How the U.K. Became World Leader in Sequencing the Coronavirus Genome

The daily operation is part of a Covid-19 surveillance system that has made the U.K. the world’s leading sequencer of the coronavirus genome and helped it to spot a more contagious, and possibly more deadly, variant of the virus that in most countries would have long gone unnoticed.

Viral sequencing—producing a kind of bar code for the virus—has in recent months emerged as crucial in the global hunt for versions of the pathogen that are better adapted to infect humans, evade vaccines and possibly to kill. Virus variants first identified in the U.K., South Africa and Brazil have provoked concern among experts.

The variant the sequencers uncovered in the U.K., which is now the dominant variety in the country, has a mutation that appears better able to bind onto human cells. Studies suggest it is 50% more transmissible than the previous prevalent variant while other research suggests it could be at least 30% more deadly.

New viral variants are more likely to be spotted in the U.K. than anywhere else. As of Jan. 29, the U.K. had submitted 44%, or around 190,000, of the genomes held in a global library run by the nonprofit Global Initiative on Sharing All Influenza Data, or Gisaid. That is around 5.1% of the nearly four million cases detected in the U.K.

The U.S. is fast increasing its sequencing capabilities—but only a handful of other countries have contributed more than 1% to the library, which means scientists’ understanding of where and how the virus is mutating is patchy.

That represents a weakness in the global response to the pandemic: Speedy detection of new variants allows governments to adjust restrictions and limit travel from countries where new troublesome variants are prevalent. It also can help vaccine developers update vaccines.

The U.K. says it plans to address that weakness by exporting its expertise to countries with limited sequencing capabilities.

Half of the genome sequences in the U.K. were generated at the Wellcome Sanger Institute, the facility in Cambridgeshire that stores, sorts, samples and sequences genomes from the byproducts of positive Covid-19 tests from five large laboratories around the U.K.

The U.S. has increased its contribution to the global coronavirus genome database since December and has so far added 20% of the total. It has assessed about 0.3% of America’s Covid-19 cases.

Anthony Fauci, President Biden’s chief medical adviser for the Covid-19 pandemic, said on CBS on Sunday that U.S. authorities need to expand genomic surveillance to identify variants of the virus.

Britain’s capabilities are partly built upon history. British scientists discovered the DNA double helix and were part of the international team that first sequenced the human genome.

“The U.K. was one of the first countries in the world to recognize the need for an infrastructure for viral genomic sequencing and we’ve backed it with huge investment long before Covid emerged,” Health Secretary Matt Hancock said in a speech on Tuesday.

The country’s data-rich, state-run National Health Service is also closely linked with an extensive network of researchers in its universities and the pharmaceutical industry.

Nonetheless, the U.K.’s large-scale sequencing of the coronavirus almost didn’t get off the ground.

On March 4, when the U.K. had four known cases of Covid-19, microbiologist Sharon Peacock got on the phone with a group of other scientists who agreed with her that sequencing the virus’s genome to monitor mutations would be vital to track its spread through the country and identify the source of outbreaks.

They met opposition. Some scientists thought large-scale genome sequencing of a virus that mutates more slowly than some others, such as influenza, would be futile.

“At the time, there were people saying there wouldn’t be enough mutational difference to make this worthwhile,” said Dr. Peacock, who is now director of Covid-19 Genomics U.K., a network established to trace the coronavirus’s family tree.

On March 11, the same day the World Health Organization declared a global pandemic, Dr. Peacock held a meeting in London at the Wellcome Trust with 19 others, including clinical virologists, technologists, experts in human genome sequencing and vaccinologists, to thrash out a plan for large-scale sequencing of the coronavirus.

“It wasn’t like a standard scientific meeting, it was a huge debate how we could do this,” recalled Dr. Peacock. By the end of the day they had a blueprint and submitted it to England’s chief scientific officer on March 18. It was accepted and 20 million pounds, equivalent to $27 million, of government funding was awarded on April 1 to set up COG-UK.

“This was pace over perfection and that’s been the case ever since, but I’m delighted that our consortium of over 600 people can contribute to our understanding of disease,” she added.

Yet the country’s success in variant discovery appears to be due more to serendipity than strategy.

The scale of the U.K.’s genomic sequencing output—that it has assessed up to 10% of all positive coronavirus tests in the U.K. at some points during the pandemic—was intended to identify superspreader events where identical sequences, closely related to their predecessors, emerge at the same time.

When an RNA virus like the one that causes Covid-19 replicates inside a new host, mistakes can be made in its genetic code. Most don’t matter, some are proofread and corrected and sometimes no mistakes are made at all. But some of the errors, or mutations, are large in number or important in changing the virus to affect its biology, in rare cases giving it an advantage over its predecessors.

Coronaviruses mutate more slowly than some other viruses such as influenza, so initially scientists didn’t think there would be enough mutations to make large-scale genomic sequencing worthwhile.

But because the virus has infected so many people—over 100 million world-wide so far—it has had many opportunities to mutate. Some changes, including one in the U.K. variant now reported present in at least 64 countries, confer evolutionary advantages over their forebears that make that version of the virus more transmissible.

The new variant came to experts’ attention in November, when a version with a large number of significant changes from its predecessor began to accumulate in a corner of southeast England, creating an outcrop of identical genomes that flashed red on genomists’ screens.

Initially, the sequencers didn’t know whether the variant was gaining prominence because of widespread flouting of coronavirus restrictions or whether it was the cause of a flare-up in new cases, Jeffrey Barrett, director of the Covid-19 Genomics Initiative at the Wellcome Sanger Institute, said in an online seminar this month.

By the final week of November, it was becoming clear that in exactly the same spot the mutant genomes were congregating, Covid-19 cases were accelerating in the community despite compliance with a national lockdown.

Trawling back through the genome databases, sequencers found the first occurrence of the heavily mutated variant on Sept. 20 in Kent, in southeast England, and another a day later in London. Geographical matching of cases to genomes enabled the virus detectives to say with a high degree of certainty that the correlation wasn’t a coincidence and designated the virus as one of concern.

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