Biology 446    Unsolved Problems Fall 2020

Lecture notes for the August 12th class

Systematic research strategies:

How serotonin and auxin were proven to exist, how their chemical structures were discovered, and multi-billion dollars per year industries developed from theories about biological control mechanisms.

1) Grind up tissues.

2) Fractionate the tissue homogenate. (such methods as centrifugation, chromatography differing solubility in salt solutions, many others) .

3) Compare your dozens of separated fractions: For example: Which fractions produce the most smooth muscle contraction (if you are trying to discover "serotonin").
(or which plant tissue fractions stimulate the most elongation of oat seedlings) .

These comparison methods are the actual "bioassays."

Any criterion you can use to test which fraction contains more of your hypothetical factor "serotonin"

4) Narrow down the possible components, ideally until you identify which ONE chemical is producing the most effect.

5) [if possible], purify or even synthesize this one chemical.

6) Synthesize slightly different chemical structures.

        Examples: Prozac, 2-4D herbicides.

7) Persuade legislatures to change patent laws to make such chemicals patentable.

Optional additional reading, NOT required:
lecture notes on bioassays from my embryology course in 2017


What can go wrong?

An enzyme that oxidized a steroid hormone to form a more effective steroid was thought to be a new protein hormone.

A gel that accelerated reaggregation of dissociated embryonic cells was assumed to function as a selective cell-cell adhesion substance, (but really, it was DNA, acting as a non-specific goo).

Fibronectin was independently co-discovered by 4 different research laboratories as "spreading factor", "Large Extracellular Transformation Sensitive Protein" (LETS)


Genetic Screens

Eric Wieschaus won the 1995 Nobel Prize for a years-long, painstaking research project to isolate mutants in Drosophila and screen them for abnormalities in embryological development.


You are NOT responsible for details of auxin structure, specific effects of serotonin, or details of the work Wieschaus did. However, among the choices of questions for the final exam, there might be something along the following lines. (These are questions from the list from which last year's exam questions were chosen.)

"What are bioassays, and how are they used to discover the molecular causes of various biological phenomena? Please include some specific examples."

"What are genetic screens, what do researchers use them for? And list as many discoveries as you can remember that were made using a genetic screen."