In the midst of the SARS-CoV-2 pandemic, it is worth remembering that as late as the 1970s many leading scientists concurred with the Nobel winning virologist Sir Frank Macfarlane Burnet, who declared that “the most likely forecast about the future of infectious disease is that it will be very dull” and nothing like the previous fifty years. While “isolated outbreaks of fatal infections,” such as had happened with the Marburg and Lassa viruses, would “doubtless occur in the future,” Macfarlane Burnet and his co-author David White wrote, these “will presumably be safely contained.”
Something, to say the least, has gone tragically wrong. New viruses and new strains are appearing all the time, and old ones are wreaking new havoc.
Just consider the last decade, when the World Health Organization declared a Public Health Emergency of International Concern five times (excluding the special case of a polio declaration in 2014). A PHEIC is defined as “an extraordinary event,” in which the spread of a disease constitutes a threat to other countries and might require coordinated international action. We’re now averaging one every two years. “Extraordinary”—uncommon, atypical, exceptional—doesn’t mean what it used to mean.
The PHEIC declarations are part of a system of health regulations enacted in response to the 2002–03 Severe Acute Respiratory Syndrome (SARS-CoV) outbreak. Like SARS, which originated in Guangzhou, China, the five extraordinary events in recent years have all been viral.
In 2009–10, it was the novel influenza A H1N1 pandemic, first identified in Mexico. In the United States, there were 275,000 hospitalizations and 12,500 deaths. A report in the Lancet estimated the worldwide death toll at about 285,000 over the period from April 2009 to August 2010, with the possible fatality range extending from 152,000 at the low end to 575,000 at the high. In contrast with most influenza strains, 80 percent of deaths were of people younger than age 65.
From 2014–16, there was a major outbreak of Ebola in Western Africa. The nearly 29,000 cases across 10 countries led to 11,325 deaths.
In 2015–2016, the Zika virus epidemic spread across Latin America and the Caribbean into the southern US, and was later reported in Southeast Asia and Africa. Over 2015 and 2016, the Pan American Health Organization reported 730,000 suspected cases in the Americas. Zika is linked to Guillain-Barré syndrome, a life-threatening condition marked by temporary paralysis, and there were more than 3,700 confirmed cases of microcephaly and other adverse birth outcomes.
Starting in 2018, another Ebola outbreak began spreading through the Congo and Uganda. There have been more than 3,300 confirmed cases and more than 2,100 deaths so far. In 2020, SARS-CoV-2, originating in China, has spread to every country in the world, with deaths above a quarter million and growing daily.
In addition, there was another outbreak in 2012, of Middle East respiratory syndrome coronavirus, or MERS-CoV, which reached 27 countries. Most of the reported cases were in Saudi Arabia and MERS did not receive a PHEIC. There have been more than 2,000 confirmed cases and more than 700 fatalities.
New pathogenic forms of avian flu have also been identified in recent years. Small outbreaks of the deadly H5N1, for instance, were reported in 2003–04 across nine Asian countries, and of H7N9 in China beginning in 2013.
All of these “extraordinary events” involve zoonotic diseases, in which a pathogen “spills over,” or “jumps” from an animal to humans. The influenza A and coronavirus variants were all novel, while Ebola and Zika had never appeared in the affected regions before.
Viruses are highly dynamic microbes. But there are significant barriers that inhibit the flow of a virus from a host species to humans. In some cases, and through a complex set of processes, vulnerabilities, and exposure conditions, viruses in the host species can mutate into a distinct strain that might be released (“shed”) from the host, survive/spread (such as by mosquitos or human-to-human with Zika), and overcome the innate immune response and become infectious to humans.
Though little is known, the viral hosts of Ebola are believed to be bats, with transmission to humans through close contact or consumption of the bushmeat of various infected species of animals such as monkeys. In the case of influenza A H1N1, a leading theory is that in the intercontinental pig trade, live animals infected with three different flu viruses were brought in contact and transmitted their viruses to each other. These parent viruses genetically interacted within a pig host and created a reassortment with new, never-before-seen qualities that subsequently jumped to humans on a single occasion. Just this process was earlier identified for HIV, where a novel combination of two monkey viruses arose in a chimpanzee, which was later eaten by humans.
With the novel corona viruses, a somewhat different process is in operation. In these cases, an “intermediate host” is involved in which the original virus, from a bat, undergoes reassortment, creating a new pathogen that can jump to humans. With SARS-CoV-2, for instance, the current best candidate for the intermediary is the pangolin, a scaly mammal sold for its scales and meat in China’s wild animal markets. In the pangolin and/or in a human, the virus exchanged genes to acquire features that allow it to bind with human cells and invade them. The original virus in the horseshoe bat did not have these features. It acquired them later.
Under normal circumstances, zoonotic spillover is a “relatively rare event.” The barriers to spillover are formidable and require many factors to align within a specific time frame to create danger to humans. The problem is that our exploitive relationship to the natural order is greatly magnifying the possibility of spillover and increasing virus virulence. In every case I have mentioned, biologists tell compelling stories of how human action—our industrial farming and dense animal production systems, our petrochemicals and technological interventions, our destruction of natural ecosystems and biodiversity, our live animal markets, our consumption patterns and global travel—is directly contributing to the constant outbreaks we are now facing.
The genesis of SARS-CoV-2 is the latest and most devastating example. Might this be the shock that will jolt us into both recognizing our need and giving us the will to address our practices? We can no longer be surprised by emerging diseases and basically do nothing structural. Medicines and vaccines have played an enormous role in the reduction of the disease burden. But the world that Macfarlane Burnet envisioned in 1972 has not come about. We have to change the conditions that produce pandemics rather than hope for one-at-a-time biomedical and public health responses. As I wrote four years ago, in response to the Zika virus, for “many, many vulnerable people, new vaccines will always arrive too late.”