Welcome to the fifth video of the Paleopathology Module. In this video, we'll be talking about a very old disease, leprosy. You may be familiar with pop culture references to leprosy. For example, from the movies The Motorcycle Diaries, Braveheart, and the City of Joy. From these and other sources, perhaps you know of the disease from the skin lesions and facial disfiguration that it can cause. The bacterium Mycobacterium leprae causes leprosy. Initially, the infection is without symptoms for 5 to as many as 20 years. And it's a person's immune response to the pathogen that determines the type of leprosy they develop. Now, there are different systems to classify the type of leprosy. But most simply, we can think of it as two types. The first, called tuberculoid leprosy, is much more mild. Maybe only causing a few sores on the skin. And it's minimally contagious. This is the form that arises when a person's immune response is strong. The second type is what people typically think of when they think of leprosy. It's the type we have evidence for in ancient skeletons. In this type, called lepromatous leprosy, the immune response is poor. The disease becomes more contagious. And it causes granuloma inflammation of the nerves, skin, respiratory tract and eyes. And this may result in a lack of ability to feel pain, and thus repeated injures leading to infection. One main focus in osteoarchaeology is to understand the antiquity of this disease. That is, when leprosy, also known as Hansen's disease, first appeared. So as mentioned, we know it's an old disease. It's one we have skeletal evidence for from as far back as 2000 BC in sites in India and Pakistan. A classic marker of the disease constituting irrefutable evidence is something called the rhinomaxillary complex. This involves atrophy of the nasal spine, atrophy in recession of the alveolar process of the anterior maxilla, and endonasal inflammatory changes. And you can see this here. The disease spread to Europe after the fourth century BC, probably in conjunction with Alexander the Great's army. But it did not become a serious health problem in Europe until the Middle Ages. That's when we begin to have a lot of skeletal evidence for the disease in many different countries. So given the antiquity and spread of the disease and its apparent shift in virulence over time. And virulence means the ability of the pathogen to cause disease. Osteoarchaeologists are very interested in if, when, why, and how the leprosy pathogen changed and evolved over time, and hence how this variably affected past populations. It's worth keeping in mind that leprosy is a disease that still affects hundreds of thousands of people today. In 2014, the World Health Organization estimated the number of cases of leprosy to be over 200,000. With 14 countries containing 95% of the cases. Of these, India had the greatest number, followed by Brazil and Indonesia, some parts of Africa, and the Western Pacific. And this is despite the fact that there are very effective treatments for leprosy that reduce its transmissibility to nearly zero. So while the disease is no doubt declining in prevalence, work remains. And bettering our understanding of the pathogen can be useful in this regard as well as into offering insight about the evolution of infectious diseases. All archaeological cases of leprosy that have been genetically identified belong to the Mycobacterium leprae species. But within that species, there are many different strains and subtypes. In 2005, geneticists traced the origins and probable worldwide distribution of leprosy from East Africa or the Near East along major human migration routes from the past. They found that there were four strains of Mycobacterium leprae, with specific regional locations. Strain 1 occurs predominantly in Asia, the Pacific and East Africa. Strain 2 in Ethiopia, Malawi, Nepal, in North India and New Caledonia. Strain 3 in Europe and North Africa and the Americas. And Strain 4 in West Africa and the Caribbean. And then later research by these same scholars broke these four strains into 16 subtypes labeled A to O. Which strains contain which subtypes is shown in this diagram. So with the use of advanced methods of ancient pathogen DNA genotyping, osteoarchaeological research has investigated the strains and subtypes of leprosy in different areas and time periods. Already, several of the modern subtypes have been found in ancient peoples. This approach allows for the reconstruction of the spread of leprosy strains and subtypes. And to speak to us today about a multidisciplinary leprosy case study from the UK that she headed up is Dr Sarah Inskip. Dr Inskip, thank you for joining us today. To begin, can you set the scene for us? So tell us where you were, what you were doing, and why you decided you needed to gather more evidence. >> So while we were working at the University of Southampton, we undertook some recuration of one of the collections there, the Great Chesterford collection, which is an Anglo-Saxon cemetery on the Essex and Cambridgeshire border. And while we were doing this, we found a skeleton that had lesions that had previously been unreported. And this included periosteal new bone on the tibia and the fibula. Osteitis on the metatarsals and the tarsals. And then pencilling and thinning of the metatarsals and the phalanges. Now, this lead us to a possible diagnosis of leprosy. However, the facial skeleton was not preserved. And this meant that we could not make a definite diagnosis of the disease. So we needed to do further research to try and confirm this. >> I see, so then as a next step, you compiled a team of paleogeneticists and paleobiologists to determine if indeed this was leprosy. And if so, what was the strain and the subtype? So can you tell us about the results of that research? >> Yes, so working with Professor Michael Taylor at the University of Surrey, we first wanted to check the preservation of the DNA within the individual. And this was very good. So the next step was to then undertake a screening to check for the leprosy genomic DNA. And this confirmed the presence of the disease within the individual. After this, we undertook typing to try and see which strain it was. And it turned out to be Strain 3 of subtype I. And this is interesting because it appears in later medieval Britain, but also in Denmark and in Sweden. Interestingly, it's also the strain that we see today in the Americas. >> That is interesting. So then as the next step, you put together a team of isotope chemists, a team of isotope chemists, for a dual purpose. To see how long ago the individual lived, and also to assess their birthplace to see if they were local or non-local. So can you tell us about those results? >> Yeah, so we wanted to place the individual within a wider context of the disease in terms of understanding its origin and its evolution. And so the first thing we did was undertake carbon dating analysis. And this proved to be of a 5th to 6th century date. After this, we then wanted to see if the individual was local or non-local. And using strontium and oxygen isotope analysis, we identified that it was very unlikely that the individual was from within the UK. And an origin more in Germany or Denmark was far more likely. Now, considering the Anglo-Saxon population movements across Europe in this period, it possibly suggests a Scandinavian origin for this strain of the disease in England at this time. >> Interesting, to conclude then, can you tell us, in your opinion, what are the main contributions of this research? >> Yeah, so it's difficult to pick out one thing, as there were many aspects of this research that were really good. And the first thing is the reanalysis of old curated collections. The fact that we went back to a collection that was originally excavated in the 50s and 60s and we were able then to contribute something new and significant was really good. Secondly, we were able to possibly demonstrate the origin of this strain of the disease in the Americas from Europe. And then finally, I think using a multidisciplinary approach to paleopathology. And demonstrating the importance of using multiple types of evidence to create a wider story. >> Great research, Doctor Inskip. Thank you again for sharing this with us today. Today we've learned about leprosy. About how it affects a person's body and skeleton, about its antiquity and spread across the globe. And about how with a keen eye for pathological lesions and advanced biochemical methods, including ancient pathogen DNA, we can learn a lot about the presence and spread of leprosy in the past. Coming up next is the Paleodiet Module. What did our ancestor actually eat? Is there any truth to these so-called Paleo diets, or to claims that we've evolved to eat only certain foods? Stay tuned to find out.
