By Armando Varela-Ramirez
For many decades, scientists have recognized that animals, tissues, and cells used in all facets of basic and clinical experimental biology respond differently depending on their gender origin.
In 2005 Jocelyn Kaiser highlighted the possibility that females and males may process some drugs differently. For instance, the aspirin-antithrombotic activity evaluated in multiple clinical trials showed that it is unevenly effective for both genders. Supporting this argument, Spranger et al. (1989) found that effective inhibition of platelet aggregation by aspirin depends on the presence of testosterone; thus the aspirin-antithrombotic effect is preferentially beneficial for men.
Currently in biomedical research, the numbers of female and male lab animals are imbalanced, with fewer female lab animals than male. In 2008 Constance Holden noted that female participants should be included in numbers similar to that of males in clinical trials funded by the U.S. National Institutes of Health (NIH), to reflect the disease prevalence or translate therapeutic recommendations in an ample population context. And in 2010 Irving Zucker et al. noted that “the male gender still dominates animal studies.” Some scientists argue, however, that female animals exhibit more instability due to their normal cyclical reproductive hormones. Based on this type of evidence, Allison M. Kim et at. (2010) suggested that sex bias in trials and treatment must end in order to benefit both women and men.
Last year, a report from an expert group headed by Londa Schiebinger issued the report Gendered Innovations: How Gender Analysis Contributes to Research. This was followed by a comment from Elizabeth Pollitzer asserting that cell sex matters in biological research. These two publications cited numerous reports endorsing gender differences between biological specimens in response to multiple stimuli and conditions.
These two articles inspired our initiative to explore this gender difference in the anticancer high-throughput-screening drug discovery arena. We studied fourteen cell lines, seven in each gender group, by exposing them to a collection of 81 novel drugs. Findings indicate that 79 of the 81 drugs were markedly more toxic for male-origin cells than for female-origin cells; therefore, the winner is … female cells!
Coincidentally, in May the NIH unveiled new policies to ensure that the research it funds considers both females and males in cell and animal studies, a policy change also reported in the New York Times. This policy change underscores that the gender of cells and organisms must be taken into account and should be equally balanced in biological research.