DNA
En historisk bakgrund
lutad mot Nobelprisen
Gustav Bohlin
Linköpings Universitet
2014-04-28
2
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1902 Fischer – Sugar/purine synthesis (Chemistry)
•
1982 Klug – Structure nucleic acid-protein complexes
crystallography (Chemistry)
•
1910 Kossel - Nucleic structures
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1933 Morgan - Chromosomes heredity
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1983 McClintock - Mobile genetic elements
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1946 Muller - Mutations X-ray
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1987 Tonegawa – Genetic principle for antibody diversity
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1957 Todd – Nucleotides, nucleotide co-enzymes
(Chemistry)
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1989 Altman & Cech – Catalytic properties of RNA
(Chemistry)
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1958 Beadle, Tatum & Lederberg - Genetic physiology
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1989 Bishop & Varmus - Retroviral oncogenes
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1959 Ochoa & Kornberg Biological synthesis of RNA/DNA •
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1962 Crick, Watson & Wilkins – Structure of DNA
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1993 Mullis & Smith – PCR and other (Chemistry)
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1995 Lewis, Nüsslein-Volhard & Wieschaus – Genetic
control of embryo development
1968 Holley, Khorana & Nirenberg - Genetic code
•
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1969 Delbruck, Hershey & Luria – Genetic structure of
viruses
2002 Brenner, Horvitz & Sulston – Genetic regulation of
organ development and apoptosis
•
2006 Fire & Mello – RNA interference/gene silencing
•
1970 Leloir – Sugar nucleotides role in synthesis of
carbohydrates (Chemistry)
•
2006 Kornberg – Eukaryotic transcription molecular basis
(Chemistry)
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1972 Anfinsen, Moore & Stein – Ribonuclease (Chemistry) •
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1975 Baltimore, Dulbecco & Temin – Tumor viruses
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1965 Jacob, Lwoff & Monod – Genetic control of
enzyme/virus synthesis
•
•
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1993 Roberts & Sharp – Split genes
•
1978 Arber, Nathans & Smith – Restriction enzymes and
application to molecular genetics
•
1980 Berg, Gilbert & Sanger – Biochemistry and
sequencing techniques for nucleic acids (Chemistry)
•
2007 Capecchi, Evans & Smithies – Knockout mice
2009 Blackburn, Greider & Szostak – Telomeres and
telomerase
2012 Gurdon & Yamanaka – Reprogramming of mature
cells to stem cells.
Innan Nobel
• Friedrich Miescher upptäckte DNA (nuklein)
1869.
• Spekulerade i samband mellan nuklein och
ärftlighet men övergav dessa idéer.
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Innan Nobel
• Gregor Mendel 1822-1884
• “Experiment på växthybridisering” 1865
• Egenskaper ärvs från en generation till en
annan. Recessiva eller dominanta
• Begrepp som genetik, gen, fenotyp och
genotyp lanserades under 1910-talet
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I Mieschers fotspår
• De fem nukleotidernas struktur beskrevs
under 1900-talets första årtionden av Albrecht
Kossel (NP Medicin, 1910), Emil Fischer (NP
Kemi, 1902) och Pheobus Levene.
• Einar Hammarsten på Karolinska Institutet
framstående i nukleinsyreforskning (och
tongivande i Nobelkommittén).
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I Mendels fotspår
• Thomas Hunt Morgan (NP Medicin, 1933),
visade 1911 att de ärftliga anlagen sitter på
kromosomerna.
• Hermann Joseph Muller (NP Medicin 1946),
lyckades inducera mutationer genom
röntgenstrålning.
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“What is the nature of the elements of heredity that Mendel postulated
as purely theoretical units? What are genes? Now that we locate them
in the chromosomes are we justified in regarding them as material
units; as chemical bodies of a higher order than molecules? Frankly,
these are questions with which the working geneticist has not much
concern himself, except now and then to speculate as to the nature of
the postulated elements. There is no consensus of opinion amongst
geneticists as to what the genes are, whether they are real or purely
fictitious.”
T.H. Morgan 1933
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“If one assumes that the genes consist of known substances, there
are only the proteins to be considered, because they are the only
known substances which are specific for the individual.”
Caspersson, T., Hammarsten, E,. Hammarsten H., (1935) Interactions of proteins and nucleic
acid. Transactions of the Faraday Society 31:367–389.
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Mystiska indicier som aldrig fick Nobelpris
• Griffith, 1928
• Avery, McCarty & MacLeod, 1944
• Avery & McCarty, 1946
• Chargaff, 1950
• Hotchkiss, 1950
• Hershey & Chase, 1952
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Genombrottet
• Watson & Crick 1953 (NP Medicin, 1962)
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Genombrottet
• Watson, Crick & Wilkins 1953 (NP Medicin,
1962)
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Molekylärbiologins födelse
for their discovery of…
13
•
1958 …that genes act by regulating definite chemical events/concerning
genetic recombination and the organization of the genetic material of
bacteria.
•
1959 …the mechanisms in the biological synthesis of ribonucleic acid and
deoxyribonucleic acid.
•
1962 …the molecular structure of nucleic acids and its significance for
information transfer in living material.
•
1965 …genetic control of enzyme and virus synthesis.
•
1968 …the genetic code and its function in protein synthesis.
•
1969 …the replication mechanism and the genetic structure of viruses.
•
1970 …sugar nucleotides and their role in the biosynthesis of
carbohydrates.
•
osv..
Fram till idag
for their discovery of…
14
•
2006 …RNA interference – gene silencing by double-stranded RNA.
•
2006 …the molecular basis of eukaryotic transcription (Chemistry)
•
2007 …principles for introducing specific gene modifications in mice by
the use of embryonic stem cells.
•
2009 …how chromosomes are protected by telomeres and the enzyme
telomerase.
•
2012 …that mature cells can be reprogrammed to be pluripotent.
•
osv?
• Medicinpriser oftare till upptäckter rörande
fysiologiska funktioner
• Kemipriser oftare till upptäckter av
analystekniker
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• Medicinpriser oftare till upptäckter rörande
fysiologiska funktioner
• Kemipriser oftare till upptäckter av
analystekniker
• Men undantag finns förstås!
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Framtidens priser?
• Epigenetik – Adrian P. Bird, Howard Cedar &
Aharon Razin
• DNA-nanoteknik – A. Paul Alivisatos, Chad A.
Mirkin, Nadrian C. Seeman
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