Basic Science Partnership (BSP)

1. Basic Science Partnership(BSP) Matthias S. Schedl Summer program 2010

2. Course reading • Text: GLASS, J. D. (2007): Experimental Design for Biologists. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. • Supplement reading: CERF, O. et al. (2009) : Tests for determining in-use concentrations of antibiotics and disinfectants are based on entirely different concepts: “Resistance” has different meanings. International Journal of Food Microbiology 136, 247–254.

3. Syllabus • 4 discussions/ lectures • Individual talks from different labs • Last session of course  your presentations from your lab projects

4. Independent Project/Presentation • Each student should create a 15 minute PowerPoint presentation on the current lab project • Explain: • 1.basic biology behind the mechanisms being researched • 2.include techniques as a methods section • Your results section (optional)

5. Outline for our course: • Session 1 • Book chapters 1-9 • Session 2 • Book chapter 10, plus additional paper • Session 3 • Book chapters 11-14 • Session 4 • 15-19 • Quiz

6. This time ... • Since you did not have the book so far I will cover the first chapters today and you should read them up until next time. • Additional literature: • Supplement reading: CERF, O. et al. (2009) : Tests for determining in-use concentrations of antibiotics and disinfectants are based on entirely different concepts: “Resistance” has different meanings. International Journal of Food Microbiology 136, 247–254.

7. CHAPTER 1-9 Key words: Hypothesis Problem/Question framework System establishment Model building

8. Philosophy of Science by Sir Karl Raimund Popper • Why do we set up hypothesis in science today? • Karl Popper: • Born in Vienna, Austria worked in London, UK • Schools: • Analytic • Critical Rationalism • Fallibilism • Evolutionary epistemology • Liberalism Source: http://www.nndb.com/people/164/000087900/

9. Philosophy of Science by Sir Karl Raimund Popper • How did Popper developed his ideas about science and philosophy? Source: http://www.nndb.com/people/164/000087900/

10. Philosophy of Science Sir Karl Raimund Popper • Physical world • Subjective personal perceptions • Objective abstract products of the human mind Source: http://www.knowledgejump.com/knowledge/popper.html

11. Who was Popper? • He attended the local Realgymnasium • Went to the University of Vienna in 1918 • In 1919 Popper joined the left-wing politics, the Association of Socialist School Students, Soon abandoned it entirely because of the doctrinaire character.

12. Karl R. Popper (1902-1994) • He discovered the psychoanalytic theories of Freud and Adler, and listened entranced to a lecture which Einstein gave in Vienna on relativity theory. • The dominance of the critical spirit in Einstein, and its total absence in Marx, Freud and Adler, struck Popper as being of fundamental importance.

13. Karl R. Popper (1902-1994) • For Popper the critical spirit in Einstein theory had crucial and testable implications which, if false, would have falsified the theory itself. • The total absence of critical spirit in Marx, Freud and Adler, couched in their theories in terms which made them amenable only to confirmation.

14. Karl R. Popper (1902-1994) • The dominant philosophical group in Vienna at the time was the Vienna circle, the circle of ‘scientifically-minded’ intellectuals. • The principal objective of the members of the Circle was to unify the sciences, which carried with it, in their view, the need to eliminate metaphysics.

15. Karl R. Popper (1902-1994) • Popper became increasingly critical of the main tenets of logical positivism. • He articulated his own view of science, and his criticisms of the positivists, in his first work, published under the title Logik der Forschung in 1934.

16. Karl R. Popper (1902-1994) • The book attracted more attention than Popper had anticipated. • Popper was invited to lecture in England in 1935. • The growth of Nazism in Germany and Austria compelled him, like many other intellectuals who shared his Jewish origins, to leave his native country.

17. Karl R. Popper (1902-1994) • After a teaching position in New Zealand in 1937 he finally moved to England in 1946 to teach at the London School of Economics, and became professor of logic and scientific method at the University of London in 1949. • His ideas finally became so prominent that biological science almost always starts with formulating a hypothesis.

18. What is a hypothesis? • Definition: A research hypothesis is the statement created by a researcher when they speculate upon the outcome of a research or experiment. Why do we need hypothesis in science? Every true experimental design must have this statement at the core of its structure, as the ultimate aim of any experiment.

19. Hypothesis • Usually the hypothesis is the result of a process of inductive reasoning where observations lead to the formation of a theory. Scientists then use a large battery of deductive methods to arrive at a hypothesis that is testable, falsifiable and realistic.

20. Hypothesis • If a research hypothesis, stands the test of time, it eventually becomes a theory, such as Einstein’s General Relativity. • Even then, as with Newton’s Laws, it can still be falsified or adapted.

21. Hypothesis • The precursor to a hypothesis is a research problem, usually framed as a question. • The research hypothesis is a paring down of the problem into something testable and falsifiable.

22. Popper rejected the term of classical empiricism, and of the classical observationalist-inductivist account of science that had grown out of it. What is Critical Rationalism?

23. What is Critical Rationalism? • Scientific ideas can only be tested indirectly because scientific theories are abstract and human knowledge generally, is irreducibly conjectural or hypothetical, and is generated by the creative imagination of humans.

24. What is Critical Rationalism? • No number of positive outcomes at the level of experimental testing can confirm a scientific theory, but a single counterexample is logically decisive: it shows the theory, from which the implication is derived, to be false. • Hence falisfication

25. What does it mean a hypothesis is falsifiable? The term "falsifiable" does not mean something is false; rather, that if it is false, then this can be shown by observation or experiment. Popper's account of the logical asymmetry between verification and falsifiability lies at the heart of his philosophy of science.

26. What does it mean a hypothesis is falsifiable? • Falsifiability, as defined by the philosopher, Karl Popper, defines the inherent testability of any scientific hypothesis. • Science and philosophy have always worked together to try to uncover truths about the world and the universe around us. Both are a necessary element for the advancement of knowledge and the development of human society.

27. When is a hypothesis not practicable? • Human Genome Project • Why did scientists not set out a hypothesis such as: • “There are ten genes in the genome involved in insulin production” Source: http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml

29. Critical Rationalist : Here the scientist uses prior knowledge to frame a hypothesis and formulate a conclusion about the unknown. Question/answer methodology: The scientist uses prior knowledge upon which to ask a question about the unkown. Difference between critical rationalist and question/answer framework

30. CHAPTER 4

31. Comparing the different approaches • Decide on an experimental project • Make a hypothesis • Subject the hypothesis to falsification • Get a result • Determine whether the result holds true in repeating • Decide on an experimental project • Ask a question • Get an answer • Ask the question again and observe its accuracy Critical Rationalism Question/answer mode

32. A system of sequential queries • Why don’t you set up a hypothesis to walk to Harvard Medical School when you are at Boylston Street ?

33. A system of sequential queries • You could formulate a hypothesis: • “Walking on Boylston towards Brookline will take me to LHRRB in the Longwood area.”

34. A system of sequential queries • You could formulate a hypothesis: • “Walking on Boylston towards Brookline will take me to LHRRB in the Longwood area.” • This hypothesis can than be subjected to falsification. • Why don’t we do that?

35. What is the inductive space? • The background information that is already existing about a specific question prior to the study • Example in Chapter 6: • Why can the question be:  “What is the function of MuRF1?” given we know MuRF1 is a protein.

36. Types of questions • The open- ended question • “What color is the sky?” • Define the scope of the problem • The close- ended question • “The sky is red” • Two analyses: • Red, not- red

37. Discrete questions • Not all open- ended questions are all encompassing Project B Project A Which genes are implicated in glucose metabolism What is the role of gene X in glycose metabolism ? What is the function of gene X?

38. Discrete questions Project A Project B Discrete question after projetc study ? Which genes are implicated in glucose metabolism What is the role of gene X in glycose metabolism ? What is the function of gene X?

40. Inductive reasoning • Initial observation lead to the discovery of a certain pattern. • This allows a tentative prediction to be made which leads to a general theory about how things work.

41. Inductive reasoning • Charles Darwin for example observed the variety of Darwin finches on the Galapagos islands and based on that build his theories.

42. Inductive reasoning • After some thought and reasoning, he saw that these populations were geographically isolated from each other and that the variation between the sub-species varied over distance.

43. Inductive reasoning • He therefore proposed that the finches all shared a common ancestor, and evolved and adapted, by natural selection, to exploit vacant ecological niches. This resulted in evolutionary divergence and the creation of new species, the basis of his ‘Origin of Species’.

44. Inductive reasoning • This was an example inductive reasoning, as he started with a specific piece of information and expanded it to a broad hypothesis. Science then used deductive reasoning to generate testable hypotheses and test his ideas.

45. Inductive reasoning • In the lab nowadays you do not have to travel to the Galapagos islands in order to expand your inductive space. • You would rather consult a computer and do a web search

46. Deductive reasoning • Deductive reasoning is what most scientists recognize as the standard scientific method, where a researcher starts with a wider theory. • The researcher generates a testable hypothesis and designs an experiment to observe the results, and prove or disprove the theory.

47. Deductive reasoning • Deductive reasoning, starts with a general principle and deduces that it applies to a specific case. • Inductive reasoning is used to try to discover a new piece of information while deductive reasoning is used to try to prove it.

48. Deductive reasoning Example • J. J. Thompson’s Cathode Ray-Experiment was an excellent example of this process, where he had ideas about how electrons behaved and generated theories about their nature. • Therefore, Thompson generated hypotheses, designed experiments and tried to find conclusive answers to add credence and weight to his initial theory.

49. J. J. Thompson’s Cathode Ray-ExperimentDeductive reasoning • He found that by applying a magnetic field across the tube, there was no activity recorded by the electrometers and so the charge had been bent away by the magnet. This proved that the negative charge and the ray were inseparable and intertwined. http://www.experiment-resources.com/cathode-ray.html#ixzz0pFB6EBah

50. J. J. Thompson’s Cathode Ray-ExperimentDeductive reasoning • Out of this deduction Television was developed • Thompson receiver the Nobel prize in Physics in 1906. http://www.experiment-resources.com/cathode-ray.html