On 17 January 2024, public health experts including Tedros Adhanom Ghebreyesus, the Director-General of the World Health Organization (WHO), held a roundtable titled “Preparing for Disease X” at the World Economic Forum of Davos (WEF). In light of the recent COVID-19 pandemic, the panel discussed what had failed in the global response to the pandemic and what could be improved.
But the mention of a mysterious “Disease X” just one year after the end of a pandemic became fodder for conspiracy theories on the Internet. Some people suggested that a new manmade pandemic was about to be unleashed, while others claimed that the WEF and WHO were simply fear-mongering to acquire global control over national public health policies.
Given the misunderstanding over what “Disease X” is and what the roundtable was about, this Insight article will examine what “Disease X” means in the context of preparedness to help readers distinguish between accurate information and conspiracy theories.
What is Disease X?
The term “Disease X” certainly has a mysterious ring to it, which may have contributed to the spread of unverified claims about it. However, Disease X is merely the name given to a possible, still unknown, pathogen of pandemic potential that may emerge one day.
During the WEF discussion panel, Tedros defined Disease X as “a placeholder for unknown disease”. He explained that the WHO keeps a list of known emerging diseases to be monitored, such as Ebola and Zika. He also emphasized that the WHO is aware that not all potentially dangerous pathogens are known to us and that it is very likely that, one day, one such pathogen will emerge. The WHO thus needed a name for that threat, hence “Disease X”.
On its website, WHO explains that:
“Disease X represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease. The R&D Blueprint explicitly seeks to enable early cross-cutting R&D preparedness that is also relevant for an unknown ‘Disease X’”
Thus, Disease X isn’t a real pathogen, nor is it evidence that a pandemic will arrive shortly. Rather, it encapsulates the idea of a new pathogen with pandemic potential that may one day emerge and must be acknowledged. It is a bit similar, then, to the idea of “the Big One”, the hypothetical, massive earthquake that may one day hit California.
Contrary to what some may believe, Disease X isn’t a new concept and existed well before the WEF’s 2024 meeting and even the COVID-19 pandemic. Documents from the WHO explain that it took its roots in the West African Ebola crisis in between 2014 and 2016. During these years, an outbreak of Ebola that began in Guinea spread to neighboring Sierra Leone and Liberia, and even countries further away, like Spain, Italy, the U.K., and the U.S.. Seven people were diagnosed with Ebola in the U.S. and one died.
Witnessing first-hand the threat of emerging diseases and the need for a coordinated global response, member nations of the WHO requested the organization to strengthen “global preparedness and ensur[e] WHO’s capacity to prepare for and respond to future large-scale outbreaks and emergencies with health consequences”.
The WHO responded to the request by establishing a research and development (R&D) blueprint in 2015 to improve preparedness against pandemics. One important outcome of that blueprint was a shortlist of dangerous pathogens with pandemic potential for focusing funding, research and preparedness efforts.
WHO experts selected those pathogens based on several criteria:
- Human transmissibility: how easily the pathogen can spread among the population
- Severity: how likely it is that an infected person will die
- Spillover potential: how easily a pathogen that usually infects other animals will be able to infect humans
- Evolutionary potential: how fast the pathogen evolves, thus hampering efforts to develop vaccines against it
- Available countermeasures: whether or not there are effective ways to prevent transmission, cure, or at least mitigate the consequences of infection
- Difficulty of detection: whether or not the disease could spread undetected among the population, increasing the risk of detecting it when it is too late
- Public health context of affected areas: whether the disease is likely to occur in areas ill-equipped to handle the crisis
- Potential scope of the outbreak: how likely it is that the disease will spread worldwide
- Potential societal impact: how likely it is that the disease will disrupt the stability and functioning of society
This meant that some well-known diseases like AIDS, tuberculosis, and malaria were set aside. Although these can be deadly and have a clear pandemic potential, we already have functional monitoring and prevention systems, as well as therapies for these diseases, making them less of a priority.
The six known diseases that did make the shortlist were Crimean-Congo hemorrhagic fever, filovirus diseases (Ebola and Marburg), highly pathogenic emerging coronaviruses relevant to humans (MERS and SARS-Cov-1), Lassa Fever, Nipah, and Rift Valley Fever.
However, the WHO also included a seventh item to the list: “a new disease”. The reason is that the emergence of a new infectious disease in the future is plausible. Indeed, several of the six priority diseases listed above only appeared in people in the recent decades. For instance, Ebola was first described in 1976, Nipah in 1999, SARS-CoV-1 in 2003, and MERS in 2012.
Available data indicate that these viruses appeared in humans because of spillovers from animal reservoirs (zoonotic infection). For example, the MERS coronavirus jumped from camels to humans[1]. The Nipah virus is believed to be carried by fruit bats, and then spread to pigs before passing to humans.
Furthermore, many pandemics have struck humanity over the course of history, such as the Black Plague during the Middle Ages; the Spanish, Asian, Hong Kong, and swine influenza; and HIV/AIDS.
This history demonstrates a fact of life: that new pathogens emerge from time to time, and that some of these can cause pandemics. Therefore, there is no plausible reason to believe that this wouldn’t happen again. The emergence of SARS-CoV-2, the virus that causes COVID-19, in late 2019 proved the WHO right.
The WHO then updated its pandemic potential list in 2017 and again in 2018, with new diseases such as Zika entering the list. Although no references to a hypothetical unknown disease appeared in the 2017 version, the more recent 2018 version brought back that concept under the name “Disease X”. The WHO announced that it will update the list again in 2024.
In summary, “Disease X” is a concept that has existed in the international health community since at least 2015. It acknowledges that we don’t know all the pathogens that may one day cause a pandemic and that the global public health community should be prepared both against the outbreak of known pathogens and the possible emergence of a new one.
The importance of preparedness
Preparedness is necessary to effectively respond to a new pathogen, should one emerge. This includes running outbreak simulation exercises, reviewing and updating current guidelines, and coordinating and improving synergy between all the stakeholders of a health crisis response. This is well illustrated by the title of an editorial from The Lancet Respiratory Medicine dedicated to the topic: “failing to prepare means preparing to fail”.
Reviews of the way countries and the international community handled the COVID-19 pandemic showed that pandemic preparedness at local, national, and international levels was subpar at best.
The 2022 World Disasters Report from the International Federation of Red Cross and Red Crescent Societies (IFRC) stated that countries were too slow in reporting and addressing the initial outbreak of COVID-19. It also pinpointed the underperforming system of manufacturing, distributing, and stockpiling of crucial resources such as protective gear, drugs, and vaccines.
Additionally, it highlighted the lack of health crisis response guidelines at every administration level, underprepared health system and social security safety nets, and a lack of international collaboration, leading to the widening of socioeconomic inequalities in facing the pandemic.
A reviewing commission organized by The Lancet, which gathered 173 experts on public policy, international cooperation, epidemiology and vaccinology, economics and financial systems, sustainability sciences, and mental health, also shared their views on the way the COVID-19 pandemic was handled.
The commission identified failures in:
- The timely communication of the initial outbreak of COVID-19 and the airborne nature of the disease
- Adequately channeling equipment, resources, and funding toward the more at-risk communities
- Releasing timely and accurate data about COVID-19 cases, deaths, and SARS-CoV-2 variants[2].
Not only was the world unprepared for a pandemic, but it remained so after COVID-19. “As of the time of writing, all countries remain dangerously unprepared for future outbreaks,” the IFCR wrote in its report.
The editorial of The Lancet Respiratory Medicine echoed this sentiment, stating that “at present, many countries are severely underprepared to enact any plans for future pandemic prevention or response […] to fully prepare for future pandemics, investment in mechanisms to prevent, detect, and respond to emerging pathogens is crucial.”
Both the IFCR and the Lancet commission also emphasized the importance of multilateral collaboration in the world’s response to emerging biological risks. Thus, far from being mere fear-mongering, talks about Disease X are actually part of a necessary and overdue effort to shore up the world’s ability to prepare for public health crises.
Examples of misinformation about Disease X
The inclusion of Disease X in talks at the World Economic Forum led to numerous comments on the internet, sometimes misrepresenting the concept of Disease X. Many claims implied that Disease X is mostly an attempt at a power grab by institutions like the WHO, either by causing or organizing a new pandemic, or fear-mongering by warning about an imminent threat that actually doesn’t exist.
For instance, a tweet by osteopath Joseph Mercola claimed that “the reason we can be sure there will be additional pandemics, whether manufactured using either fear and hype alone or an actual bioweapon created for this very purpose, is because the takeover plan, aka The Great Reset, is based on the premise that we need global biosecurity surveillance and centralized response.” Mercola has spread health misinformation in the past. Robert Malone, Peter McCullough, and Russell Brand, who also spread misinformation on COVID-19 and COVID-19 vaccines, shared similar views. As we have shown above, these claims are inconsistent with reality: pandemic preparedness efforts are needed because we know new diseases emerge. These efforts do not show in any way that pandemics are “planned” or “manufactured”.
Some internet users cited two U.S. bills with “Disease X” in their title as proof that the U.S. government “already knew” about Disease X, implying that there was a covert, orchestrated attempt to push a narrative about a fake pandemic called “Disease X” or to set the stage for an actual disease with that name.
The two bills in question, HR3832 and S2093, were introduced in mid-2023. Their aim was to expand the priorities of the U.S. Biomedical Advanced Research and Development Authority (BARDA) in order to develop research programs and countermeasures for the hypothetical emergence of Disease X.
However, these claims are misleading. As we explained above, “Disease X” is simply a placeholder for a potential new pathogen with pandemic potential.
As we also explained, the COVID-19 pandemic showed that the global community was unprepared for that type of crisis. Thus, there are reasonable, scientific grounds for increased international collaboration in preparing for emerging diseases, including via discussions and laws. This makes the accusation of fear-mongering unsubstantiated.
Other claims implied that Disease X would result from pathogens created in the laboratory for their intentional release into the population. For instance, Mercola commented, “It’s pretty easy to predict a new viral outbreak if you have said virus waiting in the wings” in his tweet (mentioned earlier), implying that people advocating for increased pandemic preparedness were also creating a new pathogen in the lab.
Along the same lines, Brand commented that “gain of function research is leading to new outbreaks” and asked “how do you know that something is going to emerge?” In this manner of “just asking questions”, Brand implied that advocates of pandemic preparedness may be aware of laboratory research leading to upcoming outbreaks. However, there is no evidence that past pandemics, like the plague, the Spanish flu, or HIV/AIDS are the result of gain-of-function research. Thus, there is no basis to Brand’s comment in absence of additional data.
Proponents of those claims, like Mercola, Brand, or John Campbell, paired their comments on Disease X with mentions of recent research by Chinese scientists on a pangolin coronavirus called GX_P2V. Wei and colleagues published a preprint (a study that hasn’t yet been peer-reviewed) reporting that the coronavirus GX_P2V was able to infect so-called “humanized mice”, which were genetically modified to have their cells express a human protein called ACE2. ACE2 is the molecular receptor that SARS-CoV-2 uses in order to enter and infect our cells. Wei et al. reported that GX_P2V infection in those humanized mice had a 100% death rate.
The direct association of the research by Wei et al. with comments on Disease X strongly implies that this research could lead to a future pandemic or, more broadly speaking, that Disease X will come from laboratory research.
However, there is no basis for the claim that this research on GX_P2V is paving the way for the next pandemic. Angela Rassmussen, a virologist at the University of Saskatchewan, explained on Twitter/X that the results from the preprint by Wei et al. don’t necessarily represent the ability of the virus to cause disease in humans. This is because the researchers used a type of mice that express abnormally high levels of the human receptor ACE2 on all cells. However, this isn’t what happens in the human body, where only certain tissues carry the ACE2 receptor and only at moderate levels.
“The reason why this was so deadly in these particular mice is because they are engineered to support massive virus growth. There is a gain of function in the mice—high levels of human ACE2 everywhere—not the virus.”
In summary, past pandemics, as well as the emerging pathogens on the current WHO shortlist, most often came from wildlife and spilled over to humans. While the possibility of a future lab leak cannot be ruled out, there is currently no reason to assume, in the absence of additional evidence, that the term “Disease X” coined by the WHO refers specifically to lab-engineered pathogens.
REFERENCES
- 1 – Mohd et al. (2016) Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir. Virology Journal.
- 2 – Sachs et al. (2022) The Lancet Commission on lessons for the future from the COVID-19 pandemic. The Lancet.