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第 6 單元:生物學是物理科學的延伸嗎?. Is biology an autonomous science?. 4-12-2010. 周成功. 本著作除另有註明外,採取 創用 CC 「姓名標示-非商業性-相同方式分享」台灣 2.5 版 授權釋出. What is scientific method?. 大胆的假設 小心的求証. Sir Francis Bacon (1561-1626). Bacon’s Methodology of Science Examine an large number of cases Using Induction
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第6單元:生物學是物理科學的延伸嗎? Is biology an autonomous science? 4-12-2010 周成功 本著作除另有註明外,採取創用CC「姓名標示-非商業性-相同方式分享」台灣2.5版授權釋出
What is scientific method? 大胆的假設 小心的求証
Sir Francis Bacon (1561-1626) Bacon’s Methodology of Science Examine an large number of cases Using Induction Employing no pre-judgement, i.e. not theory- or hypothesis-driven
Galileo GalileiItaly, 1564-1642 Galileo and Shakespeare were born the same year. Experiments and instruments Galileo disproved Aristotle’s hypothesis that heavy objects fall with greater speed than light objects. Electron
Sir Karl Popper (1902-1994) 1902: Born in Vienna 1945: The Open Society and its Enemies 1946: London School of Economics 1949: University of London 1959: The Logic of Scientific Discovery 1963: Conjectures and Refutations: The Growth of Scientific Knowledge 1965: Knighted by Queen Elizabeth II
The principle of Induction (歸納法) If a large number of swans have been observed under a variety of conditions and all swans were seen as white, then by induction all swans have the property white. Valid general laws can be inferred from true observation statements. But, ….. Vera Buhl
Falsification • Science progresses by eliminating theories that have been falsified. • A scientific theory cannot be shown to be true. But some scientific theories do have varying degrees of success. They resist falsification. • Scientific theories are those that can be falsified. • Good scientific theories do not make themselves immune from falsification by use of ad hoc hypotheses
Thomas S. Kuhn (1922-1991) • The Structure of Scientific Revolutions • The University of Chicago Press, 1962. • No reference to Popper
Kuhn’s History of Science Descriptive Project: Immature Science Revolution Crisis Normal Science Anomalies
Against Method (1975) Paul Feyerabend (1924- 1994) Grazia Borrini-Feyerabend
Feyerabend There is no rationally justifiable scientific method. • Scientists do (ought to do?) whatever does not inhibit progress: • Theory acceptance is ideological, not rational “…there is only one principle that can be defended under all circumstances and in all stages of development. It is the principle that anything goes” (AM 28)
Does biology have the same scientific characters as physics??
“Postage stamp collection” Ernest Rutherford
“…there are no ‘absolute phenomenon’ in biology. Everything is time-bound and space-bound…” Max Delbruck
Is biology an autonomous science? Whether and how biology differs from the other natural sciences, such as chemistry or physics?
"Nothing in biology makes sense except in the light of evolution.“T. Dobzhansky 1900 - 1975. Biology: a science with history
Is evolution of galaxies (history of universe) equivalent to biological evolution? • Evolution of galaxies is transformational , not variational evolution. • Radioactive decay, controlled by physical laws is a teleomatic (spontaneous toward the end state) process, not a teleonomic one (goal-directed).
物理學:科學的模範生 • 從加利略到牛頓所建立科學的典範 • 不受時空限制的物理定律. • 物理定律不討論“運氣”的角色 • 科學方法就是嚴格控制所有變數的實驗 • “觀察”與“比較”是不太科學的方法 • Feyman: Characters of Physical Law (天下文化)
對生物學來說 • 生命源起於三十八億年前的地球 • 時空的限制 • 永遠準備“例外”的出現 • 對現象的解譯常有多重可能的臆測,而非完全依賴嚴格的物理律. • Two key questions in biology. • “How?” or “how come?” • “Why?” or “what for?”
兩種類型的生物學 . • “How?” or “how come?” • 功能生物學 (Functional Biology) • “Why?” or “what for?” • 演化生物學 (Evolution Biology)
Prediction (預測) • 物理律最重要的條件! • 從天王星繞日軌道的觀察不符合牛頓力學的計算,推論應有一尚未被觀察到的行星存在! • 根据相對論,光經過一個重力場時会產生偏折的現象. • For functional biology: yes! • For evolutional biology: probably no! • 討論未來的生命型式在自然界会如何改變是沒有意義的!
Solar eclipse of 29 May 1919 • Newton: deflection = 0.87 arc seconds • Einstein: deflection = 1.74 arc seconds • Observations: • Crommelin expedition 1.98 0.16 • Eddington 1.61 0.40 • Einstein is overnight sensation Peter, Einstein, Eddington and the 1919 Eclipse, arXiv:astro-ph/0102462; 2001
Teleology(目的論) • 討論目的是生物學中一亇重要的問題! • 物理科學不討論物理現象有什麼目的! • 我們會不会討論河床中圓滑卵石存在的目的? • 讓它們更容易安逸地躺在河床上!?
Population (群體) • 我們會不会說這是“一群”氫原子? • No!對物理學家,宇宙中每一亇氫原子都是完全相同無可分辦的! • 但是對生物學家,“一群生物”中每一亇生命亇體都是獨一無二的!
Is cause the same thing in functional and evolutionary biology?
侯鳥在秋天“為什麼”要向南飛? How? and Why?
How? • 外在環境如氣温,日照等因素的改變。 • 內在生理因素如腦中感光 (温) 受體誘發行為的改變。 • 怎麼作到的(原因)。 • 生理、生化的機制。 • 不問這個機制怎麼來的 (歷史)!
Why? • 每隻候鳥都攜帶了一套獨特的“遺傳程式” • 這套“遺傳程式”從何而來? • 為什麽猫頭鷹不南飛?
猫頭鷹不需要這套天冷南遷的“遺傳程式”! • 候鳥吃昆蟲,天寒蟲少,必須演化出一套獨特的“遺傳程式”,讓他們在變天前往南飛才能存活下來 (生態的原因)。 • 演化的原因:解譯了歷史!
生物學的歷史面向-和物理最大的不同 根據現存的種種蛛絲馬跡去重新建構或還原歷史事件。 永遠是個有些根據的理論,但永遠無法用嚴謹的實驗証明! 生物的歷史(演化) —幫助我們去暸解生物世界一個重要的基石
生物學:一亇帶着歷史經驗的科學 “Any living cell carries with it the experiences of a billion years of experimentation by its ancestors” “ A physicist looks at biology” Max Delbruck, 1949
"Nothing in biology makes sense except in the light of evolution." T. Dobzhansky 1900 - 1975.
Salvador Luria and Max Delbruck (1969 Noble laureate in medicine) 1943 – Studies of bacterial resistance to bacteriophage T1 Adaptation or Spontaneous mutation
Pick resistant colony re-infect-still resistant Subculture + excess T1 phage plate E. Coli culture (wild-type) adaptation Phage-resistant E.coli 李承維 Question:Was this resistance acquired through adaptation to exposure to the phage (mutated to survive) OR was it a spontaneous mutation which occurred randomly regardless of exposure (i.e. it was there before exposure to phage)? Adaptation Versus Spontaneous Mutation Key concept in the theory of evolution!
resistant bacteria exists even they have NEVER been exposed to T1 • when T1 added, T1-resistant bacteria selected for spontaneous Pick resistant colony re-infect-still resistant Subculture + excess T1 phage plate E. Coli culture (wild-type) Phage-resistant E.coli 李承維
1943 Salvador Luria and Max Delbruck used E. coli and T1 phage to test hypothesis (adaptive vs spontaneous) Luria-Delbruck ‘Jackpot’; fluctuation test V II III VI VII VIII I IV Cultures Media and phage plates 李承維
phage adaptation 李承維 Resistance is the result of adaptation to the selective pressure (phage). Every bacteria has a small but constant chance of acquiring resistance upon exposure to T1 phage. If true, the number of resistant cells should only depend on the # of bacteria and phage. Hypothesis: if constant amount of bacteria and phage are added and incubation time is constant, then all plated cultures should adapt similarly, resulting in similar #’s of resistant colonies on the plates (no fluctuation)
李承維 Resistance is a result of spontaneous, random mutations even in the absence of phage If so, then there will be a great fluctuation (differences) in the number of resistant colonies when plated
Conclusions: resistance occurs as a result of random, spontaneous mutations that happen at various time points BEFORE exposure to selective agent.
The Nobel Prize in Physiology or Medicine 1959 “for their discovery of the mechanisms in the biological synthesisi of ribonucleic acid and deoxyribonucleic acid” Arthur Kornberg Seveto Ochoa KANO PHOTO
Kornberg’s enzyme- DNA polymerase • Polymerization • 3’-5’ exonuclease “editing” • 5’-3’ exonuclease “nick-translation”
The bacterial chromosome and its manner of replication as seen by autoradiography. (John Cairn. J Mol Biol. 6:208-13. 1963) • 1. One DNA molecule/chromosome per bacteria • 2. One replication origin per chromosome (bacteria/viruses). Interpretation of the autoradiogram:
Is Kornberg enzyme really responsible for DNA replication in vivo?
Isolation of an E. coli strain with a mutation affecting DNA polymerase Paula de Lucia & John Carins Nature 224: 1164-1166 (1969)
學術發現的四個階段法國數學家朋加萊 (H. Poincare) 準備 (Preparation) 潛伏 (Incubation) 豁然開朗(Illumination) 証明 (Verification)