Book Notes : The Century of the Gene, Evelyn Fox Keller

FOX KELLER, CENTURY OF THE GENE

**1**
5 A convert -> transformed expectations
6 "Sequence gazing" -- new era of "genomic analysis"

=> Fall of Celera: with all Venter's promise, why is he out? Why is Sequenom selling equipment? Market & state out of balance? Good/bad?

6 Walter Gilbert - "vision of the Grail"
7 call for FUNCTIONAL GENOMICS; the sequence not end, but tool
8 gap "genetic info" : "biological meaning"
9 no more extreme reductionism
10 defying classification between animate and inanimate || "gene talk"

**2**
13 Darwin - mechs of transformation, not conservation
14 problem of "trait stability" presupposed the gene *
15 developmental stability - metazoan orgs *
15-6 WEISMANN'S QUESTION
17 GERM PLASM (Weissman's term)
18 Two Articles of Faith
1. Genes the fundamental unit of bio
2. fixity of material element
20 "spontaneous transmutation" of atoms, chems
23 famous "blender experiment" -- Hershey and Chase
25 1968 - a restriction enzyme
27 50s & 60s ORNL - radiation damages expers
28 "communicative" - a network, not an individual (gene) DNA REPAIR MECHS
29 radiation biology - suspect (under AEC)
31 stability of genes - "biochem dynamics rather than mob. status"
32 balance between mutability and stability a product of evolution => repair mechs that sacrifice fidelity -> genetic

variations
33 error-prone mech of repair -> EVELYN WITKIN ('67)
34 stab/mut at mercy of enymatic processes; balance varies in response to cellular reg (not trad. DNA neo-Darwin

view)
35 MUTATOR GENES - defective genes supp to reg stab.
36 RECOMBINATION -> all somatic cells, diff in sex (?)
=> diff for bact. & human sex cells?
37 mechs for evolvability
=> Radman: "positively selected" mutagenesis (?)
a challenge to neo-Darwinism? (38)
39 GERHART & KIRSCHNER - evolvability
41 mechs of stab not a prod of n.s. (but isn't all?)
42 DYSON's answer to LIFE - dual origins of Ilahita Arapesh

**3**
48 Problem: self-reproduction to a particle
49 Two tasks for Muller: find gene's structure & function (animism, monster by tail [48])
53 BEADLE-TATUM : one gene-one enzyme
54 Central Dogma (simplicity itself)
55 JACOB & MONOD - structureal, regulator genes
57 OPERON MODEL (split genes)
59 Late 70s : Exons and Introns (junk DNA)

63 ONE GENE - MANY PROTEINS

63 Who chooses the protein? "reg dynamics of the cell"
63 true Gene - mRNA transcript (itself not fixed?)
65 FIGURE?
64 ALLOSTERY: changes in structure of protein
67 concept of gene in blatant disarry
GELBART - gene concept with bit of baggage
69 the word GENE
70 VALUE OF HGP - exposed naivite of hopes
71 gene no longer unit of intergenerational memory (?)
71 DNA - indispensable raw material, but no more than that
72 need new words
73 instructions in every cell (EV NEC)
76 Mayr: bean-bag genetics
77 WADDINGTON : development perspective
78 epigenetic theory
85 theoretical analysis of BONNER "genetic program"
88 cloning - enucleated ooplast - NOT cytoplasm of ord. cell -> epigenetic factors req. epigenetic inheritance
90 obstacle to reprogramming - relationship betwe. nucleus & cytoplasm
95 "something that is historically defined"
97 "master control gene" quibble
100 interactions as important as structure
program irreducible?

**4**
104 development: Gould's videotape countless plot variations - same ending
108 Kant on the question of self-org
111 GENE-KNOCKOUTS, redundancy - sometimes improve function
112 extensive polymorphism
113 NULL MUTANTS
113 "Redundancy strikes fear into the hearts of geneticists" Sydney Brenner
115 unit of selection - the whole organism
118 CANALIZATION - many variations, one end
124 behavior-based robotics - situatededness and embodiment
128 HGP - bioinformatics
128 "single genes do not affect phenotype" James Bailey
130 the major shift
131 Jacob - "bricolage"

**CONCLUSION**
136 popular image of gene dislodged
138 EFK on words
140 the marker

Don't scientists require great precision in the language they use? Well, yes and no--that is, in some ways they do, but in other wasys, just as in ordinary communication, too much precision would in fact be paralyzing. Where precision is necessary (and absolutely so) is in particular laboratory practices. Moreover, it is from the specificity of the experimental context in which they are invoked that technical terms acquire the precision they need. Terms like gene may be subject to a variety of different meanings; but locally, misunderstanding is avoided by the availability of distinct markers directly and unambiguously tied to specific experimental practices. Within that practice, the marker has a clear and unambiguous reference. Change the practice, and different markers will need to be employed. And inevitably, these different markers will pick out somewhat different physical entities.* Nevertheless, as long as one stays within the context of a given and clearly understood set of experimental conventions, the term gene can still safely serve as an operational shorthand indicating (or pointing to) the marker of immediate experimental significance. (139-140)

*For example, in one context, the term may refer only to regions of DNA characterized as an "ORF of length x," while in another, it might include noncoding regions of DNA that are used as templates for RNA molecules. In yet a third context, it might refer to the mature (postsplicing) RNA molecule used in the actual translation process.

[And in a fourth, an outlandish promise of return on investment.]

143 biotech marketing

COMMENTS
DNA as necessary vs. sufficient [EFK 99]
DNA (HGP) ----> phenotype (medicine) -- filling in the middle parts the hard part
single gene (ie discrete) mutations - only viable targets?

3 big changes
HGP - race
Maezenich - special ed
EFK - gene

New Heresy
one gene - many proteins
one protein - many functions

single mutation -- sickle cell

Two things marketed
1. HG Sequence
single mutation -> disease -> drug
2. Personalized medicine
80% of people don't respond to drug therapies
Drs not needing to see patient

Affymetrix patent estate for sale

Prions - proteins that cause disease

ORF - Open Reading Frames
encode for a protein (start-end signals) but don't know which protein