Here is the full text of Dr. Chuck Murry’s talk titled “Regrowing heart muscle with stem cells” at TEDxSeattle conference.
For over 20 years, Dr. Chuck Murry has studied the causes of cardiovascular disease and researched harnessing the potential of stem cells to repair damaged heart muscle. In this talk, he shares his journey and groundbreaking research, providing hope through evidence that we can heal the heart.
Dr. Chuck Murry – TEDx Talk TRANSCRIPT
I’d like to tell you about a patient named Donna. In this photograph, Donna was in her mid-70s, a vigorous, healthy woman, the matriarch of a large clan. She had a family history of heart disease, however, and one day, she had the sudden onset of crushing chest pain.
Now unfortunately, rather than seeking medical attention, Donna took to her bed for about 12 hours until the pain passed. The next time she went to see her physician, he performed an electrocardiogram, and this showed that she’d had a large heart attack, or a “myocardial infarction” in medical parlance.
After this heart attack, Donna was never quite the same. Her energy levels progressively waned, she couldn’t do a lot of the physical activities she’d previously enjoyed. It got to the point where she couldn’t keep up with her grandkids, and it was even too much work to go out to the end of the driveway to pick up the mail.
One day, her granddaughter came by to walk the dog, and she found her grandmother dead in the chair. Doctors said it was a cardiac arrhythmia that was secondary to heart failure. But the last thing that I should tell you is that Donna was not just an ordinary patient. Donna was my mother.
Stories like ours are, unfortunately, far too common. Heart disease is the number one killer in the entire world. In the United States, it’s the most common reason that patients are admitted to the hospital, and it’s our number one health care expense. We spend over $100 billion — billion with a “B” — in this country every year on the treatment of heart disease. Just for reference, that’s more than twice the annual budget of the state of Washington.
What makes this disease so deadly?
Well, it all starts with the fact that the heart is the least regenerative organ in the human body. Now, a heart attack happens when a blood clot forms in a coronary artery that feeds blood to the wall of the heart. So this plugs the blood flow, and the heart muscle is very metabolically active, and so it dies very quickly, within just a few hours of having its blood flow interrupted.
Since the heart can’t grow back new muscle, it heals by scar formation. This leaves the patient with a deficit in the amount of heart muscle that they have. And in too many people, their illness progresses to the point where the heart can no longer keep up with the body’s demand for blood flow. This imbalance between supply and demand is the crux of heart failure.
So when I talk to people about this problem, I often get a shrug and a statement to the effect of, “Well, you know, Chuck, we’ve got to die of something.”
And yeah, but what this also tells me is that we’ve resigned ourselves to this as the status quo because we have to. Or do we? I think there’s a better way, and this better way involves the use of stem cells as medicines.
So what exactly are stem cells?
If you look at them under the microscope, there’s not much going on. They’re just simple little round cells. But that belies two remarkable attributes.
The first is they can divide like crazy. So I can take a single cell, and in a month’s time, I can grow this up to billions of cells. The second is they can differentiate or become more specialized, so these simple little round cells can turn into skin, can turn into brain, can turn into kidney and so forth.
Now, some tissues in our bodies are chock-full of stem cells. Our bone marrow, for example, cranks out billions of blood cells every day. Other tissues like the heart are quite stable, and as far as we can tell, the heart lacks stem cells entirely. So for the heart, we’re going to have to bring stem cells in from the outside, and for this, we turn to the most potent stem cell type, the pluripotent stem cell.
Pluripotent stem cells are so named because they can turn into any of the 240-some cell types that make up the human body. So this is my big idea: I want to take human pluripotent stem cells, grow them up in large numbers, differentiate them into cardiac muscle cells and then take them out of the dish and transplant them into the hearts of patients who have had heart attacks. I think this is going to reseed the wall with new muscle tissue, and this will restore contractile function to the heart.
Now, before you applaud too much, this was my idea 20 years ago. And I thought I was young, I was full of it, and I thought, five years in the lab, and we’ll crank this out, and we’ll have this into the clinic. Let me tell you what really happened.
We began with the quest to turn these pluripotent stem cells into heart muscle. And our first experiments worked, sort of. We got these little clumps of beating human heart muscle in the dish, and that was cool, because it said, in principle, this should be able to be done.
But when we got around to doing the cell counts, we found that only one out of 1,000 of our stem cells were actually turning into heart muscle. The rest was just a gemisch of brain and skin and cartilage and intestine. We weren’t able to ready to begin animal testing.
So how do you coax a cell that can become anything into becoming just a heart muscle cell?
Well, for this we turned to the world of embryology. For over a century, the embryologists had been pondering the mysteries of heart development. And they had given us what was essentially a Google Map for how to go from a single fertilized egg all the way over to a human cardiovascular system.
So we shamelessly absconded all of this information and tried to make human cardiovascular development happen in a dish. It took us about five years, but nowadays, we can get 90% of our stem cells to turn into cardiac muscle — a 900-fold improvement. So this was quite exciting.
This slide shows you our current cellular product. We grow our heart muscle cells in little three-dimensional clumps called cardiac organoids. Each of them has 500 to 1,000 heart muscle cells in it. If you look closely, you can see these little organoids are actually twitching; each one is beating independently. But they’ve got another trick up their sleeve.
We took a gene from jellyfish that live in the Pacific Northwest, and we used a technique called genome editing to splice this gene into the stem cells. And this makes our heart muscle cells flash green every time they beat.
Now I personally find this quite aesthetically satisfying. The Jellyfish uses this as part of its courtship ritual. We’ll use it for quite a different purpose in just a moment.
OK, so now we were finally ready to begin animal experiments. We took our cardiac muscle cells and we transplanted them into the hearts of rats that had been given experimental heart attacks. A month later, I peered anxiously down through my microscope to see what we had grown, and I saw … nothing. Everything had died.