Responding to the Virus

It seems everyone is asking how a tiny snippet of RNA can bring the world to its knees. From an infectious disease perspective, the real question is: How did we get through 102 years since the last outbreak of such global proportions? One answer, of course, is vaccines. A second is a half-century of public and private investment in basic research and epidemiological infrastructure.

When I teach about infectious disease and vaccination strategies, my students and I work through a seductively gamelike simulation of an intentional smallpox release in a medium-sized city. The data reveal a clear trade-off: either effective vaccination or “withdrawal to home” are the only winning strategies.

And so the race for a Covid-19 vaccine is on. Building on years of prior work, researchers went from viral genome sequence to injecting a candidate vaccine into a human volunteer in nine weeks rather than the typical nine-plus years. Multiple possible vaccines are now in clinical trials. But more potential trade-offs await us.

The costs of not getting this vaccine and its rollout right are staggering. Should we try to stack the odds in our favor by leapfrogging over normal testing protocols and challenge human volunteers with controlled exposure to the live virus after administering a candidate vaccine? Or should we follow more cautious, perhaps safer, paths, while prolonging the pain of shuttered economies and social upheaval?

Vaccine development is built on millions of hours of basic research—grad students and post-docs in labs around the globe, investigating phenomena whose significance may not be immediately obvious. They use genomic tools developed to help us understand evolutionary relationships among obscure critters or proteins to trace the global transmission and vulnerabilities of a virus with a universally recognizable name.

In the spring, international teams of researchers analyzed tens of thousands of sequences from each of thousands of individual nasal cavity and lung cells to figure out which specific cells have the appropriate constellation of receptors and accessory proteins to harbor a virus that has made a mockery of our best (and worst) laid plans.

The computational and biological technologies that enabled these analyses were only a twinkle in their developers’ eyes 30 years ago, when I was a Ph.D. student sequencing five short bits of yeast DNA at a time. But without a sustained commitment to basic as well as applied research over that time span, the current studies would have been inconceivable.

Researchers estimate that SARS-CoV-2 may have diverged from its closest known relative, found in a bat from Yunnan Province in China, 40 to 70 years ago. In the virus’s evolutionary journey, its ancestors appear to have made undetected pit stops in pangolins and probably people. As we deal with today’s crisis, we also need to lay the groundwork to respond to the virus of tomorrow, one that is evolving right now, perhaps through a critter most of us barely know exists.