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[jenne at fiedlerfamily.net]

Beer, Antibiotics, Ancient Nubia?!

Take two beers and call me in 1,600 years
Natural History; New York; May 2000; George J Armelagos;

Volume:
              109
Issue:
              4
Start Page:
              50-53
Abstract:
The discovery of tetracycline, an antibiotic, in the bones of mummies that
lived during the fourth century AD in Nubia was quite
surprising. Researchers found that the tetracycline was formed as a result
of the ancient Egyptians' beer- and bread-making processes.

Full Text:
Copyright American Museum of Natural History May 2000

[Headnote]
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 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 Collinspainstakingly 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.

But none of this told us why the antibiotic was showing up in the ancient
bones. In nature, tetracycline is produced by streptomycetes, moldlike
bacteria commonly found in soils. These slow-growing cells do not do so
well in the wet, acidic soils where most bacteria flourish, but they have
the edge in hot, dry, and neutral-to-alkaline environments. Ten-year-old
spores survive in dry sand and are easily cultured.

[Illustration]
Caption: A model from an Egyptian tomb in Thebes, ca. 2009-1998 B.C.,
reveals an ancient connection between making bread and brewing
beer.

Initially we thought that during famine or drought, the ancient Nubians
and Egyptians might have been forced to eat moldy grain. (Even one or two
grams of tetracycline consumed by humans in a single day will produce
fluorescence in bone.) The warm, dry alkaline environment of storage bins
made of mud could have been an ideal environment for streptomycetes. But
we learned that when they are growing well, streptomycetes actually
produce little tetracycline. Given the degree of tetracycline labeling in
the Nubian and Egyptian remains, we had to consider other possibilities.
The key turned out to be beer, known as bosa in much of present-day
Africa.

Searching through both ancient and later texts, Everett Bassett, Margaret
Keith, and other members of our team realized that in the region's grain
processing, there was an important link between bread baking and beer
brewing.  Egyptian art also shows baking and brewing in constant
association. In fact, baked bread is an essential part of the traditional
beer recipe still used today by villagers who live along the Nile.

The beer produced in ancient times, according to Barry Kemp, author of
Ancient Egypt: Anatomy of a Civilization, was quite different from the
modern commercial product: "It was probably an opaque liquid looking like
a gruel or soup, not necessarily very alcoholic but highly nutritious. Its
prominence in the Egyptian diet reflects its food value as much as the
mildly pleasurable sensation that went with drinking it: ' University of
Cambridge archaeologist Delwen Samuel and his colleagues from the British
brewery Scottish and Newcastle have undertaken extensive research on
brewing and baking in ancient Egypt. They analyzed the remains of food
left in tombs as offerings and the residues of beer and crumbs of bread
encrusted on pottery shards and vessels. They even examined floor
sweepings from tombs and living areas.

Successful brewing depends on the use of a grain that provides enough
sugar for fermentation. In modern recipes, grain is made to germinate and
is then heated and dried to halt the process. Known as malting, this
procedure releases the enzyme diastase, which converts the starches in
grain to maltose sugar. The malt is then boiled, strained, and incubated
with yeast. In the traditional Egyptian method, bread dough is set out to
capture airborne yeast. (Other traditional recipes actually add bosa that
was held back from previous batches for this purpose, since the liquid
contains yeast.) When baked, the bread forms a crust but is removed from
the oven before the center has had a chance to cook, allowing the yeast to
grow in the warm, slightly cooked dough. The partially baked bread is then
broken up and added to a broth of malted grain to make the beer.

[Illustration]
Caption: Egyptian painted limestone relief of ripe barley, ca. 1345-1335
LC.

We theorized that airborne streptomycete spores were captured in the
ancient brewers' dough during its exposure to the air and that the
streptomycetes then produced tetracycline while the yeast grew in the
partially baked bread.  To investigate brewing's capacity to give rise to
tetracycline, Daniel Popowich and Brennan Posner, undergraduates at Emory
University, added streptomycetes during two experiments with the
traditional process. In the first, they added a small colony of
streptomycetes to the just-baked bread; in the second, they added the
streptomycetes to the mixture of malted grain and bread. The second
technique was the more successful and produced significant amounts of
tetracycline.

The fermenting brews of ancient times, we concluded, provided the somewhat
harsh environment in which the streptomycetes were stimulated to yield
tetracycline in quantity. Nowadays, companies that make pharmaceuticals
deliberately control and limit certain nutrients as a way of forcing
streptomycetes to make tetracycline.

Given that the ancient Nubians and Egyptians were getting doses of
tetracycline, another question is whether this afforded them any medical
benefits. In Food: The Gift of Osiris, William J. Darby and coauthors
provide archaeological, historical, and ethnographic accounts of beer's
use as a mouthwash to treat the gums, as an enema, as a vaginal douche, as
a dressing for wounds, and as a fumigant to treat diseases of the anus
(the dried remains of grains used in brewing are burned to produce a
therapeutic smoke). This shows that even in the distant past, Egyptians
and their neighbors appreciated beer's medicinal qualities.

Today tetracycline remains the drug of choice in the treatment of both
acne and gingival disease. Researchers studying gum disease originally
assumed that the tetracycline worked because of its antibiotic qualities.
But tetracycline also appears to inhibit collagenase, an enzyme that
breaks down collagen.  There has been a concerted effort to produce
chemically modified tetracyclines (CMTs)  that have this effect but not
the antibiotic qualities. In addition, both tetracycline and CMTs have
proved to be very effective in inhibiting matrix matallproteinases,
enzymes involved in a number of bone and connective-tissue diseases, such
as rheumatoid arthritis, osteoarthritis, periodontal disease,
osteoporosis, and even cardiovascular disease. The ingestion of
tetracycline may thus have had real medical benefits for ancient Nubians
and Egyptians.

As we enter the new millennium, many people are concerned that our own use
and abuse of antibiotics in medicine, agriculture, and even manufactured
products has been encouraging the rise of antibiotic-resistant bacteria.
When we reported the discovery of tetracycline in ancient bones in the
journal Science, we wondered whether, owing to long-term ingestion of the
antibiotic, the Nubian and Egyptian populations might have suffered an
increase in disease caused by resistant bacteria. To test this, we have
examined the bones in our sample for signs of periosteal
reactions-roughened surfaces that form as a result of bone infection. We
have found no evidence that infections became more intense during the
centuries represented by the bones, as would be expected if more resistant
bacteria had evolved. But during our own lifetimes, 1,600 years later,
many of us may well fall victim to bacteria that are resistant to all the
known antibiotics. If we do, our bones will reveal this to archaeologists
of the future.


-- Jadwiga Zajaczkowa
jenne at fiedlerfamily.net OR jenne at tulgey.browser.net OR jahb at lehigh.edu
"Are you finished? If you're finished, you'll have to put down the spoon."