5 challenges we could solve by designing new proteins

I'm going to tell you about the most
amazing machines in the world ...

And what we can now do with them.

Proteins,

some of which you see inside a cell here,

carry out essentially all the important
functions in our bodies.

Proteins digest your food,

contract your muscles,

fire your neurons

and power your immune system.

Everything that happens in biology --

almost --

happens because of proteins.

Proteins are linear chains
of building blocks called amino acids.

Nature uses an alphabet
of 20 amino acids,

some of which have names
you may have heard of.

In this picture, for scale,
each bump is an atom.

Chemical forces between the amino acids
cause these long stringy molecules

to fold up into unique,
three-dimensional structures.

The folding process,

while it looks random,

it is in fact very precise.

Each protein folds to its characteristic
shape each time,

and the folding process takes just
a fraction of a second.

And it's the shapes of proteins

which enable them to carry out
their remarkable biological functions.

For example,

hemoglobin has a shape
in the lungs perfectly suited

for binding a molecule of oxygen.

When hemoglobin moves to your muscle,

the shape changes slightly

and the oxygen comes out.

The shapes of proteins,

and hence their remarkable functions,

are completely specified by the sequence
of amino acids in the protein chain.

In this picture, each letter on top
is an amino acide.

Where do these sequences come from?

The genes in your genome
specify the amino acid sequences

of your proteins.

Each gene encodes the amino acid
sequence of a single protein.

The translation between these amino
acid sequences and the structures

and funcions of proteins

is known as the protein-folding problem.

It's a very hard problem

because there's so many different
shape a protein can adopt.

Because of this complexity,

humans have only been able
to harness the power of proteins

by making very small changes
to the amino acid sequences

of the proteins we found in nature.

This is similar to the process
that our Stone Age ancestors used

to make tools and other implements
from the sticks and stones

that we found in the world around us.

But humans did not learn to fly
by modifying birds.

(Laughter)

Instead, scientists inspired by birds,
uncovered the principles of aerodynamics.

Engineers then used those principles
to design custom flying machines.

In a similar way,

we've been working for a number of years

to uncover the fundamental principles
of protein folding

and encoding those principles
in the computer program called "Rosetta."

We made a breakthrough in recent years.

We can now design completely new proteins
from scratch on the computer.

Once we've designed the new protein,

we encode its amino acid sequence
in a synthetic gene.

We have to make a synthetic gene

because since the protein
is completely new,

there's no gene in any organism on earth
which currently exists that encodes it.

Our advances in understanding
protein folding

and how to design proteins,

coupled with the decreasing cost
of gene synthesis

and the More's Law increase
in computer power,

now enable us to design tens
of thousands of new proteins

with new shapes and new functions
on the computer,

and encode each one of those
in a synthetic gene.

Once we have those synthetic genes,

we put them into bacteria

to program them to make
these brand new proteins.

We then extract the proteins

and determine whether they function
as we designed them to do

and whether they're safe.

It's exciting to be able
to make new proteins

because despite the diversity in nature,

evolution has only sampled a tiny fraction
of the total number of proteins possible.

I told you that nature uses
an alphabet of 20 amino acids,

and a typical protein is a chain
of about 100 amino acids,

so the total number of possibilities
is 20 times 20 times 20, 100 times,

which is a number on the order
of 10 to the 130th power,

which is enormously more
than the total number of proteins

which have existed
since life on earth began.

And it's this unimaginably large space
we can now explore

using computational protein design.

Now the proteins that exist on earth

evolved to solve the problems
faced by natural evolution.

For example, replicating the genome.

But we face new challenges today.

We live longer, so new
diseases are important.

We're heating up and polluting the planet,

so we face a full host
of ecological challenges.

If we had a million years to wait,

new proteins might evolve
to solve those challenges.

But we don't have
millions of years to wait.

Instead, with computational
protein design,

we can design new proteins
to address these challenges today.

Our audacious idea is to bring
biology out of the Stone Age

through technological revolution
in protein design.

We've already shown
that we can design new proteins

with new shapes and functions.

For example, vaccines work
my stimulating your immune system

to make a strong response
against a pathogen.

To make better vaccines,

we've designed protein particles

to which we confuse
proteins from pathogens,

like this blue protein here
from the respiratory virus RSV.

To make vaccine candidates

that are literally bristling
with the viral protein,

we find that such vaccine candidates

produce a much stronger
immune response to the virus

than any previous vaccines
that have been tested.

This is important because RSV
is currently one of the leading causes

of infant mortality worldwide.

We've also designed new proteins
to break down gluten in your stomach

for Celiac's Disease,

and other proteins to stimulate
your immune system to fight cancer.

These advances are the beginning
of the protein-design revolution.

We've been inspired by a precious
technological revolution:

the Digital Revolution,

which took place in large part
due to advances in one place --

Bell Laboratories.

The Labs was a place with an open,
collaborative environment

and was able to attract top talent
from around the world.

And this led to a remarkable
string of innovations --

the transistor,

the laser,

satellite communication

and the foundations of the internet.

Our goal is to build
the Bell Laboratories of protein design.

We are seeking to attract
talented scientists from around the world

to accelerate the protein
design revolution,

and we'll be focusing on five
grand challenges.

First, by taking proteins from flu strains
from around the world

and putting them on top
of the design protein particles

I showed you earlier,

we aim to make a universal flu vaccine,

one shot of which gives a lifetime
of protection against the flu.

The ability to design --

(Applause)

The ability to design
new vaccines on the computer

is important both to protecting
against natural flu epidemics

and in addition, intentional
acts of bioterrorism.

Second, we're going far beyond
nature's limited alphabet

of just 20 amino acids

to design new therapeutic candidates
for conditions such a chronic pain,

using an alphabet
of thousands of amino acids.

Third, we're building
advanced delivery vehicles

to targe existing medications
exactly where they need to go in the body.

For example, chemotherapy to a tumor

or gene therapies to the tissue
where gene repair needs to take place.

Fourth, we're designing smart therapeutics
that can do calculations within the body

and go far beyond current medicines,

which are really blunt instruments.

For example, to target a small
subset of immune cells

responsible for an autoimmune disorder

and distinguish them from the vast
majority of healthy immune cells.

Finally, inspired by remarkable
biological materials

such as silk, Abalone shell,