Deep in a secret lab in a rogue state, Agent Orange is designing the perfect bioterror weapon: a chimeric virus that will be partly measles to make it super-infectious (measles has one of the highest values of R0known, ~15, meaning that on average each infected person will infect 15 others); it will be partly Ebola, to make it super-lethal (Ebola kills ~70 per cent of infected persons, one of the highest lethalities); and, just for good measure, Agent Orange is adding the bacterial cholera toxin and the enzymatic toxin ricin that comes from castor beans. Released into the world from a wildlife market in a remote location, nobody will suspect that this is the dastardly work of the rogue state.
This fictional scenario is technically possible - the molecular tools for assembling a super-virus are common and relatively easy to use - but there are a number of reasons why a conspiracy like this would make no sense.
One is that viruses are finely tuned to interact with a particular host, so mixing and matching parts of unrelated viruses is unlikely to work. Not only do they have to latch onto cells, but once inside they each have a specific way to hijack the cellular machinery to make more viruses. Each of these steps requires careful coordination among the viral proteins and the host proteins, so having a mixture of viral parts is far more likely to mess up the virus than to make it more powerful.
Another is that it is trivial to tell when a genome has been tampered with if we have some examples of un-tampered genomes.
To see why this is, remember that a genome is just a string of letters, made of DNA in humans, but RNA in coronaviruses. DNA and RNA have only four letters (A,C,G, and U for RNA), but pretend for a moment that they include all the letters of the English alphabet. The coronavirus genome might then read:
IAMACORONAVIRUSGENOMEMADEOFRNA
Reading genomes has become one of the fastest and cheapest things that scientists can do, to the point that many molecular biologists now do little else. So if virologists studying an outbreak found a genome that read:
IAMACORONAVIRUSandebolavirusGENOMEMADEOFRNA
they would immediately know that the genome had been modified. Genetic tampering is literally that easy to detect.
Of course, if the change is subtle it would be harder to notice, but then it would also have less effect. And, just like words in English where a change in spelling usually messes up the mianing (oops, I mean meaning), changing letters is more likely to stop the virus from working properly than make it work better.
As I mentioned in a previous column, viral genomes do change rapidly. The machinery that copies them in your cells - the RNA-dependent RNA polymerase in the case of coronavirus - does not spend a lot of energy trying to ensure perfect copies. Instead, it copies sloppily, generating lots of variants, most of which do not work.
Occasionally, however, there is a variant that works well enough to make more copies. Sometimes, the mutation - the change in the genome - allows it to infect a host that it could not infect previously.
By reading the genomes of lots of viruses found in nature, scientists can measure the natural variation, again making it easy to detect unnatural changes that were introduced by humans in a lab.
Our knowledge of natural variation also allows us to detect viral re-assortment: when two related viruses infect a host at the same time, they can mix and match their genetic elements. This is part of the reason that the influenza virus changes so much every year, making it difficult for vaccine producers to know which vaccine will be needed next year.
Two final thoughts about viruses as weapons: since nobody can control the spread of viruses, they are just as likely to infect the citizens of the country that makes them as the citizens of other countries, making them a poor choice of weapon. Also, the whole point of terrorism is to terrify people that the terrorists might strike again. If nobody knows that a virus was created by terrorists, then they aren’t terrorized. So the rogue state would gain no leverage by releasing a secret virus that it did not take responsibility for.
- Stephen Rader is a Professor of Biochemistry at the University of Northern British Columbia. His laboratory studies how RNA is processed by our cells, and he is the founder of the Western Canada RNA Conference.
