Differences between ethnic groups and differences between sexes illustrate why one species cannot predict drug and disease response for another. There are many differences between sexes and even more between species. If different sexes respond differently to drugs and disease then it only follows that different species will demonstrate even more diverse reactions.
Kim et al.:
Biological differences also affect the way men and women respond to medications and therapeutics. For example, women wake faster from sedation with anaesthetics such as propofol and nitrous oxide, recover more slowly and develop more side effects such as headaches, nausea and vomiting. Anaesthesiologists have learnt that dosage calculations must take into account a patient's sex and, in the case of women, the stage of their menstrual cycle.
Despite the obvious physical and physiological differences between men and women and the abundance of literature on the way sex influences metabolic activity, drugs are rarely prescribed with such variations in mind. A 2005 study of 300 new drug applications between 1995 and 2000 found that even those drugs that showed substantial differences in how they were absorbed, metabolized and excreted by men and women had no sex-specific dosage recommendations on their labels (1). This may be part of the reason why women are 1.5 times more likely to develop an adverse reaction to prescription drugs than men (2).
“Good, well-promulgated research into sex differences will benefit everyone.”
Another problem is the lack of awareness among doctors about the importance of sex-specific differences. For example, a 2005 survey showed that only one in five physicians was aware that more women than men die from cardiovascular disease each year. In 1996, the American Board of Internal Medicine recommended that “internists should be trained to provide comprehensive care to men and women based on an awareness of the influences of gender ... on an individual's health”. Yet an independent survey conducted a decade later concluded that few US medical schools had fully incorporated sex-based education into their curricula, or offered courses or clerkships in women's health. (3)
Differences between species or sexes are based, in part, on differences in gene expression. For example, Yang et al. studied gene expression profiles in male and female mice and showed that hundreds of genes are expressed differently (4). Mostertz et al. studied human genomes and revealed that differences in the activation of signalling pathways between men and women suffering from non-small-cell lung cancer (5). The gene expression differences between species are even more varied.
Zucker and Beery 2010:
In the 1990s, several surveys showed a significant sex bias in animal experiments in many biological disciplines, with researchers using a disproportionately high number of male animals. Given that animal models underpin the development of treatments for numerous diseases, this has serious implications for healthcare in women. So, to test whether or not the situation has improved, we recently conducted our own survey of almost 2,000 animal studies that were published in 2009 (ref. 1). We found a male bias in 8 out of 10 biological disciplines . . .
This revealed several alarming things. For example, diagnoses for anxiety and depression are more than twice as common in women than in men, but fewer than 45% of animal studies into these disorders apparently used females. Women have more strokes than men, with poorer functional outcomes, but only 38% of animal studies into strokes used females. Some thyroid diseases are seven to ten times more common in women, but only 52% of animal models used females. Other researchers have found that rodent studies into the effects of drugs on behaviour use males nearly exclusively, despite there being well-established differences in the ways men and women absorb and excrete drugs. (6) (Emphasis added.)
Zucker and Beery describe the situation adequately but I completely disagree with their assumption that animal models underpin the development of treatments for numerous diseases and therefore female animals should be used to study diseases of female humans. Species differences far outweigh the sex differences. The correct conclusion to draw from the fact that men and women respond differently to drugs and disease is that society should fund studies on women when searching for treatments for diseases affecting women.
There continues to be a notion among scientists and the media that there is a one to one correlation between animals and humans; that what happens in an animal is predictive for what will happen in humans. This notion is both dangerous and false.
1. G. D. Anderson, J Womens Health (Larchmt) 14, 19 (Jan-Feb, 2005).
2. Y. Zopf et al., European Journal of Clinical Pharmacology 64, 999 (2008).
3. A. M. Kim, C. M. Tingen, T. K. Woodruff, Nature 465, 688 (2010).
4. X. Yang et al., Genome Research 16, 995 (August 2006, 2006).
5. W. Mostertz et al., JAMA 303, 535 (February 10, 2010, 2010).
6. I. Zucker, A. K. Beery, Nature 465, 690.