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June 2000 Issues 1

Salty secrets of shrunken testicles
NS 4 Mar 2000
IODISED salt may have caused a drop in men's sperm counts since the 1950s, according to scientists in America. They say that iodine deficiency, while stunting brain development, also appears to boost sperm counts. Our bodies need iodine to make the thyroid hormone thyroxine, which is vital for developing brains. But in some parts of the world crops contain little iodine. A deficiency can cause impaired mental development, so iodine is added to salt. In the 1990s James Crissman of the Dow Chemical Company in Michigan and colleagues at the University of Illinois in Urbana looked at data showing a sharp drop in sperm levels around 1960. They worked out that the men's average date of birth was 1924-when iodised salt was introduced in America. To test the link, Crissman's group raised female rats on an iodine-deficient diet and mated them with healthy rats. The offspring were subsequently weaned by their iodine-deficient mothers and later fed low-iodine diets. He found that the offspring had larger testicles and produced more sperm than normal rats. "They ended up with testes twice as big as normal," says Crissman. Richard Sharpe of the Medical Research Council's Reproductive Biology Unit in Edinburgh says there are cases of men with underactive thyroids having enlarged testicles. But he is sceptical: "Sperm count data are so variable." And Crissman warns against cutting down on iodine. "There's a danger people could get exactly the wrong message and decide that sperm counts are more important than brain development.' Ian Sample

Source: Toxicological sciences (vol 53, p 400)

Summer of the WIMPs
NS 4 Mar 2000
Does dark maner rain down on Italy in June?

SEASONAL variations in the number of particles colliding with the Earth strongly suggest that WIMPs exist, say Italian researchers. WIMPS, otherwise known as weakly interacting massive particles, may be the dark matter that many astronomers believe makes up 90 per cent of the mass of the Universe. Last month, at a meeting on dark matter at Marina del Rey in California, the team said that three years of observation have confirmed its initial claim to have discovered WIMP-like signals (New Scientist, 16 January 1999, p 24). But American researchers still remain unconvinced. Since 1997 a Chinese-Italian team has been using a particle detector in the Gran Sasso Laboratory deep inside a mountain in the Apennines to detect heavy particles. After analysing three years of data, the researchers say that about 7 per cent more particles with a mass of about 50 protonsthe size that WIMPs are expected to be-hit their detector in summer than in winter. Because of its orbit around the Sun, the Earth moves faster relative to the centre of the Galaxy in June than in December. The researchers argue that the Earth therefore sweeps up more of these particles during the northem summer. However, at the same meeting, an American researchers said that after a year-long run of their WIMP detector they haven't picked up any seasonal variation in their signals. The team, which includes researchers from seven universities and three national laboratories, conclude that they had not found any WIMPS. 'The two experiments appear to be inconsistent," says the Americans' project manager, Roger Dixon of the Fermilab particle physics lab near Chicago. "This doesn't mean necessarily that one is wrong and one is right. We have to go back and understand the difference," he says. One difficulty is that the two groups use different technologies to detect WIMPs. While the Italians have a 100kilogram sodium iodide detector sited 1400 metres underground to shield it from background interference caused by cosmic radiation, the Americans have an extremely sensitive 0.5-kilogram germanium and silicon crystal detector about 10.5 metres underground in California. The Americans use software and additional detectors to get rid of all events not caused by WIMPS. Alessandro Bettina, director of the Gran Sasso Laboratory, says because of the drastic elimination of non-WINW signals, 'they may have thrown out the baby with the bathwater." Some of the WIMP-like signals came from neutrons and a few of them may be WIMPS, admits David Caldwell of the University of Califomia at Santa Barbara. But the Americans remain unconvinced by the Italians' efforts to tease out the seasonal variations from the huge amount of background noise. Typically, a 0.5-kilogram detector would catch one WIMP per week, and this is 'hard work," says Michael Tumer, a theoretical cosmologist at Fermilab. But Turner, who coined the word says he feels the dark-matter problem will be solved very soon: "We now have instments that are sensitive enough to detect these particles." Alexander Hellemansi, Naples

Gene Police
NS 4 Mar 2000

WHAT would happen if you scaled the gates of Buckingham Palace and strolled across the courtyard to have a chat with the Royal Family? You wouldn't get far before the guards identified you as an intruder and wrestled you to the ground. Casual visitors aren't wekome in those exalted precincts. Nor are casual genes welcome in the high society of a cell's genome. There, too, intruders usually mean trouble. A gene that doesn't belong might come from a virus trying to commandeer the cell's machinery to make more viruses. Or it could be a transposon-a good-for-nothing bit of selfish, parasitic DNA that hangs around the genome like an unemployed relative. Whatever their origin, these unwanted visitors often trigger a security crackdown within the cell that silences the offending gene every bit as swiftly and vigorously as guards would deal with a placard-waving hooligan at the Queen's front door. This genomic police force operates in everything from protozoa and fungi to plants and fruit ffies. And within the past few months, as researchers have begun to flesh out its details, they are discovering that "gene silencing" may be a defence system as old as nucleated cells themselves. Already, genetic engineers-who once viewed gene silencing as a nuisance, because it can switch off the genes they have so painstakingly inserted-are using it as a tool to switch off genes at wfll, potentially revealing gene functions or generating genetically modified crops that lack natural toxins and allergens. Researchers first became aware of this security force 10 years ago when Richard Jorgensen and his colleagues at DNA Plant Technology in Oakland, California, tried to deepen the colour of petunia petals by inserting extra copies of a gene for an enzyme called chalcone synthase (CHS), which plants use to make red, blue and purple pigments. To their astonishment, they found that some modified plants made less pigment, producing white or partially white flowers instead of the normal pink and violet. 'We were totally surprised," says Jorgensen, who is now at the University of Arizona in Tucson. "Basically the conversation was 'what the heck did we do wrong?'It took a while before we realised that this was something interesting.' Not only had the gene they inserted failed to work, but the plant's own copies of the CHS gene had fallen silent as wefl. That meant the plant cells must somehow have used information about the inserted gene to seek out and inactivate similar genes. Eventually the scientists established that the cells had made an RNA copy, or transcript, of the inserted gene-the first step in the production of a gene's protein product. Ordinarily, this messenger RNA (mRNA) carries the genetic information out of the nucleus to the sites where proteins are made. But in Jorgensen's petunias, the cells somehow destroyed the mRNA before it could be used to make the CHS protein. Other researchers later dubbed this process 'post-transcriptional gene silencing" (PTGS), and it has since been found in bread mould, nematode worms, fruit flies and protozoa. Geneticists now suspect that PTGS has, at one time or another, operated in all organisms with nucleated cells, though vertebrates may have lost it during their evolution (see "A spanner in the works', page 30). You might @ a foreign gene would be hard to spot amid all the hustle and bustle as the cell produces MRNA from its own genes in the course of its daily business. In fact, the interloper usually leaves a telltale footprint-a doublestranded RNA molecule, something rarely seen m a normal cell. Double-stranded RNA is to cells what the wolf's snout and big teeth under Grandma's nightcap were to Little Red Riding Hood: a sure sign that something is amiss. Recall that DNA, the stuff of genes, is made of two complementary strands joined into a double helix. When a legitimate gene becomes active, the cell always makes an mRNA copy from just one of these two strands, the one identified by the proper [email protected] instructions. Since the other strand is not copied, the MRNA never finds a complementary strand to pair with, so it remains single-stranded.

Alarm bells

Many viruses, on the other hand, use RNA as their genetic material and create double-stranded RNA temporarily as they create new copies of their genome. Even viruses that use DNA as their genetic material often pack genes onto both strands to save space. If such viruses transcribe overlapping genes from complementary strands at the same time, the two MRNA molecules that result could pair up just as their parent DNA strands did. Bingo: [email protected] RNA that will set the ceh's alarm bells nngmg. Something similar happens with transposons. These bits of selfish DNA carry the gene or genes needed to cut them'c selves out of the host chromosome and reinsert elsewhere. Some can also make copies of themselves. Each of a transposon's genes is usually transcribed from only one DNA strand-like the ceu's own genes-to give single-stranded, .sense" MRNA. But transposons insert themselves into DNA more or less at random. If a transposon inserts next to, or into, a host gene, then some or all of the transposon genes may get transcribed when the host tries to transcribe its own gene. And if this accidental transcription reads the "wrong" strand of the transposon-because it happened to insert backwards compared with the host DNA-the result will be 'antisense" RNA. This is complementary to the sense RNA and binds to it easily, once again yielding double-stranded RNA (see Diagram). The more successful the transposon, the more copies of its DNA insert into the host and the more likely this becomes. Exactly the same thing happens to the genes inserted by genetic engineers and the genes of viruses that insert DNA into their host's chromosomes, for example HIV. Of course, the gene-silencing system may respond to other alarms as wen. "Everybody believes that double-stranded RNA is a trigger," says Jorgensen. "But there may be triggers and triggers." Sometimes it is enough to insert a single extra copy of the CHS gene into petunias, if that copy makes lots of MRNA. Since genes make up only a small fraction of the genome, it is unlikely that a single inserted copy will land close enough to an existing gene to make antisense RNA, so perhaps cells also induce gene silencing if they are swamped by a particular MRNA, as would happen during successful viral infections. Whatever the other possibilities, doublestranded RNA causes a massive genesilencing response. Even a few doublestranded molecules per cell injected into nematode worms can silence perhaps thousands of copies of single-stranded mRNA from the nematode's own versions of the gene, Andrew Fire and his colleagues at the Camegie Institution of Washington showed in 1998 (Nature, vol 391, p 806). Somehow-in a way that no one understands yet-the nematode's cells are able to take up this RNA and trigger silencing.

Geneticists now use the technique to switch off particular genes at will to study their function. The same approach works for Drosophila and protozoa. In plants, too, gene silencing breaks the bounds of individual cells. It can spread from one part of a plant to another, and even from one plant to another through a graft. Botanists have speculated that the invaded cell might run off many short, single-stranded, antisense RNA copies using part of the double-stranded RNA as a template. These short RNAS, they reasoned, could act as a combination "Wanted" poster and death warrant, binding to any complementary MRNA in the cell-foreign or native-and marking it for destruction. By travelling through the pores that link plant cans, these warrants could spread silencing throughout the plant.

Puzzle pieces

In the past year, researchers working on fungi, plants and nematodes have each confirmed parts of this speculation. The first piece of the puzzle turned up last May in a study of bread mould with a mutation that disabled the gene-silencing process. When researchers at the University of Rome sequenced the mutant gene, they found it closely resembled a plant gene for an enzyme called RNA-dependent RNA polymerase (RdRP), which makes RNA copies from an RNA template (Nature, vol 399, p 166). This enzyme is exactly what's needed to run off the short antisense RNA death warrants predicted by the theory. The second piece turned up in October, when David Baulcombe and Andrew Hamilton of the John Innes Centre in Norwich showed that tobacco plants in the throes of PTGS really do produce short fragments of RNA, about 25 nucleotides long, which is complementary to MRNA from the gene being silenced (New Scientist, 6 November 1999, p 25). They also showed that the spread of FRGS through the plant parallels the spread of these fragments, which implies that the fragments are indeed the death warrants responsible for transmitting PTGS between cells. Also in October, Ronald Plasterk of the Netherlands Cancer Institute in Amsterdam supplied a third piece of the puzzle. Plasterk's team studied nematodes with defective PTGS and found that one of the mutations, in the MUTT gene, blocks the production of a protein that resembles an RNA-digesting enzyme (Cell, vol 99, p 133). Since the mutant nematodes are otherwise healthy, they don't appear to need this protein for the cell's run-of-the-mill housekeeping. This suggests that it is dedicated to digesting mRNAs during silencing. These puzzle pieces fit together nicely enough to suggest that the picture is more or less the same in different organisms. 'These phenomena look similar in plants, fungi and nematodes," says Baulcombe. 'Our working hypothesis is that they use similar mechanisms.' If so, this implies that PTGS is an ancient defence mechanism that arose many hundreds of millions of years ago in the common ancestor of all these groups. Gene silencing is so effective at crushing gene expression that every successful virus in an organism with silencing must have evolved some way to hide from it, escape from it or fight back. Many plant viruses, says Baulcombe, have chosen the third option. Several research groups, including Baulcombe's, have shown that a number of plant viruses produce proteins that suppress silencing. Exactly how the suppression works no one knows, but different viruses clearly target different parts of the system. Some viruses bring silencing to a halt throughout the plant, while others only block its spread to new leaves. Not surprisingly, some plants strike back. A group at the National University of Singapore has shown that a species of tobacco possesses an anti-anti-silencing mechanism. The plant's cells recognise the protein that cucumber mosaic virus uses to inhibit PTGS. They then commit suicide, depriving the virus of its host and stopping the infection before it spreads. Besides its effect on viruses, gene silencing also helps to keep transposons in check-especially in reproductive cells, where they can do the most damage. In nematode worms, for example, transposons are usually active in normal cells but silent in the cells that make eggs and sperm. But m many mutants with impaired silencing, the transposons become active in these cells as well, researchers at the University of Massachusetts reported in October (Cell, vol 99, p 123). Gene silencing has also proved useful in genetic engineering of crops. In fact, one silenced product-a canned tomato pure-e-has already reached the market. T'he pur6e is made from tomatoes genetically engineered by Zeneca to contain a short section of the gene for polygalacturonase, an enzyme which digests the cell walls in ripening fruit. This induces PTGS and silences the plant's own polygalacturonase gene, producing tomatoes that can stay on the vine longer, develop more flavour and eventually yield better purse. According to Wolfgang Schuch, a researcher at Zeneca's labs in Norwich, the company is now testing this technology in other crops. Schuch declines to say exactly what they hope to achieve, but there are obvious targets. Switch off the right genes, for example, and crop plants will no longer make toxins or allergens. Allergen-free peanuts must be on the biotech industry's wish fist. Then, of course, there are possibilities for creating new flower colours and patterns-although it turns out that this is old news. In 1838, a century and a haff before Jorgensen's experiment, breeders making crosses between petunia species created flowers with a star pattem of white stripes. By accidentally duplicating a CHS gene, and probably therefore overproducing CHS MRNA, they too had induced gene silencing.

A spanner in the works

If gene silencing really is an ancient Immune system, then our own ancestors must have had all the equipment to carry it out. But although plenty of researchers have looked, no one so far has demonstrated a clear-cut case of post-transcriptional gene silencing in humans or other vertebrates. it may be that we have lost the ability in favour of a more drastic response to the double-stranded RNA that so often gives viruses away. In mammalian cells, double-stranded RNA activates an enzyme called PKR, which shuts down the cell's protein synthesis machinery, slowing viral replication. Sometmes tt also Induces the cell to commit suicide, depriving the virus of its host. In addition, double-stranded RNA tuggers the prodticton of interferon, which among other functions Increases the production of PKR. This amplifies the effect of even a whiff of double-stranded RNA. The importance of PKR became even clearer last October, when Allan Lau and his colleagues at San Francisco General Hospital and the University of Califomia at San Francisco showed that Inhibiting PKR could tum a normally short-term infection into a chronic one (Proceedings of the National Academy of Sciences, vol 96, p 11 860). Deprived of PKR activity, cuftured human cells infected with a virus called EMCV fail to kill themselves, Instead releasing new virus parucies. Many viruses, including HIV and Influenza, produce proteins that inhibit PKR activity. Perhaps, says Randal Kaufman, an immunologist from the Howard Hughes Medical Institute and the University of Michigan, drugs that boost PKR function could help fight such diseases.

Stephen Day is a science writer in York

Stop the trials
NS 18 Mar 2000
Activists demand a rethink on gene therapy

While gene therapy researchers are still reeling from the unexplained death of 18-year-old Jesse Gelsinger last September during a clinical trial, critics of biotechnology are calling for an immediate moratorium on the use of some techniques. Jeremy Rifkin, an activist who sued the US National Institutes of Health in 1989 in an effort to stop the very first gene therapy trial, returned last week to accuse its Recombinant DNA Advisory Committee (RAC) of failing to protect patients. "You're just getting around to asking questions that you should have asked ten years ago,' he said. Rifkin formally asked the committee to request the Food and Drug Administration to halt all gene therapy trials using viruses, except those involving patients with life-threatening diseases for which there are no other treatments. Stewart Newman, a biologist from New York Medical College who represents the lobby group Council for Responsible Genetics, joined Rifkin in his call for a partial moratorium. "Science can go on under such tancesUseful data can be gathered," Newman says. George Annas, a prominent bioethicist at Boston University, also spoke last week of the need for a temporary moratorium to regain the public trust. However, Nancy King, a member of the RAC from the University of North Carolina, argues that although risks to patients must be minimised, "those risks can be addressed on a basis that allows for more flexibility than a moratorium". Other RAC members also see no need for a moratorium, but some institutions are voluntarily suspending gene therapy trials. Beth Israel Deaconess Medical Center in Boston, for example, has shut down a cancer trial and a haemophilia trial to review the safety data. And the University of South Florida recently shut down three gene therapy trials that used a lipid genecarrying system after another unexplained death during a similar trial last September at a different university. These voluntary efforts are being matched by a lightening of controls by the FDA. Last week, the agency announced that r-esearchers must now submit detailed plans explaining how they will monitor each trial's safety, and provide more evidence that their viral preparations are free from contamination. Hall Boyce, Washington DC

Early debut NS 18 Mar 2000

LAND plants made their big entrance on Earth some time during the Cambrian, tens of millions of years earlier than the fossil record had led scientists to believe. American researchers have found fossilised plant spores in rocks from the Grand Canyon and Tennessee dating back to between 510 and 500 million years ago. The oldest plant traces found before this were similar fossil spores from the middle Ordovician, 470 million yearn ago. The Cambrian spores cluster in groups of two or four, a rare feature found in primitive modern plants like the liverwort, says geologist Paul Strother of Boston College's Weston Observatory in Weston, Massachusetts. He presented the findings this week to a Geological Society of America meeting in New Brunswick, New Jersey. Strother's research shows that early plants were spreading in moist regions on the land at the same time that animal life-then still confined to water-was rapidly diversifying in the Cambrian explosion that produced virtually all major modern groups. Other palaeobotanists are intrigued. "The big question is what they are," says Patricia Gensel of the University of North Carolina in Chapel Hill. Genetic studies indicate that land plants evolved from green algae. Jeff Hecht

Smash hits
NS 18 Mar 2000
Did asteroids have a hand in evolution of life on Earth?

GLASS beads in soil from the Moon may help explain why there was an explosion in the number of species on Earth around 570 million years ago. Scientists in California say the beads hint that bombardment of the Moon and Earth by asteroids and comets stepped up around the time of the so-called Cambrian explosion, and might have spurred the rapid evolution of life. It's impossible to know how often asteroids and comets smashed into the Earth in prehistoric times because erosion and the shifting of the continents have erased most craters. 'The Earth is very fickle in terms of Preserving evidence of these impacts,' says Paul Renne of the University of Califomia at Berkeley. But the relative calm on the Moon has preserved craters for billions of years, and knowing lunar impact rates may indicate how often the Earth was hit. Scientists have estimated past impact rates on the Moon by counting craters in lava flows sampled during the Apollo missions and dated back on Earth. The findings suggest the rate has gradually decreased since the Moon formed. But Rerme's Berkeley colleague Richard Muller devised a more precise way to pin down the rate by dating tiny glass beads found in a soil sample returned by Apollo 14. The beads, roughly 200 micrometres across, formed when small impacts melted the soil. Lunar soil contains radioactive potassium, which decays to form gaseous argon-40. On melting, the gas would have escaped before the glass solidified. But any argon-40 produced afterwards would be trapped and accumulate in the beads, allowing the impact to be dated. A single soil sample also contains glass beads formed by impacts hundreds of miles apart, because 'lunar gardening" mixes the soil over huge areas. "The surface is continually being bombarded, ejecting material at high speed, and there's no atmosphere with friction to stop it flying over a very large area," says Renne. So the proportion of beads with different amounts of argon-40 gives a measure of how impact rates changed over time.

The results suggest that the number of impacts decreased over the past 3-5 billion years to a low point between 400 and 600 million years ago. But since then, they have increased nearly fourfold. "That was completely surprising," says Rene. It's possible that the rates increased because large asteroids in the Solar System collided and broke up over time, boosting the number of small objects hurtling around the Sun. The researchers say the impact rate on Earth would also have increased at that time-potentially coinciding with the Cambrian explosion. Biologists have speculated that asteroid impacts triggered ttus diversification by wiping out some animals and creating new ecological niches. Palaeobiologist Simon Conway Morris of Cambridge University says there's little evidence on Earth to back this speculation. "Nonetheless, this lunar link is intriguing. The Cambrian explosion is still a bit of an enigma." Astronomer David Hughes of the University of Sheffield argues that although small asteroids pockmark the Moon, they burn up in Earth's atmosphere. "The results are interesting, but you can't compare what they've been finding on the Moon with what we find on Earth." Hazel Muir

Source: Science (vol 287, p 1785)

Quantum Twister
Dragging light into a vortex
NS 18 Mar 2000

Leonhardt and Piwnicki have come up with a simple answer: instead of trying to capture light when it's going full tilt, they plan to slow it down. A lot. The speed of light is constant in a vacuum, but it changes when the light travels through another medium. In water, for instance, light goes at roughly three-quarters of its speed in empty space, slowing to 220 million kilometres per second. That's still pretty quick, but in the past year researchers have done much better: 8 metres per second in a vapour of rubidium atoms (New Scientist, 20 February 1999, p 10), and as slow as 50 centimetres per second-less than walking pace-in a special, ultracold state of matter known as a Bose-Einstein condensate. And as Leonhardt and Piwnicki have shown (Physical Review Letters, vol 84, p 822), when a light-slowing medium moves, it can pull the light along with it' Light facing a fast enough headwind will go backwards. "If the velocity of light is low compared with the velocity of the medium, then the motion of the medium is overwhelming," Leonhardt says. Blowing light around isn't quite the same as sucking it in. But Leonhardt and Piwnicki believe that if they created a swirling vortex in a medium like this, it would actually swallow light. C)n Earth, the nearest things we have to black holes are vortices. Tornadoes, for example, can suck up trees, roofs and trucks. Their power comes from the low pressure in the centre of the vortex. And according to Leonhardt and Piwnicki's calculations, a vortex should apply the same sort of inward force to light. If the vortex rotates much faster than the light can move, any ray that strays too close to its centre will get caught and dragged inexorably inwards (see Diagram). The light will eventually be absorbed by the gas. So just like a real black hole, the vortex has an event horizon beyond which escape is impossible. "This is a really exciting idea," says Lene Hau of the Rowland Institute for Science in Massachusetts and of Harvard University. Hau led the team that first slowed light down to a pedestrian pace in a Bose-Einstein condensate. Within a couple of months, she hopes to slow light down to just a centimetre per second. But condensates have a few drawbacks. To prevent light escaping, the material in a vortex must move much faster than the light within it. Even when light speed is just a centimetre per second, the vortex would only begin to suck in light when it moves at 2 metres per second. However, quantum vortices generally try to minimise their angular momentum by splitting into several slower vortices. So it would be difficult to create a single vortex that spins fast enough. "I'm already raising my eyebrows at two metres per second-that's quite a bit," Hau says.

Setting the trap

What's more, if you spin a condensate rapidly, all the gas is squeezed out , towards the edges, leaving a hollow core. With most gases, this "eye of the hurricane" would be wider than the event horizon, leaving no condensate at the centre to trap the light. Making black holes out of condensates begins to look difficult. An ordinary gas might work better. "If you use a classical gas, you can accelerate it to large velocities and create classical vortices," Leonhardt says. A spinning bath of rubidium atoms kept at about 100 'C might just do the trick, he believes. Researchers have already managed to slow light to 8 metres per second in this kind of system. To trap light travelling at this speed, you need a vortex spinning at more than 300 metres per second. That's pretty fast, but not impossible to achieve. Unfortunately, these high velocities present a problem of their own. Hau first has to prime her gas by firing in a laser beam of a precise frequency That puts the atoms into a special quantum state that allows the gas to slow light of another frequency. But because of the Doppler shift caused by a rapidly spinning vortex, atoms will see the laser beam's frequency rise and fall as they move back and forth. "If you start to get large Doppler shifts, you might move outside the right bandwidth," says Hau. The the priming wouldn't work. But Leonhardt isn't unduly concemed. If this does tum out to be a problem, he says, you could tune the laser so it worked just in the interesting region near the event horizon. Even if all these problems can be overcome, Matt Visser, a physicist at Washington University, St Louis, thinks that Leonhardt and Piwnicki's prototype will need some tweaking before it is accepted by the relativity community as a proper black hole. He says that they need to increase its sucking power by making the medium flow towards the centre, as well as around it."They've got the basic structure right, and it's relatively straightforward to modify this model so you do get a proper black hole," Visser says. Leonhardt disagrees with Visser's calculations, but admits that inward gas motion would help. In his simple spinning vorapproaching from one side of the u ie wind-is swallowed much than light approaching on the which gets whipped around faster by the swirling gas (see Diagram). It would be very hard to make such a vortex eat light on both sides. The solution may be as simple as pulling the plug. If gas is pumped out of the centre of the vortex, the rest of it will move towards the middle, dragging the light with it. You would be sucking up light with a vacuum cleaner. Whatever the eventual solution, Leonhardt believes that optical black holes are about five years of experimenting away. All those years of work will prove worthwhile if they help reveal the secrets of quantum gravity. The two greatest theories of the 20th century are quantum mechanics, which describes how particles interact with each other via electromagnetic and nuclear forces, and Einstein's general relativity, which describes how space is bent by matter and energy, and how that produces the force of gravity. Blending the two theories to create a quantum theory of gravity has proved a mathematical nightmare. Scientists need a theory of quantum gravity to describe the very beginning of the Universe, when matter was incredibly dense. But with the tenuous matter around us now, gravity is desperately weak on quantum scales. No one has devised a way to measure its effects. Leonhardt points out that in an optical black hole, light experiences a kind of gravitational field-and a very strong one. In an optical black hole, the swirling gas tells space how to bend, at least as far as a beam of light is concerned. "This could be used for making predictions in quantum gravity," Leonhardt suggests. Visser is also hopeful. "It gives you a realistic hope for experimentally testing at least part of the final theory of quantum gravity," he says. "That would be a vast improvement over the current situation." There is already one famous prediction in this field just waiting to be tested. Back in 1974, Stephen Hawking showed that black holes shine. According to quantum field theory, pairs of particles constantly pop into existence, recombine and disappear again. These "virtual" particles live on borrowed energy, and they can't exist for very long. But if the particle pair happens to be born just above the event horizon of a black hole, gravity can rip the pair apart. One of the particles falls into the hole while the other half gains some energy, allowing it to zoom off into the cosmos. Leonhardt compares the black hole to an amplifier, boosting vacuum noise into a real signal. No one has been able to confirm Hawking's prediction. The black holes we know about are too big to produce a measurable effect. A big hole has gentler gravitational forces at its event horizon than a small one, so it produces less radiation. Microscopic black holes would be bright enough, and they might have been produced in the early Universe, but none has yet been seen. An optical black hole should produce Hawking radiation of its own, as pairs of virtual photons are dragged apart by the flow. Leonhardt is now trying to work out whether it will be detectable or not. He says he is convinced that Hawking must be right, but it would be very satisfying to be able to prove it. "It would be very significant," agrees Visser, a specialist in relativity, black holes and quantum gravity. "Unless we're lucky and find a microscopic black hole left over from the big bang, the only way we're going to be able to test Hawking radiation is through something like this." This much could be done with an optical black hole made from classical gas. And if physicists succeed in making holes using condensates, another aspect of quantum gravity could be laid bare. In an optical black hole based on quantum flows, the effective curvature of space would be quantised too. No one knows exactly what this quantisation will do to gravity. C)ne way to measure it might be to see what Hawking radiation does to the vortices themselves-whether they dissipate, as real black holes are supposed to do. "We would be seeing something similar to the quantum structure of a gravitational object," says Leonhardt. Leonhardt is confident that his optical black holes could provide a new way of tackling the most crucial questions in physics. His device might darken the lab, but our view of the Universe could become a lot clearer. El

Michael Brooks is a science writer based in Sussex

Judging gene foods
NS 15 Apr 2000
An impartial panel could quell health and environmental fears

ARE genetically modified foods safe to eat? A grand forum of internationally renowned scientists and other experts might soon be helping the world decide. The forum would regularly provide govemments with an independent, state-ofthe-art consensus on what the latest science tells us, helping to resolve intemational divisions on GM food safety. The forum is the brainchild of John Krebs, the British scientist who chaired the Organization for Economic Cooperation and Development's recent summit conference in Edinburgh on the safety of GM foods. Krebs, who also chairs the British government's new Food Standards Agency, says that the GM foods forum could resemble the Intergovernmental Panel on Climate Change. The IPCC is a global coalition of scientists that meets regularly to review the scientific consensus on global warming. Consumer groups are sceptical, however.

Sue Mayer of the pressure group GeneWatch UK doubts that a committee of "grandees" would work in an area where most pressure has come from grassroots consumer campaigns. "It will be too distant from ordinary people, and could even make matters worse,' she says. Krebs included the proposal in his final report from the Edinburgh conference, pL,,blished last week and sent to governments of the world's eight most powerful nations. Ministers from these G8 countries will discuss this and Krebs's other proposals in July when they next meet, in Okinawa, Japan. Krebs says his proposed forum would not just include scientists but, crucially, other "stakeholders" whose views on the politics, economics, ethics and morals of biotechnology would feed into reports by the forum. He also believes that developing countries should be widely represented on the panel, given the enthusiasm for GM foods they expressed in Edinburgh. "The real push for GM is taking place in developing countries, particularly China, South America and Africa," he says. "It shouldn't be limited to a group of wealthy countries," agrees a spokesperson from the Panos Institute, a London-based think tank on Third World issues. Krebs's report also addresses some consumer issues, including a call for reassessment of "substantial equivalence", whereby regulators assume GM plants to be identical with their natural counterparts, apart from an inserted trait such as resistance to weedkillers or viruses. "We've been critical of [substantial equivalence] for some time," says Mayer. "We don't feel the system is set up to identify unexpected changes in food." Additionally, Krebs' report reflects unanimous feeling from Edinburgh that consumers must be told on labels when a product is genetically engineered, even ff it is identical to a rival product manufactured without GM technology. Mona Patel of Britain's Consumers'Association wonders how Krebs's forum will interact with other intemational food groups. For example, the UN's Codex Abmentarius Commission, which sets intemational food standards, is already looking into sudi issues as labelling and substantial equivalence. Meanwhile, a report published last week by the US National Research Council calls for a tightening up of US regulations on GM plants and improvements in the methods by which their toxicity and allergenicity is tested. But it cautiously pronounces GM foods safe, given the lack of adverse data so far. Andy Coghlan

Quantum Nation Quantum Computing in Biology. 2000
NS 15 Apr 2000
'The idea may not be so ludicrous: quantum physics is not foreign to biology'

Received wisdom is that quantum physics, aside from a few minor details, has nothing to do with biology. Sure, it underlies the chemistry of all molecules, including biological ones, but the quan tum weirdness is kept well out of sight. Even physicists have reason to be scom fulFor 15 years, they have struggled to build a quantum computer, a device that could exploit the peculiar properties of the quantum world to do calculations with a style and speed to put any ordi nary computer to shame. Physicists gen erally concede that the task is so formi dable that a practical quantum computer won't exist for decades. So Patel's proposal, which he unveiled in an electronic preprint in February ( 0002037), is a radical one by anyone's stan dards. The forces of evolution, he claims, may have solved the problem of quantum computing several billion years ago. It's a startling idea-but if true, it could explain a puzzle at the core of biology. Biologists have known for half a cen tury that the sequence of bases along each str.lnd of DNA encodes biological recipes for making proteins, Each base is one of four possible kinds - cytosine (C), guanine (G), adenine (A) and thymine (T). So there is a fundamental difference between the four-letter code of DNA and the strings of Os and ls in any computer, where there are only two altematives. This is where the mystery begins: why four rather than ust two? A binary code ought to be better. Mod em computers use only two characters so they can store information using very sim ple components. To store a 0 or 1, the tran sistors inside a microchip only need two states, "on" and 11 off". More characters in the code would demand more compli cated and costly devices. Binary logic also cuts down on mis takes. Imagine walking to a distant hilltop and then trying to transmit a message back to a friend. You might carry 26 flags, one for each letter, and try to spell out messages that way. But on a breezy day an E might look like an F, and a P like an R. You'd be better off using just two flags, one black, one white, and expressing let ters as strings of the two. Then your friend would face nothing but simple black white decisions, and you could be more confident in your communications When it comes to handling information, com puter scientists agree that binary is best. So why doesn't biology use it? Several billion years ago, when the first self-replicating molecules were evolving, this simplest of all codes ought to have been the first to arise, and should have defeated other, more error-prone codes in the evolutionary race. Or might there be something mysteriously efficient about the number 4? Patel thinks there is. To see why, we need to think in terms of computation. "Computation is nothing but the processing of information," he says, "so we can study what DNA does from the viewpoint of computer science." A biological computation happens every time a cell divides: the data stored in one set of DNA molecules gets copied into another set. In a stretch of doublestranded DNA, bonds link the bases along one strand to those on the other, with every C bound to a complementary G, and every A to a T. just before cell division, enzymes unzip the strands, exposing the bases to the cell's intemal soup of raw materials. Another enzyme known as a DNA polymerase then marches along each of the two strands, triggering each base to pair up with a complementary base from the soup. Step by step, the polymerase copies the genetic information and creates two new double-stranded DNA molecules identical to the oi&nal. But there's more to this than the simple copying of data. As Patel sees it, the soup of bases is like a disorganised database containing four kinds of entry. The polymerase's task is to find an entry of one particular kind. As the polymerase repeatedly searches for the right base in the alphabet soup, it is doing computations. And here lies the nub of Patel's idea: we would expect the polymerase to search in the best way possible. So what is the best of all possible ways to search a database? In conventional computing, the best you can do is trial and error. To search for one kind of object in a jumble of N different kinds, @ou try one after another until you get lucky. This way you will find the right thing after an average of N attempts. For instance, it takes four tries on average to find a heart by cutting a shuffled pack of cards. This is just like the soup of bases, which would get shuffled by thermal motions after each attempt. So molecular biologists assume that DNA polymerase works in the same way.

Every so often, a base of some random kind wanders past the polymerase. It becomes attached to the growing chain if it happens to be the correct base, and wanders off again if it isn't. In that case, a polymerase would need to test an average of four bases before finding the right one. Normally, this is the best that can possibly be done. But, says Patel, it is possible to do better by exploiting one of the weirder consequences of quantum mechanics. In an ordinary computer, a transistor can be either on or off, so a bit is always either 1 or 0. An alternative is to exploit quantum physics, and to store information using single quantum particles such as electrons. One might store bits in an electron's spin, for example, which can be either "up" or "down". The key is that the quantum world also allows other seemingly nonsensical possibilities: an electron's spin can be either up nor down, but a superposition of both but in @r tion both So a string of electrons can hold on to not jus one distinct string of Os and ls, but every conceivable string all at once. As a consequence, a computer handling information in quantum fashion could do parallel processing on an outrageous scale, testing many possibilities at the same time. In 1997 mathematician Lov Grover of the IBM Research Division showed that a quantum computer can search a database far faster than any classical device. It starts with a superposition of all the different items in a database, and alters this quantum state to amplify the desired item and make the others fade away. For a huge database, the time savings are huge, and even for smaller values of N the quantum procedure is faster. Coincidentally, Patel and Grover were graduate students together at Caltech in the early 1980s. "We met again last year," says Grover, "through a mutual interest in quantum computing." To Patel, Grover's algorithm suggested an intriguing question: might biochemistry pull off a quantum computation? Grover's mathematics gives an exact formula for the number of quantum attempts, Q, needed to find one specific element in a database of N things. It tums out that if N = 4, then Q = 1. In other words, a quantum computer can distinguish between four distinct possibilities with just one attempt.

Of course, it would also take a single quantum step to distinguish between two possibilities. But with a four-base code, DNA only needs to be half the length. So biology might have decided to use four bases instead of two so that replication of the molecule can happen twice as quickly. For Patel's idea to work, the DNA polymerase would have to be able to manipulate the biochemical soup around it, watching over the base-pair bonding process to ensure that it occurs in a coherent, quantum-mechanical way. Each time the enzyme moves to a new base on the strand of DNA it is copying, it sets up a quantum superposition of the four bases that lie somewhere in its vicinity, with one ghostly component corresponding to each. According to quantum theory, such ghosts act like independent waves that move towards the exposed base on the DNA strand. Next, Patel believes, the superposition of the four "incoming" waves starts to interact with the exposed base. This should alter the four waves in different ways, he says, making them interfere with one another in such a way that the ghosts for each incorrect base cancel out, while those for the correct base reinforce. At this point, the C-G-A-T superposition collapses, leaving the correct base bound to the DNA chain with a hydrogen bond. In other words, the enzyme should act hke a sort of waveguide, ushering the component wave for the correct base into its proper resting place, while rejecting the others-carrying out Grover's quantum search in the process. "The quantum search scheme he shows is very nice," says Grover, "although a few of the details are somewhat speculative. If true, it is another instance where nature first figured out how to do things better than us." Perhaps the biggest "if" is whether the noisy environment within the cell would permit all this quantum business. The greatest obstacle to building a quantum computer in the lab is the need to isolate aH its working parts from extemal disturbances, as almost any interference will destroy the fragile quantum dynamics. In all their attempts so far, physicists have tried to do this by cooling their apparatus down to near absolute zero. At the temperature inside a living cell, the enzyme and the four bases ought to suffer an annihilating storm of abuse, which should wipe out any possibility of quantum behaviour. So DNA polymerase would somehow have to protect the environment around the growing DNA strand, permitting the quantum computation to go forward undisturbed. Patel points out that the configuration of electrons around atomic nuclei helps to shield some nuclear properties from their environment. Nuclear spins remain in quantum superpositions for several seconds. He suggests that something similar happens in biochemistry No one knows whether DNA polymerases really have all these properties, and yet the idea may not be so ludicrous: quantum physics is not as foreign to biology as one might think. In photosynthesis, biology exploits quantum possibilities at a scale above that of single molecules. When a photon is absorbed by a photosynthesising cell, its energy excites an electron into a delocalised state spread out over tens of molecules. Patel's proposal is more radical, in that it involves quantum superpositions of whole molecules. The more massive the object, the less obvious its quantum nature should be: lightweight electrons flaunt their quantum properties, while whole molecules are usually more coy. But some researchers have begun to suspect that all enzymes may depend on a quantum process involving protons-still 150 times lighter than bases, but 2000 times heavier than electrons. Last year, [email protected] Judith Klinsman and colleagues from the University of Califomia at Berkeley demonstrated that to speed up crucial cellular chemical reactions, some bacterial enzymes rely on the tunnelling of protons-a quantum process that allows a particle to pass through a barrier even if it hasn't got enough energy to climb over. VVhat's more, they manage the feat even at room temperature. Finding out whether DNA polymerases perform even more daring quantum tricks will require careful experiments. In the meantime, Patel is trying to see where else the quantum connection leads. Every protein in the human body is a string made from 20 different kinds of amino acid. Why 20? Here again, Patel thinks, the signs point to quantum computing.

To set the stage for the making of proteins, a strand of messenger RNA copies the genetic information from DNA and carries it out to a ribosome, one of the cell's protein manufacturing plants. The ribosome steps along the messenger RNA, and to each set of three base pairs attaches a TRNA, a stringy molecule with three base pairs at one end and an amino acid at the other. Once again, the ribosome faces a search: to build the right protein, it has to repeatedly find a TRNA corresponding to just one of the 20 kinds of amino acid in the soup. The number 20 would seem to have little connection to anything. Patel points out, however, that this is just the right number to set up another super-efficient quantum search: for according to Grover's algorithm, a three-step quantum search can find an object in a database containing up to 20 kinds of entry. Like the number of bases, then, the number of amino acids seems to be just right if biology has set things up so that the protein manufacturing process is, in a quantum sense, as efficient as it can be. "The numbers are certainly very provocative," says Grover. As Patel puts it, 'This is the first time they have come out of an algorithm that performs the actual task accomplished by DNA." But do these numbers really point to quantum computers at the heart of life? Evolutionary biologists are not convinced. "This field is rife with premature speculation," says Laurence Hurst of the University of Bath. "The history of the 20 amino acids problem has seen some of the most ingenious explanations, which at first looked even better than this one." They were all shot down in flames, he adds, when the biochemistry of the code was finally unravelled. With regard to the number of amino acids, Hurst points to one specific issue that Patel concedes is rather troubling: that the correspondence between tRNAs and amino acids isn't one-to-one. "There may be 20 amino acids," says Hurst, "but the same amino acid can get put onto different tRNAs, and the TRNA does the interacting. So it seems to me that there are more than 20 types to be found." Even if Patel's idea won't stretch this far, it may still explain why there are four bases in the basic structure of DNA. "Apoorva generates a lot of ideas," says Grover, "and I think irrespective of how the biological and chemical aspects tum out, this one will make an impact." And after all, why wouldn't evolution exploit any quantum avenues open to it? If the cell spums quantum tricks, wouldn't that need some [email protected] of its own? Fl

Mark Buchanan writes about physics and other tields from the village of Notre Dame de Courson in northern France. He can be contacted at [email protected]

Further reading: "Enzyme dynamics and hydrogen tunnelling in a thermophilic alcohol dehydrogenase," by Amnon Kohen and others, Nature, vol 399, p 496 (1999) "How nature harvests sunlight," by Xiche Hu and Klaus Schulten, Physics Today, August 1997, p 28