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)