reed magazine logospring2006

life in venice title

Top-down or bottom-up?

Some skeptics doubt whether the efforts of ProtoLife and its collaborators will produce anything useful. Among them are molecular biologists who point out that billions of years of evolution have gone into the current design of natural organisms. “To pretend to do life with simple chemistry is a nice ambitious idea,” biochemist Pier Luigi Luisi of the University of Rome told the journal New Scientist. “But it’s probably not going to be very efficient.”

In contrast to ProtoLife’s “bottom-up” approach of trying to create living cells from scratch, some researchers are trying to exploit the capabilities of existing cells. Their method involves retrofitting naturally occurring bacteria, and stripping out components to find the minimal set required for life. Among those pursuing this “top-down” approach is genome-sequencing pioneer J. Craig Venter, whose self-named institute is attempting to develop a basic cell to serve as a platform for adding on useful functions, such as genetic instructions for producing biofuels or drug compounds that are difficult to synthesize in the laboratory.

Szostak, the Harvard scientist, is leading an effort that borrows one of the information-conveying molecules used by living cells in nature: RNA. Szostak’s lab hopes to equip artificial cells with an RNA genome capable of self-replication.

Packard, Bedau, McCaskill, and Rasmussen at ProtoLife are attempting something “radically different,” says chemist Andrew Pohorille, director of the NASA Center for Computational Astrobiology.

“The McCaskill-Rasmussen project is probably the most difficult and I would not bet any money on its completion by 2016,” says Pohorille. “All other projects are aimed at constructing simple forms of life as we know it. . . . Rasmussen’s vision is to construct a ‘living’ system that is truly different from terrestrial life. He wants to test the limits of what it means to be alive, with a long-term thought of creating alternative life forms on earth or looking for them elsewhere in the universe.”

Pohorille is convinced, however, that ProtoLife’s chemical experiments are heading in the right direction. “I have come to the conclusion that some sort of evolutionary strategy is more likely to succeed,” he says. “McCaskill’s group seems to arrive at the same conclusion, trying to jumpstart natural selection using microfluidics.”

Luisi at the University of Rome is deeply skeptical of ProtoLife’s chances. “The attempt at making cells without the natural macromolecules of life—DNA and enzymes—and of utilizing only synthetic chemistry, this is the great shortcoming,” he says. “If you take biological living cells as the standard, only poor approximations will be possible.”

Packard counters that while his artificial cells “won’t be able to do anything as sophisticated as contemporary cells, the real question is whether those few simple things will be interesting and powerful.” He seems convinced they will be.

Packard and Bedau acknowledge that top-down projects will probably be the first to produce artificial life. But they assert that bottom-up projects are likely to prove more valuable in the long run, both scientifically and commercially.

First, they hope to create truly alternative life forms and generate new concepts of how life might appear elsewhere in the universe. “If you’re taking existing cells and modifying them, then you might not understand a lot of why things are working, because nature has provided it,” Bedau says. “We are not constrained by the way life arose.” The commercial advantage comes from developing capabilities beyond the limits of natural life forms. “So, for example, you could make forms of life that depend on food that is toxic to every known form of life,” he says.

And Packard has a lot riding on that possibility. The European Commission has contributed about half-a-million euros to ProtoLife’s operating budget; Packard has invested three times that, and has brought in other investors as well. So while his interest in the venture is partly intellectual, he also firmly believes that a profitable business can develop out of the research. “Even though Prediction Company was successful, it didn’t give me enough liberty that I can treat this investment lightly,” he says. “If I ever become convinced there’s no business possibility, I’ll instantly dissolve the company.”

next page