Rees, Massachusetts Institute of Technology,
technique, providing means to change individual Packer, Badran, Bryson, Liu Harvard University
chemical letters of DNA without need to cleave DNA
5 Jan 2018 Researchers identify pre-existing antibodies targetingCharlesworth, Deshpande, Stanford University
CAS9 proteins raising possibility of immune Dever, Dejene,Gomez-
responses undermining utility of CRISPR-Cas9 for Ospina, Mantri, Pavel-Dinu,
gene therapy Camarena, Weinberg, Porteus
27 Aug 2018 First CRISPR-Cas9 clinical trial launched Vertex Pharmaceuticals, CRSIPR
Therapeutics
24 Nov 2018 First gene-edited babies announced by Chinese Jiankui Southern University of Science and
scientist Technology of China
14 Dec 2018 New gene modification technique (CRISPRa) makes Matharu, Rattanasopha, University of California San Francisco
it possible to increase expression of its target gene Tamura, Maliskova, Wang,
Bernard, Hardin, Eckalbar,
Vaisse, Ahituv
21 Dec 2018 CRISPR-Cas9 editing helped restore effectiveness of Kmiec, Bialk, Wang, Hanas Helen F Graham Cancer Center and
first-line chemotherapies for lung cancer Research Institute
23 Jan 2019 CRISPR-Cas9 used to control genetic inheritance in Grunwald, Gntz, Poplawski, University of California San Diego
mice Xu, Bier, Cooper
30 Jul 2019 World Health Organisation called on countries to ban
experiments that would lead to more gene-edited
babies
21 Oct 2019 New DNA editing technique called 'prime editing' Anzalone, Randolph, Davis, Massachusetts Institute of Technology,
published Sousa, Koblan, Levy, Chen, Harvard University
Wilson, Newby, Ranguram,
Liu
30 Dec 2019 Chinese scientist convicted for using CRISPR-Cas9 Jiankui Southern University of Science and
in human babies Technology of China
4 Mar 2020 First patient received gene editing therapy with Pennesi Oregon Health and Science University
CRISPR directly administered into the body
June 2020 Research published casting doubt over safety of Francis Crick Institute, Columbia University,
using CRISPR-Cas 9 to modify human embryos Oregon Health & Science University
7 Oct 2020 Nobel Prize in Chemistry awarded to Emmanuelle Doudna, Charpentier University California Berkeley, University of
Charpentier and Jennifer Doudna 'for the Umea
development of a method for genome editing'.
27 Sep 2022 FDA gives Vertex green light to submit rolling
application for review of CRISPR based therapy to
treat sickle cell disease and beta thalassemia
10 Nov 2022 Small clinical trial shows CRISPR promising tool for Foy, Ribas, Mandl PACT Pharma
editing immune cells to enhance their capacity to
destroy cancer cells
23 Nov 2022 New CRISPR gene editing tools found in thousands Al-Shayeb, Skopintsev, University of California Berkeley
of phages Soczek, Stahl,Zheng Li,
Smock, Eggers, Pausch,
Cress, Huang, Staskawicz,
Savage,Jacobsen,
Banfield, Doudna
https://www.whatisbiotechnology.org/index.php/science/summary/crispr
PharmacoGenetics
 Genetic Polymorphisms

PharmacoEpiGenetics
PharmacoGenetics
Pharmacokinetics Pharmacodynamics
Absortion Receptors
30-90%
Distribution Ion channels
variability
Metabolism Enzymes
Excretion Proteins

Safety Efficacy

Pathogenic mechanisms
Transcriptomics
Proteomics
Metabolomics

Metabolism DRUGS Disease

Cacabelos (2005)
Index: 52,000 entries
Drugs: 7,750
Brand Names: 31,750
Pharmacological
Categories: 1,891
Genes: 4,450
Diseases: 9,200
Primera Guía Mundial de Farmacogenómica
En los últimos 20 años se han publicado interesantes obras de farmacogenética y farmacogenómica, centradas
fundamentalmente en la explicación conceptual de la disciplina y su potencial aplicación en determinadas patologías.
Ejemplos de estas obras magníficas (y pioneras) son la de Kalow, Meyer y Tyndale en 2001, la del American College of Clinical
Pharmacy en 2004, la de Cavallari, Ellingrod y Kolesar en 2005, la de Hall y Pirmohamed en 2006, la de Qing Yan en 2008, la
de Nadine Cohen también publicada en 2008, y la más reciente de Altman, Flockhart y Goldstein en 2012.
Asumiendo la necesidad de popularizar la farmacogenómica, haciéndola extensible y accesible a cualquier médico, ante la
necesidad de administrar cualquier fármaco, la World Association of Genomic Medicine (WAGEM), acordó en 2008, durante
su reunión fundacional en La Coruña, la creación de una base de datos de farmacogenómica práctica para la comunidad
médica y científica de cualquier nacionalidad. El Ist Meeting of the World Association of Genomic Medicine, celebrado el 12-
13 de diciembre de 2008, contó con la Presidencia de Honor de sus Majestades los Reyes de España, y el aval de autoridades
nacionales y extranjeras, 40 Rectores de Universidad, 20 Presidentes de Colegios Médicos, 15 Presidentes de Asociaciones
Farmacéuticas, 8 Presidentes de Reales Academias y 28 Presidentes de Sociedades Médicas. Entre los ponentes más
destacados de la reunión estaban Urs Meyer (Suiza), John Cockcroft (Reino Unido), Filippo de Braud (Italia), Gerardo Jiménez
(México), Masatoshi Takeda (Japón), Marvin Edeas (Francia), Francesco Marotta (Italia), Allen Roses (USA), Munir
Pirmohamed (Reino Unido), Ian Hall (Reino Unido), y Amalio Telenti (Suiza). El Comité Fundacional de WAGEM prometió en 3-
4 años poner en marcha la Website EPG (EuroPharmaGenics) y publicar en formato libro y CD la primera guía mundial de
farmacogenómica, que ahora ve la luz en cumplimiento de lo prometido.
La Guía Mundial de Farmacogenómica (The World Guide for Drug Use and Pharmacogenomics)(WGPGX) es el resultado de
un trabajo multidisciplinar de más de 5 años en el que han participado muchas personas, las cuales, además de aportar su
experiencia profesional, tenían la misión de rastrear las principales bases de datos del mundo y revisar miles de trabajos
sobre genética, genómica, farmacología, metabolismo, terapéutica y farmacogenética, con el fin de sistematizar el
conocimiento disponible sobre farmacogenómica en una base de datos interactiva y en una obra útil para médicos,
genetistas, farmacólogos, farmacéuticos, biólogos moleculares, investigadores, profesionales de la salud, agencias
reguladoras, administradores de la salud y todo tipo de usuario con la voluntad de formarse y entender las claves de una
farmacogenómica práctica y eficaz.
La Guía WGPGX se divide en cinco partes: (i) Fármacos, (ii) Genes, (iii) Referencias, (iv) Apédice, y (v) Index. La Sección de
Fármacos incluye 1.395 productos farmacéuticos en orden alfabético. La sección de cada fármaco incluye el siguiente
contenido: Nombre Genérico, Nombre Comercial (en 27 países europeos, América del Norte (Canadá, USA), Latinoámerica,
y Asia (Japón)), Combinaciones Farmacológicas, Estructura Química, Categoría Farmacológica, Mecanismo de Acción, Uso
Terapéutico, Usos Alternativos, Implicaciones en Embarazo y Lactancia, Contraindicaciones, Peligros y Precauciones,
Reacciones Adversas (cardiovasculares, cerebrales/nerviosas, dermatológicas, endocrinas, metabólicas, gastrointestinales,
génito-urinarias, hematológicas, hepáticas, loco-regionales, neuromusculares, esqueléticas, renales, respiratorias,
miscelánea), Farmacogenética (genotipos de riesgo, genes relacionados con el metabolismo del fármaco, condición de
sustrato, inhibidor o inductor), Interacciones Farmacológicas, Interacciones Nutricionales y Nutracéuticas, Dosis,
Farmacocinética y Farmacodinámica (absorción, distribución, unión a proteínas, metabolismo, biodisponibilidad, vida
media, excreción), y Consideraciones Especiales (dieta, edad, sexo, monitorización).
La Sección de Genes incluye 447 genes de relevancia farmacogenética. Cada entrada contiene los siguientes epígrafes:
Nombre del Gene, Nombres Alternativos, Símbolos, Locus (localización cromosómica), Códigos Pharm GKB y OMIM,
Estructura del Gen, RNA, Proteína, Función, Enfermedades Relacionadas, Fármacos Relacionados (sustratos mayores,
sustratos menores, inhibidores potentes, inhibidores moderados, inhibidores débiles, inductores), Modelos Animales,
Variantes Alélicas, SNPs selectos, Evolución, Genómica, Farmacogenómica e interacciones fármaco-gen.
La Sección de Referencias ofrece 2 categorías de referencias: (i) Websites y Bases de Datos Internacionales, y (ii) 17.947
referencias bibliográficas ordenadas alfabéticamente por autor y gen, seleccionadas de un montante global de más de
100.000 referencias revisadas.
El Apéndice comprende 4 sub-secciones: (i) Clasificación de Fármacos, (ii) Genes y Enfermedades (clasificación alfabética
de genes relacionados con enfermedades específicas), (iii) Enfermedades y Genes (clasificación alfabética de
enfermedades asociadas a genes específicos), y (iv) Sinopsis Farmacogenética (clasificación alfabética de fármacos con
los genes potencialmente involucrados en su farmacogenética).
El índice contiene aproximadamente 52.000 entradas divididas en 5 secciones: (i) Fármacos (7.750 entradas), (ii) Nombres
Comerciales (31.750 entradas), (iii) Categorías Farmacéuticas (1.891 entradas), (iv) Genes (4.450 entradas), y (v)
Enfermedades (9.200 entradas).