Life from Scratch: Relaunching Biology from the Beginning

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A short stroll from Boston's Charles River, behind a sheath of blue glass on the seventh floor of a Harvard Medical School research building, Jack Szostak is getting set to replay the greatest event on Earth.

He and his 15-member team of graduate students and young postdoctoral research fellows are well on their way to startingbiology from scratch--more than 3.5 billion years after it first emerged.

The feat would qualify as creation of life in a test tube if it weren't for one thing: Szostak's lab does not rely much on test tubes. "I know exactly where it will happen," said postdoc Alonso Ricardo, from Cali, Colombia. It will most likely be in a 1.5-milliliter tapered plastic centrifuge tube "smaller than my little finger." And unlike the first time--when life formed on its own--the second time it will get a boost from human ingenuity and the lab's elaborate organic chemistry equipment.

Szostak's endeavor is very different from another artificial life project led by biologist and entrepreneur J. Craig Venter. Venter's team is using chemical sequencing machines to make a panoply of genes for the highly evolved parts of a modern microbe. Recently he and his colleagues announced that they had inserted an entire genetic blueprint, modeled on a known microbe but built from scratch, into a microbe of another species where the synthesized DNA took over (SN: 6/19/10, p. 5). Venter's ultimate aim is to build designer organisms with novel and fully contemporary genomes.

Szostak has a far more fundamental aim: to show how unguided natural events might have led to life on Earth in the first place, and to show how the scenario might also play out in myriad other places in the universe. Like bookends on a long row of volumes, the two exercises would frame the story of evolution so far.

In his neat corner office outside the rows of lab benches and work bays, the 57-year-old biochemist leaned forward and explained a deep motivation: "What we'd like to see is, from initial chaos and randomness, how something useful emerges. What we are trying to do, to understand, is how Darwinian evolution can emerge from chemistry.... If we can get a self-propagating chemical system that can evolve, yeah, I'd call that life."

A place to start

Szostak brings a lot of tools to the project. He has already made his mark on biology throughout a career puzzling over and exploring the workings of DNA and its cousin, RNA. He was a winner last October of the Nobel Prize in physiology or medicine, along with Elizabeth Blackburn of the University of California, San Francisco and Carol Greider of Johns Hopkins University School of Medicine in Baltimore. In the 1980s they showed how telomeres, distinctive caps on the ends of chromosomes, protect a living cell's DNA and genes from degradation.

Szostak, a U.S. citizen now, was born in London, where his father was stationed with the Royal Canadian Air Force. After returning home, Szostak enrolled in McGill University in Montreal at age 16. At 19 he took his degree in cell biology to graduate school at Cornell University. He dove into genetics. Nature published an extract from his biochemistry Ph.D. thesis--on synthetic RNA. At 26 he joined Harvard's faculty, where he is now a professor of genetics and a Howard Hughes Medical Institute investigator.

By the mid-1980s, electrifying word swept the field of DNA and RNA research. Tom Cech of the University of Colorado at Boulder and Sidney Altman of Yale University independently discovered that RNA--believed to be a mere messenger, carrying genetic blueprints from DNA-based genes to cellular machinery for making proteins--had another trick. It could fold into complex shapes, forming an enzyme that vastly speeds up the natural rate of some reactions (SN: 11/27/82, p. 342). Until then, the only known enzymes were specialized proteins. How life had first made proteins without enzymes, which presumably had to be proteins themselves, had been a chicken-and-egg conundrum. …