Beware ‘Disease X’: the mystery killer keeping scientists awake at night
Over two days in early February, the World Health Organisation (WHO) convened an expert committee at its Geneva headquarters to consider the unthinkable.
The goal was to identify pathogens with the potential to spread and kill millions but for which there are currently no, or insufficient, countermeasures available. As the meeting opened, the city’s eponymous lake reflected a crisp blue winter sky. Only as the meeting progressed did an icy rain set in.
It was the third time the committee, consisting of leading virologists, bacteriologists and infectious disease experts, had met to consider diseases with epidemic or pandemic potential. But when the 2018 list was released two weeks ago it included an entry not seen in previous years.
In addition to eight frightening but familiar diseases including Ebola, Zika, and Severe Acute Respiratory Syndrome (SARS), the list included a ninth global threat: Disease X.
What is Disease X?
Disease X is not a newly identified pathogen but what military planners call a “known unknown”. It’s a disease sparked by a biological mutation, or perhaps an accident or terror attack, that catches the world by surprise and spreads fast.
By including it on the list, the WHO is acknowledging that infectious diseases and the epidemics they spawn are inherently unpredictable. Like the Spanish flu which killed 50m to 100m people between 1918 and 1920, Disease X is the catastrophe nobody saw coming until it was too late.
“Disease X represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown,” says the WHO.
It has been included on the list not to terrify us, but to ensure that the global health community builds the resilience and capacity needed to tackle all threats – not just the predictable ones.
Where might it come from?
One source of Disease X could be the deliberate utilisation of infectious disease as a weapon.
While bio-weapons have been used since the middle ages (the Tartars catapulted the cadavers of plague victims into the besieged seaport of Caffa in 1346, for example), new scientific developments including gene editing and an exponential increase in computing power make it easier than ever to develop lethal biological agents.
The US and USSR explored bio-weapon development during the Cold War and both continue to hold live cultures of deadly pathogens, including the smallpox virus, in secretive and (hopefully) secure labs. More recently, the Iraqi military toyed with botulinum toxins under Saddam Hussein, Al Qaeda operatives experimented with anthrax and, in 2014, a laptop captured from Islamic State (IS) was found to contain instructions on how to weaponise the plague virus.
Watch list | Diseases threatening a public health emergency*
- Crimean-Congo haemorrhagic fever (CCHF)
- Ebola virus disease and Marburg virus disease
- Lassa fever
- Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS)
- Nipah and henipaviral diseases
- Rift Valley fever (RVF)
- Disease X
*Diseases posing significant risk of an international public health emergency for which there is no, or insufficient, countermeasures. Source: World Health Organization (WHO), 2018
North Korea and Syria are also thought to have bio warfare capability. Syria, which has been using chemical weapons against civilian populations in the current conflict, suffered a rare smallpox outbreak in 1972 and is believed to have held wild smallpox strains within its military-industrial complex ever since. Equally alarming, anthrax antibodies were detected in the blood of a North Korean military defector last year, raising fears that Pyongyang has a store of weaponised anthrax.
On the bright side, the number of incidents involving bioweapons to date has been very low, with hoaxes far outnumbering genuine attacks. Non-state actors, including IS, appear to lack the capacity to develop a bio-weapon with large scale reach.
But this could change. It has long been feared, for instance, that military grade pathogens could leak from Soviet labs onto the black market and into the hands of terrorists.
Only last year Canadian researchers published a peer-reviewed paper detailing how they had synthetically engineered horsepox (a close relative of the smallpox virus) from scratch using equipment now which falls within the reach of many terror groups.
The paper’s publication has been widely condemned as a security breach. The details provided could “substantively assist those with lesser degrees of experience to synthesize smallpox”, said one critic.
“The synthesis of horsepox virus takes the world one step closer to the reemergence of smallpox as a threat to global health security”, said another.
What about animals?
Bio-weapons are one risk, animals another.
The most probable source of Disease X is zoonotic diseases, or Zoonoses. These are diseases present in wild and domesticated animals that can be transmitted to humans.
Some 70% of newly discovered diseases in the last century have been zoonotic. The hemorrhagic bug Ebola is a prime example. The 2013-2016 West African pandemic is believed to have started when a one-year-old boy was bitten by an Ebola-infected bat in Guinea. The disease spread to his mother, sister and grandmother and then on to kill more than 11,000 people in Guinea, Liberia and Sierra Leone.
HIV is also a zoonosis. The human HIV epidemic most likely began when someone killed and ate a wild chimpanzee. It has since infected some 70m people and killed 35m.
Domestic livestock are the most likely incubator for Disease X. Large groups of farm animals (chickens, pigs and even camels) kept in close quarters create ideal breeding conditions for zoonotic disease. The viruses, constantly mutating, move rapidly from wild animals to farm animals and then on to humans. They can be spread by ticks but the fastest moving are airborne.
Disease X could be a mutation of an existing animal disease like avian influenza or African swine fever or it could be a brand-new pathogen that moves from animals to humans. As we farm, mine and colonize ever more remote locations of the planet, the more likely we are to come into contact with as yet unknown animal bugs. Cutting down the African bush for farmland or mining the Brazilian rainforest presents a constant risk of exposure to new zoonotic diseases.
Hiding in plain sight
Although the WHO focuses on unknown pathogens in its description of Disease X, another major pandemic risk comes from the potential evolution of existing diseases.
HIV, Tuberculosis, and influenza have already demonstrated their capacity for devastating epidemic spread. Global health infrastructure currently keeps them under control through a combination of surveillance, effective treatments – and good luck.
Influenza is one of the biggest threats. This was proven in 2009 when H1N1 (swine flu) went rapidly pandemic. 213 countries and territories reported cases of the virus and an estimated 285,000 people died in its wake.
That is a massive number, but it represents a case fatality rate of just .02%. Approximately one out of 5 people on the planet were infected, but very few died. In other words, H1N1 was highly infectious, but it was not highly virulent.
On the other hand, H151 avian influenza has a mortality rate in humans of about 60%. At present, H151 does not spread human-to-human. However, it could easily evolve and a virus with the infectiousness of H1N1 and the mortality rate of H151 would be devastating.
Tuberculosis (TB) is another continually evolving disease. The most basic forms of TB infection are cured with simple antibiotic treatment, but the bacteria which cause Tuberculosis are rapidly developing resistance to antibiotics. In 2016, an estimated 490,000 people worldwide developed multidrug resistant TB and it has been reported in 117 countries worldwide.
HIV is a third existing pandemic that could slip out of control. Antiretroviral drugs (ARVs) allow people with the condition to live normal healthy lives. However, HIV is also becoming resistant to treatment. Among countries that report relevant data to the WHO, 10-15% of people are diagnosed with HIV which is resistant to the standard antiviral treatments.
These numbers could get worse. “HIV is the fastest mutating organism on the planet”, said Dr. Edsel Salvana, an infectious disease specialist at the University of the Philippines. “We are seeing new strains of HIV that are highly aggressive and develop drug resistance faster. We need to stay on top of this with careful surveillance, and we need to develop new and more durable drugs.”
At a glance | Notable plagues from history
- Plague of Athens (430 BC): One of the first recorded, the Plague of Athens killed a quarter of the city’s population. The disease that caused it is still unknown.
- Black Death (1347 to 1353): The Black Death, caused by bubonic plague, killed some 50m people in Europe in less than a decade.
- First Cholera Pandemic (1817 to 1824): The death toll from the first cholera pandemic is unknown but from its origins in India, cholera spread worldwide, killing tens of millions. There is currently a serious outbreak in Yemen.
- Spanish Flu (1918 to 1919): Caused by the H1N1 virus, Spanish flu spread worldwide infecting a third of the global population. It killed between 50m and 100m people.
- Ebola (2013 to 2016): The virus primarily affected West Africa and killed over 11,000 people. It was started after a bat bit a one-year-old boy in Guinea.
Doing battle with Disease X
How do you prepare for a threat you cannot predict?
The WHO has chosen a tried and tested approach to preparing for Disease X. Its doctrine flies under the age old banner of “preparedness”.
By improving disease surveillance and strengthening the capacity of local health systems across the globe, it aims to spot an outbreak early, contain it and kill it off before it spreads.
Few experts, if any, disagree with the approach – it’s really the only one we have – but many wonder if adequate health care facilities exist on the ground internationally to make it work.
Dr Nahid Bhadelia, Medical Director of Special Pathogens at Boston University Medical Center, compared the system of preventing the spread of new diseases to a city building a series of dams or seawalls to protect itself from floods. In the case of diseases, the presence of a strong local health system provides the vital early warning and treatment needed to contain the outbreak.
“Not helping strengthen international capacity to combat infectious diseases is like refusing to build barriers against the tide in some parts of our ‘global city’ and expecting to be protected when the flood comes.”