Using fluorescence to expose cancer | Cédric Enguehard | TEDxLimoges

Bad, good; the boundary is sometimes hard to determine.

When the disease is in our tissues, shedding light on this boundary becomes a vital matter. Open the directory of dysfunctions of the human body, an encyclopedia, one needs to choose a cause. For this speaker, it was to be to separate what is well from what is not.

A former student at the University of Limoges and a doctorate from the XLIM laboratory, previously at AMCAD Engineering, Cédric Enguehard is one who seeks out, and his business creation has one mission: to arm medical science against that invisible malignancy that makes diagnosis difficult. To eliminate guesswork from interpretation: to bring out, to determinedly distinguish, to demarcate, what is clearly bad. If we're going to cut the grass, we might as well cut it as short as possible under the feet of the Grim Reaper.

This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at http://ted.com/tedx

A few years ago, Limoges university
hospital practitioners

and Faculty of Medicine researchers

were in discussion.

And they wanted to know
if there was something

that might aid them
during cancer surgeries.

What they found
did not really satisfy them.

So, they straightway
launched a research program.

This research involved medics,

researchers in biology,
in chemistry, physicists,

from various institutes,
and from various organizations.

The first time I heard
of this research program and its work,

I was right away attracted by the elegance
of the solution it proposed.

And then I saw very quickly

the incredible impact
this technology could have for patients.

So I decided to quit my job to dedicate
all of my time to this project,

and I was joined by two friends,
Alexis and Virgile.

Today, we are trying to transform

this beautiful technology
into a real tool.

So, how can we see what is not visible?

Most of what surrounds us
that we call invisible

is just too small for us to perceive.

It's the case, for example, in diseases
that we cannot see directly.

What we can see are the symptoms
that inform us that something is wrong.

Certain diseases come
from external factors

like viruses or, say, bacteria.

Other illnesses come from our own body.

That's the case for cancer.

Throughout our life,
right now as I am talking to you,

all of us, we all have cells
that regenerate and renew themselves

in a cycle that we might consider
to be birth, life, and death.

All this at the cellular level.

For example, the liver renews
all of its cells in 400 days.

This is not an excuse
for your next night out -

you will agree.

And some other cells
are renewed even faster.

That's the case for the intestine.

The intestine renews its cells
entirely every five days.

And during our entire life,
we are all going to lose

about the equivalent
of 20 kg of dead skin.

Think about that
when you see dust at home.

Unfortunately, in this process,
some cells may degenerate.

This can have several causes:

our lifestyle, inherited factors,
or our environment.

And these cells will start to degenerate.

For example, some of them
will become immortal.

When I first heard
some cells become immortal,

I thought we were all going to live long.

In fact, no, it just brings
processes to a complete end,

with the consequence
that the organ becomes non-functional.

So, at the root of a disease as serious,
as terrible, as cancer,

there are just tiny cells.

And a cell measures about 10 micrometres,

which is nearly 10 times smaller
than the diameter of a hair.

It is really small.

(Applause)

They are tiny, and cannot be seen
with the naked eye.

They also have an incredible quality
that is really vicious,

which is that they make themselves
invisible to our immune system,

and so our body cannot
defend itself against them.

There are different methods
to discover cancerous lesions.

For example, tumour marking:

We take a sample, we mark it,

and we get to detecting lesions

of several tens of thousands
of cancerous cells.

There's also imaging.

We inject a tracer into the patient,

use a device like
a PET scanner or a scintigraph,

and we can see lesions
of a few millimetres in size.

But already, the cancer
consists of tens of millions,

even hundreds of millions, of cells.

For a tumour to be
visible to the naked eye,

when it's nearly a centimetre across,

we're into hundreds of millions of cells,

even billions.

During the life of the patient,

most of these cancers are going
to be treated by surgical means.

That is, a man or a woman
will go to this organ,

which she or he knows is sick,
and will remove the tumour cells.

But at some point, despite
all their expertise and experience,

they'll need to ask themselves:

Should I continue
to scrape away at this organ?

Should I continue to remove
a small part of this organ?

If I continue, I may remove
some healthy, functional tissue,

and I may thus compromise
my patient's quality of life.

That's very clear when it's about
lesions in the brain, for example.

On the other hand, if I stop,
if I leave it as it is,

I take the risk of there
remaining cancer cells,

and then the cancer
may come back and re-advance.

It is precisely to see
the invisible boundary

between healthy cells
and those that are cancerous

that this project was started.

Imagine a cell.

So here, clearly, I shrank.

On this cell, there are
lots of tiny molecules.

These small molecules, all different,

can tell us about the internal functioning
and mechanism of the cell.

So, all we have to do is find the molecule
that tells us the cell is cancerous,

and we're there.

In biology, there are antibodies -
you've already heard about them -

and antibodies know how to do many things,

in particular, to recognize
and hook onto these molecules.

And onto our antibody,
we can hook a fluorophore,

a type of biological lantern

that re-emits light
when light is shone on it.

So, we attach this fluorophore
to our antibody,

and the moment our antibody
hooks onto the molecule,

it will signal to us
that that one is cancerous.

This is already a very big step.

But they went even further
in their research.

It so happens that when the antibody
hooks its molecule, it changes shape,

it's as if it folds its arms.

And this is great because there is
another physical effect called FRET -

Förster Resonance Energy Transfer.

I feel like I've lost you all.

This superb effect - it's quite easy
to understand, but it's incredible.

You have two fluorophores,
of different colours, one red, one green.

Each shines in its place,

but at a given moment,
at a really precise distance,

they will exchange their energy,
one will transfer its energy to the other.

And so our green fluorophore
begins to become dimmer,

while the red fluorophore
begins to become much more intense.

The idea behind it was
to take these two fluorophores,

hook them to very specific
places on our antibody,

so that when it recognizes
a cancerous cell,

by hooking onto it, it will change colour.

So, instead of seeing light
slightly green and red,

the surgeon will only see red light,

telling her or him that she or he
should continue to perform their surgery.

But to go even further,
we took these small antibodies

and put them at the end of a small
optical fibre about 2 mm in diameter,

to come directly into contact
with the patient's tissue.

By injecting a light beam,

we are able to tell whether or not
the tissues are cancerous,

whether or not to continue
to perform the surgery

to give the patient the best chance.

It's thanks to this project

that we can improve
the patient's quality of life

by making detectable what was invisible.

Thank you.

(Applause)