Origins-Of-Life Research Rescued From Scientific Fringe

Bolstered by new scientific evidence, research into how self- replicating organisms emerged from basic organic molecules present on the early Earth is moving away from the scientific fringe and into the mainstream. Although there are only a handful of people who would call themselves origins-of-life researchers, the field is undergoing a renaissance, with a wide array of disciplines, such as radio astronomy, planetary science, molecular biology, and biochemistry, converging to make advances. Work on AIDS, on microbes living near hydrothermal ocean vents, and on the composition of interstellar gases are all contributing to answering questions about the origin of life. Molecular biology, the darling of today's biological sciences, is leading the pack. Molecular biologists Sidney Altman at Yale University and Thomas Cech at the University of Colorado are not origins-of-life researchers, but their work has largely been responsible for retrieving this field from the outer reaches of science. They won the Nobel Prize in chemistry in 1989 for their finding that RNA can cut, splice, and assemble itself. This has created an origins-of-life revival by demonstrating that an RNA-only world may have been the first form of life. "Initially, origins of life was just a topic for armchair speculation," says Gerald Joyce, a biochemist at Scripps Research Institute in La Jolla, Calif. Then came the classic work of chemist Stanley Miller, currently at the University of California, San Diego. In the early 1950s, Miller found that electrical discharges in a test atmosphere of ammonia, methane, and water produce amino acids and other organic molecules that could form the building blocks for life (S.L. Miller, Science, 117:528-9, 1953). There was growing excitement in the discipline until the 1960s, Joyce says. The field fizzled out when the next step linking these prebiotic chemicals to some sort of primitive living organisms could not be taken. It turns out there is more to life's origin than simply mixing the right chemicals together. "It's difficult to put some chemicals in a test tube and expect life to come crawling out," he says. And that's when the disrepute began to creep into the field, as the science became mired in phenomenology; that is, work revolved around producing curious molecular polymers--"protein blobs," as Joyce calls them. "But the action in life is genetics," he says. Amino acid polymers, although they catalyze reactions, do not carry information and are not "alive." At this point, "it became a field that tended to attract the flakier element," he says. And that's where things pretty much stood until Altman and Cech's work. "That's the point at which the field became relegitimatized," he says. But, just as happened following Miller's work, there was an overswing, an expectation that very soon "the answer" would be found. Today, the debate centers on whether RNA was the first form of life. "It looks like it's very reasonable to say there was a time when life was based on RNA," says Joyce. "But it's hard to imagine how the RNA world would have popped out of the soup," he says. Many researchers feel it would be too complicated first to form RNA monomers and then make the transition to complex polymers that are self-replicating, carry genetic information, and catalyze reactions. The debate continues over whether the RNA world came first or whether some biochemical system preceded this and then somehow gave rise to the RNA world. Joyce's interest is in RNA, and as a reflection of the cross- fertilization between other fields and origins-of-life research, he is funded by both NASA's exobiology program and the National Institutes of Health's division of AIDS research. He has recently received a great deal of notoriety for work on forcing a ribozyme to "evolve" in a test tube into a DNA-cleaving enzyme (A.A. Beaudry and G.F. Joyce, Science, 257:635-41, 1992). This work is of interest to the AIDS research community because it could solve a basic problem: how to develop an effective agent against a virus that constantly mutates. The answer is to develop a ribozyme that not only attacks HIV but also is capable of mutation in response to the virus' transformations, says Joyce. For origins-of-life workers, it demonstrates how RNA can be transformed into a multipurpose enzyme, lending credence to the notion that an RNA world existed. Joyce, however, has some doubts that this RNA world was the earliest form of life. "While there is good evidence to suggest that an RNA-based life form existed at an early stage in evolutionary history, there are several reasons to believe that Darwinian evolution did not begin with RNA," he wrote (G.F. Joyce, The New Biologist, 3:399-407, 1991). "It is difficult to see how activated mononucleotides could have been synthesized under plausible prebiotic conditions. The problem is not so much the availability of purines, pyrimidines, phosphate, and simple sugars, but the difficulty in assembling these components without the aid of biological catalysts." James P. Ferris, editor of the journal Origins of Life and Evolution of the Biosphere, says that assembling RNA polymers probably wasn't all that difficult. In a recent issue of Science (257:1387-89, 1992), he reports that montmorillonite clays can act as a surface for absorption and concentration of RNA monomers and as a catalyst. This clay acts as a proto-enzyme, bringing compounds together and catalyzing their condensation. And it does this with pretty good precision. Ferris has found that 85 percent of the polymers he produced are linked together in the same 3' to 5' orientation found in living RNA. "I think what we're trying to demonstrate is the feasibility of the origins of life, not that this is exactly how it happened," says Ferris. "A lot of people think the RNA world was too complicated to be first." But as a result of his recent findings, he says, "I myself am not convinced the RNA world was that complicated." Norman Pace, a biologist at Indiana University, wrote a recent review for Cell on research on life's origins, but considers himself a skeptic and on the outskirts of the field. Entitled "Origin of life--Facing up to the physical setting" (N.R. Pace, Cell, 65:531-3, 1992), his review was intended to deliver a dose of reality to a field in which "there's a high bullshit coefficient" and in which "speculation runs rampant," he says. The ancestry of microorganisms is traceable--by way of molecular comparisons of ribosomal RNA--to their most likely common ancestor, the so-called archaebacteria. "If the environment in which life arose was similar to that occupied by the most recent common ancestor, life probably arose in a geothermal environment at relatively high temperature," he wrote. And that means the classic notion of life evolving on the Earth's surface at moderate temperatures is probably incorrect. He posits that hydrothermal vents--where life forms use chemical energy to sustain life instead of sunlight--most closely resemble the prebiotic environment. The central focus of Pace's studies is in identifying geothermal microbes, under a grant from the Department of Energy, and his work is an example of how a wide range of research is contributing to progress in determining the origin of life. But while he says that geothermal vents hold a lot of promise as the cradle of life on Earth, he doesn't have a scenario for how a simple organic chemical made the transition into "life." But no matter what is eventually found, "it's going to be simple," he says. "I believe life was inevitable, and it happened with the formation of the Earth." Using evidence from deep-rock drilling, Cornell University geophysicist Thomas Gold has found a "deep, hot biosphere" of bacteria that live deep within the planet and thrive on chemical energy sources, such as hydrogen and methane (T. Gold, Proceedings of the National Academy of Sciences, 89:6045-49, 1992). His work has implications for the search for life's formation not only on Earth, but also on other planets. "As long as you think life is possible only on the surface, then only Earth can support it. But the moment you talk about stuff inside, Earth is not unique at all," says Gold. "Every solid planet has similar circumstances, with hot interiors and chemical processes that will always supply an energy source for bacteria." John Rummel, NASA's exobiology program manager, says research such as that of Gold and Pace is interesting because "it tells you that life is a lot stranger than you might think." Much of the origins-of-life research is funded under the program Rummel heads, but despite major cuts in the NASA budget for fiscal year 1993, "we're certainly holding our own," he says. Although the life sciences division is down by $12 million from FY 1992, the exobiology program will be held level at $6.3 million or may even increase slightly in FY 1993. So researchers should not shun this line of work. In fact, Rummel says, "I'm always interested in hearing about new research and new ideas." While funding may not hold back the search for life's beginnings, the answer will not be forthcoming soon, says Ferris. It's been about 4 billion years since life evolved and the Earth's surface has undergone big change. "I don't think we're ever going to know `the answer,' " he says, "because the answer has been demolished by life." "It's a bit of a difficult problem," Joyce says. "And I don't think it's going to be solved in our lifetime."

Origins-Of-Life Research Rescued From Scientific Fringe

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