Tuesday, July 26, 2005

Worm's life   posted by Razib @ 7/26/2005 11:11:00 PM

In 1998 the C. elegans genome was complete. Two years later we had the draft of the human genome. The connection between these two events is the "hook" for Andrew Brown's In the Beginning Was the Worm: Finding the Secrets of Life in a Tiny Hermaphrodite (also author of the The Darwin Wars, which focuses on the life of George Price and his influence on seminal figures in evolutionary biology like J.M. Smith and W.D. Hamilton). I actually didn't find the last part of the book that interesting because the topic has been pretty well done. Who wants anymore anecdotes on the toothy Jim Watson? Rather, the first 150 pages (out of some 200) which chronicled the persistence of the brilliant Sydney Brenner1 and the team of researchers that he gathered around him in the late 1960s and 1970s before the worm was "hot" is an interesting anecdote laced analysis of the sociology and psychology of science. This isn't surprising, Brown has a background as a religion reporter, which showed in The Darwin Wars, and here he goes out of his way to note the quirky socio-religious backgrounds of many of the early wormers (Quakers, Jews and other assorted nonconformists).

There is scientific detail in the book, the simple anatomy of the worm is sketched out (~1000 cells, eukaryotic and multicellular, but not too much!), the benefits of selfing hermaphroditism is highlighted (recessives can be snatched out as one out of four self-crosses are homozygous on the two alleles which produce a non-dominant phenotype) as well as the utility of the rare males in swapping alleles between the lineages. I felt Brown spent way too much time ruminating on Brenner doing Assembly coding back ~1970, it boggles the mind.2 But the meat of the book is the sociology, personality and philosophy. Some of the anecdotes are really bizarre...who would have guessed that the first "picks" were actually toothpicks! The researchers would spend an hour each morning sharpening them and discarding their pile throughout the day. When one of them got the bright idea of sticking a platinum filament to a tong-handle Brenner disapproved, suggesting that brilliance doesn't forbid obstinacy.

But there are also the "big picture" questions. How far can reductionism go? What is the worth of a model organism? Is there any real point in the Human Genome Project beyond the "It was there" aspect? The book only really gives a good answer on the last question, chalking up Sydney Brenner's skepticism of the enterprise to age and ego (Brown was gentler, but that's what he was saying). There are many golden roads, but many dark and thankless ditches in science, and I think the fact that for every winner (as the worm people were) there are innumerable losers. That's how lab science works, it isn't measured in individuals as much as man hours many times (the mapping of the worm nervous system for example seemed to be a chore of herculean tedium). The decisions people make aren't always justifiable, but some of the times their hunches hit paydirt. The good angel on your right shoulder and the bad angel on your left shoulder both give a skewed view of who you are to God on the day of judgement, but summed together they hit the proper mark. Science is filled with good angels and bad angels, and the God of Spinoza judges fairly in the end.

Addendum: Non-science types might find the bitchness of the "fly" (Drosophila) people to the worm people pretty funny. I wonder though, do astrophysicists who study black holes look down on those who model neutron stars???

Update Rikurzhen: Most of the tools are now in place to dissect worm biology from a systems level down to molecules. If there is a logical limitation to reductionism, work on the worm will soon the bumping into it. The genome is complete and feature annotation is greatly simpler in a 100MB genome (worms) than a 3000MB genome (mammals). Reverse genetics using RNAi is ridiculously easy to do (>80% of known genes have been assayed by RNAi for many, many phenotypes). Worms can be grown to population sizes unimaginable for other multicellular model organisms, and many phenotypes can now be assayed with automation. But obviously the most important question is whether this model organism can keep producing new insights into (human) biology. I anticipate that "$1000 genome" sequencing technologies are going to accelerate work on new/existing model organisms just as much as they will human genetics.

1 - Brenner's father was an illiterate. He, on the other hand, matriculated as an undergraduate at the age of 14.

2 - I recall that back in the 1990s the WordPerfect guys were forced to write the app in Assembly so that they could be closer to machine language and optimize performance. Of course, soon enough Word blew them out of the water, partly because Microsoft could push it via its Office Suite, but also because they were coming out with new versions slapped together (I assume) in a human friendly VB IDE at a much faster clip.