LONDON – Suddenly, the coronavirus seemed to change.
For months, Dr. Steven Kemp, an infectious disease specialist, examined a global library of coronavirus genomes. He was studying how the virus had mutated in the lungs of a patient struggling to get rid of a violent infection at a hospital near Cambridge, and he wanted to know if these changes would show up in other people.
Then, in late November, Dr. Kemp made a surprising combination: some of the same mutations detected in the patient, along with other changes, were appearing repeatedly in newly infected people, mainly in Britain.
Worse, the changes focused on the spike protein the virus uses to attach itself to human cells, suggesting that a virus that is already wreaking havoc around the world was evolving in a way that could make it even more contagious.
“There is a load of mutations that occur together at the same frequency,” he wrote on December 2 to Dr. Ravindra Gupta, a Cambridge virologist. Listing the most worrisome changes, he added: “ALL of these sequences have the following peak mutants”.
The two researchers did not know it yet, but they found a new variant of the highly contagious coronavirus that has since spread across Britain, shaken scientists’ understanding of the virus and threatened to delay the global recovery from the pandemic.
The news spread through a consortium of British disease scientists, long-standing carriers of genomics who helped track the Ebola and Zika epidemics. They met on Slack and on video calls, comparing notes while looking for clues, including a tip from South African scientists about another new variant there. Still others appeared in Brazil.
For almost a year, scientists observed only incremental changes in the coronavirus and expected more of it. The new variants forced them to change their thinking, foreshadowing a new phase of the pandemic in which the virus could evolve enough to undermine vaccine effectiveness.
But the path to its discovery was traced with little acclaim in March, when Britain decided to start sequencing massive samples of coronavirus. The country produces half of the world’s inventory of coronavirus genomes, providing unparalleled insight into how the virus changes and how people brought it to Britain last year and are now taking the variant out.
For Britain, the discovery came too late to avert a new punitive wave from Covid-19, which put its hospitals on the verge of having to deny essential care. The variant was already spreading rapidly, spurred on by relaxed government restrictions during the fall and early winter.
But Britain has raised an alarm for the world, allowing countries to close their borders and start frantically looking for a variant they would not otherwise have noticed for months. British scientists quickly published studies that convinced skeptics of its potency.
“The UK has got a lot of things wrong about this pandemic, especially not learning lessons about the importance of reacting early,” said Neil Ferguson, an epidemiologist and government adviser. “But the UK has an unrivaled surveillance system for Covid. We can monitor very small changes in the virus. “
Britain’s laboratories, after testing swabs for the virus, send the remaining material in refrigerated vans to the Wellcome Sanger Institute, a genomics laboratory, where they are stored in cavernous freezers.
There, the robots separate the positive samples and deposit them in small, cookie-like dishes. The machines then map their genomes, said Jeffrey Barrett, who runs the sequencing project, producing 30,000 genetic letter codes that are loaded into a library on the Internet. The task of making sense of mutations lies with biologists like Andrew Rambaut, a professor in Edinburgh, who determine where they fit into the evolutionary tree.
The effort spawned more than 165,000 sequences in Britain. The United States, with five times as many people, has sequenced some 74,000 genomes. Germany sequenced some 3,400, less than half of what Britain uploaded to the global database on Thursday alone.
“This has totally revolutionized the way we deal with the virus,” said Judith Breuer, a virologist at University College London.
The campaign took shape on March 4, before 100 coronavirus infections were found in Britain, when a Cambridge microbiologist, Sharon Peacock, sent a flurry of emails to British genomicists, asking each: “Can you tell me call, please. ”
In two weeks, the newly formed consortium secured £ 20 million, about $ 27 million, in government funding.
“It’s a close community, and in March, it effectively put aside any rivalries, any egos, and just said, ‘We can play a key role in managing the pandemic,'” said Thomas Connor, a scientist from Wales who built a platform to compare and analyze genomes.
Among the samples sequenced last summer were those of a 70-year-old man with lymphoma, admitted in May to a Cambridge hospital for treatment of Covid-19. Dr. Gupta, a part-time clinician, began treating the patient, whose anti-cancer drugs had exhausted his immune response. Isolated in an isolation room, the patient struggled to breathe. Even after several rounds of treatment, including plasma with antibodies from recovered patients, the virus did not disappear.
Instead, he mutated. Britain’s sequencing efforts opened a window for these changes: over 101 days in the hospital, the viral particles that ran through the man’s lungs were sequenced 23 times, a veritable treasure trove of clues.
The patient died in August, apparently without having infected anyone else. But mutations in his virus eventually provided scientists with an important theory about how the British variant originated: eluding the immune defenses of someone like the Cambridge patient, who had a weakened immune system and a long-term infection.
“We call this a gold standard patient to assess different viral populations in a host,” said Dr. Kemp.
A mutation that the patient had, labeled 69-70del, changes the shape of the peak protein. Another, N501Y, can help the protein bind more strongly to human cells.
Dr. Kemp researched these changes every few days in the global database, finding little reason to worry. Then, in late November, he abruptly noticed many genomes, mostly from Britain, that had these mutations and a number of others that could change the way the virus entered human cells. He called Dr. Gupta to the computer to have a look.
Eventually, British scientists detected 23 mutations that distinguished these genomes from the oldest known version in Wuhan, China – enough to be considered a new variant, once marked as B.1.1.7. In an evolutionary tree made by Dr. Kemp, it stood out as a single, thin branch.
“I didn’t expect anything like that,” said Gupta. “At the end of November, it was all about the hope of vaccines and there was no evidence of new variants coming.”
The number of mutations in the spike protein has particularly shaken him, he said, calling it “a ‘wow’ moment.”
At the same time, public health experts in England were puzzled by an unexplained outbreak of coronavirus cases. A blockade eased the virus across England, but not in Kent, a London borough with fruit orchards in the south east. Cases were coming up in schools. One in 328 residents has been infected.
Only on December 8, at their regular meeting with genomicists, did public health officials conclude that the cause was probably a new variant. Looking back at their databases, scientists found that it had been collected for the first time in September and spread as people returned to offices and frequented restaurants and pubs at the request of the government.
The researchers eventually convinced themselves that the variant was, in fact, more transmissible – about 30 to 50 percent more – but only after they had assembled a patchwork of less conclusive clues.
“There is not a completely unambiguous line of evidence – science only generates this kind of assurance over longer periods of time,” said Oliver Pybus, an evolutionary biologist at Oxford. “It was another case of different and independent lines of evidence coming together.”
After the scientists presented their findings on December 11 to a government advisory body, Dr. Ferguson, the epidemiologist, was concerned that “it would almost certainly force us into another block”. He sent a text message to Prime Minister Boris Johnson’s chief scientific adviser, warning about the variant.
On December 22, government scientists said strict measures, including closing schools, were needed to suppress the variant. But Johnson allowed people in parts of England to gather for Christmas and did not impose a blockade across England until January 4.
It is estimated that the variant accounts for more than 80% of positive cases in London and at least a quarter of infections in other parts of England, and appeared in more than 50 countries. American health officials warned on Friday that the British variant could be the dominant source of infection in the United States in March.
In the past few days, Dr. Gupta and Dr. Kemp started using blood serum from vaccinated people to determine whether the variant could weaken the potency of the vaccines.
“The world has been informed for a long time that coronavirus mutations don’t really matter,” said Dr. Gupta. “But we found that the mutations occurred and had an impact on the virus’s fitness.”