The New York Times, August 18, 2005
Michael Ellison has a dream: to reconstruct a living thing inside a computer, down to every last molecule. It is, he said, “the ultimate goal in biology, to be able to do this.”
It’s a dream that Ellison, a biologist at the University of Alberta, shares with other scientists, who have imagined such an achievement for decades.
Understanding how all of the parts of an organism work together would lift biology to a new level, they argue. Biologists would be able to understand life as deeply as engineers understand the bridges and airplanes that they build.
“You can sit down at a computer, and you can design experiments, and you can see the performance of this thing, and then you can figure out why it’s done what it’s done,” Ellison said. “You’re not going to recognize the full return of the biological revolution until you can simulate a living organism.”
In the past few years, this fantasy has become plausible, and Ellison is part of an international team of biologists who are now trying to make it a reality. They have chosen to re-create Escherichia coli, the humble resident of the human gut that has been the favorite species for biology experiments for decades.
“We picked the simplest organism about which we know the most,” Ellison said.
Scientists may know more about E. coli than they do about any other species on earth, but that doesn’t mean that creating a virtual E. coli will be a snap.
Many mysteries remain to be solved, and at the moment even a single E. coli may be too complex to re-create in a computer.
But the effort is worthwhile, some scientists argue, because it would become a powerful tool for drug testing, for genetic engineering and for understanding some of life’s deepest mysteries.
Discovered in 1885, Escherichia coli soon proved easy to raise in laboratories. Its popularity boomed in the 1940s, when scientists figured out how to use it to pry open the secrets of genes.
In the 1970s, scientists figured out how to insert foreign DNA into E. coli, turning them into biochemical factories that could churn out valuable compounds such as insulin.
“Everybody studies E. coli for everything,” said Gavin Thomas, a microbiologist at the University of York in England.
Research on E. coli accelerated even more after 1997, when scientists published its entire genome. They were able to survey all 4,288 of its genes, discovering how groups of them worked together to break down food, make new copies of DNA and do other tasks.
But despite decades of research, many of E. coli’s genes still remain a mystery – “probably around 1,000 genes,” Thomas said.
“There’s a lot more we need to know about E. coli before we can build a really solid model.”
To find out more, E. coli experts have been joining forces. In 2002, they formed the International Escherichia Coli Alliance to organize projects that many laboratories could do together.
In one project, researchers have created more than 3,900 different strains of E. coli, each missing a single gene. “It would have been foolish for two or three labs to carry this out at the same time and compete with each other,” said Barry Wanner of Purdue University, who led the project.
Soon scientists will be able to order the entire collection of these strains for their own research. “We’ve done a variety of simple tests, but we can’t do every conceivable experiment,” Wanner said. “But a hundred other laboratories can do hundreds of other ones.”
As knowledge of E. coli grows, scientists are starting to build models of the microbe that capture some of its behavior. Bernhard Palsson of the University of California at San Diego models E. coli’s metabolism. Like other living organisms, E. coli breaks down food with enzymes. It then uses other enzymes to refashion the fragments into new molecules. Palsson and his colleagues have reconstructed the interactions of more than 1,000 metabolism genes.
They can predict how fast the microbe will grow on various sources of food, as well as how its growth changes if individual genes are knocked out. Based on experiments with real E. coli, the researchers find the model gives the right predictions 78 percent of the time. Now they are expanding their model to 2,000 genes.
A full-blown model of E. coli would be able to swim, eat food, fight off invading viruses, make copies of its DNA and do many other tasks all at the same time. Scientists agree that building a multitasking model would be a daunting job. “Technically, that’s incredibly more difficult,” Thomas said.
Ellison and his colleagues have decided to take the first steps toward creating a full-blown model.
They want to begin by simulating a simplified E. coli. “We’re going to strip E. coli down to about one-quarter of its original size,” Ellison said.
Wanner is working with colleagues in Japan to make this minimal E. coli. They hope to produce a stripped-down E. coli with only around 1,000 genes within two years. Ellison and his colleagues then hope to create a virtual twin, in an endeavor they have dubbed Project Gemini.
A full-blown model of E. coli is worth the effort, many scientists argue, because of its potential benefits. Scientists could adapt the E. coli model to more complex human cells to simulate how they react to different drugs.
“Then you can really do genetic engineering,” Ellison said. “I mean where you can actually design an organism or change it in massive ways.”
A virtual E. coli could allow scientists to see in advance how major changes to the microbe would affect it.
“That opens up a huge amount of opportunity,” Ellison said.
Copyright 2005 The New York Times Company. Reprinted with permission.