DNA

The Story of the Genetic Revolution

James D Watson, Beaverton Library, 576.5 WAT 2017

• p8-10 Gregor Mendel peas, careful statistics, and math 1856-1868 (yellow dominant) died 1884

  • "Versuche über Pflanzenhybriden" ("Experiments on Plant Hybridization") published in 1866 in Verhandlungen des naturforschenden Vereines in Brünn, referenced three times in 35 years

• p11-13 Thomas Hunt Morgan Columbia U. fruit flies 1901- , crossover
• p37 Oswald Avery identified DNA as "transforming principle", denied Nobel because Swedish chemist Einar Hammarsten believed genes were proteins
• p40 Maurice Wilkins from nuclear physics to X-ray diffraction of DNA
• p42 23yo Watson postdoc at Cambridge under Max Perutz and Lawrence Bragg, shared lab with 35yo ex-physicist Francis Crick
• p43 31yo physical chemist Rosalind Franklin, mountaineer, high society, impatient with fools.
• p45 Watson at first confused "unit cell" with "assymetric unit", DNA crystals water rich.
• p46 Erwin Chargaff found A/T and G/C ratios close to unity
• p47 Franklin's "photograph 51" B type, more water, taken by her student Raymond Gosling
• p48 density measurements favored two chain rather than three chain
• p49 February 28, 1953, base molecules pair edge to edge with hydrogen bonds, two for A=T, three for G≡C (purine to pyrimidine). Appeared in Nature April 25 p737.
• p57 Meselson-Stahl experiment with heavy/light nitrogen isotopes and centrifugation showed hybrid (half weight) first generation, light and hybrid second generation.
• p57 Nobel physiology-or-medicine 1962 to Crick, Wilkins, and Watson; Franklin died of ovarian cancer in 1958, age 37
• p58 Watson speculates if she had lived, Franklin would have shared the Chemistry prize with Wilkins in 1962
  • Watson: Franklin refused for a long time ... DNA was a helix, data from her work was absolutely critical.

• p63 1941 Beadle and Tatum mutated red mold Nerosposa Crassa, found strain 299 that couldn't synthesize something from minimum medium, but could if vitamin B₆ added. → thus "one gene, one enzyme"

• p67 Watson and George Gamow RNA Tie Club. 20 members, one for each amino acid. Gamow had ALA tie pin, Watson PRO, Teller LEU, Feynman GLY, Chargaff LYS, Crick TYR, Delbrück TRY, Brenner VAL, Orgel THR, others I haven't heard of (yet).
• p69 Crick proposes adapter molecules
• p73 Nirenberg and Mathaei make "UUUUUU" RNA, which synthesizes chains of polyphenylalanine, hence codon UUU. Khorana figured out much of the rest. They shared the 1968 Nobel Prize for Physiology or Medicine.

• p93 Abraham Lincoln High School science club run by stockroom supervisor Miss Sophie Wolfe. Students Arthur Kornberg (1936), Paul Berg (1943), and Jerome Karle (1933) are Nobel laureates.

• p95 1974 Science Moratorium letter, February 1975 Asilomar conference, led to modified K-12 variant of E. coli requiring artificial nutrients.

• p104 Sanger sequencing: solution of bases with a few modifed "dideoxy" bases that terminate chains. Sort the segments by mass (hence length) with electrophroresis, then measure which dideoxy base terminates the segment. So, position on the gel is position on the chain.

• p110 Herb Boyer and Bob Swanson start Genentech to make human insulin (51 amino acid) genes inserted into bacteria (but without the human introns, thus bypassing regulations and moratorium rules. Licensed to Lilly, IPO brought in $38M, share value to $66M to each founder.

• p127 Martin Shkreli's Turing Pharmaceuticals generic toxoplasmosis drug Daraprim hiked price from $13.50 to $750 per tablet. Rival Imprimis manufactured a Daraprim generic for a dollar.

• p142 Bacillis thuringiensis Bt bacteria toxin against lepidopteran caterpillars, beetle and fly larvae, now added to Bt crops (corn, potato, cotton, soybean) ... massive pesticide reduction.

• p145 Bruce Ames quote: "There are more rodent carcinogens in one cup of coffee than pesticide residues you get in a year."
• p151 Starlink corn approved for feed, not people, but cross contamination made that impossible.
• p165 Max Hoffman Foundation pledged $36M for $75M UC telescope, other donors balked. W.M. Keck Foundation paid entire project (now the Keck Telescope on Mauna Kea), so Hoffman money redirected in 1985 to a UC Santa Cruz -based Human Genome Project. Funding from NIH and DOE (for radiation mutations) supplanted that. Conference at Cold Springs Harbor Lab in 1986, estimated $3B for 3B base pairs with Sanger sequencing.
• p224 Cost per genome $1K in 2016, compared to straight line Moore's Law

Extracting DNA

• p262 DNA can survive up to 50,000 years if corpse dries fast enough.
• p264 Mitochondria 16600 base pair loop, 500 to 1000 per cell
• p265 humans differ from Neanderthal 5% out of 379 base pairs confirmed by two labs
• p265 5 cm Neanderthal bone from Vindija cave in Croatia 1980 , 40kya, 1 million bases, 55% of Neanderthal genome 2010 Science Pääbo.
• p286 most recent common human ancestor 150 kya, not much variation time