What unites all of these approaches is the idea that it might be possible to design a perfect antigen—a single entity that inspires universal immunity. Jacob Glanville, a forty-year-old computational “immuno-engineer” who studies antibody targeting, has come up with an alternative path. In 2012, Glanville left Pfizer, where he was a principal scientist, to start an immunology Ph.D. at Stanford and launch an antibody-discovery company called Distributed Bio. Several years earlier, researchers at the biotechnology company Crucell had shown that a few fortunate people already have antibodies that work against many different strains of the flu; Glanville took notice. Somehow, the immune systems of those flu-resistant people had solved most of the universal-immunity problem on their own, without access to designer antigens. Glanville wanted to understand how this was possible, and why it happened so rarely.

Every HA protein is different. Any single antibody that works against multiple versions, therefore, must have found a way to attack a shared weak spot. Ideally, our immune systems, when faced with a range of related foes, would seek out their common Achilles’ heel. And yet they do not seem to be very good at identifying areas on proteins that are “conserved” across many variations. Immunologists have offered a few explanations for this weakness. Some have argued that conserved sites too closely resemble our own cellular structures: it would be risky for the immune system to start attacking them with antibodies.

Glanville thought that the story might be simpler. Using cloud computing, he ran hundreds of millions of simulations of antibodies attaching to HA proteins. He found that only one in a million antibodies successfully docked to a universally conserved site. The problem, it turned out, was that each viral strain contains many more sites that mutate than conserved sites. This was true even for the stems of the HA mushrooms. The stems may be less mutable than the caps, but they, too, differ more than they are alike. This, Glanville thought, did not bode well for attempts to create stem-based universal vaccines.

Still, some people’s immune systems had managed to create near-universal flu antibodies; this suggested that the problem was solvable.