Thousands of songs, poems, and a Greek chorus of psychologists, therapists, and best friends have tried to answer this question, but the man who may have come up with the answer never wrote a line of iambic pentameter.
Chuck Murry, M.D., Ph.D. heads the lab at the University of Washington that set out to unlock the secrets of healing as it relates to that most sensitive of organs, the human heart. His appearance at TEDx Seattle 2018 provided an intriguing and powerful overview of research he initially launched 20 years ago. Dr. Murry is not looking for ways to mend relationships or restore balance after a breakup so much as his team has taken on the real impact of a damaged, or compromised heart — a failure to recover.
Heart disease is the number one killer for both men and women, snatching over 600,000 American lives each year. “Well Chuck,” said one of his friends, “we’ve gotta die of something.” Yes, but a byproduct of heart disease is the $100,000,000,000 tab that patients, their families, and insurance companies pay for the privilege of dying of heart disease. The GDP of many countries across the globe doesn’t add up to that number. So, heart disease is a cruel and costly killer.
When someone has a heart attack, let’s say a severe one, and is not immediately treated, the heart does what it knows how to do after a disaster. The primary strategy is to knit the damaged area back together with scar tissue. And therein lies the problem. Scar tissue doesn’t contract efficiently, leaving the heart like a car running on one cylinder. Ca chunk, ca chunk.
Dr. Murry wondered if there were a way to reconstruct and mend the attack areas of the heart by using heart muscle cells. The dilemma is that heart muscle cells are only found in the heart and all of them already have a job. This unfortunate reality nudged his thinking into the realm of stem cells, those controversial chameleon-like cells that can take on several cell identities and have proven themselves viable in the treatment of leukemia and other dangerous medical conditions.
Stem cells are found throughout the human body, making it a “natural” move for the researchers to concoct an environment in which these microscopic units could turn into heart muscle cells. Cells introduced to a heart muscle cell medium did transform. Unfortunately, the result was a diverse selection of cells: skin cells, muscle cells, tissue cells, and heart muscle cells. No, as Goldilocks would have said, “Not quite right.”
Dr. Murry shared that he next looked to “pluripotent stem cells”, an even more compliant type of stem cell, often called master cells. With a wider range of options, the researchers at Dr. Murry’s lab hoped to coax the pluripotent stem cells into transforming into heart muscle cells. Over several critical days, they all stared into the Petri dish. Will they? Won’t they?
They did! In the bottom of the dish resided a collection of the first ever pluripotent stem cell/heart muscle cells. As a Eureka moment, the doctor and his team couldn’t ask for much more. Yet, to fulfill on Dr. Murry’s dream, those cells had to segue from dish to living being and then, function correctly. The cells in the dish weren’t yet cells happily replicating in a guinea pig, much less a human being.
As Dr. Murry narrated episode after episode of his Herculean task, the audience held its breath with every snag, and then gratefully released it when the signs were auspicious. Would the cells beat in synchrony with the host cells? Ooops, not really. Tweak. Adjust. Snip. Would the guinea pigs natural pacemaker teach the newcomers how to march? Yes! Bu-bump, bu-bump. Regrettably, those same guinea pigs developed arrhythmias (abnormal heartbeats) after several weeks. with the new heart muscle cells “wreaking havoc like misbehaving teenagers,” stated Dr. Murry. Tweak. Adjust.
Snip. The arrhythmias subsided and the heart muscle cell program was ready for further tests with macaque monkeys who had suffered artificial heart attacks. By way of comparison, a healthy heart muscle, of which we have a right and left, has an average left ventricular ejection fraction of 65–70%. In layman’s terms this means that with each contraction, the left ventricle pumps out 65–70% of the blood that has filled it. That amount drops to 40% or less after a cardiac episode.
Thus, a measure of the successful integration of the new heart muscle cells would be found in the amount of blood the heart could pump with each beat. The higher the percentage, the healthier the heart, since a weak contraction means the heart will begin overworking, putting both heart and patient risk again. After 4 weeks of careful monitoring, the macaques pumping skills had risen to 48%. Not stellar. Not even close.
Still, Dr. Murry is patient, as evidenced by his two-decade pursuit of a real remedy to heart damage. He waited and watched, week after week. Gradually, the monkeys turned a corner and began to show increased signs of recovery. Three months after the pluripotent stem cells became heart muscle cells and were transplanted into the macaques’ injured hearts, the ventricular ejection fraction had risen to 62%, close to a normal healthy heart response. Heartening news, indeed!
Dr. Murry’s work is not over, but he doesn’t begrudge the process, the bumps, frustrations, and setbacks when a successful therapeutic methodology is almost within view.