The Impossible Heart

As for the rejection issues that have long bedeviled transplant efforts, removing the original cells and reseeding the heart with those of the recipient will, theoretically, eliminate problems associated with mechanical hearts. There’s no reason, Taylor says, why someone with a bio-artificial heart should need anti-immune drug therapy.

Making the bio-heart stronger is the U of M lab’s near-term priority. This involves coaxing cells to put on mass, through density and numbers, to build muscle. By the time the process has advanced to the point where a transplant can be performed in humans, there may be better approaches to solving life-threatening cardiovascular problems than transplanting an entire reseeded organ. That is why the lab is also researching, for instance, how to use new cells to reverse atherosclerosis, a leading cause of heart attacks and strokes.

Taylor keeps a pig’s decellularized heart in a jar in her office. Sometimes she picks up the jar and turns it in her hand. The heart floats, in limbo, waiting to meet its destiny. Could this ghostly white organ one day end up in a human? For all her optimism, Taylor doesn’t want to raise false hopes for the 30,000 Americans currently awaiting a donor heart. Yet, when asked if her breakthrough should accelerate the process, she smiles broadly and says, “Absolutely!” She says she can’t wait to enlarge her already wide circle of fellow problem-solvers and to bring skeptics, especially the tissue engineers over whose work she’s effectively leapfrogged, into the tent. “I’m a collaborator, and that’s what science is all about,” she says. “I’m also a very idealistic person.”

Taylor insists she has no illusions about who really deserves the credit for the world’s first perfusable bio-artificial heart. In her mind, the credit belongs to Mother Nature. “For a while, we were calling the heart our smart heart because we figured it could tell the cells what to do, and in many ways it did,” she says. “When we saw the heart beating, that was the eureka. That was fascinating and fabulous.”

Once the team had the bio-heart up and running, Taylor was faced with a quandary. To whom to tell the story—and how to best tell it? Determined as always to “swing for the fences,” Taylor devised a two-pronged scheme. They’d sell Tissue Engineering an article about the decellularization; Nature Medicine would be the lucky recipient of the sexier story about how the team reseeded the scaffold with new cells to create a beating heart.

But both publications wanted all or nothing. So Taylor opted to focus on Nature Medicine, where she had already been published. The editorial process is byzantine, and peer review in such a prestigious journal can be daunting. At Nature Medicine, three individuals—each an expert in a relevant field—have the power to accept or reject a submission.

It took Taylor two years and countless revisions before Nature Medicine accepted her paper. The team felt thoroughly beaten up by the process in which they’d all participated, throwing in additional facts and comments until it was looking to them more like a tuna hot dish (Taylor is still working up the courage to try this Minnesota delicacy) than a scientific journal article. After two rejections, Taylor had to make a choice. Should she appeal? Ask the U of M to cough up more funding for additional experiments to prove perfusability? Try to get a biotech company interested? Give up? She decided to appeal.

Christmas 2006 was an especially trying time. The group needed a lift, so Taylor went shopping at Target and bought a wind-up toy heart for everyone in the lab. Someday, she told the team, we’ll have an “off-the-shelf organ” on sale at Target too.

They sent off a revision on May 31. More waiting. Then, on a day like any other October-in-Minnesota day, they received an acceptance letter. Three months later, Nature Medicine led its January 13 online edition with the bio-heart story, including videos of the beating organ that triggered a cascade of attention. One media outlet would see the heart beating in another outlet’s video and give Taylor a call. She was getting so many calls she thought about disconnecting her phone. She’s still not answering media e-mails.

Of the scientists interviewed for this article, it was clinical heart doctors such as surgeons Jay Traverse at the U of M and Abbott Northwestern Hospital in Minneapolis and Francis Pagani at the University of Michigan who seem to most appreciate Taylor’s accomplishment. Like Taylor, they focus on the human patient whose heart isn’t working right. While each is well aware of the obstacles remaining between the slippery little blob hanging in a jar in a university research lab and the full-sized organ their patient must have to stay alive, both Pagani and Traverse can’t wait for the clinical trials to begin. And they say they’re confident there will be clinical trials—maybe not next year or the year after, but soon.

While she officially puts the time frame at ten years, Taylor the self-described enthusiastic idealist believes she can have a heart up and ticking and transplanted in a human even sooner, depending on how willing other labs are to share their data as scientists elsewhere attempt to replicate her experiment and take it one step further. Still, first things first. “We need to prove to ourselves that the heart truly is perfusable, that it can support a blood supply,” she says. “That’s what keeps me awake at night. Figuring out ways to test that.”

An important test of perfusability involves the transplantation of the heart into a rat’s abdomen. The bio-heart isn’t strong enough yet to keep the rat alive, so its own heart stays put, while scientists monitor blood flow and the animal’s reaction to the new heart in the abdomen. There may be other issues Taylor hasn’t foreseen, she says, emphasizing that she and her team are exploring new territory—which is precisely why she finds it such a thrilling adventure, like her mother’s long-ago adventure overseas when there wasn’t a job in her own country that would satisfy her curiosity about the world.

“It really did break in a big way,” Taylor says of the headlines the bio-heart story drew worldwide early this year. “That speaks to three things: the need out there, that it’s a story that makes sense to people, and that it’s a platform and not just bacteria in a dish.” Twenty-two million Americans are living with heart failure, and that number will grow as baby boomers move into their sixties and seventies. It’s impossible to estimate how many millions of people around the world need not just new hearts but new valves or vessels and how many need other organs.

Heart researchers in competing labs immediately expressed their astonishment at both Taylor’s achievement and their own thickheadedness. It’s so simple, one tissue engineer said to The New York Times; so obvious. This reminded Taylor of another Times reporter, one who, in 1998, covering her breakthrough at Duke, had asked, If it’s so simple, why hasn’t it been done already? To which she replied with her now stock spiel about out-of-the-box thinking. As devoted as she is to her rules to live by, when it comes to science, “Break the rules” is rule number one.

She was disappointed when some people questioned her methods, looked for flaws, kibitzed about the team’s initial failure to garner NIH funding, or complained that certain members of Taylor’s team hadn’t received enough credit. “The team is always the first thing I talk about,” she says. She frets about Ott’s departure. She misses him and hopes that one day he’ll again be part of her lab, this time with clinical surgery credentials to add to his PhD.

Ott, for his part, says he would love to work with Taylor again: “It would not have been possible to achieve these milestones in a lab where out-of-the-box approaches and a creative, sometimes unconventional way of looking at things were less welcome than in hers. I remember the countless afternoons and evenings we spent brainstorming and discussing scientific questions. And, in the end, we made tremendous progress in the fields of cardiac regeneration and cardiac tissue engineering. We had a good mix of translational researchers, allowing us to generate new data, always keeping the human application in perspective.

“When Thomas and I saw the first heartbeats and called her right away—it is hard to put these feelings into words . . . .”