Adventures in the environment and genes

Abstract

I was greatly honored by the invitation to give the Cutter Lecture, and following the practice of some other Cutter Lecturers I would like to offer some reflections on my career in Epidemiology, and draw some lessons about best practices that I wish I had known 35 years ago when I first considered this career. I will mention along the way some mentors and colleagues, but I apologize in advance to the many I will not name who have my gratitude and respect. Like many Australian physicians of the era, I was first properly exposed to population health during elective term experiences in Papua New Guinea, and subsequently in Dares-Salaam, Tanzania. After some clinical training, I enrolled in the MPH program at HSPH, vaguely expecting to wind up working for an NGO in a refugee camp. I had never really thought much about research, although an interest in trekking in the Himalayas and some minimal mountaineering experience had me reading papers on altitude sickness, and resulted in a co-authored review in the 1984 Christmas edition of the Medical Journal of Australia [1]. It was readily apparent that altitude sickness resulted from a combination of extreme environment, and inter-individual susceptibility, so I suppose the die was cast for a career investigating the inter-individual variation of environmental response. My thesis in the Nurses’ Health Study was on risk factors for non-melanoma skin cancer, again a combination of environmental exposure and susceptibility. Using the relatively crude graphics programs of the time, the papers featured a series of three-dimensional plots showing the relation between the two (Fig. 1) [2]. The Nurses’ Health Study held (and still holds) a weekly meeting of faculty, students and staff that were a model of collaborative development of questionnaires, grants and analysis plans. I probably learned as much about Methods in those meetings as I did in the classroom. My interest in what was then called International Health was still present, and towards the end of my doctorate I worked with Lincoln Chen as Executive Director of the AIDS and Reproductive Health Network. We developed a series of studies on HIV prevalence and incidence, and I collaborated with colleagues in Kenya and Tanzania examining HIV risk factors among women [3, 4]. We found to our horror that the prevalence was much higher than expected, meaning that studies initially designed as cross-sectional screens designed to facilitate case-control studies could be analyzed using prevalence risk ratios and then turned into prospective studies with annual incidence rates of several percent. Laptop computers had been recently introduced, and I spent many happy evenings in Nairobi and Dar-esSalaam watching logistic models that would now converge in seconds gradually converging over hours, all the while hoping the electricity did not suddenly fail. A blackout would crash the program; a power surge might fry the laptop. I still recommend some international work to anyone early in their career who has the freedom to experience it. Meanwhile, a project had been rather grudgingly funded by the site visitors to Walter Willett’s otherwise enthusiastically received Program Project, and we assembled an all-star cast of nutritional epidemiologists who were willing to share data post-publication, initially on diet and breast cancer. This became the Pooling Project of Prospective Studies of Diet and Cancer. In retrospect, we should have had a nifty acronym and logo, but consortium acronyms were not yet de rigueur. It was a great way to work with an international cast of epidemiologists and thus hear a diversity of opinions and approaches. We published a string of largely null papers [5] with the exception of a pooled analysis of alcohol and breast cancer [6]. For our annual meetings we would assemble a set of data tables the size of a phone book, and spend a day * David J. Hunter [email protected]