The History of the “Gene”
Metaphor … is the lifeblood (ha!) of good scientific
prose.”– Matt Ridley, 2003
I. Human Context
A. Abstraction
1.
Universal use of models, metaphors and analogies
2.
emphasize what is important to the communicator (maps)
3.
may contain unacknowledged associations and baggage
(entrainments).
B.
Story telling – we like simple narratives
C. Politics
1. Tribalism - The closer people are to us, the more special they seem
a. Your kids
b. Your football team
c. Your country or ethnic group
2. Political decisions rarely made by logic (Watson’s strategy)
The notion that science and objective thinking are
unnatural human activities seems quite radical at first. But when you think about it, monogamy,
honesty, and democratic government are unnatural human behaviors as well. - Alan Cromer in Connected Knowledge, 1997, p 22.
II. Scientific Context
A.
Process
1. Finding the “Low-Hanging Fruit”
a. Mechanics
b. Mendel – 7 genes, 7 chromosomes
c. Diseases inherited in a Mendelian fashion
2. Hierarchical Reductionism (Dawkins)
B. Chaos Theory (The Butterfly Effect)
1. Complex systems are not predictable, except in a broad sense (the strange attractor)
2.
System become complex in the chaotic sense when three
or more factors interact to produce a property (recursion).
3. Chaos has only been studied in mechanical systems since the 1980s. Prior to then, physicists simply didn’t work on mechanical problems that weren’t simple enough to be described by non-recursive equations.
III.
Historical Context
A. Long-standing recognition that “Like begets like.”
B. 1800s - serious inquiries into how you get an organism.
1.
2. Developmental Biologists – Preformation versus Epigenesis
a.
Epigenecist position: structure arises gradually from no
material antecedent: preformationist position: structure is inherent and
unfolds.
b.
Preformationsists ridiculed – homunculi and embôitment
c.
Materialism and vitalism – events proceed by cause and
effect and just because you can’t see something doesn’t mean it isn’t there.
d.
Modern synthesis – elements of both, insights found in
neither
…what could be more fantastic than the claim that the
egg contains thousands of instructions, written on molecules that tell the cell
to turn on and off the production of certain substances that regulate the speed
of chemical reactions? The notion of
preformed parts seems far less contrived to me.”” Stephen Jay Gould, Ever Since
3. Geneticists – Mendel (not as completely marginalized as you might think).
a. found a reproducible system – peas are highly inbred
b. found a controllable system – easy to determine mating
c. picked just the right genes – binary and deterministic
d.
picked just the right number of genes (7 and peas have
7 pairs of chromosomes)
C.
Late 1800s to early 1900s – looking at the gene. What do scientists do when they examine
something they don’t understand? Gen, gene and similar terms with the same root
as genesis – to give rise to.
1. identified with the chromosome – genes “carried on” the chromosomes.
2. identified with phenotypic trait – gene for white eyes in fruit flies.
3. identified with specification of enzymes. Ridley’s third definition: Garrod (1902) A gene is something that protects you from disease – one gene, one prevention. He was working with the inheritance in humans of alkaptonuria. Later, Beadle and Tatum (1940s) explicitly recognized that the gene specified and enzyme- “One gene, one enzyme.” They said nothing about what the gene was, in a physical sense.
4.
indivisible unit of function, Ridley’s second
definition of the gene: DeVries – A pangen (gene) a separate unit or particle
specifying a characteristic or trait.
D.
Identification of
1.
Genes are part of chromosomes, composed of protein,
2.
It’s
a. Dead bacteria can transfer something to
live bacteria that makes them deadly (virulent) by allowing them to make a
protective capsule.
b. Neither proteases, nor RNAses, nor
lipases (destroy cell membrane), nor polysaccharidases (destroy the capsule)
affect transformation.
c. DNAses abolish transformation.
d. Conclusion: information to transform is
in the
3. It’s a Double Helix! (Watson, Crick, Franklin, Wilkins and Chargaff, early 50s)
a. Basic chemical studies: sugars linked to
phosphates and 4 different bases stuck to the sugars.
b. Chargaff’s rules – A=T, G= C
c. Wilkins and Franklin: X-ray data
suggested helical structure made up of two similar parts running the length of
the molecule.
d. Watson and Crick
i. two sugar phosphate strand running
antiparallel.
ii. The bases on the inside, the
sugar-phosphate backbone on the outside
iii. Hydrogen bonding from base pairing
(A to T and G to C) holds strands together.
It has not escaped our notice that the specific pairing we have
postulated immediately suggests a possible copying mechanism for the genetic
material. - J. D. Watson and Frances Crick. (1953) A structure for
deoxyribonucleic acid. Nature 4356, April 26.
4. Ridley’s
first definition of the gene: the gene is an archive stored digitally in
E. Figuring Out How it Works
W. Wyatt Gibbs (2001) Cybernetic Cells. Scientific American 265(2): 52 -57,
Quoting Drew Endy, "A useful model must suggest a
hypothesis that forces the model builder to do an experiment."
1. How do you use the information to make proteins? The Central Dogma – beware of using irony around the lay public.
Milord, 63
brave men have died getting information I now offer you. – Robert Heinlein,
2. How do you decide which proteins to make and when? Ridley’s fifth definition of the gene. Jacob and Monod – A gene is a switch, or at least something that comes with a switch.
a.
In the 1970’s, the promoter and repressor regions that
flank the part of the
b. Now they are called controlling elements, because they are generally docking sites for protein that affect the rate of transcription.
c.
The word “gene” is reserved for parts of the
It may be in
the interpretation and analysis of differentiation that the new concepts
derived from the study of microorganisms will prove of the greatest value ....
Eventually, however, differentiation will have to be studied in differentiated
cells. - J. Monod and F. Jacob (1961).
IV. The Human Genome Project
A. Money, Politics and Optimization
1. Convincing the government to spend the money.
2. Convincing scientists to sequence the entire genome, “junk’ and all.
B. Results
1. fewer genes than we’d guessed
2. more variation in the proteins that any one gene can produce
3. more of the genome devoted to intron and control elements than to coding for specific proteins sequences.
4. “administratively
top-heavy” - more genes code for
proteins involved in binding to
C. Spin-offs
1. Sequencing
technology is vastly faster.
2. You can sequence other organisms and play “compare and contrast.” - fruit flies, roundworms, Arabidopsis. Then mice and chimpanzees.
3. You
can sequence pathogens. SARS was
sequenced within one month of its identification. During the anthrax investigations, the source
of the bacterium could be narrowed down solely based on its
4. Allows for specific looks at the working of individual genes.
1. Identifying Risk – the two-edged sword
2. Understanding the disease process – herceptor
3. Undreamt possibilities
Ridley, Chapter 9:
The Seven Meanings of Gene