By March of last year, when COVID-19 began popping up in South Africa, de Oliveira’s team was ready to go. A key question for genomic surveillance in the early days was simply how COVID-19 had gotten into the country. So scientists used genomes to reconstruct the virus’s path: The coronavirus had been introduced multiple times, mostly from Europe. Over the course of 2020, the pandemic waxed and waned, and de Oliveira and his colleagues kept gathering sequences.

In November, an entirely new pattern appeared. Doctors in South Africa’s Eastern Cape told de Oliveira that cases were spiking again, seemingly out of nowhere. Had the virus changed? Could it have mutated? His team moved quickly to sequence samples from 50 clinics in the region within a week, and they found a surprising lack of diversity. The samples from all 50 clinics were closely related, with almost all the same mutations. They looked like one variant. Because he had data from the previous seven months, de Oliveira knew that this was strange; normally, if he sampled 50 clinics, he might find 30 or 40 different versions of a virus. And because he had data from all over the country, he could see that this variant was now creeping into other regions. All those months of sequencing had paid off, but the news was bad. The virus really had changed. And the new variant was taking over.

In early December, de Oliveira shared some preliminary results with an old colleague, Andrew Rambaut, who specializes in the evolution of new viruses. The two of them had overlapped at Oxford some 15 years ago; Rambaut is now at the University of Edinburgh, in the U.K. De Oliveira flagged one particular mutation, called N501Y, which sits in a key region of the spike protein that binds directly to human cells.