It is the perfect argument for a scientific thriller: the rescue of the smallpox virus to use as a biological weapon. Although that disease was officially eradicated in 1980, the cause, of which samples are kept in two high-security laboratories, remains the largest serial killer in history. In recent centuries he has killed more people than all natural catastrophes, epidemics of plague and wars together. Canadian virologist David Evans has shown that such a fearsome recovery would be possible.
The proof? His team managed to assemble the horse pox virus – which was extinguished decades ago – by collecting pieces of its genetic sequence. It is not surprising that this work highlights the dangers of synthetic biology, although it is not understood that it was rejected by two important journals. “We were very careful not to break any Canadian law and nobody was surprised,” says Evans, who is a researcher at the University of Alberta.
– How did the initiative to recreate the pathogenic agent of the horses?
A pharmaceutical multinational called Tonix was interested in finding alternative vaccines for the human disease. They contacted me to check the issue of the licenses for the different Vaccinia strains (in reference to the family of the smallpox viruses), and we ended up discussing their history. The chief scientist of immunology knew very well how Edward Jenner invented the vaccine in 1796. And the conversation led to modern immunotherapy. Then we realized that we did not really know where that virus came from.
“Apparently, Jenner observed that milkmaids who milked cows infected with bovine smallpox were protected against the disease that killed humans.
That’s what the legend says, but if you read his book and others of the time you will discover that some researchers already suspected that Jenner used the equine pox virus. Maybe it was transmitted from the horses to the cows, and, from there, Jenner was able to take advantage of it.
-What did you do next?
We decided it was worth using the equine virus as a vaccine, but we did not get samples. I suggested then that we rebuild it.
-And how do you get that?
Some viruses, very simple, consist of ribonucleic acid (RNA), which you can use to infect cells and get them to make them. But in the case of smallpox, we talk about DNA, which is also not infectious. Then we take advantage of a phenomenon called reactivation. If you have a cell previously inoculated with any smallpox virus – not necessarily the same one you are trying to rebuild – you can re-infect it with the DNA of yours. In the case of the equine pathogen, because its genome is too large, it is split into pieces that overlap and transfer them to the infected organism. The viruses that are already there classify and organize these fragments. The trick is to separate the one that interests you from a soup.
-And do not worry about incubating extinct viruses?
Yes, and I would like to know if someone can misuse this. We know that there are stocks of the smallpox virus in Russia and the United States, but I would not be surprised if there were other hidden consignments… There are many ways to cause panic and with something yes and besides, it would not be the only case.
-It’s not very reassuring… What other cases do you mean?
The rinderpest virus, which was eradicated, could be assembled relatively easily. Or the polio, which has almost disappeared. Mobile phones have been used to activate explosives, and GPS tells you where you are when you get lost, but also guides smart bombs. All these technologies can be used for various purposes.
– And what is your practical goal?
We modify viruses to treat gallbladder cancer: they can directly kill malignant cells or provide immunity to them. We will undertake the first clinical trials within one or two years. When journalists ask me about the danger of smallpox, I usually answer them with another question: what do you worry about more, this disease or cancer? We can not rule out GPS or mobile phones, which make our lives easier.
-Rescatar virus assembling your DNA in the laboratory is a part of synthetic biology. Could you consider creating life from inert matter, or will you always work with living elements?
It all depends on where you put the line to say “from here, this is science fiction”. A few years ago, Craig Venter analyzed the genome of a bacterium and deduced the minimum number of genes he would need to live. But you can try to go a step further and ask yourself: “Why does the genetic code have only four letters – nucleotides A, T, C, G-? Could it be different? ” Synthetic nucleotides have been introduced into bacteria to see if they are capable of using them and if other molecules can recognize them. We would then be talking about very interesting life forms. If what worries people is that they escape from the laboratories, I would tell them to stay calm: here we feed them correctly; outside, they can not grow.
-If we ever managed to manufacture synthetic life, would the mystery of what exactly life be solve?
It is easy to explain: it is a series of autonomous chemical reactions that manage to reproduce. Imagine a pond full of molecules on a primitive Earth, subject to sunlight and ultraviolet rays. There, the RNA strands manage to produce copies of themselves, in a reaction that grows exponentially. We speak, then, of a system capable of self-replication.
– Where would the mystery then be?
Life is not reduced only to a set of chemical reactions. In our case, it is a complex form, conscious of itself. Why? This is a much more interesting question.