Nature, the most deadly bio-terrorist of all

2005: Epidemics - It may not be in the next 12 months, but very soon, a new and virulent strain of f

The cover of a recent issue of National Geographic magazine posed a simple, contentious question: "Was Darwin wrong?" Readers who nervously opened their copies, expecting to read a creationist diatribe designed to appease America's religious right, were pleasantly surprised, however. The answer was spelt out in giant letters on an inside page: "No, the evidence for evolution is overwhelming." Below, the distinguished science writer David Quammen hammered home the case by describing a powerful mix of geological evidence, taxonomic data, DNA studies and observations of living creatures that support the theory of natural selection. But what really grabbed attention was Quammen's additional, and considerable, reliance on medical studies - the appearance of new diseases in our midst and the deadly changes that continually occur to existing illnesses - to support his case. "There is no better or more immediate evidence supporting Darwinian theory than this process of forced transformation among our inimical germs," he stated.

You can see his point. The capacity for rapid change among disease-causing microbes makes them painfully difficult to treat and should remind us powerfully that no species, least of all Homo sapiens, is immune to the forces of natural selection. The idea - prevalent in the 1960s and 1970s - that we had defeated infectious diseases was simply wrong, as recent appearances of new illnesses such as Aids, West Nile fever and severe acute respiratory syndrome (Sars) should remind us.

We are, to put it bluntly, locked in permanent evolutionary war with the earth's bacteria and viruses. Sometimes we mount an effective Big Push, making inroads against a particular illness. (Total victories, such as the eradication of smallpox, are rare.) On other occasions, the enemy breaks through our battle lines with catastrophic effects, and an epidemic - such as the flu outbreak that devastated postwar populations in 1918 - ensues. On our side, we have an arsenal of antibiotics, antiviral drugs, vaccines, pesticides and antiseptics to protect us. On their side, there is the simple, mind-bogglingly multitudinous nature of germs combined with their perpetual, random attempts to mutate past our defences.

Clearly, we need to be eternally vigilant when dealing with our unseen enemies. But are we? Are epidemics a greater or lesser threat than they used to be? And what should governments and public health authorities do to prevent them? And if attacks are inevitable, from what direction will they come and in what form? All good questions, though none is easily answered - except perhaps the last, as Neil Ferguson, professor of mathematical biology at Imperial College London, explains. "Most new epidemics are likely to be zoonotic. In other words, they will be diseases of animals and birds that will be passed to men, women and children, transformed to become infectious among humans, and then passed to other people."

Recent examples of viruses picked up from animals and transformed so they can infect humans include Aids, from chimpanzees, and ebola fever from monkeys. Many of these diseases come from the developing world where man and beast mingle more freely than in the west, though it would be wrong to think that every zoonotic disease has this geographical origin. One of the deadliest to appear in recent years was BSE, created and nurtured by our own agricultural habits - the cannibalistic feeding of cattle with the remains of other cattle. This allowed a rare livestock disease to become amplified into a major epidemic and then be passed into the human food chain, causing outbreaks of the brain disease variant CJD.

But merely getting into the human system, before mutating in a way that is harmful, is not sufficient to cause widespread worry. For alarm bells to ring, a condition must also make its hosts infectious so that the disease can be passed to those with whom they have come into contact. Thus BSE and ebola probably fail the epidemic test, serious threats though they may be. To cause real concern, a new illness must make each of its victims capable of spreading infection to others, and not just occasionally. They must pass on viruses to several others. There needs to be reliable person-to-person infection, in other words. Then we can be sure of having a full-blown epidemic on our hands.

So are there any diseases poised to spread among us in this way? The answer, sadly, is yes. "I think it is fair to say that avian flu now presents us with a very real danger of reaching the status of a pandemic, which means it will spread not just across a country like an epidemic but across continents," says Ferguson. It is a fear shared by many other doctors, scientists and epidemiologists.

Avian flu first made headlines when an outbreak in Hong Kong killed six people in 1997. Widespread deaths were avoided only by city authorities destroying - with commendable fleetness - the city's entire poultry population of about 1.5 million birds, thus preventing the disease from taking a deadly grip of the city. Further fatal outbreaks occurred in Holland in February 2003 and in Vietnam in January 2004, this last case triggering particular alarm, as it was caused by the viral sub-type H5N1, which mutates its outer protein coat with the dazzling rapidity of a quick-change artist. It can also pick up genes from other viruses infecting their newly acquired host. In addition, H5N1 is highly pathogenic. In other words, it poisons those who carry it.

Medical experts now fear the virus is about to make a new and deadly attack. They worry the strain could be picked up from poultry and infect a person already carrying a human flu virus. That individual would become a "mixing vessel" for the emergence of a novel sub-type virus, one that has enough human genes to make it pass easily from person to person while also carrying an equal number of pathogenic avian flu genes. "Such an event would mark the start of an influenza pandemic," states the World Health Organisation (WHO).

Scientists estimate that, at worst, a mutant strain created this way would have a lethality of 5 per cent. In other words, one in 20 patients would die, worse than the great 1918 pandemic that killed roughly 20 million people, but which may have infected more than a billion. Could such terrible attrition really occur today, with all the medical knowledge that we have acquired?

Ferguson sees little grounds for comfort. "On the positive side, there is at least one very good antiviral drug, Tamiflu, that could protect populations and stop infected people dying. But to be any use it would have to be stockpiled in advance. In Britain alone, the bill would run to more than £100m - to guard against a threat that does not even exist yet. More to the point, Tamiflu is made by Roche, which has one factory dedicated to its manufacture and currently has a massive backlog of orders. So the prospect of stockpiling does not present much comfort at the moment."

The alternative is to make a vaccine. These take months to develop and manufacture, however, a point stressed by Dr Ron Cutler, of the University of East London's School of Health and Bioscience. "New flu vaccines normally protect only 80 per cent of cases and may last only one year," he further says. "On the other hand, a vaccine against a different strain could provide some protection, so it is always worth taking a flu shot that your GP offers you. It is not a guarantee, but it could help."

Then there is the issue of who will receive vaccines and drugs. Most estimates suggest that, at best, there will be supplies for about a third of the population. So will the old, the asthmatic and immuno-suppressed - people who are considered to be the most vulnerable to flu - be the ones to get priority treatment? The answer is probably no. Many NHS executives argue that workers in transport, emergency services, IT and other key industries should be the first to be treated, so that the country is kept running. During the fuel crisis of 2000, industry staff - even journalists - were given petrol rations in preference to those with medical needs. The same priorities are likely to be adopted again. The old and sick may be left to fend for themselves.

It is a grim scenario, one that reveals our vulnerability to a disease that is usually regarded as a fairly innocuous threat. But how did this happen? In what way has the world altered to make us so vulnerable? The answer is: in many ways. Some developments have helped us in our fight against disease, in particular those brought about by the rise of modern medical science. However, others continually put us at risk. "A hundred years ago, if you travelled you had no choice but to take your time," says Cutler. "If you got ill, you either died where you were or you got better and moved on. The disease generally stayed where it was."

Not today. We jump on a plane, pick up a virus, bring it home and pass it on to others before we develop a single symptom ourselves. We may have developed a formidable capacity to create vaccines and drugs, but we are up against a rapidly mutating enemy which is now being passed around with frightening speed. That, of course, is evolution.

We can gain an insight into the dangers we face by considering two recent disease outbreaks. First, there is the case of West Nile fever, which is spread by mosquitoes and which affects much of Africa, Asia and parts of Europe, causing flu-like symptoms and only rarely triggering fatal complications. Then, in 2002, West Nile appeared in the United States and since then has affected thousands of Americans, killing dozens of them during summer months when mosquitoes are at their most active. Intriguingly, the US disease appears to have far more severe neurological side effects than its Old World counterpart. (As to its source, says Maria Zambon, of the UK's Health Protection Agency. West Nile was "spread to the US by a mosquito or a bird that had hitched a ride on a transcontinental airliner.")

And then there is Sars. The disease, which had never previously been detected by scientists, erupted in China in the late months of 2002. Patients exhibited initial flu-like symptoms, fever, body cramps and headaches, and went on to develop pneumonia. Within weeks, Sars had moved to North America, and then on to Europe before ending up being sent back to Asia - a spread that occurred at breakneck speed, though this time the agent of transfer was not insectivorous but human. A flash of a boarding pass and the virus, already multiplying in the cells of human hosts, moved on to new, infectious pastures.

The consequences were distinctly unpleasant. Of the 8,000 patients who came down with Sars round the world, 774 died. As to the source, scientists have now pinpointed the most likely culprit: the civet, a tree-dwelling creature which is related to the mongoose and is considered to be a great delicacy in China. A mutated corona virus from a restaurant in Guangdong Province, where a waitress was serving stir-fried civet, is thought to be one of the sources of last year's Sars outbreak.

In the case of Sars, there is a further lesson for us. While public health authorities mopped up the H5N1 flu outbreak of 1997 with commendable, forthright action, in the case of Sars, they were far less impressive. At one point in Hong Kong, they tried to confine doctors, nurses and other staff to hospitals to which victims had been taken. The aim was to get them all to sit out the outbreak and to stop the disease oozing across the city. So the staff simply climbed to second-floor windows and jumped out, says Cutler. In addition, masks that were supposed to halt the spread of the disease (Sars is passed in the tiny droplets of water we expel when we breath and talk) were not effective, and allowed the virus particles to escape through their relatively large pores. Doctors and health officials were dealing with the unknown and were struggling to adapt against the forces of natural selection - a tricky business, as we have seen.

With Sars, the world was lucky. At first, the condition seemed to be that deadly influenza which doctors had been fearing: one that would not respond to a Big Push. Hence the panic. To their relief, however, doctors found that symptoms of Sars appeared before victims become infectious, so health authorities could break the disease's chain of transmission by isolating patients. None the less it brought near-paralysis to Hong Kong, caused the city's stock market to crash and frightened the living daylights out of half the planet's doctors.

"We were still relatively lucky with Sars," says Zambon. "The next time may not be so pleasant." Which brings us back to flu. Consider the basic facts: we have several strains of deadly avian flu infecting the poultry of south Asia and we have millions of people who keep chickens and ducks in their yards and huts in one of the world's most densely populated areas. On their own, these two factors are ideal for creating a deadly new flu virus. On top of that, we have the bonus factor of cheap, global air travel ready to whisk newly infected humans round the planet. And given that flu victims become infectious before their symptoms develop, the situation looks extremely dodgy, to say the least.

On the other hand, it would be misleading to suggest the situation is hopeless. Fifteen different vaccines are now being tested by drug companies in the west. With luck, one could provide reasonable protection against that deadly new virus when it emerges. And the prospects of a pandemic are certainly being taken very seriously by health officials. Nevertheless the signs suggest that we may soon be in for a short, sharp lesson about the potential dangers of evolutionary biology.

Not that this education should be necessary. While flu pandemics erupt (roughly every 30 years) and then fade, humanity has had the example of a scourge - Aids - that has been inexorably enveloping the planet for 20 years and which should have already taught us everything we need to know about natural selection and disease. Like the agent responsible for flu, HIV (the Aids virus) mutates at a startling rate. More importantly, it attacks the very defence cells that should protect us against disease. And its symptoms appear long after a person has infected others, usually by sexual contact. It is almost perfectly adapted to cause widespread loss of life. Today there are 40 million victims of the disease, of whom 2.2 million are children under the age of 15. In 2004, there were 3.1 million deaths from Aids. Far from fading, Aids continues its deadly spread. This is an agent ideally adapted to make the most of the sweeping social transformations, population movements and cultural changes rippling across our planet. A virus like this was bound to evolve, it would seem.

But then, as Zambon says: "Nature has always been the ultimate bio-terrorist."

Robin McKie is science editor of the Observer