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The Science Behind The Infected

 

Spoiler Alert: This page is intended for people who have already read The Outbreak, or the first book in the For Those In Peril series, Those In Peril On The Sea, and may contain information that spoils your enjoyment of the story if you have not done so yet.

In the world of the For Those In Peril series, a mutated virus creates violent and cannibalistic infected out of normal humans. There are three key premises behind this virus, all of which are consistent with modern scientific knowledge. The first of these is rabies. While rabies is not a common disease in many western countries, in other parts of the world it is still widespread and kills around 50,000 people each year. Until a vaccine was created in 1885, rabies was pretty much one hundred percent fatal. While a small number of people were reported to have survived before the introduction of the vaccine, these remain unsubstantiated. Since the invention of a vaccine, if someone thinks they have been bitten by a rabid animal and receives it before they start to show any symptoms it is usually sufficient to ward it off.  However, if the first symptoms have started to appear (meaning the virus has reached the brain), then the disease remains fatal in almost all cases. Most of those who have survived have been given an intensive treatment known as the Milwaukee Protocol. This protocol requires a dedicated medical team, and involves putting the person into a chemically-induced coma while they are given anti-viral drugs. This treatment is still experimental, and only six people have been cured with it.

Rabies itself is a pretty terrible and terrifying disease, especially in the final stages. People with it thrash around in anger and rage, trying to attack anyone who comes near them. Such patients have to be restrained to prevent them injuring themselves or those around them. The virus that causes it spreads almost exclusively through bites. This is because it can be found in large amounts in saliva, which is produced in vast quantities, causing those infected to froth at the mouth. When a rabid animal bites someone and breaks the skin, saliva gets into the wound and takes the infection with it, so passing it on. Unlike most infections, rabies does not travel through the blood-stream. Instead, it slowly and inexorable makes its way along the peripheral nerves towards the brain. Once there, it gradually spreads until it has taken over. The rate of spread along the nerves is very measured and time between being bitten and the infection reaching the brain is dictated by the distance between wound and the head, meaning the further the original bite is from the head, the longer it will take to develop symptoms. As yet there have been no confirmed cases of human-to-human transmission, but it is theoretically possible. The most likely reason that such transmissions do not occur more frequently may be due to the fact that human teeth are poorly adapted for biting through the skin of others.

The second premise behind the Haitian Rabies Virus (as the disease is called in The Outbreak and in For Those In Peril On The Sea) is a technology known as small interfering RNA, or siRNA.  Since it was only invented in the late 1990s, this is a relatively new technique in the tool kit of molecular biologists. Yet, it is one which holds a lot of potential. The siRNA approach involves creating a short piece of RNA that has been specifically designed to attach itself to a DNA sequence in an organism's genome. When this happens, that specific stretch of DNA can no longer be read by the body's own mechanisms and so any genes that it is a part of cannot be expressed. While this is primarily used to work out the function of specific genes, it is also thought to potentially have therapeutic effects. In particular, it is thought that it could be used to create vaccines for viral diseases that are otherwise untreatable. This is because it can be used to 'knock out' key genes within the virus. This has been shown to work in a 'proof of concept' trial that created a post-exposure vaccine that has been shown to cure 100% of non-human primates infected with the most lethal strain of the Ebola virus. However, possible therapeutic uses of siRNA are hindered by a number of potential problems. In particular, siRNA can sometimes attach itself to the wrong sections of DNA, so silencing non-target genes and this can have unintended consequences.

The final premise is the role of drug trials in the development of new pharmaceuticals. All drugs must be shown to be effective against a specific disease or condition, and also to have sufficiently few, minor, or at least acceptable side effects before they will be granted a license. While these are meant to be done in carefully-controlled trials, there are regular charges and rumours of drug trials not being conducted properly. Worse, it has been alleged that western pharmaceutical companies have conducted illegal trials in areas such as India or Africa, often using untested drugs on people who have not or cannot provide their full consent. Even when drug trials are set up and run properly and legally, things can go unexpectedly, and horribly, wrong. In particular, in phase one trials, the first on humans, drugs that worked perfectly well in animal models can be found to have very different, and sometimes potentially fatal, effects. In one well-known case, six people who received a new drug designed to modulate the immune system experienced catastrophic and systematic organ failure caused by an immune response known as a cytokine storm.  While the men eventually recovered, it is likely all suffered permanent damage to their bodies.

In the world of the For Those In Peril series, these three premises are combined to create the perfect storm. An siRNA-based vaccine is created against the rabies virus that is meant to weaken it to the point where the normal human immune response can clear it from the body (this is effectively the basis for the Milwaukee Protocol where anti-viral drugs aim to boost the immune system to the point where it can eliminate the virus). This vaccine is found to work well in animal trials, but in the rush to get the drug to market, so that it can be monetised, someone in the company developing it decides to run a phase one trial not in the confines of a western hospital, but in an illegal trial in a developing county (in this case Haiti). This means that when the vaccine starts to show unexpected effects, there's no way to control it. The scenario behind the these unexpected effects is that the strain of the rabies virus found in Haiti is subtly different from the one the vaccine has been tested on in the lab. The slightly different gene sequence means that the siRNA vaccine latches onto the wrong part of the virus's genome. When the virus attempts to deal with this attack by re-organising its genome, it results in a series of mutations. This causes the virus to both dramatically speed up the time it takes to reach and infect peoples' brains, taking minutes or hours rather than the days or weeks that would be the case with the real rabies virus. This is achieved by the mutated virus being able to carried in the blood and pass the blood-brain barrier to take over the brain rather than having to crawl slowly along nerves. The mutations also makes the virus less lethal, so it no longer kills people, but no less ferocious in its effects on their brains. This means people infected with it are left in the crazed and violent pre-terminal phase of rabies for the rest of their lives. Therefore, while it is hoped that this scenario never comes to pass, from a scientific perspective it remains feasible, at least in principle.  

 

 
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Last modified: 04/30/14