Leprosy has plagued humans for thousands of years, but a new genetic analysis of the pathogen that causes the disfiguring disease has come to the surprising conclusion that its DNA is essentially unchanged since medieval times.

The discovery, published this month in the journal Science, suggests that the disease’s retreat in Europe during the 14th and 15th centuries was probably the result of human adaptation to the bacterium that causes leprosy rather than due to any change in its DNA.

Few diseases have ravaged mankind the way leprosy has. It tortured ancient Chinese, Indian and Egyptian civilizations, and descriptions of it have been found on Egyptian papyrus documents that date to about 1550 B.C., according to the National Institute of Allergy and Infectious Diseases. For centuries, victims were quarantined in leper colonies and treated as pariahs.

Triggered by an infection with the bacterium Mycobacterium leprae, the disease causes victims to develop painful skin lesions and sores, and lose feeling in their limbs.


Leprosy was a particular scourge in medieval times, affecting up to a quarter of all people living in Northern Europe before it began to wane, according to historians of the National Park Service, which administers a former leper colony in Hawaii.

The retreat baffled Johannes Krause, a paleogeneticist at the University of Tuebingen in Germany. Did the bacterium evolve into a less virulent strain, or had something else driven it off the continent?

To find out, Krause and his colleagues examined five skeletons in museum collections of leprosy victims in the 10th through 14th centuries. They checked for any remnants of M. leprae DNA.

It was a long shot, they realized: the amount of bacterial DNA in ancient skeletons is usually minuscule. In one case, only 0.005% of the DNA recovered from the skeleton of a bubonic plague victim was from the disease-causing pathogen, Krause said.


Imagine his surprise when his team realized that 40% of the DNA obtained from one of the skeletons -- teeth that belonged to a Danish person who died in the 14th century -- came from M. leprae. To recover so much DNA from such old skeletons “was incredible,” Krause said.

The samples allowed Krause’s team to sequence virtually the entire genomes of the medieval M. leprae strains. Then the scientists compared them to the genomes of 11 modern leprosy strains.

That analysis revealed another surprise: The pathogen had barely changed in 1,000 years. Out of the 3.3 million chemical letters in the bacterium’s genome, only 20 were different, Krause said.

The results were unexpected because “bacteria normally evolve quickly,” according to Dr. Maria Ochoa, director of the Hansen’s Disease Clinic at Los Angeles County/USC Medical Center, which treats people with leprosy. Ochoa was not involved in the study.


To Krause, the discovery strongly implied that leprosy’s retreat in the Middle Ages wasn’t due to a mutation that made the bacterium less dangerous.

Instead, strict quarantine efforts and the emergence of other debilitating pathogens may have led to leprosy’s decline in medieval Europe, the researchers wrote in the scientific journal Cell. For example, bubonic plague arrived in the 14th century and killed 30% to 50% of Europeans within five years, many of whom probably had leprosy.

Gene changes in humans also played a role. Mutations in an immune system gene called TLR2 make people resistant to leprosy, and some of these mutations are more common in Europeans, studies have shown.

Today, leprosy is extremely rare in the United States, with only 6,500 known cases, according to the U.S. Department of Health and Human Services.


Norwegian physician Gerhard Hansen identified M. leprae as the cause of leprosy in 1873, and a drug treatment was found in the 1950s. By the 1970s, multi-drug therapies that combined dapsone with other medications allowed patients to be cured.

Leprosy remains a problem in developing countries like India, Brazil and Angola, however. At the beginning of 2012, 181,941 people worldwide were known to be affected by leprosy, the World Health Organization says.

The analysis of M. leprae’s genome also revealed that much of it is made up of pseudogenes -- formerly functional genes that essentially become inert. The large presence of pseudogenes is a sign that the organism is highly adapted to its environment and has little ability to evolve, said Richard Truman of the National Hansen’s Disease Program at the U.S. Health Resources and Services Administration.

“You kind of wonder how this thing is even functional,” said Truman, who was not involved in the study.


The Science study suggests humans have outcompeted the pathogen, but M. leprae is not completely vanquished. Two of the 11 modern strains have a mutation in the folP1 gene that makes them resistant to dapsone.

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brad.balukjian@latimes.com