Medieval DNA, Modern Medicine (Lessons From The Black Death)

Will a cemetery excavation establish a link between the Black Death and resistance to AIDS?

Beneath Eindhoven's modern skin of brick and asphalt lie the bones of its medieval townspeople. Studying their DNA may reveal the origin of the genetic resistance to AIDS. (Courtesy Laurens Mulkens)

From the start, Nico Arts sensed that the frail remains of a child buried in front of a medieval church altar had an important story to tell. Arts is the municipal archaeologist in Eindhoven, a prosperous industrial city in the southern Netherlands whose medieval streets vanished long ago beneath a modern warren of concrete and steel. In the late winter of 2002, Arts and his team were conducting a test excavation near St. Catherine's Church in the city center, in advance of the development of a new public square. Arts believed he had found someone very important, such as the son or daughter of a former lord of Eindhoven. He persuaded forensic scientists at the University of Louvain in Belgium to test for ancient DNA. The chances of finding it seemed slim because water dissolves DNA, and the repeated pumping of groundwater from underground parking lots over the past decade could have periodically soaked the child's bones. But in 2004, Arts received some unexpected news: one of the child's milk teeth yielded DNA. It was the first time usable amounts of this molecule had been recovered from an ancient body in the Netherlands, and it showed the child was a boy.

This chance discovery of ancient DNA has led to one of the most ambitious archaeological projects ever to come out of the Netherlands--a massive excavation in the St. Catherine's Church cemetery and the establishment of a major ancient human DNA databank. With $3.4 million in funding, Arts and a team of archaeologists and physical anthropologists have now unearthed the skeletons of more than 750 Eindhoven citizens. And over the next two years, University of Leiden geneticist Peter de Knijff will attempt to recover DNA from these remains. "We expect that at least 75 percent of all individuals will have ancient DNA and proteins," says Arts.

Eveline Altena prepares to take a DNA sample from a recently excavated molar. The tooth's pulp cavity seals off DNA from contaminants, making it the best place to look for intact genetic samples. (Courtesy Laurens Mulkens)

For researchers, the Eindhoven DNA bank could prove a major windfall, paving the way for a host of new studies. To unravel the mysteries of human disease, researchers are increasingly studying genetic variations in human populations that increase the risk of illnesses, such as diabetes, or boost resistance to infections such as malaria. By studying the variants over time, researchers hope to advance knowledge of these diseases and gather clues to produce vaccines or new drug treatments. And such medical research is where the Eindhoven DNA bank, which spans 600 years of history, could really shine.

The Dutch team hopes, for example, that their project will reveal the origin and prevalence of a genetic variant that increases resistance to one of the world's most lethal viruses--HIV. Today, nearly 10 percent of people of northern European descent possess this variant, known as the CCR5D32 allele, and the discovery is sparking the development of a new class of AIDS-fighting drugs. Evidence suggests that this mutation first arose 3,100 to 7,800 years ago, but how did it become so prevalent across Europe in an age before the AIDS epidemic? Could this mutation also have boosted resistance to an earlier epidemic, such as smallpox or the Black Death? In search of new data, Knijff and his team will search for this variant in the DNA of Eindhoven's citizens. "There is no doubt that these studies are valuable," says Susan Scott, a University of Liverpool historian who has written extensively on the Black Death and its possible connection to the HIV-resistance variant. "Whilst I don't think [ancient DNA] studies will yield a vaccine for AIDS, they may assist molecular geneticists to develop some gene therapy."

For Arts and many of his colleagues, the bold project has ushered in a new era in archaeological research. "It makes archaeology much more relevant than it ever has been before," says Eveline Altena, a University of Leiden doctoral student in charge of recovering ancient DNA from the Eindhoven burials. "If we can use archaeological samples to answer medical questions, how cool is that?"

Heather Pringle is a freelance science journalist and author of Master Plan: Himmler's Scholars and the Holocaust.

Does one blood type get sicker than another, or is one type more apt to become sick?

http://www.hhmi.org/cgi-bin/askascientist/highlight.pl?kw=&file=answers%2Fimmunology%2Fans_034.html

Provided by Matthew McCarthy, HHMI medical fellow, Harvard Medical School, Boston

The sorting of blood according to certain cell-surface characteristics has helped scientists understand why in some cases a blood transfusion may save a life and in others it may cause death. The first blood group to be characterized was the ABO group in 1900, and this classification system remains one of the most medically relevant.

People are divided into one of four categories: A, B, AB, and O, depending on the structure of a particular sugar molecule on the surface of their red blood cells. This sugar is referred to as an antigen. People with type A blood have the A antigen, while people with type B blood have the B surface antigen. Those with type AB make both antigens, and type O people produce neither antigen. Someone with type A blood will reject type B blood via antibodies that recognize and destroy blood cells that have antigens of a different group.

Blood types are genetically inherited, but the environment can influence which blood types will be passed on. An example is seen with the Black Plague, which killed millions of people in Europe in the 13th and 14th centuries. The disease was caused by a bacterium that resembled type B blood and used this quality to evade destruction by the human immune system. As a result, people with type B blood died in far greater numbers than those of other blood types. By the 15th century, fatalities from the plague had decreased significantly as type B blood was systematically phased out in that part of the world.

Although certain blood types increase susceptibility to disease, others confer resistance, as seen with the sickle-cell mutation. Certain people have a type of blood that appears deflated and shaped like a sickle. People in this group are predisposed to sickle-cell anemia. At first glance, one might wonder why evolution has allowed for this blood type to be passed down through the generations if it can cause disease. The answer is that the deflated, sickle-shaped blood cells are actually protective against malaria. And the very people who possess this type of blood have ancestors who used to live in places where malaria was a major cause of death, such as central Africa.

More recently, scientists have noted that people with type O blood are more susceptible to the Norwalk virus, which causes diarrhea, and to Helicobacter pylori infection, which can cause ulcers. This finding has led scientists to ask, Why does type O blood continue to be passed from one generation to the next if it increases the risk of infection and disease?

Using the model of sickle-cell anemia, researchers hypothesized that type O blood could increase the risk to one infection (Norwalk virus) while conferring resistance to a more serious infection. In March 2005, a group in Hong Kong confirmed this hypothesis, showing that people with type O blood have a decreased risk of contracting SARS (severe acute respiratory syndrome), a deadly disease that afflicted people in Asia, Canada, and the United States during an outbreak in 2002–2003.

Recent research has shown that people with type A blood have an increased risk of cancer of the esophagus, stomach, and pancreas. As you learn more about blood types and their role in disease, a great question to think about is, Why would evolution ever allow us to pass down blood types that increase our risk for cancer?

As you can see, a particular blood type may predispose you to one disease while simultaneously protecting you against another.

References

Cheng, Y., Cheng, G., Chui, C.H., Lau, F.Y., Chan, P.K., Ng, M.H., Sung, J.J., and Wong, R.S. ABO blood group and susceptibility to severe acute respiratory syndrome. JAMA 293 (12): 1450–51, 2005.

Hutson, A.M., Atmar, R.L., Graham, D.Y., and Estes, M.K. Norwalk virus infection and disease is associated with ABO histo-blood group type. Journal of Infectious Diseases 185 (9): 1335–37, 2002.

Williams, T.N., Mwangi, T.W., Wambua, S., Alexander, N.D., Kortok, M., Snow, R.W., and Marsh, K. Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases. Journal of Infectious Diseases 192 (1): 178–86, 2005.

"More than likely the resistance developed during a period when a Founder Population lived in a rodent infested region ~ probably the Arctic ~ they would have made their way South over thousands of years, gradually blending into the local population."

This article is a condensed version from the one in Archaeology Magazine. In the magazine version, it has this to say:

Most researchers now believe that the Black Death was the bubonic plague. Caused by the bacterium Yessinia pestis, it spread from rats to humans, usually by means of an infected flea.
But historical records show that the Black Death occurred in areas such as Iceland, where there were no rats. As a result, historian Susan Scott and Liverpool zoologist Chris Duncan suggest that Black Death was a viral hemorrhagic fever, akin to the Ebola Virus.
No one, however ,debates its lethal effect. In just three years, the Black Death swept across Europe, as far north as the Arctic Circle, claiming the lives of 40 percent of its inhabitants. And over the next three centuries, it struck repeatedly on the continent, filling graveyards whenever it appeared."

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