Human-Organs-on-Chips are microfluidic cell culture microchips lined with living human cells that simulate the functions of human organs, including the lung, intestine, kidney, skin, bone marrow and blood-brain barrier. Engineered by Dr. Donald Ingber and Wyss Institute researchers in 2010, these microchips have the potential to revolutionize drug development, disease modeling, and personalized medicine. But they may also revolutionize courtroom toxicology testimony.
Human-Organs-on-Chips are three-dimensional human tissue models which will reduce the reliance of traditional animal models and cell cultures. The result is a faster, more accurate, and realistic high-throughput screen which can be used to predict whether a candidate compound is safe or toxic in humans.
In the above video, Dr. Donald Ingber and Wyss Institute researchers discuss Human-Organs-on-Chips (Introduction to human-organs-on-chips).
The “Human-Body-on-a-Chip” will rapidly assess systemic responses to potential environmental insults, new drug candidates, and provide higher-level information on drug safety and efficacy. Imagine if an opposing expert was prepared to testify that your client’s drug, chemical, or product caused an adverse health effect in a specific organ system on a computer chip. Specifically, this technology could theoretically give an opposing expert the ability to demonstrate that living organ cells responded adversely to a drug or chemical at issue in the case. In contrast, imagine if you were able to demonstrate that these human cellular systems – functioning exactly the same as in a living, human being – were not adversely affected by your client’s drug or chemical.
According to the National Institute of Health, approximately 30 percent of drug candidates have failed in human clinical trials because they were found to be toxic despite promising pre-clinical studies in animal models. Another 60 percent fail due to lack of efficacy in humans. Human-Organs-on-Chips were designed to address these issues.
To date, Human-Organs-on-Chips do not exist for environmental toxicity screening. However, they have the potential to stimulate the overall physiological response to toxicants. Beginning with the lung chip (inhalation) or gut chip (ingestion), the multi-system Body-on-Chips network may be able to simulate the time-course and adverse event pathway of bioactivation, metabolism, and transport of toxic agents to and from various organs. This technology will therefore provide an as-yet nonexistent tool to interrogate these systems in isolation, but in the context of normal physiological functioning.
The following animation from Wyss Institute demonstrates how Human-Organs-on-Chips and Body-on-Chips work (Human-Organs-on-Chips).
Although making great strides, Dr. Ingber acknowledges that Human-Organs-on-Chips technology is “still in its infancy” and requires more validation to predict human responses using well-characterized drugs or chemical exposures. Key challenges include identifying the source of human cells, reproducing the complex architecture of human organs in miniature, and linking them to correctly replicate organ interactions. Critics counter that this technology will not capture crucial aspects of living, whole body physiology.
For the present, Human-Organs-on-Chips provide an innovative alternative to traditional screening models, but their potential to predict clinical responses in humans could have profound effects on drug discovery, personalized medicine, and environmental toxicology testing in the future.
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