#### How To Invent and Discover; Methods that make you smarter: Nov 13, 2017

(You, too, can be prescient!)

Automatically inventing new theories that make most of the same predictions as an existing theory:

Consider the following pairs of words: Stimulate-Inhibit; Increase-Decrease; Pull-Push; Raise-Lower; Maximize-Minimize; Contract-Expand; you can think of more pairs of opposites.

Next, Consider Any Hypothesis!/ Probably this hypothesis contains at least two words from the list of paired opposites; I will assume it does, or that you can find words in the hypothesis that have opposites.

Finally, substitute the word "Stimulate" where the existing hypothesis says "Inhibit",
and also substitute the word "Minimize" where the existing hypothesis says "Maximize"

Making two of these substitutions will produce a new and different theory that makes most of the same predictions as the original hypothesis.
Making four of these substitutions, or six or eight, or any even number of opposite word substitutions will also generate new hypotheses that can explain the same phenomenon.
Automatic hypothesis generation!

An example is that Malcolm Steinberg's Differential Adhesion Hypothesis ("Cells maximize their areas of adhesion with each other"; versus "Cells contract (=minimize areas) more at interfaces with the culture media and with other differentiated cell types.

Maximizing areas of contact equals minimizing areas of non-contact.

Try to think of other examples in which competing hypotheses are related to each other in this way, by means of two, or four, or six, 8, or 10 substitutions of opposite words.

Notice that if a hypothesis contains three such words, A, B, and C then you can Substitute Not-A for A and substitute Not-B for B. Or alternatively substitute Not-C for C. and Not-A for A. etc.
AB, BC, AC; AB, AC, AD, BC, BD; What about hypotheses that contain five such words; how many pairs would there be? How many different combinations of four?

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Incidentally, in Projective and Euclidian geometry, you can reverse substitute the words "Line" and "Point", and generate new theorems that will automatically be true of the original theorem was true. Historically, this realization was an enormous breakthrough in mathematics of the early 1800s. Hundreds of previously unknown theorems got discovered automatically, just by interchanging the words line and point,
(in Solid Geometry, reverse the words "point" and "plane", and leave "line" unchanged. And in electric circuits you can substitute capacitances for inductances and vice versa, and the new circuit will accomplish the same task. Such facts are called "Duality". Wikipedia articles about such things make them seem more difficult than necessary.

I suggest that you just skim these articles, without expecting to understand much of it. And if you understand one-tenth of a percent of this stuff, then please explain it to me. It's enough to know that it exists, in case Biology needs it, and finds uses. I wish one of my high school or college math teachers had told me about any of this. It is a misguided policy not to teach anything that students can't yet be tested on.

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Automatic Methods for Inventing More Cures for Cancer.

Make a list of frequent abnormalities that have been discovered in cancer cells.

1) Uncontrolled DNA synthesis;
2) Uncontrolled Mitosis;
3) Defective cell-cycle controls;
4) Uncontrolled invasive cell locomotion;
5) Anaerobic metabolism (glycolysis instead of Krebs cycle);
6) Weakened traction; 7) Lowered viscosity of membrane fluidity (I am not sure about); 8) Disorganized cytoskeleton (actin, myosin, microtubules);
9) Lack of reflection symmetry of shapes of cell nuclei (This is consistently true)
10) Secretion of certain proteolytic metallo-proteases; (which used to be a big deal)
11) Cytoplasmic lipids and integral membrane proteins "leak" into plasma membranes and vice versa [Which I am not so sure about]; 12) 13) 14) 15) 16)

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Make a list of methods that can kill cells.

A) Activate (de-repress) apoptosis. De-repress even just a few caspase enzymes
B) Punch holes in plasma membranes. (as is done by "complement proteins")
C) Over-increase cytoplasmic concentrations of certain normal contents (including calcium ions).
D) Damaging DNA, if the "Start Checkpoint" mechanism is working.
E) Merely trick the Start Checkpoint into believing that some DNA is hopelessly tangled.
F)
G)
H) Find more methods to kill cells...

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Combine one from column A with one from column 1.
A1, B1, C1, B1, B, 2 etc five times eleven is 55 methods for selectively killing cancer cells. Selectivity is the key need, so you just kill those cells with any property that is usually only or mostly found in cancer cells.

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The Principle of Bioassays:
How to discover which particular chemicals serve as enzymes, hormones, or are needed or sufficient to accomplish some particular function.
How hydroxy tryptamine was discovered to be serotonin. (Smooth muscle contraction)
How indole acetic acid was discovered to be auxin. (stimulation of plant shoot bending)
Both earning tens of billions of dollars.

The Principle of Artificial Synthesis of lots of abnormal chemical analogs of biologically important substances, like serotonin and auxin.
For example, substitute a sulfur atom where a nitrogen should be, or substitute bromine or chlorine where methyl groups should be.
2,4-D is an auxin analog. Prozac is a serotonin analog.
Some analogs will over-stimulate, some analogs will poison, and there is no principle for predicting which (despite what patent lawyers argue.)

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The Principle of Genetic Screens:
How to discover which genes control any given biological process.
Find mutants in which some important process is either prevented or increased.
Use genetics to find out how many different genes affect a process.
Sequence these genes; find out which code for enzymes, which for structures etc.
Use Powerpoint to make convincing diagrams of your conclusions.