Drug development and preclinical/clinical research have traditionally focused more on the male physiology and less on the female one. For example, more men are enrolled in clinical trials than women are and more male animals are used in biomedical research. This can be seen when looking at Figure 1.
While such bias in research may not seem relevant for drug development, it actually leads to results that are strongly biased towards half of the world’s population. In extreme cases, the outcome of this bias leads to drugs that are either ineffective or — worse— toxic for women. Each failed clinical trial costs several million dollars to pharmaceutical companies and research institutes.
Additionally, according to PETA, 90% of animal approved clinical trials fail in humans, which only results in more unnecessary lost money. What if we could test drugs without using animals? Or create clinical trials that aren’t biased towards the male physiology?
When products are designed based on the average male, there is a risk for harm towards women. For example, historically, data has been taken from male drivers. They have been overrepresented in traffic data and seatbelts and airbags have been designed and evaluated for the typical male occupant. According to the US National Library of Medicine at National Institute of Health, when the data from automotive crashes in the United States was analyzed between male and female from 1998 and 2008, it was shown that a belt-restrained female driver was 47% more likely to sustain a severe injury than a male driver. These results are shocking.
Beyond automotive safety systems, the importance of equal testing for both male and female is imperative. Another example is lung disease. This can be seen in Figure 2. Male and female lung size, hormone levels, and genetics are only a small sample of the drastic differences in their biologies. Biological sex can change the prevalence, severity, and course of human illness.
According to Harvard University, “if the standard dose of a drug is calculated for a male with average body size and metabolism, giving females that same dose might lead to a higher rate of accidental overdose.”
Women carry the XX chromosomes while men the XY chromosomes. This means that women and men carry different genes. The different gene expression is reflected in a different production of hormones that influence our physiology and behaviors. It doesn’t make sense to develop drugs based on one sex.
Ignoring sex and gender differences across the research lifecycle has the potential to compromise the accuracy of science, resulting in detrimental health outcomes, increased health costs, and it has implications beyond health, including social services and aged care.
If sickness varies depending on sex, treatment should also be different depending on sex. It’s obvious these issues require the urgent need for more physiologically relevant models of human organs.
This is where organ-on-a-chip comes in.
An organ-on-a-chip (OoC) is a 3D cell culture chip that replicates how a certain organ works. It’s best to think of it as a type of artificial mini-organ that lets researchers study how the body works without using animals or people.
The engineered individual silicone modules are clear and flexible, only about the size of a computer memory chip. They contain specific human cells that can replicate the functions and workings of a given organ. For example, kidney-on-a-chip, lung-on-a-chip, etc. OoC devices can be used to understand drug effects and study both male and female physiology equally. Not only that, they’re significantly more cost-efficient and more accurate than animal testing.
This sounds like an advanced device from the future, but OoC devices are already here. They’ve earned the interest and attention of scientists hoping to fix the broken drug discovery and development process.
How does it work?
Fluid runs through tiny, thin, hollow channels that interconnect various cells and carefully expose them to drug treatments given by researchers. Mechanical forces can be used to mimic the physical movements of living organs, such as breathing motions for the lung-on-a-chip. The best part is that these chips are completely translucent — they let us see what we haven’t before. They give us a chance to see the inner workings of human organs.
The only major drawback of using OoC devices is the fact that they can’t yet copy the way a given organ is affected by other organs that aren’t close to them in the human body.
The cells used in OoC devices are either 1) bought from a cell bank, 2) primary cells from a patient biopsy, or 3) immortalized cells.
OoC devices are the perfect candidate to study sex differences in biomedical research and drug development.
To unlock the potential of OoC in drug discovery and disease modeling, it’s key that we raise as much awareness as possible. The best targets are labs that might be using such technologies to have a complete and unbiased understanding of their research topic, or to assess the effect that sex can have on drugs.
A team of women and I competed in the Women’s Brain Project Hackathon and are researching the potential for organ-on-a-chip to decrease gender bias in the healthcare industry.
To assess and create awareness on sex and gender bias we collected data from two groups: academic and industrial experts, and the general public. For people involved in private or public research, industries and academics, we published an 18-question-survey titled, “Sex and gender bias in preclinical and clinical research on women’s health.”
We designed an informative one-page fact sheet to summarize the purpose of our investigation through the expert-survey. It reports some context with examples of gender bias in drug development and diseases studies, and proposes OoC as a possible solution to avoid sex bias in preclinical research. The fact sheet was sent to our expert audience along with the survey.
The general audience was addressed in a similar way by proposing an 8-question-survey titled, “Organ-on-a-chip survey.” A short informative blurb was included in the non-expert survey to explain OoC. This was advertised via social media platforms in order for the survey to reach a more wide and varied audience.
In both surveys, the age range was organized in three groups: under 18, between 18–40, and over 40 years old. Organization and analysis of collected data had the main purpose to evaluate the percentage of people who were aware of gender bias in medicine and drug development.
Overall we reached 143 people in 15 different countries.
General Audience Survey Results
The non-expert survey found that 74% of people believe there is a gender bias in healthcare, whereas 25% do not. The 25% was 74% male. The lack of awareness is blatantly obvious.
Additionally, it was found that 92.4% of participants responded positively when asked if they were interested in learning more about the potential for organ-on-a-chip in the healthcare industry.
Expert Survey Results
We believe that the 40% of people that answered “maybe” would change their mind if offered more data about this.
When asked, “Which organ-on-a-chip would you invest in to assess drug safety in preclinical studies?” liver, heart and brain-on-a-chip were most popular.
We have targeted both a public and an expert audience and we were impressed by the interest that the topic generated. Among the expert group, 50% of the participants do not record the sex of their animal or
cell models. We hope that our factsheet document and the links shared with the survey, generated some additional thinking and the participants will from now on take in consideration the sex-variant in their studies. Among
the public group, many participants were also under 18 years old. It is crucial for the young population to get to know the presence of sex-bias in medicine and its combined danger.
Sex and gender should be considered throughout the research process, from the design of research questions to the interpretation of study results, with segregation of results by sex or gender. That vision was shared by the expert community. We believe there is a need to guide researchers and companies developing organ-on-a-chip solutions to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine. This will benefit men’s and women’s health alike. Researchers and organ-on-chip developers should not repeat the mistakes and the bias already present in our drug discovery and toxicology study.
With so many individuals responding positively to our work and saying they are interested in the potential of OoC, this should be deemed a a success. From now on, our team will be acting as role models to make sure biases will be corrected, or better — not created. We are proud to act as ambassadors of the Women’s Brain Project and we believe the community we reached will support new ways of thinking.