The best minds in virology are trying to unravel a mystery: How did a lethal coronavirus jump from the wilds of rural China to major human population centers? And what chain of genetic mutations produced a pathogen so perfectly adapted for stealth and mass transmission?
Deciphering the creation story of SARS-CoV-2, as the virus now rampaging around the globe is known, is a crucial step toward arresting a pandemic that's killed 270,000-plus and triggered what could be the worst economic collapse since the Great Depression.
While crash vaccine programs are underway in the US, Europe and China, an inoculation to ward off the virus may not be ready for months, and the jury's out on potential treatments. In the meantime, to reduce the risk of deadly secondary outbreaks or the emergence of an entirely new strain, disease chasers need to retrace the pathogen's journey around the globe. That means heading back to China, where it all started sometime in 2019.
We have some kind of a missing link in that story between the origin of the virus and when it started to circulate in humans.
Last week, the World Health Organization sought permission from Beijing to send a new scientific mission for more epidemiological detective work. China, which let a WHO team into the country in early February as its epidemic raged, hasn't yet signed off.
President Xi Jinping, who's personally overseeing China's virus response and investigation into how the outbreak started, is keeping tight control over Chinese scientific research, which must be approved prior to publication by authorities, according to two people familiar with the situation.
However, as death tolls and joblessness rise worldwide, pressure on Beijing is intensifying to allow international researchers back in to interview survivors, do field work, and examine virus samples that the country has been stingy about sharing, according to the US.
Nearly half a year into a historic global health crisis, there are still enormous gaps in our knowledge. Those unanswered questions are hampering our ability to contain the outbreak and to prevent future pandemics, while fueling a war of words between the US and China over the origins of the virus.
Roughly 70% of emerging infectious diseases in humans are zoonotic, or transmitted from animals to people. Genome sequencing of SARS-CoV-2 shows it's related to two other deadly coronaviruses that originated in bats.
1 million to 7 million people every year in Southern China and Southeast Asia may get infected with bat viruses. Most don’t spread readily between people and many fizzle out before reaching major population centers.
Severe acute respiratory syndrome, which started in China in 2002, and Middle East respiratory syndrome a decade later spread to humans via a secondary animal source. In the case of SARS, experts pointed to civet cats - small, sleek nocturnal mammals used in wildlife dishes in China - as the probable conduit. With MERS, camels are believed to be the carrier.
It's presumed that SARS-CoV-2 has made a similar journey, yet investigators have yet to identify an intermediate animal host, according to Peter Ben Embarek, a WHO food safety and animal diseases expert. "We have some kind of a missing link in that story between the origin of the virus and when it started to circulate in humans," he said.
That raises the disturbing possibility that an unknown animal source is still spreading the disease, known as Covid-19. WHO researchers reported Friday that household cats can transmit the virus to other felines, though there's no evidence yet that pets can pass it along to humans.
Standing in the way of a new scientific mission to learn more about the origins of the virus in China are practical issues of conducting impartial investigations in an authoritarian political system" - and a US-China geopolitical rivalry that's turned especially acrimonious of late.
The Trump administration has accused Beijing of a massive cover-up about the severity of its epidemic. It has claimed, without providing evidence, that an accidental leak of the virus might have occurred at a bio-research lab in Wuhan, the city in central China where the outbreak was first identified. A Chinese official, in a tweet, accused the US military of introducing the pathogen to the country.
Scientists who have studied the genetics of the virus are convinced it's of natural origin rather than designed in a lab. An accidental release from the research center in Wuhan is possible in theory, but "just so implausible," according to Stanley Perlman, a professor of microbiology and immunology at the University of Iowa, who has visited the facility and rates it highly.
One reason is the reputation of Shi Zhengli, a 56-year-old deputy director of the Wuhan Institute of Virology. In 2004, Shi found a natural reservoir of coronaviruses in bat caves near Kunming, a city in China's southern Yunnan province. In February she published a paper in the journal Nature saying that the genomic sequence of the new pathogen was 96% identical to that of a coronavirus identified in Yunnan.
Shi told Scientific American that a review of genetic characteristics of viruses she's worked with in the lab didn't match those of the coronavirus spreading in humans. In a social media post the virologist said she would "swear on my life" the pathogen causing havoc had nothing to do with her lab. US Secretary of State Michael Pompeo has backed off earlier claims of "enormous evidence" that the virus escaped from a Wuhan laboratory.
That still leaves scientists asking where and how the virus did jump into humans. So-called wet markets that sell live animals, like one in Wuhan to which many of the first cases of the illness were traced, have previously been implicated in the spread of disease. In this case, however, experts aren't sure whether the outbreak actually started at the market, or was just discovered there.
Peter Daszak, a disease ecologist at nonprofit EcoHealth Alliance, said it's likely that Covid-19 began before the December starting point currently assumed, perhaps even outside of Wuhan. He estimates that 1 million to 7 million people every year in Southern China and Southeast Asia may get infected with bat viruses. Most don't spread readily between people and many fizzle out before reaching major population centers, he said.
"This particular outbreak probably was in people circulating in South or Central China back in November" or even earlier, he said.
Another scenario envisions someone closely tied to the wildlife trade bringing infected animals to the Wuhan market. Once the virus reached the flourishing megacity of 11 million, it grew exponentially.
Another crucial question is whether the virus moved to humans directly from bats or through a secondary source. If it's the latter, the farmed or wild animal may still be spreading the infection. Pangolins"-scale-covered mammals that look a bit like anteaters" - have been suggested as one possibility, though the evidence is preliminary. If Covid-19 came directly from bats, it's crucial to nail down where this happened, so that the authorities can institute preventive measures, such as keeping people out of the caves in which the flying mammals dwell.
Figuring out all of this will take plenty of scientific detective work. Viruses constantly incur small mutations in their genetic material. By following a trail of genetically similar versions, disease trackers can identify the progression of the pandemic through time. "Counting the mutations, you can kind of backtrack your virus to where it all started," said WHO animal virus expert Embarek.
Tracing back the virus to its ultimate origin will also take cooperation from the Chinese government"-and a bit of luck. Investigators will need unfettered access to the Wuhan market, its wildlife vendors, patient data and animal population.
Yet the price of keeping SARS-CoV-2's origins shrouded in secrecy would be steep. If the current crisis has taught us anything, it's this: As human populations expand and encroach on wildlife habitats, the risk from dangerous animal viruses continues to grow. And in an interconnected world, epidemics that were previously localized can race around the globe with blinding speed.
Without better research and surveillance systems of emerging animal viruses and regulation of traditional markets and wildlife trade worldwide, the risks of future pandemics runs high.
"If we don't do anything, if we continue what we have been doing for the past 50 years," said Daszak, "there will be another one."