Tuesday 14 October 2014

Sorcerer

I don't think  he's a sorcerer but J Craig Venter (Happy Birthday 1946 boy) has been involved in so many shape-shifting projects that normal people might be a little envious. Last night my roomie at The Institute gave me a New Scientist article (How to be a Genius by David Dobbs 18 Sep 2006) which holds with Edison that genius is 99% perspiration. If I haven't seen as far as Craig Venter it's probably because I've been too lazy and/or complacent.  I've been both of those and am reasonably
smug content with myself so my main feeling about Venter is admiration. At least two of his game-changing projects might have won him a Nobel Prize for Medicine and Physiology, if he hadn't pissed off so many people along the way.   I've never met him but I don't get the sense that he's obtusely boorish, he just tends to tell it like it is.  Having served in a front line triage centre in Vietnam as a very young man, he's seen things and done things that the rest of us have not been challenged by.

He certainly annoyed me (so much for "Dr Equanimity") more than 20 years ago when I was just starting to motor in the world of bioinformatics. I was tasked to work out how synonymous codon usage worked for humans.  The database was tiny in those days, although we thought it was huge and gathering a robust dataset that wasn't padded out with duplicates or fragments was a lot of hard work. Book-keeping and keeping track of all the data - just to big to be processed one-a-time - needed coding and attention to detail.  in 1991, there were a little over 1000 human genes (now >130,000) to play with. We were scooped by our rivals in Paris because they were less pedantic, a little more slap-dash and that bit quicker than we were.  Their paper said what ours would have said despite their data being noisier.  This was true because the available data was broad enough that a few errors didn't affect the overall picture. Dang! Very shortly afterwards a paper was published by a team from Venter's lab that reported fragmentary sequences from 600 novel genes expressed in the human brain. In one swoop they had increased the available data by 60%!  Because each of these genes was only partly sequenced, I didn't have the tools or the mindset to incorporate the data into my analyses. I therefore thought the whole submission was an annoying barrage of noise that would just get in everybody's way.  I was completely wrong, locked into past processes and incapable of seeing that this approach was an immensely powerful tool for understanding a) the scope of human genetic diversity and b) the locations where, and activity with which, each gene was 'expressed'. I caught up about 10 years later and published an analysis of these quick-and-dirty "expressed sequence tags" (ESTs). Mobilising ESTs to study human health could have snagged a Nobel, except that Venter tried to patent his newly discovered information to win time to generate gene-based therapeutics for megapharma. Not the sort of thing a gentleman would do.

He could also have secured a prize for geeing up the Human Genome Project from outside, so that it raised its corduroy trousers off the comfy chair in the Senior Common Room, took off its tweed jacket and started to race to deliver under the threat that Venter's team would raise capital and hire bodies and buy equipment and deliver the human genome within 18 months. Venter was gracious enough to suggest that the huge, methodical and slightly unwieldy international consortium could have the mouse genome to play with after his efficient capitalist machine had knocked off The Big One. You can see how that sort of play would annoy The Suits and their tweed-jacket boffins - do you hear a grinding of pipe-stems? It didn't turn out like that though: the Wellcome Trust (whose senior people went to the same school as the genome chappies) freed up a barrel of cash for the 'public' venture and the two projects finished neck and neck in 2003. That was at least 2 years ahead of schedule.  That's a lot of time if you're dying from a genetic disease.

I wrote in May 2013 about Venter's announcement of the creation of "the first bacterial genome whose parent was a computer". That was clever and I got a kick out of solving the puzzle that Venter's chaps had embedded in the genetic code of their artificial life-form.  But that project was a mix of technology and bravado rather than being a game-changer. I'm probably wrong in that assessment also. Sequencing the genome of his poodle Shadow showed a hubris not calculated to please the rank-and-file.

Another insight that deserves enormous credit was Venter's project to sample the microbial flora of the whole ocean. Human genome not big enough? He kitted out his private yacht Sorcerer II as a floating laboratory and sent it off on a round the world cruise sampling the sea-water at intervals and purifying the DNA out of the soup that came up in their nets. The DNA enabled his people to say how many bacteria of what types were present in each different part of the wet globe. That was a Great Leap Forward for microbial ecology and I think it has been widely under-appreciated for both its vision and its achievements. The big surprise was that the ocean is a very poorly stirred soup.  The microbial community in the Caribbean is significantly different from the bugs you find off the coast of Ireland despite the fact that the Gulf Stream (aka North Atlantic Drift) connects them in a warm bath that moves relentlessly East by North-East at nearly 10km/h (it takes about a month to arrive here). The bacteria seemingly don't go with the flow. That's really surprising.

Time for old fashioned joke:
Q. Are you a sorcerer?
A. No, I drink out of a cup like everyone else.
But Craig Venter drinks different harder stuff than me, that's why he has the yacht and I have a

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