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PNAS Classics
PNAS Classics are landmark papers from the archives of PNAS—significant scientific reports that have withstood the test of time. The authors of PNAS Classics opened new avenues of research within their respective fields. These groundbreaking discoveries offer insights into how the best science is practiced. Each Classic article is accompanied by a Classic Perspective written by a scientist in the field and a Classic Profile written by a science writer. Together these newly commissioned articles recall the impact of these discoveries, describe how they have advanced the field, and set them in current scientific context.
Biochemistry: Phillip Sharp
Image courtesy of M. Scott Brauer, with
permission of MIT News.
Perspective
Arnold J. Berk
Discovery of RNA splicing and genes in pieces
PNAS 2016 113:801
[Full Text] [PDF]
Classic Article
Susan M. Berget, Claire Moore, and Phillip A. Sharp
Spliced segments at the 5′ terminus of adenovirus 2 late mRNA
PNAS 1977 74:3171
[Full Text] [PDF]
Mathematics: Gérard Debreu
Image courtesy of Konrad Jacobs,
copyright Mathematisches
Forschungsinstitut Oberwolfach.
Commentary
Partha Sarathi Dasgupta, and Eric S. Maskin
Debreu’s social equilibrium existence theorem
PNAS 2015 112:15769
[Full Text] [PDF]
Classic Article
Gérard Debreu
A Social Equilibrium Existence Theorem
PNAS 1952 38:886
[Full Text] [PDF]
Medical Sciences: Robert C. Gallo
Image courtesy of the National Institute
of Allergy and Infectious Diseases.
Perspective
John M. Coffin
The discovery of HTLV-1, the first pathogenic human retrovirus
PNAS 2015 112:15525
[Full Text] [PDF]
Classic Article
Bernard J. Poiesz, Francis W. Ruscetti, Adi F. Gazdar, Paul A. Bunn, John D. Minna, and Robert C. Gallo
Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma
PNAS 1980 77:7415
[Full Text] [PDF]
Biochemistry: Peter H. Duesberg and Peter K. Vogt
Image courtesy of Mark Dastrup.
Commentary
Klaus Bister
Discovery of oncogenes: The advent of molecular cancer research
PNAS 2015 112:15259
[Full Text] [PDF]
Classic Article
Peter H. Duesberg and Peter K. Vogt
Differences between the Ribonucleic Acids of Transforming and Nontransforming Avian Tumor Viruses
PNAS 1970 67:1673
[Full Text] [PDF]
Neurobiology: Marcus E. Raichle
Image reprinted with permission from
Elsevier.
Perspective
Manu S. Goyal, Siddarth Venkatesh, Jeffrey Milbrandt, Jeffrey I. Gordon, and Marcus E. Raichle
Feeding the brain and nurturing the mind: Linking nutrition and the gut microbiota to brain development
PNAS 2015 112:14105
[Full Text] [PDF]
Core Concept
Helen H. Shen
Core Concept: Resting-state connectivity
PNAS 2015 112:14115
[Full Text] [PDF]
Classic Article
Marcus E. Raichle, Ann Mary MacLeod, Abraham Z. Snyder, William J. Powers, Debra A. Gusnard, and Gordon L. Shulman
A default mode of brain function
PNAS 2001 98:676
[Full Text] [PDF]
Mathematics: Lloyd Shapley
Image courtesy of
Shutterstock/PerseoMedusa.
Perspective
Eilon Solan and Nicolas Vieille
Stochastic games
PNAS 2015 112:13743
[Full Text] [PDF]
Classic Article
L. S. Shapley
Stochastic games
PNAS 1953 39:1095
[Full Text] [PDF]
Chemistry: Linus Pauling and Charles D. Coryell
Image courtesy of J. Barton.
Perspective
Kara L. Bren, Richard Eisenberg, and Harry B. Gray
Discovery of the magnetic behavior of hemoglobin: A beginning of bioinorganic chemistry
PNAS 2015 112:13123
[Full Text] [PDF]
Classic Article
Linus Pauling and Charles D. Coryell
The Magnetic Properties and Structure of the Hemochromogens and Related Substances
PNAS 1936 22:159
[Full Text] [PDF]
Classic Article
Linus Pauling and Charles D. Coryell
The Magnetic Properties and Structure of Hemoglobin, Oxyhemoglobin and Carbonmonoxyhemoglobin
PNAS 1936 22:210
[Full Text] [PDF]
Biology: Alfred J. Lotka
Image courtesy of MetLife Archives.
Profile
Sharon Kingsland
Alfred J. Lotka and the origins of theoretical population ecology
PNAS 2015 112:9493
[Full Text] [PDF]
Perspective
John W. Terborgh
Toward a trophic theory of species diversity
PNAS 2015 112:11415
[Full Text] [PDF]
Classic Article
Alfred J. Lotka
Analytical Note on Certain Rhythmic Relations in Organic Systems
PNAS 1920 6:410
[Full Text] [PDF]
Biochemistry: Tony Hunter and Bartholomew M. Sefton
Image courtesy of Shutterstock/bitsite.
Perspective
Tony Hunter
Discovering the first tyrosine kinase
PNAS 2015 112:7877
[Full Text] [PDF]
Inner Workings
Jessica Marshall
Inner Workings: Tyrosine kinases, their discovery and impact
PNAS 2015 112:7886
[Full Text] [PDF]
Classic Article
Tony Hunter and Bartholomew M. Sefton
Transforming gene product of Rous sarcoma virus phosphorylates tyrosine
PNAS 1980 77:1311
[Full Text] [PDF]
Astronomy: Edwin Hubble
Image courtesy of NASA.
Commentary
Neta A. Bahcall
Hubble’s Law and the expanding universe
PNAS 2015 112:3173
[Full Text] [PDF]
Inner Workings
David J. Harris
Inner Workings: Hubble’s quarter century in orbit has opened a universe of possibilities
PNAS 2015 112:3176
[Full Text] [PDF]
Classic Article
Edwin Hubble
A relation between distance and radial velocity among extra-galactic nebulae
PNAS 1929 15:168
[Full Text] [PDF]
Mathematics: George D. Birkhoff and J. v. Neumann
Image courtesy of Goethe University
Frankfurt.
Perspective
Calvin C. Moore
Ergodic theorem, ergodic theory, and statistical mechanics
PNAS 2015 112:1907
[Full Text] [PDF]
Core Concept
Steven Ashley
Core Concept: Ergodic theory plays a key role in multiple fields
PNAS 2015 112:1914
[Full Text] [PDF]
Classic Article
J. v. Neumann
Proof of the Quasi-Ergodic Hypothesis
PNAS 1932 18:70
[Full Text] [PDF]
Classic Article
George D. Birkhoff
Proof of the Ergodic Theorem
PNAS 1931 17:656
[Full Text] [PDF]
Astronomy: W. Baade and F. Zwicky
Image courtesy of ESA/NASA.
Commentary
Adam S. Burrows
Baade and Zwicky: “Super-novae,” neutron stars, and cosmic rays
PNAS 2015 112:1242
[Full Text] [PDF]
Core Concept
Maggie McKee
Core Concept: Supernovae and the accelerating universe
PNAS 2015 112:1243
[Full Text] [PDF]
Classic Article
W. Baade and F. Zwicky
On Super-Novae
PNAS 1934 20:254
[Full Text] [PDF]
Classic Article
W. Baade and F. Zwicky
Cosmic Rays from Super-Novae
PNAS 1934 20:259
[Full Text] [PDF]
Evolution: Carl R. Woese and George E. Fox
Image courtesy of William Petri Jr.
(University of Virginia, Charlottesville,
VA).
Perspective
Jeremiah J. Faith, Jean-Frédéric Colombel, and Jeffrey I. Gordon
Identifying strains that contribute to complex diseases through the study of microbial inheritance
PNAS 2015 112:633
[Full Text] [PDF]
Inner Workings
Elie Dolgin
Inner Workings: Malnutrition, gutted
PNAS 2015 112:641
[Full Text] [PDF]
Retrospective
Larry Gold
The kingdoms of Carl Woese
PNAS 2013 9:3206
[Full Text] [PDF]
Classic Article
Carl R. Woese and George E. Fox
Phylogenetic structure of the prokaryotic domain: The primary kingdoms
PNAS 1977 74:5088
[Full Text] [PDF]
Physiology: M. S. Gazzaniga, J. E. Bogen, and R. W. Sperry
Commentary
Michael S. Gazzaniga
The split-brain: Rooting consciousness in biology
PNAS 2014 111:18093
[Full Text] [PDF]
Inner Workings
Helen H. Shen
Inner Workings: Discovering the split mind
PNAS 2014 111:18097
[Full Text] [PDF]
Classic Article
M. S. Gazzaniga, J. E. Bogen, and R. W. Sperry
Some functional effects of sectioning the cerebral commissures in man
PNAS 1962 48:1765
[Full Text] [PDF]
Cell Biology: Peter Novick and Randy Schekman
Logbook image courtesy of Peter
Novick.
Commentary
Peter J. Novick
A pathway of a hundred genes starts with a single mutant: Isolation of sec1-1
PNAS 2014 111:9019
[Full Text] [PDF]
Inner Workings
Jessica Marshall
Inner Workings: Protein secretion
PNAS 2014 111:9021
[Full Text] [PDF]
Classic Article
Peter Novick and Randy Schekman
Secretion and cell-surface growth are blocked in a temperature-sensitive mutant of Saccharomyces cerevisiae
PNAS 1979 76:1862
[Full Text] [PDF]
Biochemistry: Marshall W. Nirenberg and J. Heinrich Matthaei
Courtesy of Marshall W. Nirenberg from
the National Library of Medicine.
Commentary
C. Thomas Caskey and Philip Leder
The RNA code: Nature’s Rosetta Stone
PNAS 2014 111:5758
[Full Text] [PDF]
Inner Workings
Jessica Marshall
The genetic code
PNAS 2014 111:5760
[Full Text] [PDF]
Classic Article
Marshall W. Nirenberg and J. Heinrich Matthaei
The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides
PNAS 1961 47:1588
[Full Text] [PDF]
Medical Sciences: Michael S. Brown and Joseph L. Goldstein
Classic Profile
Prashant Nair
Brown and Goldstein: The Cholesterol Chronicles
PNAS 2013 110:14829
[Full Text] [PDF]
Classic Perspective
Randy Schekman
Discovery of the cellular and molecular basis of cholesterol control
PNAS 2013 110:14833
[Full Text] [PDF]
Classic Article
Michael S. Brown and Joseph L. Goldstein
Familial hypercholesterolemia: Defective binding of lipoproteins to cultured fibroblasts associated with impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme a reductase activity
PNAS 1974 71:788
[Full Text] [PDF]
Zoology: Rita Levi-Montalcini
Image courtesy of Presidenza della
Repubblica.
Classic Profile
Nicholette Zeliadt
Rita Levi-Montalcini: NGF, the prototypical growth factor
PNAS 2013 110:4873
[Full Text] [PDF]
Classic Perspective
Antonino Cattaneo
Immunosympathectomy as the first phenotypic knockout with antibodies
PNAS 2013 110:4877
[Full Text] [PDF]
Retrospective
Leslie Lars Iversen
Rita Levi-Montalcini: Neuroscientist par excellence
PNAS 2013 13:4862
[Full Text] [PDF]
Classic Article
Rita Levi-Montalcini and Barbara Booker
Destruction of the sympathetic ganglia in mammals by an antiserum to a nerve-growth protein
PNAS 1960 46:384
[Full Text] [PDF]
Genetics: Barbara McClintock
Photo by Ross Meurer. Image courtesy
of the Barbara McClintock Collection,
Cold Spring Harbor Laboratory Library
and Archives.
Classic Profile
Sandeep Ravindran
Barbara McClintock and the discovery of jumping genes
PNAS 2012 109:20198
[Full Text] [PDF]
Classic Perspective
Nina V. Fedoroff
McClintock’s challenge in the 21st century
PNAS 2012 109:20200
[Full Text] [PDF]
Classic Article
Barbara McClintock
The origin and behavior of mutable loci in maize
PNAS 1950 36:344
[Full Text] [PDF]
Evolution: Carl R. Woese and George E. Fox
Photo by Jason Lindley; used with
permission of the College of Liberal Arts
and Sciences, University of Illinois at
Urbana–Champaign.
Classic Perspective
Norman R. Pace, Jan Sapp, and Nigel Goldenfeld
Phylogeny and beyond: Scientific, historical, and conceptual significance of the first tree of life
PNAS 2012 109:1011
[Full Text] [PDF]
Classic Profile
Prashant Nair
Woese and Fox: Life, rearranged
PNAS 2012 109:1019
[Full Text] [PDF]
Classic Article
Carl R. Woese and George E. Fox
Phylogenetic structure of the prokaryotic domain: The primary kingdoms
PNAS 1977 74:5088
[Full Text] [PDF]
Biochemistry: Paul Greengard
Classic Perspective
Solomon H. Snyder
What dopamine does in the brain
PNAS 2011 108:18869
[Full Text] [PDF]
Classic Profile
Sandeep Ravindran
Paul Greengard: Signals underlying moods, addictions, and brain disorders
PNAS 2011 108:18872
[Full Text] [PDF]
Classic Article
John W. Kebabian, Gary L. Petzold, and Paul Greengard
Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the "dopamine receptor"
PNAS 1972 69:2145
[Full Text] [PDF]
Physics: Julian Schwinger
Image courtesy of the Smithsonian
Institution Archives (SIA).
Classic Perspective
Silvan S. Schweber
The sources of Schwinger's Green's functions
PNAS 2005 102:7783
[Full Text] [PDF]
Classic Article (Part I)
Julian Schwinger
On the Green's functions of quantized fields I
PNAS 1951 37:452
[Full Text] [PDF]
Classic Article (Part II)
Julian Schwinger
On the Green's functions of quantized fields II
PNAS 1951 37:455
[Full Text] [PDF]
Biochemistry: Kathleen Danna and Daniel Nathans
Image courtesy of Susie Fitzhugh.
Classic Perspective
Richard J. Roberts
How restriction enzymes became the workhorses of molecular biology
PNAS 2005 102:5905
[Full Text] [PDF]
Classic Profile
Christen Brownlee
Danna and Nathans Restriction enzymes and the boon to modern molecular biology
PNAS 2005 102:5909
[Full Text] [PDF]
Classic Article
Kathleen Danna and Daniel Nathans
Specific Cleavage of Simian Virus 40 DNA by Restriction Endonuclease of Hemophilus Influenzae
PNAS 1971 68:2913
[Full Text] [PDF]
Genetics: Matthew Meselson and Franklin W. Stahl
Image courtesy of Caltech Archives.
Classic Perspective
Philip C. Hanawalt
Density matters: The semiconservative replication of DNA
PNAS 2004 101:17889
[Full Text] [PDF]
Classic Profile
Tinsley H. Davis
Meselson and Stahl: The art of DNA replication
PNAS 2004 101:17895
[Full Text] [PDF]
Classic Article
Matthew Meselson and Franklin W. Stahl
The replication of DNA in Escherichia Coli
PNAS 1958 44:671
[Full Text] [PDF]
Mathematics: John F. Nash
Image courtesy of Getty Images.
Classic Profile
Erica Klarreich
The Mathematics of Strategy
[Full Text]
Classic Perspective
Charles A. Holt and Alvin E. Roth
The Nash equilibrium: A perspective
PNAS 2004 101:3999
[Full Text] [PDF]
Classic Article
John F. Nash
Equilibrium points in n-person games
PNAS 1950 1:48
[Full Text] [PDF]
Astronomy: Edwin Hubble
Image courtesy of Caltech Archives.
Classic Profile
Christen Brownlee
Hubble's guide to the expanding universe
[Full Text]
Classic Perspective
Robert P. Kirshner
Hubble's diagram and cosmic expansion
PNAS 2004 101:8
[Full Text] [PDF]
Classic Article
Edwin Hubble
A relation between distance and radial velocity among extra-galactic nebulae
PNAS 1929 15:168
[Full Text] [PDF]
Developmental Biology: Robert Briggs and Thomas J. King
Image courtesy of Dr. Kitai Kim and M.
Willy Lensch.
Classic Profile
Christen Brownlee
Nuclear transfer: Bringing in the clones
[Full Text]
Classic Perspective
J. B. Gurdon and J. A. Byrne
The first half-century of
nuclear transplantation
PNAS 2003 100:8048
[Full Text] [PDF]
Classic Article
Robert Briggs and Thomas J. King
Transplantation of living nuclei from blastula cells into enucleated frogs' eggs <
PNAS 1952 38:455
[Full Text] [PDF]
Chemistry: Linus Pauling, Robert B. Corey, and H. R. Branson
Image courtesy of Caltech Archives.
Classic Profile
Christen Brownlee
The protein papers
[Full Text]
Classic Perspective
David Eisenberg
The discovery of the α-helix and β-sheet, the principal structural features
of proteins
PNAS 2003 100:11207
[Full Text] [PDF]
Classic Article
Linus Pauling, Robert B. Corey, and H. R. Branson
The structure of proteins: Two hydrogen-bonded helical configurations of the polypeptide chain
PNAS 1951 37:205
[Full Text] [PDF]
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