Sunday, December 26, 2010

Thoughts on Venter's "A Life Decoded" [[* lifedecode0mg *]]

In relation to:
A Life Decoded: My Genome: My Life
J. Craig Venter

Enjoyed this book very much. Some random thoughts below, mostly as a bulleted list.

* The book begins with the contrast of airport blue-sky openness to security now -- an example of what happens when a technology matures!

* Some interesting points about the race to sequence the genome and its ending :
- Initial names for Celera included "sexigenics," "Ventipillar," and "Ventipede". (The last two were derived from the association with Mike Hunkapiller.)
- After much negotiation, Compaq/DEC beat IBM in performance and became the genome-assembly computer even though IBM offered their computer for free.
- There appeared to be great security paranoia at the Celera campus -- worries about snipers in the trees and photographing of Venter's screen from afar.
- Venter says that he was initially dissatisfied with Blair's proposal for the 26 June 2000 White House speech and threatened to boycott the event. Moreover, according to Venter, at the actual speech Blair moderated quite a bit, praising Celera and not specifically highlighting the Sanger Center.
- According to the book the genome race contained lots of "(S)lander"

* Some notable points on assemblies of Celera Genomes :
- Two largest contributions to the Celera genome came from Venter's and Hamilton's Smith's sperm. The other contributors were from three women of Asian, African and Hispanic origin. More specifically, 60 pct of the Celera genome derives from Venter. Most of these came from short PE libraries (e.g. 2kb). Longer paired-end fragments were derived from H Smith. Venter repeatedly emphasized the importance of the PE libraries with a range of spans for the Celera assembly.
- Venter claims he did a test run of shotgun assembly on the published worm genome as a benchmark while he was doing the fly. He also claims that the Celera fly matched almost all of the existing fly genetic associations and also the 25 pct of the sequence done by the BGP.

* Lots of discussion of Venter's own genome and health phenotype. In particular:
- Venter suffered from diveriticulosis which is opening of gut leading to peritonitis and may be caused by stress.
- Nice discussion of the kilobytes of sequence that Venter shares with the chimp but is not in the human reference and how this extra sequence affects (e.g. lengthens) a particular zinc-finger TF.
- Venter remarks on his CHF polymorphism and his elevated risk of macular degeneration (AMD).

* Some tidbits on all the personal battles:
- Venter chronicles his similar battles with Haseltine (HGS) and Tony White (PE).
- The book describes the creation of dbSNP in rather negative terms as part of Merck's "spoiler" corporate strategy.
- A big success of TIGR was connecting a yeast mismatch repair homolog with a region of the human genome associated with colon cancer.
- HGS tried to block publication of the HI genome by legal action.
- An interesting description of Watson and Crick as the original bad boys of molecular biology in contrast to the Franklin with Wilkins in the middle.

* Some miscellaneous tidbits on the sequencing of bacterial genomes :
- The publishing of the smallpox genome was rather controversial as potentially the virus could be recreated from the sequence. The sequence itself was done by a shotgun approach.
- The error rate in Mycoplasma sequencing was originally 1 in 10K, now 1 in 500K. This low error rate is necessary for the synthetic life experiments.
- The synthesis of viral DNA genomes prompted the creation of a presidential commission on the ethics of this -- in particular, how it relates to the synthesis of deadly pathogens.
- Emphasizes that Rusch et al. Found lots of photoreceptors and lots of eukaryotic-like-kinases than in bacteria.

* The book provides a perspective on the relative difficulties of extramural university scientists and intramural NIH researchers in getting NIH funding for large and small projects. It also contains some useful remarks on the joint formation of TIGR and HGS with Steinberg and the way the former non-profit was connected to the later for-profit venture.