Thinking about Everyone’s Health

My last post dealt with an almost trivial – although symptomatic – issue of everyday sexism. This one deals with something of rather larger magnitude, but one that is much lower beneath the radar than it warrants: health, and health differentials by gender.
Earlier this summer the Lancet ran a story headlined ‘Patients’ sex may impact efficacy of immunotherapy in cancer treatment’ – in other words, treating men and women as identical might not lead to the best outcomes.  This was the result of a large scale meta-analysis of other trials, and the article went on to specify that ‘individual trials likely cannot reliably show the interaction between sex and treatment efficacy’, since more than half the trials had a third or less women involved. By lumping men and women together in variable proportions, the trials were simply hard-pressed to come up with definitive answers about the consequences.

The issues of how gender impacts on different aspects of research design have been explored for many years by Stanford’s Londa Schiebinger, with a website (Gendered Innovations) detailing some of the case studies that show how badly the sexes may be served by poorly designed and ill thought-through research programmes. Needless to say when I say ‘sexes’ what I really mean is that too often experiments are only (or largely) carried out on or with males. I first met Londa back in 2010 and had the pleasure of meeting her again this week. What horrified me in our recent conversation was the sense that, in the UK at least, many things have not moved on at all since that first conversation. The problem is most acute in healthcare and clinical research, although there are issues in a range of areas and, increasingly, this is an issue in AI.

Although the UK has taken a pioneering approach to tackling issues surrounding gender in the scientific workforce through the Athena Swan Award scheme, an approach many other countries around the world are now developing and adopting including the USA, when it comes to incorporating gender issues into research design we seem to be dragging our feet. The NIH in the USA

‘expects that sex as a biological variable will be factored into research designs, analyses, and reporting in vertebrate animal and human studies.’

Furthermore that

‘more often than not, basic and preclinical biomedical research has focused on male animals and cells. An over-reliance on male animals and cells may obscure understanding of key sex influences on health processes and outcomes.’

These are strong words, but their impact and importance is clear. If you only carry out research – even on primary cells, let alone on human subjects – which look at the response or behaviour of the male, extrapolation to the female may be a dangerous and ill-informed thing to do. Researchers really need consciously to study both sexes; consciously to disaggregate studies by gender.

Horizon2020 likewise draws attention to the issues in its information for applicants, although in less strong words

‘you are invited to explore whether and how the gender dimension is relevant to your research. In the proposal template (section 1.3) you are asked “to describe how sex and/or gender analysis is taken into account in the project’s gender content.”’

However a quick search of the MRC and Wellcome guidelines throws up nothing equivalent. Google searches of either of these funders plus ‘gender’ simply throws up references to issues such as gender composition of teams, the gender pay gap and the importance they place on diversity. Hugely, hugely important issues – but utterly different.

How is it that the UK funders are not concerned about whether you are plating male or female cells? Given that in so much of our life we are told women, for instance as in my last post, can’t drive or pilot a plane and this is usually attributed to our hormones, it seems ironic that pre-clinical trials can be done without considering in detail whether (for instance) the sex hormones are getting in the way of a treatment protocol. Drugs and other interventions that benefit one sex may actively hinder the health of the other. I first became aware of this well over a decade ago during my time on the Governing Body of the Institute of Food Research: a presentation on the impact of soy protein in the diet indicated that the desirability was different for men (for whom there might be a beneficial impact on prostate cancer) and women, where the presence of the phyto-oestrogens in the soy might not be such good news. This position is supported by (for instance) a current statement from Australia, specifically highlighting that women who have already had breast cancer should avoid consuming high quantities of soy but there might indeed be a protective effect for men with respect to prostate cancer.

If you start searching on the web, plentiful stories come up from the clinical world pointing out that gender differences matter in risk and treatment (see Gender Differences in Cancer Susceptibility and Sex and Gender-related disparities in Colorectal Cancer Risk to get you started) and treatment (e.g. Gender Differences in the Effects of Cardiovascular Drugs). Those of an old enough generation will remember what happened when thalidomide was given to pregnant women; it may have had the potential to be a drug with all kinds of good outcomes on men and non-pregnant women, but the consequences for the developing embryo were profound and terrible although it was specifically seen as a drug to treat morning sickness. It would seem some of the lessons about ensuring that due thought is given to testing the relevant population and not some presumed ‘male by default’ patient have not been adequately learned. The implication of all these studies is that (women’s) lives and health are being put at unnecessary risk and that money may be being wasted.

In the UK we cannot afford to rest on our Athena Swan laurels (if such we have) without paying attention to the importance of incorporating gender into research methodologies. It may come as no surprise to know that where there are diverse teams carrying out the research, the question of gender is more likely to turn up in the design of the experiments. Another reason why we need more women entering the STEM professions to make sure women aren’t inadvertently shortchanged by the biomedical establishment in their experimental programmes – another fact I should perhaps raise at the upcoming discussion at NESTA of the Biomedical Bubble report. Researchers should remember that ‘Every Cell has a Sex’.

As a corollary, these issues do not just apply in the medical arena, although here they are manifest. There are many other fields where related problems arise. As a new entrant to the field, let us not forget the fact that AI has many pitfalls for those who don’t focus on gender. Some readers may remember a couple of years ago the revelation that training a bot using Twitter rapidly incorporates both misogynistic and racist terms into the lexicon. Londa Schiebinger has again highlighted this fact recently. Let us not permit another domain to grow in which gender gets ignored to everyone’s detriment.