What the sugar coating on your cells is trying to tell you | Carolyn Bertozzi

This is a talk about sugar and cancer.

I became interested in sugar when I was in college.

Not this kind of sugar.

It was the sugar that our biology professors taught us about

in the context of the coating of your cells.

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 in, let's just call it the 1980s --

people didn't know much about why our cells are coated with sugar.

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 and M.

And 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 that are 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.

And 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?

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 O.

How many people are also blood type O?

Put your hands up.

It's a pretty common one,

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.

(Laughter)

But for those of you who share the blood type O 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 O.

Now, how many people are blood type A?

Right here.

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 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,

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

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 times,

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.

You know, 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.

And these immune cells go around and 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 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.

In fact, one of those drugs

may well have spared President Jimmy Carter's life.

Do you remember, President 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, it's so remarkable

that provocative statements like this one:

"Cancer is having a penicillin moment," people are saying,

with these new immune therapy drugs.

I mean, that's an incredibly bold thing to say about a disease

which 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,

well, it 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 sialic acids are telling the immune cell,

"Hey, this cell's all right. 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, right?

It's amazing.

And 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)