6 minute read
‘Human-on-a-Chip’
Hesperos Replicates Inter-Connected Organs Systems to Reduce Animal Testing
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BY MEAGHAN BRANHAM
Photography by Julie Fletcher
How many human organs can you fit in your hand? It seems a gruesome question at first, one you’ve (hopefully) never thought about.
But Dr. James “J” Hickman and Mike Shuler have thought about it — in fact, they’ve dedicated their careers to creating a technology that allows a system of human organs, from the heart to the lungs to neurons and more, to be reproduced on microchips that can be inter-connected, and it all can fit right in the palm of your hand. Their creation could be the answer to an ongoing crisis in the world of drug and chemical testing.
The pioneers of this “human-on-a-chip” technology have been commercially developing the groundbreaking devices in our own backyard since 2014 out of the Orlando-based facility of Hesperos Inc., founded by Hickman and Shuler. The chips are poised to eliminate many of the issues that make current pharmaceutical, cosmetic and food testing so difficult: high expense with low success rates, inhumane and inefficient animal testing, and limited opportunity for testing in human trials.
“The classic drug development pipeline relies heavily on animal models, and we now know that nine out of 10 drugs that proved safe and effective in animals fail to translate to human studies,” Hickman says. “So that's where this technology slots right in.”
Shuler, who has a daughter with Down syndrome, describes the difficulty that comes even with traditional human clinical trials: “One of the caveats of drug development is that different people react differently to any particular drug. For somebody who’s not in the ‘typical’ population, physicians often have trouble
— Dr. James "J" Hickman deciding how to prescribe drugs. So this technology allows us not only to look at rare diseases, but also to build models that are more specific to individual members of the population for such diseases as cancer.”
The chips themselves, in their simplest terms, are tiny re-creations of human organs. These surrogates are designed to mimic the function of their human counterparts and are flexible enough to re-create breathing motions, undergo muscle contractions, and handle many other movements particular to the function of that organ.
A patient’s cells can be introduced to the environment of the chip, which is specific for each organ “mimic.” The chips can be connected as well, as they are in Hesperos’ two-, three- and four-organ platforms. Once ready, medicines, chemicals, patient sera, and whatever else might need to be tested can be introduced to the chip or system of chips, allowing scientists to observe how they interact with these human organ mimics, record the effects on the organs, and replicate how those effects would appear to a doctor first seeing a patient in a clinical setting.
“We can look at the beat frequency, for instance, and conduction velocity and force of the heart,” Hickman says. “For the brain, where we can look at the processing of information, we can look at how motor neurons connect the muscle and how those units work.”
A Meeting of the Minds
Thirty years ago, as a faculty member at Cornell University since 1974, Shuler was honing in on the concept of “artificial animals,” work that would be the basis for the “body on a chip.” In 1998, he shifted his focus to the human body, wondering if by doing so he could steer researchers away from animal testing by providing a more accurate re-creation of the human body.
Meanwhile, Hickman graduated from Massachusetts Institute of Technology (MIT) in 1990 and was building on the work in nanoscience he spearheaded there. Applying it to biology, Hickman zeroed in on the clinical readouts that are tied to physiological, mechanical and electrical reactions. For instance, by placing human neurons on small pieces of metal called electrodes, he could see when those neurons started or stopped firing in response to a nerve agent.
The two met at talks and conferences in their respective fields over the years, but it wasn’t until 2009 that they started to think about what their work might look like together: a human body on a chip that would recreate multi-organ systems and could show researchers the immediate and long-term functional effects of drugs. Hesperos was starting to take shape.
When circumstances pushed them to find new avenues of development and income beyond their academic grants, they adapted yet again.
“There came a point at which we thought we could continue this research in our academic positions, then a grant, unexpectedly, was discontinued. The National Institutes of Health suggested there were other avenues for additional funding, but only if we formed a company and applied for funding through things like Small Business Innovation Research (SBIR) grants,” Hickman says. “We used our own money to start the company. The two of us have never taken a salary. We’ve written grants and have commercial contracts, but we still to this date have not taken any outside investments. We’re a 100% employeeowned company.”
Community partnerships and initiatives, like those with the University of Central Florida (UCF) Business Incubation Program and the Florida High Tech Corridor Council, helped keep the revolutionary project going.
“We were able to start it up for very low cost and low overhead, allowing us to focus the money we had on our employees and research,” Hickman says. In the initial stages, the two found that their many public presentations — probably 20 a year each, Hickman guesses — were all they needed to get the word out. “That was pretty much our marketing for the first two or three years.”
Another partnership, Hickman’s relationship with John Reed, head of research at Swiss multinational pharmaceuticals and diagnostics company Roche at that time, would lead to their first commercial contracts.
“Mike and I had seen a particular pattern through the years: Technologies come up, people oversell them, and they just collapse upon themselves and never really get integrated the way they could have,” Hickman says. “We figured if we could actually start the company, have principles in place to get the technology out there to help people, and then maintain those principles, we could really change how drug discovery gets done.”
Changing the Infrastructure
Nearly 10 years into that mission, Hesperos has made a name for itself as one of the only companies in the world offering the “human-on-a-chip” model. Partnerships with AstraZeneca, Roche and more have led to research on treatments for everything from autoimmune diseases to Alzheimer’s Disease to cancer.
“This can significantly reduce the development timeline required to get a new therapeutic to a patient,” says Nate Post, the company’s director of business operations. “The platform gives researchers unprecedented visibility into specific disease states and how the human body will respond to treatment — something that previously could only be determined in clinical trials. This is particularly exciting for patients battling rare diseases, since many have no existing treatment options.”
In a world with only 400 active research programs working on the 7,700 known rare diseases, that ability is a powerful thing. Right now, according to the team, pharmaceutical spending for larger-scale conditions and diseases is at about $2 billion per drug, a number derived from dividing the overall R&D spending by the number of drugs approved that year, usually with a success rate of about 10%.
“If we can double that to 20%,” Hickman adds, “then we have the potential to not only increase the number of drugs tested, but to decrease the cost per drug by around a billion dollars.”
Beyond pharmaceuticals, Shuler says, the possibilities expand even further: “This technology applies to the whole range of toxicology: foods, cosmetics, chemicals. And it has an important role to play.”
