“ ‘Doing One’s Damndest with No Hold Barred’: Pluralism in Methodology in History and Philosophy of Science”

1. “ ‘Doing One’s Damndest with No Hold Barred’: Pluralism in Methodology in History and Philosophy of Science” Springer Lecture International History and Philosophy of Science Teaching Conference Calgary June 25, 2007

2. Outline • Introduction: The Importance of History and Philosophy in Teaching Scientific Methodology A. “Should History of Science Be Rated X?” B. History and Philosophy of Science are complementary but they are not the same • Logic of Science: What It Can Teach • The Case History Method A. Development of the Mendelian-Chromosome Theory of Heredity (MCTH) B. Methodological Points C. Extensions to Social/Political Context

3. Outline • Introduction: The Importance of History and Philosophy in Teaching Scientific Methodology A. “Should History of Science Be Rated X?” B. History and Philosophy of Science are complementary but they are not the same • Logic of Science: What It Can Teach • The Case History Method A. Development of the Mendelian-Chromosome Theory of Heredity (MCTH) B. Methodological Points C. Extensions to Social/Political Context

4. Background (Addison-Wesley, 1982) (Wiley, 2001)

5. Should the History of Science be Rated “X”? [Stephen Brush: Science 183 (1974):1164-1172] • Should students be exposed to the real history of science? - Brush’s answer was to assert that the “real” history of science would clearly undermine the textbook picture of scientific process - Whig history and the cult of “objectivity” - We know so much better now than our predecessors • Brush ends up supporting use of accurate history

6. Major Pointsin Today’s Talk • History and philosophy of science can be useful in teaching both the concepts and methods of science • A historical and philosophical approach can humanize science as a more every-day sort activity - which can empower students • An important component of science is its socio-economic context: cultural factors that play a part in how concepts are formulated and understood • Accurate use of case histories can provide one of the best ways to introduce “methods” in science

7. Outline • Introduction: The Importance of History and Philosophy in Teaching Scientific Methodology A. “Should History of Science Be Rated X?” B. History and Philosophy of Science are complementary but they are not the same • Logic of Science: What It Can Teach • The Case Study Method A. Development of the Mendelian-Chromosome Theory of Heredity (MCTH) B. Methodological Points C. Extensions to Social/Political Context

8. Logic of Science • Components: - Observation(s) - Fact(s) - Conceptualizations • Processes - Induction - Deduction (If . . . Then reasoning, hypothesis testing)

9. Outline • Introduction: The Importance of History and Philosophy in Teaching Scientific Methodology A. “Should History of Science Be Rated X?” B. History and Philosophy of Science are complementary but they are not the same • Logic of Science: What It Can Teach • The Case History Method A. Development of the Mendelian-Chromosome Theory of Heredity (MCTH) B. Methodological Points C. Extensions to Social/Political Context

10. Case History Method

11. DEVELOPMENT OF THE MENDELIAN CHROMOSOME THEORY OF HEREDITY (MCTH) • Time Frame: 1866-1920 • Core Idea: Units of heredity are located in a linear array on structures known as chromosomes in the cell nucleus • Involved the joining of two independent lines of investigation:

12. The Mendelian-Chromosome Theory Is An Interfield Theory Mendelian-Chromosome Theory of Heredity (MCTH) Mendelian Plant Hybridization Exps Cytological Study of Chromosomes

13. Standard Story • Mendel’s work, published in 1866, was ignored for 35 years, rediscovered in 1900 and rapidly accepted thereafter • In 1910 T.H. Morgan (Columbia Univ), looking for Mendelian variations, found a white-eyed male Drosophila, & established the idea of sex-linkage • The linkage concept was extended to all the chromosomes by Morgan and his group, who then developed the method of chromosome mapping • The new science of “genetics” developed largely as an academic effort with little or no connection to agricultural or commercial interests

14. Almost All Aspects of this History are Misleading • It makes the development of ideas seem too logical and neat • Ignores controversies and biases that were an important part of the story • Provides no historical/social/economic context • It obscures some of the real logic and creativity in science, the unclear path and fumbling steps as biologists at the time were experiencing their work • Supports the “treasure-hunt” concept of knowledge-building

15. Core Mendelian Concepts • Traits (characters) in organisms are represented by two “factors” each passed down from the organism’s parents • Traits can have two (or more) forms (tall, short) • Dominance and recessiveness (symbolized T, t; Y,y) • Members of each pair of factors separate from each other (segregate) in forming germ cells (gametes) • When considering 2 or more traits, maternally-derived factors and paternally-derived factors assort independently of one another: TtYy yields TY, Ty, tY, and ty gametes • Hybrids do not breed true

16. Rediscovery and Early Promotion • Mendel’s work was rediscovered independently by three investigators in 1900 (Carl Correns, Hugo De Vries and Erich von Tschermak-Seysenegg) • Initial promotion carried out particularly by William Bateson in England and U.S. • Mendel’s ideas provided what appeared to be the first comprehensive concept of heredity

17. Reception of Mendel’s Work • Highly favorable reaction in agricultural circles - Provided a method for the analysis of hybrids - Mendel’s approach was highly empirical, experimental, quantitative and predictive - It thus fit perfectly the demands of industrial agriculture at the time for predictability and control • Many academic biologists (including the English biometricians) were far more skeptical

18. Opposition to Mendelism • One of those biologists who was critical of Mendelism was T.H. Morgan (1866-1945) at Columbia University. • Morgan’s background • - B.A. State University of Kentucky, 1886 • - Ph.D. Johns Hopkins, 1891 • - Wrote his thesis on the morphology and phylogeny of the “Pycnogonids” (sea spiders) Morgan and his son at Woods Hole, 1907

19. Morgan’s Morphological Work • Aim was to determine the evolutionary relationships of the Pycnogonids to other invertebrates: Arachnids or Crustaceans • Morgan found the early embryology supported an Arachnid ancestry • He soon abandoned morphology as too speculative, inconclusive

20. From Morphology to Experimental Embryology, 1891-1900 • Disenchanted with morphology, Morgan was inspired by the experimental embryology of Hans Driesch at the Naples Zoological Station (1891, 1895) • Experimentation became a symbol of the “new biology” The Stazione Zoologica in 1874

21. Morgan’s Opposition to Mendelism, 1903-1909 • Did not seem universal • Dominance and recessiveness are not usually as clear cut categories as “tall” and “short” in peas • Mendel’s system could not explain inheritance of sex • Mendelian”factors” (not yet called “genes”) were hypothetical units • To explain complex cases Mendelians invented new “factors” arbitrarily:

22. “In the modern interpretation of Mendelism, facts are being transformed into factors at a rapid rate. If one factor will not explain the facts, then two are invoked; if two prove insufficient, three will sometimes work out. The superior jugglery sometimes necessary to account for the results are often so excellently explained because the explanation was invented to explain them, and then presto! Explain the facts by the very factors that we invented to account for them.” [Morgan, “What are factors in Mendelian inheritance?” American Breeders’ Association Report 5 (1909): p. 365]

23. 6. Mendel’s “Factors” sound like the old embryological theory of preformation • Preformation was a 17th - early 19th century view that the embryo was fully formed within the egg or sperm • By 1830 it had been rejected by most embryologists • Preformation ignored the qualitative process by which new form arises from undifferentiated matter Hartsoeker, 1694

24. Development of the Chromosome Theory • By 1900 it had become clear that chromosomes: - Had something to do with heredity either directly or indirectly - Existed in pairs in the cell nucleus - Each pair was qualitatively different (“individuality of the chromosomes”) from the others

25. Between 1890 and 1910 Two Lines of Work Implicated Chromosomes In . . . • The determination of sex • Mendelian heredity, as possibly equivalent to Mendel’s “factors” • Both areas were a matter of considerable controversy

26. Two Contrasting Theories of Sex Determination, 1890-1910 • External Factors: Factors external to the sperm and egg, acting on the fertilized or unfertilized egg, determine sex • Internal Factors (to sperm or egg): Some intrinsic factor within the gametes (one or both) determines sex at the time of fertilization

27. Much Attention Directed at the “Accessory Chromosome” As Sex Determiner • In many organisms one pair of chromosomes con-sists of two different-sized members, or of only a single member; the lone chromosome or its smaller partner were called the Accessory Chromosome • Was it a sex-determining chromosome?

28. The Chromosomal View Gained Considerable Support by 1905 Edmund Beecher Wilson (1856-1938 Nettie M. Stevens (1861-1912)

29. 1905-08 Wilson and Stevens Formulated A Chromosome Theory of Sex Determination • In most animals: XY or XO = male, XX = female • In birds and Lepidoptera: XY = female, XX = male • By early May, 1905,Stevens had cometo a firm conclusion that the XY (XO) relationship determined sex. Wilson was less sure, until he read a draft of Stevens’ paper in late May. He published his results in October, Stevens in November Accessory chromosomes

30. Unification of the Chromosome and Mendelian Theories As early as 1902 Walter S. Sutton, a student of E.B. Wilson, was studying meiosis in the grasshopper; he suggested that: • The movement of chromosomes during formation of germ cells parallels Mendelian segregation • The distribution of maternal and paternal members of each pair to the poles appeared to be random, leading to a large number of possible combinations: 2N = 10: 1,024 2N = 20:1,048,576 • By 1905 Wilson and others supported the parallel

31. Morgan Opposed the Chromosome Theory, Especially in Relation to Sex • Chromosomes dissolve after mitosis/meiosis and thus may not maintain any structural integrity • Differing patterns of male and female chromosome complements: XY, XO = male, XX = female (mammals, insects) XX = male, XY = female (birds, butterflies) • Preformation argument: Postulating chromosomes as causal agents doesn’t explain anything: they are simply structures

32. Morgan Also Opposed Natural Selection as the Main Mechanism of Evolution: • Selection of small individual variations, on which Darwin relied, could never create a new species • Small individual variations were often trivial and non-adaptive • Small variations, even if adaptive, would be swamped out by interbreeding with the more common form • As an alternative, Morgan supported Hugo De Vries’ “Mutation Theory”, 1901-1903: New species arise in one step (“Mutation”) from their parents

33. 1907-1909: Morgan and His Students Had Been Raising Fruit Flies to Test, Alternatives to Darwinian Theory • Neo-Lamarckism: - Student had raised the fruit fly, Drosophila for 60+ generations in the dark, to see effects on eyes - Results were completely negative • Hugo De Vries’ “Mutation Theory”: - In order to try to create De Vriesian mutations, Morgan radiated flies, altered diet, temperature - Results were negative

34. Drosophila, However, Did Turn Out To Be A Favorable Laboratory Organism • Produces new generation in 12-15 days • Easy to keep in laboratory • Produces large number of offspring each generation

35. By 1909, Morgan Ha Become Discouraged with Drosophila Work • In December he told his Yale colleague Ross Harrison: “I have wasted two years [on these flies] and gotten nothing from it.” • Starting in January, 1910, he noticed some small but discrete variations (which he called “mutations”): Trident, Olive, Speck • They were not species-level differences, however • They all showed some characteristics of Mendelian inheritance, but were not clear-cut

36. Morgan’s “Trident” Mutation

37. Then, By Chance, in May, 1910, Morgan Found Another Mutation: • Drosophila normally have brick-red eyes  • One day he observed a white-eyed male fly in his cultures • The eye-color was a clearly discontinuous variation and proved to be easier to work with

38. Morgan Bred the White-eyed Fly to Red-eyed (Wild-type) Female White MaleXRed Female F1 All Red Offspring Red F1 MaleXRed F1 Female F2Red FemalesWhite FemalesRed MalesWhite Males 2,459 0 1,011 782 The red/white-eye ratio was 3:1, but . . . All the white-eyed flies were male!

39. Morgan’s Initial Explanation • The 3 : 1 ratio, and the dominance of red over white suggested a Mendelian pattern • But how explain that only males showed the recessive condition? • Morgan symbolized the mating as follows: Parental generation: Red Female= RRXX x White Male = WWX_ F1 Generation: Females= RWXX(red) MalesRWX(red) 50% 50%

40. Morgan’s Cross Could Be Written as Follows: P1 Red Female xWhite Male RRXXWWX Gametes WX WX X F1 RWXX RWX Red Females x Red Males Gametes WX RX RX W F2 RRXX RWXX RWX WWX Red Female Red Female Red Male White Male There was one problem: Would have to assume the Rfactor always segregated with the X factor in F1 males & these males would produce no WX gametes

41. Testing Hypotheses • Morgan proceeded to provide a set of tests, for example, in the make-up of the F2 females: “. . . There should be two classes of females in the F2 generation, namely RRXX and RWXX. This can be tested by pairing individual females with white males (WWX). In the one instance (RRXX) all the offspring should be red — RWXX and RWX — and in the other instance (RWXX) there should be four classes of individuals in equal number, thus: RWXX, WWXX, RWX, [and] WWX. Tests of the F2 red females show in fact that these two classes exist.” [Morgan, Science 32 (1910): 121]

42. The Test in Morgan’s Notation: Parent F1 Female x White Male (Red-eyed) (White-eyed) RWXX WWX F2Red Females White Females Red Males White Males 129 88 132 86 RWXX WWXX RWX WWX Equal Numbers? • By July 1910, Morgan had accepted the general Mendelian scheme, but not the notation • He had accepted the basic chromosome theory of sex determination, but did not claim W and R were physical parts of the X chromosome: Only their movements were correlated with movement of the X

43. By 1911, however, Morgan had begun to put all the pieces together: • Factor for eye color is physically part of X-chromosome • Called it “Sex-limited” • Do not have to assume that in F1 males R and X always segregate together, while W and X never do • This scheme provided a mechanistic materialist basis for Mendelian inheritance

44. Adopting A Chromosomal Explanation Solved 2 Other Problems • In 1906 Bateson and Punnett had observed 2 Mendelian anomalies: - Some characters appeared to be inherited (linked) together - But in a small percent of cases, these “linkages” were disrupted & recombination occurred • Bateson and Punnett had developed a complex, philosophically idealist theory to explain these results: - Attractions - Repulsions

45. A Similar Case Occurred in Drosophila • Body color and wing type are both sex-linked • Morgan crossed: Black-vestigial x Yellow-Wild B V b v • F1 Females heterozygous BbVv, males all bv • Got 17% recombinants: Yellow-normal wing & black body-vestigial wing • If these traits are linked on X-chromsome, how can we explain this?

46. Chromosomes Provided an Answer: • Wilson had shown Morgan a 1909 paper by Belgian cytologist F.A. Janssens, hypothesizing chiasmata, crossing-over of homologous chromosomes during meiosis • If Mendelian factors linked on chromosomes, and • If homologous chromosomes somehow exchanged parts during synapsis, • Then . . . Linkage could be broken and recombination could occur [Janssen’sChiasmatype Theory:, La Cellule 25 (1909): p. 412]

47. Morgan Used Janssen’s Theory To Develop A New Technique: Chromosome Mapping • If frequency of crossing-over is a function of distance of two factors apart on the chromosome, • If crossing-over is random event, • Then . . . Cross-over frequencies in phenotypes of dihybrid crosses is a function of the relative distance apart of factors on the chromosome

48. Morgan Explained this Idea to An Undergrad Student, A.H. Sturtevant (1890-1970) Working in His Labortory • That same day, Sturtevant analyzed data already collected on 5 sex-linked factors in Drosophila (3 shown here) [From John A. Moore, Heredity and Development (N.Y. Oxford, 1963: 104] • This became the first-ever chromosome map  • [Sturtevant, Journal of Experimental Zoology 14 (1913): 43-59] [From Sturtevant, Journal of Experimental Zoology 14 (1913): 43-59]

49. The Group Approach MBL 1920 • The Morgan group worked as a collective team - Everyone participated in planning the experiments and discussing the results as shown here during a Woods Hole summer “lab meeting” Columbia, 1919 • Such informality was unheard of in Europe

50. Meanwhile, Many New Types of Mutants Turned Up inCultures Top left: Bridges & Morgan, “Third Chromosome Group…” (Carnegie Institution of Washington, 1923), Pl I. Bottom, left: Morgan, Evolution and Genetics (Princeton, 1925): p. 97; Right, Morgan & Bridges, “Sex-linked Inheritance . . .” (Carnegie Institution of Washington, 1916): Pl II