How to Live Longer The Big Think

Death...

sooner or later,

we'll all have to face it.

It's an inevitable part of life.

But medicine is engaged in a never-ending battle

to delay this final moment,

and, today, a biomedical revolution is promising to extend our

lifespan further than ever before and improve the quality of our lives

in old age.

With a Nobel Prize in physiology and a career spanning over four decades,

cell biologist and geneticist Paul Nurse is uniquely placed to explore

this fast-moving field of science.

We are beginning to understand the complexities of how cells work and how

that applies to how tissues and organs and bodies work.

And critically,

we can now imagine ways we can intervene with some of these complex

-processes.

-With the help of the BBC's archive,

Paul is going to take us to the extreme frontiers of medicine...

..where pioneers are experimenting with ground-breaking treatments...

Gene editing holds enormous potential in the treatment of cancers, and that

journey's really just beginning.

..where controversial figures may be going too far...

Why should I give up? I'm not the type to give up.

..and where ethical dilemmas abound.

We could start seeing the emergence of genetic haves and have-nots.

For Paul, the big question is not just what science can do to fix our

bodies and extend our lives

but whether it's right to use all the tools and techniques available.

If we don't keep society properly engaged and content with what we're

doing, then we will not be able to use science to help humankind.

We all hope to escape death for as long as possible.

And thanks to modern medicine,

we're now able to do this better than ever before.

In fact, our lifespan is increasing by two-and-a-half years every decade,

and a third of all babies born today can expect to live to 100 years.

Modern medicine is transforming our lives.

We're living longer, but it can come at a cost.

Old age itself brings with it a range of debilitating illnesses.

Many of the diseases of old age are a result of accumulating damage as

we live longer and longer.

Three diseases in particular have

become the main killers in the developed world,

cancer, heart disease and dementia...

..and it turns out that conquering all three diseases may be possible

with a single deceptively simple approach...

..understanding the fundamental building block of our bodies, the cell.

The cell is the basic unit of life. It's life's atom.

We are all made up of billions of cells, and they are extraordinarily

complicated. Many people think that CERN,

the Large Hadron Collider in Geneva, is the most complicated machine

known to man, but I tell you,

that is trivial compared with every one of those cells,

those billions of cells that makes up every one of us.

Throughout his career,

Paul Nurse has attempted to unlock the secrets of the cell and

understand how it relates to illnesses.

So, many of the diseases of old age -

heart disease, dementia, cancer -

can be traced back to cells.

So, knowing how cells work is important for understanding disease,

and knowing how we can fix cells provides us new ways of thinking of

how we can cure disease.

And by curing these illnesses,

we should be able to extend our lives even further and make our

old age a healthier experience.

Today, our ability to understand and manipulate the cell is creating

extraordinary new opportunities to tackle age-related diseases.

Half of us will be diagnosed with cancer at some point in our lives,

and there is one risk factor that is bigger than all others...

age.

Cancer is caused by genetic damage, and that genetic damage accumulates

over the years, and when enough genes become damaged,

then the cells go out of control,

they divide in an uncontrolled manner, and that forms a tumour.

So, in theory, curing cancer should be straightforward.

All you need to do is fix those faulty genes.

It's a technique known as gene therapy.

But although it may sound simple,

it is, in fact, one of the greatest challenges in modern medicine...

..and one fraught with ethical dilemmas.

The very first attempts at gene therapy in the 1990s didn't involve

cancer patients but young children who were born with a genetic disease.

One of them was four-year-old Ashi DeSilva.

She had a faulty gene that meant her immune system didn't work properly.

Ashi had a disease called ADA deficiency.

She never left the house except to go to the hospital or to the doctor.

She was just kept in quarantine because she was constantly sick.

In 1990, French Anderson and his team extracted blood from Ashi.

Then they took a healthy immune-system gene from a donor and put it into

her white blood cells in the lab.

The cells with the new, healthy gene

were then reinjected into Ashi's bloodstream.

Then they waited to see if the genetically modified

white blood cells would work.

Within six months,

her family began to realise that she wasn't sick at all any more,

that she was starting to do all the things that normal kids do,

and what tipped it over for the parents was in the spring,

so about six months after she started therapy,

the whole family came down with the flu...

and the first one up and playing was Ashi.

And the parents could not believe THEY were sick in bed

and their immune-deficient child was up playing around.

Ashi's gene-therapy treatment was successful,

but it wasn't perfect.

Her body still created its own blood cells with the defective gene,

so Ashi needs regular injections of healthy genes for the rest of her life.

French wanted to find a way to cure

someone with a disease like this for ever.

He thought he might be able to achieve this by injecting the

healthy genes directly into a foetus in the womb.

In theory, if the genes made it into the foetal cells,

the child would go on to create cells with healthy genes for ever.

It would be cured.

It seemed the perfect solution,

and in 1998, he decided to make it public.

We brought this to the government regulatory committees, basically,

three years before we anticipate being ready to actually do a clinical protocol.

And as expected...

..there was considerable interest in this topic.

As we did not expect,

there was a considerable amount of hysteria about this topic.

The cause of the hysteria was down to the fact that some of the cells

in an early embryo will turn into egg or sperm cells, and if the new gene

accidentally ends up in these, it will affect what's called the "germ line".

We need to think carefully about changes to genes that end up being

inherited from one generation to another, because that doesn't simply

affect the individual you're trying to treat for disease

but will affect subsequent generations, as well.

Many people seem to feel that...

..our honest statement,

that there might be a very low level of inadvertent germ-line gene

transfer, might really be hiding that we're trying to get into the

germ line, we're trying to redesign babies.

The stage was set for a mighty ethical battle.

French was convinced that foetal gene therapy could work and was

responsible. Set against him were moralists and some scientists who

feared it would lead to designer babies.

But in the end, it all came to nothing.

The difficult part of gene therapy had always been getting the healthy

gene into a cell.

French had used a virus.

These viruses had been modified so that they wouldn't cause an infection

as they transported the healthy genes inside the cells.

In other clinical trials, these modified viruses also seemed to be working.

But then, one gene-therapy trial in Philadelphia went dramatically wrong.

Jesse Gelsinger had been injected with a modified cold virus as part of a

gene therapy treatment, but the virus was

not as safe as scientists had thought.

Within a week, it had attacked all his major organs and he died.

Jesse's tragic death changed everything.

It was clearly far too early to think about using this potentially

dangerous technique in the womb.

A few years later, French Anderson's career was

destroyed when he was jailed for sexual offences.

The challenge of getting a

healthy gene safely into a cell seemed insurmountable.

But what if there was an altogether different way of doing gene therapy,

one that didn't require a virus to carry new genes into the human body?

It's an idea that has been central to Paul's career.

He has spent most of his life studying yeast, and by working with

this tiny, simple microorganism, he found a way to get a new gene into a cell.

In 1981,

we developed techniques that allowed us to introduce genes into yeast

cells and to very precisely replace one gene with another.

And that's actually the main reason I've worked on yeast for all

these years, because I could do such precise experiments.

This method would later be dubbed "gene editing".

Just like early gene therapy,

the purpose of gene editing is to modify genes.

But the way the two methods work is fundamentally different.

Early experiments with human cells were rather crude.

Genes were added, they could integrate anywhere in the genome.

They might or might not work,

they might damage other genes where they'd integrated,

and you really didn't know what was happening.

Gene editing, on the other hand, is much more precise.

It fixes the faulty gene by snipping

it out and replacing it with the correct one.

For example, if you have a damaged gene and you were just introducing

genes randomly, you're still left with that damaged gene.

But if you can gene-edit it,

then you can replace that damaged gene with one that works perfectly.

Doing this in yeast is relatively straightforward.

What I've got here is an example of an experiment

where we've done gene editing of yeast.

We've put DNA into the yeast cell and transformed how it behaves.

In this experiment, Paul took two yeast cells.

He then gene-edited one of them to enable it to grow in a Petri dish

containing particular types of nutrients.

So, if you look here, you will see

all these little sort of cream blobs here.

Each of these contain about 100 million yeast cells, and each one of

them grew from a single cell by repeated divisions.

Now, on this plate, we put yeast cells that have been treated with the gene.

These were gene-edited. So, these colonies here could grow,

whereas here, we didn't treat them with DNA, and you can see there's no

colonies growing at all, because they couldn't grow without that new gene.

Gene editing in yeast was a big step forward,

but developing the same technique in much more complex human cells would

prove extremely challenging.

If we take the genome in a human cell, it's much, much bigger,

it's much more tangled up,

and you can't use those simple methods to get access,

so you have to use other molecular tricks to expose the gene and allow

it to be changed by the genes that you're introducing.

These new molecular tricks would eventually be developed, and in 2015,

gene editing hit the headlines.

A baby girl from London has become the first person in the world to

receive a revolutionary genetic treatment

which doctors have described as almost a miracle.

The little girl was diagnosed with leukaemia when she was just

three months old. After all conventional treatments failed,

doctors at Great Ormond Street decided the only option left was an

experimental technique.

The pioneering scientist behind this treatment was Professor Waseem Qasim.

For several months,

he had been working on a new type of leukaemia treatment in which

white blood cells are engineered to recognise cancer cells.

White blood cells are the body's soldiers.

They circulate the body, cleaning up infections,

dealing with intruders, and are essential to stay in good health.

Waseem focused on a type of white blood cell called a T cell.

T cells, in particular, are thought to contribute to what we call immune

surveillance, so they circulate the body looking for abnormal cells and

will deal with them. But in some patients, that doesn't happen and

leukaemias and cancers can develop.

So, Waseem and his team took a batch of T cells from a donor and

engineered them to be able to recognise and attack cancer cells.

But they had to make another key

change because of a dangerous property of T cells.

T cells can also mistake a patient's own tissue as foreign and attack it,

so the next step was to gene-edit the T cells

to prevent this potentially

deadly side effect.

So, by the end of the process,

those cells will then only recognise leukaemia cells and won't harm any of

the normal tissues in the body.

The little girl only needed a small phial of these modified blood cells

and within weeks, it was clear that it had worked.

The cancer cells were knocked out,

but the rest of the body was left untouched.

Since then, another child has been treated successfully, and clinical

trials for children and adults have just started.

But, for Waseem, this is just the beginning.

Gene editing is a very fast-moving field, and the latest technique, Crispr,

is set to revolutionise what can be done because it is much faster and

more precise than previous methods.

We think Crispr will be able to target a much larger number of sites in the

genome and will form the basis of the next generation of gene editing

as we go into the next few years.

So far, gene editing has been used for leukaemias and lung cancers,

but in the future,

the hope is to use it for different types of cancer and

perhaps even to repair other damage caused by ageing.

However, gene editing is such a precise and powerful technique that

it leads to profound ethical and social issues.

For many years, we've imagined using gene therapy and manipulating human

genes, but it was rather theoretical.

But the modern technique of Crispr, allowing very precise gene editing,

changes that situation completely.

We've been discussing these ethical problems on and off, but because we

couldn't do it, it didn't have any urgency.

Now we can do it, it has REAL urgency.

The fears aren't so much to do with treating cancer and thereby

extending life, it's more that gene editing could also be used in other ways,

for example, to modify human embryos.

And this is already happening.

Scientists at the Francis Crick Institute will soon be the first in the UK to do this.

So far, it's only being done for research.

None of the embryos will be allowed to develop beyond seven days.

But some fear this may be the beginning of a slippery slope

towards designer babies.

Fertilisations were all very successful.

There are a few things we'd like to have modified, if possible.

We'd like her to be musical and, if possible,

also, we want her to be ambitious.

Well, we don't want to tamper with the physical side of things

-in any way.

-No,

except that we would like her to have my father's red hair.

Ah. Well, let's see if we can make a budding musician out of her.

For critics, this 1980s vision of genetic engineering no longer seems

-so far-fetched.

-Once we produce genetically modified human embryos

in labs around the world, it's

really not that big of a jump to try to initiate a

pregnancy with one of those.

And it also raises the spectre of genetic discrimination.

You could find wealthy parents buying the latest offspring upgrades

for their children, genetic changes that either did or even that were thought

to make their children superior in some way. And there we could start

seeing the emergence of genetic haves and have-nots.

Some people have called them genetic castes.

People have thought about this,

they've called them the Gen-Rich and the Naturals, and we could be seeing

much greater forms of inequality

even than the already-horrendous levels of inequality we live with.

I'm not really impressed by slippery-slope arguments.

If we can learn something of great value, then that is a great prize to

be won. It doesn't mean that automatically leads to the next step and the

step after that and the step after that.

We still have control over those later steps.

Now that the gene genie is out of the bottle,

society will have to decide what

limits should be placed on this emerging technology.

The danger is that powerful new genetic techniques for curing diseases

such as cancer could be ruled out because of the risk that these same

techniques might be used for less noble causes.

But targeting faulty genes in our cells is just one approach to dealing with

age-related diseases.

Conditions such as dementia that are caused by degeneration in the brain

may benefit from another method,

one using a type of cell called a stem cell.

A stem cell divides and forms cells that then go on to make tissues and

different organs in the body.

They are really the basis of how we make ourselves.

It's this extraordinary ability to turn into almost any type of cell

inside the body which has led some scientists to wonder -

could stem cells be used to create

new brain cells and so regenerate our brains?

As we grow older, our bodies wear out, our organs deteriorate,

our cells stop functioning properly.

And the signs of time are particularly visible in one organ...

..our brain. Almost all aged brains show signs of degeneration,

even if they don't belong to someone who suffers from dementia.

This happens even though our bodies work hard to keep any form of

degeneration at bay throughout our lives.

Many people think that our body is static and that we have what we

have, but in fact, that's not the case.

We're constantly replacing cells, about two million or so every second.

Some are lost through wear and tear, some just reach the end of their

life and others deliberately self-destruct.

The life cycle of every cell is carefully controlled, and a healthy body

always has just the right number of each type of cell.

You have cells in the stomach here and in the gut in particular

where you can have very rapid turnover, because the gut particularly is a

very harsh environment, and so there's a constant high rate of turnover of cells.

In fact, in the gut it's about every two or three days cells have to be

replaced. And then you've got organs like the liver...

..where there's a sort of gradual turnover of cells every few months.

Even structures that you think may be very static, like bones

for the skeleton here, is turned over probably once every ten years or so,

so if we didn't have that self-renewal, you'd completely lose your skeleton,

which would be pretty bad!

This natural ability of our body to replace cells begs one question.

Could we somehow harness it to renew

and regenerate ourselves indefinitely?

I think it's starting!

Well...here we go again.

Today, the idea of regenerating our brains or any other organ is no longer

the science fiction it once was...

..because we now know that it's stem

cells that fuel this constant tissue renewal.

So, stem cells are really central to understanding development and have a

role later in life for making all

the different tissues and organs of our body.

Most organs have their own supply of them.

Even the brain contains stem cells, but only in very limited areas.

As a result, when nerve cells are lost in people with dementia,

the brain doesn't have the capacity to repair the damage.

But what if healthy stem cells could be injected directly into the brain

to help repair it?

The first steps towards this goal were taken in the early 1980s by

Anders Bjorklund at Lund University in Sweden.

He was interested in Parkinson's,

a degenerative brain disease that often leads to dementia.

If this is the brain...

..the area we are interested in is an area up in the forebrain called

the striatum, which regulates movement.

Normally, dopamine neurons send nerve fibres up to the striatum,

which produce dopamine in the striatum.

In the Parkinson's patient,

dopamine is missing in this area, and that is,

in all likelihood, the major cause of their symptoms.

Anders realised that crucial dopamine-producing brain cells were missing

in Parkinson's disease...

..so he decided to take dopamine cells from a rat foetus and inject them

into the brain of an adult rat unable to produce dopamine in one part of

its brain.

The hope was that this would

replenish the dopamine and restore its motor function.

The results were remarkable.

This rat lacks dopamine in one half of its brain and is moving around in

circles because of this imbalance.

But when a rat in a similar condition has had foetal dopamine cells

transplanted, it behaves normally and no longer moves in circles.

The success of experiments like these led scientists to consider

transplanting foetal brain cells into humans.

But they immediately faced strong opposition.

The way in which you collect the foetal tissue is from...

..women who've decided to have a termination of pregnancy,

an abortion. This has always been a highly controversial area.

For some, abortion itself is anathema.

For others, the ethical issues have more to do with the point at which

it becomes unacceptable to take material from a developing foetus.

Most people - not all people,

but most people - are comfortable with work on the first week or two of a

human embryo, when it's a ball of cells, and most people would be extremely

uncomfortable doing similar things with a much more advanced foetus,

at 20, 22 weeks, for example.

And somewhere between these limits,

there's a place where it becomes unacceptable,

but how can we define that place? And that's a really difficult debate to

have, because there are clearly benefits to be gained,

but there are also great concerns about the sanctity of human life.

In the 1980s, the White House put a ban on all federal funding for this

kind of research in the United States.

But back in Sweden, human trials eventually got the go-ahead.

And so, after 30 full rehearsals for the surgery,

the Swedish team was ready and two patients with advanced Parkinson's

disease underwent a transplant of foetal dopamine cells.

But one year after the surgery, the patients were only slightly better.

These initial results didn't tell the whole story, though.

Over time, when they waited,

they started to see some fairly dramatic results, and in the best-case

scenario, patients, five or ten years after having the transplant,

had, on scanning of the brain,

normal dopamine levels produced by the dopamine cells they'd grafted.

The patients clinically looked normal,

they looked as though they hadn't got Parkinson's disease, and they'd

managed to stop all of their medication.

These extraordinary results caught the world's attention, and several

groups tried to replicate the Swedish study.

But they didn't succeed,

so the area of foetal cell transplants was effectively killed off...

..that is, until Roger Barker and Anders Bjorklund took a closer look at the

data and realised that there were significant differences in the way these

latest studies had been conducted.

The main difference, I would say, between the Swedish studies and many

of the studies that followed on was that the Swedish study used quite a lot

of tissue, so you were never going to see a big effect if you didn't put

in enough of the cells you wanted.

And the other thing that became clear was that younger patients,

slightly earlier in the disease course, probably benefit most from this.

So, Roger and Anders decided there was enough encouraging evidence to

justify a new study on Parkinson's patients.

Their latest study is already under way.

So far, nine patients have been treated with foetal dopamine cells and

another five are to follow in 2017.

It's too early to say whether the transplants have worked or not,

but the results so far are encouraging.

I'm just going to pull you backwards and I just want you to keep your

balance. So, one, two, three.

Very good.

But for Roger, foetal transplants are just a stepping stone.

Even if this trial works and the foetal dopamine cells do end up curing

Parkinson's disease, there's a practical problem with this approach.

We simply can't get hold of enough foetal tissue to treat the number of

patients we need to treat.

So, the next step for Roger is to create the same kind of dopamine cells in

the lab.

To do this, he needs to start off with a particular type of stem cell,

an embryonic stem cell.

When the egg gets fertilised and we get the cells developing in the very

early embryo, these are called embryonic stem cells.

Embryonic stem cells are cells which can turn into any cell in the body,

and every single one of us began life as an embryonic stem cell.

Embryonic stem cells are the most versatile of all stem cells, and Roger

and his team have already been able to coax them into dopamine cells in

the lab.

But embryonic stem cells come with their own ethical problems.

Embryonic stem cells are produced from leftover embryos from IVF

procedures, so they would be discarded normally,

but, in this instance, they're being used to make embryonic stem cells, and

some find this an ethical issue.

They feel that the sanctity of human life would mean that they shouldn't

be used for this purpose.

My own personal view is that we SHOULD use early embryos to make embryonic

stem cells. I think that's a good thing.

It's making use of this life that's never going to be developed to help

other people's lives.

Because of the ethics surrounding embryonic stem cells,

scientists have long been looking for an alternative source for

regenerative cells.

And on their hunt for a new type of stem cell, one obscure experiment with

frogs conducted in the 1960s would prove crucial.

-ARCHIVE:

-Dr John Gurdon at Oxford University wanted to test the idea that each

of the millions of specialised cells in our bodies contains the complete

genetic blueprint for a whole new individual.

He chose frogs for his experiments because they are cheap,

easy to look after

and they lay large numbers of eggs which can put up with rough treatment.

Eggs from a green female are set out on a microscope slide with the part

containing the nucleus facing upwards.

The nucleus contains the female chromosomes, which Dr Gurdon destroys

by exposing the eggs to ultraviolet light.

Next, albino tadpoles are dissected to provide cells for transplantation.

Gurdon uses cells from the tissues lining the tadpole's intestine.

With the micromanipulating gear,

Dr Gurdon inserts one albino cell nucleus into each egg.

Each batch of eggs is put into a dish of solution, and within a few hours

some of the transplanted nuclei will

begin dividing and subdividing normally.

And this is the point of Dr Gurdon's experiment.

It proves that each intestine cell nucleus can be switched on to multiply

into dozens, hundreds,

thousands and millions of cells which make up a living creature.

As the cells multiply, they also specialise to form skin, muscle, eyes,

brain tissue and so on.

John Gurdon effectively managed to reprogram a tadpole cell and switch its

genes from the duties of a gut cell to those needed to develop into an

entire frog.

John Gurdon's work changed the way that we think about how cells become

specialised. What it showed was that even in specialised cells, all the

genes were there that can make other cells,

but what matters is which genes are

turned on and which genes are turned off.

John Gurdon's discovery turned on its head the view that becoming a

specialised cell is a one-way system.

This bold experiment suggested that even when cells perform one

specialised role they still retain all the instructions needed to turn

into any other type of cell.

This raised the possibility that perhaps we could create stem cells from

something like skin or fat cells.

It took 50 years, but in 2006,

a young Japanese researcher called Shinya Yamanaka finally made a

-breakthrough.

-What he showed is that he could take an adult cell and treat

it in a particular way to turn it into a cell that had more stem cell

properties, that could turn into other sorts of cells.

And this actually removes the need to always work with embryonic stem cells,

and so that removed that ethical problem.

It was also a great bit of science.

These new stem cells are already proving an invaluable tool in the lab,

where they are helping scientists study dementia.

The hope is that one day these cells can be used to regenerate many

different parts of the brain and ultimately allow us to live longer.

But stem cells are not only showing great promise because of their ability

to regenerate tissues inside the body.

Some scientists have started using

them to create whole new organs in the lab.

Our heart beats, without ever stopping, about 100,000 times every day...

..and yet it is one of the few organs where cell renewal doesn't take place,

or if it does, it does so at an almost imperceptible pace.

This makes the heart extremely vulnerable, and any damage you accumulate

during your lifetime simply remains there.

A few years ago, I was privileged to go to Antarctica to visit Scott Base,

and they made me have a full medical because there's no hospitals near

Scott Base, of course.

And that revealed that I had major coronary disease.

Five of my arteries feeding the heart had partial blockages.

That meant, within weeks, I was in hospital and I had a quadruple heart

bypass, but I'm very lucky because I was a disaster waiting to happen.

But not everyone is as lucky as Paul.

Ageing can also lead to much more severe heart failure, and in some cases,

the damage will be so big that the only hope of survival

is a transplant.

Surgeons had long dreamt of doing something as extreme as a transplant,

but this remained firmly in the realm of fantasy...

..until one man made headlines around the world in 1967.

The world's first heart transplant has been performed.

Medical history has been made in South Africa.

Newspapers everywhere carry banner headlines and for medical men as far

away as the Soviet Union, there is a claim for the dramatic breakthrough.

The surgeon was Dr Christiaan Barnard,

an outsider who had taken the world completely by surprise.

That was a new experience,

because I've never seen a human being that was

actually alive without a heart inside his chest.

And I realised at that stage that I was doing something different.

I'd never done this before,

and I realised that I have to put a heart back there.

The patient was Louis Washkansky.

For the first time, a transplanted heart beat inside the chest of another

human being.

It was amazing to see how he lost all evidence of heart failure.

The swelling in his legs disappeared and he was well, mentally well,

and I really did not believe that it will not be successful.

Sadly, Louis Washkansky died two weeks after transplantation,

but despite the death of his patient, Barnard's life was transformed.

I'm a celebrity, everybody wants to talk to me,

everyone wants to meet me.

I get invitations left, right and centre. It was exciting.

Naturally, other doctors wanted to share his popularity.

In 1968, transplant fever gripped the world.

102 people were given new hearts in 18 different countries.

But as the '60s drew to a close,

the heart transplant dream was beginning to fade.

The problem was that patients required huge amounts of drugs to stop the

rejection of their newly transplanted heart.

And even with the drugs, the survival rates made grim reading.

Cardiac surgeons who knew absolutely nothing about transplantation,

transplant immunity, the immune transaction of rejection,

wanted to show that they also could transplant the heart, with a 100%

mortality, and that was a disaster.

The man who started it all, Christiaan Barnard,

may have become a celebrity,

but many other medics were getting anxious, and when the BBC invited him to

face his peers, he got a kicking.

The nauseating publicity, I think, has done harm to the profession,

it's done harm to yourself.

We're going to get so many failures that the public reaction against it

will effectively postpone the day when we can all say that this can be

safely done.

It wasn't until the discovery of the drug ciclosporin years later that

organ rejection could be properly controlled.

When you are on the edge of modern advances, it can be quite a risky

venture. In hindsight, Christiaan Barnard got it right,

but it probably would have only required a few more failures and we'd

judge him, perhaps, quite differently.

But thanks to ciclosporin,

heart transplants eventually succeeded and survival rates began to soar.

But this also meant the demand for organs rocketed.

And it soon became clear that, when it came to heart transplants, demand would

always outstrip supply,

so the race began to find an alternative.

One of the most obvious questions was could we build an artificial heart.

But for many people, artificial

organs raised fears of Frankenstein science.

And look, here's the final touch.

-The brain you stole, Fritz.

-Yes!

-Think of it,

the brain of a dead man waiting to live again in a body I made with my

own hands. With my own hands!

Let's have one final test. Throw the switches.

For the scientists working in this field, however,

"Frankenstein science" simply means that their research is pushing the

boundaries of the possible. Doris Taylor is one of them.

In her quest to help us conquer the degeneration caused by ageing,

she uses real hearts as a starting material.

The heart is made from billions of muscle cells,

but what Doris is most interested in is the support structure they're

built on, so she drains the heart cells to expose this scaffold and then

uses stem cells to build up the required heart cells on top of it.

You need a scaffold,

you need a place to put those cells so they know that they're a heart.

She started by taking a rat heart and removing all its cells.

Then she successfully introduced stem cells to the rat heart scaffold and

made it beat again.

Now she's gone one step further.

She's trying the same method on human hearts.

It's a process which, for now, begins with a donor heart.

First, Doris needs to hang it in the best position possible to strip it of

its own cells.

It takes three days for the scaffold to emerge - a fine mesh of collagen,

originally secreted from the heart cells that are no longer there.

And that we call our "ghost heart". It's beautiful.

It's when stem cells are placed on the ghost heart that their amazing

potential for regeneration can be realised.

But how do they really know how to be a heart?

We think it's architecture.

If you think about it, cells in a dish beat,

but that doesn't make a heart.

When we put them back in this scaffold, they find themselves in the right

place. They're surrounded by the right things.

They know they're in a thin region or a thick region, and we really think

that to build an organ is not just a combination of cells,

it's cells and architecture and physiology.

Doris's ultimate goal is to create the scaffold from pigs' hearts.

The thought would be that we would take a heart, probably from a pig...

..do this process, wash all the cells out...

..and then take your cells...

..and grow enough of them to repopulate this with your cells,

build a heart that matches your body.

If this works, it will be revolutionary.

But using pigs to grow human body parts is not uncontroversial.

In thinking about this, I don't think it's really an ethical problem,

it's more of, if I can be colloquial,

more of a sort of "yuck factor" problem.

It just doesn't seem quite right.

And that still needs to be discussed, because yuck factors can influence

whether something is accepted or not.

But even if Doris's approach works and society accepts using animal parts

for human transplant, could science provide a better solution?

What if we could create an entirely artificial organ from scratch?

One of the scientists pursuing this radical idea is

Professor Paolo Macchiarini of the Karolinska Institute in Sweden.

His approach is to create a scaffold from plastic and then,

in the same way as Doris, seed it with stem cells.

The heart is an exceptionally complex structure,

so Paolo decided to start with something much simpler,

the windpipe, or trachea.

And, in 2011, he achieved the seemingly impossible.

Surgeons in Sweden have carried out the world's first transplant using a

synthetic organ.

The recipient, a 36-year-old man, is said to be recovering well.

After this initial success,

two more synthetic tracheas were implanted into patients who suffered from

cancerous growths on their windpipe.

But soon things started to go wrong.

Both these patients died shortly after their surgery.

If you have a patient that dies because of the new technology,

then you always ask yourself, "Did I do something wrong?

"Do I have the right to continue? Should I continue?"

But still, you learn only by doing.

It's going to be quite difficult to distinguish the two...

-measurements that we get.

-Difficult but not impossible, right?

'So, this is an interesting case.'

Here we have a surgeon wanting to do experiments right on the edge of our

understanding. We probably have leadership at the Karolinska who perhaps

didn't pick up the warning signs that something was not working well, and

there is a sort of atmosphere that develops that allows, perhaps, risks to

take place.

Despite these setbacks,

Paolo carried on with his highly experimental work on patients...

..and so over the next three years he implanted six more synthetic tracheas.

Dmitri Onogda was his ninth patient.

In 2007, Dmitri was involved in a serious road accident.

His windpipe was so badly damaged that he is unable to speak and can only

breathe through a hole made in his throat.

Dmitri's only hope of being able to breathe and speak normally again is to

have a new windpipe, so he's agreed to undergo this operation.

The patient had a car accident,

had multiple surgeries and then

complication over complication after these surgeries.

Here is the point where you have your vocal cords.

Paolo's team has extracted some of Dmitri's bone marrow and then isolate

stem cells from it.

The hope is that by adding them to the scaffold they will grow into the

same cells that make up the windpipe.

The aim is not to build a completely finished windpipe in the lab.

Paolo believes that once the scaffold is inside the body,

the stem cells on the surface will give out a signal that will attract

more cells to it and it will eventually develop into a fully functioning

windpipe after transplantation.

Can we have a smaller suction?

When do you need it?

-As soon as possible.

-OK.

He is above 90. So, that's not a problem. As long as it is not 40,

that's OK.

Don't do what you want. Go up in this here.

I want to see the scaffold, if it is OK or not.

Yes.

-So, looks perfect.

-So I start the next one.

After six hours,

Paolo is satisfied that the stem- cell-coated scaffold is in place.

Everything OK.

Yeah. Sure, yes, you are alive!

Sadly, Dmitri's plastic trachea never functioned.

It had to be removed and replaced by one from a donor,

but Dmitri survived.

However, he is one of only two plastic-trachea patients still alive today.

It's not clear whether the deaths were related to the windpipe surgery...

..but by the end of 2014, allegations emerged against Paolo.

It was questioned whether he had exaggerated the success of his implants

in scientific papers and conducted

enough basic research before the human trials.

If you have a clinical situation where you are...

forced to take a risk,

then you take it if you see any chance to help the patient.

It appears Paolo was hoping that ultimately history would vindicate

the risks he took.

Being at the cutting edge...

..you are always wrong...

until sooner, more likely later, you demonstrate the opposite.

Why should I give up? I'm not the type to give up.

But in March 2016, Paolo was fired from the Karolinska Institute.

We really do have to pay attention to this, because we have to maintain

standards but we also have to have the possibility of doing experimental

interventions like this but doing them properly.

The real issue here, for me, was that the basic research of understanding

what was going on here had not been carried out adequately

so that you could more safely do the interventions in human beings.

For Paul, these failed experiments

are a reminder of how complex our cells are.

As for heart transplants, the immediate future is still human donors.

But perhaps there is an altogether simpler way of overcoming the diseases

of old age.

What if we could just stop getting old?

For me, ageing is things just breaking down.

Everything breaks down - our human bodies, also our cars.

It's the wear and tear of working over many years that things just stop

working properly.

But not everyone agrees with the wear-and-tear theory of ageing.

I think a lot of the evidence that we're finding now is that ageing isn't

just a consequence of things falling apart in response to direct insults

of daily living,

some of it is the body's own activities causing the ageing process.

It's actually the real biology of

the cells themselves that's going wrong.

Professor Dame Linda Partridge studies the genetics of ageing with the

hope that one day she can slow it down.

Her experimental subjects - fruit flies.

In particular, she has been investigating the effects of a gene

-called chico.

-It turns out that if you knock out this gene,

the fly lives about 30% longer than usual.

But what's more, without the chico gene the flies also become healthier.

They learn better when they're old, they've got better immunity,

they move around more.

They don't only outlive the control flies

but they remain active long after the controls are dead.

Linda then went on to show that there is a similar gene in mice.

It isn't called chico in the mouse,

it's called insulin receptor substrate 1,

which doesn't sound quite so interesting, but if you knock it out,

again you see this nice increase in lifespan, and also as it gets older,

the mouse shows a broad-spectrum improvement in health and resistance to

disease, so it's a very similar story,

just a single gene but a very broad-spectrum effect of removing it.

When single genes are changed, animals that should be old stay

young and are able to resist age-related diseases.

So does this mean we can begin to think of ageing itself as a disease?

I would regard ageing as the king of all diseases.

It's regarded as normal because ageing is something that happens to

everybody. If they live that long, we tend to take it for granted.

And if ageing is a disease, perhaps it can one day be cured

or at least postponed.

The next step now is to look for similar genes in humans, and early results

suggest that they do indeed exist.

But as tempting as it may be to knock out these genes, there is a problem.

They turn out to be important early in life.

We think that these genes and their activity are very valuable in young

organisms, so we're definitely not

talking about genetic manipulation of people.

For Linda, rather than knocking out these ageing genes,

the way forward will be using drugs to alter their activity later in life.

What we'd love to be able to do is to take humans in middle age

and start to use drugs to control the activity of these processes that

turn out to be damaging as they get old and in that way prevent

ageing-related diseases.

Whether or not you think that ageing in humans will one day be a curable

disease, one thing recent developments in biomedicine show us is that most

of our age-related illnesses begin with the cell and the genes within it.

Today, we're at the start of an exciting new era.

Science is making huge leaps in tackling the killer diseases that cut us

down in old age.

Advances in science are really leading to a potential revolution in

the way that we can treat disease, ways that involve gene editing,

ways that involve stem cell therapies.

So, there's a real promise for the future.

But for Paul, none of this must

happen without exploring the ethical implications.

We have to have a society comfortable with the applications of

science to medicine. And that means having proper debate with society,

so that they

are engaged and feel comfortable with what scientists are trying to do,

because if we don't,

then scientists will lose their licence to operate and the whole of

society will lose out.

But ultimately, we also need to ask ourselves how far we want to push

the boundaries in our quest to prolong life.

I've never seen anything like it.

It means Linden found a way to stop ageing, maybe permanently.

I hope you are wrong. It will be a disaster.

Overpopulation, starvation... It will be the end of this planet.

Or the beginning of a new civilisation.

Come on, Dr Land.

Sooner or later, we all have to surrender our places to others, and the more

gracefully we do it, the better.

For Paul, the science that aims to conquer the diseases of old age

may deliver a bigger prize than extending life.

I think all of us would like to live longer, as long as it's healthy,

but do we really want immortality?

Is there perhaps not a curse in living forever?

All the trials and tribulations of life that we have, would never end.

But what we should aim at is maybe living the longest normal span that

we can imagine with a very healthy body and mind, and that's what

I would aim at.