Lecture one: what is life?

1. Lecture one: what is life?

2. “Unity is plural and, at minimum, is two” Buckminster Fuller

3. Take home quiz 9-18-2017 • 試用三個 Key concepts 來解釋生物演化。 • What is the major difference between “galaxies evolution” and “biological evolution”? • you provide an example (not the one in the reading assignment) to explain “genetic drift”?

4. Genetic Drift 有100對夫婦來到一個荒島，其中有個男生帶了一個十分獨特的基因突變，但這個人特別風流瀟灑，和每個女生都有一段情，往後的子孫中這個獨特的基因突變出現的頻率應遠高於200分之一！

5. Take home quiz 9-18-2017 • How important of Mendel genetics is to Darwin’s evolution theory?

6. Charles Darwin (1809 –1882)

7. Darwin • Fail in studying medicine in Edinburgh. “The instruction at Edinburgh was altogether by lectures, and these were intolerably dull, with the exception of those on chemistry….to my mind there are few advantages and many disadvantages in lectures as compared with reading…. Dr. xxx made his lectures on human anatomy as dull as he was himself, and the subject disgusted me.” Charles Darwin 1876

8. Darwin • Study theology in Cambridge, but fall in love of natural history. • Natural Theology (1802) by Willian Paley • The metaphor of watch. • A Preliminary Discourse on the Study of Natural Philosophy (1830) by John Frederick William Herschel • The problem of the creation of life from nonlife. • How does the observed diversity of the natural world arise? • “Mystery of mysteries.”

9. Darwin • In Aug. 1831, he was invited to be a “gentleman scientist” in the exploratory survey ship: the Beagle. • Dec. 27, 1831 to Oct. 2, 1836. • Why on earth were living things organized in this manner? • Two facts stood out after he came back • the fossils coexist with the same living variants • 13 different species of finch

10. Two key stimulations Common practice of farmer:variation with artificial selection； Oct 1838: An essay on the Principle of population (by Malthus at 1798)

11. In his 1859 On the Origin of Species by Natural Selection. In his 1837’s notebook

12. Darwin vs Wallace • By the winter of 1938, the natural selection theory has been formulated. • 1844, he wrote a 255 pages essay for friends. • Both papers presented on July 1, 1858 at Linnean Society at London. • 1855, a paper published in the Annals and Magazine of NaturalHistory. • By the winter of 1857, he formulated his theory on natural selection. • In June 1858, he send his draft to Darwin

13. No one was enthusiastic about either study In May 1859, the president of the society remarked that the past year had not yielded any particularly noteworthy discoveries!

14. On Nov. 23, 1859, 1,250 copies of “On the origin of species by means of natural selection.” were published at 15 shillings a copy.“ All copies were sold on the first day.”

15. Survive of the fittest Herbert Spencer first used the phrasein his Principles of Biology (1864), 

16. Chapter Titles • On the Origin of Species • Variation under Domestication • Variation under Nature • Struggle for Existence • Natural Selection • Laws of Variation • Difficulties on Theory • Instinct • Hybridisation • On the Imperfection of the Geological Record • On the Geological Succession of Organic Beings • Geographical Distribution • Geographical Distribution continued • Mutual Affinities of Organic Beings: Morphology: Embryology: Rudimentary Organs • Recapitulation and Conclusion

17. The power of Selection, whether exercised by man or brought into play under nature through the struggle for existence and the consequent survival of the fittest, absolutely depends on the variability of organic beings. Without variability, nothing can be effected; slight individual differences, however, suffice for the work, and are probably the chief or sole means in the production of new species. Charles Darwin (1868)

18. “Our ignorance of the laws of variation is profound. Not in one case out of a hundred can we pretend to assign any reason why this or that part differs, more or less, from the same part in the parents.” On the Origin of Species - Chapter 5: Laws of Variation 

19. Darwin and the blended inheritance • On the Origin of Species(1859): he identified the inheritance of acquired characters as one of the sources of variation on which natural selection acts. • Variation of Animals and Plants Under Domestication (1868):Darwin offered his “provisional hypothesis of pangenesis” to account for a whole range of phenomena related to heredity and development.

21. Jenkin, F., Origin of Species. North British Rev. 46: 277–318; 1867. Nevertheless, until reading an able and valuable article in the ‘‘North British Review’’ (1867), I did not appreciate how rarely single variations, whether slight or strongly-marked, could be perpetuated (Darwin 1859, pp. 111–112). The sixth edition of The Origin of Species, 1872

22. Gregor Mendel (1823-1884)

23. “This seems to be the one correct way of finally reaching a solution to a question whose significance for the evolutionary history of organic forms cannot be underestimated” Mendel, G., 1866 Versuche über Pflanzenhybriden. Ver. Naturforsch. Ver. Brünn 4: 3–47.

24. Three key concepts of Neo-Darwinism: 變異、遺傳 與天擇 生物性狀的變異：來自基因隨機突變的結果； 來自基因的變異可以忠實地遺傳到下一代； 環境的適應決定了誰是未來的主流！

25. Take home quiz 9-18-2017 • 四海之內，皆兄弟也！這句話有科學根據嗎？ • 生命能否存在於一個 close system? Explain your answer. • What is SNP? How does one specific SNP affect phenotype of the individual? • Why don’t use DNA as template for protein translation? • 1928年，弗雷德里克·格里菲斯發現了轉化現象：死亡的細菌可以將遺傳物質「轉化」到其他依然活著的細菌內。這對分子生物學的影響是什麼？ • 怎麼樣才算真正完全回答 or 瞭解 what is life?

26. Why at 30’s many physicist become interested in biology? 現代主義的全盛時期：1910年—1930年 現代主義以科學為基礎，重視理性與邏輯，實驗探証。其中牛頓、達爾文及弗洛伊德為現代主義的典範。

27. M a x L u d w i g H e n n i n g D e l b r u c k 1906—1981

28. Max received his Ph.D. under Max Born and Walter Heitler from Tubingen in 1930 • In 1928, he spend 18 months at Bristol and became very friendly with Cecil F. Powell, P. M. S. Blackett, P. A. M. Dirac and H. W. P. Skinner • 1931, he received Rockefeller Fellowship to spent the spring and summer with Niels Bohr in Copenhagen. Then another 6 months with Wolfgang Pauli in Zurich. • “I do not mind if you think slowly. But I object when you publish more quickly than you think.” • In1932, he accept an appointment as assistant to Lise Meitner at the Kaiser Wilhelm Institute for Chemistry in Berlin. • Before returning to Berlin he paid a short visit to Copenhagen to hear Bohr deliver his famous address, "Light and Life“ .

29. Timofeef-Ressovsky, N. W., K. G. Zimmerand M. Delbruck, U¨ ber die Natur der Genmutation und der Genstruktur. Nachr. Ges. Wiss. (On the nature of gene mutation and gene structure)Go¨ttingen, Fachgr. 6 N.F. 1. 13: 190–245; 1935. Size and stability of gene

30. What is life? The Physical Aspect of the Living Cell. Feb. 1943 at Trinity College, Dublin

31. In 1937, he attained a fellowship from Rockefeller Foundation—which was launching the molecular biology research program.  The term molecular biology was coined by Warren Weaver in 1938

32. Entering biology world • THE GROWTH OF BACTERIOPHAGE. Ellis EL, Delbrück M. J Gen Physiol. 1939 Jan 20;22(3):365-84. • THE GROWTH OF BACTERIOPHAGE AND LYSIS OF THE HOST. Delbrück M. J Gen Physiol. 1940 May 20;23(5):643-60. • ADSORPTION OF BACTERIOPHAGE UNDER VARIOUS PHYSIOLOGICAL CONDITIONS OF THE HOST. Delbrück M. J Gen Physiol. 1940 May 20;23(5):631-42.

33. 生物演化的三步曲：變異、遺傳 與天擇 How to experimentally prove Darwin is right: gene mutation is spontaneously generated and is preexisted before the selection!

34. Luria, S. E., and M. Delbru¨ck, 1943 Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28: 491–511. Fluctuation test!

35. Fluctuation Test

36. 碰到phage，只有resistant mutant才能存活！

37. If the mutation is spontaneously and randomly occured, can we estimate the mutation rate from this experiment?

38. The distribution of a random event can be described by Poisson distribution. The probability of observing kevents (resistant colony appeared or not appeared in the plate) in an interval is given by the equation Which k event you will choose? Colony number in the plate: 0, 1, 2, …., 1508

39. The simplest way of determining Px is to determine the frequency of zero events.

40. Mutation rate = number of mutant / total number of cell divisions. The number of cell divisions is approximately equal to the number of cells in the population (N).

41. Exercise 1, To determine the frequency of StrR mutants a fluctuation test was done with 50 tubes each containing 108 cells and 42 of the tubes contained no mutants. 2, To determine the frequency of Pro-mutants a fluctuation test was done using 20 tubes with a final concentration of 107 bacteria each. From each tube 0.1 ml of culture was plated on medium that selects for Pro-mutants. Seventeen of the tubes yielded putP mutants but 3 of the tubes yielded no mutants.

42. Why the rate of mutation to StrR is so much less than the rate of mutation to Pro-?

43. “Suppose [an] imaginary physicist, the student of Niels Bohr, is shown an experiment in which a virus particle enters a bacterial cell and 20 minutes later the bacterial cell is lysed and 100 virus particles are liberated. He will say: “How come, one particle has become 100 particles of the same kind in 20 minutes? That is very interesting. Let us find out how it happens! How does the particle get in to the bacterium? How does it multiply? Does it multiply like a bacterium, growing and dividing, or does it multiply by an entirely different mechanism ? Does it have to be inside the bacterium to do this multiplying, or can we squash the bacterium and have the multiplication go on as before? Is this multiplying a trick of organic chemistry which the organic chemists have not yet discovered ? Let us find out.

44. This is so simple a phenomenon that the answers cannot be hard to find. In a few months we will know. All we have to do is to study how conditions will influence the multiplication. We will do a few experiments at different temperatures, in different media, with different viruses, and we will know.” Perhaps we may have to break into the bacteria at intermediate stages between infection and lysis. Anyhow, the experiments only take a few hours each, so the whole problem can not take long to solve.” [Eight years later] he has not got anywhere in solving the problem he set out to solve. But [he may say to you] “Well, I made a slight mistake. I could not do it in a few months. Perhaps it will take a few decades, and perhaps it will take the help of a few dozen other people. But listen to what I have found, perhaps you will be interested to join me.”  From 'Experiments with Bacterial Virus (Bacteriophages)',  Harvey Lecture (1946), 41, 161-162.

45. Phage group at Cold Spring Harbor Laboratory , New York

46. "Well, the phage group wasn'tmuch of a group. I mean it was a group only in the sense that we all communicated with each other. And that the spirit was—open. This was copied straight from Copenhagen, and the circle around Bohr, so far as I was concerned. In that the first principle had to be openness. That you tell each other what you are doing and thinking. And that you don't care who—has the priority"

48. Watson & Crick May 21, 1953 at Cambridge, UK

50. Watson & Crick : Genetic Implications of the Structure of Deoxyribonucleic AcidNature May 30, 1953 “it therefore seems likely that the precise sequence of the bases is the code which carries the genetic information”