to talk to you all about how we might repair

the damaged brain,

and I'm particularly excited by this field,

because as a neurologist myself,

I believe that this offers one of the great ways

that we might be able to offer hope

for patients who today live with devastating

and yet untreatable diseases of the brain.

So here's the problem.

You can see here the picture of somebody's brain

with Alzheimer's disease

next to a healthy brain,

and what's obvious is, in the Alzheimer's brain,

ringed red, there's obvious damage -- atrophy, scarring.

And I could show you equivalent pictures

from other disease: multiple sclerosis,

motor neuron disease, Parkinson's disease,

even Huntington's disease,

and they would all tell a similar story.

And collectively these brain disorders represent

one of the major public health threats of our time.

And the numbers here are really rather staggering.

At any one time, there are 35 million people today

living with one of these brain diseases,

and the annual cost globally

is 700 billion dollars.

I mean, just think about that.

That's greater than one percent

of the global GDP.

And it gets worse,

because all these numbers are rising

because these are by and large

age-related diseases, and we're living longer.

So the question we really need to ask ourselves is,

why, given the devastating impact of these diseases

to the individual,

never mind the scale of the societal problem,

why are there no effective treatments?

Now in order to consider this,

I first need to give you a crash course

in how the brain works.

So in other words, I need to tell you

everything I learned at medical school.

(Laughter)

But believe me, this isn't going to take very long.

Okay? (Laughter)

So the brain is terribly simple:

it's made up of four cells,

and two of them are shown here.

There's the nerve cell,

and then there's the myelinating cell,

or the insulating cell.

It's called oligodendrocyte.

And when these four cells work together

in health and harmony,

they create an extraordinary symphony of electrical activity,

and it is this electrical activity

that underpins our ability to think, to emote,

to remember, to learn, move, feel and so on.

But equally, each of these individual four cells

alone or together, can go rogue or die,

and when that happens, you get damage.

You get damaged wiring.

You get disrupted connections.

And that's evident here with the slower conduction.

But ultimately, this damage will manifest

as disease, clearly.

And if the starting dying nerve cell

is a motor nerve, for example,

you'll get motor neuron disease.

So I'd like to give you a real-life illustration

of what happens with motor neuron disease.

So this is a patient of mine called John.

John I saw just last week in the clinic.

And I've asked John to tell us something about what were his problems

that led to the initial diagnosis

of motor neuron disease.

John: I was diagnosed in October in 2011,

and the main problem was a breathing problem,

difficulty breathing.

Siddharthan Chandran: I don't know if you caught all of that, but what John was telling us

was that difficulty with breathing

led eventually to the diagnosis

of motor neuron disease.

So John's now 18 months further down in that journey,

and I've now asked him to tell us something about

his current predicament.

John: What I've got now is the breathing's gotten worse.

I've got weakness in my hands, my arms and my legs.

So basically I'm in a wheelchair most of the time.

SC: John's just told us he's in a wheelchair

most of the time.

So what these two clips show

is not just the devastating consequence of the disease,

but they also tell us something about

the shocking pace of the disease,

because in just 18 months,

a fit adult man has been rendered

wheelchair- and respirator-dependent.

And let's face it, John could be anybody's father,

brother or friend.

So that's what happens when the motor nerve dies.

But what happens when that myelin cell dies?

You get multiple sclerosis.

So the scan on your left

is an illustration of the brain,

and it's a map of the connections of the brain,

and superimposed upon which

are areas of damage.

We call them lesions of demyelination.

But they're damage, and they're white.

So I know what you're thinking here.

You're thinking, "My God, this bloke came up

and said he's going to talk about hope,

and all he's done is give a really rather bleak

and depressing tale."

I've told you these diseases are terrible.

They're devastating, numbers are rising,

the costs are ridiculous, and worst of all,

we have no treatment. Where's the hope?

Well, you know what? I think there is hope.

And there's hope in this next section,

of this brain section of somebody else with M.S.,

because what it illustrates

is, amazingly, the brain can repair itself.

It just doesn't do it well enough.

And so again, there are two things I want to show you.

First of all is the damage of this patient with M.S.

And again, it's another one of these white masses.

But crucially, the area that's ringed red

highlights an area that is pale blue.

But that area that is pale blue was once white.

So it was damaged. It's now repaired.

Just to be clear: It's not because of doctors.

It's in spite of doctors, not because of doctors.

This is spontaneous repair.

It's amazing and it's occurred

because there are stem cells in the brain, even,

which can enable new myelin, new insulation,

to be laid down over the damaged nerves.

And this observation is important for two reasons.

The first is it challenges one of the orthodoxies

that we learnt at medical school,

or at least I did, admittedly last century,

which is that the brain doesn't repair itself,

unlike, say, the bone or the liver.

But actually it does, but it just doesn't do it well enough.

And the second thing it does,

and it gives us a very clear direction of travel for new therapies --

I mean, you don't need to be a rocket scientist

to know what to do here.

You simply need to find ways of promoting

the endogenous, spontaneous repair that occurs anyway.

So the question is, why, if we've known that

for some time, as we have,

why do we not have those treatments?

And that in part reflects the complexity

of drug development.

Now, drug development you might think of

as a rather expensive but risky bet,

and the odds of this bet are roughly this:

they're 10,000 to one against,

because you need to screen about 10,000 compounds

to find that one potential winner.

And then you need to spend 15 years

and spend over a billion dollars,

and even then, you may not have a winner.

So the question for us is,

can you change the rules of the game

and can you shorten the odds?

And in order to do that, you have to think,

where is the bottleneck in this drug discovery?

And one of the bottlenecks is early in drug discovery.

All that screening occurs in animal models.

But we know that the proper study of mankind is man,

to borrow from Alexander Pope.