Before the coronavirus pandemic, clues from Chinese scientists were overlooked

In late December 2019, eight pages of genetic code were sent to computers at the National Institutes of Health in Bethesda, Maryland.

Unbeknownst to U.S. officials at the time, the genetic map that landed on their doorstep contained critical clues about the virus that would soon cause a pandemic.

The genetic code, submitted by Chinese scientists to a massive public repository of sequence data run by the US government, described a mysterious new virus that had infected a 65-year-old man weeks earlier in Wuhan. At the time the code was sent, Chinese officials had not yet warned about the unexplained pneumonia that was sickening patients in the central city of Wuhan.

But the US repository, which was designed to help scientists share everyday research data, never added the submission it received on December 28, 2019 to its database. Instead, three days later, it asked the Chinese scientists to resubmit the code with certain additional technical details. That request went unanswered.

It took almost another two weeks before a separate pair of virologists, one Australian and the other Chinese, worked together to determine the genetic code of the new coronavirus onlinewhich set off a frantic global effort to save lives by building tests and vaccines.

The first attempt by Chinese scientists to make the crucial code public was first revealed in 2012 documents released Wednesday by House Republicans investigating the origins of Covid. The documents amplified questions that have circulated since early 2020 about when China learned of the virus that caused the unexplained outbreak — and also drew attention to gaps in the U.S. system of monitoring for dangerous new pathogens.

The Chinese government has said it immediately shared the genetic code of the virus with global health officials. Republicans in the House of Representatives said the new documents suggested that was not true. News accounts And Chinese social media posts have long reported that the virus was first sequenced in late December 2019.

But lawmakers and independent scientists said the documents offered tantalizing new details about when and how scientists first sought to share these sequences globally, illustrating the difficulty the United States has in selecting pathogens of concern from the thousands of everyday genetic sequences that exist be subjected to investigation. his warehouse every day.

“There would never be an ambulance in the normal 3 p.m. traffic,” said Jeremy Kamil, a virologist at Louisiana State University Health Sciences Center Shreveport. Referring to the 2019 coronavirus code, he said: “Why would you allow this sequence to sit there under the same process as a sequence I just got from a new snail species I found in a canyon?”

A spokeswoman for the Department of Health and Human Services, which includes the NIH, said in a statement Wednesday that the genetic code was not published because it “could not be verified, despite NIH follow-ups to the Chinese scientist for more information. information and a response.”

In a earlier letter to Republicans in the House of RepresentativesMelanie Anne Egorin, a senior health ministry official, said the series had initially been subject to a “technical, but not scientific or public health assessment”, as was usual. After the Chinese scientists did not hear back about the requested corrections, the database known as GenBank automatically removed the submission from the queue of unpublished sequences on January 16, 2020.

It is not clear why the Chinese scientists did not respond. One of the petitioners, Lili Ren, who worked at a pathogen institute within the state-affiliated Chinese Academy of Medical Sciences in Beijing, did not respond to a request for comment. The Chinese embassy said China's response was “science-based, effective and consistent with China's national reality.”

But the same series that Dr. Ren sent to GenBank was made public in another online database known as GISAID on January 12, 2020, shortly after other scientists posted the first coronavirus code. Dr.'s group Ren also resubmitted a corrected version of the code GenBank in early February And published a paper describes his work.

The two-week period between when the code is first sent to the US database and when China shares the sequence with global health officials “underlines why we do not receive any of the so-called 'facts' or data” from the Chinese government can trust the Chinese government. Republican leaders of the House Energy and Commerce Committee said.

Jesse Bloom, a virologist at the Fred Hutchinson Cancer Center in Seattle, said the genetic sequence in anyone who looked at it in late December 2019 would have strongly suggested that a new coronavirus caused the mysterious cases of pneumonia in Wuhan. Instead, official Chinese timelines indicate that the government only made this diagnosis in early January.

“If this series had become available, the prototype vaccines probably could have been started immediately, and that would have been two weeks earlier than they were started,” said Dr. Bloom.

The documents, first The Wall Street Journal reports thisprovide no insight into the virus's origins, Dr. Bloom and other scientists said, as the sequence contained no special clues about the virus's evolution and was later made public anyway.

But they do provide new details about the pace at which Dr. Ren worked to map the virus. The swab containing the virus they analyzed was taken on December 24, 2019 from the 65-year-old patient, a vendor at the main market where the disease first spread. Within four days, scientists sent the genetic data of that virus to GenBank.

“That's incredibly fast,” said Kristian Andersen, a virologist at the Scripps Research Institute.

At the time, finding a new coronavirus in the patient's sample would not have proven that it was that pathogen, and not another virus or bacteria, that caused his illness, Dr. Andersen, although it would have been a reasonable hypothesis.

That consideration seemed to weigh on the Chinese scientists who studied samples from early patients. A researcher from a Chinese commercial laboratory who worked with Dr. Ren collaborated, wrote about a blog at the end of January 2020 that although she had identified a new virus in hospital samples, this in itself did not demonstrate that the virus was causing pneumonia cases, delaying an official announcement.

In early 2020, the Chinese government also issued guidelines that discouraged certain lines of scientific research and limited the release of data on the virus.

Even after the virus's genetic code was sent to the US repository, it would have been difficult for US officials staffing the research-oriented database to notice. The repository contains hundreds of millions of genetic sequences. Much of the process of screening them is automated.

And at least until Chinese officials started sounding the alarm in late December 2019, almost no one would have known to look for a novel coronavirus among the piles of entries.

“At the time, there was no way that anyone at NCBI would realize the importance of this,” said Alexander Crits-Christoph, a computational biologist, referring to the NIH center that manages GenBank. In addition, genetic repositories such as GenBank should keep in mind that they will have to release sequences publicly, he said, because researchers often use the same data to prepare journal articles.

Still, some scientists believe that U.S. and global health officials have been slow to modernize databases like GenBank so they can obtain sequences that could have crucial public health implications.

For example, such a database could automatically scan for new pathogens whose genetic codes overlap with those known to be dangerous, said Dr. Kamil. And it could allow these series to be more widely distributed even as health officials wait for missing details or revisions.

“Give those ranges concierge care, my God,” he said. “Why haven't the agencies responsible for public health and global health stepped up their game and said, 'This is the year 2024, we have to be safer so things like this don't happen again?'”