ABC of Scientific Research - A few personal notes Mu-ming Poo May 12, 2010, Beijing

1. ABC of Scientific Research - A few personal notes Mu-ming Poo May 12, 2010, Beijing

2. Five Principles of Graduate Study

3. Five Principles of Graduate Study 1. Knowing how the facts were obtained is more important than knowing the facts (Five “W”: What, Who, When, Where, Why) Importance of knowing the history The history is missing in scientific papers “The Eighth Day of Creation” by Horace F. Judson (Cold Spring Harbor Lab Press, 1976)

4. 2. Knowing how to find the facts is more important than knowing the facts Information overload Do not simply download and readall the papers! “Excessive nonselective reading is hazardous to your health!”

5. 3.Knowing how to present the facts is as important as knowing the facts Presentation is a process of logical integration Science is a social phenomenon Part of the fun in science lies in the communication

6. 4. Knowing what’s unknown is more important than knowing what’s known Incompleteness & questionable reliability of existing knowledge A good vs. bad review paper Science progresses by revising existing knowledge

7. 5. Knowing how to educate yourself is more important than finding someone to educate you Reading first-hand accounts by great scientists “The Double Helix” by James Watson (W.W. Norton & Company, 1968) “What Mad Pursuit” by Franics Crick (Basic Books, Inc. 1988) “Advice to a Young Scientist” by P. B. Medawar (Harper & Row Pub. 1979) “A Passion for Science” by Lewis Wolpert ( Univ. Penn. Press, 1988)

8. More Biographies • “A Feeling for the Organism” • (The life and work of Barbara McClintock) • by Evelyn Keller(W.H. Freeman and Company, 1983) • “Recollections of my Life” by Roman Y Cajal • (The MIT Press, 1989) • “Time, Love, Memory” (Life of Seymor Benzer) • by Jonathan Weiner (Random House, 1999) • “The Excitement and Fascination of Science- • Reflections by Eminent Scientists” • Collections of autobiographic essays, multi-volumes • (Annual Reviews Inc.)

9. More Biographies • “A Feeling for the Organism” • (The life and work of Barbara McClintock) • by Evelyn Keller(W.H. Freeman and Company, 1983) • “Recollections of my Life” by Roman Y Cajal • (The MIT Press, 1989) • “Time, Love, Memory” (Life of Seymor Benzer) • by Jonathan Weiner (Random House, 1999) • “The Excitement and Fascination of Science- • Reflections by Eminent Scientists” • Collections of autobiographic essays, multi-volumes • (Annual Reviews Inc.) • For a list of recommended books and personal comments on books • by eminent scientists, send E-mail to mpoo@berkeley.edu

10. Exploratory Research vs. Hypothesis-Driven Research

11. Exploratory Research Recent discoveries on cell reprogramming - Inducible pluoripotent stem cells (iPs) - Transdifferentiation of pancreas cells

12. Exploratory Research Recent discoveries on cell reprogramming “In biology, a possible mechanism (which does not violate physical and chemical principles) that may be useful to the organism is likely to have been discovered by evolution. -

13. Exploratory Research • Recent discoveries on cell reprogramming • - In biology, a possible mechanism (which does not violate physical and chemical principles) that may be useful to the organism is likely to have been discovered by evolution. • “Quick and dirty experiments” (Julius Axelrod)

14. Hypothesis-Driven Research A good hypothesis proposes the obvious missing links between the known phenomena A good hypothesis makes specific statements on the causal relationships among a few key phenomena Hypothesis is there to be refuted, not to be proved (One can never “prove” a hypothesis)

15. ABC of hypothesis-driven research • Known: A → B in one system, and B → C in my system • My Hypothesis: A → B → C in my system. • B mediates A’s effect on C • ______________________________________________________________ • Experimental Tests: • 1. Does A → B in my system? Yes! • Does A → C in my system? Yes! • Is B required for A → C? • (Knockout out B, or pharmocological inhibition) • Yes! “B is necessary for A → C” - “Necessity” condition • 4. Is B sufficient for C in the absence of A? • Yes! “B is sufficient” - “Sufficiency” condition

16. However • Quantitatively, under physiological conditions, does A produces sufficient amount of B, which is enough to induce C? • Does A really induces no C in the absence of B? If not, may be A → B’ → C. • In the absence of A, providing the amount normally induced by A is sufficient to induced C?

17. However • Quantitatively, under physiological conditions, does A produces sufficient amount of B, which is enough to induce C? • Does A really induces no C in the absence of B? If not, may be A → B’ → C. • In the absence of A, providing the amount normally induced by A is sufficient to induced C? If not, then they are multiple pathways from A to C!

18. Prospective Research vs. Retrospective Research

19. On Innovative (Creative) Research Novelty（新颖性） Significance (重要性) Continuity (连续性） Uniqueness (独特性） Completeness (完整性） Timeliness（及时性）

20. How to do creative work Broad scientific exposure (广铺触角） Learn the history（探索历史） Selective Reading (挑选性阅读） Taking risk(敢于冒险） Positive attitude towards critiques (正面对待批评） Learn from creative minds (向有创造性思维的科学家学习）