Red Hair Research
Like many people who qualified in the early 1980s research in genetics was both highly fashionable (and therefore fundable) and promising. After an MRC Training Fellowship with Chris Redfern in Newcastle I spent a year in Pierre Chambon’s rather large laboratory laboratory in Strasbourg. I learned a lot there including that I was not cut out to work in a factory or other institutions of ‘big science’.
In the late 1980s after working on mouse knockouts of retinoid receptors I returned to Newcastle and started work on skin cancer genetics before concentrating on the genetics of sun sensitivity (sun is the main aetiological factor for skin cancer). Along the way, either in collaboration or alone, my lab took part in some mapping and positional cloning projects for a variety of genodermatoses (e.g. Darier’s disease, Monilethrix & pachyonychia congenita).
In 1995 in collaboration with Tony Thody (Newcastle) and Ian Jackson (MRC HGU, Edinburgh) my lab identified a ‘gene for red hair’ (the melanocortin 1 receptor). The gene is pleiotropic, with loss of function leading to freckling, poor tanning responses, ease of burning after sun exposure, and a shift in the ratio of eumelanin to pheomelanin (in hair at least).
Subsequently we were been able to date when the mutations arose, studied the genetic epidemiology of the receptor, and described its use as a predictor for melanoma and other forms of skin cancer (it is not much use). We then developed some new in vivo assays that allow a more quantitative approach to the study of human tanning and how this relates to genotype. Much of this work involved collaborations with Ian Jackson, here in Edinburgh, and Rosalind Harding, a quantitative geneticist, in Oxford. I have summarised some of this work in articles in the Annual Review of Genetics and the American Journal of Human Genetics. For an informal review for non-experts and journalists click here. The tail end of this work appeared in 5 papers mostly in the Journal of Investigative Dermatology in 2004, 2005 and more recently here.
There is a second question: given that pigmentation is only one method of protection against UV, the other being epidermal thickening, why do those with a limited ability to produce pigment not switch on to a greater degree epidermal thickening? We don’t know the answer to this, and although we have published methods based on transmission spectrophotometry through epidermis in vitro , although we found the approach we used — reflective confocal scanning microscopy — technically ill suited for our purpose.
My final paper on ‘red hair’ is a review with Rosalind Harding on the evolution of skin and hair colour. Time to hand on to the young people. It is open access in the JID here
Finally, my own view is that diagnosis aside, non-melanoma skin cancer (NMSC) is not a big research issue in terms of human need. What is required for NMSC is early diagnosis—and that is what I would like to achieve with automated systems/cognitive prostheses. Melanoma remains a more serious issue, and I still remain puzzled by so much of its epidemiology (see a review by me here)
A guide for non experts is here