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Let There be Life Phil Cohen New Scientist 6 July 96

AT 3.5 BILLION years old, fossilised bacteria are the earliest evidence of life on Earth, and yet these relics, with names like Chromoccoceae and Oscdlotorioceoe, are identical to the sophisticated modern cyano- bacteria that cover the globe from Antarctica to the Sahara. Evidence of any simpler incarnation fried in the intense heat of the young Earth before conditions were favourable for lossilising its remains. In the absence of any rock-solid evidence. biologists have been free to speculate about the nature of the mysterious fledgling life form that came into existence some 4 billion years ago, and from which every plant, animal and microbe alive today eventually descended. All agree that early life, by definition, must have been capable of replicating and evolving. To do these things, most biologists have assumed that the ancestral life form needed a rudimentary instruction manual-a set of primitive genes -that was copied and passed from generation to generation. In the past year or so, a majority view has emerged on which molecules first acquired these abilities and so sparked life on the planet Earth. Buoyed by some spectacular breakthroughs, most biologists are now convinced that life began when molecules called RNA took on the tasks that genes and proteins perform in today's sophisticated cells. In the once controversial 'RNA world' theory, the chance production of largish RNA molecules was the crucial and committing step in the emergence of life itself. For many, this has become the only acceptable version of events. But just when it looked safe to carve the RNA world theory in stone, its opponents are staging a spirited counterattack. Scientists in this second group don't agree on the details of their alternative visions, but they all make a claim that seems almost blasphemous in the era of molecular biology: far from being the first spark of life, they say, the RNA instruction manual was a mere evolutionary afterthought that helped fan its flames. What is more, they claim thdt the evidence proving their case will be in by the end of the decade.

A tricky problem

All modern life forms, be they germs, geraniums or Germans, have genes. The genes are made of DNA, which is made up of nucleotides; it is the sequence of (hese subunits that encodes the cell's instruction manual. The DNA is translated into RNA (also made up of nucleotides) which provides the blueprint for protein construction. The proteins, in turn, do all the metabolic grunt work such as catalysing the chemical cycles that capture energy for the cell. They are also needed to translate DNA into RNA

to make DNA copies to pass to the daughter cells. in other words, proteins, DNA and RNA are all essential for life as we know it. For decades, this menage a trois was the undoing of many a biologist trying to come up with believable scenarios for how life first appeared. Take away any one of the three and life grinds to a halt. But coming up with a plausible story for how DNA, RNA and proteins suddenly popped into existence simultaneously on a lifeless planet was just as tricky. The first chink in this intellectual impasse appeared in the 1980s. Then Tom Cech at the University of Colorado and Sydney Altman at Yale University discovered that two naturally occurring RNA molecules sped up a reaction that snipped out regions of their own nucleotide sequence. RNA, it turned out, had some catalytic muscle of its own. The catalytic RNAs became known as ribozymes. Theoreticians jumped on this discovery, envisaging a long ago world in which RNA ruled the planet. First, by virtue of its ability to act as a template for new RNA molecules, RNA perfect for storing and passing on information. Second, by virtue of its ability to snap bonds between atoms, RNA was also a catalyst. Most crucial to the theory's credibility, the scientists proposed that RNA once catalysed the creation of fresh RNA molecules from their nucleotide building blocks. Eventually, the free-wheeling RNA molecules would have acquired membranes and taken on additional catalytic tasks needed to run a primitive cell. But RNAs reign did not last. Under the pressure of natural selection, the proteins, which are better catalysts than RNA, and the DNA, which is less susceptible to chemical degradation staged a cellular coup d'etat relegating RNA to its present role as a DNA-protein go-between.

Jack Szostack

Not surprisingly perhaps, those inclined to scepticism argued that it was too great a leap from showing that two RNA molecules partook in a bit of self mutilation in a test tube, to claiming that RNA was capable of running a cell single-handed and triggering the emer- gence of life on Earth - Jack Szostak, a biochemist at Massachusetts General Hospital in Boston, set out to prove the sceptics wrong. He reasoned that the first RNA molecules on the prebiotic Earth were assembled randomly from nucleotides dissolved in rock pools. Among the millions of short RNA molecules, there would have been one or two that could copy themselves -an ability that soon made them the dominant RNA on the planet. To mimic this in the lab Szostak and his colleagues took between 100 and 1000 trillion different RNA molecules, each around 200 nucleotides long, and tested their ability to perform one of the simplest catalytic tasks possible: cleaving another RNA molecule. They then carried out the lab equivalent of natural selection. They plucked out the few successful candidates and made millions of copies of them using protein enzymes. Then they mutated those RNAs tested them again, replicated them again, and so on to evolve some ultra-effective new RNA supplying ribozymes. In the past few months, David Bartel a biochemist at the Whitehead Institute for Biomedical Research near Boston and a former member of Szostak's team, has gone one better. He has evolved RNAs that are as efficient as some modern protein enzymes. The problem with most ribozymes is that they are as likely to snip an RNA molecule apart as stitch one together which makes copying a molecule fifty nucleotides long (the minimum size necessary to catalyse a chenical reaction) a Sisyphean task. Bartel's new ribozymes, on the other hand, can stitch small pieces of RNA together without breaking larger molecules apart. What is more his ribozymes use high-energy tri-phosphate bonds similar to ATP as their fuel, speeding the reactin up several million-fold. "We've got ribozymes doing the right kind of chemistry to copy long molecules" says Szostak "We haven't acheived self-replication from single nucleotides yet, but it is definitely within sight".

Stanley Miller

Electriciity and hot air

Still, for the RNA world to have worked, it would have needed a supply of adenine, cytosine, guaning and uracil, [the nucleic acid bases that along with sugar and phosphate, make up nucleotides. Back in the 1950s, Stanley Miller, a 23-year-old doctoral student at the University of Chicago, announced that he had made amino acids, the pieces that click together to make proteins, with little more than a stuttering spark of electricity shot through hot gas circulating in some glass tubing. The discovery was hailed as the first evidence that a lifeless planet could have spat out any of the raw materials needed for carbon-based life.

Millers spark was a stand-in for primeval lightning and the hot air, containing ammonia, hydrogen, water vapour and methane, was meant to mimic Earth's atmosphere 4 billion years ago. Besides creating amino acids, other researchers quickly demonstrated that the rich organic gook spewed out by Miller's decidedly non-biological combination also harboured chemical reactions that created huge amounts of adenine and guanine. Cytosine and uracil, however, remained elusive. For this reason, and others, Miller's experiment did not convince everyone. Many atmospheric scientists argued that, unlike MIller's experimental setup the incipient earth was hydrogen-starvedand entirely unsuitable for organic synthesis outside of a few havens, such as deep-ocean vents. This glitch led to the proposal of an alternative-to some fanciful theory: that the organic building blocks came from outer space. For much of his career, Jeffrey Bada a geochemist at Scrips Institute of Oceanography, had argued that this was impossible. But a few months ago, Bada's own research forced him to change his mind. He found evidence that "mother lodes' of buckyballs have been delivered intact to Earth from outside the Solar System. Bada and his colleague Luann Becker made their find at Sudbtlry, Ontario, where a nieteoroid the size of Mount Everest crashed 2 billion years ago. At first, Bada assumed that the buckyballs, football-shaped molecules made up of carbon aloms, had formed from vaporised carbon at the time of the impact. Then he discovered that they were loaded with helium, an element that has always been rare on Earth, but is abundant in inter-stellar space. What is more, the the single impact site contained about 1 million tons of extra-terrestrail buckyballs. If complex buckyballs could fall on earth without burning up so could complex organic molecules. "This blew our minds," says Bilda. "We never expected it to be possible"

And while Bada's conversion was taking place, Miller, now at the University of California, San Diego had not given up on the idea that the primeval organic slime-wherever it came from-could have spawned the missing nucleic acid buses, cytosine and uracil. Last summer, 43 years after his original experiment, he and his student Micliael Robertson discovered a way for the primordial pond to make them by the bucket- load. The secret ingredient was urea. Although urea is produced in Miller's original experimental setup, it never reaches a high enough concentration. But when he added more of the chemical, it reacted with cyanoacetaldehyde (another byproduct of the spark and hot air churning out vast amounts of the two bases. Miller argues that urea would have reached high enough concentrations as shallow pools of water on the Earth's surface evaporated-the 'drying lagoon hypothesis". And in the last few months, another gap in the RNA world theory has been plugged. "The real question," says Jim Ferris, a chemist at Rensselaer Polytechnic Institute in Troy, New York, "is how did we get from a prebiotic concoction to [the first] long pieces of RNA? What was the bridge to the RNA world?" In test-tube versions of the prebiotic world-as yet unblessed with protein enzymes or ribozymes, nucleotides link up , but only a few at a time. Once three or more have connected, the RNA chain snaps-long before it has reached the magic length of fifty nucleotides needed to catalyse production of more RNAs. In May, Ferris reported in Nature that he had found a means by which the first large chains could have been forged. When his team added montmorillonite, a positively charged clay that they think was plentiful on the young Earth, to a solution of negatively charged adenine nucleotides, it spawned RNA 10-15 nucleotides long. If these chains, which cling to the surface of the clay, were then repeatedly 'fed" more nucleotides by washing them with the solution, they grew up to 55 nucleotides long. The clay gets RNA off the hook of having to take on the tasks of information storage and catalysis in one fell swoop, says Ferris. It would catalyse RNA synthesis, stocking pools with a large range of RNA strands that, as Szostak and others have shown, would evolve a catalytic capacity of their own. In theory, an RNA catalyst would be born that could trigger its own replication from single nucleotides. And with all the new evidence that is now available the apostles of the RNA world believe that their theory should be taken, if not as gospel, then as the nearest thing to truth that the science of the origins of life has to offer. Not everyone agrees.

Power shortage

Evolutionary biologist Carl Woese of the University of Illinois says the genetic evidence contradicts the RNA world theory. And if that weren't bad enough, he also argues that the RNA world scenario is fatally flawed because it fails to explain where the energy came from to fuel the production of the first RNA molecules or copies that would be needed to keep the whole thing going. In test-tube RNA worlds, the elongating RNA molecules are fed artificially activated nucleotides, boosted with their own triphosphate bond to ensure that they come with an energy supply. In nature, such molecules only exist inside cells, and they have never been created in a Miller-type experiment. "The RNA world advocates view the soup as a battery, charged up and ready to go," Woese complains. On the primordial Earth, that energy had 10 come from soniewhere, and it had to be coupled to production or else it would quickly disappear into the ether. In Woese's view the critical step that ultimately spawned life was not a few stray RNA molecules, but the emergence of a biochemical machine that transformed energy into a form that was instantly available for the production of organic molecules.

The energy machine

Gunter Wachtershauser, an organic chemist at the University of Regensberg in Germany has suggested just such a machine. According to his picture, iron and sulphur in the primordial mix combined to form iron pyrites. Short, negatively charged organic molecules then stuck to its positively charged surface and 'fed" off the energy liberated as more iron and sulphur reacted, creating longer organic molecules. The negatively charged surfaces of these molecules would attract more positively-charged pyrite, and the cycle would continue. And by Wachtershauser's reckoning, this energy-trapping cycle could easily have evolved into life forms that now exist-as chance ensured that one of the growing organic molecules was eventually of the right composition to catalyse its own synthesis. Ultimately, cycles of organic molecules would evolve that could trap their own energy-at which point they could do away with the inorganic energy cycle. According to Woese, Wachtershauser's theory and the RNA world theory are all testable, if only you know where to look for clues. The physical record of Earth's earliest life forms may have been erased, he says, but their "echoes, carried all the way through from pre- cellular times- remain encoded in the genes of modern organisms. Six years ago, Woese with Otto Kandler of the University of Munich and others, used those clues to transform our understanding of recent evolution. By using the mutation rates of genes as their guide. they pruned the tree of life, which traces how different species evolved, from five main sections to just three. Woese says that a similar type of genetic analysis now shows that, contrary to the view of RNA world advocates, replication of RNA appears to have been a late development in evolution ' and not its starting point. If RNA molecules had been responsible for the emergence of life, then the ancestral cell-which was supposedly descended from the initial RNA life forms, and the ancestor of all current life fornis-would have had a sophisticated machinery for copying RNA. The genes encoding that machinery would have been subjected to selection pressures from the get-go, and so should be present in every modern organism in a 'relatively unaltered state. But, says Woese, when biologists look at these genes, species from the three branches of the tree of life have little in common. That shows, says Woese, that the machinery needed to copy RNA was a work in progress in the common ancestor cell, and that subsequent evolution on the three branches of the tree Solved its inefficiencies in very diffelrent ways. In Short, RNA replication cotild not have been the trigger for the energetics of life. "Only the mere essence was there at the time of ihe common ancestor," Woese says.

And, he warns, "we're only beginning to unlock the secrets of the common ancestor.' Comparisons of genes may soon reveal the identity of the first energy-producing metabolic cycle, he says. Assuming for a monient, that the metabolic cycle was the initial life form, theni when the first genes appeared, they would have been coopted into ratcheting up the efficiency of the metabolic cycle by producing enzymes to catalyse each step. These genes would then have been Subjected to selection pressures for longer than any others, and should be present in all modem organ- isnis in a similar stite. Until recently, an all-out search for this first metabolic cycle has been impossible, because only bits and bobs of DNA sequence were available from a few organisms. But genome projects are gathering momentum spewing out complete sequences of organisms, every gene faster than the scientists can analyse them. This month, Woese and his colleagues plan to be the first to publish the sequence of an archaebacterium, Methanococcus jannaschii, a resident of boiling, deep-ocean vents. Woese predicts that 100 whole genome sequences will be in the databases by the end of the decade. Enough perhaps to finally track down the primordial energy cycle. Woese and Wachtershauser may be ruffling the feathers of RNA world enthusiasts by suggesting that an energy producing metabolic cycle, not RNA, triggered life on Earth. But Stuart Kauffman, a theoretical biologist at the Sante Fe Institute in New Mexico is leaving them speechless by suggesting that life forms may exist that have no need of RNA or DNA or any other 'aperiodic solid'. What is more, he says, the emergence of life wasn't some chance event, but something that was bound to happen under the conditions of the primitive Earth.

Out of chaos

Kauffman argues that the emergence of life on Earth is not the success story of a sin- gle type of illolectile, stich as RNA, slowly evolving to take on the catalytic burden of self- replication. in his view, the process was far more democratic. According to complexity theory, when a system reaches some critical level of complexity, whether it is made of stocks and shares or molecules, it naturally generates a degree of complex order. Likewise, he says, the mundane mix of nucleotides, lipids and amino acids that made up the primordial soup would in one magic instant have become an integrated system as the natural consequence of being part of a chaotic and complex mess. Under such conditions, he says, self- replicating, "life-like" order is not a chance occurrence, it's a dead cert. In Kauffman I view, the modern manage a trois of protein, RNA and DNA is not a conundrum, but a natural consequence of how life began. He has demonstrated his theory using a computer model of the primordial stew. This shows that when a group of molecules, computer equivalents of simple organics with a few rudimentary catalytic skills-reach a critical level of diversity they spontaneously form an "autocatalytic set": a molecular cooperative that replicates as a group and evolves to create ever more complicated members. In other words, an autocatalytic set is a life form. What is more, says Kauffman, any sufficiently diverse mix-whether it is of carbon compounds or particles in an intergalactic dust cloud will form autocatalytic sets, live, and evolve. True, says Kauffman, RNA and DNA are part of all life today, but they arose as an accessory to an already flourishing ancestral autocatalytic set. Before genes existed, natural selection exerted its forces on the autocatalytic sets, ensuring that they were not biological dead-ends, but living systems capable of evolving to best suit their environment. But many bench biologists scom such ideas as cyberfantasy. 'It's a pretty thought," says Gerald Joyce, who studies test-tube evolution at the Scripps Research Institute in San Diego. "But to be convinced, I need to see this auto-catalytic gemish." And there's the rub. To prove Kauffman's theory you would need to analyse the contents of a pot in which percolated billions of different organic molecules, identify the autocatalytic entities and isolate them, and put them through their self-replicating cycles. Such an experiment stretches the bounds of what is technically feasible. After years of trying to persuade the RNA world enthusiasts of the errors of their ways, however, Kauffman says he has gathered allies in biochemistry (he refuses to name names) who are willing to take on that task. He expects results in two to three years. But in the short-term at least, most biologists say that the RNA world theory will prevail. Not unnaturally that worries those in opposition such as Woese, Kauff- mati, and Wachtershauser. "RNA chauvinism dominates the text-books," says Gary Olsen, Woese's colleague at the University of Illinois. And that's a mistake, he warns, because the RNA world "as a theory it is only partly proven. The rest is speculative optimism."

The World according to RNA:
Experiments lend support to the leading theory of life's origin.
Scientific American Jan 96 John Horgan

In 1981 Francis Crick commented that 'the origin of life appears to be almost a miracle, so many are the conditions which would have to be satisfied to get it going." Now, several findings have rendered life's conception somewhat less implausible. The results all bolster what is already the dominant theory of genesis: the RNA world.

The theory helped to solve what was once a classic chicken-or-egg problem. Which came fint, proteins or DNA? Proteins are made according to instructions in DNA, but DNA cannot replicate itself or make proteins without the help of catalytic proteins called enzymes. In 1983 researchers found the solution to this conundrum in RNA, a single-strand molecule that helps DNA make protein. Experiments revealed that certain types of naturally occurring RNA, now called ribozymes, could act as their own enzymes, snipping themselves in two and splicing themselves back together again Biologists realized that ribozyrnes might have been the precursors of modem DNA-based organisms. Thus was the RNA-world concept bom. The first ribozytnes discovered were relatively limited in their capability. But in recent years, jack W. Szostak, a molecular biologist at Massachusetts General Hospital, has shown just how versatile RNA can be. He has succeeded in evolving ribozymes with unexpected properties in a test tube. Last April, Szostak and Charles Wilson of the University of California at Santa Cruz revealed in Nature that they had made ribozymes capable of a broad class of catalytic reactions. The catalysis of previous ribozymes tended to involve only the molecules' sugar-phosphate "backbone," but those found by Szostak and Wilson could also promote the formation of bonds between peptides (which link together to form proteins) and between carbon and nitrogen. One criticism of Szostak's work has been that nature, unassisted, was unlikely to have generated molecules as clever as those he has found; after all, he selects his ribozymes from a pool of trillions of different sequences of RNA. Szostak and two other colleagues, Eric H. Ekland and David P. Bartel of the Whitehead Institute for Biomedical Research in Cambridge, Mass., addressed this issue in Science last July. They acknowledged that it would indeed be unlikely for nature to produce the most versatile of the ribozymes isolated b)Szostak's rrlethods. But they argued that the ease with which these ribozymes were generated in the laboratory suggested that they were almost certainly part of a vastly larger class of similar molecules that nature was capable of producing.

Szostak's work still leaves a major question unanswered: How did RNA, self-catalyzing or not, arise in the first place? Two of RNA's components, cytosine and uracil, have been difficult to synthesize under conditions that might have prevailed on the newborn earth four billion years ago. The origin of life "has to happen under easy conditions, not ones that are very special," says Stanley L Miller of the University of California at San Diego, a pioneer in origin-of-life research. tzst June, however, Miller and his U.C.S.D. colleague Michael P. Robertson reported in Nature that they had synthesized cytosine and uracil under plausible "prebiotic" conditions. The workers placed urea and cyanoacetaldehyde, thought to have been common in the "primordial soup," in the equivalent of a warm tidal pool. As evaporation concentrated the chemicals, they reacted to form copious amounts of cytosine and uracil.

Nevertheless, even Miller believes that a molecule as complex as RNA did not arise from scratch but evolved from some simpler self-replicating molecule. Leslie E. Orgel of the Salk Institute for Biological Studies in San Diego agrees with Miller that RNA probably "took over" from some more primitive precursor. Orgel and two colleagues recently noted in Nature that they had observed something akin to "genetic takeover" in their laboratory. Orgel's group studied a recently discovered compound called peptide nucleic acid, or PNA; it has the ability to replicate itself and catalyze reactions, as PNA does, but it is a much simpler molecule. Orgel's team showed that PNA can serve as a template both for its own replication and for the formation of RNA from its subcomponents. Orgel emphasizes that he and his colleagues are not clain-dng that PNA itself is the longsought primordial replicator: it is not clear that PNA could have existed under plausible prebiotic conditions. What the experiments do suggest, Orgel says, is that the evolution of a simple, self-replicating molecule into a more complex one is, in principle, possible. Szostak, Miller and Orgel all say that much more research needs to be done to show how the RNA world arose and gave way to the DNA world. Nevertheless, life's origin is looking less miraculous all the time. -John Horgan

Molecules of Ancient Life Born Again NS 17 Oct 98 10

THE molecular machinery that assembles proteins in cells evolved billions of years ago. Now chemists in Colorado say a test-tube experiment may have re-enacted a crucial part of that process. Their fendings may give a rare insight into the factors that drive evolution. The protein factory of cells Is the ribosome. Built of RNA-A chemical relative of DNAand many proteins, the ribosome reads the genetic code and fuses amino acids to make proteins. But many biologists believe that in the earliest forms of life, all crucial functions of the cell were performed solely by RNA-like molecules. If so, it should be possible to find RNA molecules that can imitate the ribosome's function. Biliang Zhang of the University of Massachusetts in Worcester and Tom Cech of University of Colorado at Boulder reported a step towards that goal last year. They isolated RNAs that could efficiently link specific amino acids together (Nature, vol 390, p 96). These pseudo-ribosomes were selected from a random pool of 1015 synthetic RNAS. But Cech says the results became even more startling when they subsequently examined the sequences of the RNAS. RNA, like DNA, is composed of four chemical bases. They found that a small region of many of the RNAs they selected was 70 per cent identical to some regions of the ribosomal RNA. "We not only copied ribosome function, we seemed to have recapitulated its evolution," says Cech The two researchers then removed or mutated these sequences in the synthetic RNAs. If the similarity to ribosomal RNA was just a coincidence, this would have only a minor effect on their function. But, as they report in this month's Chemistry and Biology (vol 5, p 539), any change to this region cut the activity of the RNA by a factor of between 20 and 600. Now Zhang and Cech hope to find out if this region in both the modern ribosome and the synthetic RNA have the same role in the fusion reaction, such as holding the amino acids in the correct position. "if they converged on the same molecular solution, then we might be able to find out what happened four billion years ago by studying a test tube," says Cech. Philip Cohen

Polarized Life Sci Am Oct 98 13

For Europe, 1848 was a year of revolutions-one of which was scientific. Then, the young Louis Pasteur showed that certain organic molecules come in two mirror-image forms, one that rotates polarized light to the right, the other to the left. Such inolecules are said to have a definite halldedness, or chirality. And it has long been a great mystery why organisms show "homochirality," or, more specifically, an overwhelming preference to build their cells with right-handed sugars and left-handed amino acids. But now astronomers have stumbled on what may be an important piece of the puzzle. This past July in Science, Jeremy Bailey of the Anglo-Australian Observatory and seven colleagues reported that they had discovered large areas of circularly polarized light coming from a region of star formation in the constellation Orion. (The circular polarization of a light wave refers to the orientation of its oscillating electric field, which rotates 360 degrees clockwise or counterclockwise during each cycle.) Some of these immense patches emit circularly polarized light that is predominantly right-handed, some left-handed. The astronomers were measuring the polarization that can come about when celestial dust grains scatter light from nearby stars. By doing so, they hoped to learn more about the makeup of these particles. For a while, they detected or 2 percent circular polarization at most. Then, according to team member James H. Hough of the University of Hertfordshire in England, one night their primary targets were obscured, and the researchers said to themselves, "Let's look at Orion; it's always interesting." They were stunned to find as much as 17 percent circular polarization. Bailey realized that such high percentages might have relevance to the enigma of biological homochirality. Even if lifeless, such dusty regions probably contain organic molecules, including amino acids, a supposition based in part on the discovery of extraterrestrial amino acids within the meteorite that fell on Murchison, Australia, in 1969. The handedness of life could be explained if circularly polarized ultraviolet light bathed the dusty cloud that condensed into our own solar system and preferentially destroyed the right-handed amino acids. (Laboratory experiments show that SL)ch selectivity readily occurs, but whether the right or left-handed form breaks down depends on the spectrum of the light.) When the first life-forms eventually emerged, they used the more numerous left-handed amino acids to build proteins, which were shaped in a way that naturally favored right-handed sugars. One ol)jection to this hypothesis is that the astronomers observed only circularly polarized infrared light (a wavelength that can pierce dusty regions), whereas ultraviolet light is needed to weed out chiral molecules. But the researchers' computations showed that the scattering of light from elongated grains aligned by a magnetic field should generate circularly polarized ultraviolet along with infrared. Another objection is that perhaps life needed no external influence beyond chance to choose its handedness. Perhaps so, yet last year's discovery that even the nonbiological amino acids in the Murchison meteorite tend to be left-handed argues that some extraterrestrial mechanism must have operated to create this imbalance. sci(ntists have invoked many other ideas to explain the chirality bias, such as tiny asymmetries in fundamental physics, light from exotic neutron stars and spontaneous chemical reactions. Though possible, these are only speculations, whereas the astronomers' new work, in the words of Dilip K. Kondepudi, a physical chemist at Wake Forest University who studies homochirality, "gives us some hard facts." -David Schneider