Indigestible Discoveries Assignment

Biology 446   Unsolved Problems   Albert Harris   October 13, 2014


(Please think seriously about these questions and be ready to state your opinions in class)

#1) Regarding the Question Whether Cancer Cells Grow Abnormally Fast

Keep in mind what you learned about the recent history of stomach ulcer treatments: i.e. a century of plausible guesses about worry and spicy food dominated the search for cures!

Ask yourself whether as big a mistake might now be dominating cancer research
The following sentence is quoted from the Wikipedia article about cancer chemotherapy.
"Traditional chemotherapeutic agents act by killing cells that divide rapidly, one of the main properties of most cancer cells." That is an accurate summary of current beliefs and motivations.

Could it be as big a mistake as the belief that worry causes ulcers? Please be prepared to answer Pro or Con.


#2) What are some unsolved problems about bone formation?

a) How are locations and directions of maximum stress detected?
(As part of the explanation why bone gets made stronger at places and orientations of most imposed force).

b) And what are possible mechanisms by which lack of gravity produces either decreased deposition of bone or increased dissolving of bone? by osteoclasts.

c) Experimentally, (how?) can increased dissolving be distinguished from decreased deposition?

d) How do osteocytes cause formation of bone? Do osteocytes secrete bone?
( In the sense of secreting calcium ions and phosphate ions into vesicles at high enough concentration so that calcium phosphate crystals precipitate.) Hint: If that happened, then transmission electron microscopy would easily detect CaPO4 crystals inside vacuoles. (But there aren't any!)
If osteocytes don't secrete bone, then what DO osteocytes do, that causes bone to form?

In contrast: Osteoclasts are known to secrete hydrogen ions and proteolytic enzymes into a sealed-off volume of extracellular fluid sealed between broad, thin, sheet-like osteoclasts. Note that this process cannot occur without having a continuous line of water-proof adhesions attaching the outer edge of each osteocyte to the bone.
e) Please think carefully whether dissolving of bone could be prevented or reduced by producing leakage of acid and/or enzymes out from under osteocytes.

f) Strontium is one of several elements that (somehow!) gets deposited as part of bone, as if it were calcium. The antibiotic "tetracycline" somehow also gets deposited as part of bone. Strontium is said to be "bone seeking", as if that phrase explained or implied anything in particular. Please think carefully about what properties might be the explanation of "bone seeking", and by what experimental methods could conceivably be used


#3) What are the unique properties or components of macrophages?

a) For example, if somebody claimed that microglia aren't a special kind of macrophage, then what sort of evidence could or would decide whether this claim is true or not?

b) Regarding " galvanotaxis": the directional locomotion of macrophages toward positive electrodes, this has been reported to be true of monocytes and for osteoclasts. But all other differentiated cell types either crawl directionally toward the negative electrode, or line up perpendicular to electric fields.
Please invent some possible mechanisms for these differences in response to voltage gradients. (For example, effects on " resting potential", which all differentiated cells have, not just nerves & muscles.)

c) Please consider the possibility that differing production and response to electric voltages may be part of the methods by which ossification detects gravity and other forces. For a long time, it was a very popular theory that bone uses the property of being piezoelectric to produce voltages at locations of stress, and in proportional to amounts of stress, combined with more bone supposedly getting made where these piezoelectric voltages. Special machines were used to pump small voltages through broken bones in hospital patients (This was done here at Memorial Hospital). Apparently, it doesn't work very well, but the subject certainly deserves more attention. Please be ready to express some possible explanations or medical uses for such phenomena.


#4) Regarding the "Clock and Wave-Front" explanation for controlling locations of separations between somites: (Note: Don't worry if you don't know these answers; Just think about them.)

a) Was this theory really suggested by Rene Thom's mathematical concept of "Catastrophe Theory"?

b) How conclusively does current evidence prove that the true mechanism of somite separation is a clock and wave-front?

c) Suppose that the oscillations of retinoic acid, growth factors, etc. are not causes of somite segmentation, but side-effects of some other mechanism.

d) Somites are only transient structures; Blocks of cells separate from each other during embryonic development; and the boundaries of these blocks control (or are highly correlated with) future locations of segmental nerves, ganglia, areas of skin innervation, arteries and ribs. However, somites only continue to exist temporarily, before their component cells disperse. Therefore, why don't the molecular patterns directly control these many anatomical segments?
Either the blocks of cells are side-effects of molecular patterns, or the molecular waves are side effects of the separation of the mesodermal cells into blocks. Which are causes and effects among the following three:

Clock and wave-front
Physical rearrangement of cells to form somites
Location of segmental nerves, ribs etc.

Does "Clock" cause "Location"? With "Physical" as a side-effect?
Or is "Physical" part of the cause of "Clock"? Does "Location" depend on both "Clock" and "Physical"?
Why don't papers about "Clock" ask why chemical patterns don't directly control "Location"?

Because somites are only temporary, why form them unless physical forces are part of the cause of segmentation? And please suggest better symbols to help visualize these questions.


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