Harvard Scientists Invented a Biohybrid Fish That Swims Using Human Heart Cells

Here’s your dose of weird science for today: Harvard University researchers have invented a new “biohybrid” fish that uses human heart cells to emulate the physics of a pumping heart to autonomously swim.

Yes, it all sounds a bit Frankensteinian, but it’s all in the service of life-changing research.

“My interest is in pediatric heart disease,” Kit Parker, a Harvard bioengineer and a lead researcher of the project, told The Daily Beast. “I want to build a tissue-engineered heart for a sick kid born with a malformed heart. But I can’t put that heart into a living child without having ever tested it myself.”

The way to test that, Parker has found, is to build these marine biohybrids that can demonstrate whether a culture of engineered heart cells can really beat and function like a natural heart is supposed to. “Biohybrid” basically means a combination of living cells with synthetic materials—made of living materials, but functioning more-or-less like a device or piece of new technology.

Several years ago, he found himself frustrated with the current state of therapeutics for the heart. “They seemed to perform so poorly, as if there was something we are misunderstanding about the heart,” he said.

Around that time, Parker began taking his then-toddler daughter to the New England Aquarium and was inspired by the jellyfish. “I’m looking at it, and thinking, ‘It pumps, it looks like a heart pump,’” he said. “I’m thinking, ‘I could build that damn thing.’”

Parker and his team ended up building a biohybrid jellyfish that swam around using beating heart cells derived from a rat—to exciting media fanfare. Parker and his team would end up following up with a biohybrid stingray made again with cardiac rat cells, and taught to contract in response to blinking lights.

That work eventually led to the biohybrid fish unveiled today in a new paper published in Science. The fish is modeled after a zebrafish (an animal whose skin is transparent, making it very attractive for study among physiologists and bioengineers).

The body of the fish is made of five different layers: a line of cardiac muscle tissue derived from human stem cells; a rigid layer of paper built using lasers; a layer of gelatin, another layer of paper, and a final layer of muscle tissue. It’s the tail fin where these two layers of muscle cells really shine: As one side of the fin’s cardiac cells contract, the other side stretches—and vice versa. This cycle causes the tail fin to move back and forth and propel the fish forward autonomously.

“These are principles borrowed from the human heart,” said Parker. “And the amazing thing is that this was powered on its own. It swims faster than anything else that we’ve ever built. And it lives longer,” lasting about 108 days before the team finally terminated the experiment. The biohybrid fish actually learned to swim more efficiently and exhibit a better rhythm over time.

Another leg of the study involved the creation of an autonomous pacing node (like a pacemaker) that was able to modulate the frequency and rhythm of these contractions inside the biofish.

Michael Rosnach, Keel Yong Lee, Sung-Jin Park, Kevin Kit Parker

Armed with a better sense of the electro-mechanical signaling and physical movement of a beating heart, the authors of the new study hope to take these insights forward into engineering tissue that could one day be used to grow an artificial heart that’s fit for transplantation and save a child’s life; as well as create better pacemaker devices that can keep a damaged heart alive for longer.

Though the new study won’t directly lead to a breakthrough artificial pediatric heart next year, Parker and his team are already moving forward with plans to build artificial heart tissue in three dimensions and simulate the chambers that make up a human heart.

Others have already started jumping off the new findings in their own way. William Poole, a cardiologist at Boston Children’s Hospital, is working with Parker to learn how to conduct clinical testing on tissue “chips” that act as a microcosm for heart disease and can be experimented on and studied, without having to endanger actual human participants. A year ago, Parker and Poole already began using the data from this experiment to simulate pediatric heart disease in the lab and test out drugs, pacemakers, and other interventions.

But Parker’s most immediate goal, he said, is to stay out of jail. “I’m not kidding—the last time we [built a biohybrid], the U.S. Attorney General’s office here in Boston started investigating us for misuse of grant funding” awarded by the National Institutes of Health. It was only after three NIH program officials published a paper that discussed the scientific merits of the project that the investigation was dropped.

“If you’re working outside of the box, not everyone is going to receive you with open arms,” said Parker. “But there’s a difference between being unconventional and being crazy. And I think now people are starting to catch on.

“So the first priority is to stay out of the big house,” said Parker. And then we can do some science. The long-term goal here is to save some sick kids.”