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HOW DID LIFE BEGIN? In bubbles? On comets? Along ocean vents? Scientists find some surprising answers to the greatest mystery on earth. By J. MADELEINE NASH/LA JOLLA THE PRIMORDIAL CHEMISTRY LAB Life's beginnings did not have the benefit of Miller's glass bottles, test tubes and vials. So how did nature bring the right ingredients for life together in an orderly fashion? One possibility recently suggested by Louis Lerman, a researcher at Lawrence Berkeley Laboratory, is that bubbles in the ocean served as miniature chemical reactors. Bubbles are ubiquitous, Lerman notes; at any given time, 5% of the ocean surface is covered with foam. In addition, bubbles tend to collect and concentrate many chemicals essential to life, including such trace metals as copper and zinc and salts like phosphate. Best of all, when bubbles burst, they forcibly eject their accumulated molecules into the atmosphere, where other scientists feel the most important chemistry takes place. Biologist Harold Morowitz of George Mason University in Fairfax, Virginia, suspects that life arose in a less ephemeral chemistry lab than a bursting bubble. He focuses on Janus-faced molecules found in nature called amphiphiles. These molecules have one side with an affinity for water and another side that is repelled by water. Bobbing in the primitive oceans, the molecules would have hidden their water-hating sides away by curling into tiny spheres. These spheres, known as vesicles, would have provided an ideal setting for chemical reactions and could have been precursors to the first cells. ``Once you have these little vesicles,'' says Morowitz, ``you're on the way to life.'' Which came first, though, the membrane or the metabolism? Gunter Wachtershauser, a patent attorney from Munich who also happens to be a theoretical chemist, believes that what we call life began as a series of chemical reactions between certain key organic molecules. Instead of being enclosed in a membrane, he says, they might have been stuck like pins in a cushion on the surface of some accommodating material. Wachtershauser's surprising candidate for this all-important material: pyrite, or fool's gold. Since the shiny crystal carries a positive electrical charge, it could have attracted negatively charged organic molecules, bringing them close enough to interact. Wachtershauser thinks these reactions could have led to the development of something similar to photosynthesis. Still unanswered is the riddle of how these molecules came to reproduce. Chemist A.G. Cairns-Smith of the University of Glasgow thinks the answer may lie not in glittery fool's gold but in ordinary clay. The structure of certain clays repeats the same crystalline pattern over and over again. More important, when a defect occurs, it is repeated from then on, rather like a mutation in a strand of DNA. While few scientists believe such inorganic materials are actually alive, a number take very seriously the idea that clay or mineral crystals could have served as molecular molds that incorporated life's building blocks and organized them in precise arrays. MOLECULAR ANCESTORS Even if one accepts the fact that organic molecules can spontaneously organize themselves and, further, that these molecules might spontaneously reproduce, there remains a fundamental chicken-and-egg problem. Modern cells are made of proteins, and the blueprints for the proteins are contained in long strands of DNA and RNA. But DNA and RNA cannot be manufactured without an adequate supply of proteins, which act as catalysts in the construction process. How, then, could nucleic acids get started without proteins, or vice versa? One solution was put forward a decade ago, when researchers discovered that certain RNA molecules can act both as blueprints and catalysts, stimulating reactions between themselves and other molecules. Up to that point, scientists had thought of RNAs as merely molecular messengers carrying genetic instructions from DNA to the cell's protein factories. Suddenly RNA was seen in a totally different light. If RNA could catalyze reactions, perhaps at some point in the past, it spurred its own replication. Then it could have been much more than DNA's intermediary: it could have been DNA's ancestor. According to this line of reasoning, the first organisms lived in an `` RNA world,'' and DNA did not develop until life was speeding down the evolutionary turnpike. While searching for that ancient precursor of life last April, Scripps Research Institute's Joyce stumbled on the molecule that so tantalized him. A bit of synthetic RNA sloshing around in a test tube suddenly attached itself to a piece of protein and embarked on a course of nonstop replication. For a moment, this molecular upstart seemed close to the breakthrough Joyce had been seeking. The molecule, he acknowledges, is not alive. Magical as it seems, it cannot replicate without a steady supply of prefabricated proteins. To qualify as living, a molecule would need to have the ability to reproduce without outside help. An important step in this direction was recently taken by Harvard molecular biologist Jack Szostak and his graduate student David Bartel, who mimicked the prolific chemistry of primitive earth by randomly generating trillions of different strands of RNA. Eventually the scientists came up with a good five dozen that were able to join themselves to other strands suspended in the same test tube. The process of linkage, explains Szostak, is critical to the formation of complex molecules from simple building blocks. What's exciting, he says, is this part of the origin-of-life puzzle does not look quite so daunting as before. One of these days, both Joyce and Szostak believe, when someone fills a test tube with just the right stuff, a self-replicating molecule will pop up. If that happens, the achievement could be as upsetting as it is amazing. For it would challenge the most fundamental conceptions of what life is all about. Life, to most people, means animals or plants or bacteria. Less clear cut are viruses, because they are nothing more than strands of nucleic acid encased in protein, and they cannot reproduce outside a living cell. As scientists close in on life's origins, the working definition of life will be pondered, debated and perhaps even expanded. If a sliver of fully functional RNA arises in a test tube and starts building its own proteins, who is to say it is any less alive than the strand of RNA doing the same thing inside a cell? Some people will always hold to the belief that it is a divine spark, not clever chemistry, that brings matter to life, and for all their fancy equipment, scientists have yet to produce anything in a test tube that would shake a Fundamentalist's faith. The molecule in Joyce's lab, after all, is not as sophisticated as a virus and is still many orders of magnitude less complex than a bacterium. Indeed, the more scientists learn about it, the more extraordinary life seems. Just as the Big Bang theory has not demystified the universe, so progress in understanding the origin of life should ultimately enhance, not diminish, the wonder of it. With reporting by David Bjerklie/New York, Barry Hillenbrand/London and James O. Jackson/Gottingen Copyright 1993 Time Inc. All rights reserved.

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