April 2, 2004

Column: Researchers seek to create a living cell

SHARON BEGLEY, The Wall Street Journal

As any geek who ever soldered together a circuit board from off-the-shelf parts can testify, if you truly want to understand how something works, you need to build it yourself.

That approach doesn't raise any eyebrows when applied to gizmos and gadgets, but now a loosely organized band of scientists is extending it in an audacious way. In hopes of answering the age-old question "what is life?" they are trying to assemble -- from off-the-shelf, nonliving molecules -- a living cell.

"Creating a cell from scratch is probably at least 10 years away, but it is going to happen," says Mark Bedau of Reed College, Portland, Ore. "We're in for some very interesting, very profound new ways of thinking about what life is, and about where you draw the boundary between life and nonlife."

One of the deepest mysteries in biology is how molecules that are no more alive than the tip of a pencil can form a reproducing, metabolizing, evolving organism. If you plop a droplet of any of the molecules that make up living cells (fats, amino acids, water, DNA, other organic molecules) onto a glass slide, it just sits there. No one would mistake it for a living thing. Yet when the right ingredients assemble in the right proportions, the result comes alive, as it did on Earth some 3.8 billion years ago.

The transformation is so profound that most scientists until the 19th century believed in the theory called vitalism. This holds that living things possess a mysterious "vital spark" that endows them with life, and that life cannot be explained by mere chemistry and physics. But today, harnessing no more than thermodynamics, electromagnetism and chemistry, scientists are taking steps toward creating a living cell.

The first step is to separate the would-be cell from the outside world, and this turns out to be startlingly simple. Several researchers have created little self-replicating vesicles, minuscule bubbles much like the membranes around living cells. In a special mixture of oil and water, Luigi Luisi of the Swiss Federal Institute of Technology, Zurich, has found, membranes form spontaneously, grow by incorporating small molecules from the outside world, and reproduce by pinching themselves in two, like amoebas.

Dr. Luisi's vesicles fulfill two of the main requirements for life, growing and reproducing. In addition, says David Deamer of the University of California, Santa Cruz, a living cell must transform raw materials and energy into more of itself (metabolize), and also evolve. Although no one has gotten a single vesicle to carry out all of these reactions, Prof. Deamer and his colleague Pierre-Alain Monnard are coming close.

"As they form, the vesicles capture a polymerase enzyme that strings together small molecular building blocks into more complicated molecules," says Prof. Deamer. "The vesicles take in molecules from the outside, and the polymerase uses them as nutrients and as an energy source to synthesize RNA," a cousin of DNA.

Other groups of scientists have gotten simple amino acids to link together into proteins, like beads linking into a biological necklace. The reaction occurs on the surface of the vesicle, which somehow jump-starts the assembly. The vesicles created in the lab are not just dumb containers; they support biological reactions.

Last fall, molecular biologist Jack Szostak of Massachusetts General Hospital, Boston, and colleagues reported that common clay particles have an unsuspected talent. They can speed up the conversion of little clusters of molecules into vesicles, making the formation of a cell membrane even easier. Inside the vesicle, the clay particles grab hold of short bits of RNA and assemble them into a long strand. Voila: a little sphere containing genetic material able to grow and copy itself.

The missing ingredient in this cell wannabe is metabolism, but Steen Rasmussen of Los Alamos National Lab thinks he can provide it. He and Liaohai Chen of Argonne National Lab have designed a microscopic container with metabolic molecules and genes whose electrical properties drive metabolic reactions. The scientists have demonstrated experimentally that this micrometabolism can produce exactly the molecules the container is made of (so the system would be able to grow).

"All the pieces are there -- self-assembling container, genes and metabolism that captures energy from the outside world," says Dr. Rasmussen. "The question is, how do we get it to reproduce? If we do, then most people would say it is alive."

If researchers manage to create living cells from scratch, their mastery of the machinery of life could blur the line between alive and not-alive. Combining the traits of artificial cells with nanotechnology, Dr. Rasmussen and colleagues wrote in a recent issue of Science, could produce machines that "would literally form the basis of a living technology possessing powerful capabilities and raising important social and ethical" questions. Adds Prof. Bedau, "It will be crossing a threshold, enabling technologies we can't even imagine now."

Scientists are close enough to creating life in the lab that it is time to start a public debate about what that would mean -- for traditional views of the sanctity of life as well as for whether the creators will be able to control their creations.

Copyright 2004 Dow Jones & Co. Inc.