Uur ahin and zlem Treci Meet the scientist couple driving an mRNA vaccine revolution TED
Chris Anderson: Dr. Şahin
and Dr. Türeci, welcome.
Such a treat to speak with you.
Özlem Türeci: Thank you very much, Chris.
It’s a pleasure to be here.
CA: So tell me, as you think back
over the last 18 months,
what words pop to mind for you?
ÖT: Well, one word which comes
to mind is breathless.
It was indeed a breathless 16,
17 months for us.
When we started in January last year,
it was already at that time clear to us
that we were already in a pandemic.
What was not known was how fast
this pandemic would evolve
and whether we would have the time
in the first place
to have a vaccine ready
soon enough in due time.
And understanding this,
it meant for us that there was not
even one day to lose.
And this was the mindset
of the entire team
here in Mainz and at BioNTech
and later on also of our partners
which were involved,
Pfizer and others,
to keep going and be fast.
CA: I mean, it’s so extraordinary
that the ideas and the work in your minds
have now impacted hundreds of millions,
perhaps billions of people.
That must feel overwhelming.
And yet, I know at the same time,
you don’t believe in this notion
of a flash-in-the-pan ideas.
Steven Johnson, the author, in his book
“Where [Good] Ideas Come From,”
speaks of the slow hunch,
that the best ideas
happen over many years.
And I know that you believe
that is true in your case.
I’d like us to go back a couple of decades
to – tell us how this began.
How did you meet?
ÖT: We met on an oncohematology ward,
Uğur being a young physician,
and I was still in medical school
training on ward.
Which means we met in one of the worlds
which became important to us,
the world of patient care,
of treating oncohematology patients.
And we soon found out
that there was a second world
which we liked,
namely the world of science.
We were haunted by the same dilemma,
namely that whereas there was not much
we could offer our cancer patients,
there were so many potential technologies
we encountered in the lab
which could address this.
So one of our shared visions
was to bridge this dilemma
by working on bringing
science and technology fast.
And that’s an important word here.
Fast to the patient’s bedside
to address high medical need.
CA: So I think the first company
you founded nearly 20 years ago
was to use the power of the human
immune system to tackle cancer.
Uğur Şahin: We were always interested
in using the patient’s immune system
to fight cancer
and other type of diseases.
As immunologists, we knew how powerful
the human immune system is.
But it was also clear
that the human immune system,
in the case of cancer,
did not fight cancer cells.
It could fight it, but it didn’t.
And for that, we wanted
to develop immunotherapies.
That means treatments
that use the power of the immune system
and redirect the power
of the immune system to cancer cells.
It was clear that in
the university setting,
we could not continue
to develop monoclonal antibodies
because the cost for development
of monoclonal antibodies
before you can start a clinical trial,
was in the range of 20, 30 million euros,
and therefore we decided
to start a company to get the funding.
CA: Now, soon after
you started this company,
you decided to get married.
Tell me about your wedding day.
ÖT: Day was well planned, a quick wedding.
And thereafter we went back
to the laboratory
and our guests at our wedding,
that was basically our team,
our research team.
So no time to lose, Chris.
CA: (Laughs)
That was a pretty special honeymoon.
I mean, it seems like
your love for each other
is very much bound up
in your love for this work
and your sense of
the importance of this work.
How would you characterize
those intersecting relationships there?
UŞ: We are really two scientists.
At the end of the day, we love what we do,
and for us,
we don’t differentiate between
work and life balance.
It’s for us really a privilege
to be scientists,
to be able to do what we love.
And therefore, we combine our normal life
with our professional life.
And therefore, this is pretty
normal for us.
CA: So talk to me about this
extraordinary molecule RNA,
and how you got interested in it
and how it became, as I understand it,
an increasing focus of your work.
And indeed, it led
to the founding of BioNTech.
Talk about that.
UŞ: Yeah, mRNA is a natural molecule,
it’s one of the first molecules of life.
It is a carrier of genetic information.
But in contrast to DNA, it’s not stable.
So it can be used to transfer
information to human cells.
And the human cells can use
this information to build proteins,
which can be used
for therapeutic settings,
for example, to make a protein
which is a vaccine,
or to make a protein which is an antibody,
or to make a protein
which is another type of drug.
And we were fascinated
by this molecule class,
because it was very clear
that mRNA can be produced
pretty fast, within a few days.
And we were, as MDs,
we were particularly interested
to develop personalized medicines.
That means a treatment and immunotherapy
specifically designed
for a cancer patient,
because one of the key challenges
in cancer treatment,
is that every patient
has a different tumor.
If you compare two tumors
of two patients
with the same type of tumor,
the similarity of the tumors
is less than three percent
and 97 percent is really unique.
And today, it’s still not possible
to address the uniqueness
of the tumor of a patient.
And therefore,
we were seeking for a technology
which could be used for immunotherapy
and which could be used
to develop a treatment
within the shortest possible time.
The idea to get the genetic
sequence of the tumor
and then make a vaccine
which is personalized,
within a few weeks.
CA: Is it fair to say
that almost all of the significant things
that happen to us biologically
are actions done by proteins,
and that it’s mRNA that actually
makes those proteins?
If you can understand
the language of mRNA,
you can get involved in pretty much
everything of significance
to the well-being of a human being.
ÖT: Exactly.
So in principle,
the information instructions
are in the DNA.
These have to be translated into protein
because proteins are the actors
which keep our cells alive
and our organism functional.
And the way how to translate
what is instructed by DNA
in a fashion that it is well-timed
and happens at the right places,
into protein,
there is messenger RNA.
Messenger RNA sort of instructs when
and how much of which protein
has to be built
in order to ensure
the activity of our body.
CA: So you can almost think of DNA
as the sort of The Oxford English
Dictionary of Language.
It sort of sits there
as the reference point.
But for the actual living work,
the living work of language
out there in the world instructing things,
that is done by mRNA.
UŞ: Yeah, absolutely, it is possible.
So the human cells,
exactly, DNA is like a library.
If you have the platform
for the messenger RNA therapy,
you can deliver any type of message
and the body cells ensure
that the message is translated
into the right protein.
ÖT: A high advantage of mRNA
is that it is so versatile.
You can deliver all sorts of messages,
as Uğur has called them.
On the one hand, you can deliver
the blueprint for the protein
which you want
to be produced in this cell.
But you can, with the same molecule,
also design into the mRNA
instructions how this protein
should be built,
instructions to the protein
factories of the cell.
So you can define
whether you want this protein
to be built in high amounts
or for a long duration,
how the pharmacokinetics
of this protein should be in the cell.
CA: So talk about January of last year
when you first heard about this new
virus that was spreading.
UŞ: So in the end of January,
we read a paper published
about this outbreak in Wuhan,
and realized that this new outbreak
has all features to become
a global pandemic,
and we were concerned
that our life will change,
that this outbreak could change
the fate of mankind.
And we knew that we have this
messenger RNA technology,
which was actually developed
for personalized cancer therapy.
But the idea of personalized
cancer therapy
is to get the genetic
information of the patient
and then make a vaccine
as fast as possible.
And we had now the same situation.
It was not a personalized vaccine,
but it was a genetic
information of the virus,
which was released two weeks earlier.
And so this genetic information
of this virus was available,
and our task was to make
a vaccine as fast as possible.
And the challenge at that time point was,
there was almost nothing known
about this virus.
It was a completely new virus.
We had some assumptions
which target which molecule
encoded by the virus
could be the right target.
That means the molecule which can be used
to precisely engineer an immune attack.
This is the spike protein.
It is on the surface of the virus.
And there’s not only one copy
of the spike protein on the virus,
but multiple in the range
of 20, 25, 30 spike proteins.
And the spike protein has two functions.
One function is really to enable
that the virus sticks to human cells.
For example, it sticks to cells
in the human lung.
And the second is that the spike
protein acts as a key.
It allows the virus
to enter into the cells.
Our goal was to engineer
an immune response.
CA: You’ve got a slide showing the T-cell
response to your vaccine.
How long were you into the process
before you saw this
and you saw, wow, there really is
a spectacular response going on here?
ÖT: We saw this already
in the animal models
because they are also meant to assess
the immune response.
And what is shown on this slide
is on the left side, a lymph node
from a setting where there was no
RNA treatment or RNA vaccination.
And on the right side,
a lymph node of a treated organism,
in this case, an animal.
And the localization matters.
And we have constructed
our RNA nanoparticles,
with encapsulation into lipids
such that the mRNA
is carried into lymph nodes,
not just anywhere,
it’s carried into lymph nodes
and in the lymph nodes
it reaches a very special cell type,
which is called dendritic cells,
and these cells are coaches
of the immune system.
So they are the generals which call
all the different special forces
and train them on the wanted
poster of attacker.
And it’s very important
that you reach those cells.
On the right side, you can see
the effect of reaching those cells.
You see many red dots.
And these are T-cells which have been
trained to recognize the antigen,
the protein which mRNA has delivered,
and they have expanded
to a sort of army of clones, so to say.
So all these red dots are an army
which only knows one goal,
namely attacking this specific
protein encoded by the mRNA.
CA: So it’s really stunning
that within just a few days
of your looking at this sequence
of the most dangerous pathogen
to hit humanity in 100 years, I guess,
that you were able to come up
with these these candidate vaccines.
And I guess over the course
of the next weeks and months,
you had growing confidence
that, wow, this was going to work.
It wasn’t until the results
of the human trials came out,
I guess in November of last year,
that you really knew.
Tell us about that moment.
ÖT: It was a Sunday
when we were waiting for these results,
which are assessed in such trials
by an independent committee
and Uğur said, “So let’s see
how the data will look like.”
It was not clear whether it would be
a thumbs up or down.
And we were very relieved.
And I felt blessed to hear
that the vaccine was efficacious
and it was highly efficacious,
over 90 percent.
CA: And that more than 90 percent
almost disguises the full extent,
because that’s just against any kind
of level of infection of COVID.
Severe infection and fatalities
were almost completely protected against,
I think.
And it must have been
an ecstatic moment for you.
Certainly was for so many people
around the world.
UŞ: Yes, absolutely.
So this was a Sunday evening,
and there were a handful of people
knowing that an effective vaccine
is existing against this global pandemic.
And we were so excited and so happy
and we shared of course
this information the next day.
CA: So based on what’s happened
this time around
and the amazing acceleration,
compared with any other
vaccine development,
I mean, if we were hit by another virus,
could you picture that next time
we could accelerate the time line
further still if need be?
UŞ: Yes, Chris, this is
an excellent question.
Actually, the world was not prepared
to deal with such a pandemic.
The science and the vaccine developers
reacted in an excellent fashion.
And it is incredible and wonderful
that it was possible to come up
with an effective vaccine
while a pandemic is ongoing,
in less than 12 months.
But the challenges
that we have at the moment
is that we don’t have
sufficient production capacity.
Ideally, we would be
prepared the next time,
not only to develop a vaccine
in light speed,
but also to to make and distribute
the vaccine in light speed.
So what we need now is an additional
element which was not existing,
is manufacturing capacity.
And idle manufacturing capacity.
We must be bringing us into a position
that we can produce
12 billion doses of vaccine,
if you consider prime boost,
within less than six months.
And this is technically possible.
So this can be done if governments
and international organizations invest
into manufacturing capacity,
invest into keeping this idle capacity,
and also come up with a standard
time span and process
to enable even faster response.
So we in principle,
we might be able to manage
to come up with a vaccine
and start distribution
in even less than eight months.
CA: What does what’s happened
in this last year tell you now
about the prospects
for using mRNA to treat cancer
and indeed other diseases?
Where is this heading?
UŞ: What we have now is now
an approved technology
and a first approved product.
The development of the coronavirus
mRNA vaccine shows the power
of the mRNA
and it shows also
the safety of this approach.
And it shows
that it opens up a door for new technology
and for new type of treatments.
And the mRNA molecules
that we are currently using for cancer,
we have more than 10 products now
in clinical development,
are diverse against different
types of cancer.
We are very confident that the success
that we have generated now
for our infectious disease vaccines
can be continued with our
cancer immunotherapies.
CA: Some people may hear this
and say this is just another type
of drug that’s coming along.
But I think on the mental model
you’re talking about,
we should think about it
as much more revolutionary than that,
that typically a drug, a traditional drug,
kind of changes the chemical environment,
the background of an entire
area of the body.
But your –
If you understand the language of mRNA,
you can do something much more
specific and precise.
Is that something like
a fair way to think about it?
ÖT: Yes, indeed.
It could be the next revolution
in the biopharm landscape.
UŞ: At the end of the day,
disease is a situation
where the communication
between cells is disturbed.
So, for example, autoimmune disease
is a disease condition
where immune cells attack normal cells.
And indeed, we could engineer
messenger RNA therapies
which could teach the immune system
to stop to do that,
without inhibiting the whole
immune system,
by just communicating
with the immune cells which are attacking.
We could be precise and more specific.
CA: The success of BioNTech
over the last couple of years,
I think the value
of the company has rocketed
because of the amazingness
of what’s happened.
I mean, it’s made you both
extremely wealthy,
I think you’re both billionaires now.
How have you been able to respond to that?
Sometimes so much money
brings its own problems with it.
Is that proving a distraction?
ÖT: For a company
which sees innovation as its core mission,
too much money is never a problem.
Because innovation really means
that you have to invest.
Otherwise, we will only have
two type of products
or incremental improvement
for solutions of high medical need.
UŞ: It really gives us the chance
to transform our company.
So we were when we started –
When we compare ourselves
with the situation we had
at the beginning of 2020,
we had a number of product
candidates in clinical testing,
but the company required funding
every year or every second year.
Now we have a situation to really address
the full vision of the company.
We started BioNTech
with the idea really
to provide novel treatments
wherever there is a high
unmet medical need.
And we now can do that
in a much larger and broader scale,
and bring our innovations
faster to patients.
CA: You are both from families
who immigrated from Turkey to Germany.
Immigrants have faced hard times
in many countries, including Germany.
And yet you, I think,
have helped transform
the debate about immigration,
in Germany and elsewhere,
just by the extraordinary success
that you’ve achieved
creating this world-leading
company in Germany.
Do you take joy for the impact
you may have had on this issue?
UŞ: It is somehow surprising
because the way how we do science,
and how we recognize how people work
effectively in teams together
is not to us from where
the person is coming,
but what the person can contribute.
So in our company, we have
employees from more than 60 countries.
So we are an international
group of scientists,
as any other research institution.
So we have to recognize
that globalization really helps
to bring people, scientists
or other engineers into one place,
allowing to work together
and to come with extraordinary results.
For us, this is somehow surprising
that this is seen as special.
It is just the way how excellent
research and science work.
CA: Well, it’s extraordinary and inspiring
what you’ve achieved,
and it’ll be very exciting to track
progress over the coming years.
Thank you so much. Thank you.