Ultimate List of Final Exam Questions:The final exam will consist of ten questions from the list below, from which you should answer your choice of any six questions.If each of your six answers doesn't at least fill the front and back of one sheet of paper, then you are probably not answering in enough detail or depth. You will not need blue-books. I will bring a large package of xerox paper, and a stapler. Please write your name on each page that you write, to minimize the chance of papers getting mixed up or staples becoming detached. The final exam is "Open Book". You can and should bring your class notes and use them to help you answer the questions. It is even OK if you prepare for the exam by writing outlines of what you would answer for each of the fifty-one questions, and use those outlines as the basis for your answers on the exam itself. It is also OK to discuss the questions with any other members to the class prior to the exam, but please don't just copy their outlines. Your own answer will be better. (But please don't ask faculty members, graduate students or others, until after the exam. And please don't ask me to tell you the answers. I am willing to make hints or suggestions, or to clarify the questions, but not simply to answer them.) {I solemnly promise to be fair in grading conclusions that I disagree with at least as favorably as I grade answers that happen to match my current opinions. In other words, please don't try to guess what I believe, and argue in favor of it. Strategically, you could be better off to present well-argued opinions that are different from mine. Please believe me about this. A. H.} As these sample questions suggest, you will be very wise to review the summaries about Popper and Kuhn; But I do not suggest rushing to read the original books by either of these philosophers of science. The final exam will count 40% of your final grade. The Erroneous Paper Report will count 30%. QUESTIONS 1) Regarding leg regeneration of salamander legs, cell marking studies show that regenerated muscles and cartilages develop from cells that had previously been parts of muscles and cartilages in the stump. Assuming that all differentiated cell types of regenerated legs likewise regenerate from cells their same cell type, argue pro or con that regeneration works by rearrangement of differentiated cells. 2) Embryonic development of legs and other organs has long been assumed to work by controlling cell differentiation according to location. Argue pro or con whether this generalization is true or false (about the beliefs of biologists and textbooks.) Argue pro or con whether this assumption is accurate or not, as regards how development really works. 3) H. V. Wilson believed that dissociated sponge cells either redifferentiate according to their random locations, or possibly that undifferentiated archeocytes (= stem cells) differentiate into whichever cell type is needed at their random location. What is a third possibility? How might Wilson's assumptions about cell sorting be related to the first sentence of question number two? 4) How would sponge cell reagregation be explained by the differential adhesion hypothesis? 5) Design an experiment (or as many experiments as you can) that could be able to disprove or confirm either the differential adhesion hypothesis or the differential interfacial contraction theory. You are allowed to add or "knock-out" genes for adhesion proteins; you are allowed to measure forces at different locations; you can use drugs that inhibit or stimulate cell contraction; you can do genetic screens for mutations that alter gastrulation, neurulation or other rearrangements of cells; and you can apply any other method that you know about or can invent. 6) In the game "20 Questions", you try to identify an unknown something based on asking 20 yes or no questions about it. Please invent 10 "yes or no" questions the answers to which would be most useful in finding a cure for cancer. The questions must be "yes or no", and not something like "what causes spontaneous remissions" For each of your questions, explain why you expect the answer would be, or might be, so useful. What would you conclude if the answer to that question were "yes"? What would you conclude if the answer to that question were "no"? 7) The same question regarding Multiple Sclerosis: Invent 10 yes or no questions; explain the implications of each "yes" and each "no" answer. 8) The same question regarding Muscular Dystrophy. 9) The same question regarding Amyotrophic Lateral Sclerosis ( = Lou Gehrig's Disease). 10) Argue pro or con: so far, knowledge of the molecular cause of cancer (or Multiple Sclerosis; or Muscular Dystrophy; or ALS) has been little or no help in treating or curing these diseases. 11) How might treatment of any of these 4 diseases be helped by finding differences in the DNA base sequences (i.e. differences between people with one of these diseases, as compared with normal people)? 12) Please discuss what relevance the following has for cancer and autoimmune diseases: The first billion dollar drug was a stomach ulcer treatment, with temporary effects, which patients had to keep taking permanently. Meanwhile, the medical main-stream strongly resisted use of an easily-testable, long lasting and cheap cure for ulcers (consisting of a combination of antibiotics and bismuth). Meanwhile, stomach ulcers killed six thousand Americans per year.
13) Discuss whether or not the following quotes are true of research topics discussed in this course. 14) In the history of medical science, have "paradigm shifts" (often? usually? seldom? always? never? by definition?) been necessary for the development of new kinds of cures for diseases. 15) Argue pro or con, the Genome Project is extremely non-revolutionary (in Kuhn's sense), or even anti-revolutionary (which might mean either that it tends to reinforce current paradigms, independent of how true they are; or might mean that the popularity of genomics to administrators is as a way to avoid paradigm shifts, or the need for them) 16) Argue pro or con: Major paradigm shifts, more than new data, are more necessary for finding cures for cancer and/or autoimmune diseases. Are the current paradigms like gold mines from which almost all the ore has already been removed? Discuss the practicality of systematically trying to break free from the interlocking concepts and interpretations of a paradigm that currently dominates a research subject.
17) Which of the following was a bigger conceptual change? (and why?) 18) Experimenters tested the effect of inserting an (already recombined) antibody-coding DNA sequence into the genome of mice; the effect was that all the B lymphocytes produced by these transgenic mice had binding sites of the exact same shape. Figure out what this shape was. Figure out why this result was caused by mechanisms that reduce the frequency of autoimmune diseases. 19) Suppose that the transgenic DNA sequence mentioned in the preceding question coded for antibodies specific for one of several blood group antigens: Explain what would happen if you crossed animals with this trans-gene with animals that had the gene for that same blood group antigen. Also explain how such transgenic animals could be a powerful tool for studying the mechanisms that normally prevent auto-immune diseases. 20) Humans with type A blood don't make antibodies whose binding sites fit the type A antigen. Explain why not, in terms of the clonal selection theory? What did you believe was the reason, before you learned about the clonal selection theory? 21) Invent at least one coherent hypotheses to explain why only one particular protein gets attacked by the immune system in Multiple Sclerosis (i.e. considering that there are thousands of proteins in the body for which no corresponding autoimmune disease occurs, in contrast to hundreds of thousands of victims of MS). 22) Without at least one hypothesis, nobody can design an experiment, and nobody could interpret the meaning of the results of an experiment, except in terms of some theory. Explain why or why not, using examples from research topics studied in this course.
23) Discuss whether several specific scientific breakthroughs are paradigm-shifts (in Kuhn's sense), or whether that is not a helpful way to think. For example, did Watson and Crick achieve a paradigm shift, as opposed to simply discovering some new facts? 24) Discuss pro or con whether the popularity of Kuhn's paradigm-shift concept was itself a paradigm shift in respect to scientists' thinking. 25) Argue pro or con whether cancer research needs a big paradigm shift more that it needs more data. (Include discussion of what the dominant paradigms currently are, as regards cancer and cancer treatments). Hint: Rate of growth. Treatment by what kinds of poisons? Whether treatments should suppress abnormalities, and as opposed to what? 26) Argue pro or con: Frequent use of the words "recognize", "self" and "non-self" traps people's thinking in an outdated paradigm about the mechanisms of immunity and the causes of autoimmune diseases. Explain the paradigm, and why it is out of date. 27) Discuss whether actual events in the modern history of biology and medicine confirm (or contradict) Kuhn's philosophical ideas. In particular, consider relations of erroneous papers to paradigms that have subsequently been disproven. 28) What about Karl Popper's key concept of disprovability? Please either criticize or praise several biological theories, as regards their potential susceptibility to disproof. For example, to what degree did they "stick their necks out? You could start with Manning et al.'s paper about "co-action". 29) Remember the time lapse videos that were shown in class (bubbling of membranes, long hollow strands of plasma membrane). Please propose at least one testable theory about the cause of these phenomena, in relation to changes in the cytoskeleton's attachment to the plasma membrane, or in terms of physical properties of the membrane, or in relation to how cells crawl. 30) Popper has been criticized on the basis that what seems like a disproof in terms of one paradigm will usually make perfect sense in terms of some other paradigm. Whether a phenomenon disproves a theory will (always?) depend on some other theory. Discuss examples in biology? Or argue that there aren't any examples. 31) In what sense did Watson and Crick use the classic elementary "Scientific Method" (about formulating theories, etc.), except that instead of testing their hypotheses by doing experiments on DNA, their experimental tests were based on other people's data, facts in books, geometrical models, and what else? 32) Does it (should it?) help research scientists to learn about the Philosophy of Science? It what ways might it help? In what ways might it hinder? (maybe by distraction?) 33) Most philosophers of science started out wanting to be research scientists (Kuhn, Haraway, Sklar & most others) but failed as scientists. Does that discredit their philosophical beliefs? Or does experience in research improve their insight into the conceptual foundations of science, even if (or especially if) their own research was for some reason not successful? (Think how much you can learn about hammers by hitting yourself on the thumb.) Where possible, give examples. 34) Will the mechanism of cell differentiation ever be discovered if it depends on parts of the genome that are especially difficult or impossible to sequence (for example, highly repeated sequences, heterochromatin, non-pairing sequences, pseudogenes, or reasons yet to be discovered). Conversely, what should we conclude if no explanations get discovered for the self perpetuation, mutual exclusiveness, and other aspects of cell differentiation? Is non-discoverability of any given mechanism evidence that they are caused by something that our methods can't detect? 35) Guess some particular scientific phenomenon, that is currently taught as fact, that you think is most likely to be disproven. Discuss your reasons, such as evidence against the current paradigm, lack of sufficient evidence in its favor, logical flaws, etc. 36) Predict (and explain your reasoning) two or three major breakthroughs that seem to you very likely to occur soon? Will these (probably?) be new facts, new interpretations of old facts, or new connections between "old" facts (that had already been discovered)? 37) What revolutionary paradigm shifts have changed scientists' explanation of aging? What future reinterpretations are most needed? 38) Kuhn claims that even the strongest evidence against a paradigm (a disproof) will not be sufficient to cause scientists to stop believing a popular theory, until and unless some new paradigm becomes available. Contrast this with Popper's key idea of disprovability. List specific biological examples where this was true, and other examples where it was false. (Hint: The paradigm that cancer cells grow too fast, and chemotherapy kills by inhibiting growth. This set of paradigms was disproven by discovery of certain cancers caused by lack of apoptosis, which are nevertheless treated successfully by drugs designed to inhibit growth. You can include this example, if you wish; but try to think of others.) 39) List examples of paradigm shifts from your own education, where you once accepted one set of related assumptions, but then switched to another set, and perhaps a third or a fourth. For example, what different sets of assumptions have you held regarding how people with type A blood manage not to attack it with antibodies. (In high school, I assumed this was somehow because of genetic linkage; what about you?) 40) Argue true or false, Darwinian Evolution was a paradigm shift, rather than just a set of factual discoveries.
41) For several years, Popper claimed that Darwinian Evolution wasn't truly "scientific" (because he believed that there were no experiments that could possibly disprove it, in the sense that its supporters could always invent a plausible explanation). Do you agree? What arguments can you make against such an opinion? 42) Can you avoid future mistakes by careful analysis of past mistakes? Was that belief the foundation of this course? Did you change you mind about this? Had you previously considered the issue? (Please don't answer this question unless you have some new or especially strong beliefs or experiences on the subject). 43) It is still not known whether or not leg regeneration in salamanders has the same basic mechanism as their original embryonic development. Please argue pro or con (or both?), displaying as much knowledge as you can, including knowledge indirectly related to regeneration. 44) List as many surprising facts as you can about multiple sclerosis. For as many as possible of these surprising facts, suggest at least one way in which that fact might be useful for developing a new cure, or for improving treatments now in use. (And the more, the better.) 45) Imagine that Watson had been an ordinarily generous person: Write an imagined page-length autobiographical description of how he synthesized facts and ideas that he learned from Franklin, Crick, Pauling, Delbrück, Bragg and others, leading to a Nobel Prize, shared between himself, Franklin and Chargaff. Your answer could be phrased as if it were his acceptance speech for his share of that Nobel Prize. 46) Argue pro or con: Cyto-differentiation must depend on (what kind of?) similarities in DNA sequences near the "luxury genes" of each cell type. 47) Invent and explain a molecular mechanism able to prevent cells from transcribing the luxury genes characteristic of any more than one differentiated cell type. If possible, suggest testable predictions of your hypothesis. 48) If you fuse two different kinds of cancerous cells, would you expect the fused cells to have cancerous behavior? Or not? (Why?) should your answer depend on whether the two kinds of cancerous cells belong to the same differentiated cell type? 49) What have you been taught and/or learned in this course that is most directly contrary to something that you were taught in some other course? Please make lists of arguments and evidence on both sides of this difference of belief. 50) Please invent and answer some question about a topic covered in the course, but which especially interests you and about which none of the questions asked above gave you a chance to demonstrate the excellence of your understanding or the depth of your insight (= that you wish I had asked) 51) True, false, sometimes: Until completed, paradigm shifts seem like disagreements about minor facts.
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