A bacteriaeating virus that can prevent a global health crisis
Transcriber: Yuankai Gu
Reviewer: David DeRuwe
Do you ever think about how you could die?
I do, and whenever I do,
I catch myself thinking
about the most horrible ways of dying,
like car accidents, murder, or war.
But then the scientist in me
reminds me to be rational
and that the most likely way
that I could die
is from a regular human disease,
most likely at old age.
Statistically, the three most likely ways
a human being could die today
are from a cardiovascular disease, cancer,
or respiratory disease.
This list is probably
not surprising to you,
but there’s another silent threat
that is slowly emerging
and that could dominate this list
in just a few decades from now:
antimicrobial resistance, or AMR.
This abstract term is something
that WHO refers to
as one of the biggest threats
to global public health.
A highly-cited study left
by the government of the U.K in 2014
estimated that AMR could cause
up to 10 million deaths per year in 2050.
To put this number into perspective,
that is 25 percent more than all
of the predicted cancer deaths combined.
AMR is serious - so what exactly is it?
When microorganisms
such as viruses, bacteria, fungi,
or parasites affect your body,
they usually can be treated
with antimicrobial drugs -
for example, antibiotics if the infection
was caused by bacteria.
But bacteria and other
microorganisms evolve,
and every time we use
antimicrobial drugs to kill them,
there’s a tiny probability
that this microorganism
develops a mechanism to survive.
Paradoxically, this means
the more we use antimicrobial drugs,
the less these will work.
What worries me that in some instances,
we may be running into
an exponentially growing problem.
Six years ago, we had
about 1000 resistant cases a year per day.
Three years ago, we had 2000.
By now, we probably
have around 4000 cases,
and the number that associates to death
is growing accordingly.
It is important to understand
that AMR in this way acts like a pandemic,
but very differently from pandemics
you are more familiar with,
such as COVID-19 or the Spanish flu.
Such viral pandemics often feel like
a tsunami, delivering rapid destruction,
perhaps in multiple waves.
But tsunamis eventually also go
and leave space for recovery.
AMR is far more consequential
than a tsunami.
AMR compares more
to tectonic plates shift -
slowly evolving,
but with the potential to fundamentally
change life on this planet.
In AMR, antibiotic-resistant bacteria
are not only the most prominent example,
but also its biggest contributor.
And a reason for this
is that antibiotics have been a miracle;
antibiotics have saved hundreds
of millions of lives
since the discovery of penicillin in 1928.
And because antibiotics are so effective,
we use them everywhere,
even in agriculture or animal breeding.
But every time we do, we risk
increasing antibiotic resistance
in all of these areas.
And this is really troubling
because antibiotics are so essential
to our entire health care system.
Think about the last time
you used antibiotics,
perhaps to treat an infection,
or perhaps also to prevent
an infection after surgery.
Many patients need antibiotic treatment
against chronic diseases such as cancer.
Antibiotics currently enable
a host of treatment strategies;
without functioning antibiotics,
these would fail.
With this perspective
of heading into a post-antibiotic era,
what could help?
Although we’ve experienced
how devastating viruses can be,
ironically, in this case,
a virus could be actually one
of the solutions to the antibiotic crisis.
There’s one type of virus
that does not attack human cells,
but instead bacteria.
This type of virus
is called “bacteriophage.”
Bacteriophages or just phages
are fascinating.
It may be surprising to you
that phages are actually the most abundant
biological particle on Earth.
For every grain of sand this planet has,
there’s about a trillion in phages,
and luckily for us, they have been
battling bacteria for billions of years.
They hunt bacteria
because phages need bacteria
as a host to reproduce themselves.
They do so by infecting
bacteria with their DNA
and exploiting their internal mechanisms
to generate new copies of themselves.
Once enough new phage copies
are made in the bacteria,
these new phage copies will eventually
destroy the bacteria from the inside.
And exactly this mechanism
of infecting and killing
can be leveraged to treat
infections with bacteria even then,
and those become resistant to antibiotics.
This has a lot of potential.
And as a matter of fact,
it already has been done many times.
Especially East European countries
have been applying phage therapy
for almost a century now.
In countries like Georgia,
you will receive them in a pharmacy.
In Western countries the knowledge
about phage therapy
has fallen behind
the success of antibiotics.
But this is changing.
Scientists and clinicians
are rediscovering the power of phages
due to the pressure to treat
more and more resistant infections.
This new hope in phages motivates
around a dozen biotech companies
all over the world
to develop new phage therapies.
Most of those biotech companies
aim at capitalizing off
one of the biggest advantages of phages,
which is their incredible selectivity.
Every phage kills only
a very narrow range of bacteria,
often only even one subspecies.
For therapy, this means you will kill
only those bacteria
that actually make you sick.
This is in stark contrast
to most antibiotics
that also will kill bacteria
that benefit your health.
As you see, selectivity of phages,
could be a big advantage,
but it also means
that we can probably not just use
a single phage to kill all bacteria
but that we potentially need
an arsenal of different phages,
depending on the diversity of bacteria
we’re trying to target.
This increases the complexity and costs.
To circumvent this limitation,
many biotech companies
develop cocktails of several phages
to widen the range of bacteria that
can be targeted with a single medication.
But there’s a twist.
On one hand, we try to take advantage
of the selectivity of phages;
on the other hand, we’re forced to develop
broadly effective phage cocktails
to treat more patients.
Doesn’t this leave behind
the actual power of phages,
and what’s the difference
to the classic antibiotic approach?
With broadband approaches we might
be at risk of repeating the same events
that led us to AMR in the first place.
And it’s not so unlikely
that this can happen.
Scientists are very well aware
that bacteria also develop resistances
against phages quite rapidly.
A great solution would be
personalized phage cocktails
tailored to any individual patient.
But as you can imagine from ordering
an alcoholic cocktail at a bar,
personalized cocktails
take additional time and effort,
and phage cocktails are similar.
If you want to use a phage
as an ingredient to a cocktail,
you’ll first have to produce this phage
within its host bacteria.
This requires keeping bacteria alive
in a cultivated environment,
which is not always possible.
If you want to use a different phage,
you would have to develop a new process.
This is very difficult to standardize
and hence, to scale to new phages.
So wouldn’t it be great if we had
a single bacteria-free system
that could synthesize any type
of phage every time we need it
very much like a phage printer.
I’m very fortunate to be part of a team
that is tackling exactly this problem.
My colleagues invented
an artificial bacterial system
to produce any type of phage.
And this is not an easy task
because it requires, to emulate
a living organism, the host bacteria.
Remember how I told you that phages
infect bacteria with their DNA,
and that they do so to hijack bacteria,
to generate new copies of themselves?
This is exactly what we’re emulating.
And as you can imagine, there are
a ton of dynamic elements within bacteria
that change all the time.
The inside of bacteria
is made up of molecules
that you can think of as machines
that interact with each other
to translate phage DNA
into phage proteins.
Those phage proteins are
the building blocks of functional phages.
So a clever idea is to take all of the
molecules that are inside of bacteria
and put them into a more manageable
artificial environment.
To do this, we can grow
large amounts of bacteria up front,
eventually harvest them, and store it.
And once we need a new phage,
all we need to do now
is simulate infection
by adding the corresponding
phage DNA into the system,
All of this normally happens
within bacteria.
For us, it happens without bacteria.
Because in this way,
we’re removing the barrier of handling
living bacteria in phage production,
we can scale personalized
phage cocktails much easier
with three key advantages:
First, we’re potentially maximizing
efficacy in treating patients
because patients will receive a medication
optimized for them and not for others.
Second, we’re mitigating
the development of AMR
because bacteria would have
to simultaneously develop
many resistance mechanisms
against several phages.
The third advantage is not so obvious.
Unlike, for example, antibiotics,
phages are not a static chemical compound.
Like bacteria, they co-evolve to keep
using bacteria as their reproduction host.
This means whenever bacteria develop
a resistance against one particular phage,
there’s a very high chance
that there is already another phage
that has capabilities to overcome
even this new resistance mechanism.
And because with our system,
it is so easy to swap phages,
we can fully take advantage
of this natural evolution of phages.
We could even use the system
to speed up evolution.
Of course, this does not mean
that we can start treating
masses of patients immediately.
We first have to prove
that our synthetic phages
are both safe and effective
through clinical trials.
But once we can show this,
we can hopefully use the system
to help those patients
who are constantly struggling
with resistant infections.
I am certain that phages
will make a contribution
to solving the antibiotic crisis.
Although the phage community
is still waiting for the first trials
to confirm efficacies of phage therapy,
there have been dozens
of positive reports all over the world.
From a teenage girl
in the UK with cystic fibrosis,
who had an antibiotic resistant infection
after a lung transplantation,
to a man in Israel whose infected leg
was saved from amputation,
phages have demonstrated their power.
Such and many other reports
have been even so convincing
that Belgian regulators recently decided
to speed up access to phage therapy
by systematically allowing
personalized therapy with natural phages
without clinical trials.
This is unique in Western medicine.
We urgently need
such forms of productivity
because the rate at which AMR
has spread is already higher
than the rate at which
new antimicrobial drugs are approved.
With much more awareness
for the significance of AMR,
clear economic incentives
for biotech companies,
and new ideas for regulatory pathways,
I’m certain we can use phages
with other antimicrobial drugs
to stop AMR from becoming
the cause of 10 million deaths per year.
Thank you.
(Applause)