"It was certainly interesting, and a little bit out of the ordinary, but you'd be surprised at some of the things we get around here," said Lee Shepard, the society's vice president of collections.
The tiny specimen, found carefully wrapped inside a letter dated 1876 that a Richmond man mailed to his father in Charlottesville, provides a glimpse of what would evolve into modern day immunization.
"Dear Pa … the piece I inclose is perfectly fresh and was taken from an infant's arm yesterday. …" the letter read. "Dr. Harris says the inclosed scab will vaccinate 12 persons, but if you want more, you must send for it. I will pin this to the letter so that you cannot lose it as you did before."
Before the injectable smallpox vaccine became widely available in the 1940s, people would rub smallpox scabs on their skin with hopes of building immunity. Benjamin Franklin used this method on his 4-year-old son, but instead of protecting him the limited infection killed the child in 1736.
"I long regretted bitterly, and still regret that I had not given it to him by inoculation," Franklin wrote in his autobiography.
"Back in the day, before we even had the word 'virus,' the best way to protect yourself was to inoculate yourself and hope you would only get a mild infection and become protected," said Dr. William Schaffner, chief of preventive medicine at Vanderbilt University Medical Center. "But sometimes you could get a bad case instead of a mild case, and even spread it to others."
Thanks to the smallpox vaccine, which uses the related cowpox virus, the disease was eradicated in 1980. Only two live samples are known to exist: one at the U.S. Centers for Disease Control and Prevention in Atlanta, and one in Russia. But worries that a hidden stash could be used by terrorists still loom. So when word of the smallpox scab got out, some people got worried.
"I just knew smallpox was a nasty, highly contagious disease," said Nick Radonic, an electrical engineer from Derwood, Md., who read about the exhibit in the Washington Post Feb. 26. "So if there was a free sample floating around some place, even accidentally, the downside was enormous. I said, 'I have to do something here.'"
The smallpox virus is relatively hardy, and capable of living in a scab for months or even years, Schaffner said -- but likely not 135 years. Nevertheless, Radonic emailed the Virginia Historical Society to express his fears. He also told a family friend who worked at the National Institutes of Health. And on March 21, Shepard got a call from the CDC.
"They were very calm, not alarmist, and said, 'You probably know why we're calling," he said.
Two days later, CDC staffers donning protective gear seized the skin and took it back to their Atlanta headquarters to study its scabby secrets and ensure it was no longer infectious.
"We did testing to look for evidence of variola," the most severe form of the smallpox virus, "and it was negative," said Dr. Inger Damon, chief of the CDC's pox and rabies branch.
Further tests revealed the scab probably contained vaccinia, the cowpox virus, which suggests the scab came from someone who was inoculated with the milder strain to boost immunity.
"We're trying to get more information to get a better understanding of what vaccines looked like during the Civil War," she said. "It's very interesting in terms of historical reference, in that it demonstrates that this concept of arm-to-arm vaccination really did happen."
The "Bizarre Bits" exhibit, which ended March 27, was intended to showcase some of the society's more "unexpected" pieces.
"We get loads of just strange things that are always fun and interesting and sometimes, well, they'll stop you in your tracks."
Among them, an image of Robert E. Lee on his horse Traveller carved out of tree fungus and a wreath made from the hair from more than 100 humans. But Shephard's favorite find was a 1850s love letter from a naval officer to his wife, which contained fingernail and toenail clippings.
"He says in the letter that he kissed them before he put them in there because they'd be the first thing to touch her lips," Shepard said. "Clearly he'd been out on the water a long time."
CDC officials told Shepard they'd return the scab, which has been irradiated to kill any remnants of life, as soon as possible.
"It's been a very positive experience for everyone involved," Shepard said. "You never can tell what kind of research can be motivated by what's in your collection. That happens all the time here."
ABC News' Karin Halperin contributed to this story.