— Exactly 45 years ago, WHO declared complete victory over the smallpox virus in nature. Has smallpox really been eradicated?
“For a long time, no epidemics, epidemics, or even isolated cases of smallpox have been detected in the world. Therefore, according to official criteria, yes, smallpox has been defeated in nature.
I would like to point out here that, as humanity, we often empathize with the fact that different animal, plant and similar species are constantly disappearing on the planet. However, for some reason, we forget that viruses are also part of a completely living entity. And in this case, following the rule of constant struggle between species, our species – humanity – defeated the type of smallpox viruses.
We live in a pretty cruel world; Either we are them, or they are us. In this case, people defeated smallpox.
—Is there really no smallpox left anywhere in nature?
“We should not completely ignore the fact that smallpox still exists in nature, for example in some cemeteries.” It is also known that the virus is stored in at least two laboratories in the world: in Atlanta and the Vector Center in Novosibirsk.
— At least you said, is there really more to this place?
– I’m sure there are many more. These are just two famous places. I think there are a few other places like this, at least in the same countries – the USA and Russia. Most likely smallpox is stored in China. I would also suggest that the stored virus must be in the UK.
— Why should we hide this virus?
— In all developed countries that have biological services, one way or another, subordinate to the Ministry of Defense, the smallpox virus is considered one of the potential means of biological weapons.
There were debates about this before at different levels: Is it worth saving the virus or not? But after the report on the creation of a synthetic horsepox virus was presented at a closed meeting of the World Health Organization (WHO) smallpox advisory committee in Geneva in November 2016, it became clear that this was not a fundamental point.
— If it’s a closed meeting, how do you know?
– In this respect reported in the scientific journal Science 2017.
– So who created the synthetic virus?
— This was by virologist David Evans of the University of Alberta in Edmonton. The university is located in Canada. There, Evans led a team that had scientists send them pieces of DNA through the mail, and then, like pieces of a puzzle, they pieced smallpox together from them. There is little evidence that horsepox is dangerous to humans, but the same strategy could be used to recreate smallpox. But I haven’t seen an article on how to do this; Neither Nature nor Science wanted to publish it. They later published a brief report without details in PLOS One.
— Is it difficult to assemble such a virus?
—As a scientist interested in reverse genetics, a method that can be used to produce a synthetic virus, I understand that creating an artificial smallpox virus is not a fairly trivial task.
And even for a professional biological laboratory. The smallpox virus consists of more than 200 thousand nucleotides, so it is very large. Obtaining such long chains is difficult even by current genome engineering standards.
However, this is possible. Evans created the horsepox virus, the closest relative of the Vaccinia virus. And this is the same virus that forms the basis of the smallpox vaccine that allows the World Health Organization to tackle this disease.
– Wait a minute, wasn’t cowpox used for this vaccine? After all, was it cowpox used by Edward Jenner, the first vaccinator on the planet at the end of the 18th century?
– Humanity thought it was cowpox until it became possible to compare viruses genetically. And it turned out that the virus used in the vaccine was closer to horsepox, not cowpox. For this reason, the virus that forms the basis of the smallpox vaccine was called vaccineovirus. And so it’s pretty well studied. Scientists have been working with it for a long time.
– So how is it used?
“They are genetically modifying it, creating various recombinant vaccine viruses, trying to make a delivery vehicle out of it – the same one used in the Sputnik V vaccine – but only adenovirus 5 and 26 are getting there.
If the adenovirus can be compared to a small car into which very little genetic information can be loaded, then the vaccine virus is a huge, empty truck. But this is also a bad thing because huge structures like the vaccinia virus genome are very difficult to assemble.
It is absolutely impossible to do this at home, without special skills and special equipment, so for now I do not take into account the terrorist threat.
But there are probably 100 laboratories in the world that can actually do this, the majority of which are concentrated in the United States, Canada, the European Union, Russia, China, and perhaps Japan and Korea.
— Some articles say that this is also cheap, only 100 thousand dollars and six months of work. This is true?
– I believe it is much more expensive. After all, you should have first-class experts working in your laboratory. And as you know, they are expensive.
— What synthetic viruses are currently available? Polio? Corona virus? Herpes? Cold?
– Yes, they already exist. This is published information. And the most dangerous of these is, of course, the flu. It’s even more dangerous than smallpox.
First, the influenza virus, unlike the smallpox virus, was not defeated. Although we have been struggling with vaccines for a long time. This means he knows how to resist professionally. Therefore, it poses a huge problem for humanity every year.
Second, the design of the virus, which consists of eight segments, suggests the ability to quickly replace segments – new segments then appear. Sometimes three different influenza viruses swap parts, resulting in a rheostantant that is no longer captured by any antibodies, even after vaccination.
Can you imagine an attacker who knows how to infect people extremely effectively by overcoming the immunity created by vaccines? Moreover, it may be based on another bird flu that is far from humans…
The other thing is that we can quickly produce a vaccine against the virus so we can do something against it.
— Could attackers one day use synthetic biology methods to create a “Frankenstein virus” with the most powerful “attack tools” against different viruses?
“Nature has already created everything and tested various types of viruses throughout the long history of the existence of this planet.
So isn’t there a means of transportation that can immediately set out, sail the sea, and fly in the air? Because this means that the device becomes heavy with a lot of equipment and then loses its speed due to special transport means. We are currently dealing with ideal “Frankenstein viruses” that nature itself created and tested.
— Is it now possible to create a virus that has never existed in nature?
– Yes, and this is being done. Including my genome engineering laboratory at MIPT.
But compared to nature, we are only so-so creators. We only know how to mix dyes, that is, how to make chimeras from existing viruses. Maybe we can add a few individual mutations. But what we are currently doing with adeno-associated viruses in our laboratory is, of course, aerobatics.
We are essentially creating synthetic forms of viruses that have never existed before on planet Earth.
– Why do you create them?
“We use them as a way to deliver gene therapy drugs. Such drugs are already entering the market. For example, we have already registered in Russia the American gene therapy drug Luxturna for hereditary retinal dystrophy. Or more recently in Russia, adeno as a means of distribution Another drug that also contains related viruses has been introduced: Zolgensma for gene therapy of spinal muscular atrophy.
— I remember the story of Zolgensma. At first in Russia people waited for this medicine for a very long time, they fought for it, and then two children died from this medicine…
“That’s why we create viruses that don’t exist in nature.
The drug “Zolgensma” is made on the basis of adeno-associated virus, serotype 9 (AAV9). What is the disadvantage of this type of viruses? Their capsids, that is, the surface proteins of viruses, are made on the basis of wild-type viruses, that is, those that occur in nature. We encounter them in daily life and develop antibodies against them.
Since our “weapons” are already tuned to these viruses, an injection of such a gene therapy drug will be neutralized by the adaptive immune system.
What happened to these two children? Doctors used this drug and also prescribed immunosuppressive drugs, just in case. They were later gradually cancelled. After that, the immune system “saw” the viruses and began to attack them, destroying the livers of these children. What to say? The immune system did what it was supposed to do.
We decided to overcome this problem by creating viruses that do not exist in nature and that the immune system can never encounter. This allows gene therapy to be administered to 100% of potential patients.
— Why else are synthetic viruses that do not exist in nature needed?
– They will be useful in providing the substance of any vaccine – the same Sputnik V, for example.
Synthetic forms can be made to fight cancer. These are called oncolytic viruses. They will effectively multiply in cancer cells, which will signal the immune system that they are infected. And he will destroy them. So, here such synthetic viruses are used as bait.
My point is that despite the risks associated with the development of synthetic biology, this approach can bring many benefits.