Dr Helen D. Donoghue, Centres for Clinical Microbiology and The History of Medicine, University College London
Tuberculosis is a major cause of death today, and leprosy is the greatest cause of infection-related disability, so it is essential to understand the nature of these diseases in the past. Both tuberculosis and leprosy cause distinctive palaeopathology in skeletal remains and these were the first infectious diseases identified by aDNA using PCR. However, skeletal disease occurs in only 3-6% of TB cases so M tuberculosis biomarkers also occur in specimens with non-specific or no visible pathological changes.
Working with aDNA, stringent precautions are needed to avoid contamination with modern or amplified DNA and independent verification is required. Other specific biomolecules, such as lipids and proteins, provide robust confirmatory data and this area is of expanding interest. Unlike human DNA, traces of ancient pathogens will not be distributed evenly throughout the body. A good understanding of the natural history of the infectious agent and of its interaction with its host is necessary, to identify the likely site in the body of any biomolecular traces of the microbe. Extraction of aDNA must overcome problems of taphonomic damage, covalent cross-links and co-extraction of inhibitors. Specific primers designed for short fragments and linked to fluorescent probes give good results, especially if targeted at multi-copy loci. Recently NGS and WGS have been used to investigate historical tuberculosis.
Tuberculosis and leprosy are major infections today, although infected people with effective immunity may remain healthy for years, suggesting long-term co-existence of host and pathogen and clonal selection. In well-preserved ancient samples, the M tuberculosis complex and M. leprae can be genotyped. Such studies have provided direct evidence of extinct lineages and have also shown that archaeological aDNA may resemble extant strains. Such work provides real-time calibration to aid the assessment of the rate of evolutionary change.
Helen Donoghue received her Special Honours B.Sc in Microbiology in 1967, and PhD in Bacteriology in 1971 from the University of Bristol, UK. She spent six years as a post-doctoral research scientist in the Medical Research Council Dental Unit at the University of Bristol Dental School. In 1976 she moved to the University of Bradford, UK as Lecturer in Medical Sciences and in 1980 moved to University College London (UCL) as Senior Lecturer in Oral Microbiology in the Dental School. From 1992-2011 she was Senior Lecturer, Department of Medical Microbiology, later renamed as the Centre for Infectious Diseases and International Health, Division of Infection and Immunity, UCL. She has taught several generations of medical, dental and science undergraduate and postgraduate students. Her present position at UCL is Honorary Senior Lecturer, Division of Biosciences, Centre for The History of Medicine and Division of Infection and Immunity, Centre for Clinical Microbiology. She is a Fellow of the Royal Society for Tropical Medicine and Hygiene and member of several microbiological and professional societies. Initially her research interest was the microbial ecology of the human commensal oral flora. On transferring to the UCL Medical School she has worked primarily on the pathogenic mycobacteria. Her principal research expertise is in human pathogens, primarily Mycobacterium tuberculosis and Mycobacterium leprae, especially the detection and characterization of their DNA in archaeological material, using PCR. Her recent publications are on the molecular characterization of ancient M. tuberculosis and M. leprae and how this contributes to our understanding of the origin and evolution of pathogenic bacteria and their hosts.