Viral Pandemics
by Michela Mazzon in Biology

American Red Cross nurses tend to Spanish flu patients in the Oakland Municipal Auditorium, 1918.

With the latest panic on Ebola melting away, it seems another feared disease has been contained and controlled. But why is it that, after all of our advance in medicine, we still rely on containment rather than cures? Michela Mazzon fills us in.

narrated by Angus Waite

music by Kai Engel and Dexter Britain

Michela Mazzon

Michela Mazzon

Michela is a Research Associate at UCL’s Laboratory for Molecular Cell Biology, where she works on the development of a new broad-spectrum antiviral drug and tries to understand the molecular basis of the interaction between viruses and cells. She likes to spend her free time enjoying modern art, friends’ company, and a good sci-fi book.

By the time the Spanish flu pandemic was over in 1918, it had claimed an estimated 50 million lives. Symptoms started like any ordinary flu, with a cough, chills and fever, but for many the symptoms could get so bad that they never recovered. Fluid would fill their lungs and they would struggle for air until they suffocated. Surprisingly, the victims were mainly young and healthy individuals as their prompt immune system overreacted to the infection, killing the person in an attempt to get rid of the virus.

In 2005, scientists managed to sequence the RNA genome of the virus responsible for the Spanish flu, after it was isolated from the frozen corpse of a native Alaskan woman who had been buried for nearly eighty years in permafrost. They discovered that this 1918 flu strain was in fact a subtype of the avian flu virus.

Many more epidemics have struck the world since 1918. Recently in 2004, we have seen the avian flu H5N1, swine flu H1N1 in 2007, and another avian flu H7N9 in 2013. Each of these made the headlines, threatening to become the next, long-feared, global pandemic, but each one was also rapidly contained by quarantine measures on an international scale.

Yet in 2003, a new virus reminded us that flu is not the only pathogen we should be wary of. SARS, or Severe Acute Respiratory Syndrome, spread to 29 countries in just a few months, killing nearly 10 percent of the people it infected, and costing billions of dollars to national economies. Since then, we have learnt of the great importance of acting rapidly and globally to contain the spread of infectious diseases.

However, the recent epidemic of Ebola in West Africa has again shown our unpreparedness in the face of emerging infections, especially in terms of vaccines and antiviral drugs. Why, almost 100 years after the Spanish flu, are we still so unprepared and heavily reliant on containment rather than protective measures?

The problem lies in the nature of the viruses themselves.

First of all, viruses not only use our living cells to replicate, but once inside the cell, they also systematically divert every cellular activity towards the generation of more copies of the virus itself. The inextricable link now established between the virus and the cell makes it very hard for an anti-viral treatment (and even for our own immune systems!) to discriminate between the two, and thus to destroy the virus without harming the cell.

Secondly, viruses greatly differ in their composition, their target organs or cells, and their mechanism of infection. This makes it very difficult to identify common patterns that may help develop universal treatments. The vast majority of treatments developed so far are very virus-specific; they selectively target only specific viral components. For example, drugs developed against critical proteins of HIV wouldn’t work against other viruses. Our effort to keep up with the large diversity of known and unknown viruses comes at a huge financial cost, and likely won’t be rapid enough to be sufficiently effective.

Finally, we cannot predict when new viruses will emerge. The emergence of a new virus depends on a random combination of events that cause an existing virus, often infecting other animal species, to mutate in a very particular way that happens to overcome all of the biological barriers that would otherwise stop it from spreading to humans. At the same time, a rapid increase in world population, together with deforestation and uncontrolled urbanisation, have brought humans and animals in close enough contact to provide these mutated viruses the perfect environment to spread.

And while viruses mutate and adapt quickly, introducing errors and alterations in their own genome, humans can’t. In front of a new virus rapidly spreading in our body, the immune system simply doesn’t have the time to evolve the correct tools to contain the virus without damaging the person. It often just fires all the most potent antiviral mechanisms, and these end up severely and irreversibly damaging our own cells. This was exactly the case for most of the largest epidemics on record, including the Spanish flu, SARS, and also for a number of viruses that cause haemorrhagic fever, like the dengue virus.

It’s very hard to find a way to stop the unknown. We don’t know what a new virus will be like, and we don’t even know how our immune system will react to it. A deeper knowledge of the entire system, virus and cell, is required before we are able to develop effective countermeasures. Are there common mechanisms that some, or all pathogens share? Can we target these to fight different infections? Can we predict which viruses are more likely to emerge or re-emerge from the wild by studying the viruses currently infecting the animals we come into contact with? And can we learn how to tune our own immune system and the armoury of tools that our cells have evolved to keep pathogens away? The scientific tools now available, and the large amount of information that we have acquired so far, can help scientists advance their knowledge of infectious disease and develop new ways not only to contain, but also, and more importantly, to prevent and control infections.

Our body doesn’t evolve at the same rate as viruses, but our scientific knowledge and progress do, and they are likely to be the most potent tools we have to free the world from pandemics.

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