Inferior: How Science Got Women Wrong – and the New Research That’s Rewriting The Story. Angela Saini
the social sciences Sarah Richardson questions the idea that every cell in the body is intrinsically different depending on someone’s sex, and that this leads to the gaps we see between women and men. ‘It is a widely shared consensus among social scientists that genomics is transforming social relations,’ she writes. ‘The same may be said of genetic research on sex and gender.’ Arthur Arnold, for instance, describes the effect of sex-biasing factors in our genes as a ‘sexome’ (like the genome, but for sex difference). ‘You can think of the cell as this kind of big network,’ he tells me. ‘Males and females are different because they have different levels of sex-biasing factors, and they pull on the network at various points.’ This idea suggests that even though the sex chromosomes are only one of the twenty-three pairs of chromosomes we have, their effects are wide-ranging.
Richardson warns against this focus on genetics as an umbrella explanation for sex difference because of how it blurs away the effects of society and culture, as well as other biological factors. Age, weight and race, for example, are known to have a huge impact on health. Hormones are important too. She notes that the body of genetic evidence when it comes to sex differences paints an overwhelming picture of similarity. Indeed, Arnold himself admits to me that his idea of the sexome is ‘more of an evocative phrase’ than a solid theory backed up by research.
The debate around just how deep the dividing line is between women and men continues to rage inside the scientific community. It has been fuelled most recently by anger over exactly the opposite problem: the habit in medical research of leaving women out of tests for new drugs, because their bodies are thought to be so similar to men’s.
‘It’s much cheaper to study one sex.’
‘Let’s face it, everyone in the biomedical community has spent their lives studying one sex or the other. And it’s usually males,’ says Steven Austad. When it comes to the basic machinery of our bodies, scientists have often assumed that studying one sex is as good as studying the other.
‘I one time looked into the rodent literature on dietary restrictions,’ recounts Austad. ‘There are hundreds and hundreds of studies. And I found that there was only a handful that included both sexes. And to me that just typifies the fact that people seem to be willing to extrapolate from one sex and just assume that everything they find is going to be true in the other sex.’
In 2011 health researcher Annaliese Beery at the University of California, San Francisco, and biologist Irving Zucker at the University of California, Berkeley, published a study looking into sex biases in animal research in one sample year: 2009. Of the ten scientific fields they investigated, eight showed a male bias. In pharmacology, the study of medical drugs, the articles reporting only on males outnumbered those reporting only on females by five to one. In physiology, which explores how our bodies work, it was almost four to one.
It’s an issue that runs through other corners of science too. In research on the evolution of genitals (parts of the body we know for certain are different between the sexes), scientists have also leaned towards males. In 2014 biologists at Humboldt University in Berlin and Macquarie University in Sydney analysed more than three hundred papers published between 1989 and 2013 that covered the evolution of genitalia. They found that almost half looked only at the males of the species, while just 8 per cent looked only at females. One reporter, Elizabeth Gibney, described it as ‘the case of the missing vaginas’.
When it comes to health research, the issue is more complicated than simple bias. Until around 1990, it was common for medical trials to be carried out almost exclusively on men. There were some good reasons for this. ‘You don’t want to give the experimental drug to a pregnant woman, and you don’t want to give the experimental drug to a woman who doesn’t know she’s pregnant but actually is,’ says Arthur Arnold. The terrible legacy of women being given thalidomide for morning sickness in the 1950s proved to scientists how careful they need to be before giving drugs to expectant mothers. Thousands of children were born with disabilities before thalidomide was taken off the market.
‘You take women of reproductive age off the table for the experiment, which takes out a huge chunk of them,’ continues Arnold. A woman’s fluctuating hormone levels might also affect how she responds to a drug. Men’s hormone levels are more consistent. ‘It’s much cheaper to study one sex. So if you’re going to choose one sex, most people avoid females because they have these messy hormones … So people migrate to the study of males. In some disciplines it really is an embarrassing male bias.’
This tendency to focus on males, researchers now realise, may have harmed women’s health. ‘Although there were some reasons to avoid doing experiments on women, it had the unwanted effect of producing much more information about how to treat men than women,’ Arnold explains. A 2010 book on the progress in tackling women’s health problems, co-written by the Committee on Women’s Health Research, which advises the National Institutes of Health (NIH) in the USA, notes that autoimmune diseases – which affect far more women than men – remain less well understood than some other conditions: ‘Despite their prevalence and morbidity, little progress has been made toward a better understanding of those conditions, identifying risk factors, or developing a cure.’
Another problem is that women may respond differently from men to certain drugs. Medical researchers in the mid-twentieth century often assumed this wasn’t a problem. ‘There was a notion that women were more like little men. There was a notion that if this treatment works in men, it will work on women,’ says Janine Clayton, director of the Office of Research on Women’s Health at the NIH in Washington, DC, which funds the vast majority of American health research.
We now know this isn’t necessarily true. In 2001, New Zealand-based dermatologist Marius Rademaker estimated that women are around one and a half times as likely to develop an adverse reaction to a drug as men. In 2000 the United States Government Accountability Office looked at the ten prescription drugs withdrawn from the market since 1997 by the US Food and Drug Administration. Studying reported cases of adverse effects, it found that eight posed greater health risks to women than to men. The withdrawn drugs included two appetite suppressants, two antihistamines and one for diabetes. Four of these were simply given to many more women than men, but the other four showed this effect even when men took them in more equal numbers.
‘You have to be concerned that there were serious enough side effects, not just a minor side effect but a serious enough adverse effect that resulted in the drug being withdrawn. I think that tells us that we’re only just seeing the tip of the iceberg of this issue,’ Janine Clayton tells me. This has become a huge concern for women’s health activists, particularly in the United States, and has been one of the mandates of the Office of Research on Women’s Health since 1990.
‘As clinicians, we know very well that diseases show up differently in men and women. Every day, men and women present to the emergency room with different symptoms with the same condition,’ says Clayton. ‘So heart attacks, for example, have different symptoms. Our research has shown that women who are going to have a myocardial infarction [heart attack] are more likely to have symptoms like insomnia, increasing fatigue, pain anywhere in the head all the way down to the chest, the weeks before they have a heart attack. Whereas men are less likely to have those symptoms, and are more likely to present with the classic crushing chest pain.’ Given differences like these, she believes that excluding them from drug trials for so many years must have affected women’s health. ‘It’s certainly a real possibility that the reason there are more adverse events in women than in men is because the whole process of drug discovery is tremendously biased towards the male,’ agrees Kathryn Sandberg.
Again, though, this line of thinking risks drawing divisions between women and men, when the picture of disease is far more complicated. While there’s a clear benefit to better understanding women’s bodies and having drugs that suit both sexes, the emphasis on sex difference starts to make it seem as though women’s bodies are from Venus and men’s are from Mars. ‘Given the well-documented history of methodological problems with sex difference research, as well as harmful abuses of sex difference claims by those who would limit women’s opportunities, it is remarkable to find women’s health activists promoting, with little qualification, sex-based biology’s expansive