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The Six Most Important Experiments in the World: Number 6, Artificial Life
Discover, December 2007

The Six Most Important Experiments in the World: Number 6, Artificial Life
Discover, December 2007
In the mid-1990s, Craig Venter rose to fame by claiming that he and his colleagues would decipher the human genome long before a huge team of government scientists would. He at least managed a tie: Both groups have provided increasingly accurate versions of the genome since 2000, and Venter has just published the first genome sequence from one person (himself) that includes all the chromosomes inherited from his parents. As important as sequencing the human genome has been, however, Venter is overseeing another experiment that could someday eclipse it. Scientists at the J. Craig Venter Institute and Venter’s biotech firm, Synthetic Genomics, are trying to make a genome from scratch. “I plan to show that we understand the software of life by creating artificial life,” Venter declares in his new memoir, A Life Decoded.

Venter first announced this plan in 2002, and he has been doggedly pursuing it ever since. Step one of the plan: Identify the fewest number of genes a microbe needs to survive in a lab. The scientists would then synthesize that minimal genome from raw ingredients and insert it into a host cell. The genome would make its own proteins and gradually transform the cell into a new creature.
To build the minimal genome, Venter turned to a microbe he and his colleagues had already been studying for several years, a pathogen known as Mycoplasma genitalium that causes urinary tract infections. He and his colleagues had determined (pdf) that the parasitic microbe has just 482 genes (18,000 reside in a human). They then began testing each of those genes to see which were essential to the microbe’s survival. Last year, they reported that M. genitalium can survive without 100 of its genes. “We know which genes we can eliminate one at a time, but we don’t know which we can eliminate together,” Venter says. To see if the remaining 382 genes meet the minimum requirement for life, Venter’s team will have to build a genome with them and drop it into a cell.

Venter sees a minimal genome as an opportunity to build life from the ground up, like an engineer assembling a piece of technology.
Venter knew that no one had ever successfully transplanted a bacterial genome, and there were a lot of reasons to suspect it might not work. “Cells in general don’t like another cell’s DNA injected into them,” he says. But this June, he and his colleagues delicately teased out the entire genome of Mycoplasma mycoides (which infects goats) and slipped it into Mycoplasma capricolum, a related but distinctly separate species. Tests revealed that the recipient bacteria lost their old genomes, while the donor genomes began to take over. “It’s the key breakthrough in this field,” Venter says.
Now Venter’s team is creating a minimal genome themselves and transplanting it into a cell. Until recently, scientists have been able to synthesize only relatively small pieces of DNA, and they’ve had a difficult time ensuring that the actual molecule turns out to have the sequence it’s supposed to. A number of groups of scientists are developing new methods to create accurate chunks of DNA. Venter’s team is one of them. They’re borrowing a DNA-building enzyme produced by a virus that does a good job of gluing together genetic building blocks. In 2003, they reported that they had synthesized the 5,386 “letters” in the DNA of a virus that infects bacteria. When they inserted the DNA into a microbe, it produced new viruses. Today the scientists are figuring out how to cement dozens of those 5,000-letter-size chunks into a single piece of DNA big enough to hold an entire Mycoplasma genome.

Venter hopes to have the first synthetic species within the next few months. In contrast to the images from Frankenstein movies, the man-made creature would barely eke out an existence in the pampered confines of a laboratory flask. But Venter sees its creation as the foundation for a new kind of genetic engineering. Today scientists engineer microbes either by adding a few extra genes or fine-tuning the genes they already have, tinkering on top of nature’s templates. Venter regards a minimal genome as an opportunity to build life from the ground up, like an engineer assembling a new piece of technology.

Venter doesn’t plan on designing those genes from scratch, however. He and his colleagues have been trawling the world’s oceans for microbes and sequencing their genes. Last April, they announced that they had raised the total number of known genes from 4 million to 10 million. His colleagues are still out at sea, still finding new genes. “By next April, we will have doubled the number againóthat’s my hope,” Venter says.

Along with the ocean, Venter is also searching for microbes in the air and deep underground. BP has joined in a partnership with Synthetic Genomics to sequence genomes from microbes that live in coal mines and oil wells. From this vast collection of genes, Venter hopes to build microbes that can produce hydrogen gas or be an efficient source of solar energy. Some microbes could clean up dangerous pollution or fight global warming. To handle the staggering task of testing all of the potential combinations of genes, Venter and his colleagues are going to set up an army of robots to build a million synthetic organisms a day.

Other scientists (including Jay Keasling, last year’s DISCOVER Scientist of the Year) are having great success adding handfuls of genes to E. coli and other microbes to make a variety of valuable products, including medicines and jet fuel. But no one is running Venter’s kind of experiment. No one else can. It requires years of expensive grunt work and offers no guarantee of success. It is hard to imagine a conventional academic researcher finding enough long-term funds to conduct such an experiment. It is impossible to imagine impatient stockholders allowing a biotech company to do so. Venter has the rare privilege of running his own institute and company, with a staff of hundreds (and that’s not counting all his robots).

People may eventually look back on Venter’s experiment with artificial life the way we look back from our laptops to the days when computers filled entire floors of buildings. Rob Carlson, a biotech expert at the University of Washington, points out that the science behind Venter’s work is getting cheaper and more powerful year by year. “You won’t require a university; you won’t require the National Science Foundation,” Carlson says. “You can do it in your garage if you want.” Out of a million garages, a million new species may bloom.

Copyright 2007 Carl Zimmer
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