is biology an autonomous science? 本著作除另有註明外，採取創用 cc...
TRANSCRIPT
Is biology an autonomous science?
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
周成功長庚大學生命科學糸
99 年 4 月 12 日
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
Jean-Pol GRANDMONT
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
Normal Science
Anomalies
Crisis
Revolution
Against Method (1975)
Paul Feyerabend (1924- 1994)
Grazia Borrini-Feyerabend
What you have seen? A rabbit or a duck?
Feyerabend
There is no rationally justifiable scientific method.
(i) Scientists do (ought to do?) whatever does not inhibit progress:
(ii) 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??
古典物理學家怎麼“看”生物學？
“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
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 ?
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 DelbruckSalvador Luria and Max Delbruck (1969 Noble laureate in medicine) (1969 Noble laureate in medicine)
1943 – Studies of bacterial resistance to 1943 – Studies of bacterial resistance to bacteriophage Tbacteriophage T11
Adaptation or Spontaneous mutationAdaptation or Spontaneous mutation
Question:Question: Was this resistance acquired through adaptation toexposure to the phage (mutated to survive) OR was it aspontaneous mutation which occurred randomly regardlessof exposure (i.e. it was there before exposure to phage)?
Adaptation Versus Spontaneous MutationAdaptation Versus Spontaneous MutationKey concept in the theory of evolution!
adaptation
E. Coli culture
(wild-type)
Subculture
+ excess
T1 phage
plate
Pick resistant colony
re-infect-still resistant
Phage-resistant E.coli李承維
• resistant bacteria exists even they have NEVERNEVER been exposed to T1
• when T1 added, T1-resistant bacteria selectedselected for
spontaneous
E. Coli culture
(wild-type)
Subculture
+ excess
T1 phage
plate
Pick resistant colony
re-infect-still resistant
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
李承維
I II III IV V VI VII VIII
Cultures
Media and phage plates
Hypothesis: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)
Resistance is the result of adaptation to the selectivepressure (phage). Every bacteria has a small but
constant chance of acquiring resistance upon exposureto T1 phage. If true, the number of resistant cells should
only depend on the # of bacteria and phage.
phage
adaptation
李承維
Resistance is a result of spontaneous, randomResistance is a result of spontaneous, random
mutations even in the absence of phagemutations even in the absence of phage
If so, then there will be a great fluctuation (differences) in the number of resistant colonies when plated
李承維
Conclusions:resistance occurs as a result of random, spontaneousmutations 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”
Seveto Ochoa
KANO PHOTO
Arthur Kornberg
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)
博蘭霓 (Michael Polanyi 1891-1976) )
• 影響一個人研究最重要的因素，是他不能明說、從他的文化與背景中經由潛移默化而得的支援意識 (subsidiary awareness)
• 未可明言的知識 (tacit knowledge)
• 支援意識是隱晦，無法明確描述• 邏輯與方法論不能對創作活動中最重要的關鍵加以界定，更談不上指導了！
學術研究是一條寂寞而漫長的道路，沒有一種出自內心的召喚，沒有那種圈外人嗤之以鼻的「陶醉感」，可能還是去從事學術研究以外的事比較
好 !每個人的生命都是一次獨一無二的經歷，可以追求的事物很多，但是都該
懷抱著熱情去作才值得。 給給給給給給給給給給給給給給 .1990
Physicalism vs Vitalism
• To explain all biological process in term of physical and chemical laws.
• Living organism had some constituent that distinguished it from inert matter.
Organicism • A whole is more than the sum of its parts
– Living beings are not just piles of characters or molecules, because their function depends entirely on their organization, their mutual interrelations, interactions, and interdependencies.
– The genetic program.
– New properties emerge at higher levels of integration which could not have been predicted from a knowlede of the3 lower-level components (emergence)
• Organicism is antireductionism and yet remained mechanistic.
The fundamental differences between living organisms and inert matter
The complexity of living systems
– An open system.– The homeostasis is made by feedback control.– Compare to world weather or galaxy, the
complexity of living systems exists at every hierarchical level.
– They act as though they were a homogeneous entity.
– Their characteristics cannot be deduced from the most complete knowledge of the components.
Organization into populations
• For Plato, variable classes of entities consist of imperfect reflections of a fixed essences.
• In 1859 Darwin introduce the entirely new concept of variable populations composed of unique individuals.– Every water molecules are identical.– Every human being are unique (different).
Possession of a genetic program• Why organisms are unique?
– They have a mechanism for the storage of historical acquired information.
– A historically evolved genetic program coded in the DNA of the nucleus.
• Genotype versus phenotype,– The genotype (genetic program) is the product of a
history that goes back to the origin of life and thus it incorporates the “experiences” of all ancestors.
– The genotype endows organisms with the capacity for goal-directed processes and activities.
Comparative versus experimental method
• Functional biology– The ever-repeated question is “How come”
• How does it function?• How does something operate?• The chief technique is the controlled experiment just like
chemist or physicist does.
• Evolutionary biology– The basic question is “Why?” or “What for?”– Every organism is the product of a long history– Everything is time-bound and space-bound– There are no absolute phenomena in biology– Observation and comparison
What is the cause of bird migration?
• An extrinsic physiological cause– Cold air or short daytime.
• An intrinsic physiological cause– Photo- or temperature- sensor tie in with migration
• A genetic cause– An acquired genetic program in the course of the
evolutionary history
• An ecological cause– Insect eater, must migrate before the winter come– The owl?
Proximate versus Ultimate causes
• Proximate cause: concerned by functional biologist.– Photo- or temperature- sensor tie in with migration
• Ultimate cause: concerned by evolutionary biologist. – An acquired genetic program in the course of the
evolutionary history
• Ultimate cause– Insect eater, must migrate before the winter come
– The owl?
Concepts in biology
• is entirely different from that of the physical sciences and cannot be reduced to it.– “meiosis” plays in the life of an organism
cannot be described only by physical law or chemical reaction, even though physico-chemical principles are operating!
Law versus theories
• No law in biology as the law in physics.– F=MA– E=MC2
• Many theories, but there is hardly a theory in biology with no exception.– Life history theory
Prediction
• Is an essential qualification for physical law!– Predict the existence of one unknown planet
(Neptune) due to the abnormal movement of Uranes.
– Predict the path of light would be curved when it pass through a big mass.
• For functional biology: yes!
• For evolutional biology: probably no!
Teleology
• From egg to adult: a process with a purpose or with a predetermined state?– Important question in biology– Not in physical sciences
• More smoothing and rounding does not make a pebble better adapted for its existence in a river bed!
• Uranus revolves around the Sun once every 84 Earth years. Its average distance from the Sun is roughly 3 billion km (about 20 AU). The intensity of sunlight on Uranus is about 1/400 that on Earth. Its orbital elements were first calculated in 1783 by Pierre-Simon Laplace. With time, discrepancies began to appear between the predicted and observed orbits, and in 1841, John Couch Adams first proposed that the differences might be due to the gravitational tug of an unseen planet. In 1845, Urbain Le Verrier began his own independent research into Uranus's orbit. On September 23, 1846, Johann Gottfried Galle located a new planet, later named Neptune, at nearly the position predicted by Le Verrier.
For biology-
• Life was originated around 3.8 billions years ago and was restricted to the earth!
• Always has exceptions.
• Explanation usually were not based on universal laws but rather were pluralistic.
• Is biology a “dirty science”? Not much better than “postage stamp collection.”
版權標示頁
作品作品 授權條件授權條件 作者作者 // 來源來源
http://commons.wikimedia.org/wiki/File:Francis_Bacon,_V
iscount_St_Alban_from_NPG_(2).jpg
2010/09/27 visited
http://commons.wikimedia.org/wiki/File:Galileo_Galilei_4.jpg 2010/0927 visited
Electron
http://commons.wikimedia.org/wiki/File:Krzywa_wie%C5
%BCa_w_Pizie_i_Galileusz.png
2010/09/27 visited
LSE library http://commons.wikimedia.org/wiki/File:Karl_Popper.jpg 2010/09/27 visited
Vera Buhl http://commons.wikimedia.org/wiki/File:2010-07-07_(22)_Höckerschwan,_White_swan,_Cygnus_olor,_Ginsheim-Gustavsburg_Altrhein.JPG 2010/09/27 visited
Jean-Pol GRANDMONT
http://commons.wikimedia.org/wiki/File:Cygnus_atratus_J
PG1.jpg
2010/09/27 visited
作品作品 授權條件授權條件 作者作者 // 來源來源
http://www.cambridge.org/us/catalogue/catalogue.asp?
isbn=0521792061 2010/10/26 visited
Grazia Borrini-Feyerabend
http://commons.wikimedia.org/wiki/File:Paul_Feyerabend_
Berkeley.jpg 2010/09/27 visited
Thomas Kuhn
http://commons.wikimedia.org/wiki/File:Duck-
Rabbit_illusion.jpg 2010/10/26 visited
“Postage stamp collection” Ernest Rutherford
“…there are no ‘absolute
phenomenon’ …..”Max Delbruck
"Nothing in biology makes sense
……...“T. Dobzhansky
作品作品 授權條件授權條件 作者作者 // 來源來源
Peter, Einstein, Eddington and the 1919 Eclipse, arXiv:astro-ph/0102462; 2001
http://commons.wikimedia.org/wiki/
File:Harfang_en_vol_2.jpg 2010/10/27 visited 原為加拿大魁北克官網圖片http://www.drapeau.gouv.qc.ca/emblemes/harfang/galerie-images.html
“Any living cell carries with it the
experiences of a billion…”Max Delbruck
臺灣大學動物所 李承維
臺灣大學動物所 李承維
臺灣大學動物所 李承維
adaptation
E. Coli culture
(wild-type)
Subculture
+ excess
T1 phage
plate
Pick resistant colony
re-infect-still resistant
Phage-resistant E.coli
Luria-Delbruck ‘Jackpot’; fluctuation test
I II III IV V VI VII VIII
Cultures
Media and phage plates
phage
adaptation
作品作品 授權條件授權條件 作者作者 // 來源來源
臺灣大學動物所 李承維
KANO PHOTO http://www.flickr.com/photos/kano_photo/4644652930/ 2010/09/27 visited
http://commons.wikimedia.org/wiki/
File:Arthur_Kornberg_1969_B.jpg 2010/09/27 visited
John Cairns, The bacterial chromosome and its
manner of replication as seen by autoradiography,
Journal of Molecular Biology, Vol 6, 208-213; 1963
Isolation of an E. coli Strain
with a Mutation affecting DNA
Polymerase
PAULA DE LUCIA & JOHN CAIRNS, Isolation of an E.
coli Strain with a Mutation affecting DNA Polymerase,
Nature 224, 1164 – 1166; 1969
P52~P55 摘 錄 至 人 間 詞話
清末 王國維 人間詞話
作品作品 授權條件授權條件 作者作者 // 來源來源
P56 摘錄至給準備投考研究所同學的一封信
1990 給準備投考研究所同學的一封信