Reviewers (rightly) asked for more information about the origin/passaging history of the virus we’re using— Coxsackievirus B3 strain H3 (derived from CVB3 strain Nancy). Sounds boring, but the answer is *wild*.

I knew that Nancy was the name of a child infected in the 1940s. I should have known that Joseph Melnick—one of the “founding fathers of virology”—discovered the CVB3-Nancy strain. I had no idea that Nancy was Melnick’s DAUGHTER. Father of virology indeed.

But it gets wilder. Melnick and 5 other members of the CVB research group at Yale had *lab acquired infections* w various CVB strains. Two were from mouth pipetting gone wrong and two were from likely from a spill… all in one year (1949). Wild wild west of virology back then.

One event involved lab member FL who, ~2 weeks into the job, spilled a tube of virus. Another new lab member- GJ, also ~2 weeks into the job, helped them clean it up. Can you imagine? Both became infected. (The lack of privacy/reporting rules back then was shocking.)

Back to Nancy. She didn’t catch her father’s lab-acquired strain, but she did become infected with a strain carried by her mother around the same time. Joseph Melnick became infected with both strains (!). We know this from the impressive early serology.

Turns out Nancy’s strain replicated well in mice and, later, in cultured HeLa cells. A model virus was born, and it’s still used today, 70+ years later. But back to the original question—where did our CVB3-H3 virus come from?

Nancy’s momNancyMiceGiven to Jack Woodruff, grown in HeLa-type cellsGiven to Sally Huber, infected miceIsolated a plaque, called H3 Grown in HeLa cellsCloned to generate plasmidSent to someone who sent it to @VignuzziLab who sent it to usHeLa cells. Easy.

Lessons learned: 1) History is fascinating, 2) We complain about bureaucracy, but lab biosafety rules and protection for human subjects are GOOD, 3) Nowadays, viruses shouldn’t be named after infected people (Nancy) or places (Coxsackie, NY).

Links to papers: https://rupress.org/jem/article-pdf/92/5/463/1184564/463.pdf

https://www.acpjournals.org/doi/pdf/10.7326/0003-4819-33-1-32