The mission has become politically charged as China seeks to avoid blame for alleged missteps in its early response to the outbreak.
A major question is where the Chinese side will allow the researchers to go and whom they will be able to talk to.
Yellow barriers blocked the entrance to the hotel, keeping the media at a distance. Before the researchers boarded, workers in full protective gear could be seen loading their luggage onto the bus. The driver wore a full-body white protective suit and the researchers wore masks.
Earlier this month, former WHO official Keiji Fukuda, who is not part of the team in Wuhan, cautioned against expecting any breakthroughs, saying it may take years before any firm conclusions can be made on the virus's origin.
"This is now well over a year past when it all started," he said.
"So much of the physical evidence is going to be gone. The memories of people are imprecise and probably the physical layout of many places are going to be different."
Among the places the WHO team might visit are the Huanan Seafood Market, which was linked to many of the first cases, as well as research institutes and hospitals that treated patients at the height of the outbreak.
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The mission only came about after considerable wrangling between the two sides that led to a rare complaint from the WHO that China was taking too long to make the final arrangements. China has strongly opposed an independent investigation it could not fully control.
While the WHO was criticized early on, especially by the United States, for not being critical enough of the Chinese response, it recently accused China and other countries of moving too slowly at the start of the outbreak — drawing a rare admission from the Chinese side that it could have done better.
Overall, though, China has staunchly defended its pandemic response.
"The WHO and global experts have given their full affirmation of China's epidemic prevention success and past origins tracing work," Foreign Ministry spokesperson Zhao Lijian said Wednesday. "Both sides have a basic consensus on cooperation on origins-related research, and related work is progressing smoothly."
Chinese officials and state media have tried to cast doubt on whether the virus started in China. Most experts believe it came from bats, possibly in southwest China or neighboring areas of Southeast Asia, before being passed on to other animals and then to humans.