Over the past decades, the efficiency of the drug development process has declined rapidly – fewer and fewer drugs make it to market. Alarmingly, more than half of all new drug candidates fail when they are first tested in humans, either because they cause previously undetected toxic side-effects, or because they simply don’t work.
It is clear that for the drug development process to become more efficient, we need better ways to predict what will work in humans and what will not work. Similarly, there is a big societal need to be able to accurately predict which substances in our environment, our industrial and consumer products, and in our food, are healthy or toxic for humans.
In short: we need predictive models of the human body.
Predictive Models and Human Complexity
The development of predictive models is a grand challenge in science and engineering. How will we capture the complexity of the human body? Many substances are taken up, degraded and excreted by various organs, and a substance showing toxicity for one tissue type may not predict the response of the human body as a whole. And how will we address differences between people? A drug that may work for people of certain ages, of a certain gender, or for people with a specific genetic background, may not work or even be toxic for others.
Animal models, computational models, genetic screening. They all have added value in predicting the effects of substances on health and safety in humans, but none of them are well-suited to capture both the complexity of human tissues and the full diversity of individuals in a population. That is why researchers all across the world are working on the development of stem cell-based organs-on-chips.
Organs-on-chips are realistic laboratory models of human tissues and organs, based on the culture of human stem cell-derived tissues in microfluidic devices. Nanosensors and microactuators are integrated in the devices and generate a dynamic and realistic cell culture microenvironment. As a result of this technical-biological integration, organs-on-chips exhibit specific functions that are similar to those found in human organs.
Organs-on-Chips at the MIRA Institute
At the MIRA Institute, we develop organs-on-chips to investigate the safety of health products and to understand the mechanisms of disease. We hope that in the future organs-on-chips will find widespread use in biomedical science and will progressively replace animal models as the mainstay in efficacy and toxicity testing.