‘This is a bit of a hobby horse of mine,’ says Dorothy Crawford, Robert Irvine Professor of Medical Microbiology at Edinburgh University. ‘It is really very irritating that the media tend to label every nasty illness a virus. Viruses are actually very different from bacteria. In fact, about the only thing which they have in common, apart from the fact that they cause illness, is that they’re very small. But even here, viruses are in fact much smaller than bacteria; for example, you can’t see viruses without an electron microscope, whereas you can see bacteria with an ordinary light microscope. Indeed, until the electron microscope was invented, people weren’t at all clear about what viruses were; they thought that they were probably just very small bacteria, but in fact they’re very different.

‘Bacteria are single celled organisms, which have the ability to exist independently of other organisms,’ Crawford explains. ‘They are able to metabolise and to reproduce on their own. Viruses, on the other hand, are obligate parasites; they are only able to reproduce within a host organism. They can’t do anything until they get inside a living cell. Once they’re there, they have mechanisms which enable them to take over the cell, and to use the cell’s organelles in order to reproduce themselves. They have nucleic acid – DNA or RNA – so they have inherited characteristics; but apart from that there isn’t really much to them.’

The fact that viruses do not produce their own energy and cannot reproduce without hijacking the cells of a living host raises the question as to whether they are alive or not. Does Crawford have a view about this?

‘Well, it’s a question which I sometimes ask my students,’ she replies. ‘It’s a good debate, but I’m not sure how much it matters. Ultimately it hinges on how life is defined. If life is about reproduction, then viruses are alive; but if it is about the ability to metabolise, then they’re not. I guess, if pushed, I’d come down on the side of viruses not being alive. They just don’t seem to have life-like characteristics.’

If viruses then are just sets of genetic instructions, how do they cause illnesses? Presumably it has something to do with the way that they hijack a host’s cells?

‘Yes, that’s right,’ Crawford confirms. ‘A virus is just a piece of genetic material which will replicate itself if it can. If it can’t, then it won’t survive, so, in that sense, reproduction is what viruses are all about. If a virus gets into a cell, and it finds all the material it requires, reproduction occurs automatically via biochemical reactions. The consequence is a lot of new viruses. This process upsets the host cell, and will very often kill it. So, if a flu virus, for example, gets in via a person’s nose, and infects their respiratory epithelium, then, if enough copies are produced, killing a lot of host cells, the infected person is going to feel pretty ill.

‘However, not all viruses work this way,’ Crawford says. ‘Other viruses, for example, go into a cell, and then stimulate it so that the cell replicates itself. The virus requires the enzymes which are found in the cell when the cell is growing. This process, if it is not checked, can result in a cancer; there is a breakdown in the normal checks on cell division, so unless the immune system notices what is going on, you can get a tumour.’

Viruses, of course, can cause huge numbers of deaths. For example, the influenza pandemic in 1918 is estimated to have killed 20 million people. However, most viruses do not have this kind of impact. Is there something about what it takes for a virus to be successful which makes really high casualty figures relatively unlikely?

‘The key thing is how the body responds to a virus,’ Crawford answers. ‘The 1918 flu virus was completely new, so nobody was immune to it. Generally speaking, the human body is not prepared for completely new infections, so you get a worse illness the first time a particular virus comes around. In evolutionary terms, those who are most susceptible to new viruses die out; therefore, they don’t produce offspring, which means that populations become more resistant to specific viruses over time. This would likely be the case with the SARS virus. If it keeps turning up, then eventually people will have more resistance to it. But, of course, there is such a long time between generations of humans that it would be more than a century before any significant resistance emerges.’

What about an illness like Ebola fever; isn’t it just too deadly to be a major threat?

‘Probably that’s true,’ Crawford confirms. ‘If you’re infected with Ebola, then you’re too ill to move anywhere, so whilst it’s an explosive outbreak, it doesn’t spread very far. Also, in the case of Ebola, its method of transmission goes against it. It is spread by close contact, whereas the viruses which result in pandemics are spread through the air. Having said that, though, something like HIV is very successful, because it is so insidious; it is possible to be infected and not to know it. It also exploits a sure-fire mechanism for going from one individual to another. So whilst it is slow spreading, compared say to flu, it is extremely difficult to eradicate.

‘The other point to make is that part of the danger of viruses is that they can be unpredictable. For example, when the H5N1 avian flu first appeared in Hong Kong in 1997, it wasn’t clear how it would develop. Although it killed quite a high proportion of the people it infected, it turned out in the end that it wasn’t very infectious; it wasn’t able to spread very quickly. The authorities in Hong Kong were quick off the mark, and by killing thousands of chickens they were able to prevent it from running out of control. It re-emerged in Hong Kong and the Far East in 2003. Again, it killed large numbers of chickens but not many humans. Thankfully it looks as if it isn’t the kind of virus which is going to cause a pandemic. But this wasn’t clear at first, and for a while it was quite frightening. Of course, the chances are that someday a new strain of flu will emerge which does have the potential to cause a pandemic, but we now have very sophisticated monitoring mechanisms in place, so just maybe we will be able to do something to stop it spreading.’

Given the dangers which influenza poses, and given the length of time that the virus, in one form or another, has been around, what has prevented us from developing a vaccine which is effective against all its strains?

‘The flu virus changes the whole time, it’s constantly mutating, and the changes which occur can be very large; that’s gene swapping, rather than just single base pair swapping,’ replies Crawford. ‘This means that all you can really do is to second guess which particular strain is going to appear twelve months down the line. The World Health Organisation (WHO) produce a vaccine based on what they think will be the most prevalent strain of flu. But, of course, if a completely new strain turns up, then it takes time to create a new vaccine, by which point it may well have spread a long way. The policy we have at the moment is a sensible compromise; we vaccinate on the basis of what we think is likely to be around, and we target old people and people with chronic illnesses, because they’re at most threat from the virus.’

The threat posed by viruses such as influenza has been exacerbated in recent times by the huge growth in international air travel. The outbreak of SARS which occurred at the beginning of 2003 illustrates this point nicely. The illness was largely confined to areas in East and Southeast Asia. However, there was an outbreak in Toronto, Canada, which it proved possible to trace to one woman – Sui-Chu Kwan – who had contracted the disease during a visit to Hong Kong.

‘International travel does have a huge impact on the potential for a virus to spread,’ Crawford confirms. ‘But the speed with which the authorities responded to SARS was pretty impressive. Also, it is likely that the effects of globalisation will be somewhat mitigated by the monitoring processes which are now in place. But, in the end, a lot of this comes down to chance; sometimes you can just be unlucky.’

If there is an outbreak of a disease such as SARS, what kind of strategy is it best to pursue in order to keep it in check?

‘Well, it partly depends on whether you have a vaccine or not,’ Crawford replies. ‘In Toronto, for example, if there had been a vaccine for SARS, then they could have vaccinated all the people who had had some contact with the first victim. The idea is to ring-fence the infection in an attempt to stop it spreading. However, there is always some dispute about what kind of policy is most likely to be effective. For example, during the recent foot-and-mouth disease outbreak in the UK, there was a huge amount of debate about whether vaccination was appropriate; whether it would make the problem worse or better. After the outbreak was over, they looked at the issue using some very sophisticated mathematical models; and what the models suggested was that if they had ring-fenced the infected farms, and used targeted ring vaccination around them, then that probably would have cut the duration of the epidemic. But the problem is that if an epidemic springs up very quickly, it is only really possible to do this kind of modelling after the event.’

There has, of course, been some success in combating viruses. In 1980, for example, the WHO declared that the smallpox virus had been eradicated from the world. Are the advances in molecular genetics likely to bring more of this kind of success? Presumably the more that we know about how viruses work, the easier it is to develop the means to combat them?

‘That’s right,’ Crawford replies. ‘Viruses are so small that they were among the first entities to have their genomes sequenced. We’ve learnt a huge amount; we know, for instance, that certain genes have specific roles to play in the way in which viruses transform the cells which they attack. The big hope in virology is for the development of antivirals which work like antibiotics. There has been tremendous success with HIV, for example. We now have something like fifteen drugs which we can use to keep the illness under control; and from the time of the first generation drugs, these have been developed on the basis of knowing which genes are required for particular functions of the virus, and then blocking them in various ways. This has been very effective. Almost certainly there will come a time when we can treat viruses with antivirals just as we treat bacterial infections with antibiotics.’

Although it is undoubtedly the case, as we have seen, that increased understanding of the workings of viruses will bring benefits in terms of our ability to treat a variety of illnesses, it also brings with it a number of new problems. Particularly, there are issues to do with the possibility that genetically modified viruses might be employed as terrorist weapons.

‘This is a very real threat,’ Crawford says. ‘Just think about the flu virus for a minute. If somebody produced and released a new strain of flu, then there is a good chance that we’d get a pandemic as a result. It is possible that it wouldn’t kill huge numbers of people, but it would certainly cause massive disruption and lay a lot of people low for a while. But what about if somebody produced something just a little bit more lethal than flu, but which spreads in the same way; that could be devastating.

‘If there are people with skills like mine, who are also bioterrorists, then they can do this kind of thing. They could manipulate a virus and produce, for example, some kind of hybrid between Ebola and smallpox, and that would be horrific. It is a real possibility. I’ve never really been able to understand why people talk so much about Anthrax as being the great threat. Although I’m not a bacteriologist, it does seem that it is rather hard to infect large numbers of people with it. But this just wouldn’t be the case with a virus; smallpox on its own, for example, could be devastating.’

Perhaps the other major concern facing microbiology at the present time has to do with bacteria, rather than viruses, and the fact that the shelf-life of the current crop of antibiotics might be coming to an end. The problem has been caused by the fact that bacteria have evolved resistance to the antibiotics currently in use (in part as a result of the overuse of antibiotics). Is this something that we should be worried about?

‘Definitely,’ replies Crawford. ‘In a way, this is more worrying than something like SARS. Although SARS hit the headlines, it wasn’t a big epidemic, and it was very efficiently dealt with. But MRSA, for example, has been in our hospitals for quite some time, and it isn’t something we’ve been able to deal with properly.

‘There are various things we should be looking at here. First, we need to control the free sale of antibiotics across the counter, and to regulate which antibiotics are used with which particular diseases. There are good data which show that where you get the free sale of antibiotics, you get more resistance developing in bacteria in the community. Second, we need to look at the issue of animal feed. This is a particular problem in the USA, where the gene pool of bacteria is being affected by the fact that antibiotics are given to animals for no good reason. And, of course, the other thing we have to do is to develop new antibiotics.’

One moral of the story of increasing bacterial resistance is that it is the nature of evolution that we’re always likely to be involved in a battle – an arms race, if you like – with infectious agents like bacteria and viruses. Does Crawford see a day when we might win this battle once and for all?

‘The first thing to say is that we’re always going to be in a catch-up situation with respect to microbes,’ she replies. ‘Their short replication time means that they can mutate very rapidly, whereas it takes us much longer to adapt to them. HIV, for example, changes very quickly, so although there is an immune response at first, in the end the immune system isn’t able to cope.

‘In terms of the general point about whether we are ever likely to live in a microbe free environment, the idea might be that because we’ve managed to eradicate one virus, in the end we’ll eradicate all viruses. But I doubt that this will ever happen; not least there will always be new mutations which will mean that viruses which in the past were not able to infect us, will become infectious.

‘Also, it is not entirely clear it would be a good idea to live in a microbe free environment,’ Crawford says. ‘For example, there is the possibility that by eradicating a virus you will create a space which other entities will come to fill. So whilst it was a good thing that we got rid of smallpox, there is the chance that monkey pox will take over where smallpox left off. It isn’t entirely clear how much sense this idea makes, but it is certainly something we have to think about.’

Aren’t there also some radical types who argue that because viruses are a life form they should be preserved?

‘Yes, but I don’t have any sympathy with that view,’ Crawford responds. ‘I would have pressed for the complete elimination of the smallpox virus. Of course, whether that would have been a good thing is now complicated by the terrorist issue.’

How much threat are human beings under from microbiological agents of illness? There is an argument that the genetic diversity of the human species will afford us a certain amount of protection against even the most devastating of pandemics.

‘Yes, this is my view,’ says Crawford. ‘In any pandemic, it is only a proportion of the people who get infected who get ill. It’s what we call the iceberg effect. With any virus, there will likely be a varying proportion of people that you would never know were infected unless you did an epidemiological study. It is certainly the case with flu, and is massively the case with polio. So yes, I think that human beings are genetically diverse enough to be able to deal with the threat from microorganisms.’

Extracted from What Scientists Think (Routledge) by Jeremy Stangroom.