Good mutants | Nico Katsanis | TEDxAthens

Mutation in popular culture is deemed a disease for humanity. From the X-MEN to real life examples, Dr. Katsanis draws a line and explains the future of genetics, diseases, and the evolution of humanity.

Dr. Katsanis is the Director of the Centre for Human Disease Modelling, Professor of Cell Biology and Distinguished Professor of Paediatrics at Duke University. He obtained his first degree in Genetics from UCL in London in 1993, then in 2002 he became an Assistant Professor at the Institute of Genetic Medicine, Johns Hopkins University and was promoted to Associate Professor in 2005.

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

(Greek) Good afternoon.

I apologize I have to speak in English,

I have done my entire
education in English,

but I hope everybody
will be able to follow.

So thank you, Manoli,
for the kind introduction.

It is very good to be with you.

Today, we are going to talk
about one word, and one word only,

and that word is "Mutants."

Now, let us all be honest with each other.

We do not bring positive images
in our minds when we think about mutants.

We do not look at each other and say

"Oh, he looks so mutant"
or "You are such a mutant"

as a term of endearment.

Before I go any further,
I need to make sure

that you can tell everybody
that you cannot catch a mutation,

and no, you do not get
mutations by spider bites.

Just thought to put that out there.

But culturally, for a very long time,

we have considered a mutant
to have a negative connotation,

and the picture
that you will see behind me

are these horrible monster
creatures in some cave.

In fact, as I was looking around
to see appropriate pictures,

I actually found a mutant zombie.

As if being a zombie is not bad enough,
you have to be a mutant zombie. OK.

(Laughter)

However, here is the thing.

It is all not true.

The word mutant

simply means a change in DNA,

and it does not have a positive
or negative qualifier

about what it does.

All it talks about is the fact
there is a position in your DNA

that is different from what is
the reference position,

and we have known about this
for the best part of 100 years,

since we started manipulating DNA
in flies and other creatures.

And in many ways, we are all mutants,
and I will come to that in a moment.

So, now we have the mutant misnomer.

There is a second misnomer
I would like to talk about.

And the second misnomer is "Healthcare."

This is where I work - this is where
I am privileged to be able to work;

it is a wonderful place.

But I would like to ask if anybody here
has gone to the doctor, lately,

and said, "Doctor,
I am feeling really well today;

I am feeling really healthy.
Please help me."

(Laughter)

So in essence, healthcare
is a beautification

because in reality
it ought to have been "sickcare."

We care for the sick, not for the healthy.

Yes, I understand
that we aspire to be healthy,

but, really, we look after the sick.

So, let's try to think about the problem
of healthcare and sickcare

in a slightly different angle.

It is true and it is appropriate

that we spend significant
amounts of effort and resources,

throughout the world,
to care for the sick.

Indeed, some will say
that we are not spending enough,

and I will agree with this.

However, I would pose it to you

that it is just as informative

not only to understand
why people get sick,

but it is also to understand

why people who should be ill are not.

Think about this for a moment.

So here is a perhaps
somewhat unsettling statement.

A subset of us probably should not exist

or should be very ill,
as children, as neonates.

And the reason for this

is because some of the information
that we carry in our genomes

is predicting a catastrophic disorder

from which we might not
have been able to recover.

And yet, here we are,
able to enjoy each other's company.

I think that is wonderful,
but I also think that it is interesting

because if we can understand
what it is that protects us from illness,

maybe that will be our alternative
path to new therapeutics,

to help people who are about
to develop such illnesses.

And I would argue that this is an area
that we are under-resourced

and we have under-considered.

OK.

So everybody's going
"Oh God, what is in the next slide."

We are in Greece, my home country,

and sometimes when I think
about the archetypal Greek,

what do I think about?

Here is one of our beloved children,
Dimitri Mitropoulos,

but he seems to be doing a bit of this,

and it is true that many of us
have a habit of smoking too much.

We also eat late, and some of the things
that we eat are not particularly healthy.

There is gyro up there,
there is kokoretsi.

We just had Easter, yes?

Some of you might know
that the European Union

has issued an advice
against eating kokoretsi

because it is considered to be
deeply unhealthy for you.

But we do all these things, and we have
been doing them for a very long time.

And yet, and yet, and yet,

we seem to enjoy among
the largest longevity rates in Europe.

We have much lower
cardiovascular disease rates

than you would have expected
from our lifestyle,

and we are generally
considered to be well hardy.

Why is that?

Well, there is a number of reasons.

Of course, before
McDonald's invaded our land,

we enjoyed the Mediterranean diet:
oils, fruits, nuts, fish.

I cannot tell you anything more
about this, because I am a geneticist.

I can tell you a little bit about this:

It is not just our diet
that helps protect us

from the evils of smoking
and kokoretsi and all the rest of it,

it is we now understand

that we have changes,
mutations in our DNA,

that are protecting us
from some catastrophic disorders.

Now, this is not new information,
and it is a little bit puzzling

that perhaps we are not spending
as much time as we should.

Consider this: red blood cells,
they carry oxygen around your body -

you need them, trust me.

So we understand that
when we have particular mutations

that cause these red blood cells
to change shape,

we get things like sickle-cell disease,

and the oxygenation
of our tissue is reduced.

That is a very bad thing;
it is not comfortable.

Unless you happen to live in a place

in which malaria is endemic
and has high frequency.

Because if that is the case,

those sickle-shaped cells
actually protect you from malaria.

So let us take a step back for a moment.

We have a bad mutation
that causes sickle-cell disease,

that becomes a good mutation

if you happen to live in an area
where malaria is very prevalent.

I guess the point that I am trying to make
is that there are no absolutes,

there is no absolute bad, there is
no absolute good with mutations.

A mutation is a mutation,

and it depends in what context
you evaluate the type of information

and help you might be able to get.

So then, is it possible for us
to use our genome

not only to find these bad mutations,

but also to find some
good mutations that can help us?

Well, it is.

I have aspirational goals toward this,
but this is not science fiction,

this is happening in labs
around the world right now,

and by the way, if my lab is watching,
I hope you are going to work right now.

(Laughter)

Here are the covers
of two very famous issues

of the very well-known
journals "Nature" and "Science,"

that in 2001 published the first draft

of the blueprint of life,
the human genome.

It was a draft, but it worked very well.

It took a best part of ten years
to decode one genome,

and then what happened?

We did what we are really good at.

We scaled, we miniaturized,
we made things cheaper.

It's no different
from the old Cray computers

to the thing that you got
in your pocket now as your smartphone.

It used to cost millions
and millions of dollars,

now it costs a few thousand dollars
and the costs continue to crash.

As of right now,

there is tens of thousands of genomes
that have already been sequenced,

and it is my prediction -

and I assure you it is not
a visionary prediction -

that within the next few years,

we will have hundreds of thousands

and millions, and eventually
billions of genomes.

Well, when that happens,
we have an opportunity.

In addition to finding all the changes
in the genomes that make us sick,

we can actually find

some of the changes
that make us feel better.

Some of you might have heard
about something called the blue zones.

Blue zones are areas in the planet
in which people live longer,

and they don't just live longer,
they live longer, healthier.

The island of Ikaria, some of you will
see on this map is one of them,

with a mean individual,
the inhabitant of the island,

will live an average of ten years
longer than elsewhere in Europe.

Yes, we should sequence those individuals,

but we should not just look
for these blue zones.

So here is the thing.

As I look around you,
I am confident to say

that there is at least two or three of you
whose genome is containing something

that is deeply protective
from a catastrophic disease.

I would actually argue

that there is more of you than that,
but I don't have enough of a sense yet.

So I'm thinking not just
those who are on the blue zones,

but across the country,
across the continent, across the globe.

As we start accumulating genomes,

we are going to start finding
these good mutants,

people who should have been
very, very ill but they are not,

and they are not,

because they have mutations
in other genes, and they protect them.

OK, that is good, that is great.

You will say that is eight billion of us,
and I will say, "Yeah that is good,

but I am a little impatient;
it is not quite enough, give me more."

What else can we do?

Well, we have been studying
human genetic disorders

for the best part of 100-120 years.

And one of the things that we do
is we model these genetic disorders

in a variety of animals: mice, rats,

fish, worms, flies, a whole host.

And what we typically like to do
is say, "Aha, there is a gene

that when it is missing in a child,

is causing a very severe
metabolic disease,

and I need to understand why."

Well, I am going to go ahead,

and I am going to delete
exactly the same gene in a mouse

or a fly or a worm or a fish.

And I am going to recreate
this disease in this model

in such a way that I can study it.

And I must tell you, we get more excited
when we achieve that goal

because now we have
a malleable tool to study a disease.

I would argue that we should
get even more excited,

that we delete those genes
in these model organisms,

and we fail to generate this disease.

Why?

Because the question then becomes:

Why is it that when a little baby
is missing a particular gene,

it is going to have a very dim future -
and I consider that unacceptable -

[while] when I delete the very
same gene in a rat or a mouse,

the mouse does not care?

My sense

is [that] understanding
why these model organisms, these animals,

have the capacity to miss these genes
and still be healthy

will surely help us, guide us,
towards better therapeutics.

If we think a little bit
broader - the planet -

there is an enormous number
of species around the planet,

and we are well on our way
of sequencing all of them.

We will have the genomes
of thousands of species, very soon.

It is not a bold prediction to say

that among the species
we are going to encounter mutations

that in the human being cause catastrophe,

but in those species
they are fully tolerated.

Let us work together
to understand the differences,

to understand why in a worm,
or in a fish, or an ant, or a giraffe

and I do not care what,

a gene that causes a catastrophic disease
in a human is actually tolerated.

And yet you will say, "Greedy, greedy,
now all the species,

we have now eight billion humans
and all the species on the planet".

I hate to tell you this,
but I am still not satisfied.

Scientists by definition are impatient,
and we offer no apologies about this.

So here is the thing.

There is something else that we can do.

And the other thing we can do
is go directly into cells.

The picture that you see behind [me]
is just a picture of a cell,

and it is quite tenable for us to obtain
ill cells from every human genetic disease

that has ever been discovered.

For rare human genetic disorders -
and this is something that is my passion -

there is about 10,000-12,000
of them, give or take,

and if somebody said to me,

"Let us establish cells
from 12.000 human genetic disorders,"

I would say, "Well that is hard,

but it is not impossible,
by any stretch of the imagination."

We do not need to invent technology,
we just need to invest time.

And time is something
we have a little bit of.

And then what are we going to do?

Well, we live in a brand new world.

Again, I am sure my predecessor
and the ones before said the same thing,

and it is a wonderful thing
about humanity,

but it is true, we live in a world
where, for the first time ever,

we have the capacity to edit the genome.

Some of you might have
heard about an enzyme, CRISPR-Cas9.

The bottom line is you can go ahead and
at will direct it, you can delete genes,

you can change the lettering of genes,
you can change the order of genes,

you can pretty much do whatever you do.

It is like Microsoft Word without the bugs,
the hacking, and the virus threats.

But, we can do this.

So now, what you can do is you can take
each of the 12.000 diseases that you have,

and in each cell go and systematically
delete one gene at a time.

And you can discover
which genes, when missing,

will actually protect, cure,
restore the original dysfunction.

And when you actually combine that
with a pharmacopoeia that we have,

you can have hyper
accelerated drug discovery.

This is not going to work
for every human genetic disorder,

but I am convinced is going to work
for a significant fraction thereof.

And given that for
genetic disorders right now

our therapeutic options
are precious, few, and limited,

I strongly welcome this bold idea

because after all, sometimes
it's good to be a mutant!

Thank you.

(Applause)