Librarian Susanne Caro was leafing through an 1888 book on Civil War medicine when she spied a small, yellowed envelope tucked between the pages. Freeing it, she read the inscription "scabs from vaccination of W.B. Yarrington's children" in the corner, with the signature "Dr. W.D. Kelly," the book's author.
Embarking on some quick research, the 23-year-old Santa Fe, N.M., woman soon decided not to open the envelope. "The only thing I could find connected with it," she said, "was smallpox."
After a cross-country relay involving the FBI, the National Museum of Civil War Medicine in Frederick and the District's Walter Reed Army Medical Center, the envelope rests in a freezer at the Centers for Disease Control and Prevention in Atlanta, awaiting a battery of tests.
Researchers believe the scabs found in March are either from smallpox vaccine patients or from victims, whose scabs were used in an early inoculation procedure. At the very least, inoculation scabs would shed light on the historic development of American vaccines for smallpox, which though eradicated a generation ago has returned to public consciousness as a potentially devastating weapon for bioterrorists.
There's also a slim chance, researchers say, that the scabs could yield live smallpox virus -- believed to reside in only two laboratories in the world -- and provide valuable information on the deadly plague.
"This could lead to a greater evolutionary understanding of the smallpox vaccine we're using in the U.S.," said Inger Damon, chief of the CDC pox virus group. Referring to the envelope, she said, "It all depends on what's in there."
On March 31, Ryan Rokicki, collections manager at the Civil War medicine museum in Maryland, received an e-mail from Caro, at the College of Santa Fe's Fogelson Library. The same day she found the scabs, she looked up the museum on the Internet and wrote: "My first question is could these be dangerous?" Her second question, would the museum want them?
"I'm, like, 'What are we going to do with these?' " Rokicki recalled. But when he told museum Executive Director George Wunderlich, the director was fascinated.
Wunderlich knew that during the late 1800s, pus or bits of scabs from smallpox patients with mild cases were implanted in the skins of healthy people to generate a mild illness that bestowed lifetime immunity. The practice, introduced in Europe and the United States in the early 18th century, predates the cowpox-based vaccine that became standard in the 19th and 20th centuries. It probably originated in Asia and Africa: In China, the CDC says, smallpox scabs were once ground up and inhaled to provide immunity.
Wunderlich called Paul Sledzik, forensic anthropologist and curator of anatomical collections at the National Museum of Health and Medicine, a division of the Armed Forces Institute of Pathology at Walter Reed. The institute's anatomical specimen collection, one of the oldest and most comprehensive in the world, includes a cross section of the foot of an infant who died of smallpox in the 1920s, encased in plastic in a process that likely killed the virus.
"To be able to look at [an untreated] specimen from the 19th century using the tools of today is incredible," Sledzik said in an interview. "If you want to look at disease evolution, this would be the perfect opportunity to do that."
Sledzik called his colleague Ann Nelson, a pathologist at the institute on Walter Reed's Northwest Washington campus. She immediately contacted the CDC, which with the Institute of Virus Preparations in Moscow holds the only known stocks of live smallpox. "We needed to get this to the people who know best what to do with it," Nelson said.
Army and CDC researchers thought it unlikely the scabs harbored smallpox. Yet, scientists have long questioned how long the disease lasts in victims' graves, possessions or tissue. In the late 1960s, a study published by the World Health Organization used scabs stored in envelopes to show that the virus stayed viable that way for at least 13 years, likely longer. In 1985, the British medical journal Lancet published a paper suggesting that smallpox could live as long as a century in the crypts of victims interred in cool, dry climates.
Within days, two FBI agents visited the Santa Fe library to pick up the scabs. They questioned a surprised Caro for half an hour, asking who had last used the book and whether she felt the borrower may have "planted" the scabs inside, Caro recalled. Her answer "was a great big no," she said.
Caro said she gave the agents research showing that Kelly, the book's author, had done work on childhood vaccinations in the late 1800s. How the book reached the library was unclear. Caro handed over the envelope, and "they put it in a paper bag," Caro recalled. "So I thought, 'Well, it can't be that bad.' "
FBI spokesman Doug Beldon said agents delivered the scabs to the New Mexico Department of Health. On April 3, the same day it received them, the department forwarded them to the CDC, in a triple-bagged overnight mail package labeled "diagnostic specimens," said department spokeswoman Beth Velasquez.
In Atlanta, "we were intrigued by the whole story," said Damon, the CDC's pox virus chief. The scabs "will be potentially the oldest material we'll have looked at in terms of being able to determine any kind of genomic characterization," she said. Through a series of tests slated for next year, the CDC hopes to develop a genetic portrait of the virus used in the vaccine -- likely cowpox, a nonlethal virus used in inoculations in 1796 by Edward Jenner. That could bring insight into the evolution of smallpox vaccine in the United States, of great interest amid fears of bioterrorism.
If the scabs do yield live smallpox, the laboratory could grow it, compare it to more modern strains and study how vaccines function against them. But Damon called that possibility "highly unlikely," particularly in a sample so old. Several years ago in Kentucky, she said, a construction crew unearthed a metal coffin containing the mummified corpse of an apparent smallpox victim that researchers traced to the mid-1800s. The CDC checked the tissue for live virus and came up empty.
Before the smallpox saga got underway, the Fogelson Library agreed to donate Dr. Kelly's 130-year-old collection of scabs to the Frederick Civil War museum. But by the time the CDC finishes its work, there won't be much left. "We'll take a picture of them," Damon said.
That's enough for Wunderlich, the museum director. "I knew from the very beginning that, especially if they find really bad stuff in there, they're not going to let them go," he said.
"The main thing is we were able to help get them to the right place."
Staff researcher Bobbye Pratt contributed to this report.