Newsletter

You are here

Scientific progress

11 - 09 - 2017

Gender: a variable to take into account in scientific research

 

In June 2015, the American National Institutes of Health (NIH) expressed their wish to have gender be considered as a variable as important as the weight or age of a person and for it to be taken into account just the same. This would concern in vitro, in vivo and clinical trial research. More specifically, how and why can we include the gender variable in experimental protocols? Elements of response.

 

  In June 2015, the American National Institutes of Health (NIH) announced the implementation of a new policy. It aims at making scientific research conducted on animals as well as humans consider gender as a variable, just as weight and age already are. As a matter of fact, the scientific community has understood over the years that men and women hold more biological differences than you may think. Therefore, not taking gender into account as a fully fledged variable comes down to risking skewed results.     An article to convince the scientific community     By qualifying gender as a fundamental biological variable, Terri Lynn Cornelison and Janine Austin Clayton, two researchers from NIH proved that the “the under-representation of female animals and female cells in preclinical research has led to a poorer understanding of female biological, physiological and pathophysiological mechanisms compared to males”, and went further in showing that “without data collected from females, it’s impossible to determine if the results obtained on male animals and on their cells apply also to female animals and their cells.” For years, the number of in vitro, in vivo and clinical research have been conducted this way - it was surely easier considering hormonal variations - almost exclusively on male organisms. As a result, certain medications were introduced to the market without being sufficiently tested on female organisms and women. Hence, female patients stated secondary effects that hadn’t been ascertained at all or just a little, during preclinical and clinical trials. According to the NIH, a report from multiple studies of scientific literature revealed that, for diseases predominantly affecting women, out of all the studies on animals including the gender variable, only 12% actually used female animals. In November 2016, two prominent women researchers thus wrote an open letter to the scientific community, which was published in the Journal of the American Medical Association (JAMA) to summon more transparency, and heighten scientists’ awareness to how important it is to take gender into account as an experimental variable.     Non-Negligible genetic and physiological differences     Terry Lynn Cornelison and Janine Austin Clayton explain in their article published by scientific journal Gender and the Genome that significant data supports the concept of gender as a biological “basis” variable. Thus, gene expression strongly differs according to gender. For example, amongst mice 72% of genes from the liver, 68% of genes from adipose tissue and 14% of cerebral genes are expressed differently if the subject is male or female. Amongst men, we are particularly aware that cardiovascular and metabolic risks differ according to gender. Furthermore, there are physiological differences because of hormonal variations (testosterone, oestrogen and progesterone amongst others), especially in the brain, therefore causing important implications on how cerebral vascular accident (CVA), neurodegenerative diseases and mental illnesses are treated.     Let’s take gender into account, but how?     Aware that it isn’t always clear to scientists how the inclusion of gender as a variable should affect their way of working, Terri Lynn Cornelison and Janine Austin Clayton wrote a couple of guidelines and recommendations to that effect.       Inter alia, they advise researchers to consider the influence of gender right at the design phase of the study and keep it in mind throughout the preparation of the questions they’ll be studying. Furthermore, they recommend researchers question existing scientific research on the ties between the chosen theme of the study and gender. Subsequently, males and females will obviously have to be incorporated in the experiments, and lead pilot studies such as the addition of hormonal treatment to tissue culture. Then comes the data analysis stage, where researchers will be weary of indicating if the data differs according to gender, and finally the interpretation of the results, where the gender variable should also appear. Regarding the studies where the experiences have only ever been carried out on males, the authors warn the scientific community that a solid justification is needed to explain the absence of testing on females. Studies on exclusively male organs (ex: prostate) would justify this kind of approach, as well as working on non-human primates, where the number of individuals is very limited. However, justifying the absence of both genders by the expenses that would ensue is obviously not an acceptable answer to the NIH.   On their website, the NIH, who finance many studies, summarise the different steps that researchers should take in 4Cs : Consider, Collect, Characterise and Communicate.   Hélène Bour