## Top of the tree

What do civil servants and monkeys have in common (ignoring a purportedly greater than average interest in bananas)? This question isn't an invitation to heap scorn on the political establishment. After all, in these interesting times such an invitation seems hardly necessary. I'm referring, instead to the Whitehall studies, examining health and mortality outcomes for members of the British Civil Service. The original study began in 1968 and ran for a decade, while Whitehall II began in 1985. The findings from these prospective cohort studies continue to influence policy both nationally and internationally into the present day.

The central findings from Whitehall, however, still carry an element of biological mystery. The results demonstrated a clear social gradient in mortality and morbidity, even after controlling for pre-existing conditions and risk factors. By focusing on a related set of occupations, the studies avoided confounding arising from unaccounted-for occupational exposures, and made the case that something inherent in the social structure altered the incidence of cardiovascular and other diseases. This was visible even between better-off grades where creature comforts were amply catered for. One of the original researchers, Professor Sir Michael Marmot, subsequently pointed to a possible explanation using cortisol as a proxy measure for job-related stress and lack of decision autonomy. Others examined the reduction in workplace predictability at lower social grades, and the potential for greater self-esteem to moderate the inflammatory stress response. Clearly something is going on, and debate will doubtless continue, but the bottom line is that it may not be ethically possible to design studies that fully explain the social gradient in health outcomes amongst humans.

Anyway, this might be an appropriate moment to bring the monkeys back on-stage (not a phrase I imagine I'll write again any time soon)! In November 2016, researchers examined the effect of social status on immune function amongst a colony of rhesus macaques. As captive subjects, they shared identical standards of nutrition, enclosure quality and veterinary care. As monkeys, they did not differ by smoker status, alcohol consumption or gym membership. Since female macaques form stable dominance hierarchies based on the order of introduction to the group, this allowed for multiple groups to be formed with known individuals placed in different positions in the hierarchy. Measurements demonstrated that social subordination, in and of itself, generated a pro-inflammatory response and altered gene-expression in circulating immune cells. More work will undoubtedly follow, but although we must always be cautious around applying results between species, we may be nearing an understanding of the biological basis for those Whitehall study findings.

References

Marmot, M. (2014) Review of social determinants and the health divide in the WHO European Region. World Health Organisation Europe. ISBN 978 92 890 0030 7.

Vaananen, A. (2008) Lack of Predictability at Work and Risk of Acute Myocardial Infarction: An 18-Year Prospective Study of Industrial Employees. Am J Public Health. doi: 10.2105/AJPH.2007.122382.

O'Donnell, K. et al. (2008) Self-esteem levels and cardiovascular and inflammatory responses to acute stress. Brain, Behavior, and Immunity. doi: http://dx.doi.org/10.1016/j.bbi.2008.06.012.

Snyder-Mackler, N. et al. (2016) Social status alters immune regulation and response to infection in macaques Science doi: 10.1126/science.aah3580.

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