An emergency response team on 11 January at work in the Huanan Seafood Wholesale Market in Wuhan, China, initially said to be the source of COVID-19.

By Jon CohenJul. 10, 2020 , 4:30 PM

Science's COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

The two-person team from the World Health Organization (WHO) traveling to China today to address the origin of the COVID-19 pandemic is unlikely to come home with answers. Rather, the duoan epidemiologist and an animal health expert whose names have not been releasedwill discuss with Chinese officials the scope of alarger international mission later, according to a WHO statement.

But this initial trip offers real hope that the mystery of the virus origins, which has become a political powder keg and the subject of countless conspiracy theories, will finally be investigated more thoroughly and transparently. (A similar WHO-led mission to examine how China was handling its fight against the virus, launched after weeks of diplomatic wrangling, returned in February with a surprising wealth of information.)

Science must stay open to all possibilities about the pandemics origins, Mike Ryan, executive director of WHOs Health Emergencies Programme, said at a press conference on 7 July. We need to lay out a series of investigations that will get the answers that Im sure the Chinese government, governments around the world, and ourselves really need in order to manage the risk going forward into the future.

Questions range from hunting for animals that might harbor the virus to examining the possibility that it came from a laboratory. There are plenty of details to investigate, and it could be a long road. Origin riddles for other new infectious diseases often took years to solve, and the route to answers has involved wrong turns, surprising twists, technological advances, lawsuits, allegations of cover ups, and high-level politics. Determining how a pathogen suddenly emerges in people requires a lot of sleuthing, but past successes offer clues of where to look for new insights, as do the few data points that now exist for SARS-CoV-2, the virus that causes COVID-19.

The initial, tidy origin story told by health officials in Wuhan during the first few weeks of January was that a cluster of people connected to a seafood market developed an unusual pneumonia, and that the outbreak stopped after the market was closed and disinfected. But confusion about the origin of the novel coronavirus identified in Wuhan patients arose when researchers published the first epidemiologic studies of the citys outbreak:Four of the first five casesconfirmed to have SARS-CoV-2 infections had no link to the market.

Soon, other theories emerged. Some believe its no coincidence that the city is host to the Wuhan Institute of Virology (WIV), home to leading bat coronavirus researcher Shi Zheng-Li. Her group, one of the first to isolate and sequence SARS-CoV-2, has trapped bats in the wild for 15 years, hunting for coronaviruses to help identify pandemic threats. In theirfirst report about the new virus, the scientists described a bat coronavirus in their collection that was 96.2% similar to SARS-CoV-2.

U.S. President Donald Trump early on endorsed speculation that the virus entered humans because of an accident at WIV. Amore contentious theoryis that the lab created the virus. (Researchers at the lab insist neither scenario has any merit, and evolutionary biologists elsewhere have argued the virus shows no evidence of having been engineered.)

The most popular hypothesis is that SARS-CoV-2 spread into humans from an intermediate host, an animal species susceptible to the virus that acted as a bridge between bats and humans. In the case of severe acute respiratory syndrome (SARS), civets turned out to play that role for the responsible coronavirus. For Middle East respiratory syndrome (MERS), also a coronavirus disease, itquickly became clearcamels were the culprit because highly similar viruses were found in the animals and people caring for them.

Chinese officials have reported conducting tests for SARS-CoV-2 at the Wuhan seafood market but what they foundremains sketchy. Chinas state-run news agency, Xinhua, said environmental samples tested positive for the virus in a zone of the market that sold wildlife, but the report had no details about the results or even a list of the species for sale. Other studies have discovered similarities between SARS-CoV-2 and a coronavirus found in pangolins, an endangered species that eats ants, but the pangolin virus is more divergent genetically from SARS-CoV-2 than the closest bat virus and theres no evidence pangolins or their scalesused in traditional Chinese medicinewere sold at the market.

Some more fringe theories still suggest SARS-CoV-2 came fromsnakes,cometary debris, or aU.S. Army lab.

So, assuming WHOs team and the Chinese government work out a deal for an international mission to study the pandemics origins, where would it start? Here are some key questions that need answers.

Scientists realized camels were the source of Middle East respiratory syndrome when highly similar viruses were found in the animals and people caring for them.

Another outstanding question is whether Shis team or other researchers in Wuhan manipulated bat viruses in gain-of-function experiments that can make a virus more transmissible between humans. In 2015, Shi co-authored a paper that made a chimeric SARS virus by combining one from bats with a strain that had been adapted to mice. Butthat workwas done at the University of North Carolina, not in Wuhan, and in collaboration with Ralph Baric. Did Shis group later carry out other gain-of-function studies in Wuhanand if so, what did they find?

Finally, diplomatic cablesfrom the U.S. Embassy in Beijing in 2018 warned that a new, ultra-high security lab at WIV had a serious shortage of appropriately trained technicians and investigators. Did Shis team ever work with coronaviruses in that lab, and, if so, why?

If history repeats itself, it might take yearsor even decadesto crack this case. Scientists havent unequivocally identified Ebolas source 45 years after its discovery. But the key, time and again, to clarifying the origins of emerging infectious diseases is unearthing new data. WHOs push to organize the probe promises to, at the very least, accelerate what has been a plodding pursuit for answers.

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A WHO-led mission may investigate the pandemic's origin. Here are the key questions to ask - Science Magazine