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Meselson, Stahl, and the Replication of DNA

Meselson, Stahl, and the Replication of DNA: A History of "The Most Beautiful Experiment in Biology"

Frederic Lawrence Holmes
Copyright Date: 2001
Published by: Yale University Press
Pages: 528
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  • Book Info
    Meselson, Stahl, and the Replication of DNA
    Book Description:

    In 1957 two young scientists, Matthew Meselson and Frank Stahl, produced a landmark experiment confirming that DNA replicates as predicted by the double helix structure Watson and Crick had recently proposed. It also gained immediate renown as a "most beautiful" experiment whose beauty was tied to its simplicity. Yet the investigative path that led to the experiment was anything but simple, Frederic L. Holmes shows in this masterful account of Meselson and Stahl's quest.This book vividly reconstructs the complex route that led to the Meselson-Stahl experiment and provides an inside view of day-to-day scientific research--its unpredictability, excitement, intellectual challenge, and serendipitous windfalls, as well as its frustrations, unexpected diversions away from original plans, and chronic uncertainty. Holmes uses research logs, experimental films, correspondence, and interviews with the participants to record the history of Meselson and Stahl's research, from their first thinking about the problem through the publication of their dramatic results. Holmes also reviews the scientific community's reception of the experiment, the experiment's influence on later investigations, and the reasons for its reputation as an exceptionally beautiful experiment.

    eISBN: 978-0-300-12966-3
    Subjects: History of Science & Technology

Table of Contents

  1. Front Matter
    (pp. i-vi)
  2. Table of Contents
    (pp. vii-viii)
  3. Preface
    (pp. ix-x)
  4. Acknowledgments
    (pp. xi-xii)
  5. Introduction
    (pp. 1-10)

    In April 1953, the American biologist James D. Watson and the British physicist Francis H. C. Crick proposed in a brief paper inNaturea “structure for the salt of deoxyribonucleic acid (D.N.A.).”¹ Soon known as the double helix, their structural model attracted immediate interest. Not only did the model decisively swing opinion to the view that DNA was the chemical basis of the classical gene; it suggested also how the DNA molecule might function in genetic replication. Coupled with the recently established doctrine that genes control life by directing the synthesis of proteins, the advent of the double helix...

  6. CHAPTER ONE The Replication Problem
    (pp. 11-48)

    One of the most famous sentences in the recent literature of science is the statement near the end of the brief article inNaturein which Francis Crick and James Watson announced, in April 1953, their proposed structure for deoxyribose nucleic acid:

    It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.¹

    Crick has since written that his enigmatic assertion had been “a compromise, reflecting a difference of opinion.” He had thought that the paper should discuss the genetic implications, whereas “Jim was against it. He suffered...

  7. CHAPTER TWO Meselson and Stahl
    (pp. 49-74)

    In 1953 Matthew Meselson, a first-year graduate student in the Chemistry Division at Caltech, made an appointment to introduce himself to Max Delbrück. Meselson stepped into Delbrück’s office with trepidation, for he had been warned in advance that Delbrück might be caustic. Despite this reputation, he was not unfriendly, but hewascharacteristically abrupt. As soon as Meselson sat down in front of his desk, Delbrück asked what he thought about the two papers Crick and Watson had recently published inNature. When Meselson confessed that he knew nothing about them, Delbrück exclaimed, “What! The most important development in biology...

  8. CHAPTER THREE Twists and Turns
    (pp. 75-115)

    While Meselson and Stahl deferred their mutual interest in the DNA replication problem to attend to more immediate tasks, others took up the challenge posed by Max Delbrück’s provocative paper on the subject. Responses appeared on two widely divergent levels. On an abstract plane that appealed particularly to physicists there appeared topographical models suggesting alternatives to Delbrück’s scheme for resolving the unwinding dilemma. On an experimental plane some of the members of the phage network sought to trace the patterns of distribution of parental DNA molecules into progeny DNA. Somewhere between these levels, Jim Watson himself took Delbrück’s objections seriously...

  9. CHAPTER FOUR Crossing Fields: Chemical Bonds to Biological Mutants
    (pp. 116-156)

    “At the end of the summer,” Matt Meselson wrote to Jim Watson a little later, “I began to look for an entry point into biology by reading about the structure and chemistry of the purines and pyrimidines.”¹ Intending to study the subject systematically, he checked out a workbook, serial number 786, from the Gates and Crellin Laboratories of Chemistry. Meselson used the workbook as a repository for references to relevant books and articles and for summaries of the portions of what he read that were most pertinent to his interests.²

    Sometime early in August 1956, Meselson began to read intensely...

  10. Chapter Five Dense Solutions
    (pp. 157-182)

    While Matt Meselson was crossing the boundary from physical chemistry into biology during the summer of 1956, Frank Stahl was considering a move that would forestall their intended collaboration. The offer from Gunther Stent to join him at Berkeley attracted him very much. He had earlier turned down a position in the department of Geoffrey Brown at the University of Michigan because he felt “the need to get more momentum research-wise before I get hit with teaching duties.”¹ At Berkeley, however, he would do only research. Moreover, in spite of some misgivings about Stent’s recent publications, Stahl regarded him as...

  11. CHAPTER SIX The Big Machine
    (pp. 183-214)

    On 21 October 1956, Frank Stahl typed out a three-page “5-BromUracil Prospectus,” intended probably to let Max Delbrck know what he and Matt Meselson were planning.¹ The title expressed the common grounding in this molecule of a series of investigative projects that were similar to those described by Stahl five weeks earlier in his letter to Levinthal. (See pp. 158–159.) Stahl’s decision to remain at Caltech enabled him to integrate what he had then described as the separate plans of Meselson and himself. Diverse as the individual research problems appeared, they could now be viewed as “lots of threads...

  12. CHAPTER SEVEN Working at High Speed
    (pp. 215-271)

    At the dedication of the Church Laboratory in November 1956, Robert Sinsheimer, who had recently accepted a position in the Biology Division at Caltech, delivered a special lecture titled “First Steps Toward a Genetic Chemistry. In it he warned that the evidence linking genes with the chemistry of DNA was “at present necessarily circumstantial.” Most of it served merely to “present DNA as a likely candidate for a genetic role.” There was no experimental evidence to support the “postulate that the information is carried as a nucleotide sequence—we simply lack any credible alternative hypothesis.”¹ He appeared equally skeptical about...

  13. Chapter Eight The Unseen Band
    (pp. 272-302)

    As the new opportunities created by the density gradient method deferred Meselson and Stahl’s attack on the DNA replication problem at the beginning of 1957, the problem was not left waiting for them to get around to it. Contrary to the prediction by Delbrück and Stent that further elucidation would emerge from work on bacteriophage, the next significant advance came from experiments on bean plant seedlings.

    Several investigators had attempted, during the early 1950s, to introduce radioactive isotopes into dividing cells to study the manner in which chromosomes are organized and synthesized. Alma Howard and S.R. Pelc, for instance, incorporated...

  14. Chapter Nine One Discovery, Three Stories
    (pp. 303-318)

    At the end of September Meselson received the15N he had ordered from the Isomet Corporation. The isotope arrived in the form of ammonium nitrate, contained in small vials.¹ He and Stahl decided not only to switch from 5-BU to15N to produce heavy DNA but at the same time to carry out the transfer experiments with bacteria in place of phage.² Although their shift was abrupt, it was not unpremeditated. In early February, Meselson had already contemplated using bacteria, when he still envisioned doing the experiments only with 5-BU. In the research statement he submitted then, he had outlined...

  15. Chapter Ten An Extremely Beautiful Experiment
    (pp. 319-351)

    Frank Stahl flew back from his job interview in Missouri hopeful about his prospects there. A former classmate from Rochester who was already at the university depicted it to him as a pleasant place in which to work. Its rural atmosphere appealed to Stahl. The university had been strong in classical genetics but was off the beaten track for the newer molecular genetics—a situation that seemed to him advantageous, because he would be able to test his abilities independent of the ideas of other people. He thought also that he would have an opportunity to take students who were...

  16. Chapter Eleven Centrifugal Forces
    (pp. 352-387)

    By the time Matt Meselson interrupted his work in mid-December, word of the spectacular experiment he and Frank Stahl had performed was already spreading through the community of scientists concerned with the biological role of DNA. In December, Paul Zamecnik invited Meselson to be a featured speaker at the Gordon Conference on Nucleic Acids and Proteins, to be held in New Hampshire the following June, and to talk on the DNA density transfer experiment. He was to share with Herbert Taylor the opening session on DNA synthesis, with Gunther Stent as commentator and Cy Levinthal as moderator.¹ By this time...

  17. Chapter Twelve The Subunits of Semiconservative Replication
    (pp. 388-411)

    The immediate impact of the publication of the Meselson-Stahl experiment inPNASin the summer of 1958 extended well beyond the circle of biologists already engaged with the replication of DNA. When Joseph Fruton read their paper, for example, he concluded that what he and his wife had treated in their biochemistry textbook as an ingenious speculation was a real thing. He remained skeptical that all DNA is in helical form, but he now regarded the complementary base pairing mechanism as fundamentally important.¹

    Carolyn Walch was one of eight biology majors who had graduated from Swarthmore College in the spring...

  18. Chapter Thirteen Images of an Experiment
    (pp. 412-434)

    In 1965 James Watson published a molecular biology book for introductory students. It would have been unwise to attempt such a book five years earlier, he wrote in the preface, but now that biology has a “sound basis,” it is “time to reorient our teaching and to produce new texts” that will give new rigor, perspective, and enthusiasm to biologists of the future.¹ Based on lectures he had given at Harvard, Watson’s bookMolecular Biology of the Genetransformed the events from which molecular biology had emerged into a pedagogically structured compendium of the field.

    After eight chapters on classical...

  19. Chapter Fourteen Afterword
    (pp. 435-447)

    What part has the Meselson-Stahl experiment played in the development of molecular biology in the postwar period? In his history of molecular biology, the French biochemist Michel Morange has invoked two other pivotal experiments in the identification of the genetic role of DNA as representative of two fundamental roles of experiment: “There exist in science two types of experiment, of different nature and function. The experiment of Avery [identifying the bacterial transforming factor as DNA in 1944] . . . is an example of the first category: without aprioriideas, the investigator discovers a surprising, novel, unexpected phenomenon. The...

  20. Abbreviations Used in Notes
    (pp. 448-448)
  21. Notes
    (pp. 449-496)
  22. Index
    (pp. 497-504)