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NARRATOR:
The destruction could only take place if there was a unanimous decision, but the idea was vetoed. Politicians could not agree what to do with the virus. Meanwhile, disaster struck. It was in Birmingham, in a lab that was studying the links between smallpox and other animal pox viruses. One summer a medical photographer, Janet Parker, was working in her office one floor above the smallpox lab.

ALASDAIR GEDDES:
The call came at 8 o'clock in the evening and I have to say that every part of that evening, which continued until 4 o'clock in the morning, remains etched in my mind. The very thought that the disease might have come back was absolutely shattering, although I didn't believe that this had happened. Got into my car, drove to the hospital went into the room and I didn't need to go any further. It was a horrifying experience to be faced with what clearly was the rash of major smallpox.

NARRATOR:
Like a Houdini, the killer virus had escaped captivity. There was a public enquiry, but it was never resolved what had actually happened. In order to infect Janet Parker the virus would have had to have escaped from the ground floor lab, travel upstairs, perhaps through air ducts or along corridors, and into Janet Parker's office. To this day no-one knows how the killer managed to do it.

ALASDAIR GEDDES:
The patient was transferred to the smallpox hospital where she rapidly became critically ill and a few days after admission she died. I had the misfortune to treat the last case of smallpox in the world and I sincerely hope that I will never see another one.

NARRATOR:
No-one was going to take any more risks with the virus. The World Health Organisation decided to remove it from every research lab around the world and fly the samples to just two top security laboratories on either side of the Iron Curtain.

DONALD HENDERSON:
The thought that that virus might escape, that we might again get smallpox re-established throughout the community is so frightening that no laboratory director wants to treat this virus in any other way but with the most rigid secure precautions.

NARRATOR:
Thousands of miles from Moscow, deep in the snows of Siberia, lies VECTOR, Russia's high security biological research laboratory. Guarded day and night, here 2,000 scientists work intimately with the most lethal viruses and bacteria on the planet - Ebola, Marburg, Congo fever. They work in bio-safety 4 laboratories, hot zones, the stuff of science-fiction. P4 labs are extraordinary. The scientist enters the viruses' domain sealed inside his own bubble, never even breathing the laboratory air. The spacesuits are sealed and pressurised. Only under these extreme conditions is anyone allowed to work with this lethal virus. On the other side of the world the Americans work under identical conditions. To ensure the virus never escapes from the lab, at the end of each day's work the scientists shower in disinfectant before they and their spacesuits re-enter the outside world.

DR BRIAN MAHY:
If there was ever any release of the virus into the current, susceptible population, I would be totally devastated. I believe that it is our responsibility to prevent that and keeping that virus as long as we have it here is a continuous worry to us.

NARRATOR:
The fear now is of terrorism.

BRIAN MAHY:
Smallpox has always been at the top of any list of possible terrorist weapons. I don't believe that this is an idle threat, this is a serious threat and one which, God forbid, it would never happen, but nevertheless we need to do everything we can, not only to preserve the virus and keep it here, but as soon as possible to destroy the infectious virus so that that threat no longer exists.

DONALD HENDERSON:
During the 1980s it became clear to everyone that there was a building pressure on the part of all countries to come to the end of this programme and draw a line with the destruction of the virus. The US scientists and Russian scientists who, at that time, had the virus, worked out a series of steps to be taken to make sure that we had characterised the virus as carefully as we could and a total DNA map of the virus began to be constructed, and it was decided that this could all be done by the end of December 1993.

NARRATOR:
On either side of the Iron Curtain the pressure was on to complete the painstaking work of sequencing the DNA of this deadly virus before its scheduled destruction in 1993. Samples of two particularly virulent strains were defrosted and chemically broken down to extract the strands of DNA from the very heart of the organism. Enzymes cut the DNA into tiny fragments which were cloned ready for analysis. Hundreds of gels were made. Each cloned segment of the DNA was pushed through the electrified gel to separate out the DNA fragments. The nucleotides could then be read like a book. It took 2 years. Gene by gene the story of this virus was laid bare. Thousands of years of evolution. Fragment by tiny fragment, the whole blueprint of this killer was pieced together, but amongst these hundreds of thousands of nucleotides what was it that made smallpox so deadly to humans. Could there by somewhere in this sequence a killer gene? But all too soon it was 1993 and before that question could be answered, it was time to destroy the virus. An international expert committee had planned the event in great detail. At exactly the same time, on either side of the planet, the virus samples would be put into autoclaves and pressure heated to 120 degrees Centigrade for 45 minutes. The only known stocks of the virus would be dead and the world would at last be rid of this terrible enemy.

DONALD HENDERSON:
But it didn't happen.

NARRATOR:
They postponed the destruction because something extraordinary happened. It had started when scientists from labs around the world began to compare the genes in various pox viruses, including smallpox and vaccine, and those in gene banks. Gene banks are computer libraries that hold the genetic information of every living thing on the planet that has been sequenced:

birds, plants, mammals, even viruses. Any match between sequences is a hit. A hit means two creatures share a similar gene, they have something in common.

DR GEOFFREY SMITH:
I remember feeding the data into the computer after these months of work, going away that night, letting the computer searches be completed and coming in the following morning to see what the output was from those searches and being absolutely astonished.

NARRATOR:
The pox viruses had found hits, over and over again, but these were not hits with other viruses, nor even with other pathogens. They were hits with human genes.

GEOFFREY SMITH:
We got the most amazing surprises. This virus seemed to have genes which were completely unexpected and which we had no idea were going to be present at all. It represented the most extraordinary collection of hits that had been discovered in any virus but it was the diversity of these hits that was the astonishment. We really had no idea these would be there and there was no precedent in other virus groups for this diversity of hits either.

NARRATOR:
There was something even more bizarre. There were hits with genes from the immune system., the very system carefully designed to defend us against viruses. What were these viruses doing with genes from our own immune system?

DR PAULA TRAKTMAN:
What became clear is that within these genes were instructions that seemed to have been hijacked from the host immune response. In other words, these viruses were mimicking the host. They had stolen components from the immune and inflammatory response and this was really an astounding realisation. It was a new level of complexity, something none of us, I think, were prepared for.

NARRATOR:
But why would the pox viruses want to mimic us? To hijack our genes and incorporate them into its own DNA would have taken thousands of years of evolution. The virus had to have some diabolical reason for it. The clues had to lie in those hits with the immune system. The immune system is our defence against invaders. Complex and efficient, it swoops in and attacks any virus or bacteria that invades the body. Although it's been studied for 100 years, much of it is still a mystery to scientists. What we do know is that the whole defence depends on an intricate communication system. When cells are invaded by a virus, they send out SOS signals, tiny protein molecules that swarm out of the infected cell and hone in on surrounding healthy cells and warn them to defend themselves against the intruder. These molecules lock onto tailor- made receptors on the cell surface and flash the warning message into the cell. These messages can, for instance, tell the healthy cell to create fever or inflammation to kill the virus, or even to commit suicide so the virus cannot spread.

But scientists discovered something quite astonishing. The pox viruses had copied from us the genetic information of how to make receptors. Using these stolen genes, they manufactured decoy receptors to hijack our own messenger molecules. As the SOS messages hone in on the healthy cells, they're swept up by the viruses' fake receptors, so the warning never gets through.

PAULA TRAKTMAN:
There was a dawning of recognition that these beasts had tricks that we had never seen before and it was a sort of thrilling time.

NARRATOR:
With these tricks the pox viruses could control our fever and inflammation to suit themselves, or could prolong a cell's life to prolong their own. In fact the virus had so many different weapons it could sabotage our whole immune system and take control of our bodies.

GEOFFREY SMITH:
We had not expected that at all. It had proteins that interfered with Interferon.

PAULA TRAKTMAN:
That produce inhibitors of Interferon Alpha and Interferon Gamma.

GEOFFREY SMITH:
It had proteins which would intercept Interlukins.

PAULA TRAKTMAN:
And this theme of decoy receptors is echoed in the fact that the virus makes a decoy receptor for T.N.F.

GEOFFREY SMITH:
Proteins which complemented Complement.

PAULA TRAKTMAN:
Which is a defence that in the end blows holes in infected cells and causes them to die.

GEOFFREY SMITH:
Proteins related to Serin protiase inhibitors or serpins. It had a whole variety of these molecules.

PAULA TRAKTMAN:
So this diversity and this mimicking the immune system and using its own tricks against itself I think is astounding and really unique.

NARRATOR:
With this growing list of discoveries, it dawned on the scientific community that the virus understood us better than we understood ourselves. While battling against us for thousands of years it had unlocked the secrets of our immune system, secrets that are still a mystery to us. Scientists now began to feel that the smallpox virus might be too precious to destroy.

GEOFFREY SMITH:
The World Health Organisation had proposed that the smallpox virus should be destroyed and it was paradoxical that this proposal was being discussed at a time when we were just beginning to understand how enormously complex these viruses were and indeed how much we could learn from them. It's possible that by learning how these molecules work in the immune system, we learn about how the immune system works and that understanding may enable us to develop new drugs that will combat other infections.

NARRATOR:
If we could learn and adopt the very tactics that these viruses use to gain control of our immune system, it might give us the means to cure ourselves.

PAULA TRAKTMAN:
I think we're looking at a whole new way of treating disease. I think these viruses have illustrated for us the principles of decoy receptors, the principles of tinkering, in subtle but clever ways with the host response and I think that they're leading the way to showing us whole new ways of making drugs and treating disease.

NARRATOR:
This is already happening. In America at least one biotech company has honed in on the concept.

DR CRAIG SMITH:
If we're trying to develop a drug somewhere down the line, a new insulin or a new human growth hormone or a new protein that stimulates red blood cell development, or something that the body produces to fight off infections, clearly those would be useful drugs. If you want to find those, a short cut to finding them is clearly to focus on the genes that are in viruses because we know many of them are, in fact, exactly the kind of thing that we're looking for. By focusing on smallpox we get a concentrated short-list of what the important genes of the immune system really are.

NARRATOR:
Craig Smith recognised that viruses could hold vital clues to finding drugs, and he went on to develop a drug that mimicked the decoy receptors that smallpox makes. In this case, the drug he has produced works to control the inflammation of rheumatoid arthritis, using exactly the same tactics as the virus uses.

CRAIG SMITH:
Smallpox and viruses like it are excellent candidates to study to find, downstream, drugs that can be used to treat disease and we are willing in our case to put hundreds of millions of dollars towards that end to invest in that kind of knowledge.

NARRATOR:
Over at the high security laboratory in Siberia, this idea has caused excitement.

PROF. SERGEI SHCHELKUNOV (RUSSIAN WITH SUBTITLES):
We can synthesise individual proteins and use them for future pharmaceuticals. The smallpox virus is an outstanding example of this. It could be used to treat severe diseases that are now virtually untreatable such as septic shock, cerebral malaria, rheumatoid arthritis, acute AIDS- related conditions and so on. And this is what we're working on now.

CRAIG SMITH:
Without doubt, because of the number of genes that we know are in smallpox, there are many, many more we still have yet to discover. That's one reason why people are putting such an effort now into understanding the genes of smallpox and why we shouldn't give up until we really do understand them all because what we've accumulated so far is literally the tip of the iceberg. It would be a shame not to understand everything that that virus can tell us about how our own bodies work.

NARRATOR:
Until recently, we knew nothing of the magical secrets of the pox virus genes. We have now studied about a dozen genes, and of those two have already led to potential drug treatments:

for rheumatoid arthritis and heart disease. There are many more genes that we have yet to study in the smallpox virus, each of which might lead to new drugs, but there's something more. These genes may tell us how all other deadly viruses attack us because smallpox uses every trick there is.

WOLFGANG JOKLIK:
Smallpox is the most successful virus and the largest. It knows best how to kill. We have to find out how it does it in order to explain how other viruses kill. How Ebola kills, how AIDS virus kills, how Hantan virus kills. Smallpox has 50-100 genes that interact with human defence mechanisms. Let us make an encyclopaedia first, let us find out what these 50-100 ways are in which human defence mechanisms can be neutralised, in which smallpox virus does it. If we had this encyclopaedia, when we then turn to AIDS we could just go through all the various ways, ask does it do this, does it do that, that's one experiment in each case, and we would hopefully arrive at the specific way in which the AIDS virus counteracts human defence mechanism. Now there's no guarantee of that, but certainly smallpox virus has many more ways of interacting with human defence mechanisms than any other virus, so let us make this encyclopaedia first because that would save an enormous amount of time, and time with a highly lethal virus like AIDS means people. It saves lives.

NARRATOR:
But time may be running out for extracting the vital information from the smallpox virus. The ever-present threat of terrorism has put pressure on politicians to reopen the case for destroying the last stocks of smallpox.

NARRATOR:
On May 24th 1996, WHO gathered to decide finally the fate of the smallpox virus.

PRESIDENT:
The subject is very important and I therefore would like to appeal to your sense of responsibility.

WOLFGANG JOKLIK:
The issue of deciding whether to destroy smallpox virus is of the utmost importance. It's vitally important. It's much more advantageous to humanity to keep the virus and study it than to destroy it. I don't see what would be gained by destroying it.

PRESIDENT:
We shall now open the debate on this item.

DELEGATE:
The eradication of smallpox from the face of the earth represents WHO"s proudest and greatest achievement to date.

DELEGATE:
It was one of the most important public health achievement by...

AUSTRALIAN DELEGATE:
Any accidental release of virus from these centres could be catastrophic.

INDONESIAN DELEGATE:
Because most of the population today in the world are not immune to smallpox.

DONALD HOPKINS:
I personally do not think that the virus should be destroyed. To destroy it says that we in this generation believe that nobody ever is going to imagine a potential use for this virus and I don't think we have that much intelligence or the right to do that for all humankind.

PRESIDENT:
..federation. I give the floor to the delegate of the United States of America...

UNITED STATES DELEGATE:
...considered decision. We believe it is important that the world community move forward together in consensus to destroy the virus as...