Digest Of The. Economist. 2006(4-5)Hot to trotA new service hopes to do for texting what Skype did for voice callsTALK is cheap—particularly since the appearance of voice-over-internet services such as Skype. Such services, which make possible very cheap (or even free) calls by routing part or all of each call over the internet, have forced traditional telecoms firms to cut their prices. And now the same thing could be about to happen to mobilephone text messages, following the launch this week of Hotxt, a British start-up.Users download the Hotxt software to their handsets, just as they would a game or a ringtone. They choose a user name, and can then exchange as many messages as they like with other Hotxt users for £1 ($1.75) per week. The messages are sent as data packets across the internet, rather than being routed through operators' textmessaging infrastructure. As a result, users pay only a tiny data-transport charge, typically of a penny or so per message. Since text messages typically cost 10p, this is a big saving—particularly for the cost-conscious teenagers at whom the service is aimed.Most teenagers in Britain, and elsewhere in Europe, pay for their mobile phones on a “pre-paid” basis, rather than having a monthly contract with a regular bill. Pre-paid tariffs are far more expensive: bundles of free texts and other special deals, which can reduce the cost of text messaging, are generally not available. For a teenager who sends seven messages a day, Hotxt can cut the cost of texting by 75%, saving £210 per year, says Doug Richard, the firm's co-founder. For really intensive text-messagers, the savings could be even bigger: Josh Dhaliwal of mobileYouth, a market-research firm, says that some teenagers—chiefly boys aged 15-16 and girls aged 14-15—are “supertexters” who send as many as 50 messages per day.While this sounds like good news for users, it could prove painful for mobile operators. Text-messaging accounts for around 20% of a typical operator's revenues. With margins on text messages in excess of 90%, texting also accounts for nearly half of an operator's profits. Mr Richard is confident that there is no legal way that operators can block his service; they could raisedata-transport costs, but that would undermine their own efforts to push new services. Hotxt plans to launch in other countries soon.“The challenge is getting that initial momentum,” says Mr Dhaliwal. Hotxt needs to persuade people to sign up, so that they will persuade their friends to sign up, and so on. Unlike Skype, Hotxt is not free, so users may be less inclined to give it a try. But as Skype has also shown, once a disruptive, low-cost communications service starts to spread, it can quickly become very big indeed. And that in turn can lead to lower prices, not just for its users, but for everyone.A discerning viewA new way of processing X-rays gives much clearer imagesX-RAYS are the mysterious phenomenon for which Wilhelm Röntgen was awarded the first Nobel prize in physics, in 1901. Since then, they have shed their mystery and found widespread use in medicine and industry, where they are used to revealthe inner properties of solid bodies.Some properties, however, are more easily discerned than others. Conventional Xray imaging relies on the fact that different materials absorb the radiation to different degrees. In a medical context, for example, bones absorb X-rays readily, and so show up white on an X-radiograph, which is a photographic negative. But Xrays are less good at discriminating between different forms of soft tissue, such as muscles, tendons, fat and blood vessels. That, however, could soon change. For Franz Pfeiffer of the Paul Scherrer Institute in Villigen, Switzerland, and his colleagues report, in the April edition of Nature Physics, that they have manipulated standard X-ray imaging techniques to show many more details of the inner body.The trick needed to discern this fine detail, according to Dr Pfeiffer, is a simple one. The researchers took advantage not only of how tissues absorb X-rays but also of how much they slow their passage. This slowing can be seen as changes in the phase of the radiation that emerges—in other words of the relative positions of the peaks and troughs of the waves of which X-rays are composed.Subtle changes in phase are easily picked up, so doctors can detect even small variations in the composition of the tissue under investigation, such as might be caused by the early stages of breast cancer. Indeed, this trick—known as phase-contrast imaging—is already used routinely in optical microscopy and transmission electron microscopy. Until now, however, no one had thought to use it for medical X-radiography.To perform their trick, the researchers used a series of three devices called transmission gratings. They placed one between thesource of the X-rays and the body under examination, and two between the body and the X-ray detector that forms the image. The first grating gathers information on the phases of the X-rays passing through it. The second and third work together to produce the detailed phase-contrasted image. The approach generates two separate images—the classic X-ray image and the phase-contrasted image—which can then be combined to produce a high-resolution picture.The researchers tested their technique on a Cardinal tetra, a tiny iridescent fish commonly found in fish tanks and aquariums. The conventional X-ray image showed the bones and the gut of the fish, while the phase-contrasted image showed details of the fins, the ear and the eye.Dr Pfeiffer's technique would thus appear to offer a way to get much greater detail for the same amount of radiation exposure. Moreover, since it uses standard hospital equipment, it should be easy to introduce into medical practice. X-rays may no l onger be the stuff of Nobel prizes, but their usefulness may just have increased significantly.Here be dragonsWith luck, you may soon be able to buy a mythological petPAOLO FRIL, chairman and chief scientific officer of GeneDupe, based in San Melito, California, is a man with a dream. That dream is a dragon in every home.GeneDupe's business is biotech pets. Not for Dr Fril, though, the mundane cloning of dead moggies and pooches. He plans a range of entirely new animals—or, rather, of really quite old animals, with the twist that even when they did exist, it was only in the imagination.Making a mythical creature real is not easy. But GeneDupe's team of biologists and computer scientists reckon they are equal to the task. Their secret is a new field, which they call “virtual cell biology”.Biology and computing have a lot in common, since both are about processing information—in one case electronic; in the other, biochemical. Virtual cell biology aspires to make a software model of a cell that is accurate in every biochemical detail. That is possible because all animal cells use the same parts list—mitochondria for energy processing, the endoplasmic reticulum for making proteins, Golgi body for protein assembly, and so on.Armed with their virtual cell, GeneDupe's scientists can customise the result so that it belongs to a particular species, by loading it with a virtual copy of that animal's genome. Then, if the cell is also loaded with the right virtual molecules, it will behave like a fertilised egg, and start dividing and developing—first into an embryo, and ultimately into an adult.Because this “growth” is going on in a computer, it happens fast. Passing from egg to adult in one of GeneDupe's enormous Mythmaker computers takes less than a minute. And it is here that Charles Darwin gets a look in. With such a short generation time, GeneDupe's scientists can add a little evolution to their products.Each computer starts with a search image (dragon, unicorn, gryphon, etc), and the genome of the real animal most closely resembling it (a lizard for the dragon, a horse for the unicorn and, most taxingly, the spliced genomes of a lion and an eagle for the gryphon). The virtual genomes of these real animals are then tweaked by random electronic mutations. When they have matured, the virtual adults most closely resembling the targets are picked and cross-bred, while the others are culled.Using this rapid evolutionary process, GeneDupe's scientists have arrived at genomes for a range of mythological creatures—in a computer, at least. The next stage, on which they are just embarking, is to do it for real.This involves synthesising, with actual DNA, the genetic material that the computer models predict will produce the mythical creatures. The synthetic DNA is then inserted into a cell that has had its natural nucleus removed. The result, Dr Fril and his commercial backers hope, will be a real live dragon, unicorn or what have you.Tales of the unexpectedWhy a drug trial went so badly wrongIN ANY sort of test, not least a drugs trial, one should expect the unexpected. Even so, on March 13th, six volunteers taking part in a small clinical trial of a treatment known as TGN1412 got far more than they bargained for. All ended up seriously ill, with multiple organ failure, soon after being injected with the drug at a special testing unit at Northwick Park Hospital in London, run by a company called Parexel. One man remains ill in hospital.Small, preliminary trials of this sort are intended to find out whether a drug is toxic. Nevertheless, the mishap was so seri ous that Britain's Medic ines and Healthcare products Regulatory Agency (MHRA), a government body, swiftly launched a full inquiry.On April 5th it announced its preliminary findings. These were that the trial was run correctly, doses of the drug were given as they were supposed to have been, and there was no contamination during manufacturing. In other words, it seems that despite extensive tests on animals and human-cell cultures, and despite the fact that the doses in the human trial were only a five-hundredth of those given to the animals, TGN1412 is toxic in people in a way that simply had not shown up.This is a difficult result for the drug business because it raises questions about the right way of testing medicines of this kind. TGN1412 is unusual in that it is an antibody. Most drugs are what are known as “small molecules”. Antibodies are big, powerful proteins that are the workhorses of the immune system. A mere 20 of them have been approved for human therapy, or are in latestage clinical trails, in America and Europe, but hundreds are in pre-clinical development, and will soon need to be tried out on people.Most antibody drugs are designed to work in one of three ways: by recruiting parts of the immune system to kill cancer cells; by delivering a small-molecule drug or a radioactive atom specifically to a cancer; or by blocking unwanted immune responses. In that sense, TGN1412 was unusual because it worked in a fourth way. It is what is called a “superagonistic” antibody, designed to increase the numbers of a type of immune cell known as regulatory T-cells.Reduced numbers, or impaired function, of regulatory T-cells has been implicated in a number of illnesses, such as type 1 diabetes, multiple sclerosis and rheumatoid arthritis. Boosting the pool of these antibodies seemed like a good treatment strategy. Unfortunately, that strategy fell disastrously to pieces and it will take a little longer to find out why.The result highlights concerns raised in a paper just published by the Academy of Medical Sciences, a group of experts based in London. It says there are special risks associated with novel antibody therapies. For example, their chemical specificity means that they might not bind to their targets in humans as they do in other species.Accidence and substanceTwo possible explanations for the bulk of realityTHE unknown pervades the universe. That which people can see, with the aid of various sorts of telescope, accounts for just 4% of the total mass. The rest, however, must exist. Without it, galaxies would not survive and the universe would not be gently expanding, as witnessed by astronomers. What exactly constitutes this dark matter and dark energy remains mysterious, but physicists have recently uncovered some more clues, about the former, at least.One possible explanation for dark matter is a group of subatomic particles called neutrinos. These objects are so difficult to catch that a screen made of lead a light-year thick would stop only half the neutrinos beamed at it from getting through. Yet neutrinos are thought to be the most abundant particles in the universe. Some ten thousand trillion trillion—most of them produced by nuclear reactions in the sun—reach Earth every second. All but a handful pass straight through the planet as if it wasn't there.According to the Standard Model, the most successful description of particle physics to date, neutrinos come in three varieties, called “flavours”. These are known as electron neutrinos, tau neutrinos and muon neutrinos. Again, according to the Standard Model, they are point-like, electrically neutral and massless. But in recent years, this view has been challenged, as physicists realised that neutrinos might have mass.The first strong evidence came in 1998, when researchers at an experiment called SuperKamiokande, based at Kamioka, in Japan, showed that muon neutrinos produced by cosmic rays hitting the upper atmosphere had gone missing by the time they should have reached an underground detector. SuperKamiokande's operators suspect that the missing muon neutrinos had changed flavour, becoming electron neutrinos or—more likely—tau neutrinos. Theory suggests that this process, called oscillation, can happen only if neutrinos have mass.Since then, there have been other reports of oscillation. Results from the Sudbury Neutrino Observatory in Canada suggest that electron neutrinos produced by nuclear reactions in the sun change into either muon or tau neutrinos on their journey to Earth. Two other Japanese experiments, one conducted at Kamioka and one involving the KEK partic le-accelerator laboratory in Tsukuba, near Tokyo, also hint at oscillation.Last week, researchers working on the MINOS experiment at Fermilab, near Chicago, confirmed these results. Over the coming months and years, they hope to produce the most accurate measurements yet. The researchers created a beam of muon neutrinos by firing an intense stream of protons into a block of carbon. On the other side of the target sat a particle detector that monitored the number of muon neutrinos leaving the Fermilab site. The neutrinos then traveled 750km (450 miles) through the Earth to a detector in a former iron mine in Soudan, Minnesota.Myths and migrationDo immigrants really hurt American workers' wages?EVERY now and again America, a nation largely made up of immigrants and their descendants, is gripped by a furious political row over whether and how it should stem the flood of people wanting to enter the country. It is in the midst of just such a quarrel now. Congress is contemplating the erection of a wall along stretches of the Mexican border and a crackdown on illegal workers, as well as softer policies such as a guest-worker programme for illegal immigrants. Some of the arguments are plain silly. Immigration's defenders claim that foreigners come to do jobs that Americans won't—as if cities with few immigrants had no gardeners. Its opponents say that immigrants steal American jobs—succumbing to the fallacy that there are only a fixed number of jobs to go around.One common argument, though not silly, is often overstated: that immigration pushes down American workers' wages, especially among high-school dropouts. It isn't hard to see why this might be. Over the past 25 years American incomes have become less equally distributed, typical wages have grown surprisingly slowly for such a healthy economy and the real wages of the least skilled have actually fallen. It is plausible that immigration is at least partly to blame, especially because recent arrivals have disproportionately poor skills. In the 2000 census immigrants made up 13% of America's pool of workers, but 28% of those without a high-school education and over half of those with eight years' schooling or less.In fact, the relationship between immigration and wages is not clear-cut, even in theory. That is because wages depend on the supply of capital as well as labour. Alone, an influx of immigrants raises the supply of workers and hence reduces wages. But cheaper labour increases the potential return to employers of building new factories or opening new valet-parking companies. In so doing, they create extra demand for workers. Once capital has fully adjusted, the final impact on overall wages should be a wash, as long as the immigrants have not changed the productivity of the workforce as a whole.However, even if wages do not change on average, immigration can still shift the relative pay of workers of different types. A large inflow of low-skilled people could push down the relative wages of low-skilled natives, assuming that they compete for the same jobs. On the other hand, if the immigrants had complementary skills, natives would be relatively better off. To gauge the full effect of immigration on wages, therefore, you need to know how quickly capital adjusts and how far the newcomers are substitutes for local workers.Roaming holidayThe EU hopes to slash the price of cross-border mobile calls“TODAY it is only when using your mobile phone abroad that you realise there are still borders in Europe,” lamented Viviane Reding, the European commissioner responsible for telecoms and media regulation, as she announced plans to slash the cost of mobile roaming last month. It is a laudable aim: European consumers typically pay €1.25 ($1.50) per minute to call home from another European country, and €1 per minute to receive calls from home while abroad. With roaming margins above 90%, European mobile operators make profits of around €10 billion a year from the trade, the commission estimates.Ms Reding's plan, unveiled on March 28th and up for discussion until May 12th, is to impose a “home pricing” scheme. Even while roaming, callers would be charged whatever they would normally pay to use their phones in their home countries; charges for incoming calls while roaming would be abolished. That may sound good. But, as the industry is understandably at pains to point out, it could have some curious knock-on effects.In particular, consumers could sign up with operators in foreign countries to take advantage of lower prices. Everyone would take out subscriptions to the cheapest supplier and bring them back home, says John Tysoe of the Mobile World, a consultancy. “You'd end up with a complete muddle. An operator might have a network, bu t no customers, because they've all migrated.”Another problem with Ms Reding's plan, he says, is that operators would compensate for the loss of roaming fees— thought to account for around 3% of their revenues and 5% of profits—by raising prices elsewhere. This would have the perverse effect of lowering prices for international business travellers, a big chunk of roaming traffic, while raising prices for most consumers.The commission's proposals are “economically incoherent”, says Richard Feasey of Vodafo ne, which operates mobile networks in many European countries. Imposing price caps on roaming is legally questionable, he says, and Vodafone has, in any case, been steadily reducing its roaming charges. (European regulators prevented it from doing so for three years on antitrust grounds after its takeover of Mannesmann in 2000.) Orange, another multinational operator, says it is planning to make price cuts,too. “Of course, now everybody's got price cuts,” says Stefano Nicoletti of Ovum, a consultancy.But perhaps Ms Reding's unspoken plan is to use the threat of regulation as a way to prompt action. Operators are right that her proposals make no sense, but they are charging too much all the same. So expect them to lobby hard against the proposals over the next couple of years, while quietly cutting their prices—an outcome that would, of course, allow both sides to claim victory.Devices and their desiresEngineers and chemists get togetherTHERE used to be a world of difference between treating a patient with a device—such as a fake hip or a pacemaker—and using biology and biochemistry. Different ailments required wholly different treatments, often with little in common. But that is changing as medical advances—such as those being trumpeted at the biotechnology industry's annual gathering this week in Chicago—foster combinations of surgical implants and other hardware with support from medicines. Drug-releasing stents were one of the first fruits of this trend, which increasingly requires vastly different sorts of health-care firms to mesh their research efforts.That will be a challenge. While pharmaceutical and biotech firms are always in search of the next big thing, devicemakers prefer gradual progress. Instead of hanging out with breathless entrepreneurs near America's east and west coasts, where most drug and biotechnology firms are based, many of the device-makers huddle in midwestern cities such as Minneapolis, Indianapolis and Kalamazoo. And unlike Big Pharma, which uses marketing blitzes to tell ailing consumers about its new drugs, medical-device sales teams act more as instructors, showing doctors how to install their latest creations.Several companies, however, are now trying to bring these two business cultures together. Earlier this year, for example, Angiotech Pharmaceuticals, a Canadian firm, bought American Medical Instruments (AMI). Angiotech's managers reckon their company has devised a good way to apply drug coatings to all sorts of medical paraphernalia, from sutures and syringes to catheters, in order to reduce the shock to the body. AMI makes just the sorts of medical supplies to which Angiotech hopes to apply its techniques.One of America's biggest makers of medical devices, Medtronic, has been doing joint research with Genzyme, a biotechnology company that is also keen on broader approaches to health care. Genzyme says that it was looking for better ways to treat ailments, such as coronary and kidney disease, and realised that it needed to understand better how electro-mechanical devices and information technology work. But combining its efforts with those of Medtronic “on a cultural level is very hard”, the company says. Biotechnology firms are used to much more risky projects and far longer development cycles.Another difference is that device-makers know that if a problem emerges with their hardware, the engineers will tinker around and try to resolve the glitch. Biotech and pharmaceutical firms have no such option. If a difficulty emerges after years of developing and testing a new pill, as with Merck's Vioxx, there may be little they can do about it. “You can't futz with a molecule”, says Debbie Wang, a health-care industry analyst.Strangely, says Ms Wang, some of the most promising engineering outfits were once divisions of pharmaceutical andhealth-care companies, which got rid of them precisely because they did not appear to offer the rapid growth that managers saw in prescription drugs. Guidant, a maker of various cardiovascular devices, was spun off by Eli Lilly in 1994 and a decade later became the prize in a bidding war between Johnson & Johnson and Boston Scientific, which Boston won earlier this year.Pfizer sold Howmedica, which makes joint replacements and prosthetics, to Kalamazoo-based Stryker in 1998. Anotherjoint-replacement maker, Zimmer, was spun off from Bristol-Myers Squibb in 2001. Now both those companies are looking for ways to add “anti-interactive coatings”—ie, drugs—to their business. One of the most troublesome complications in joint replacement is infection.The big drug companies might be tempted to reacquire the firms that they let go. But, given the potential for cultural and strategic clashes, it may make more sense for a few big and broad medical-device makers, such as Medtronic, Boston Scientific and St Jude Medical, to continue consolidating their own industry while co-operating, along the lines of the Medtronic-Genzyme venture, with biotech and pharmaceutical firms as they see fit. There would still be irritation; but probably less risk of wholesale rejection.Eat less, live moreHow to live longer—maybeDIETING, according to an old joke, may not actually make you live longer, but it sure feels that way. Nevertheless, evidence has been accumulating since the 1930s that calorie restriction—reducing an animal's energy intake below its energy expenditure—extends lifespan and delays the onset of age-related diseases in rats, dogs, fish and monkeys. Such results have inspired thousands of people to put up with constant hunger in the hope of living longer, healthier lives. They have also led to a search for drugs that mimic the effects of calorie restriction without the pain of going on an actual diet.Amid the hype, it is easy to forget that no one has until now shown that calorie restriction works in humans. That omission, however, changed this month, with the publication of the initial results of the first systematic investigation into the matter. This study, known as CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), was sponsored by America's National Institutes of Health. It took 48 men and women aged between 25 and 50 and assigned them randomly to either a control group or a calorie-restriction regime. Those in the second group were required to cut their calorie intake for six months to 75% of that needed to maintain their weight.The CALERIE study is a landmark in the history of the field, because its subjects were either of normal weight or only slightly overweight. Previous projects have used individuals who were clinically obese, thus confusing the unquestionable benefits to health of reducing obesity with the possible advantages of calorie restriction to the otherwise healthy.At a molecular level, CALERIE suggests these advantages are real. For example, those on restricted diets had lower insulin resistance (high resistance is a risk factor for type 2 diabetes) and lower levels of low-density lipoprotein cholesterol (high levels are a risk factor for heart disease). They showed drops in body temperature and blood-insulin levels—both phenomena that have been seen in long-lived, calorie-restricted animals. They also suffered less oxidative damage to their DNA.Eric Ravussin, of Louisiana State University in Baton Rouge, who is one of the study's authors, says that such results provide support for the theory that calorie restriction produces a metabolic adaptation over and above that which would be expected from weight loss alone. (He also points out that it will be a long time before such work reveals whether calorie restriction actually extends life.) Nevertheless, such metabolic adaptation could be the reason why calorie restriction is associated with longer lifespans in other animals—and that is certainly the hope of those who, for the past 15 years, have been searching for ways of triggering that metabolic adaptation by means other than semi-starvation.The search for a drug that will stave off old age is itself as old as the hills—as is the wishful thinking of the suckers who finance such efforts. Those who hope to find it by mimicking the effect of calorie restriction are not, however, complete snake-oil salesmen, for there is known to be a family of enzymes called sirtuins, which act both as sensors of nutrient availability and as regulators of metabolic rate. These might provide the necessary biochemical link between starving and living longer.Universal service?Proponents of “software as a service” say it will wipe out traditional softwareSOMETHING momentous is happening in the software business. Bill Gates of Mi crosoft calls it “the next sea change”. Analysts call it a “tectonic shift” in the industry. Trade publications hail it as “the next big thing”. It is software-as-a-service (SaaS)—the delivery of software as an internet-based service via a web browser, rather than as a product that must be purchased, installed and maintained. The appeal is obvious: SaaS is quicker, easier and cheaper to deploy than traditional software, which means technology budgets can be focused on providing competitive advantage, rather than maintenance.This has prompted an outbreak of iconoclasm. “Traditional software is dead,” says Jason Maynard, an analyst at Credit Suisse. Just as most firms do not own generators, but buy electricity from the grid, so in future they will buy software on the hoof, he says. “It's the end of software as we know it. All software is becoming a service,” declares Marc Benioff of , thebest-known proponent of the idea. But while SaaS is growing fast, it still represents only a tiny fraction of the overall software industry—a mere $3.35 billion last year, estimates Mr Maynard. Most observers expect it to be worth around $12 billion by 2010—but even that is equal only to Microsoft's quarterly sales today. There is no denying that SaaS is coming. But there is much debate, even among its advocates, about how quickly it will grow, and how widely it will be adopted.At the moment, small and medium-sized businesses are the most enthusiastic adopters of SaaS, since it is cheaper and simpler than maintaining rooms of server computers and employing staff to keep them running. Unlike the market for desktop software,。
