| 
David S. Goodsell A cross section shows yellow DNA, purple ribosomes scanning white mRNA, and a jolly green flagellum.
Wet biology – science, in a laboratory, with living things – is messy. It's about petri dishes full of yeast colonies smelling faintly of beer, heavy bottles of nutrient broth, and hours of dropping a microgram of this liquid into that test tube. At worst, it's boring; at best, it's hard. So bench researchers – science's infantry�- would love to invent a new, dry biology that puts all the dirty work inside a computer. These wouldn't be approximate simulations; they would replicate every function, every process. We're talking singularity here – creating a ghost inside a machine, the apotheosis of systems biology. And now microbiologists are going for it. The International E. coli Alliance wants to scan in Escherichia coli, the single-cell workhorse of the biology lab and one of the best-understood organisms on earth. It won't be easy, but the outcome could alter our understanding of how life functions and evolves.
| 
The Scripps Reasearch Institute A bug's life: E coli in a virtual sea of nutrients.
Biologists started batting around the idea of a cell simulation in the mid-1980s, but it wasn't until last year, at a meeting in Edmonton, Alberta, that leaders in the field agreed the project was feasible. "It's not necessarily that computers are getting better, although they are," says George Church, head of the Center for Computational Genetics at Harvard Medical School. "It's more the 'genomic attitude,' that you can think about and measure comprehensive systems – initially all of the genes, then all of the RNA, all of the proteins, metabolites, and so on." Indeed, the eventual model, still decades away at the IECA's current staffing and funding levels, will describe the geometric, electrical, mechanical, and chemical properties of every significant assembly of molecules. Meanwhile, the idea is to hit a series of milestones, probably starting with a complete description of E. coli's metabolism, and then proceeding to a genetic network reconstruction, describing systems of regulatory genes and proteins. All the wet work on E. coli means lots of data, which in turn means better simulations. Technically, it'll still be tough. Though biologists have identified most of E. coli's genes, they don't know what all of them do. They'll have to nail those down. And depicting the cell's 3-D structure remains a challenge. X-ray crystallography, the classic approach to visualizing large molecules, is best suited to the nanometer scale, around a billionth of a meter; basic microscopy sees best at a scale a thousand times larger. Nobody knows what the universe looks like in between.
The project also must cope with human concerns. Microbiology is typically an independent, sometimes secretive pursuit; the IECA is asking for cooperation and openness on a scale that would dwarf even the Human Genome Project. The best-case scenario involves thousands of scientists around the world, all working for the cause.
What would success mean? A researcher might be able to ride a single enzyme from a stew of amino acids to a receptor site on the other side of the cell. A digital E. coli would be a much more interesting plaything than its real-world counterpart. Researchers could take it apart and put it back together a little differently, deleting a protein here or speeding up a cycle there – a process called virtual experimentation.
Ideally, the experience of uploading E. coli will teach researchers how to model more complex structures. Multicell organ systems might be interesting, and in the even more distant future, so would people. (Officially, the IECA has no such aspirations.) The price of drug discovery would plummet, and a working familiarity with cell processes could lead to nanobots that work at the cellular level. Biology will always be messy, but it won't always be wet.
Fred Hapgood (hapgood@pobox.com) wrote Up the Infinite Corridor: MIT and the Technical Imagination.
START
| The Meter Maid's New Best Friend
| Would You Like Wi-Fi With That?
| Better Children Through Chemistry
A Microbe Enters the Matrix
