Digest Of The. Economist. 2006(6-7)Hard to digestA wealth of genetic information is to be found in the human gutBACTERIA, like people, can be divided into friend and foe. Inspired by evidence that the friendly sort may help with a range of ailments, many people consume bacteria in the form of yogurts and dietary supplements. Such a smattering of artificial additions, however, represents but a drop in the ocean. There are at least 800 types of bacteria living in the human gut. And research by Steven Gill of the Institute for Genomic Research in Rockville, Maryland, and his colleagues, published in this week's Science, suggests that the collective genome of these organisms is so large that it contains 100 times as many genes as the human genome itself.Dr Gill and his team were able to come to this conclusion by extracting bacterial DNA from the faeces of two volunteers. Because of the complexity of the samples, they were not able to reconstruct the entire genomes of each of the gut bacteria, just the individual genes. But that allowed them to make an estimate of numbers.What all these bacteria are doing is tricky to identify—the bacteria themselves are difficult to cultivate. So the researchers guessed at what they might be up to by comparing the genes they discovered with published databases of genes whose functions are already known.This comparison helped Dr Gill identify for the first time the probable enzymatic processes by which bacteria help humans to digest the complex carbohydrates in plants. The bacteria also contain a plentiful supply of genes involved in the synthesis of chemicals essential to human life—including two B vitamins and certain essential amino acids—although the team merely showed that these metabolic pathways exist rather than proving that they are used. Nevertheless, the pathways they found leave humans looking more like ruminants: animals such as goats and sheep that use bacteria to break down otherwise indigestible matter in the plants they eat.The broader conclusion Dr Gill draws is that people are superorganisms whose metabolism represents an amalgamation of human and microbial attributes. The notion of a superorganism has emerged before, as researchers in other fields have come to view humans as having a diverse internal ecosystem. This, suggest some, will be crucial to the success of personalised medicine, as different people will have different responses to drugs, depending on their microbial flora. Accordingly, the next step, says Dr Gill, is to see how microbial populations vary between people of different ages, backgrounds and diets.Another area of research is the process by which these helpful bacteria first colonise the digestive tract. Babies acquire their gut flora as they pass down the birth canal and take a gene-filled gulp of their mother's vaginal and faecal flora. It might not be the most delicious of first meals, but it could well be an important one.Zapping the bluesThe rebirth of electric-shock treatmentELECTRICITY has long been used to treat medical disorders. As early as the second century AD, Galen, a Greek physician, recommended the use of electric eels for treating headaches and facial pain. In the 1930s Ugo Cerletti and Lucio Bini, two Italian psychiatrists, used electroconvulsive therapy to treat schizophrenia. These days, such rigorous techniques are practised less widely. But researchers are still investigating how a gentler electric therapy appears to treat depression.Vagus-nerve stimulation, to give it its proper name, was originally developed to treat severe epilepsy. It requires a pacemaker-like device to be implanted in a patient's chest and wires from it threaded up to the vagus nerve on the left side of his neck. In the normal course of events, this provides an electrical pulse to the vagus nerve for 30 seconds every five minutes.This treatment does not always work, but in some cases where it failed (the number of epileptic seizures experienced by a patient remaining the same), that patient nevertheless reported feeling much better after receiving the implant. This secondary effect led to trials for treating depression and, in 2005, America's Food and Drug Administration approved the therapy for depression that fails to respond to all conventional treatments, including drugs and psychotherapy.Not only does the treatment work, but its effects appear to be long lasting. A study led by Charles Conway of Saint Louis University in Missouri, and presented to a recent meeting of the American Psychiatric Association, has found that 70% of patients who are better after one year stay better after two years as well.The technique builds on a procedure called deep-brain stimulation, in which electrodes are implanted deep into the white matter of patients' brains and used to “reboot” faulty neural circ uitry. Such an operation is a big undertaking, requiring a full day of surgery and carrying a risk of the patient suffering a stroke. Only a small number of people have been treated this way. In contrast, the device that stimulates the vagus nerve can be implanted in 45 minutes without a stay in hospital.The trouble is that vagus-nerve stimulation can take a long time to produce its full beneficial effect. According to Dr Conway, scans taken using a technique called positron-emission tomography show significant changes in brain activity starting three months after treatment begins. The changes are similar to the improvements seen in patients who undergo other forms of antidepression treatment. The brain continues to change over the following 21 months. Dr Conway says that patients should be told that the antidepressant effects could be slow in coming.However, Richard Selway of King's College Hospital, London, found that his patients' moods improved just weeks after the implant. Although brain scans are useful in determining the longevity of the treatment, Mr Selway notes that visible changes in the brain do not necessarily correlate perfectly with changes in mood.Nobody knows why stimulating the vagus nerve improves the mood of depressed patients, but Mr Selway has a theory. He believes that the electrical stimulation causes a region in the brain stem called the locus caeruleus (Latin, ironically, for “blue place”) to flood the brain with norepinephrine, a neurotransmitter implicated in alertness, concent ration and motivation—that is, the mood states missing in depressed patients. Whatever the mechanism, for the depressed a therapy that is relatively safe and long lasting is rare cause for cheer.The shape of things to comeHow tomorrow's nuclear power stations will differ from today'sTHE agency in charge of promoting nuclear power in America describes a new generation of reactors that will be “highly economical” with “enhanced safety”, that “minimise wastes” and will prove “proliferation resistant”. No d oubt they will bake a mean apple pie, too.Unfortunately, in the world of nuclear energy, fine words are not enough. America got away lightly with its nuclear accident. When the Three Mile Island plant in Pennsylvania overheated in 1979 very little radiation leaked, and there were no injuries. Europe was not so lucky. The accident at Chernobyl in Ukraine in 1986 killed dozens immediately and has affected (sometimes fatally) the health of tens of thousands at the least. Even discounting the association of nuclear power with nuclear weaponry, people have good reason to be suspicious of claims that reactors are safe.Yet political interest in nuclear power is reviving across the world, thanks in part to concerns about global warming and energy security. Already, some 441 commercial reactors operate in 31 countries and provide 17% of the planet's electricity, according to America's Department of Energy. Until recently, the talk was of how to retire these reactors gracefully. Now it is of how to extend their lives. In addition, another 32 reactors are being built, mostly in India, China and their neighbours. These new power stations belong to what has been called the third generation of reactors, designs that have been informed by experience and that are considered by their creators to be advanced. But will these new stations really be safer than their predecessors?Clearly, modern designs need to be less accident prone. The most important feature of a safe design is that it “fails safe”. For a reactor, this means that if its control systems stop working it shuts down automatically, safely dissipates the heat produced by the reactions in its core, and stops both the fuel and the radioactive waste produced by nuclear reactions from escaping by keeping them within s ome sort of containment vessel. Reactors that follow such rules are called “passive”. Most modern designs are passive to some extent and some newer ones are truly so. However, some of the genuinely passive reactors are also likely to be more expensive to run.Nuclear energy is produced by atomic fission. A large atom (usually uranium or plutonium) breaks into two smaller ones, releasing energy and neutrons. The neutrons then trigger further break-ups. And so on. If this “chain reaction” can be controlled, t he energy released can be used to boil water, produce steam and drive a turbine that generates electricity. If it runs away, the result is a meltdown and an accident (or, in extreme circumstances, a nuclear explosion—though circumstances are never that extreme in a reactor because the fuel is less fissile than the material in a bomb). In many new designs the neutrons, and thus the chain reaction, are kept under control by passing them through water to slow them down. (Slow neutrons trigger more break ups than fast ones.) This water is exposed to a pressure of about 150 atmospheres—a pressure that means it remains liquid even at high temperatures. When nuclear reactions warm the water, its density drops, and the neutrons passing through it are no longer slowed enough to trigger further reactions. That negative feedback stabilises the reaction rate.Can business be cool?Why a growing number of firms are taking global warming seriouslyRUPERT MURDOCH is no green activist. But in Pebble Beach later this summer, the annual gathering of executives of Mr Murdoch's News Corporation—which last year led to a dramatic shift in the media conglomerate's attitude to the internet—will be addressed by several leading environmentalists, including a vice-president turned climatechange movie star. Last month BSkyB, a British satellite-television company chaired by Mr Murdoch and run by his son, James, declared itself “carbon-neutral”, having taken various steps to cut or offset its discharges of carbon into the atmosphere.The army of corporate greens is growing fast. Late last year HSBC became the first big bank to announce that it wascarbon-neutral, joining other financial institutions, including Swiss Re, a reinsurer, and Goldman Sachs, an investment bank, in waging war on climate-warming gases (of which carbon dioxide is the main culprit). Last year General Electric (GE), an industrial powerhouse, launched its “Ecomagination” strategy, aiming to cut its output of greenhouse gases and to invest heavily in clean (ie, carbon-free) technologies. In October Wal-Mart announced a series of environmental schemes, including doubling thefuel-efficiency of its fleet of vehicles within a decade. Tesco and Sainsbury, two of Britain's biggest retailers, are competing fiercely to be the greenest. And on June 7th some leading British bosses lobbied Tony Blair for a more ambitious policy on climate change, even if that involves harsher regulation.The greening of business is by no means universal, however. Money from Exxon Mobil, Ford and General Motors helped pay for television advertisements aired recently in America by the Competitive Enterprise Institute, with the daft slogan “Carbon dioxide: they call it pollution; we call it life”. Besides, environmentalist critics say, some firms are engaged in superficial “greenwash” to boost the image of essentially climate-hurting businesses. Take BP, the most prominent corporate advocate of action on climate change, with its “Beyond Petroleum” ad campaign, highprofile investments in green energy, and even a “carbon calculator” on its website that helps consumers measure their personal “carbon footprint”, or overall emissions of carbon. Yet, critics complain, BP's recent record profits are largely thanks to sales of huge amounts of carbon-packed oil and gas.On the other hand, some free-market thinkers see the support of firms for regulation of carbon as the latest attempt at “regulatory capture”, by those who stand to profit from new rules. Max Schulz of the Manhattan Institute, a conservative think tank, notes darkly that “Enron was into pushing the idea of climate change, because it was good for its business”.Others argue that climate change has no more place in corporate boardrooms than do discussions of other partisan political issues, such as Darfur or gay marriage. That criticism, at least, is surely wrong. Most of the corporate converts say they are acting not out of some vague sense of social responsibility, or even personal angst, but because climate change creates real business risks and opportunities—from regulatory compliance to insuring clients on flood plains. And although these concerns vary hugely from one company to the next, few firms can be sure of remaining unaffected.Testing timesResearchers are working on ways to reduce the need for animal experiments, but new laws mayincrease the number of experiments neededIN AN ideal world, people would not perform experiments on animals. For the people, they are expensive. For the animals, they are stressful and often painful.That ideal world, sadly, is still some way away. People need new drugs and vaccines. They want protection from the toxicity of chemicals. The search for basic scientific answers goes on. Indeed, the European Commission is forging ahead with proposals that will increase the number of animal experiments carried out in the European Union, by requiring toxicity tests on every chemical approved for use within the union's borders in the past 25 years.Already, the commission has identified 140,000 chemicals that have not yet been tested. It wants 30,000 of these to be examined right away, and plans to spend between €4 billion-8 billion ($5 billion-10 billion) doing so. The number of animals used for toxicity testing in Europe will thus, experts reckon, quintuple from just over 1m a year to about 5m, unless they are saved by some dramatic advances in non-animal testing technology. At the moment, roughly 10% of European animal tests are for general toxicity, 35% for basic research, 45% for drugs and vaccines, and the remaining 10% a variety of uses such as diagnosing diseases.Animal experimentation will therefore be around for some time yet. But the hunt for substitutes continues, and last weekend the Middle European Society for Alternative Methods to Animal Testing met in Linz, Austria, to review progress.A good place to start finding alternatives for toxicity tests is the liver—the organ responsible for breaking toxic chemicals down into safer molecules that can then be excreted. Two firms, one large and one small, told the meeting how they were using human liver cells removed incidentally during surgery to test various substances for long-term toxic effects.PrimeCyte, the small firm, grows its cells in cultures over a few weeks and doses them regularly with the substance under investigation. The characteristics of the cells are carefully monitored, to look for changes in their microanatomy.Pfizer, the big firm, also doses its cultures regularly, but rather than studying individual cells in detail, it counts cell numbers. If the number of cells in a culture changes after a sample is added, that suggests the chemical in question is bad for the liver.In principle, these techniques could be applied to any chemical. In practice, drugs (and, in the case of PrimeCyte, food supplements) are top of the list. But that might change if the commission has its way: those 140,000 screenings look like a lucrative market, although nobody knows whether the new tests will be ready for use by 2009, when the commission proposes that testing should start.Other tissues, too, can be tested independently of animals. Epithelix, a small firm in Geneva, has developed an artificial version of the lining of the lungs. According to Huang Song, one of Epithelix's researchers, the firm's cultured cells have similar microanatomy to those found in natural lung linings, and respond in the same way to various chemical messengers. Dr Huang says that they could be used in long-term toxicity tests of airborne chemicals and could also help identify treatments for lung diseases.The immune system can be mimicked and tested, too. ProBioGen, a company based in Berlin, is developing an artificial human lymph node which, it reckons, could have prevented the near-disastrous consequences of a drug trial held in Britain three months ago, in which (despite the drug having passed animal tests) six men suffered multiple organ failure and nearly died. The drug the men were given made their immune systems hyperactive. Such a response would, the firm's scientists reckon, have been identified by their lymph node, which is made from cells that provoke the immune system into a response. ProBioGen's lymph node could thus work better than animal testing.Another way of cutting the number of animal experiments would be to change the way that vaccines are tested, according to Coenraad Hendriksen of the Netherlands Vaccine Institute. At the moment, all batches of vaccine are subject to the same battery of tests. Dr Hendriksen argues that this is over-rigorous. When new vaccine cultures are made, belt-and-braces tests obviously need to be applied. But if a batch of vaccine is derived from an existing culture, he suggests that it need be tested only to make sure it is identical to the batch from which it is derived. That would require fewer test animals. All this suggests that though there is still some way to go before drugs, vaccines and other substances can be tested routinely on cells rather than live animals, useful progress is being made. What is harder to see is how the use of animals might be banished from fundamental research.Anger managementTo one emotion, men are more sensitive than womenMEN are notoriously insensitive to the emotional world around them. At least, that is the stereotype peddled by a thousand women's magazines. And a study by two researchers at the University of Melbourne, in Australia, confirms that men are, indeed, less sensitive to emotion than women, with one important and suggestive exception. Men are acutely sensitive to the anger of other men.Mark Williams and Jason Mattingley, whose study has just been published in Current Biology, looked at the way a person's sex affects his or her response to emotionally charged facial expressions. People from all cultures agree on what six basic expressions of emotion look like. Whether the face before you is expressing anger, disgust, fear, joy, sadness or surprise seems to be recognised universally—which suggests that the expressions involved are innate, rather than learned.Dr Williams and Dr Mattingley showed the participants in their study photographs of these emotional expressions in mixed sets of either four or eight. They asked the participants to look for a particular sort of expression, and measured the amount of time it took them to find it. The researchers found, in agreement with previous studies, that both men and women identified angry expressions most quickly. But they also found that anger was more quickly identified on a male face than a female one.Moreover, most participants could find an angry face just as quickly when it was mixed in a group of eight photographs as when it was part of a group of four. That was in stark contrast to the other five sorts of expression, which took more time to find when they had to be sorted from a larger group. This suggests that something in the brain is attuned to picking out angry expressions, and that it is especially concerned about angry men. Also, this highly tuned ability seems more important to males than females, since the two researchers found that men picked out the angry expressions faster than women did, even though women were usually quicker than men to recognize every other sort of facial expression.Dr Williams and Dr Mattingley suspect the reason for this is that being able to spot an angry individual quickly has a survival advantage—and, since anger is more likely to turn into lethal violence in men than in women, the ability to spot angry males quickly is particularly valuable.As to why men are more sensitive to anger than women, it is presumably because they are far more likely to get killed by it.Most murders involve men killing other men—even today the context of homicide is usually a spontaneous dispute over status or sex.The ability to spot quickly that an alpha male is in a foul mood would thus have great survival value. It would allow thesharp-witted time to choose appeasement, defence or possibly even pre-emptive attack. And, if it is right, this study also confirms a lesson learned by generations of bar-room tough guys and schoolyard bullies: if you want attention, get angry.The shareholders' revoltA turning point in relations between company owners and bosses?SOMETHING strange has been happening this year at company annual meetings in America: shareholders have been voting decisively against the recommendations of managers. Until now, most shareholders have, like so many sheep, routinely voted in accordance with the advice of the people they employ to run the company. This year managers have already been defeated at some 32 companies, including household names such as Boeing, ExxonMobil and General Motors.This shareholders' revolt has focused entirely on one issue: the method by which members of the board of directors are elected. Shareholder resolutions on other subjects have mostly been defeated, as usual. The successful resolutions called for directors to be elected by majority voting, instead of by the traditional method of “plurality”—which in practice meant that only votes cast in favour were counted, and that a single vote for a candidate would be enough to get him elected.Several companies, led by Pfizer, a drug giant, saw defeat looming and pre-emptively adopted a formal majority-voting policy that was weaker than in the shareholder resolution. This required any director who failed to secure a majority of votes to tender his resignation to the board, which would then be free to decide whether or not to accept it. Under the shareholder resolution, any candidate failing to secure a majority of the votes cast simply would not be elected. Intriguingly, the shareholder resolution was defeated at four-fifths of the firms that adopted a Pfizer-style majority voting rule, whereas it succeeded nearly nine times out of ten at firms retaining the plurality rule.Unfortunately for shareholders, their victories may prove illusory, as the successful resolutions were all “precatory”—meaning that they merely advised management on the course of action preferred by shareholders, but did not force managers to do anything. Several resolutions that tried to impose majority voting on firms by changing their bylaws failed this year.Even so, wise managers should voluntarily adopt majority voting, according to Wachtell, Lipton, Rosen & Katz, a Wall Street law firm that has generally helped managers resist increases in shareholder power but now expects majority voting eventually to “become universal”. It advises that, at the very least, managers should adopt the Pfizer model, if only to avoid becoming the subject of even greater scrutiny from corporate-governance activists. Some firms might choose to go further, as Dell and Intel have done this year, and adopt bylaws requiring majority voting.Shareholders may have been radicalised by the success last year of a lobbying effort by managers against a proposal from regulators to make it easier for shareholders to put up candidates in board elections. It remains to be seen if they will be back for more in 2007. Certainly, some of the activist shareholders behind this year's resolutions have big plans. Where new voting rules are in place, they plan campaigns to vote out the chairman of the compensation committee at any firm that they think overpays the boss. If the 2006 annual meeting was unpleasant for managers, next year's could be far worse.Intangible opportunitiesCompanies are borrowing against their copyrights, trademarks and patentsNOT long ago, the value of companies resided mostly in things you could see and touch. Today it lies increasingly in intangible assets such as the McDonald's name, the patent for Viagra and the rights to Spiderman. Baruch Lev, a finance professor at New York University's Stern School of Business, puts the implied value of intangibles on American companies' balance sheets at about $6 trillion, or two-thirds of the total. Much of this consists of intellectual property, the collective name for copyrights, trademarks and patents. Increasingly, companies and their clever bankers are using these assets to raise cash.The method of choice is securitisation, the issuing of bonds based on the various revenues thrown off by intellectual property. Late last month Dunkin' Brands, owner of Dunkin' Donuts, a snack-bar chain, raised $1.7 billion by selling bonds backed by, among other things, the royalties it will receive from its franchisees. The three private-equity firms that acquired Dunkin' Brands a few months ago have used the cash to repay the money they borrowed to buy the chain. This is the biggest intellectual-property securitisation by far, says Jordan Yarett of Paul, Weiss, Rifkind, Wharton & Garrison, a law firm that has worked on many such deals.Securitisations of intellectual property can be based on revenues from copyrights, trademarks (such as logos) or patents. Thebest-known copyright deal was the issue in 1997 of $55m-worth of “Bowie Bonds” supported by the future sales of music by David Bowie, a British rock star. Bonds based on the films of DreamWorks, Marvel comic books and the stories of John Steinbeck have also been sold. As well as Dunkin' Brands, several restaurant chains and fashion firms have issued bonds backed by logos and brands.Intellectual-property deals belong to a class known as operating-asset securitisations. These differ from standard securitisations of future revenues, such as bonds backed by the payments on a 30-year mortgage or a car loan, in that the borrower has to make his asset work. If investors are to recoup their money, the assets being securitised must be “actively exploited”, says Mr Yarett: DreamWorks must continue to churn out box-office hits.The market for such securitisations is still small. Jay Eisbruck, of Moody's, a rating agency, reckons that around $10billion-worth of bonds are outstanding. But there is “big potential,” he says, pointing out that licensing patented technology generates $100 billion a year and involves thousands of companies.Raising money this way can make sense not only for clever private-equity firms, but also for companies with low (or no) credit ratings that cannot easily tap the capital markets or with few tangible assets as collateral for bank loans. Some universities have joined in, too. Yale built a new medical complex with some of the roughly $100m it raised securitising patent royalties from Zerit, an anti-HIV drug.It may be harder for investors to decide whether such deals are worth their while. They are, after all, highly complex and riskier than standard securitisations. The most obvious risk is that the investors cannot be sure that the assets will yield what borrowers promise: technology moves on, fashions change and the demand for sugary snacks may collapse. Valuing intellectual property—an exercise based on forecasting the timing and amount of future cashflows—is more art than science.So far, says Mr Eisbruck, these bonds have generally matched investors' hopes. But regulators say that only institutional investors, such as pension funds and hedge funds, can buy them. Fans seeking a slice of the profits from the next instalment of“X-Men” must wait.Nef offThe reason HIV is so virulent may have been foundTHE human immunodeficiency virus, HIV-1, the cause of the global AIDS epidemic, is the most intensively studied pathogen in history. For all that, it still has secrets to reveal. One is why it is so deadly. Many of man's primate relatives in Africa harbour similar viruses. Yet as far as can be seen, these so-called simian immunodeficiency viruses (SIVs) have little impact on their hosts' health.Frank Kirchhoff and Michael Schindler, of the University of Ulm, in Germany, and their colleagues have been looking into why that is. Their investigation, just published in Cell, suggests it is the result of a change in the role of a single viral gene, called nef.They came to this conclusion by looking at those simian equivalents. In most SIVs, they found, one role of nef is to remove a protein called TCR-CD3 from the surfaces of the cells that host the virus. The host cells in question are immune-system cells called T-cells. Specifically, they are “helper” T-cells, which orchestrate the immune system's response to pathogens such as viruses.The way the body recognises an infection is by examining molecules from the infectious agent. These molecules, known as antigens, are picked up by so-called antigen-presenting cells that display them on their surfaces and show them to the helper cells. The job of TCR-CD3 is to assist in the recognition of these antigens. If a helper cell recognises an antigen, it becomes activated. This means that it starts secreting chemicals that stimulate the growth and multiplication of other T-cells, including the killer Tcells that destroy infected cells. Then, its job done, it dies.Usually, this response clears the infection. In the case of AIDS, though, it does not. That means the immune system continues to be stimulated, and this prolonged stimulation results in high death rates among T-cells. Eventually, that exhausts the immune system's capacity to regenerate itself. The result is a collapse in the number of T-cells, and the accompanying symptoms of AIDS.In most simian infections, this does not happen because nef keeps the TCR-CD3 level too low for this exaggerated response to occur. That is also true in a rarer form of human AIDS caused by a virus called HIV-2. This form of AIDS is found in West Africa, but has not spread much beyond that part of the world. Indeed, of the 16 immunodeficiency viruses the researchers looked at, all but five had nef genes that removed TCR-CD3 from the cell surface. Three of those five were closely related monkey viruses. The fourth was HIV-1.The fifth was the chimpanzee virus that is the direct ancestor of HIV-1. Mankind, it seems, was just unlucky that this virus made the leap across the species barrier. If the only barrier-leaper had been HIV- 2 (which is the descendent of a。
