Take Two Beers and Call Me in 1,600 Years

Natural History, May, 2000 by George J. Armelagos

Ancient Nubians and Egyptians had a way with antibiotics.

Some twenty years ago, Debra Martin placed a bit of bone from a mummy under a microscope and discovered that a person who lived in Nubia (northern Sudan) during the fourth century A.D. had apparently ingested tetracycline, a broad-spectrum antibiotic that entered the arsenal of modern medicine only in the 1950s. Finding a pair of designer sunglasses on the mummy would hardly have been more startling. And the discovery was purely serendipitous.

Today Martin is a professor of anthropology at Hampshire College in Amherst, but at the time she was a graduate student in biological anthropology at the University of Massachusetts. As part of her training, she was visiting a research laboratory at Henry Ford Hospital in Detroit, Michigan, to learn techniques for making thin sections of bones from archaeological finds. Normally she would have relied on a standard microscope, and the tetracycline would have gone undetected. But because the standard microscope was unavailable, another researcher suggested Martin try one that used ultraviolet light.

At one specific wavelength, ultraviolet light causes tetracycline to fluoresce with a unique yellow-greenish color. In the lab, researchers under the direction of Harold Frost were using tetracycline to measure the rate of bone formation. Tetracycline tends to bind with calcium and phosphorus, which make up more than 80 percent of the mineral portion of mature bone. (Patients who are taking the drug are advised not to drink milk or take antacids containing calcium, since the tetracycline will bind to the calcium and lose its antibiotic effectiveness.) Any tetracycline circulating in the body may bind with calcium that is being deposited in the bone, "labeling" (tagging) the bone with its indelible signature. In the laboratory study, people who were scheduled to have bone removed during biopsy or amputation were asked to take tetracycline at intervals before the surgery. Bone deposits formed during this period could then be identified and measured.

When Martin returned to the University of Massachusetts, where I was then teaching, she told me of her discovery, and we began to explore several issues: Was this really tetracycline? If so, was it incorporated into the bone during the subject's lifetime 1,600 years ago, or could it have been produced by organisms that invaded the remains after death? If it was ingested by ancient Nubians in their food or medications, what was its source?

That we really were dealing with tetracycline was demonstrated by James Boothe, a chemist who had worked on the initial commercial applications of the antibiotic for American Cyanamid. He was able to extract it from our Nubian bone and show that it could still kill bacteria. More recently, Mark Nelson at Paratek Pharmaceuticals has been determining its precise molecular structure (there is actually a whole family of tetracyclines in nature).

Evidence that the tetracycline was incorporated during the lifetime of the Nubian mummy came from its osteons, which are microscopic cylindrical building blocks of cortical bone (such as the outer layers of bone shafts). In response to physical stresses, bone tissue undergoes a continual process of fine-tuning. Bone cells called osteoclasts break down small amounts of bone mineral, which other cells, called osteoblasts, then replace. The result is the formation of new osteons. It takes about four months for any one osteon to become fully mineralized, and tetracycline may be incorporated during the process. When we examined bone from the Nubian mummy, we found that some osteons had layers of mineral containing tetracycline alternating with layers without tetracycline. Such a pattern could have developed only during life, not if the tetracycline was somehow introduced later; it indicated that while these particular osteons were forming, the individual was ingesting tetracycline intermittently. In most of the osteons we examined in the mummy, however, we found that tetracycline was present in all the layers, suggesting that during the four months it took for these osteons to mineralize, this individual had continuously ingested the antibiotic.

To determine the extent of tetracycline use by ancient Nubians, three undergraduate researchers in our lab at Emory University--Kristi Kohlbacher, Jennifer Cook, and Kristy Collins--painstakingly sampled thousands of osteons from our original mummy and from seventy-seven other Nubian and Egyptian remains dating from about the same era. All but four of the seventy-eight individuals showed some degree of exposure to tetracycline, and no significant differences by age or sex were evident. Even the remains of two of the three infants contained tetracycline, showing that it was passed to them in their mothers' milk.

Following the publication of these findings in the 1980s, other researchers began to report evidence of tetracycline in African prehistory. Physical anthropologist Megan Cook (then at the University of Toronto) and her colleagues, for example, found that the mummified remains of all twenty-five individuals recovered from Dakhla Oasis in Egypt, dating from the Roman period (A.D. 400-500), showed tetracycline labeling. The patterns were consistent with doses occurring at two- to three-week intervals. And Ann Grauer and I have recently reported evidence of tetracycline in bone from a Jordanian site that dates from the second century B.C. through the fourth century A.D.