reed magazine logospring2006

life in venice title

Making Life’s Building Blocks

Attempts at home-brewing life have come a long way since 1953, when chemist Stanley Miller earned a permanent place in biology textbooks with his demonstration that a mixture of water, methane, and ammonia could spontaneously form some of the basic building blocks of life. All it took was a jolt of electricity.

But a primordial soup of organic compounds is not even close to being alive by anyone’s definition. In recent years, scientists have engineered entities that satisfy some of the basic criteria for defining a life form: it must be able to regenerate itself by harvesting material and energy from its surroundings; it must be able to reproduce; and it must be able to evolve.

   

vesicle image

This self-assembled vesicle (about 100 microns in diameter) was produced at ProtoLife and exhibits some characteristics of living cells.

Biologists and chemists have now generated a menagerie of microscopic entities capable of such life-like feats as spontaneously growing and dividing. In one landmark experiment in 2004, researchers at The Rockefeller University inserted protein-making components into lifeless vesicles made of fatty acids, enabling them to take in nutrients and produce proteins for up to four days before “dying.” And scientists have amassed tremendous knowledge about DNA, RNA, and similar molecules that can store information to be passed on to offspring.

The grand challenge is getting the necessary functions to work together. “Life requires self-maintenance, self-reproduction, evolvability,” Packard explained at a scientific conference in October 2005. “Each component has been well-studied in and of itself. But putting them together so that they work in concert in a way that allows objects to reproduce is not understood at all.”

Nevertheless, he and Bedau are confident that it can be done within a decade. Their competitors agree. “I do think it is possible, although many challenges remain,” says Jack Szostak of Harvard University.

Bedau and Packard believe that they have an edge with an approach that harnesses the creative power of evolution. In Venice, ProtoLife’s chief chemist, Martin Hanczyc, is focusing on finding the right mixture of materials to form membranes to contain an artificial cell. The team has collected hundreds of likely starting chemicals, including fatty acids that comprise a class known as amphiphiles, which have parts that repel water and other parts that cling to it. This gives them the curious ability to self-assemble into tiny bubbles called vesicles.

Combining different mixtures of these molecules, the researchers are generating populations of vesicles and subjecting them to a survival-of-the-fittest winnowing. Much of the lab work consists of developing methods to screen large numbers of vesicles quickly for size, strength, and other properties. The goal is to evolve structures over many generations that have never arisen in nature or via human engineering.

It’s familiar territory for Packard, who has been interested since his graduate school days at UC Santa Cruz in the fields of machine learning and evolution. “Now, we’re using evolutionary methods in machine learning to explore these [new] biological systems,” he explains. “That’s a new frontier in biochemistry and molecular biology, and we’re finding ourselves in the middle of it.”

Bedau, meanwhile, has spent 15 years studying the way natural organisms and other systems evolve, and he’s developed statistical models to track the process of evolution. He’s adapting these to detect subtle advantages in components of would-be life forms. “Critics call it ‘irrational design,’” Bedau says, referring to the rational design process in which chemists engineer compounds to fit a pre-ordained shape. “We call it evolutionary design.”

And since the ProtoLife scientists are starting from scratch, almost anything goes. For instance, while most living cells conform to a limited size range, the scientists can make them radically smaller. Instead of DNA, they are open to using any information-encoding molecule that might work. Steen Rasmussen, a colleague who works at Los Alamos National Laboratory, has developed plans for an artificial cell literally turned inside out: It bears its genes and metabolic machinery on its outer membrane.

Another key part of their effort is to develop microscopic life-support systems for artificial cells. Chemist John McCaskill at Ruhr University in Germany is developing computer-controlled microscopic devices to control the flow of nutrients to artificial cells. The researchers plan to wean their creations from life-support systems one step at a time as the successive generations become more capable of independence.

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