We've been hearing a lot recently about the return of diseases that we thought were a thing of the past.
 

Despite better hygiene, antibiotics and immunisation, we've only ever eliminated one disease in the course of human history and that's smallpox.
 

After decades of global vaccination campaigns - in 1980 smallpox was declared eradicated. And the only two remaining samples of the virus are buried in well marked laboratories in Atlanta and Moscow.
 

But now scientists are wondering whether the spectre of smallpox might be rising from the dead. Perhaps reincarnated in its close relative monkeypox, which is alive, well and spreading in Central Africa. Rae Fry reports...
 

Rae Fry: One of the last resting places for the smallpox virus is the US Centre for Disease Control in Atlanta, Georgia. It's also the home of a breed of scientists known as the virus hunters. These hunters have best selling books written about them, and they work with the deadliest germs. And like the viruses they work with, they sometimes have to adapt rapidly to changing conditions.
 

Late last year the Chief of the Centre's special pathogens branch, Dr Ali Kahn had a call from the World Health Organisation. Dr Kahn's usual specialty is the Ebola virus. But he soon found himself in the Democratic Republic of Congo, in the middle of a civil war, investigating an outbreak of monkeypox.
 

Dr Kahn: The number of cases that were reported to us was a lot higher than had ever been previously reported for monkeypox and there were reports of a large number of cases that were being transmitted from person to person which was an extremely unusual feature. And since monkeypox is related to smallpox, although it's not the same disease, we thought that it would be a good idea to check it out despite the fact that there was a civil war going on at that time.
 

Rae Fry: One of the world's leading authorities on smallpox and the pox viruses in general is Professor Frank Fenner from the Australian National University. He played a critical role in the global eradication campaign for smallpox and he's seen monkeypox before.
 

Professor Fenner: When monkeypox first occurred it was thought to be cases of smallpox occurring in populations from which it had been eliminated, and it's very similar to smallpox in the clinical features - the rash is very similar, the only difference is that in monkeypox the lymph nodes in the groin, in the neck and elsewhere in the body have become enlarged, and they don't become enlarged in smallpox.
 

Dr Kahn: Monkeypox can look a lot like chickenpox - They're a pox like lesion that are usually all over persons body including the palms of their hands and their soles - and usually they have some swollen glands in their neck or under the arms or in their groin that's very distinctive - and that sort of picture in a young individual usually suggests monkeypox.
 

Rae Fry: Does it tend to hit children more?
 

Dr Kahn: Yes, it does tend to hit children more and that was definitely true in the past. It's much less true nowadays because people are no longer vaccinated against smallpox which is protective against monkeypox also.
 

Rae Fry: And how many of the people who are contracting the disease are dying from it?
 

Dr Kahn: Our initial figures suggested three to four percent.
 

Rae Fry: Dr Ali Kahn and before him, Frank Fenner.
 

The mortality rate for monkeypox is much lower than it is for smallpox. But when Professor Frank Fenner and his colleagues first discovered monkeypox the possibility that it could be smallpox had a potentially terrifying implication
 

Professor Fenner: It looked as though there might be an animal reservoir of smallpox, and if that had proved to be true, then eradication would have been impossible.
 

Rae Fry: It was lucky that smallpox did turn out to be an exclusively human disease, because only then did they know that when everyone in the world was immunised, the virus would disappear. The prospect of monkeypox becoming more infectious to humans is scary because a virus with a wild animal reservoir is never going to die out. And it does now look as if it's getting easier for people to catch monkeypox.
 

Dr Kahn: The disease is contracted in two separate ways. The primary way it's contracted, is from coming in contact with the natural reservoir, or the host or carrier of the disease - and that's usually squirrels as far as we know, although that data is very limited. The people would hunt the squirrel or touch a squirrel and somewhere in that process would become infected. And that, in the past has been the primary way people get infected. Over 75 percent of people probably got infected coming in contact with whatever the natural host for the virus was out in the wild. Twenty-five percent of people in the past got infected by taking care of somebody who already had the disease. So it's contagious from person to person, and that contagiousness probably had to do with direct contact, physically taking care of the patient. And the interesting feature of this disease now, compared to the past, is that probably 75 percent of cases are now transmitted from person to person as opposed to being acquired naturally from the wild.
 

Rae Fry: These are preliminary figures, but if the virus is now spreading from person to person, rather than from animal to person, the challenge for the virus hunters is to work out why? Could the monkeypox virus be turning into something else... something nastier for humans... something more like smallpox?
 

Dr Peter Jahrling is from the US Army Medical Research Institute of Infectious Diseases.
 

Dr Jahrling: We've always known that the monkeypox virus is very closely related to the smallpox virus which of course was one of the great pathogens of all time. We've also known that the monkeypox is infectious for human beings. The part of it that we've not quite understood is why is it that the monkeypox virus doesn't seem to be transmitted from person to person the way the smallpox virus was. I think the recent events in Congo suggest that this time perhaps the virus is being transmitted from person to person more efficiently than we've seen in the past, and we don't know if that's just the difference in observation and reporting, or if in fact the virus has changed.
 

Rae Fry: So now let's go back to February and the hunt for the virus in the Congo. Dr Ali Kahn's team visited 12 villages in the rainforest region where monkeypox had been reported. But their search for clues was cut short.
 

Dr Kahn: Our field work had to come to an abrupt halt. Within about six days of being physically out in the field site because of the retreating Zairean army we had very inadequate communications to let us know their movement back towards Kinshas and when we were told that they were potentially no more than a couple of hours from our field site, we were forced to evacuate our field site, which turned out to be very prudent since we heard that the retreating Zairean army went through our field site about 24 hours later and a lot of damage was done to the locals in the process.
 

Rae Fry: What kind of damage?
 

Dr Kahn: There was a number of people that were killed and property looted and then the country actually fell to the rebels within a month of our departure.
 

Rae Fry: Hardly ideal conditions for research. But as the hunters retreat, the virus advances, and the full scale of the outbreak has yet to be measured.
 

Dr Kahn: Given the short time we had available to us in Zaire, what we did is we concentrated on 12 villages and did a door to door search and a census to try to get good figures on how many people were sick in specific age groups. And what that showed us right away was that the attack rate, that the number of people who were becoming ill was two to three-fold higher than anything ever previously reported - even in so-called 'outbreak situations'. And that was only 92 people, although we were aware of over 140 people. There's a recent article put out by our colleagues in WHO again working with our Zairean colleagues suggesting that they have an additional 170 cases they've seen over the last couple of months. So it seems like an ongoing large outbreak at this point.
 

Rae Fry: To understand the dynamics of this outbreak researchers really need to know why the chain of human to human transmission is getting longer. It's important that the figures are reliable because direct infection from animals could also be increasing - especially during the civil war. Food shortages could mean people are trapping and eating more wild animals than usual. So how does a virus hunter tell the difference between a case that comes straight from an animal and one that comes from another person? Dr Ali Kahn again.
 

Dr Kahn: That can prove to be very difficult. A lot of it has to do with trying to dissect out when they got sick in relationship to each other. So people who get sick without any contact with anybody else sick within seven to 21 days of becoming ill, we presume those people are actually getting sick from out in the wild. More problematic are the people who become within seven to 21 days of having contact with somebody else. They also could have had some contact with something out in the wild, but most likely their disease is from having contact with somebody who is actually ill.
 

Rae Fry: This is not the first time there's been a human outbreak of monkeypox. There was one between 1981 and 1986 and Professor Frank Fenner studied that outbreak very closely. He's been comparing his notes from then with the figures from this most recent outbreak in the Congo.
 

Professor Fenner: It was a larger number of cases in a smaller region than we observed in any part of the outbreaks in 1980 to 1986. The mortality rate was lower, only three percent mortality rate, but the person to person infection, as judged by the same criteria that we judged person to person infection on, was much higher. So they are two major differences. Now the population is also different in that in the period that we looked at, over 70 percent of the population was vaccinated. Now vaccination stopped in 1980 with the eradication of smallpox, so a population now of children has grown up that haven't been vaccinated, and that drastically increases the pool of susceptible people.
 

Rae Fry: What Professor Fenner is saying is that the smallpox vaccine also gave immunity to monkeypox, so the fact that people aren't vaccinated these days, could be creating a newly vulnerable population. And that could be explained in the increase in transmission. In other words the virus itself isn't necessarily becoming more aggressive. One way of checking is to look at the virus's genes. And genetic studies seem to confirm that the virus hasn't changed all that much. Dr Peter Jahrling.
 

Dr Jahrling: The early results that we've heard comparing the genetic sequence of monkeypox virus isolated recently, compared with the isolates from 1972 indicate that it is very very close. So unless there's a virulence factor that's coded for the three percent difference between the recent isolates and the older ones, then in fact the virus is not changed.
 

Rae Fry: Then in that case, why the panic? Dr Jahrling himself was quoted in science last month as saying that for practical purposes smallpox is back. He agrees it's an oversimplification but says there's still cause for concern.
 

Dr Jahrling: Well I think the worst case scenario is that the virus does have a transmissibility of its big brother smallpox, and that the virus is being maintained in nature, not only in human beings as smallpox was, but in rodent hosts such as squirrels and the like, and that it will not be possible to eradicate the virus as we did successfully with smallpox. That would be the worst case scenario, and I'm not saying that's the case, but you know, it's something that we have to consider.
 

Rae Fry: The thing is that even if the monkeypox virus isn't changing its form, there's still the problem of an infectious disease that's getting worse. Dr Ali Kahn.
 

Dr Kahn: What's going on right now is not well understood, because the disease is now occurring in a different situation from what it has originally been studied, in that these people no longer are vaccinated against smallpox and vaccinia any more. So we're not sure what the normal pattern for new monkeypox will be and are only now learning that.
 

Rae Fry: On the basis of the data that you have so far, can you confidently say that this is not going to balloon out into an epidemic of major proportions?
 

Dr Kahn: No definitely not. If we were confident of that fact, we wouldn't be out there trying to collect additional data. We have no idea what's going to happen to monkeypox now that people are not vaccinated against smallpox anymore. Some of the studies done, again in the early 80's suggested that even when vaccination levels went down to zero, there never would be a risk of sustained person to person transmission. And when I say sustained person to person transmission, I'm talking about something like measles or chickenpox, and you don't need to have any contact with an animal reservoir, it can just go from person to person forever. So we do not know exactly what the new picture with monkeypox will be.
 

Rae Fry: Hunting a virus is one thing... controlling it is something else. But if the smallpox vaccine gave immunity to monkeypox, isn't the simple answer to re-introduce vaccination? Professor Frank Fenner.
 

Professor Fenner: I don't think so. I think the risk of vaccination with ordinary smallpox vaccine in Zaire at the present time, with the high level of HIV in the country, and therefore people who are immuno-suppressed, would be dangerous. That's with ordinary smallpox vaccination.
 

Rae Fry: The smallpox vaccination itself can make you sick if your immune system is not healthy. One control possibility is to give a weakened version of the vaccine. Although there's some question of whether it would actually protect against monkeypox. Another possibility - anti viral drugs, is under investigation by the US army. They weren't out looking for a treatment for monkeypox. They were using the virus as a stand in for smallpox in biological warfare experiments. Dr Peter Jahrling from the Army's Medical Research Institute of Infectious Diseases explains.
 

Dr Jahrling: Of course one of our concerns in the Army is that the smallpox virus could be used as a terrorist weapon And in one of the problems is that there is no animal model for smallpox. The smallpox virus is restricted as we've said, only to the human host - the closest virus that was available for us to model our studies on, was monkeypox. So we got into the monkeypox business for the reasons that we wanted to test the vaccines against an aerosol monkeypox threat, and we also wanted to test whether new generations of anti-viral drugs which have been produced for other diseases might be effective against monkeypox. And by inference, against smallpox.
 

Rae Fry: The anti-viral drug treatments look promising. And the US Army has asked to go along on the next mission to the Congo. But even if the medicines do work against monkeypox, they'd probably be too expensive for a poor country to afford. So trials of the weakened smallpox vaccine are continuing. All these experiments have raised some basic questions about the close relationship between an existing virus, monkeypox and one that we thought was dead and buried. Smallpox was once described as the most devastating pestilence in human history. Something, you'd think, we'd be keen to get rid of. But the monkeypox outbreak has made some scientists resurrect a debate over what should be done with the two remaining samples of smallpox. The one in Atlanta is known to be quite secure. The other is in Russia and there are concerns about its safety. Both are supposed to be destroyed in 1999. And the question of whether they should be kept for more research, is a highly sensitive one. Dr Ali Kahn.
 

Dr Kahn: I'm not sure if I'm qualified to answer that question. I'm always for more research and especially research that will clarify why smallpox is such a highly lethal disease compared to monkeypox, which has not appeared to be so compared to vaccinia which is actually the vaccine given to prevent smallpox, which is not very different from smallpox. I think those issues are very important issues. They get at the heart of what makes a virus pathogenic, or what makes a virus dangerous to humans and those issues do need to be clarified and figured out.
 

Rae Fry: Professor Frank Fenner doesn't think the virus should be kept. Perhaps that's hardly surprising since he chaired the committee that 17 years ago was able to pronounce smallpox gone from the face of the earth. In his view, the monkeypox argument for keeping the smallpox virus is unconvincing.
 

Professor Fenner: I don't think it affects the argument at all. I think there is a justification for continuing investigations of the monkeypox virus but I don't think it really affects the argument about the destruction of stocks of smallpox virus. Smallpox is a much more dangerous virus if it ever got loose, than monkeypox. Monkeypox is after all, in the wild now, and can't be got rid of.