Kathryn A. Whitehead The tiny balls of fat that could revolutionize medicine TED
What if I told you that the pandemic
will save the lives of millions of people?
It’s a difficult thing to consider,
given how many loved ones
we’ve already lost.
But throughout the course
of human history,
massive public health crises
have resulted in innovation
in health care and technology.
For example, the Black Death
gave rise to the Gutenberg press
and the 1918 flu pandemic
led to modern vaccine technology.
The COVID-19 pandemic
has and will be no different.
Just look at our vaccines –
normally developed over many years,
and the mRNA vaccines were deployed
in a mind-blowing 11 months.
How is that even possible?
It was possible because scientists
have been working for many years
to get us to the point
where we could use mRNA quickly
in an emergency situation.
Specifically,
we’ve been working on how to help
mRNA with its biggest problem,
which is that it doesn’t normally go
to the right places inside of our bodies.
Fortunately, we got around
that problem just in time,
and I’d like to tell you about
the technology that we use to do it.
When mRNA is administered,
it’s injected into our muscles
or our bloodstream,
but we actually need it
to go inside of our cells.
Unfortunately, mRNA is fragile,
and our bodies will destroy it
before it goes very far.
You can think of mRNA like a glass vase
that you’d like to send in the mail
without a box and bubble wrap.
It’ll break long before
it’s been delivered.
And without an address on the box,
your postal delivery service will have
no idea where to take it.
And so if we’re going to use mRNA
as a therapeutic,
it needs our help.
It needs protection,
and it needs to be told where to go.
And that’s where I come in.
For over five decades,
scientists and engineers like myself
have been creating the shipping materials
for nucleic acid drugs,
like DNA and RNA.
Through trial and error,
we’ve created packages
that deliver intact vases
to the wrong address;
that delivered to the right address
but with a broken vase;
packages that get ripped apart
by attacking dogs;
and packages that throw out
the mail carrier’s back.
It’s taken many years
to get the science right.
Let me show you the result,
these tiny balls of fat
that we call lipid nanoparticles.
Let me tell you what they are
and how they work.
So first of all, “nano” just means
really, really small.
Think of how small a person is
compared to the diameter of the earth.
That’s how small a nanoparticle is
compared to the person.
These nanoparticles are made up of
several fatty molecules called lipids.
Fat is an awesome packing material –
nice and bouncy.
Interestingly, our cells are also
surrounded by fat
to keep them flexible and protected.
Years ago, scientists had the idea
to create lipid nanoparticles
that would act like a Trojan horse.
Because the lipids
in the nanoparticle look similar
to the membranes that surround our cells,
the cells are willing to bring
the nanoparticle inside,
and that’s when the mRNA
is released into the cell.
So what, exactly, are the lipids
in these nanoparticles?
There are four ingredients
in addition to the mRNA,
and I’ll tell you about each one.
First, there’s a lipid
called a phospholipid.
This is the primary ingredient
in our cell membranes,
which are the walls of fat
that separate the insides of our cells
from everything that surrounds them.
Phospholipids have a head
that likes water
and a tail that likes other fatty things.
So when you throw a bunch
of phospholipids together in water,
they form this beautiful structure
called a lipid bilayer.
Here, the heads face the inside
and the outside of the cell,
which is water,
and the fat-loving parts of the molecule
hang out together in the middle.
In lipid nanoparticles,
phospholipids have a similar role
of keeping all of the other
ingredients organized.
Second, there’s a lipid
called cholesterol.
Why, if cholesterol has a bad reputation,
would we want to use it
in a therapeutic nanoparticle?
It turns out that while cholesterol can
be bad when it’s in our bloodstream,
it’s actually a really good thing
for our cell membranes.
And that’s because those phospholipids
I just told you about,
they are entirely too free
with themselves,
and they are prone to falling apart.
Cholesterol is a stiff molecule
that wedges itself
in between the other lipids
to fill in the gaps
and hold them all together.
It plays a similar role
in our lipid nanoparticles.
It provides structural support
so the nanoparticles don’t fall apart
in between the injection
and when they get into our cells.
Third, there’s a lipid called
an ionizable lipid.
Here, “ionizable” means that when
these particles are in the bloodstream,
they’re neutrally charged,
which helps with their safety.
Then they switch to a positive
charge inside of our cells,
which helps them release the mRNA.
Ionizable lipids are special because
they have to be made in the lab,
and scientists around the world
have tested tens of thousands
of these materials
to find ones that are good
at delivering mRNA safely.
And because they’re made in the lab,
they tend to be proprietary
to the company that invented them.
So, for example, Moderna and BioNTech,
the company that partnered with Pfizer,
they discovered different
ionizable lipids,
and that is the only important ingredient
in their COVID-19 vaccines that differ.
And even then, their ionizable lipids
aren’t even that different,
which is reassuring, because when
independent groups of scientists
converge on similar solutions,
it’s easier to trust the result.
Finally, one more ingredient.
This one is a polymer
called polyethylene glycol.
So let’s call it PEG. That’s much easier.
PEG is a water-loving molecule.
So it surrounds the lipid nanoparticle
and it holds it all together.
You can think of the other three lipids
as the box and the bubble wrap
for the mRNA,
and the PEG as the packing tape.
You may have heard in the news
about a tiny fraction of people
that have allergic responses
to the vaccine.
There is some evidence that PEG could be
contributing to these allergic reactions.
And that’s because people
are routinely exposed to PEG
in cosmetic and household products,
and some people have already
developed antibodies against PEG.
But why would this happen
to some people and not to others?
It turns out that every person’s immune
system is different,
and just the same way
that some people are allergic to latex,
other people are allergic to PEG.
It’s important to keep in mind, however,
that PEG has had a long
history of safe use
as part of FDA-approved drug formulations,
and these vaccine allergies could be
caused by things other than PEG.
More research is needed to get
to the bottom of these side effects.
All right, so let’s take a step back
and look at our whole nanoparticle.
Beautiful, right?
When these ingredients
all fit together nicely,
the result is a deliverywoman’s dream.
In the case of the vaccines,
after these nanoparticles
get injected into our muscle,
they take the mRNA into our cells.
There, the mRNA acts like
an instruction manual
that tells our cells
to make a foreign protein,
in this case, the coronavirus
spike protein.
When our immune cells
see the spike protein,
they rush to protect us from it,
and they teach themselves to remember it,
so that they can kill it
if it ever returns.
As we speak,
the mRNA vaccines are out there
saving lives from the coronavirus.
They were our first and best tool
to combat this nightmare,
and they are our best hope
of responding swiftly to viral variance
because we can keep our lipid
nanoparticle packaging the same,
and all we have to do is swap out
the mRNA that’s inside.
But here’s the best part:
for mRNA therapeutics,
these vaccines are only the beginning.
mRNA can be used to treat
or cure many diseases.
So in the future, we will likely have
treatments for many terrible diseases,
including cystic fibrosis,
muscular dystrophy
and sickle cell anemia.
These diseases are caused
by mutated proteins,
and we can use mRNA to ask our cells
to make the correct version
of these proteins.
We’ll have treatments for cancer –
breast, blood, lungs – you name it.
Here, we’ll use mRNA
to teach our immune cells
how to find and kill cancer cells.
And then, if we’re lucky,
we’ll have vaccines
against some of the most deadly
and feared pathogens across the globe,
including malaria, Ebola and HIV.
Some of these products
are already in clinical trials,
and the success of the COVID-19
vaccines will pave the way
for future generations of these therapies.
This is how the pandemic will save
the lives of millions.
It catalyzed the most rapid
vaccine development in history
and brought to life a niche, previously
unapproved form of technology.
And in our desperation,
we gave that technology a chance.
Now we’re collecting long-term
safety and efficacy data
from hundreds of millions of people.
And with these data,
interest in the technology,
funding for the technology
and trust in the technology
will continue to grow.
Looking ahead,
the packaging and delivery of mRNA
to the right organs and tissues
will continue to be
one of the most significant challenges
to implementing this technology.
And so my colleagues and I are going
to be busy for a very long time.
Ultimately, I’m here
with a message of hope.
We are on the cusp of a revolution.
mRNA is about to change
the world forever,
and it’s all thanks
to these fatty little balls
that take this miracle medicine
to exactly where it’s needed.
Thank you.
(Applause)