Why you should care
Because the future of heart research is here.
Mild of manner and matter of fact, Joseph Wu leads me to a room in his laboratory that’s the size of a walk-in closet. Inside, two postdocs are hunched over their work. One of them pulls a tiny glass dish out of the fridge, slips it under a high-powered microscope and lets me look. These are stem cells that have become heart cells. And they’re beating.
Da-dum. Da-dum. Da-dum.
The 45-year-old Wu is a cardiologist mastermind who is changing how we study — and, potentially, cure — heart disease, the leading cause of death of American men and women. Key to his work at Stanford’s Cardiovascular Institute are induced pluripotent stem (iPS) cells. They come from human skin or blood, and, let alone, they could theoretically grow into a mess of organ tissue: hearts, livers and lung tissue all jumbled together. Instead, and much like a gardener, Wu coaxes these iPS cells into becoming heart cells, for the relatively bargain price of $3,000 and a few weeks. Already he’s grown heart tissue, and someday, Wu believes, scientists will be able to grow an entire human heart in the lab.
Even in the shorter term, Wu’s research will change drug testing for the better. Doctors will administer drugs into petri dishes filled with stem cells, testing reactions on a small, safe scale. Clinical trials will be conducted in a dish instead of on animal or human subjects. He is “one of the most promising minds of his generation,” says Dr. Chuck Murry, of the Institute for Stem Cell and Regenerative Medicine at the University of Washington.
Wu’s work is part of a broader mission to give shape to one of the sexiest catchphrases in biomedical research and medicine today: precision medicine. Last year, President Obama declared precision medicine a national priority. But ironically, the term itself is rather imprecise. Broadly, precision medicine means taking into account individual factors such as genetics, environment and lifestyle, instead of a one-size-fits-all approach. Wu’s approach is arguably more radical than all of these: He envisions treatments based on an individual’s own iPS cells. For example, a popular breast cancer drug has an 8 percent chance of giving patients heart failure. In Wu’s world, we’d test the drug on stem cells first, and if a patient lands in that 8 percent, begin treatment for the side effects preemptively or avoiding the drug totally and avoiding heart failure, too.
What sets Wu apart, according to fellow iPS cell researcher Lorenz Studer, is his “systematic approach — he doesn’t stop at data discovery.” Indeed, Wu wants to move beyond patient-level testing and is already thinking big. His goal is to take these stem cells from thousands of patients to create a genetically diverse enough bank that will allow for “clinical trials in a dish” — Wu’s go-to phrase. Murry calls the idea “extraordinarily ambitious.”
In comparison to his ambition, Wu seems remarkably even-keeled, which he attributes to his upbringing. Like many Taiwanese, his family came to the U.S. in the 1980s, though they took the “economy ticket” path: with stops in Paraguay, Bolivia and Brazil before landing in south Pasadena. Back in Taiwan, his family owned an Asian pear-apple farm, so the family opened one up in California’s Central Valley. While his now wife was learning how to play piano, he was playing interpreter for his father and talking to adults about irrigation ditches and pesticides. He credits the early lesson in communicating with adults for his ability to punch above his weight (or age).
Drug testing as it stands is deeply flawed. On average it takes 12 years and $2 billion to bring a new drug to market, and flaws often don’t emerge until the very last stage of testing. Or until people die. When drugs are taken off the market, it’s usually because of cardiotoxicity, or death by heart failure, but no model allows us to predict cardiotoxicity as well as Wu’s. Testing drugs on stem cells will give big pharma and the FDA vastly improved heads up for toxic complications. Stem cells are “absolutely” the best avenue going forward, says Norman Stockbridge, director of the division of cardiovascular and renal products at the FDA’s Center for Drug Evaluation and Research. For now, the main hurdle remains figuring out the right electrocurrent density in the stem cells, something that a few researchers including Wu are jockeying to figure out. Once they do, “the world will change again,” says Stockbridge.
During all those years on the Asian pear farm, Wu knew he wanted to be a doctor. Though he chose academia — he avoided practicing because of the “naive notion” that he “didn’t want to associate patients with money” — he still sees a handful of patients once every two weeks. When I mention my own heart issues, by chance in his specialty, he lights up and the physician in him comes alive. For a moment I become the subject and he the interviewer. And I see why his real patients, stem cells, are so well taken care of.