Carolyn Bertozzi – TRANSCRIPT
This is a talk about sugar, and it’s not the only one we’ve heard today, but this is a talk about sugar and cancer, and that might give it a twist that is a little more unfamiliar. And I start with this slide, because this is my equivalent of when the teacher in high school says, “Sex,” and everybody pays attention. So this is, “Do I have your attention?” I became interested in sugar, actually, when I was in college – not this kind of sugar though.
It was the sugar that our biology professors taught us about in the context of the coating of your cells. And maybe you didn’t know that your cells are coated with sugar – and I didn’t know that either until I took these courses in college – but back then – and this was, let’s just call it ‘in the 1980s,’ – this was when people didn’t know much about why our cells are coated with sugar. I saved my old college notes. Do people save their notes from their college classes and dig through them once in a while?
And when I dug through my notes, what I noticed I had written down is that the sugar coating on our cells is like the sugar coating on a Peanut M&M. Do you remember that commercial from the 1970s or ’80s which is that M&M’s melt in your mouth but not in your hand? People thought the sugar coating on our cells was like a protective coating that somehow made our cells stronger or tougher, but we now know, many decades later, that it’s much more complicated than that, and that the sugars on our cells are actually very complex.
And if you could shrink yourself down to a little miniature airplane and fly right along the surface of your cells, it might look something like this, with geographical features, and now the complex sugars are these trees, and bushes, weeping willows swaying in the wind and moving with the waves. And when I started thinking about all these complex sugars that are like this foliage on our cells, it became one of the most interesting problems that I encountered as a biologist and also as a chemist.
So now we tend to think about the sugars that are populating the surface of our cells as a language. They have a lot of information stored in their complex structures, but what are they trying to tell us? And this is a very exciting area of biology and medicine that I’ve been working on now for almost 20 years in my own career. I can tell you that we do know some information that comes from these sugars, and it’s turned out already to be incredibly important in the world of medicine.
For example, one thing your sugars are telling us is your blood type. So your blood cells, your red blood cells, are coated with sugars, and the chemical structures of those sugars determine your blood type. So for example, I know that I am blood type 0. How many people are also blood type 0? Get your hands up. It’s a pretty common one, and so when so few hands go up, either you’re not paying attention or you don’t know your blood type and both of those are bad. But for those of you who share the blood type 0 with me what this means is that we have this chemical structure on the surface of our blood cells: three simple sugars linked together to make a more complex sugar, and that, by definition, is blood type 0. How many people are blood type A? Right here, so that means you have an enzyme in your cells that adds one more building block that red sugar, to build a more complex structure.
And how many people are blood type B? Quite a few. You have a slightly different enzyme than the A people so you build a slightly different structure. And those of you that are AB have the enzyme from your mother the other enzyme from your father, and now you make both of these structures in roughly equal proportions. And when this was figured out – which is now back in the previous century – this enabled one of the most important medical procedures in the world, which of course, is the blood transfusion.
And by knowing what your blood type is, we can make sure, if you ever need a transfusion, that your donor has the same blood type so that your body doesn’t see foreign sugars which it wouldn’t like, and it would certainly reject. What else are the sugars on the surface of your cells trying to tell us? Well, those sugars might be telling us that you have cancer.
So a few decades ago, correlations began to emerge from the analysis of tumor tissue, and the typical scenario is a patient would have a tumor detected – perhaps by one of the imaging methods that Adam de la Zerda talked about earlier today – and the tissue would be removed in a biopsy procedure and then sent down to a pathology lab where that tissue would be analyzed to look for chemical changes that might inform the oncologist about the best course of treatment. And what was discovered from studies like that is that the sugars have changed when the cell transforms from being healthy to being sick. And those correlations have come up again and again and again, but a big question in the field has been why? Why do cancers have different sugars? What’s the importance of that? Why does it happen, and what can we do about it if it does turn out to be related to the disease process?
So one of the changes that we study here at Stanford is an increase in the density of a particular sugar that’s called sialic acid. And I think this is going to be one of the most important sugars of our time so I would encourage everybody to get familiar with this word. Sialic acid is not the kind of sugar that we eat; those are different sugars. This is a kind of sugar that is actually found at certain levels on all of the cells in your body; it’s actually quite common on your cells. But for some reason, cancer cells – at least in a successful progressive disease – tend to have more sialic acid than a normal healthy cell would have.