REVIEW QUESTIONS FOR THE FINAL EXAM

1) If Watson and Crick hadn't published their DNA structure (if they hadn't been born) then who else would have come up with the correct idea about how amino acid sequences are coded by nucleotide base sequences? (And please explain why).

2) In what sense did Watson and Crick invent hypotheses, compare predictions of their theories with observations, modify their theories to make the fit the data better, etc. with the difference that their "experiments" consisted of looking in books, talking to other scientists, and borrowing other people's research?

3) What are some specific examples in which Kuhn's ideas were most accurate? That can include progress being blocked by the dominance of a given paradigm.
Alternatively, please describe examples where scientific progress was most different from Kuhn's ideas.

4) 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".

5) Osteoclasts need to have a large area in order to seal off broad enough areas of bone surfaces to accumulate acid and enzymes between bone and osteoclast (Analogous to fumigating a house or a tree with insecticide). Based on this need of osteoclasts, please invent one or more new strategies for curing or preventing osteoporosis in people.

6) 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?

7) In your opinion, what specific advances in knowledge would be most helpful in finding cures for autoimmune diseases? To discover a real cure, what you most need to find out IS WHAT? Please explain your main reasons for this opinion.

8) What is most misleading about the idea that the immune system can detect special properties of cells that are possessed only by "self". Do bullets work by detecting special properties of "targets"? When a bullet hits something you didn't aim at, is that because the bullet mistakenly detected "target-ness"at the wrong locations? Does the accuracy of a rifle depend how correctly it detects target-ness? Please think of a better analogy than my joke about detecting target-ness.

9) Discuss the advantages and disadvantages of depending on economic motivation to guide searches for new and better cures for diseases. What about for the purpose of concerting rapidly fatal diseases into chronic diseases, instead of into rapidly curable diseases? What ideas can you propose for improving the current system? Why might it help to make patients last longer, and apply to a wider range of treatments? (Which is exactly the opposite to what most reformers advocate.)

10) Why are macrophages so interesting? How could improved understanding and ability to control macrophages lead to treatments and cures for atherosclerosis? Ditto for osteoporosis?
What other diseases might result from misbehavior of macrophages?

11) Invent possible reasons why macrophages respond in the opposite way than other cells to electric fields, hydrophilic surfaces, roughened surfaces, proteolytic enzymes and calcium ion concentrations. Suggest experimental tests for your hypothesis.

12) Please explain the false assumption in the underlined part of the following quote from an encyclopedia:

"Antibody, also called immunoglobulin, a protective protein produced by the immune system in response to the presence of a foreign substance, called an antigen. Antibodies recognize and latch onto antigens in order to remove them from the body. A wide range of substances are regarded by the body as antigens, including disease-causing organisms and toxic materials such as insect venom. When an alien substance enters the body, the immune system is able to recognize it as foreign because molecules on the surface of the antigen differ from those found in the body".

13) Do antibodies "latch onto" antigens ...Because the shape of the binding site fits (is complementary in shape an charge distribution) to the shape of the antigen?
Because they have previously contacted those same antigens, and been imprinted with the antigen's shape? Because B-lymphocyte self-destruct if they contact recognizes the shape of the antigen?

14) 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, why it is out of date, and whether (and how) it holds back discoveries of cures for autoimmune diseases.

#15) Would/could autoimmune diseases exist if the paradigm in the previous question were really how the immune system works? Your answer might include a description of an imaginary alternative cause of autoimmune diseases.

#16) On what subject has your opinion changed the most as a result of the content of this course? (and explain why).

#17) What if Watson had never received a post-doctoral fellowship for study in Europe? Do you think that he or Crick would have made such a discovery? Discuss why, or why not.

#18) Was Watson justified in spending money donated by the public for polio research for his attempts to understand DNA structure? (In your opinion, pro and/or con)

#19) Suppose that life was discovered on another planet, and you were assigned the task of figuring out whether they had the equivalent of genes, and (if so) how those genes encode information and also copy themselves. Please include some mention of whether you would expect to find some equivalent of Chargaff's Rules.

Questions 20-22 have been removed.

#23) Humans have genes for a dozen different caspase enzymes, but nematodes have only one. Explain how this resulted in human caspases being discovered on the basis of their molecular similarity to the nematode caspase. Suggest what general principle is responsible.

#24) Do homeostatic mechanisms minimize thermodynamic free energy? Or do they just produce the same net effects? Explain, using specific and/or hypothetical examples?

#25) Why could electro-osmosis of skeletal tissues be misinterpreted as piezoelecricity? What functions could these phenomena serve in the body? How could you distinguish between them? Please include explanations of the mechanisms of both.

#26) To achieve replacement of missing body cells, which of the following do you need? (a) cells that have never differentiated, (b) cells that have reverted back to being undifferentiated, or (c) a method that can cause cells to switch from one differentiated cell type to another?
Which of these three (a, b or c) would you call "stem cells"?

#27) What additional functions, that nobody has discovered yet, might be accomplished by resting potentials or action potentials? Remember how much ATP gets constantly used up by all the two-hundred-plus differentiated cell types of the body. Surely so much energy can't be serving no function, can it? For nerves, muscles and oocytes, we know what functions are served by voltage depolarizations. It would be a major breakthrough to discover even just one additional function.

#28) What is meant by chemotaxis, haptotaxis, and durotaxis? How do these processes differ from each other? What are two different mechanisms for chemotaxis?

#29) A certain graduate student once tried to make giant (~ 50-100 times normal size) tissue culture cells. He tried culturing cells in medium containing drugs that prevented mitosis, and other drugs that inhibited cytokinesis (cleavage into daughter cells). Cells from cancerous cells continued to grow larger without apparent limit. Cells from non-cancerous cells grew to around 4 or 5 normal size, and then stopped. No more increase in size; no more DNA synthesis; no more attempts at mitosis or cleavage.

#29a) Hypothesize possible causes of such a set of phenomena. How could you test different possibilities? What would you expect happened when the culture medium was replaced with medium lacking drugs?

#30) Several introductory textbooks claim that sizes of animal cells are limited by difficulties of getting enough oxygen and/or glucose to the cells. As far as I know, there is no evidence in favor of this idea, and quite a bit of evidence against it. Please suggest either experiments or other observations that support or disprove this theory. Also suggest what mistaken assumptions have caused this fallacy.

#30a) What mistaken assumption do believers in this idea probably make about the relative rates of movements of molecules inside cells as compared with speeds of transport in blood and lymph?

#31) Antibody synthesizing "memory cells" are said to "recognize" whether other molecules are "self" or "non-self". What specific property of memory cells differs (in what way) depending on whether its binding sites fit a "self" molecule?

#32) 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.

#33) 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.

#34) 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.

#35) 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?

#36) How would sponge cell reaggregation be explained by the differential adhesion hypothesis?

#37) 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"?

#38) 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.

#39) 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)?

#40) 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 mainstream strongly resisted use of an easily-testable, long lasting and cheap cure for ulcers (consisting of a combination of antibiotics and bismuth), and stomach ulcers killed six thousand Americans per year.

#41) Without at least one hypothesis, you can't design an experiment. Nobody can 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.

#42) 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. Discuss whether a phenomenon that disproves a theory depends on some other theory. Discuss examples in biology? Or argue that there aren't any examples.

#43) 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?)

#44) 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.

#45) 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)?

#46) 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?

#47) Suppose you had a time machine, or any way of directly observing evolution, would invention of new methods shift a theory from being non-scientific to being disprovable? In other words, should we base philosophical conclusions on the availability of methods needed to disprove phenomena?

#48) 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.

#49) 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?)

#50)What is misleading about the idea that the immune system can detect special properties of cells that are possessed only by "self"? Suggest why so many scientists believe this mistaken idea.

#51) What evidence would prove that a given autoimmune disease is partly caused by genetic differences? What would prove that susceptibility to this disease results from differences in one particular gene?

#52) Hypothesize what normal functions are likely to be served by those genes that affect the probability of a person getting multiple sclerosis sometime in their life.

#53) Hypothesize what event or environmental difference might affect the probability of a person getting multiple sclerosis sometime.

#54) Discuss the advantages and disadvantages of depending on economic motivation to guide searches for new and better cures for diseases. What about for the purpose of converting rapidly fatal diseases into chronic diseases, requiring continual, life-time instead of into rapidly curable diseases? What ideas can you propose for improving the current situation?

#55) If a drug turns out to work by some completely different mechanism than proposed in the patent for a certain treatment, should that affect the validity of whatever patents apply to its sale? Please suggest arguments on BOTH sides of this question. Mention any specific examples that you know about, or can suggest.

#56) What evidence proves that either bone formation or bone destruction, or both, are either stimulated or inhibited by physical forces imposed on living bone?

#57) Compare the effects of stimulating formation of bone by osteocytes versus inhibiting the dissolving of bone by osteoclasts? By what combinations of experiments and molecular labeling could you find out which of these stimulations or inhibitions is the mechanism of a drug for treating osteoporosis.

#58) Discuss, pro or con, or whatever mixture of both pro and con: Medical science tends to regard diseases as external to the body's structures and normal activities, ignoring the extent to which medical problems result from over-activities and other abnormalities of the body's own cells.

#59) Discuss, pro or con: From H.V. Wilson, to "Positional Information", to modern hopes for medical use of stem cells, to what extent do cells' positions control what cell type they will differentiate into, and to what extent does differentiation determine where cells will move to. (And/or to what extent do scientists assume one or the other?)

#60) This question has been removed.

#61) Explain how a new alternative theory (to explain the same phenomenon) can be "automatically" created by an even number of changes in certain words. For example: Cell sorting is caused by maximization of area of cell-cell contacts. Cell sorting is caused by minimization of areas of cell-medium contact. Please include at least one other example of biological theories that have this "duality" relation to each other.

#62) Argue pro or con: Steinberg's Differential Adhesion Hypothesis implicitly assumes that embryonic cells are pulled by the maximization of their adhesions, as opposed to crawling by an equivalent to amoeboid locomotion.

#63) Are there any explanations for particular biological phenomena that you believe you, yourself, could have discovered significantly sooner than they actually were discovered if only you had realized one particular fact or principle?

#64) What are needed most: New ideas or new observations? Discuss specific examples from current biology, and from the history of Biology.

#65) Sometimes the vocabulary used in an area of biology is biased in favor of some theories and biased against other theories, sometimes making the alternatives seem illogical or improbable. Please discuss as many examples as you can think of, starting with immunology and the word "antigen".

#66) Hypothesize a set of reasons for the peculiar behaviors of macrophages that are different from most other cells (physical causes, chemical causes, functional causes).

#67) Pro or con: The reason that many diseases cannot be cured is because we don't have enough knowledge about them. Or is it more because we don't figure out how to use the knowledge we have?

#68) 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 on this list gave you a chance to demonstrate the excellence of your understanding or the depth of your insight (= that you wish I had asked)

 

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