The Big Think - Should We Go to Mars?

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