RA and The 16th Century Italian Mummy

The past calls to us. Whether through ancient relics, stone monuments, the ruins of temples, paintings on the walls of caves, or the remains of ancient rulers and saints, human history is full of questions that have bearing on the present. What was society like? What were common beliefs? Where did our ancestors come from? When did certain diseases arise, and how did they spread?

I am always amazed at how complicated answering these kinds of questions can be. For example, there is a branch of paleontology called paleopathology. Researchers here analyze the presence of diseases in human and animal skeletal remains. Certain diseases leave signature changes to remains, such as tuberculosis, leprosy, and syphilis.¹ Other diseases, such as rheumatoid arthritis and ankylosing spondylitis (an inflammatory arthritis affecting the spine) leave signature marks on the joints or spine, as well as the structure of the skeleton. Yet, one can't immediately assume that a signature mark is due to a disease that is common today. It may be an early variant of the current disease, or a disease that is unrelated but similar in its symptoms. Many variables have to be ruled out.

From the early models of inheritance via Gregory Mendel, to the discovery of the DNA double helix by Watson, Crick, Wilkins, and Franklin,¹ our understanding of genetics and inheritance has been ever increasing. In 2003, scientists around the world celebrated the completion of the Human Genome Project, with the sequencing of the entire human genome being made available freely to the public.³ Biotechnology companies have been innovating more rapid means of sequencing DNA, even from ancient sources. This allows for an immense range of inquiries into human health and novel new treatments for diseases (Biologic DMARD's like Humira and Enbrel use recombinant DNA technology⁴). It also allows researchers to look more closely into the past at the early origin of disease, as well as the distribution, spread, and evolution of pathogens or genetic susceptibilities.

Fascinatingly, there exists a 16th century Italian Mummy, entombed at the Basilica of Saint Francesco and found in 1996, that holds a lot of relevance for understanding the global history of rheumatoid arthritis. "This 50-55 year old woman, nicknamed “Braids Lady,” lived in the 16th century and her body, well examined through several diagnostic instrumental investigations, shows many pathologic signs peculiar to RA: large erosions and evident subluxation of the metatarsophalangeal joints of the hands, lateral deviation of all the fingers with typical “z” deformation of the thumbs, partial overlapping and fibular deviation of the toes, severe erosion of the right humeral head, but no involvement of the sacroiliac articulation, a prominent manifestation of ankylosing spondylitis."^5,6

The group of Italian researchers quoted above were also intent on "researching the possible presence of some RA susceptibility gene" by defining the HLA-DRB genotype of the mummy using molecular analysis of remaining tissue sections, as well bone.⁷ This region of DNA is important because, "The HLA region encodes several molecules that play key roles in the immune system. Strong association between the HLA region and autoimmune disease (AID) has been established for over fifty years."⁸ Certain genes are commonly associated as risk factors for RA. Determining if they are present in the mummy is important for making the case that she had RA rather than relying on the visible skeletal clues alone. In the publication of the study results, the researchers conclude: "We can state, by the positivity for DRB1*0101 allele in an Italian Renaissance mummy with clear 'symptoms' of Rheumatoid Arthritis, that this disease was present in the Old World before the discovery of America by Columbus in 1492."⁹

Their findings and conclusion have since been replicated by a separate team of researchers.

This does not mean that RA originated in Europe. It only clarifies any debate about whether or not RA has origins in North and South America that spread outward during the time of European exploration in the16th century. It also clarifies any debate about whether or not RA is a disease of recent origin.

A review in 2011 of the various hypotheses of RA origin and the accumulating evidence gives an overview the research: "By combining the conclusions from paleopathological studies with those from advanced immunological and genetic analyses, a modified and updated version of the Ancient Origin view now stands as the best-supported theory concerning the historical epidemiology of RA. The current hypothesis consists of the following principles:

• RA is not a disease of recent origin, and was both present and problematic hundreds, possibly thousands of years ago, potentially with a geographic distribution distinct from its current profile.
• RA occurs as a response to an environmental stimulus or stimuli experienced by genetically susceptible individuals.
• The identities and origins of these stimuli or inciting events are still incompletely known, although tantalizing clues have emerged."¹¹

Let us hope that steady progress in research and technology, as well as a deeper understanding of the causes at play, will lead to novel, safer, and more effective treatments for RA.

The Italian Mummy certainly is fascinating. You can find pictures and the full study here: http://www.paleopatologia.it/articoli/aticolo.php?recordID=39