Sometimes, going small can make a tremendous difference. That's the theory, at least, behind AAAS Fellow Kevin Healy's bioengineering innovations.
The University of California, Berkeley, bioengineering professor is developing a drug-testing tool to make the discovery of new medicines faster and cheaper. It has several names, but they all reveal its diminutive scale.
Tissue-on-a-chip. Micro-physiological system. Or micro-organos, as Healy terms it.
For the past three years, Healy and his team have been researching the smallest tissue unit that can be used to accurately reflect how the heart will respond to a drug. The goal is to use this mini platform to quickly screen out drugs that are non-starters and avoid costly clinical trials.
Currently, it costs, on average, $6 billion to develop a new medicine. Much of the time and expense goes into testing the drug's side effects, which often show up in the heart or liver. In 2012, the National Institutes for Health funded Healy and 16 other investigators to develop tissue chips. NIH plans to commit $70 million over five years to the endeavor, if funds are available.
Just how small is this tissue chip?
Healy's design is a gel block about the size of a Jolly Rancher, mounted on a glass microscope slide. At the bottom of the block is a test chamber the width of a few human hairs. Several thousand heart cells are loaded into the chamber through a pinhole. The team can observe how the beating cells change their rhythm or movement in response to drugs delivered through microports along either side of the chamber.
This system is a dramatic departure from how drugs currently are tested on animal cells in Petri dishes. Most importantly, it uses human, rather than animal, cells. And it's a system that is more true-to-life because it is three dimensional—the cells are lined up just as they would be in the heart, with the microports acting like blood vessels delivering nutrients to the heart.
"We have precise control over how the drug is exposed to the cells," Healy noted.
The system appears promising. Micro-organos exposed to drugs had reactions that were much closer to real clinical trial results than traditional test methods, Healy said.
Ultimately, the researchers want to connect chips with different tissues—lung, liver, heart and fat—to test how a drug will affect the whole interactive system.
"Before now, nobody's ever put all these tissues on the same platform," Healy said.
One day, if they are approved Food and Drug Administration, the tissue chips could be used by drug companies to help screen medicines.
The trick now is to figure out the correct ratio of chips with different tissue types, as well as the best fluid to mimic blood delivering the drug to cells.
Healy, 52, is particularly excited about the potential for the tests to be patient-specific because of the type of cells they are using. Pluripotent stem cells (iPS) are taken from an adult that are reprogrammed back to the original stem-cell state and then directed to become other tissues like heart or liver.
If iPS cells are taken from one patient and turned into several different tissues, the team suspects they can observe how a drug will affect that patient's whole system. It might also reveal how a disease like diabetes would respond to treatment.
Healy has always had an interest in biology and physiology. As a teen growing up on Long Island, NY, he lifeguarded during the summers and volunteered in hospitals.
He considered going to medical school, but decided he'd rather design new tools for doctors.
Excelling in mathematics, physics and chemistry, Healy was urged to study chemical engineering by his University of Rochester advisors. He had to decide before his first day of freshman year since the required courses were so regimented.
"I didn't choose chemical engineering, it chose me," he said.
But unlike many chemical engineers, Healy had no interest in working for the oil industry. So he headed to the University of Pennsylvania to earn a Ph.D. in bioengineering. There, he researched surface coatings on artificial devices to promote integration with the body. He also played ultimate Frisbee and his team won the 1985 national championships.
Healy spent a decade teaching at Northwestern University before coming to UC-Berkeley in 2000. Now, as chair of the bioengineering department, Healy spends more of his time in a sharp navy blazer than a lab coat. However, he seems genuinely excited to help the department grow through fundraising, developing multi-disciplinary initiatives, and developing a larger, earthquake-proof building.
Sometimes, he notes, work spills over into his personal life.
Once, a student gave some heart cells too much caffeine and they stopped beating. Healy told the student to put the cells back in the incubator and two days later they started beating again.
After that episode, Healy, a regular coffee drinker, said "O.K. I think it's time to switch to half decaf.\