The visionary engineer who created "Body-on-a-Chip" technology to transform drug development
In the high-stakes world of drug development, failure has always been an expensive constant. For decades, the path to approving new medications has been plagued by a sobering reality: over 90% of drugs that show promise in animal studies fail in human trials3 . This staggering failure rate translates to wasted years and billions of dollars—but more importantly, it delays life-saving treatments from reaching patients who desperately need them.
One chemical engineer dared to ask a revolutionary question: What if we could predict human responses to drugs without relying on imperfect animal models? That engineer was Michael Shuler, a visionary professor whose "Body-on-a-Chip" technology may fundamentally change how we develop medicines3 . His work represents a paradigm shift in biomedical research, creating miniature human mimics that stand to accelerate drug discovery while potentially reducing our dependence on animal testing.
The traditional drug development process is notoriously inefficient. Pharmaceutical companies typically spend 15 years and $3 billion to bring a single drug to market, with most resources devoted to compounds that ultimately fail8 . The central problem lies in the translation between species: a drug that works in mice often doesn't work in humans, and a drug safe for rabbits might be dangerous for people.
"Only about 10% of the drugs that enter human clinical trials come out as approved products. I talked to major pharmaceutical firms and something like two, five, six percent of animal models predict what's going to happen in humans"3
Shuler's personal experience also fueled his determination. While developing his ideas, he was caring for his daughter with Down syndrome, who faced heightened risks for certain diseases and potential unique drug responses due to her genetic makeup. "She was really the motivating factor behind pursuing this career path," Shuler acknowledged8 .
In 1989, Shuler conceived a radical approach: creating a miniature human model that could simulate how drugs travel through our bodies3 . The concept was grounded in physiologically based pharmacokinetic (PBPK) modeling—computer models that represent different human organs as interconnected compartments3 . But Shuler took this digital concept into the physical world.
The breakthrough came in 1998 when Shuler collaborated with Greg Baxter, a specialist in microfluidics—the science of manipulating fluids through tiny channels5 . Together, they transformed Shuler's macroscopic system into a revolutionary microscale device.
Their creation was extraordinary: a silicon chip about the size of a thumbnail, etched with microscopic trenches that served as artificial blood vessels5 . Different areas represented various organs—liver, lungs, fat, and others—each lined with living human cells. The sizes and layouts of these compartments were carefully engineered to mimic the fluid flows and chemical exposures cells experience in actual organs5 .
Idea of using interconnected cell cultures for drug testing3
Move to microscale systems using microfluidics3
Published three papers demonstrating functional multi-organ chip3
Commercialization of Human-on-a-Chip technology4
Improved organ models and expanded applications1
One early experiment brilliantly demonstrated the chip's potential. Shuler's team tested naphthalene—the active ingredient in mothballs—which causes lung damage in humans but not in standard cell cultures5 . The reason? Naphthalene itself isn't toxic, but becomes dangerous when transformed by the liver into reactive metabolites.
When Shuler introduced naphthalene into the chip's circulatory system, the "liver" compartment broke it down into those same toxic metabolites. These then traveled to the "lung" compartment, where they caused significant damage—mimicking exactly what happens in the human body but what standard tests had missed5 . This experiment demonstrated how Body-on-a-Chip could reveal hidden drug toxicities that conventional methods would miss.
| Testing Method | Liver Metabolite Formation | Lung Toxicity Detected | Predicts Human Response |
|---|---|---|---|
| Standard Lung Cell Test | No | No | No |
| Animal Testing | Yes | Varies by species | Inconsistent |
| Body-on-a-Chip | Yes | Yes | Yes |
Creating these sophisticated systems requires specialized materials and biological components. Here are the key elements researchers use to build functioning Body-on-a-Chip devices:
Serves as physical platform with microscopic channels
Silicon chips with etched trenches5
Provide biological functionality for each organ
Hepatocytes (liver), cardiomyocytes (heart), neurons (brain)3
Nutrient-rich fluid mimicking blood
Pinkish fluid containing nutrients, oxygen, test compounds5
Monitor cell responses and system conditions
Dissolved oxygen sensors, electrical activity monitors3
Michael Shuler's impact extends far beyond his laboratory. After joining Cornell University in 1974, he became the Samuel B. Eckert Professor of Engineering and founded the Department of Biomedical Engineering1 . His contributions have earned him some of the highest honors in science, including election to the National Academy of Engineering (1989) and the American Academy of Arts and Sciences (1996)1 .
True to his innovative spirit, Shuler continues to push the boundaries even after entering emeritus status at Cornell in 20181 . His legacy encompasses not only specific technologies but a fundamental shift in how we approach drug development.
Michael Shuler's work demonstrates how engineering principles can transform biological research. His Body-on-a-Chip technology offers a powerful alternative to traditional drug testing methods—one that could make medicine safer, more effective, and more personalized.
As these systems continue to evolve, they may eventually incorporate cells from individual patients, creating personalized chips that predict how specific people will respond to treatments3 . This represents the ultimate promise of Shuler's vision: medical care tailored to our unique biological makeup, delivered faster than ever before.
The journey from concept to impact required what Shuler identifies as three key qualities: "Confidence. Flexibility. Persistence."8 These traits enabled him to pursue an idea others thought impossible, and in doing so, he has given us a remarkable new window into human biology—built on silicon, but alive with possibility.