Unsolved Problems Nov 17. 2017
Odds and Ends       The Meanings of Unexpected Phenomena

Bioassays lead to identification of biologically important chemicals (serotonin, auxin), and synthesizing chemicals with analogous chemical structures reliably guides discovery of powerful drugs that either inhibit or exaggerate effects of the normal chemicals.

I) But you can't so confidently predict which structural analogs will block, versus which will magnify, effects of the biologically normal chemical. Replacing nitrogen atoms with sulfur, or replacing methyl groups with bromines, may produce inhibition of effects or strengthening, or no effects. You can't reliably predict which chemical analogs will have which effects. Researchers just randomly try out which synthetic analogs have what effects, by trial and error. Little or no invention is involved.

II) What kinds of discoveries should be patentable? What activities need to be incentivized?

III) In bird embryos, the hind limb begins with a single long bone (equivalent to the femur), followed by two parallel long bones (which then fuse side-to-side, to form the "tibiotarsus"), followed by three parallel long bones (which also fuse side-to-side, forming a bone named the "tarsometatarsus").

Why do these lateral fusions occur? Why don't birds simply form three long bones, end to end; that is what the end up with. Is anything gained by the fusions, or by starting with two parallel long bones, and then three parallel long bones? Also, why fuse? Why not use degeneration to get rid of one of the two, and two of the three? And why have scientists ceased even to wonder about this and other phenomena that would not have been predicted from any causal mechanism?

IV) Several researchers invented explanations based on causal mechanisms "not being able to help it", so to speak. For example, two collaborations between mathematicians and biologists guessed that more elliptical cross-sections somehow caused more parallel condensations. A prediction was that flattening the whole limb bud should have resulted in 4 or more parallel long cartilages. Another prediction was that molding hind limb buds so that their cross sections were circles, would have resulted in one row of single long bones. But no such predictions were confirmed.

Please discuss your ideas about inherent limitations on what shapes can be produced.
And whether we can learn how mechanisms work by observing what they can't seem to accomplish.

The Wikipedia articles about the tibiotarsus and tarso-metatarsus say convergent evolution occurred, but don't say why more offspring will survive as a result of forming more leg bones than needed, and then fusing them side to side.

V) Please suggest as many as possible alternative mechanisms for causing embryonic cartilages to develop in particular locations, and then to elongate, or remain rounded.

By what experiments or other observations could you test which actual mechanisms embryos actually use?

Why do you suppose that somites form sequentially, one pair at a time, first in the neck, and then progressively rearward to the tip of the tail? Imagine that a researcher discovered some treatment that caused all the somites of an animal to form simultaneously: Would that observation disprove any category of mechanisms of somite formation? (Like, for example, the theory now most accepted!)