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On Pathogens

When I was very young I had a terrible irrational fear of vomiting. In the family home, my bed shared the same wall as the family bathroom. There were several heavy drinkers in my family and I would often have to listen to them vomit over the course of an evening, while I was trying to sleep. My phobia was severe enough for me to stop eating for a while, and I developed a morbid obsession with avoiding any type of illness. Growing up, I had a younger brother and a younger sister and so, inevitably, when one of us got sick it was only a matter of time before we all were. My family referred to the stomach flu as having ‘a tummy bug’, and for the longest time I assumed that these sorts of illnesses were caused by ingesting an insect – in my head it was a small green worm. I felt instinctively that these bugs were out to get me: they wanted to make me throw up. It was me against them, a war of contrition.

As is my nature, I spent a lot of time researching. I studied the physiological mechanisms of vomiting, the neurological process, the evolutionary benefits of emesis and what it was made of. I became very jealous of rats and horses, who are unable to vomit due to the shape of their palates (of course, these animals can offer suffer greatly as a result of not being able to barf and preventing colic in horses is always a concern for those of us who keep them). Around this time, I began to read about pathogenic bacteria and viruses. I learned how microorganisms can cause food poisoning, and I became very interested in knowing more about the toxins they produce.

In my little brain, I found this all very unfair. I couldn’t reconcile why the bacteria and viruses hated us enough to make us sick. It’s very easy to anthropomorphize when you’re a little person, it’s comforting to create a perspective you can relate to, and it’s something I still do now when I’m trying to understand new ideas. Of course, microbes don’t want to make us sick. They don’t not want to, either. The same way the mountain wants us to climb to the top, and doesn’t want us to. The vast majority of bacteria and viruses we associate with do not have any deleterious impact on our health, and in many cases, they do us a great many favors. For example, in our guts, E.coli is responsible for producing a version of vitamin K. It is essential and without that flavor of E.coli we would no longer have a mechanism for obtaining it. But context is everything, and another type of E.coli can make us very sick – E.coli O157 is a very serious bacterium, and getting sick with it can lead to kidney failure and eventual death.

The process of infection is fascinating, but generally speaking it results from a proliferation of bacteria or viruses that cause damage to the cells of our body. Signs and symptoms of a disease manifest as a result of immune response to this damage, and, if the disease is not self-limiting, or the damage is severe enough, we can die. This also applies to other animals, plants, and microorganisms themselves. Some microbes are just ok at causing infections, and they usually do so opportunistically. Some are exceptionally good at spreading themselves around without killing their host – like Norovirus. Some are breathtakingly efficient at causing catastrophic disease, for example, Ebolavirus. Ebolavirus causes hemorrhagic fever and can have a mortality rate of up to 90% - it is a devastating disease most prevalently found in the poorest of communities.

There is obvious cause for humans to hate a virus like the one that causes Ebola. From a scientist’s perspective, Ebolavirus is astonishing. Now, please don’t’ assign any flippancy to this statement – I am not trying to downplay the human catastrophe that this being represents. I am not trying to suggest, for second, that we should not limit the impact of this disease or continue to perform the extraordinary work already done in developing a vaccine against this pathogen. May I request, however, that you consider the following -

Usually, it goes like this:

DNA → RNA → protein

That is to say, most living things contain a blueprint. The blueprint may be considered as a map of the potential of an organism. At any time, pieces of the blueprint are translated into metabolic activity. The blueprint is an organism’s genome, and it’s made of DNA. Metabolic activity is performed by proteins, and RNA is the intermediate between the two. The RNA produced from a piece of DNA is complementary, and this is a product of complementary base pairing. For example (we’ve all seen Jurassic Park), a sequence of DNA which reads GCGC will produce a piece of RNA that codes CGCG. This kind of code is referred to as ‘positive sense’ RNA – it makes sense, it follows the rules. Everyone knows where they are with positive sense RNA.

Viruses are obliged to be parasites of their host cells, because, broadly speaking, they comprise only two features: a genome and a protective shell. They do not contain any of the inherent mechanisms required to build proteins from DNA. So, like a molecular cuckoo, they have their host provide that capacity. This host may be mammal, plant, bacterial or unicorn. Every living thing is infected by a virus of some description. The human genome is around 8% viral in origin, in fact – and being infected by a virus is not always a bad thing. The 8% bestowed to us by viruses allowed, somewhere in the distant past, for placental birth, for the production of salivary enzymes.* The bacterium which causes the disease diphtheria is only toxic after it has been infected by a virus – bad news for us, but cause for celebration for the bacterium which becomes more evolutionarily fit as a result. However, the defining feature of a virus is ultimately that they can’t do anything of note without a host cell. After infection, they hijack the biochemistry of the cell to make progeny – and this is all about producing RNA, the intermediate in the biological scenario. RNA leads to proteins. Proteins lead to functional viruses. Functional viruses lead to the dark side**.

Now, viruses come in many different flavors and are exceptionally esoteric in these identities. Some possess genomes made of DNA – easy to transcribe into RNA using that positive sense method we mentioned earlier. Many, however, do not. Ebolavirus is particularly interesting. Its genome is made of negative sense RNA, but it also contains an enzyme which, when installed in a host, will convert the negative sense RNA to a positive sense RNA. Why is this clever? Take, for example, a positive sense RNA virus which contains five genes. When these genes are turned into proteins during the infectious cycle, they are churned out as one long chain, like a paper chain of people. In negative sense RNA viruses, proteins can be made one at a time. This means they can be altered one at a time – it allows for more evolutionary freedom. This is one of the reasons why Ebola is such a difficult disease to get a handle on. It changes swiftly, and efficiently. Ebolavirus is exceptionally good at being the Ebolavirus. A number of other viruses apply a similar strategy to their existence, and there is no analogous system of RNA production in any other living being on this planet.

I am frightened of these diseases, as many people are. I am also intimidated by viruses that never ever go anywhere near human beings - how good they are at existing, with apparently so little to work with. Because they are so good at doing what they do, and scientists are so far from being able to reverse engineer how they do it. There’s humility to be found in that. Compared to viruses, I am definitely not very good at just being Ṣiv. I have never had a singular capacity to pursue, doggedly, a specific goal (I have a very short attention span). I have always had access to food and water and shelter. I have never had to think, particularly consciously, about existing – beyond the realms of my own troublesome brain. I can make my own proteins with nothing more than a glass of water and some chicken nuggets.

Many of the really scary diseases have emerged as result of human activity, particular in third world countries and very heavily populated areas of the planet. All human viral diseases, generally speaking, are zoonoses – they were passed on to use via other animals. Many of the really scary diseases can be comfortably ignored by western communities until they encroach onto our shores. Take, for example, the scenario presented by Nathan Wolfe in his TED talk. Wolfe is a virus hunter, who travels around the world seeking out emerging viruses. His work led to the discovery of potential pathogens found in Africa, in heavily deforested areas, in areas where, due to the necessity of existing, many people hunt and eat bushmeat. This is where the crossover between animals and humans take place. Do we blame the folks who hunt bushmeat? Do we blame the corporations who deforest? Do we blame the exotic animal trade? Emerging diseases are a very blunt way of demonstrating where we, human inhabitants, are out of whack with the environment. So could you, therefore, compare a tiger turned man-eater, starving, with the option to move towards a village to hunt human prey, to a hemorrhagic fever?

What about the pathogens who are just OK at causing infections? They don’t necessarily need to, they just happen to be in the right place at the right time - right? My friend, this is the essence of microbial success. They’re extremely good at finding the path of least resistance, or the path that will lead them to, ultimately, the greater benefit. Not selfishly – because they exist in communities. All microbial work is community work, and their genetic mechanisms for doing so are handed down by millions of prior generations. One of the illnesses I was most frightened of as a kid was Norovirus. I caught it once and spent three days in bed, barfing until I cried. The Norovirus is an extraordinarily successful pathogen – it doesn’t kill its host, it’s incredibly contagious and spreads itself huge distances via projectile vomit and diarrhea. It is robust and difficult to destroy with bleach or alcohol, and it mutates constantly – we have no vaccine for the Norovirus and we are barely able to grow it in the lab. The Norovirus is very good at doing what the Norovirus is for – not making us miserable, but existing, and continuing to exist as pervasively and heartily as it possibly can. In the most difficult moments, I can remind myself that for humans, clumsy and inefficient and endearing as we are - there is great success in existing.

By the way, that virusy 8% of your genome - part of which provides us with the ability to give birth to live young instead of laying weird human eggs***? Mostly, it came from the family Filoviridae, which currently incorporates three genera: Cuevavirus, Marburgvirus and ….Ebolavirus.

 

 

*One of my students recently, and very convincingly, argued that this eventually lead to humans being able to develop the Galaxy Note.

**Couldn’t resist.  

***Probably that would not happen.