Message from the Director
The Differences Between the Sexes
Huntington F. Willard, PhD
There has been much discussion of late — from Harvard President Larry Summers to New York Times columnist Maureen Dowd to even the comics page — about 'innate differences' between males and females and what they might mean. The debates have ranged from issues of great social and academic significance (hypothesized sex differences in job aptitude or performance) to the ridiculous ("men are simpletons…women are unpredictably complex"). But to date, few of the serious discussions have centered on what should be at the top of the list: men and women differ dramatically in terms of the diseases they suffer from.
"The differences between the sexes are everywhere, of course. Men and women have well-documented differences in behavior, cognition and perception."The differences between the sexes are everywhere, of course. Men and women have well-documented differences in behavior, cognition and perception. Men and women have "their own" diseases, like prostate cancer or, as described in this issue of GenomeLIFE, ovarian cancer. Breast cancer is common in women and rare (though not unheard of) in men. Men and women differ in their response to therapeutic agents; women experience more adverse reactions to vaccines. Females have higher incidences of osteoporosis, obesity, depression, type II diabetes, and a host of autoimmune diseases. Males have higher incidences of autism, hypertension, alcoholism and Hirschsprung disease and increased mortality from melanoma. Recognition of sex differences in human health contributed to the development of a variety of women's health initiatives and the field of gender-based medicine. The NIH's Office of Research on Women's Health has an annual budget of over $41 million. The Institute of Medicine issued a report in 2001 subtitled "Does Sex Matter?" and called for significantly increased attention paid to the biological basis for sex differences.
What are the causes for these differences? A substantial body of biomedical research (and an equally substantial body of psychological and sociological research) has pointed to both hormonal and cultural effects. But the data aren't as clear-cut as one might like. Much like the study of race in our society, consideration of the biological basis for sex differences has strong social overtones that can drown out all but the most compelling data. It is difficult for scientists (not to mention editorial columnists) to maintain an air of objectivity and to separate data from interpretation or experiment from personal agenda.
Enter the genome. Frequently overlooked (perhaps because it's so obvious) is the fact that males and females have different genomes. Males have a Y chromosome with about 75 genes that do not exist in females. Females have two copies of the X chromosome and thus two copies of its 1000 genes, about 25% of which are expressed — at least some of the time — from the second, otherwise inactivated X. That means that some 300 genes — at least 1% of the total number of genes in our genome – are characteristically different (present or absent or expressed at different levels) in males and females. With complex networks of interacting gene products in different tissues, this means that an even higher proportion of biochemical or developmental pathways will differ between the sexes. Given this reality, it sometimes seems to me that we should turn the question around: can anyone imagine that men and women would not be different?
This doesn't mean that the genome accounts for everything we see that differs between two individuals who happen to be of opposite sex. Certainly not. The roles of hormones and cultural upbringing are impossible to ignore. But it does suggest that one should begin to take seriously the role of genes and genome variation — on the sex chromosomes especially — as potential determinants or modifiers of health in men and women.
It will not be easy to design the types of studies necessary to examine the possible effect(s) of one or more X genes on health, especially in women who show extreme variability in the numbers and levels of such genes expressed from their second X. But the impact of diseases that disproportionately affect females is too great not to pursue every lead. Women's health is everyone's problem and a too long neglected one.
Huntington F. Willard
Director