Doug Melton – Professor at Harvard University: Thanks, John. I’m delighted to be here today to talk about my favorite cell: the stem cell. That might be a funny thing to say.
Most people have a favorite animal or a favorite color. I actually have a favorite cell, because this cell has two amazing properties: it can make more of itself, it can renew indefinitely and it can also make any of the cells in your body. As you know, all your tissues and organs are made up of cells. And so, here we have a cell that can make anything in your body.
I’m going to tell you in the next 10 minutes that this is the beginning of a revolution in Biomedicine, not unlike the revolution the transistor caused in electronics. Most all of you have a cellphone and use a computer. Those wouldn’t exist if it wasn’t for a transistor. Before transistors, there were vacuum tubes. This cell, which we now can gain some mastery over, will change the way you think about making and maintaining human beings and fighting disease.
Now, I could talk about this in a number of contexts for lots of diseases, but I’m going to pick one. Today I’m going to talk about diabetes. I’ll come back to other diseases but I want to share with you the idea that we could create a world which got rid of diabetes. There are two kinds of diabetes, known to most people. The one which you’re reading about all the time in the newspaper now is related to excess food, lack of exercise, obesity. It’s called type 2 diabetes. And many type 2 diabetics require insulin, but not all. Some take a pill which makes them more sensitive to insulin.
The kind of diabetes I want to talk about is the one that affects children, called juvenile or type 1 diabetes. I have pictures here you see, where these children have to test their blood to know how much sugar is in it, 3 to 5 times a day, and then inject themselves with a needle or with an insulin pump, to provide insulin which is life saving.
Without the insulin, of course, people wouldn’t survive, and you need the insulin to make use of the food you eat. We’ve enjoyed, as John has just reminded us, a nice lunch, with care of Summer Shack. Well, as you’re sitting here, and your body is digesting that food and turn it into sugar, your brain and the rest of your tissues can’t make use of that without this hormone insulin.
So now I’m going to bring you back to sort of high school biology, for just about 4 or 5 slides in my presentation and it’s going to remind you about things you have some intuitive knowledge of and then I’m going to try to connect that with stem cells. So, you all have inside you, right sort of in this region of your body an organ called the pancreas, which is about the size of a banana.
Think about that like a piece of bread, like raisin bread, with little raisins peppered in it. There are 100,000 of these little spheres, shown here on the top right, that make hormones, and the blue cells in those spheres are making insulin. In diabetics, those cells are destroyed. So, as you see on the bottom right, the cells are gone. There’s no beta cells, as they’re called.
So, the patient can’t make insulin. Insulin, from the drug industry’s perspective, has largely become not a blockbuster drug. It’s widely beyond that. It’s a commodity. Nearly 25 billion dollars a year — that’s not million, billion dollars a year — is bought and sold and injected into people.
So the project I’m going to tell you about is relatively simple: instead of injecting yourself with insulin, why not give your body the cells, the factories that make insulin control your blood sugars and get rid of diabetes? I’ve already hinted that the way one would think about doing that is using my favorite cell — these human stem cells can make any part of the body and I showed you this chart because you might have a different favorite part of your body.
So you can look at this and think, “Well, if you were coming to the lab, which part would you kind of make?” I’m interested as you know, as I’ve said, in this part of the pancreas that makes the beta cells, the cells that produce insulin. So I’m going to show you now just a couple of slides that, in an unfair way, summarize about 10 years of work, trying to do what. Marco Tempest called magic, that is, to take a cell and to create mastery and dominion over it and make it become a pancreatic beta cell, make it do what we want. I’m going to just tell you how we’ve done that.
So we begin with this stem cell sometimes called an embryonic stem cell, or an induced pluripotent stem cell and we have to instruct it as to what to do because, remember, it can do anything. You can think of it like being in kindergarten and there’s all sorts of options before it. We have to first tell it to become part of the gut tube. That’s the tube, during development, that runs from your mouth to your anus as your lung, your liver, your stomach, your pancreas. That’s its first decision.
Its second decision, then, is to become pancreas. It could be the part of the pancreas that make enzymes or the part that makes hormones. Then it has to become hormone producing, but finally our goal, our target, is this beta cell, the cell that makes insulin.