The sequencing solution

YOU DON’T WANT TO BE A VIRUS IN DR. DAVID HO’S lab. Pretty much every day since the COVID-19 pandemic began, Ho and his team have done nothing but find ways to stress SARS-CoV-2, the virus that causes the disease. His goal: pressure the virus relentlessly enough that it mutates to survive, to help drug developers understand how the virus might respond to new treatments. As a virologist with decades of experience learning about another obstinate virus, HIV, Ho knows just how to apply that mutation-generating stress, whether by starving the virus, bathing it in antibodies that disrupt its ability to infect cells, or bombarding it with enough promising antiviral drug candidates to make it blink. “We actually have more mutants [of SARS-CoV-2] selected in the lab than I suspect most labs do,” says Ho.

As a result of that work, “we have basically been seeing viral evolution happen in front of our eyes for the past year and a half,” he says. Ho, director of the Aaron Diamond AIDS Research Center at Columbia University, is among the vanguard of researchers aggressively finding ways to dismantle SARS-CoV-2 from the inside out—by mining the virus’s genetic code for signs of weakness. The viral genome, it turns out, is an underutilized pool of useful information about the virus’s likes, dislikes and survival strategies, all coded in the 30,000 base pairs that make up its genome. Ho, who built his career around finding ways to control HIV with drugs, once said of the disease, “It’s the virus, stupid.” Among the many lessons that will be taught in public-health classrooms and in genetics labs around the world after the COVID-19 pandemic recedes is a corollary: “It’s the genetics, stupid.”

One of the most powerful ways of fighting a pandemic caused by a never-before-seen virus is decoding the microbial culprit’s genome. Doing so can, and should, be the top priority of public-health efforts going forward, so scientists can expose how the microbe works