HISTORY IN CRISIS: ESCAPING PANDORA’S BOX- ANOTHER NOVEL CORONAVIRUS!

Writing in the heady days of new antibiotics and immunizations, esteemed microbiologists Macfarlane Burnet and David White predicted in 1972 that “the most likely forecast about the future of infectious diseases is that it will be very dull”.

They acknowledged that there was always a risk of “some wholly unexpected emergence of a new and dangerous infectious disease, but nothing of the sort has marked the last fifty years”.
Times have changed.

From herpes and legionnaires’ disease in the 1970s, to AIDS, Ebola, the severe acute respiratory syndrome (SARS), and now Covid-19, contagious diseases continue to threaten and disrupt human populations.

We should remember the 1918 pandemic as we deal with yet another infectious-disease emergency: the growing epidemic of novel coronavirus infectious disease (Covid-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

This virus has been spreading throughout China for at least 2 months, and has been exported to at least 36 other countries, seeding more than two secondary cases for every primary case.

The World Health Organization has declared the epidemic a Public Health Emergency of International Concern. If public health efforts cannot control viral spread, we will soon be witnessing the birth of a fatal pandemic.

The Greek myth of Pandora’s box (actually a pithos, or jar) comes to mind: the ‘gods’ had given Pandora a locked jar she was never to open. Driven by human weaknesses, she nevertheless opened it, releasing the world’s misfortunes and plagues.

Of course, scientists tell us that SARS-CoV-2 did not escape from a jar: its RNA sequences closely resemble those of viruses that silently circulate in bats.

Epidemiologic information implicates a bat-origin virus infecting unidentified animal species sold in China’s live-animal markets.

We have recently seen many such emerging zoonoses, including the 2003 bat-coronavirus–derived SARS (an earlier severe acute respiratory syndrome, caused by a closely related coronavirus), which came terrifyingly close to causing a deadly pandemic that was prevented only by swift global public health actions and luck.

Now, 17 years later, we stand at a similar precipice. How did we get to this point, and what happens next?

We must realize that in our crowded world of 7.8 billion people, a combination of altered human behaviors, environmental changes, and inadequate global public health mechanisms now easily turn obscure animal viruses into existential human threats.

We have created a global, human-dominated ecosystem that serves as a playground for the emergence and host-switching of animal viruses, especially genetically error-prone RNA viruses, whose high mutation rates have, for millions of years, provided opportunities to switch to new hosts in new ecosystems.

It took the genome of the human species 8 million years to evolve by 1%. Many animal RNA viruses can evolve by more than 1% in a matter of days. Thus, it is not difficult to understand why we increasingly see the emergence of zoonotic viruses.

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We have actually been watching such dramas play out in slow motion for more than a millennium in the case of pandemic influenza, which begins with viruses of wild waterfowl that host-switch to humans and then cause human-to-human transmission.

A bird virus thereby becomes a human virus.

Coronavirus emergence takes a different trajectory, but the principles are similar: SARS, the Middle Eastern respiratory syndrome (MERS), and Covid-19 all apparently have their origins in enzootic bat viruses. The parallels between the two SARS viruses are striking, including emergence from bats to infect animals sold in live-animal markets, allowing direct viral access to crowds of humans, which exponentially increases opportunities for host-switching. Such live markets have also led to avian epizootics with fatal human “spillover” cases caused by nonpandemic, poultry-adapted influenza viruses such as H5N1 and H7N9.

One human cultural practice in one populous country has thus recently led to two coronavirus near-pandemics and thousands of severe and fatal international cases of “bird flu.”

We have reached this point because of continuing increases in the human population, crowding, human movement, environmental alteration, and ecosystemic complexity related to human activities and creations. Cartoonist Walt Kelly had it right decades ago: “We have met the enemy, and he is us.”

With Covid-19, are we seeing a replay of 1918? Although we did not “witness” the beginning of the 1918 pandemic, evidence suggests that wherever it began, it silently spread around the world, causing mostly mild cases but also mortality of 0.5 to 1% or higher — a rate that was initially too low to be detected against a high background rate of death from unrelated respiratory illnesses.

Then it suddenly exploded in urban centers almost everywhere at once, making a dramatic entrance after a long, stealthy approach. We are now recognizing early stages of Covid-19 emergence in the form of growing and geographically expanding case totals, and there are alarming similarities between the two respiratory disease emergences. Like pandemic influenza in 1918, Covid-19 is associated with respiratory spread, an undetermined percentage of infected people with presymptomatic or asymptomatic cases transmitting infection to others, and a high fatality rate.

With luck, public health control measures may be able to put the demons back in the jar. If they do not, we face a daunting challenge equal to or perhaps greater than that posed by the influenza pandemic of a century ago.

As the late Nobel laureate Joshua Lederberg famously lamented about emerging infectious diseases, “It’s our wits versus their genes.” Right now, their genes are outwitting us by adapting to infectivity in humans and to sometimes silent spread, without — so far — revealing all their secrets. But we are catching up.

As we push ahead, we should take heart in the Hesiod version of the Pandora myth, in which Pandora managed to prevent a single escape: “Only Hope was left …, she remained under the lip of the jar, and did not fly away”.