"Never trust observations until they have been confirmed by theories."
Micah Dembo (A Boston professor with whom I used to collaborate)


Why Has Physics Progressed Farther Than Biology? What lessons can biologists learn from the history of Physics?

1) Richard Feynman's Explanation: Because physicists took all the problems they could solve, and named them "Physics"; & Those problems they couldn't solve, they gave other names, like Biology & Meteorology.

2) Because physicists make more accurate measurements, that conclusively prove or disprove theories.

3) Because Biological problems are more difficult, perhaps because they are more complicated? Or other reasons?

4) Because homeostatic mechanisms cause biological properties to change in ways that hide causes behind responses. (Regardless of what phenomenon you intend to study, your results will mostly be protective responses.)

5) Biologists are not good theorists: Either misusing thories (Steinberg) or disliking them (Holtfreter, Trinkaus). Many of the best physicists are entirely theoreticians (Feynman); But theoretical biologists don't get much respect.
We could all learn much from the careful, indirect reasoning in the history of classical genetics.


Is there a limb bud medio-lateral gradient of either adhesive strength or contractile strength?

Shoulder-Arm-Elbow-Wrist-Foot-Toes Grafts get moved back toward wherever they came from.

If you graft elbow to foot: graft gets pulled medially (=proximally) back toward elbow.
If you graft elbow to upper arm: graft gets pulled laterally (=distally) back toward elbow.
If you graft foot to elbow: graft gets pulled laterally (= distally) back toward foot.
If you graft shoulder to elbow: graft gets pulled medially (= proximally) back toward shoulder.

If you explant a piece of elbow tissue into contact with a piece of foot tissue: Elbow engulfs foot.
But explants of upper arm put into contact with elbow engulf the elbow tissue.
Whichever tissue was taken from closest to the foot gets engulfed by whichever tissue came from closer to the shoulder.

These are reasons why it is worth debating about causes of sorting out.

What force drives engulfment? Do engulfed tissues adhere more strongly? Or engulfed tissues contract more strongly? (Do these differences exist before contact : Or are they induced to develop by contact between different layers?)

(Amidst debates about "positional information" and "differential adhesion", people ignore, forget or never learn observable fact(s) that cell growth, & blastema development get induced by contact between tissues of different positions along medio-lateral and other axes (anterior-posterior & dorso-ventral). What happens gets hidden by what causes it to happen.)

Is engulfment caused by the same force that pulls grafts along the medio-lateral axis?
Stronger pull on the more distal side? Either because a tension gradient already exists?
Or because increased tension is induced by contact with more medial tissue? & what additional data do we need most? & what structure-creating (or repairing) function could be served by induction of stronger tension in more lateral tissue.

Does Humerus induce Radius, and Radius induce Carpals, and Carpals induce Digits? (& retinoic acid induce humerus?) What sense could it make for each tissue to have more tension than the tissue farther outward toward the foot? ...or for strengthened contraction to be induced by contact with tissue closer to the shoulder?

Humerus- Radius/ Ulna - Carpals - Digits HRCD
Single long cartilage Two parallel long cartilages 4? nearby round cartilages Four parallel rows of long cartilages.

Do constricting forces cause cartilages to elongate? How could you reshape carpals or the patella into "long bones"?



Retino-Tectal nerve connections.

Ganglion cell axons "grow" (= crawl) across the innermost surface of the retina, converging on the blind spot?

Perhaps they are guided by chemotaxis? Please invent experiments capable of testing this explanation.

These ganglion cell axons continue crawling as a bundle (the "Optic Nerve" along the optic stalk, underneath the brain, the right and left optic nerves passing close to each other (the "Optic Chiasm"), or even interpenetrating!

Please try to invent some hypothetical mechanisms that could guide them perpendicularly past each other.

The ganglion cell axons crawl in diverging paths across the roof of the midbrain on the opposite side of the brain from the side where they originated. Right eye innervates left midbrain; Left eye innervates right midbrain. (Please invent theories that could explain (predict, produce a function).

Incidentally, very many nerves coming from left innervate right side, etc. The optic nerve is one example of hundreds. (So the cause must be something fundamental? Does it serve a function? Or is it some kind of side effect?)

In animals having stereo vision, some nerves from the right eye turn back and innervate the right optic tectum. & some nerves from the left eye turn back and innervate the left optic tectum. This turning back fails to occur in white mice, white rats & Persian cats.

On the tectum roof ("tectum" is Latin for "roof", Spanish word is "Techo") the ganglion cell axon growth cones diverge and form a map-like pattern of the parts of the retina that they came from. Nerves in the front of the retina innervate the rear of the tectum; Nerves at top of retina innervate lateral tectum.

Vertebrate nervous systems contain hundreds of such map-like connections, which are called "neural projections" A large fraction of these neural projections interconnect upside down and backwards (like the optic nerve).

Try to invent explanations, and experiments to test your theoretical reasons for these patterns.

Maybe the upside-down-ness is a fundamental hint, like Chargaff's Rules turned out to be.

Incidentally, nerves from the top half of the retina adhere more strongly to the bottom half of the tectum. This was predicted by theories of adhesion gradients, but has turned out to be caused by "ephrin" proteins that stimulate release of cell-cell adhesions. I will explain this in a subsequent lecture; but let's discuss possibilities first.


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