Friday, April 18, 2003

Craig Venter. Genius. Pain in the Neck.

A few days ago, the Human Genome Project announced that the had completed the full sequence of the human genome. Interestingly, mention of either Craig Venter or Celera Genomics was largely missing from these press releases. It's a far cry from the tensions and "war of words" between Venter/Celera and the bureaucrats of the HGP which Nature reported back in 2000, the first (previous) time that the completion of the genome was announced with great fanfare.

That somewhat preliminary announcement was driven by the HGP's very real fear that Venter and Celera would steal their thunder entirely. The announcements of the past few weeks, which are equally a publicity stunt in that they nicely coincide with the 50th anniversary of the discovery of DNA, conveniently ignore the enormous contribution that Venter and Celera made.

About a year ago, I heard Craig Venter speak in London; at that [pre-blog] time, I wrote up a report. It's interesting, it's technology [sort of -- as much as the war, anyway] and most importantly, it goes against the self-inflating tendency of the world's science bureaucrats; so here it is:

Wednesday, Feb 13th 2002

I attended Craig Venter’s talk at the Royal Institute. The R.I., along with the Royal Society, is one of the two oldest scientific societies in London (and thus the world) and the former home of greats such as Michael Faraday. The R.I. has slowly shifted its mission towards science popularization, and regularly hosts public lectures of varying magnitude, including a UK-famous Christmas lecture which is televised on BBC1 as a holiday special. The speaker this evening, Dr. Craig Venter, is perhaps the most important person in the world at the moment working on DNA. Venter is a combination of famous and infamous as something of an enfant terrible, who in the early- to mid-1990s challenged the entire basis of the long-running, government-funded Human Genome Project. When he was rebuffed by the NIH, which told him his proposed “whole genome shotgunning” methods wouldn't work, he founded Celera Genomics, took in about $100 million of venture capital, and demonstrated in dramatic fashion that his methods did in fact work, by producing an entire DNA map of not only humans, but a long list of other organisms (from plants and animals to bacteria, etc.) in record-breaking fashion. Using Venter’s methods (which the NIH grumpily and quietly adopted, so as to avoid being completely beaten and embarrassed) the current timeline to analyze a new organism’s DNA is about three months, as opposed to the 10-15 years it used to take.

Venter is interesting not only for what he can relate about the current state of DNA research, but to watch as a person -- he's a quintessential abrasive, self-confident, counter-orthodoxy guy who has made huge, important things happen despite a lot of resistance; and in the process, created a lot of critics, if not outright enemies.

A small incident at the beginning of the talk showed this side of him quite clearly. After he walked out into the presentation area of the hall –- the same small, circular, high-balconied theater that Faraday used in the 1800s -- he needed to begin with a formal greeting to the audience. In the UK, when certain persons are present, the form is, "Your Royal Highness(es), Lords, Ladies, and Gentlemen..." As it happened, in attendance this evening was HRH the Duke of Kent (who is the brother of Prince Philip, the Queen’s husband) and plenty of lords and ladies (Lady Archer, the wife of disgraced and jailed politician/Lord/author, Jeffrey Archer, was sitting directly in front of me) and thus Venter had to use this greeting. He choked on the word ‘royal’. He simply could not get it out. "Your hrgh-al highness" was as close as he could get, and off he went with his talk. The guy is a completely self-possessed, polished speaker, so I can't imagine it was nervousness -- just the rebelliousness of his soul that has made him a great scientist, made explicit in a single syllable. He’s a large, broad-shouldered man with a huge head, and his entire demeanor screamed, “I’ll be damned if I’ll say ‘royal’ to anyone.”

Another glimpse came in the question session at the end, when someone asked him, "What motivates you?" He went through a long blah-de-blah, about how when you're discovering this wonderful, important stuff that will save lives and make the world better, getting out of bed every day is no problem, etc., etc.; and then, having finished his official answer, grinned like a kid and said, "Plus, I like to win." Which was immediately obvious as the real answer, and everything before it merely a polite dressing of the simple truth.

He gave a masterful -- only word for it -- one-hour talk on the current state of DNA research, and revealed all sorts of interesting facts that I (who follow this sort of thing moderately, not closely) had been unaware of. I had coincidentally just finished reading Richard Dawkin's famous 1976 book The Selfish Gene, which is a paen to DNA determinism, and raises the competition half of Darwin's thesis upon an altar. DNA determinism, which is prominent if not predominant today, relies upon the crucial assumption of a close and programmatic link between DNA ‘genes’ and the expression of very subtle traits in an organism, such as behavior in certain specific situations (e.g. a mother defending her young).

Venter noted that the biggest news out of the Human Genome project, which caused a bit of a stir last year when it was announced, is that humans only have between 25,000 and 40,000 genes -- which is simply too few pieces of information to be able to express tiny subtleties of construction of one’s body, much less actions, behaviors, and thoughts, in the DNA itself. What this means, is that a) the varied (and possibly chaotically fuzzy) *expression* of DNA is far more important than the determinists would like to believe, and b) that both nurture and culture are far more important as well. It's sort of a victory for free will, as it were.

Venter also noted a few numbers on how close all we mammals are to each other at the DNA level:

* Humans and mice share 94.5% of their DNA
* Humans and chimpanzees share 98.73% of their DNA
* The *average* difference between one human and another is one 'base pair' (or single code letter) out of every 1200; of the 27 million code letters that make up your entire DNA, that means that the average difference between you and someone else is only 22,000 letters, which is just a few hundred genes worth of difference, since much of your DNA is basically wasted space. Just for some context, this piece of writing contains almost 8000 letters and spaces; so it represents more than 1/3 of the likely DNA difference between you and I.

The most interesting part of the talk was Venter's discussion of the ongoing work to build an actual ‘map’ of evolution by creating a hierarchy "tree" of diversification and separation in genes over time. For instance, it's pretty well established (through various other methods) that mammals diverged from other animals 600 million years ago. All mammals share a certain set of genes that can thus be 'dated' to 600 million years, and based on similar techniques (such as carbon- or sediment-dates fossils) all splits (and thus gene differences) between various mammals can be dated with a good degree of accuracy to when in the last 600 million years they occurred. The fact that all humans are basically identical -- 99.92% the same -- means that, in the past 10,000 years or so, there has been effectively zero evolution of people. By performing these sorts of difference checks -- which bits of DNA are shared between people and birds, people and frogs, people and mushrooms, people and bacteria -- you can build a map of which changes (in both modern people and modern mushrooms) happened when, and both the general rates and the exact timeline of evolution.

Venter put up all sorts of really pretty visual maps of this, which sadly I can't reproduce.

One particularly fascinating example of this is known as the CCR5 gene. This gene exists in about 9% of Caucasian people, but only .01% of blacks -- so a significant minority in one population, effectively nonexistent in the other. The gene is notable, firstly, because it provides almost 100% immunity to catching AIDS. It's thus part of the explanation why AIDS is more of a plague in Africa – it acts as a ‘damping’ factor in person-to-person communication among Caucasians, and no analogous damper exists in Africans. What's most interesting, however, is that using the same population divergence techniques described above, the emergence of this gene in the Caucasian population can be dated to about 700 years ago. Stastistically, of course, such a recent emergence is necessary to explain such a significant spread in the incidence of the gene between two different groups of humans. Circa 700 years ago was, of course, when the Black Death hit Europe (1348 - 1350) and killed off about a third of the population; and CCR5, in addition to conferring immunity to AIDS, is highly effective at conferring immunity to the plague. Thus this gene got a big boost in the Caucasian population as many people who didn't have it died; whereas in Africa, without the plague, it remained a minor factor within the genetic mix.

Overall, it was a fascinating talk that I've done only a partial job of conveying. Venter is, and will remain, one of the most important scientists of our time, and hearing him speak at length and up close was great. At 7 pounds for the tickets (!) it's an example of the great cultural benefits of being in London.

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