Obituary for Professor David Barker

David Barker invented a new field of medicine, Developmental Origins of Health and Disease (e.g. Barker, 1992, 1994, 1998). His ideas regarding the causes and potential cures for human diseases diverged from those who came before him and ignited a paradigm shift in medicine that is iconic in the late 20th century. The Barker Theory posits early pre- and post-natal influences as causal to adult disease risk, an aetiological view that casts the traditional organ-specific adult clinical approaches as mere late-comers to the event and puts out the call for interventions to promote health from the earliest ages as the prime player in curbing the global chronic disease epidemic. He wrote,

Chronic diseases are not the inevitable lot of humankind. These diseases are not mandated by the human genome. They are the result of the changing pattern of human development. We could readily prevent them, had we the will to do so. Protecting the nutrition and health of girls and young women should be the cornerstone of public health. Not only will it prevent chronic disease, but it will produce new generations who have better health and wellbeing through their lives (Barker, unpublished manuscript).

Born in London on the eve of the Second World War, Professor Barker understood from an early age the detrimental effects of social and environmental challenges to human health. At Oundle boarding school, his childhood passion for natural history observation was supported by a remarkable zoology teacher who gave him the freedom to pursue beetle-collecting and cataloguing in extra-curricular hours. His scientific acumen continued to develop as an adolescent when he was chosen for an expedition to collect plant specimens in Iceland for the Natural History Museum. Professor Barker studied human biology and anthropology, was a pupil of J. Z. Young, and earned a BSc (First Class Honours) and MBBS from the University of London. While a house physician at Guy’s Hospital, London, he published his first paper in Nature, describing the effects of testosterone and estradiol on the growth of long bones among mice (Barker & Crossley, 1962). He continued his training as a student of Thomas McKeown in Birmingham, whose views on social medicine and epidemiology emphasized the importance of nutrition and socioeconomic status for health. He received his PhD in 1966 for his work on “Prenatal influences and subnormal intelligence” (Barker, 1966). These educational experiences were fundamental to the intellectual perspectives that his subsequent work would take. His search for biological mechanisms underlying disease was firmly grounded in the knowledge that it needed to be informed by a wider biology than that of humans alone. He often expressed his admiration for Charles Darwin and wrote that,

Had Darwin been able to document the natural selection of species from the limited flora and fauna around his country mansion, he would presumably have done so! As it was, he had to endure 5 years of discomfort in cramped living conditions on a boat in order to observe the diversity of nature across the world (Barker, unpublished manuscript).

In 1969, David Barker was seconded to Markere University, Uganda, under an MRC grant to study Mycobacterium ulcerans infection, or buruli ulcer (later described by the WHO as one of the 17 neglected tropical diseases). David’s meticulous observational details identified that the soft tissue destruction attendant to the disease was associated with vegetation in and around water (Barker, 1971, 1973a). His analysis of the geographical, sex and age distribution of the disease led him to postulate that it was related to contact with certain species of grass and he described the first non-human source of mycobacteria (Barker et al., 1970). Moreover, he cultured the grasses and found mycobacteria that, when injected into mice, produced lesions analogous to buruli (Barker et al., 1972). This work formed the basis for his MD thesis, “The epidemiology of Mycobacterium ulcerans infection”, from the University of London in 1973. His position as Lecturer in Preventive Medicine in Uganda was cut short by Idi Amin’s 1971 coup d’état and he returned to England to take a position at the University of Southampton. Here, he practiced medicine, became Professor of Clinical Epidemiology in 1979 and Director of the MRC Environmental Epidemiology Unit in 1984. David became known for his textbooks on epidemiology, including four editions of Practical Epidemiology (Barker, 1973b) and five editions each of Epidemiology in Medical Practice (Barker & Rose, 1976) and Epidemiology for the Uninitiated (Barker & Rose, 1979), both co-authored with Geoffrey Rose.

In Southampton, David Barker investigated the rise and fall of diseases across time and geographic distribution (Barker, 1989; Gardner et al., 1984). He was a canny sleuth and sought clues to aetiology and evidence of modifiable environmental influences as steps towards preventive medicine. For over two decades he investigated patterns of diseases ranging from diabetes (Barker et al., 1982) and thyrotoxicosis (Barker & Phillips, 1984) to Paget’s (Barker & Gardner, 1974) and Perthes’ disease (Barker et al., 1978); gall stones (Brett & Barker, 1976), urinary stones (Barker & Donnan, 1978), gout (Gardner et al., 1982) and Henoch-Schonlein purpura (Atkinson & Barker, 1976); duodenal ulcers (Barker et al., 1981), colorectal cancer (Barker & Godfrey, 1984) and respiratory infections (Barker & Osmond, 1986b); polio (Martyn et al., 1988) and Alzheimer’s disease (Martyn et al., 1989). This prodigious work included one of his less well known scientific contributions – the initiation of what is now referred to as the “hygiene hypothesis”. A review of the time trends in appendicitis in England and Wales led to his analysis that the “dietary fibre hypothesis” did not stand up (Barker et al., 1986). Instead, he proposed, “The ‘hygiene’ hypothesis… that initial improvements in hygiene, mainly determined by provision of household amenities, reduces exposure of young children to enteric organisms and is followed by a rise in appendicitis rates” (Barker et al., 1988, p. 147). He concluded that the epidemic of appendicitis in Britain was a consequence of altered immunity in children, consequent on improved sanitation and hygiene and declining encounters with harmful bacteria during infancy, which led to an over-reaction to them when encountered in later childhood and adult life (Barker, 1985).

These geographic investigations led to the work that would consume the rest of his career. Struck by the evidence that in Britain the highest rates of ischaemic heart disease were found in the poorest areas and among the lowest income groups at a time when heart disease was seen as a disease of affluence, he initially concluded that geographical differences in patterns of mortality and morbidity in Britain are not just a legacy of past social inequalities but reflect influences still present in the environment (Barker & Osmond, 1987). This was followed by the documentation that these results were not due to nutritional disparities in adulthood (Cade et al., 1988). In a moment of insight, his photographic memory suddenly recognized that patterns of ischaemic heart disease mortality in 1968–1978 parallelled patterns of infant mortality in 1921–1925 and “environmental influences” took on a new perspective. In 1986, Barker and his colleague, Clive Osmond, put forward the observation that adverse influences in childhood, associated with poor living standards, increase susceptibility to other influences, associated with affluence, encountered in later life (Barker & Osmond, 1986a), and subsequently linked death from ischaemic heart disease to weight in infancy (Barker et al., 1989). Pursuing these ideas, he set about seeking data with which to test the hypothesis of a connection between poor pre-natal conditions and adult heart disease. The first step was found in the medical records of 5654 men born between 1911–1930 in Hertfordshire (Barker, 2003). A follow-up study was begun in the 1980s and these longitudinal data identified that both poor pre-natal and post-natal growth led to the highest death rates from ischaemic heart disease. Moreover, as birth size reflects maternal size, Barker and Osmond suggested from the beginning that interventions to reduce heart disease should aim at improving the growth of girls. Over the years, further disease-specific associations with early development were documented, the “foetal origins” view became more clearly articulated (Barker, 1995) and evidence for “foetal programming” involvement in cardiovascular and metabolic diseases expanded. In 1992, the concept of “thrifty phenotypes” was published (Hales & Barker, 1992) and interest in both theoretical speculation and evidentiary investigation of foetal correlates of lifespan health was launched worldwide, with studies ranging from animal models to the mining of human epidemiological data. While these decades saw considerable debate and response from naysayers, today more than 130 000 papers on foetal programming are cited on Pubmed and to many scientists the evidence is clear: foetal life establishes the road for health across the lifespan. David often quoted the poet William Blake in this regard, “man brings all that he has or can have into the world with him. Man is born like a garden, ready planted and sown”.

David Barker worked steadfastly to expand scientific understanding of the origins of health until his death. For many years he worked against a tide of medical opinion that was not merely intellectually resistant but personally insulting. David held steadfast to the evidence and his efforts to test his theory encompassed data from around the world and across species. Working with colleagues in Helsinki and Amsterdam, rare longitudinal data provided the fundamental documentation that growth patterns during early life, and nutritional insults specifically, write the script for subsequent health, with developmental timing and sex-specific effects (e.g. Barker et al., 2009; Roseboom et al., 2001). Building collaborations between population and laboratory scientists from Toronto, Australia, New Zealand, Saudi Arabia and France has immeasurably expanded knowledge. The study of foetal origins of diabetes in India identified the importance of phenotypic variability in classical assumptions associated with chronic disease (Yajnik et al., 2003) and includes documentation of the positive effects of maternal nutritional supplementation (Shivashankaran et al., 2011). In the last years of his life he advanced knowledge on the role of the placenta at Oregon Health Sciences University (Barker & Thornburg, 2013), and he was an inspiring teacher and scientific collaborator at Emory University in the US. His annual schedule was filled with trips abroad and working visits with global colleagues.

I had the privilege of knowing David Barker as a colleague and friend. David took pride in his recitation of the Elegy in a Country Church Yard by Thomas Grey, enjoyed English detective mystery broadcasts and told jokes that made people blush. His prodigious intellect and his enthusiasm for thinking were contagious. When David Barker said, “feast your eyes on this” he was referring to scientific data. He was electric in his intellectual excitement for making new conceptual advances. In the last months of his life, the end of a day at the computer included a safari-like bouncing ride in his jeep in the evening. With skill from his experience in Uganda, he drove precipitously through the freshly mown grass on the meadow at his farm and teased his riders by veering dangerously at the bridge over the river to “avoid the unseen hippopotamus” and haltingly proceeded to “narrowly escape attack” near the relic WWII bunker on his property. The end of such an evening’s journey was a glass of wine by the river that flowed just in front of his getaway, a shepherd’s hut, which in reality was only a short walk through the field from his meticulously organized wood-lined office. On weekends he would engage his grandchildren in a game of croquet (and teach guests from “the colonies” the strategy of the game).

David Barker was passionately committed to improving the human condition. His next goal was to see public health interventions put in place (Barker et al., 2008, 2011). He had little patience for inaction and was known for his frustration with those who believed the way forward was exclusively genetic. It was so clear to him that improving health required empowering individuals and improving nutrition, employing small and implementable steps forward. He challenged the next generation to take up the cause and generously gave us the foundation and tools to do so.

The recipient of numerous international awards, David Barker was elected a Fellow of the Royal Society and the Academy of Medical Sciences in 1998 and was awarded a CBE for his services to preventive medicine in 2005. He was past president of the Association of Physicians of Great Britain and Ireland, a Fellow of the Royal College of Physicians, the Royal College of Obstetricians and Gynecologists and the Royal College of Pediatrics and Child Health. He published more than 500 research papers and 10 books.

David James Purslove Barker is survived by his wife, Jan, eight children, 13 grandchildren and legions of present and future scientists who benefit from his extraordinary contributions. A memorial service on November 12, 2013 in Romsey Abbey celebrated the life of Professor David J. P. Barker, 29 June 1938–27 August 2013.