The Meselson–Stahl Experiment

Abstract

The ‘Meselson–Stahl experiment’, which established the semiconservative mode of deoxyribonucleic acid (DNA) replication, is situated in its scientific, historical and institutional context. Starting with the experiment's conceptual and technical challenges of developing a new method of sedimentation in a caesium chloride (CsCl) density gradient for distinguishing between parental and progeny DNAs that have been labelled by nitrogen isotopes of different masses (the heavy N15 and the normal N14); the article situates the seminal experiment in the wider context of molecular biology in the 1950s. The article also examines the institutional context of California Institute of Technology (in Pasadena, a suburb of Greater Los Angeles, CA), where Meselson was a graduate student and a research fellow in its Chemistry Division, while Stahl was a postdoctoral fellow in its Biology Division. The article emphasises the pioneering role of these two then junior scientists in collaborating in pursuit of new ideas beyond their respective disciplines of training. The role of inspiring mentors, technical resources, the social context of the Phage Group, an informal network which exchanged information on the multiplication of the simplest organism, the phage or bacterial virus and the institution of the ‘summer school’ at the Marine Biological Laboratory in Woods Hole, MA where Meselson and Stahl met for the first time, are also discussed as formative aspects of this seminal experiment.

Key Concepts:

  • Semiconservative replication: Genetic replication of only one strand in a two‐stranded macromolecule that carries genetic information, that is, DNA or RNA.

  • Density gradient: Method for differential sedimentation of macromolecules in the analytical ultracentrifuge based on the system reaching density equilibrium.

  • Isotopes: Atoms of a given element in the periodic table that differ in the number of nuclear particles, for example, normal Nitrogen (N14) has 14 nuclear particles, 7 protons and 7 neutrons, whereas heavy Nitrogen (N15) (used in this experiment) has 7 protons and 8 neutrons. All isotopes must have the same number of protons but can vary in their number of neutrons.

  • Bacterial growth: Growth of a bacterial culture either by increase in cell material or cell number. Growth of bacterial cultures is defined as an increase in the number of bacteria in a population rather than in the size of individual cells. The growth of a bacterial population occurs in a geometric or exponential manner: with each division cycle (generation), 1 cell gives rise to 2 cells, then 4 cells, then 8 cells and so forth. When bacteria are placed in a medium that provides all the nutrients that are necessary for their growth, the population exhibits four phases of growth that are representative of a typical bacterial growth curve. During the first phase, the lag phase, the bacterial cells increase only in cell size. The population then enters the log phase in which cell numbers increase in a logarithmic fashion. The log phase of bacterial growth is followed by the stationary phase, in which the size of a population of bacteria remains constant, even though some cells continue to divide and others begin to die. The stationary phase is followed by the death phase, in which the death of cells in the population exceeds the formation of new cells.

  • Phage (phage=bacterial virus) multiplication: This process begins with the adsorption of a phage particle (composed of a nucleic acid core and a protein coat) to a receptor in the bacterial wall, and continues with the injection of the phage genome into the bacterium. The phage genome reproduces itself by assembling the phage DNA and protein capsids into complete phage particles. The new phage particles are released when phage lysozyme breaks down the bacterial cell wall. 200 phage copies can be released in 20 min.

Keywords: Meselson; Stahl; DNA replication; semiconservative replication; density gradient; analytical ultracentrifuge; isotopes; phage group; critical experiment

References

Abir‐Am PG (2000) The First American and French commemorations in molecular biology: from collective memory to comparative history. In: Abir‐Am PG and Elliott CA (eds) Commemorative Practices in Science: Historical Perspectives on the Politics of Collective Memory, vol. 14 of OSIRIS, an official publication of the History of Science Society, pp. 324–372. Chicago: University of Chicago Press.

Bioessays Magazine (2003) Interview with Mathew Meselson, pp. 1236–1246. doi: 10.1002/bies.v25:12/issuetoc.

Cairns J, Stent G and Watson J (eds) (1966) Phage and the Origins of Molecular Biology. Cold Spring Harbor: Cold Spring Harbor Laboratory Press.

Chargaff E (1950) Chemical specificity of nucleic acids and mechanism of their enzymatic degradation. Experientia 6: 201–205.

Creager A (2009) P‐32 in the Phage Group: radioisotopes as historical tracers of molecular biology. Studies in History and Philosophy of Biological and Biomedical Sciences 40: 29–42.

Davis TH (2004) Meselson and Stahl: the art of DNA replication. Proceedings of the National Academy of Sciences of the USA 101(52): 17895–17896.

Delbruck M (1954) On the replication of DNA. Proceedings of the National Academy of Sciences of the USA 40(9): 783–788.

Delbruck M and Stent GS (1957) On the mechanism of DNA replication. In: McElroy WD and Glass B (eds) A Symposium on the Chemical Basis of Heredity, pp. 699–736. Baltimore: John Hopkins University Press.

Doermann AH, Chase M and Stahl FW (1955) Genetic recombination and replication in bacteriophage. Journal of Cellular and Comparative Physiology 45: 51–60.

Drake J (1997) The 1996 Thomas Hunt Morgan Medal to Franklin William Stahl. Genetics 145: 1–2.

Hager T (1995) Force of Nature. The Life of Linus Pauling. New York: Simon and Schuster.

Hanawalt PC (2004) Density matters: the semiconservative replication of DNA. Proceedings of the National Academy of Sciences of the USA 101(52): 17889–17894.

Hershey AD and Chase M (1952) Independent functions of viral protein and nucleic acids in growth of bacteriophage. Journal of General Physiology 36: 39–56.

Holmes FL (2001) Meselson, Stahl, and the Replication of DNA, A History of ‘The Most Beautiful Experiment in Biology’. New Haven, CT: Yale University Press.

Hotchkiss RD (1979) The identification of nucleic acids as genetic determinants. In: Srinivasan PR, Fruton JS and Edsall JT (eds) The Origins of Modern Biochemistry, A Retrospect on Proteins. New York: New York Academy of Sciences.

Krige J (2005) The politics of P‐32: a Cold War fable based on fact. Historical Studies in the History of Physical and Biological Sciences 36(1): 71–91.

Lederberg J (1958) Genetic recombination in bacteria, Nobel Lecture, nobelprize.org/1958.

Levinthal C (1956) The mechanism of DNA replication and genetic recombination in phage. Proceedings of the National Academy of Sciences of the USA 42: 394–404.

McCarty M (1986) The Transforming Principle: Discovering That Genes Are Made of DNA. New York: W.W. Norton and Company.

Meselson M, Stahl FW and Vinograd J (1957) Equilibrium sedimentation of macromolecules in density gradients. Proceedings of the National Academy of Sciences of USA 43: 581–588.

Meselson M (1996) Linus Pauling as an educator. In: Krishnamurthy RS (ed.) The Pauling Symposium, pp. 91–101. Corvallis: Oregon State University Libraries.

Meselson M (2004) Explorations in the land of DNA and beyond. Nature Medicine 10: 1034–1037. doi:10.1038/nm1004‐1034.

Meselson M and Stahl FW (1958) The replication of DNA in Escherichia coli . Proceedings of the National Academy of Sciences of the USA 44: 671–682.

Pauling L and Corey RB (1951) Two helical configurations of polypeptide chains. Proceedings of the National Academy of Sciences of the USA 37: 235–240.

Pauling L and Corey RB (1953) A proposed structure for the nucleic acids. Proceedings of the National Academy of Sciences of the USA 39: 84–97.

Rader KA (2006) Alexander Hollander's post‐war vision for biology: Oak Ridge and beyond. Journal for the History of Biology 39: 685–706.

Stahl FW (1956) The Effects of the Decay of Incorporated Radioactive Phosphorous on the Genome of Bacteriophage T4. PhD dissertation, University of Rochester, 1955.

Stahl FW (1996) Genetic recombination. Scientific American 274: 91–101.

Stahl FW (1998) Recombination in phage: one geneticist's historical perspective. Gene 23: 95–102.

Stahl FW (ed.) (2000) We Can Sleep Later, Alfred D. Hershey and the Origins of Molecular Biology. Cold Spring Harbor: Cold Spring Harbor Laboratory Press.

Visconti N and Delbruck M (1953) The mechanism of genetic recombination in phage. Genetics 38: 5–33.

Watson JD and Crick FHC (1953) The structure of DNA. Cold Spring Harbor Symposia in Quantitative Biology 18: 123–131.

Further Reading

Cairns J (2000) The size of the unit of heredity. In: Stahl FW (ed.) We Can Sleep Later: Alfred Hershey and the Origins of Molecular Biology, pp. 49–58. Cold Spring Harbor: Cold Spring Harbor Laboratory Press.

Chargaff E and Davidson JN (eds) (1955) The Nucleic Acids: Chemistry and Biology. New York: Academic Press.

Dekker CA and Schachman HK (1954) On the macromolecular structures of deoxyribonucleic acid: an interrupted two strand model. Proceedings of the National Academy of Sciences of the USA 40: 894–909.

Kornberg A (1957) Pathways of enzymatic synthesis of nucleotides and polynucleotides. In: McElroy WD and Bentley G (eds) A Symposium on the Chemical Basis of Heredity, pp. 579–608. Baltimore: Johns Hopkins University Press.

Kornberg A (1992) DNA Replication. San Francisco: W.H. Freeman.

Olby R (2002) Confirming a bold prediction. Nature 417: 121–122.

Schachman HK (1959) Ultracentrifugation in Biochemistry. New York: Academic Press.

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How to Cite close
Abir‐Am, Pnina Geraldine(May 2014) The Meselson–Stahl Experiment. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0025093]