THE MOLECULAR REVOLUTION: FUNCTIONAL BIOLOGY
FROM KANT TO THE HUMAN GENOME PROJECT
Fall, 1999
PROF. SLOAN

OFFICE: 344 DECIO

OFFICE HOURS: Monday: 1-3, 344 DECIO
Others by Arrangement

MEETING TIMES: 2:00-3:55  T-TH
107 O’Shaughnessy

Our goal in this course is to  explore the history and character  of functional  biology  during some of the   most critical stages  in its development over  the past 200 years. We will look both at the intellectual-philosophical issues in context, and the concrete institutional and social history of these developments. The most general thematic unifying this inquiry will be an exploration of the efforts to give a  reductive explanation of biological processes by the categories of the  physical sciences, approached not as an abstract philosophical problem, but in its concrete historical manifestations.  This will involve us in the exploration of the "vitalist" revolution, the development of biophysical approaches to living beings, the developments of genetics and molecular biology, and the application of genetic knowledge  to society.  The  approach will be selective and will focus on a case history approach.

The opening section will explore the foundations of the  reductionist program  in the nineteenth century,  emphasizing the importance  of the French Chemist Antoine Lavoisier and the "chemical revolution,"  and the  interrelations of physical and biological sciences in  the middle  to late nineteenth  century and the articulation of a "mechanistic" conception of life.  A second  section will follow  the development of classical genetics into the work of the Morgan school and the chromosome theory.  A  third  section will treat the issues of modern molecular biology from 1940 to 1990. The course will close with an examination of the  Human Genome Project.

HPS graduate students will be asked to attend the lectures and participate in  the accompanying seminar discussion that should be taken as one hour of HPS 604 (Directed Readings) credit. The meeting time for this will be arranged with the graduate students. The weekly seminar meetings will consist of student presentations and advanced  discussions of the lectures and readings.

Books available for purchase (copies will also be on Reserve of most of these books). Required texts for graduate students are starred.*   Others are available for purchase.
 

 *Lenoir, T. The Strategy of Life
 *Bernard, C. Introduction to the Study of Experimental Medicine
  Judson, Horace The Eighth Day of Creation  (CSP Press)
 *Olby, R. The Path to the Double Helix (Dover)
  *Kohler, R. Lords of the Fly:
 *Schrödinger, E. What is Life?
 *Sloan, P.R. (ed.) Reader in 19th and 20th C. Biology  (From Instructor)

Reserve Readings:  Several articles and books  will be on Reserve and you will be expected to utilize these  either as assigned or as time and interest permit.  Two fundamental texts in the Cambridge Series,  William Coleman, Biology in the Nineteenth Century, and Garland Allen, Life Science in the Twentieth Century ,  are out-of-print. Copies of these are on Reserve and you can make your own copies as needed.

Requirements:  The requirements will be regular participation and oral reports in the weekly seminars;  two take-home examinations;  and  a two-hour in-class  cumulative final   during  the regularly scheduled examination in finals week.  HPS students  may substitute a 15 page research paper for the second mid-term examination on a topic worked out with the instructor. This will be due in exam week.
Grading will be based on the following:
Seminar Reports and participation in the weekly seminar:  20%
Midterm Exams: 25% each
Final Exam: 30%

Outline of Class Meetings and Reading Assignments:

SECTION I: THE BIRTH OF  BIOLOGY

GOALS OF THIS UNIT: In this portion of the course we will examine the ways in which the original seventeenth-century  mechanistic ideal of life was originally undermined  and the transformations of functional biology which opened the nineteenth century.

8/24  Introduction to the Course:
 Lecture on Newtonian  and Cartesian Physiology;  The Vitalist Revolution of the 1760s
  Required:  Brown, "From Mechanism to Vitalism" (Reserve)
                   Mendelsohn, Heat and Life  chp. 4 (Reserve)
        Selection from Descartes, Treatise on Man  (Reader)
        Canguilhem, A Vital Rationalist, pp. 227-236 (Reserve)

8/26 Varieties of the Vitalist Program:
 Lecture on German, French, British, Scottish Vitalism ca. 1800
   Required: Selections from Blumenbach,  Hunter, Kant,   in           Reader
       Coleman, Biology, chp. 1.
       Lenoir, Strategy of Life  intro and chp. 1
      Benton, E.  1974  "Vitalism in Ninetenth Century Scientific      Thought: A Typology and Reassessment (Reserve)
         Recommended:  Hall, Ideas of Life and Matter   Vol. 2, chps  33-35   (Reserve)

Weekly Seminar Discussion: Introduction to the  literature; historiographic issues
 Discussion of Lenoir readings and Kant selection.

8/31  Lavoisier, the new chemistry, and the chemical reductionist ideal
 Lecture on the Chemical Revolution; Chemistry and  Physiology
  Required: Lavoisier, "Experiments on Respiration," (Reader)
       Coleman, Biology in Nineteenth Century   chp. 6                       (to p. 127) (Reserve)
       Mendelsohn, Heat and Life, chps. 5-6 (Reserve)
  Recommended: Holmes, F. L. Lavoisier and the Chemistry of        Life  chp. 4. (Reserve)
9/2:  Lavoisier’s Memoir on Heat: Instrumenting the Study of Life      Required: Lavoisier, "Memoir on Heat" (Reader) and Analysis of the paper.
   Mendelsohn, Heat and Life, chp. 7 (Reserve)
   Holmes, Lavoisier and Chemistry , chp.6 (Reserve)
  Recommended: Culotta"Respiration and the Lavoisier Tradition: Theory and       Modification, 1777-1850"  (Reserve)

Weekly Seminar Discussion; This will focus on Lavoisier’s papers and the chemical analysis of vital function. Lavoisier,  Holmes  readings as focus.   Student Presentation.

SECTION II: GERMAN BIOPHYSICS

GOALS OF THIS UNIT:  This section will detail  the important  developments-- scientific, sociological, and technical--that rendered the German life science tradition the most powerful force in nineteenth century biology. The unification of physical and biological science in this tradition will be of particular focus.

9/7:   Formation of the German Physiological  Tradition:
 Lecture on the Müller School
  Required:  Selection from Johannes Muller, Elements of Human Physiology
   (Reader)
   Lenoir, Strategy   chp. 2
   Kremer, Richard. "Institutes for Physiology in Prussia,       1836-1846: Contexts, Interests and Rhetoric,"in: A. Cunningham and P. Williams (eds)    The Laboratory Revolution in Medicine  (Cambridge: CUP, 1992): 72-109.
  Recommended: Broman, T. The Transformation of German Academic Medicine , chp. 5       (Reserve)
   Jungnickel and McCormmach, The Intellectual Mastery of Nature Vol          I, chp. 1-2 (on ideal of Bildung and physical science teaching) (Reserve)

9/9 :The New World of the  Achromatic Microscope
 Lecture: Atoms of Life: Cells, Vital Granules and Crystals
  Required; Selection from Schwann, Microscopical Investigations  (Reader)
   Coleman, Biology in Nineteenth Century, chp. 2 (Reserve)
   Lenoir, Strategy, chp. 3
   Maulitz, "Schwann’s Way" (Reserve)
    "Introduction" to Van Helden and Hankins "Instruments" Osiris Volume 9           (Reserve)
  Recommended: Canguilhem, A Vital Rationalist, "Cell Theory," chp. 7. (Reserve)
    Hacking, "Microscopes" in Representing and Intervening 189-209 (Reserve)

Weekly Seminar: Special  SATURDAY 9/11 workshop on historical microscopy.  Room 214 O’Shag.    9-11 am.

9/14: Energy Conservation and the  German Biophysics Program
 Lecture on German physiology and the Formulation of the Conservation of Energy:   Liebig,  Mayer,  and Helmholtz
  Required:    Helmholtz, "Interaction of Natural Forces" (      Elkana, The Discovery of the Conservation of Energy,                         chps. 4-5 (Reserve)
     Coleman, Biology, chp. 6 (pp. 127-35) (Reserve)
     Lenoir, Strategy,  chp. 5
  Recommended:
     Caneva, Robert Mayer and Conservation of Energy , chp. 3 (Reserve)

9/16: The Later German Biophysics Program: The Ludwig School and the Ideal of Analytic  Biology
    Required: "Introduction" to C. Ludwig, Lehrbuch der Physiologie        (1858)(Reader)
     Coleman, Biology   chp. 6 (pp. 135-54) (Reserve)
   Lenoir, T. "Science for the Clinic: Science Policy and the Formation of Carl    Ludwig's Institute in Leipzig," in: Coleman and  Holmes (eds.)     The Investigative Enterprise  (Reserve)
 

 Recommended:
  S. Chadaravian, "Graphical Method and Discipline: Self-Recording Instruments in    19th C. Physiology" (Reserve)
  Lenoir, "Models and Instruments in the Development of Electrophysiology"    (Reserve)

Weekly Seminar: This will concentrate on the methodology and explanatory ideals of the German physiological school as represented by Helmholtz and Ludwig. Student report on Ludwig and his school.

SECTION III: FRENCH HOLISTIC MATERIALISM

GOALS OF THIS UNIT: This section will develop the contrasting style of physiological research developed in French physiology as it was connected to  a French  intellectual heritage and  institutionalized  under different  social and political  arrangements.

9/21: French Organismic Biology
 Lecture on the Magendie Tradition: The Vivesectional Approach.
   Required:  Selection from Magendie, Compendium of Physiology (1824) (Reader)
     Bernard Introduction to Study of Experimental         Medicine,  pp. 1-57
     Coleman, Biology, chp. 6, (pp. 154-59), chp. 7 (Reserve)
   Recommended: Lesch, Science and Medicine in France, chps. 3,4 (Reserve)
    G. Canguilhem, A  Vital Rationalist,  chp. 11 (Reserve)
    C. McClellan, "Science, Intellect and Social Evolution" chps. 4-5 (Dissertation on     Reserve)
    Albury, "Physiological Explanation In Magendie’s Manifesto of 1809"        (Reserve )
     9/23:   Bernard,  the Milieu Intérieure, and Organicism
   Required: Bernard, Introduction to Study of Experimental Medicine
    pp. 59-84; 140-171
    Bernard, "The Definition of Life," (1874) (Reader)
    G. Canguilhem, A  Vital Rationalist,  chp. 12 (Reserve)
   Recommended:
    Lesch, Science and Medicine, chp. 9 (Reserve)

Weekly Seminar: This will focus on Bernard, the concept of the Milieu Interieure, and the contrast of French and German physiological programs.  Student presentation on Claude Bernard’s solution to the issue of vitality and function.

9/28:  Fin-de-siècle  Physiological Reductionism
   Required: Jacques Loeb, "The Mechanistic Conception of Life" (Reader)
    Philip Pauly,  Controlling Life: Jacques Loeb and the Engineering Ideal, chp. 8                  (Reserve)
    Allen,  Life Science in the Twentieth Century  chp. 4 (Reserve)
   Recommended:
    Pauly, Controlling Life, chp. 2 (Reserve)
    Geison, Michael Foster and the Cambridge School of Physiology chp. fill
First Takehome Midterm covering material through 9/28: Due 10/14

 SECTION IV: FORMATION OF THE CLASSICAL GENETICS PROGRAM

GOALS OF THIS UNIT: The course will now turn attention to  issues in functional biology associated with inheritance and the  transmission of  life. We will first  explore  Mendel’s original paper and its renewed appreciation in 1900 by  a tradition of botanists and zoologists,  and some of the difficulties facing Mendel’s work in relation to the tradition of developmental embryology. The importance of the separation of these issues for the work of Morgan and his school will be pursued into the chromosome theory.

9/30: Mendelism and Inheritance:
 Lecture on the Background and Context of  Mendel’s Work
   Required: Mendel, Experiments on Plant Hybridization  (Reader)
    Darwin, " Provisional Hypothesis of Pangenesis" from Variation of Plants and              Animals  (Reader)
    Gasking, "Why Was Mendel’s Work Ignored?" (Reserve)
   Recommended: Corcos & Monaghan, Guided text edition of Mendel’s Experiments on      Plant  Hybridization  (Reserve)             Weekly Seminar: Focus for this week will be on Loeb, Allen, and Pauly readings.  Student Report on      Loeb’s view of biology.

10/5:  The Science of  Genetics
   Required: DeVries, Selection from Intracellular Pangenesis  (1889)             DeVries, "The Law of the Segregation of Hybrids" (1900)  (Reader
      Weldon, "Mendel’s Laws of Inheritance in Peas," (Reader)
      Darden, "Reasoning in Scientific Change: Charles Darwin:               Hugh De Vries, and the Discovery of                  Segregation," (Reserve)
   Recommended:  Darden, Theory Change in Science  chp. 4-5 (Reserve)
     Provine, Origins of Theoretical Popululation Genetics, chp.

10/7: Materializing Mendelism; Morgan and the Chromosome Theory
   Required: Morgan, "Chromosome Groups and Heredity" (1910)            (Reader)
    Morgan, T. "Sex-Linked Inheritance in Drosophila" (1910) (Reader)
    Allen, Life Science, chp. 3, pp. 56-72 (Reserve)
    Kohler’s Lords  of the Fly  chps. 1-2
   Recommended: Darden, Theory Change, chp. 7.
Weekly Seminar: Focus for this week will be student-led discussion  on first 2 chapters of Kohler’s Lords    of the Fly

10/12: Organizing Genetic Inquiry: What is the Gene?" Morgan School Answers
   Required: Morgan, "The Localization of the Hereditary Material in the Germ      Cells" (1915) (Reader)
     Sturtevant, "The Linear Arrangement of Factors in           Drosophila" (1913) (Reader)
    Johannsen, "Some Remarks About Units in Heredity" (1923) (Reader)
    Kohler, Lords of the Fly  chps. 3-5
   Recommended:
10/14: Competing Styles of Genetic Inquiry: Chromosome Theory and Developmental Genetics: Problems    and Debates
   Required: Selection from Goldschmidt,  Material Basis of Inheritance (Reader)
   Allen, Life Science, chp. 5 (Reserve)
   Kohler, Lords of the Fly, chp. 6
   Recommended: Harwood, J. Styles of Scientific Thought: The German Genetics            Community  chp. 2 (Reserve)
Weekly Seminar: Finishing discussion of Kohler, Lords of the Fly  6-8. Student led.

FALL BREAK 10/17-10/24   Begin Olby, Path to the Double Helix  over break
 

SECTION V: MOLECULAR BIOLOGY AND MOLECULAR GENETICS

GOALS OF THIS UNIT: We are now prepared to engage  the issues of modern molecular biology and molecular genetics. In many respects these investigations will   unite the inquiries of medical physiologists, immunologists  and biochemists with the inquiries of the geneticists and eventually with the developmental embryologists. This unification raises important questions for the possibility of reduction of life to non-life. The focus will be on the developments within the British, French and American traditions.
10/26:  The Origins of "Molecular" Biology
  Lecture on the Origins of "Molecular" Biology; the Restructuring of Life Science    1930-40;
   Required: Capshew, J. and Karen Rader, "Big Science: Price to the                              Present," Osiris  7 (1992) (Reserve)
           Allen, Life Science in Twentieth Century, chps. 6-7 (Reserve)
         Kay, "Life as Technology" (Reader)
     Recommended:
       Kay, Lily The Molecular Vision of Life  chp. 2 (Reserve)
     Rasmussen, "The Midcentury Biophysics Bubble" (Reserve)

10/28: New Instruments For  Biology: the X-Ray, Ultracentrifuge, and Electron Microscope
  Lecture on the Instrumentation of molecular biology; Inquiry into microproperties    of cells.
   Required: Olby, Path to the Double Helix, chps. 1-3
   Rasmussen, Picture Control,  "Introduction" and chp. 1
10/29:  (Friday)  Special Class:  Tour of the Electron Microscope facility in Galvin Life Sciences. Time    to be arranged. This will replace class for 11/4
Weekly  Seminar:  Student-Led discussion on  Instrumentation and Theory: Rasmussen readings.

11/2:  The Nucleoprotein Theory
   Required:  Olby, Path,  chp. 7, 11
     Wrinch, "On the Molecular Structure of Chromosomes" (1935)                   (Reader)
     Gulick, "What is the Gene?" (Reader)

11/4:  Class cancelled (HSS Meetings). Begin reading  Schrödinger, What is Life?

11/9: Physicists Searching for the Paradox: The Target Theory of the Gene Guest Lecture by Prof.   Lenny Moss
   Required: Schrödinger, What is Life?  pp.1-48
     Bohr, "Light and Life" (Reader)
       Allen, Life Science , chp. 7
      Olby, Path, chp. 15
   Recommended: Yoxen, "Where Does Schrödinger’s What is Life Belong?
           (Reserve)
        Kay, "The Secret of Life," (Reserve)
11/11: Phage Genetics and the Informationist Approach to Inheritance
  Lecture on the Phage School.
   Required: Schrodinger, What Is Life?  pp. 49-91
        Olby, Path, chp. 15
        Kay, "How the Genetic Code Became a Language" Reader
   Recommended: Kay, Molecular Vision  chp. 8 (Reserve)
          Summers, W. "How Bacteriophage Came to Be Used by the                         Phage Group,"  (Reserve)
            Watson, "Growing up in the Phage School," in
           Phage and the Origins of Molecular Biology  (Reserve)
Weekly Seminar: Student-led Discussion on the Schrodinger essay,  Delbruck and the quantum-mechanical      interpretation of the gene.

11/16 The Turn to DNA
  Required: Avery, McCarty and McLeod, "Studies in the Transformation of                   Pneumococcus" (Reader)
   Hershey and Chase, "Independent Function of Viral Proteins              and Nucleic Acid,"  (Reader)
    Wyatt, H.V. "When Does Information Become Knowledge?"                    Nature  235 (1972) (Reader)

11/18:  The Double Helical Model: Evening Class:  Film Race to the Double Helix
   Required: Olby, Path, chps.  20-21
         Pauling and Corey, A Proposed Structure for the Nucleic  Acids" (Reader)
          Watson and Crick "The Structure of DNA" in Double Helix pp. 257-73
          Judson, Horace "Reflections on the Historiography of Molecular Biology" Minerva (Reserve)
 Weekly Seminar: Student-led discussion on Historiography of DNA Discovery (Judson paper)

Second Takehome  Midterm Covering material from  10/26:  Due 12/10

11/23: Molecular Biology Beyond the Double Helix:
 Lecture on Molecular Genetics  after 1953: The Role of RNA
   Required: Watson and Crick, "Genetic Implications of the Structure of DNA" (Reader)
    Jacob and Monod "Genetic Regulatory Mechanisms in the  Synthesis of Proteins" (1959) (Reader)
    Recommended:  Judson, Eighth Day of Creation  chp. 6 (Reserve)

Thanksgiving  Break: 11/25-11/28

11/30: The Operon and Code: Relating Genetics and Development
 Lecture on Jacob and Monod Paper and the Solution to Code Problem.
  Required: Jacob and Monod "Genetic Regulatory Mechanisms in the       Synthesis of Proteins" (1959) (Reader)
  Crick, Brenner et al. "General Nature of the Genetic Code for Proteins," (1961) (Reader)
   Recommended: Judson, Eighth Day of Creation, chps. 7-8
 

SECTION VI:  TRANSFORMING HUMAN GENETICS:
GOALS OF THIS SECTION:  In this unit we will examine the developments that led workers trained in  bacterial and phage genetics to extend their domain to encompass human genetics.

12/2: Preconditions  of the Genome Project: Developments in Molecular Genetics of the 1970s
 Lecture on the Eugenics Movement: Prior issues in the social application of human genetics:
  Required: Pernick, "Defining the Defective" (Reader)
  Kitcher, "Utopian Eugenics" and response by Diane Paul (Reader)
  Recommended: Kevles, In the Name of Eugenics , chps. 3-4

12/6: The Genome Project as "Big Science"
 Lecture on the Mass-Sequencing Project; The Politics of the Genome Project
  Required: Beatty, "Origins of the U.S. Human Genome Project" (Reader)
  Recommended:

 Cook-Deegan, The Gene Wars  chps. 5,7,13. (Reserve)

12/8:  Final Class: Issues and Debates over the Genome Project:
  Required: Tauber and Sarkar, "The Human Genome Project: Has Blind  Reductionism Gone Too Far?" (Reader)
 

Second Takehome Due.

Exam week 5/5-5/9  A two-hour final will be held at the scheduled time.