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 notionof a superorganism has emerged before, as researchers in otherfields have come to view humans as having a diverse internal ecosystem. This, suggest some, will be crucial to the successof 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 investigatinghow 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 circuitry. 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 indetermining 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, concentration 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 doubt 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 nuclearaccident. 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”. Fo r 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 some 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, the 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 themdown. (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 executivesof Mr Murdoch's News Corporation—which last year led to a dramatic shift in the media conglomerate's attitude tothe internet—will be addressed by several leading environmentalists, including a vice-president turned climatechangemovie star. Last month BSkyB, a British satellite-television company chaired by Mr Murdoch and run by hisson, James, declared itself “carbon-neutral”, having taken various steps to cut or offset its discharges of carboninto the atmosphere.The army of corporate greens is growing fast. Late lastyear HSBC became the first big bank to announce that itwas carbon-neutral, joining other financial institutions, including Swiss Re, a reinsurer, and Goldman Sachs, aninvestment bank, in waging war on climate-warming gases (of which carbon dioxide is the main culprit). Last yearGeneral Electric (GE), an industrial powerhouse, launched its “Ecomagination” strategy, aiming to cut its output ofgreenhouse gases and to invest heavily in clean (ie, carbon-free) technologies. In October Wal-Mart announced aseries of environmental schemes, including doubling the fuel-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 7thsome leading British bosses lobbied Tony Blair for a more ambitious policy on climate change, even if that involvesharsher regulation.The greening of business is by no means universal, however. Money from Exxon Mobil, Ford and General Motorshelped pay for television advertisements aired recently in America by the Competitive Enterprise Institute, with thedaft slogan “Carbon dioxide: they call it pollution; we call it life”. Besides, environmentalist critics say, some firmsa re engaged in superficial “greenwash” to boost the image ofessentially climate-hurting businesses. Take BP, themost prominent corporate advocate of action on climate change, with its “Beyond Petroleum” ad campaign, highprofileinvestments in green energy, and even a “carbon calculator” on its website that helps consumers measuretheir personal “carbon footprint”, or overall emissions of carbon. Yet, critics complain, BP's recent record profits arelargely 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 latestattempt at “regulatory capture”, by those who stand to profit from new rules. Max Schulz of the ManhattanInstitute, a conservative think tan k, notes darkly that “Enron was into pushing the idea of climate change, becauseit was good for its business”.Others argue that climate change has no more place in corporate boardrooms than do discussions of other partisanpolitical issues, such as Darfur or gay marriage. That criticism, at least, is surely wrong. Most of the corporateconverts say they are acting not out of some vague sense of social responsibility, or even personal angst, butbecause climate change creates real business risks and opportunities—from regulatory compliance to insuringclientson flood plains. And although these concerns vary hugely from one company to the next, few firms can besure 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 theanimals, they are stressful and often painful.That ideal world, sadly, is still some way away. People need new drugs and vaccines. They want protection fromthe toxicity of chemicals. The search for basic scientific answers goes on. Indeed, the European Commission isforging ahead with proposals that will increase the number of animal experiments carried out in the EuropeanUnion, by requiring toxicity tests on every chemical approved for use within the union's borders in the past 25years.Already, the commission has identified 140,000 chemicals that have not yet been tested. It wants 30,000 of theseto be examined right away, and plans to spend between €4 billion-8 billion ($5 billion-10 billion) doing so. Thenumberof animals used for toxicity testing in Europe will thus, experts reckon, quintuple from just over 1m a yearto 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 andvaccines, and the remaining 10% a varietyof uses such as diagnosing diseases.Animal experimentation will therefore be around for some time yet. But the hunt for substitutes continues, and lastweekend the Middle European Society for Alternative Methods to Animal Testing met in Linz, Austria, to reviewprogress.A good place to start finding alternatives for toxicity tests is the liver—the organ responsible for breaking toxicchemicals down into safer molecules that can then be excreted. Two firms, one large and one small, told themeeting how they were using human liver cells removed incidentally during surgery to test various substances forlong-term toxic effects.PrimeCyte, the small firm, grows its cells in cultures over a few weeks and doses them regularly with the substanceunder investigation. The characteristics of the cells are carefully monitored, to look for changes in theirmicroanatomy.Pfizer,the big firm, also doses its cultures regularly, but rather than studying individual cells in detail, it counts cellnumbers. If the number of cells in a culture changes after a sample is added, that suggests the chemical inquestion 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 140,000screenings look like a lucrative market, although nobody knows whether the new tests will be ready for use by2009, 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 anartificial version of the lining of the lungs. According to Huang Song, one of Epithelix's researchers, the firm'scultured cells have similar microanatomy to those found in natural lung linings, and respond in the same way tovarious chemical messengers. Dr Huang says that they could be used in long-term toxicity tests of airbornechemicals 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 developinganartificial human lymph node which, it reckons, could have prevented the near-disastrous consequences of a drugtrial held in Britain three months ago, in which (despite the drug having passed animal tests) six men sufferedmultiple 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 fromcells that provoke the immune system into a response. ProBioGen's lymph node could thus work better than animaltesting.Another way of cutting the number of animal experiments would be tochange the way that vaccines are tested, according to CoenraadHendriksen of the Netherlands Vaccine Institute. At the moment, allbatches of vaccine are subject to the same battery of tests. DrHendriksen argues that this is over-rigorous. When new vaccine culturesare made, belt-and-braces tests obviously need to be applied. But if abatch of vaccine is derived from an existing culture, he suggests that itneed be tested only to make sure it is identical to the batch from which itis 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 oncells ratherthan live animals, useful progress is being made. What is harder to see ishow 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 athousand 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 suggestiveexception. 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 aperson's sex affects his or her response to emotionally charged facial expressions. People from all cultures agreeon 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 areinnate, rather than learned.Dr Williams and Dr Mattingley showed the participants intheir study photographs of these emotional expressions inmixed sets of either four or eight. They asked the participants to look for a particular sort of expression, andmeasured 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 morequickly 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 eightphotographs 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 thebrain is attuned to picking out angry expressions, and that it is especially concerned about angry men. Also, thishighly tuned ability seems more important to males than females, since the two researchers found that men pickedout the angry expressions faster than women did, even though women were usually quicker than men to recognizeevery 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 hasasurvival advantage—and, since anger is more likely to turn into lethal violence in men than in women, the abilityto 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 getkilled by it. Most murders involve men killing other men—even today the context of homicide is usually aspontaneous 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 allowthe sharp-witted time to choose appeasement, defence or possibly even pre-emptive attack. And, if it is right, thisstudy also confirms a lesson learned by generations of bar-room tough guys and schoolyard bullies: if you wantattention, 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, mostshareholders have, like so many sheep, routinely voted in accordance with the advice of the peopletheyemploy 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 boardof 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 thetraditional 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 formalmajority-voting policy that was weaker than in the shareholder resolution. This required any director whofailed to secure a majority of votes to tender his resignation to the board, which would then be free todecide whether or not to accept it. Under the shareholder resolution, any candidate failing to secure amajority of the votes cast simply would not be elected. Intriguingly, the shareholder resolution wasdefeated at four-fifths of the firms that adopted a Pfizer-style majority voting rule, whereas itsucceedednearly 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 byshareholders, but did not force managers to do anything. Several resolutions that tried to imposemajority 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 butnow expects majority voting eventually to “become universal”. It advises th at, at the very least,managers should adopt the Pfizer model, if only to avoid becoming the subject of even greater scrutinyfrom corporate-governance activists. Some firms might choose to go further, as Dell and Intel have donethis year, and adopt bylaws requiring majority voting.Shareholders may have been radicalised by the success last year of a lobbying effort by managersagainst a proposal from regulators to make it easier for shareholders to put up candidates in boardelections. It remains to be seen if they willbe back for more in 2007. Certainly, some of the activistshareholders behind this year's resolutions have big plans. Where new voting rules are in place, they plancampaigns to vote out the chairman of the compensation committee at any firm that they think overpaysthe 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 liesincreasingly in intangible assets such as the McDonald's name, the patent for Viagra and the rights toSpiderman. Baruch Lev, a finance professor at New York University's Stern School of Business, puts theimplied value of intangibles on American companies' balance sheets at about $6 trillion, or two-thirds ofthe total. Much of this consists of intellectual property, the collective name for copyrights, trademarksand patents. Increasingly, companies and their clever bankers are using these assets to raise cash.The method of choice is securitisation, the issuing ofbonds based on the various revenues thrown off byintellectual 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 itsfranchisees. The three private-equity firms that acquired Dunkin' Brands a few months ago have used thecash to repay the money they borrowed to buy the chain. This is the biggest intellectual-propertysecuritisation by far, says Jordan Yarett of Paul, Weiss, Rifkind, Wharton & Garrison, a law firm that hasworked on many such deals.Securitisations of intellectual property can be based on revenues from copyrights, trademarks (such aslogos) or patents. The best-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 ofDreamWorks, Marvel comic books and the stories of John Steinbeck have also been sold. As well asDunkin' Brands, several restaurant chains and fashion firms have issued bonds backed by logos andbrands.Intellectual-property deals belong to a class known as operating-asset securitisations. These differ fromstandard securitisations of future revenues, such as bonds backed by thepayments on a 30-yearmortgage or a car loan, in that the borrower has to make his asset work. If investors are to recoup theirmoney, the assets being securitised must be “actively exploited”, says Mr Yarett: DreamWorks mustcontinue to churn out box-office hits.The market for such securitisations is still small. Jay Eisbruck, of Moody's, a rating agency, reckons thataround $10 billion-worth of bonds ar e outstanding. But there is “big potential,” he says, pointing out thatlicensing 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 companieswith low (or no) credit ratings that cannot easily tap the capital markets or with few tangible assets ascollateral for bank loans. Some universities have joined in, too. Yale built a new medical complex withsome 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 investorscannot be sure that the assets will yield。
