Translator: Robert Deliman
Reviewer: Denise RQ 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. And why? What does that mean? Well, what we've learned is that it has
to do with your immune system. So let me tell you a little bit about the importance
of your immune system in cancer, and this is something that's, I think,
in the news a lot these days. People are starting to become familiar
with the term cancer immune therapy, and some of you might even know people who are benefiting from
these very new ways of treating cancer. What we now know
is that your immune cells, which are the white blood cells
coursing through your bloodstream, protect you on a daily basis
from things gone bad, including cancer. And so in this picture, those little green balls
are your immune cells, and that big pink cell is a cancer cell. These immune cells go around,
and they taste all the cells in your body. That's their job. And most of the time, the cells taste OK, but once in a while,
a cell might taste bad - hopefully, that's the cancer cell - and when those immune cells
get the bad taste, they launch an all-out strike
and they kill those cells. So we know that. We also know that if you can
potentiate that tasting, if you can encourage those immune cells to actually take a big, old bite
out of a cancer cell, you get a better job protecting yourself
from cancer every day and maybe even curing a cancer. And there are now a couple of drugs
out there in the market that are used to treat cancer patients
that act exactly by this process. They activate the immune system so that the immune system
can be more vigorous in protecting us from cancer. And in fact, one of those drugs may well have spared
president Jimmy Carter's life. Do you remember Ppresident Carter
had malignant melanoma that had metastasized to his brain? And that diagnosis is one
that is usually accompanied by numbers like months to live. But he was treated with one of these
new immune stimulating drugs, and now his melanoma
appears to be in remission, which is remarkable, considering the situation
only a few years ago. In fact, so remarkable,
that provocative statements like this one, "Cancer is having a penicillin moment" that people are saying
with these new immune therapy drugs. I mean, that's an incredibly bold thing
to say about a disease, which as Adam mentioned earlier, we've been fighting for a long time
and mostly losing the battle with. So this is very exciting Now, what does this have
to do with sugars? Well, I'll tell you what we've learned: when an immune cell snuggles up
against a cancer cell to take a taste it's looking for signs of disease,
and if it finds those signs, the cell gets activated, and it launches
a missile strike and kills the cell. But if that cancer cell has a dense forest
of that sugar sialic acid starts to taste pretty good. And there's a protein on immune cells
that grabs the sialic acid, and if that protein
gets held at that synapse between the immune cell
and the cancer cell, it puts that immune cell to sleep. The scialic acids
are telling the immune cell, "Hey! This cell's alright.
Nothing to see here. Move along. Look somewhere else." So, in other words, as long as our cells are wearing
a thick coat of sialic acid they look fabulous. It's amazing. What if you could strip off that coat
and take that sugar away? Well, your immune system
might be able to see that cancer cell for what it really is,
something that needs to be destroyed. And so this is what we're doing in my lab, we're developing new medicines that are basically
cell-surface lawnmowers, molecules that go down
to the surface of these cancer cells and just cut off those sialic acids so that the immune system
can reach its full potential in eliminating
those cancer cells from our body. So in closing, let me
just remind you again: your cells are coated with sugars; the sugars are telling
cells around that cell whether the cell is good or bad. And that's important because our immune system
needs to leave the good cells alone; otherwise, we'd have autoimmune diseases. But once in a while, cancers get the ability
to express these new sugars, and now that we understand how those sugars mesmerize
the immune system, we can come up with new medicines
to wake up those immune cells, tell them, "Ignore
the sugars, eat the cell, and have a delicious snack on cancer." Thank you. (Applause)
