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  [22]Virus
  The deadly viruses that vanished without trace
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  (Credit: Science Photo Library)
  Smallpox has plagued humans for thousands of years but was eradicated
  after a sustained vaccination campaign (Credit: Science Photo Library)
  By Zaria Gorvett21st September 2020
  Scientists are only just starting to unravel why some viruses
  disappear, while others can linger and cause disease for centuries.
  I

  It was the year 1002. The English king Ethelred II – not-so-fondly
  remembered as “Æthelred the unready” – was at war. For over a century,
  Viking armies had been scoping out the land as a potential new home,
  under the command of leaders with [25]well-groomed facial hair and
  evocative names, such as Swein Forkbeard.

  So far, the Vikings had found the English resistance enticingly weak.
  But Ethelred had decided to make a stand. On 13 November, he ordered
  for every Danish man in the country to be rounded up and killed.
  Hundreds perished, and the incident went down in history as the St
  Brice's Day massacre. Ethelred’s brutal act proved to be in vain, and
  eventually most of England was ruled by Forkbeard’s son.

  But what was a bad day to be a Viking in England was a gift for modern
  archaeologists. Over a thousand years later, 37 skeletons – thought to
  belong to some of the executed victims – were [26]discovered on the
  grounds of St John’s College in Oxford. Buried with them was a secret.

  When scientists analysed DNA from the remains earlier this year, they
  found that one of the men had been doubly unfortunate. Not only was he
  violently murdered – at the time, he had been suffering from smallpox.

  And there was another surprise. This [27]wasn’t the smallpox virus that
  we’re familiar with from recent history – the kind that was famously
  driven to extinction in the 1970s by a determined vaccination
  programme. Instead, it belonged to a remarkably different strain, one
  which was previously unknown, and silently disappeared centuries ago.
  It seems that smallpox went extinct twice.

  By now the story of how new viral threats emerge should be familiar –
  the close contact with infected animals, the virus leaping between
  species, the “patient zero” who catches it first, the super-spreaders
  who carry it across the globe. But what occurs at the end of a virus’s
  existence is only just starting to gather interest. Why do some viruses
  disappear? And what happens to them?

  As the threat posed by these tiny, primitive life forms grows ever
  stronger, scientists are racing to find out.
  A global vaccination programme pushed smallpox into extinction in the
  wild, although the virus still exists in two secure laboratories
  (Credit: Alamy)

  A global vaccination programme pushed smallpox into extinction in the
  wild, although the virus still exists in two secure laboratories
  (Credit: Alamy)

  One of the most recent viruses to vanish was Sars. The world first
  became aware of its existence on 10 February 2003, after the Beijing
  office of the World Health Organization (WHO) received an email
  [28]describing “a strange contagious disease” which had killed 100
  people in the space of a week.

  The earliest cases occurred in Guangdong, a coastal province in
  southeast China known for its many restaurants serving exotic meats. At
  the time, local wet markets bustled with racoons, badgers, palm civets,
  doves, rabbits, pheasants, deer and snakes, which were often dispatched
  on the spot, mere metres from where people ate. It was common to find
  beheaded and disembowelled animals just lying around. Even in the
  earliest days of the epidemic, it was [29]clear how Sars had emerged.

Sars was driven to extinction by a combination of sophisticated
contact-tracing and the quirks of the virus itself

  Fast-forward two years, and the virus had infected [30]at least 8,096
  people, 774 of whom died. But it could have been so much worse.

  Like its close relative Covid-19, Sars had many of the necessary
  qualities for world domination – it was an RNA virus, meaning it was
  able to evolve rapidly, and it was spread through droplets expelled
  when breathing, which are hard to avoid. At the time, [31]many experts
  were concerned that the virus could cause devastation on the same level
  as the HIV crisis, or even the 1918 flu pandemic, which infected a
  third of the world’s population and killed 50 million.

  You might also like:
    * [32]What if all the world’s viruses disappeared
    * [33]The surfaces that can kill viruses
    * [34]The mystery viruses far worse than flu

  Instead, Sars disappeared as abruptly as it arrived. By January 2004,
  there were just a handful of cases – and by the end of month, the last
  suspected natural infection was announced. Oddly, while “patient zero”
  describes the first known person to be infected with a virus, there is
  no equivalent label for the last ever person to catch it in the wild.
  But this would arguably apply to a 40-year-old man with the family name
  of “Liu” from the southern city of Guangzhou. (There was another
  outbreak a couple of months later, when it is thought to have
  [35]escaped from a Beijing research lab – twice).

  So what happened?

  In a nutshell, we got lucky. According to Sarah Cobey, an
  epidemiologist at the University of Chicago, Sars was driven to
  extinction by a combination of sophisticated contact-tracing and the
  quirks of the virus itself.
  It took a global effort of surveillence and control measures to
  eliminate Sars (Credit: Reuters)

  It took a global effort of surveillence and control measures to
  eliminate Sars (Credit: Reuters)

  When patients with Sars got sick, they got very sick. The virus had a
  staggeringly high fatality rate –[36]almost one in five patients died –
  but this meant that it was relatively easy to identify those who were
  infected, and quarantine them. There was no extra spread from people
  without symptoms, and as a bonus, Sars took a relatively long time to
  incubate before it became contagious, which gave contact-tracers extra
  time to find anyone who might be infected before they could pass it on.

  “But also governments and institutions acted really fast,” says Cobey.

  The case of Liu Jianlun, who caught the virus before it had been
  properly identified, shows just how differently the Sars pandemic could
  have played out. The 64-year-old specialist in respiratory medicine
  became infected [37]after treating a patient at the hospital where he
  worked in Guangdong Province. On 21 February 2003, Jianlun travelled to
  Hong Kong to attend a wedding, and checked into a room on the ninth
  floor of the Metropole Hotel. Although he had been suffering a slight
  fever and mild respiratory symptoms for five days, he was well enough
  to do some sightseeing with a relative. But the following day his
  symptoms had worsened, so he [38]walked to a nearby hospital and asked
  to be put into isolation. By then, he had already [39]unwittingly
  infected 23 people, including guests from Canada, Singapore and
  Vietnam, who then carried the virus back to their own countries, where
  they spawned further outbreaks.

Other than Sars, only two other viruses have ever been driven to extinction
on purpose – smallpox and rinderpest, which affects cattle

  In the end, the WHO estimated that around [40]4,000 cases could be
  traced back to Jianlun, who himself succumbed to the virus. Without the
  global effort to eliminate Sars, and the virus’s built-in features that
  made this easier, there’s little doubt the pandemic could have
  [41]spiralled out of control.

  Unfortunately this situation is extremely unusual. Other than Sars,
  only two other viruses have ever been driven to extinction on purpose –
  smallpox and rinderpest, which affects cattle. “It’s not trivial. It’s
  really very difficult when you have a virus that’s well adapted,” says
  Stanley Perlman, a microbiologist at the University of Iowa.

  The war against these two viruses was won using vaccines, which are
  also set to [42]eliminate polio – [43]cases have decreased by 99% since
  the 1980s – and possibly [44]eventually measles, though recently these
  efforts have been set back by war, the anti-vaxxer movement and
  Covid-19.

  So, what about the other viruses that have plagued humanity in recent
  years? Will Ebola disappear? And where did swine flu go?
  Vaccinations can help prime the human immune system to fight off
  viruses, making it harder for them to spread (Credit: Press
  Association)

  Vaccinations can help prime the human immune system to fight off
  viruses, making it harder for them to spread (Credit: Press
  Association)

  Unfortunately, some viruses are unlikely to ever go extinct, because we
  aren’t their only host.

  In humans, outbreaks of Ebola end all the time. There have been at
  [45]least 26 across Africa since the virus was discovered in 1976, and
  these are just the ones that caused enough cases to be picked up by
  health authorities. They tend to occur when the virus hops from an
  animal – usually a bat – to a human, who then infects other humans. As
  long as there are bats, it may always be with us, regardless of whether
  there is a single person infected anywhere on the planet.

  In the West African country of Guinea, one analysis by Emma Glennon and
  colleagues at the University of Cambridge found that subtly different
  types of Ebola are likely to have jumped from an animal to a person
  [46]roughly 118 separate times, often without anyone noticing. Indeed,
  the amount of genetic variation between the strains responsible for
  different outbreaks suggests that these “spillover” events are
  alarmingly common.

  Though the 10th Ebola outbreak to have plagued the Democratic Republic
  of the Congo was declared [47]officially over on 25 June this year –
  and there’s no evidence the strain that caused it has lingered on in
  humans – by then another had already begun. The 11th outbreak is
  currently confined to the north-west of the country, and is thought to
  be caused by a [48]brand new type of Ebola, which was acquired from an
  animal entirely independent of all the others.

Mers is thought to have crossed over to people on hundreds of separate
occasions

  Local health authorities and the WHO face several other challenges when
  it comes to fighting Ebola. A lack of funding has [49]made surveillance
  of Ebola cases difficult, while the [50]presence of armed groups in the
  affected areas is making it unsafe for health workers. There is also
  reluctance among some to seek treatment for Ebola, with people
  preferring instead to stay in their communities. Of the six species of
  Ebola, there is only a vaccine for one of them – the type that killed
  11,000 people in West Africa between 2013 and 2016.

  Even with a Herculean effort to eradicate the virus from human
  populations, it will still remain circulating in its original host –
  bats.

  This means the only way to drive the virus to extinction is to
  eliminate it in the wild, which is a near-impossible task.

  Similarly Mers, which hit global headlines in 2012 when it first
  emerged after infecting humans from camels, is thought to have crossed
  over to people on [51]hundreds of separate occasions since then.
  The fight against Ebola in Africa has been complicated by the fact the
  virus continues to circulate in wild animals (Credit: Reuters)

  The fight against Ebola in Africa has been complicated by the fact the
  virus continues to circulate in wild animals (Credit: Reuters)

  “Sars went away because there's no other obvious host,” says Perlman.
  Sars is thought to have made the leap to humans via a palm civet, a
  tree-dwelling jungle mammal that’s considered a delicacy in China.
  Perlman points out that the virus couldn’t just retreat back to this
  species, because they aren’t commonly infected – the individual animal
  that gave it to a human was probably one of very few which were
  infected, and may have caught it directly from a bat.

  The same cannot be said for Covid-19, which again, is thought to have
  originally belonged to bats, before briefly being passed on to another
  animal – possibly pangolins – and eventually humans. “With Covid-19,
  the reservoir is now us,” says Perlman. In fact, it’s become so much of
  a human virus that scientists have begun to wonder if it will
  [52]spread the other way around – from humans to wildlife, in a kind of
  “reverse spillover”, if you will. This would make it even harder to
  stamp out.

  This brings us to another possible scenario, which involves viruses
  that exist continuously in people. While they may well be with our
  species forever, it turns out individual lineages of virus vanish
  remarkably regularly.

Every flu virus that existed in humans until about 120 years ago has gone
extinct

  Take the flu, of which there are two main types.

  Firstly there’s influenza A, which infects many other animals as well
  as humans – mostly aquatic birds, from ducks and geese to [53]rare
  Antarctic wildlife, such as the Giant Petrel – but is always with us in
  one form or another. This kind is responsible for the [54]majority of
  cases of seasonal flu– and it also causes pandemics.

  Then there’s influenza B, which only infects humans and – oddly –
  seals, and never causes pandemics.

  For years, it was thought that the influenza A strains we live with are
  constantly evolving to be better able to infect us. But the latest
  scientific research shows that this is not the case.

  It turns out that anyone who died before 1893 will never have been
  infected with any of the influenza A strains that exist today. That’s
  because every flu virus that existed in humans until about 120 years
  ago has [55]gone extinct. The strain that caused the 1918 pandemic has
  also disappeared, as has the one that led to the 1957 avian flu
  outbreak, which killed up to 116,000 people in the US, and the type of
  flu that was circulating in 2009, before swine flu emerged.
  Polio was recently announced to have been eradicated in Africa after a
  long-running vaccination programme (Credti: Getty Images)

  Polio was recently announced to have been eradicated in Africa after a
  long-running vaccination programme (Credti: Getty Images)

  Established flu strains tend to continue evolving down many different
  paths – then the vast majority will abruptly go extinct. Every few
  decades, a new type of flu will evolve to replace them, usually made
  from a combination of old flu viruses and new ones, fresh from animals.

  “It’s really interesting because if you're focused on any particular
  strain – or more like, any particular genetic sequence that is
  replicating itself – there is a very, very high extinction rate,” says
  Cobey. “Strains are dying out every couple years now. It’s complicated,
  but we are seeing a very high turnover.”

  Intriguingly, rather than adapting to humans over time, it seems that
  H1N1 – the type that caused the 1918 flu pandemic and swine flu, and
  has now disappeared – had been quietly accumulating mutations which
  were [56]useless or even actively harmful to its own survival.

  Now some scientists are suggesting that speeding this process up might
  allow us to use the rapid evolution of endemic human viruses to our
  advantage. The idea has been around for a while as a way to rid
  ourselves of the flu and colds – but recently it was also suggested as
  a [57]method of combating Covid-19.

Speeding up viral evolution artificially with drugs could bring some benefits

  At the heart of the plan is the biology of “RNA viruses” – a group that
  includes many of humanity’s most intractable pathogens, including HIV,
  the flu, coronaviruses, and Ebola. Their genetic material is made of
  RNA as opposed to DNA, which means that when they hijack their host’s
  machinery to copy themselves, they don’t include a “proofreading” step
  where they check for mistakes.

  This is usually thought of as a bad thing for humans, because these
  mutations mean that there’s an extraordinary amount of genetic
  diversity among RNA viruses, allowing them to evolve rapidly – so any
  vaccines or drugs that target them quickly become obsolete.

  “Although we like to think of flu strains as a unitary sequence, in
  fact, what they represent is a whole swarm of different genetic
  sequences,” says Lipton. In the short term, this quirk makes it harder
  to eradicate the flu, because among this “swarm” might be viruses that
  our immune systems do not recognise and are therefore able to sneak
  around our bodies unnoticed.

  But this staggering rate of mutation is a double-edged sword. Above a
  certain rate, mutations become harmful, leading to virus strains which
  are burdened with genetic faults that hinder their spread. Eventually,
  this can lead to their extinction.
  Viruses pick up errors in their genetic code as they spread, so in some
  cases it is possible to simply wait them out (Credit: Reuters)

  Viruses pick up errors in their genetic code as they spread, so in some
  cases it is possible to simply wait them out (Credit: Reuters)

  Speeding up viral evolution artificially with drugs that encourage them
  to mutate at an even higher rate than usual could bring some benefits.
  First, it might weaken the virus enough to reduce the amount
  circulating within individual patients. This could make it easier to
  treat in those with severe illness. There's already some evidence that
  this can work – clinical trials in the US and Japan have found that
  the [58]mutation-inducing drug "favipiravir" is [59]effective against
  the flu strain H1N1. Virologist Elena Govorkova at St Jude Children’s
  Hospital in Memphis, Tennessee, and her team have shown that the drug
  appears to make the flu virus less infectious.

  Secondly, certain virus strains, like the types of Covid-19 – of which
  there are [60]already at least six – might amass enough mutations that
  are harmful to themselves so that they disappear altogether. In India,
  there’s already evidence that this could be happening naturally. The
  virus is mutating at a staggering pace, and it’s been [61]suggested
  that it might be heading for an evolutionary cliff all on its own.

  However, regardless of how hard we try, some scientists are sceptical
  that we will ever be able to say that any virus is gone forever.

  “The term extinct is maybe misleading,” says Ian Lipkin, an
  epidemiologist at Columbia University, New York. “Viruses can be
  present in many locations – they can lurk in people, they can lurk in
  materials that are stored in freezers, they can lurk in wildlife and
  domestic animals – it’s really impossible to say if a virus has gone
  extinct.” He points out that vials of smallpox still exist in
  [62]freezers in at least two locations – and there’s an ongoing debate
  about whether to drive it to extinction more definitively.

  Since most vaccination programmes ended in the 1970s, many are
  concerned that these rare stashes of smallpox might have the potential
  to spark another major global pandemic. That’s not to mention the
  latent threat of synthetic viruses – in 2017, a team of Canadian
  scientists stitched together a horsepox virus, which is a close
  relative of smallpox and may or may not be extinct. [63]As with many
  other viruses, no one knows for sure if it has died out, but the
  scientists were able to recreate it using records of its genetic code
  and [64]scraps of DNA they ordered over the internet.

  Of course, this doesn’t mean our eradication efforts are pointless. In
  fact, Cobey thinks now more than ever we should be focused on whittling
  down the pool of human pathogens. “I hope this is a period in which we
  can reflect on, you know, what sort of illnesses we want to work toward
  eradicating,” she says. “There are lots of pathogens out there – most
  people don't appreciate just how many.”

  Who knows, perhaps Covid-19 will inspire a new scientific revolution,
  and the concept of catching several colds or the flu each year will
  become as alien as having to worry about smallpox.

  --

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