TED@BCG Toronto
Alexander Belcredi: How a long-forgotten virus could help us solve the antibiotics crisis
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Viruses have a bad reputation -- but some of them could one day save your life, says biotech entrepreneur Alexander Belcredi. In this fascinating talk, he introduces us to phages, naturally-occurring viruses that hunt and kill harmful bacteria with deadly precision, and shows how these once-forgotten organisms could provide new hope against the growing threat of antibiotic-resistant superbugs.
Alexander Belcredi - Biotech entrepreneur
Alexander Belcredi studies how viruses can help in the fight against superbugs. Full bio
Alexander Belcredi studies how viruses can help in the fight against superbugs. Full bio
Double-click the English transcript below to play the video.
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Take a moment
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and think about a virus.
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What comes to your mind?
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An illness?
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A fear?
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Probably something really unpleasant.
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And yet, viruses are not all the same.
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It's true, some of them cause
devastating disease.
devastating disease.
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But others can do the exact opposite --
they can cure disease.
they can cure disease.
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These viruses are called "phages."
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Now, the first time I heard
about phages was back in 2013.
about phages was back in 2013.
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My father-in-law, who's a surgeon,
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was telling me about a woman
he was treating.
he was treating.
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The woman had a knee injury,
required multiple surgeries,
required multiple surgeries,
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and over the course of these,
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developed a chronic
bacterial infection in her leg.
bacterial infection in her leg.
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Unfortunately for her,
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the bacteria causing the infection
also did not respond
also did not respond
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to any antibiotic that was available.
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So at this point, typically, the only
option left is to amputate the leg
option left is to amputate the leg
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to stop the infection
from spreading further.
from spreading further.
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Now, my father-in-law was desperate
for a different kind of solution,
for a different kind of solution,
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and he applied for an experimental,
last-resort treatment using phages.
last-resort treatment using phages.
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And guess what? It worked.
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Within three weeks of applying the phages,
the chronic infection had healed up,
the chronic infection had healed up,
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where before, no antibiotic was working.
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I was fascinated by this weird conception:
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viruses curing an infection.
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To this day, I am fascinated
by the medical potential of phages.
by the medical potential of phages.
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And I actually quit my job last year
to build a company in this space.
to build a company in this space.
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Now, what is a phage?
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The image that you see here was taken
by an electron microscope.
by an electron microscope.
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And that means what we see on the screen
is in reality extremely tiny.
is in reality extremely tiny.
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The grainy thing in the middle
with the head, the long body
with the head, the long body
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and a number of feet --
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this is the image of a prototypical phage.
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It's kind of cute.
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(Laughter)
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Now, take a look at your hand.
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In our team, we've estimated
that you have more than 10 billion phages
that you have more than 10 billion phages
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on each of your hands.
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What are they doing there?
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(Laughter)
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Well, viruses are good at infecting cells.
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And phages are great
at infecting bacteria.
at infecting bacteria.
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And your hand, just like
so much of our body,
so much of our body,
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is a hotbed of bacterial activity,
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making it an ideal
hunting ground for phages.
hunting ground for phages.
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Because after all, phages hunt bacteria.
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It's also important to know that phages
are extremely selective hunters.
are extremely selective hunters.
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Typically, a phage will only infect
a single bacterial species.
a single bacterial species.
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So in this rendering here,
the phage that you see
the phage that you see
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hunts for a bacterium
called Staphylococcus aureus,
called Staphylococcus aureus,
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which is known as MRSA
in its drug-resistant form.
in its drug-resistant form.
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It causes skin or wound infections.
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The way the phage hunts is with its feet.
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The feet are actually extremely
sensitive receptors,
sensitive receptors,
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on the lookout for the right surface
on a bacterial cell.
on a bacterial cell.
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Once it finds it,
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the phage will latch on
to the bacterial cell wall
to the bacterial cell wall
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and then inject its DNA.
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DNA sits in the head of the phage
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and travels into the bacteria
through the long body.
through the long body.
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At this point, the phage
reprograms the bacteria
reprograms the bacteria
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into producing lots of new phages.
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The bacteria, in effect,
becomes a phage factory.
becomes a phage factory.
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Once around 50-100 phages have accumulated
within the bacteria cell,
within the bacteria cell,
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the phages are then able
to release a protein
to release a protein
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that disrupts the bacteria cell wall.
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As the bacteria bursts,
the phages move out
the phages move out
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and go on the hunt again
for a new bacteria to infect.
for a new bacteria to infect.
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Now, I'm sorry, this probably
sounded like a scary virus again.
sounded like a scary virus again.
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But it's exactly this ability of phages --
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to multiply within the bacteria
and then kill them --
and then kill them --
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that make them so interesting
from a medical point of view.
from a medical point of view.
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The other part that I find
extremely interesting
extremely interesting
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is the scale at which this is going on.
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Now, just five years ago,
I really had no clue about phages.
I really had no clue about phages.
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And yet, today I would tell you
they are part of a natural principle.
they are part of a natural principle.
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Phages and bacteria go back
to the earliest days of evolution.
to the earliest days of evolution.
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They have always existed in tandem,
keeping each other in check.
keeping each other in check.
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So this is really the story of yin
and yang, of the hunter and the prey,
and yang, of the hunter and the prey,
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at a microscopic level.
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Some scientists have even estimated
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that phages are the most
abundant organism on our planet.
abundant organism on our planet.
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So even before we continue
talking about their medical potential,
talking about their medical potential,
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I think everybody should know
about phages and their role on earth:
about phages and their role on earth:
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they hunt, infect and kill bacteria.
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Now, how come we have something
that works so well in nature,
that works so well in nature,
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every day, everywhere around us,
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and yet, in most parts of the world,
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we do not have a single drug on the market
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that uses this principle
to combat bacterial infections?
to combat bacterial infections?
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The simple answer is: no one
has developed this kind of a drug yet,
has developed this kind of a drug yet,
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at least not one that conforms
to the Western regulatory standards
to the Western regulatory standards
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that set the norm
for so much of the world.
for so much of the world.
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To understand why,
we need to move back in time.
we need to move back in time.
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This is a picture of Félix d'Herelle.
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He is one of the two scientists
credited with discovering phages.
credited with discovering phages.
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Except, when he discovered them
back in 1917, he had no clue
back in 1917, he had no clue
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what he had discovered.
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He was interested in a disease
called bacillary dysentery,
called bacillary dysentery,
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which is a bacterial infection
that causes severe diarrhea,
that causes severe diarrhea,
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and back then, was actually
killing a lot of people,
killing a lot of people,
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because after all, no cure for bacterial
infections had been invented.
infections had been invented.
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He was looking at samples from patients
who had survived this illness.
who had survived this illness.
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And he found that something
weird was going on.
weird was going on.
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Something in the sample
was killing the bacteria
was killing the bacteria
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that were supposed to cause the disease.
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To find out what was going on,
he did an ingenious experiment.
he did an ingenious experiment.
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He took the sample, filtered it
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until he was sure that only something
very small could have remained,
very small could have remained,
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and then took a tiny drop and added it
to freshly cultivated bacteria.
to freshly cultivated bacteria.
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And he observed
that within a number of hours,
that within a number of hours,
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the bacteria had been killed.
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He then repeated this,
again filtering, taking a tiny drop,
again filtering, taking a tiny drop,
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adding it to the next batch
of fresh bacteria.
of fresh bacteria.
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He did this in sequence 50 times,
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always observing the same effect.
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And at this point,
he made two conclusions.
he made two conclusions.
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First of all, the obvious one:
yes, something was killing the bacteria,
yes, something was killing the bacteria,
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and it was in that liquid.
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The other one: it had to be
biologic in nature,
biologic in nature,
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because a tiny drop was sufficient
to have a huge impact.
to have a huge impact.
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He called the agent he had found
an "invisible microbe"
an "invisible microbe"
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and gave it the name "bacteriophage,"
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which, literally translated,
means "bacteria eater."
means "bacteria eater."
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And by the way, this is one
of the most fundamental discoveries
of the most fundamental discoveries
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of modern microbiology.
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So many modern techniques go back
to our understanding of how phages work --
to our understanding of how phages work --
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in genomic editing,
but also in other fields.
but also in other fields.
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And just today, the Nobel Prize
in chemistry was announced
in chemistry was announced
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for two scientists who work with phages
and develop drugs based on that.
and develop drugs based on that.
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Now, back in the 1920s and 1930s,
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people also immediately saw
the medical potential of phages.
the medical potential of phages.
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After all, albeit invisible,
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you had something
that reliably was killing bacteria.
that reliably was killing bacteria.
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Companies that still exist today,
such as Abbott, Squibb or Lilly,
such as Abbott, Squibb or Lilly,
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sold phage preparations.
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But the reality is, if you're starting
with an invisible microbe,
with an invisible microbe,
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it's very difficult to get
to a reliable drug.
to a reliable drug.
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Just imagine going to the FDA today
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and telling them all about
that invisible virus
that invisible virus
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you want to give to patients.
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So when chemical antibiotics
emerged in the 1940s,
emerged in the 1940s,
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they completely changed the game.
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And this guy played a major role.
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This is Alexander Fleming.
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He won the Nobel Prize in medicine
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for his work contributing
to the development
to the development
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of the first antibiotic, penicillin.
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And antibiotics really work
very differently than phages.
very differently than phages.
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For the most part, they inhibit
the growth of the bacteria,
the growth of the bacteria,
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and they don't care so much
which kind of bacteria are present.
which kind of bacteria are present.
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The ones that we call broad-spectrum
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will even work against
a whole bunch of bacteria out there.
a whole bunch of bacteria out there.
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Compare that to phages,
which work extremely narrowly
which work extremely narrowly
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against one bacterial species,
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and you can see the obvious advantage.
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Now, back then, this must have felt
like a dream come true.
like a dream come true.
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You had a patient
with a suspected bacterial infection,
with a suspected bacterial infection,
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you gave him the antibiotic,
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and without really needing to know
anything else about the bacteria
anything else about the bacteria
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causing the disease,
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many of the patients recovered.
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And so as we developed
more and more antibiotics,
more and more antibiotics,
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they, rightly so, became the first-line
therapy for bacterial infections.
therapy for bacterial infections.
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And by the way, they have contributed
tremendously to our life expectancy.
tremendously to our life expectancy.
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We are only able to do
complex medical interventions
complex medical interventions
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and medical surgeries today
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because we have antibiotics,
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and we don't risk the patient
dying the very next day
dying the very next day
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from the bacterial infection that he might
contract during the operation.
contract during the operation.
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So we started to forget about phages,
especially in Western medicine.
especially in Western medicine.
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And to a certain extent, even when
I was growing up, the notion was:
I was growing up, the notion was:
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we have solved bacterial infections;
we have antibiotics.
we have antibiotics.
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Of course, today,
we know that this is wrong.
we know that this is wrong.
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Today, most of you
will have heard about superbugs.
will have heard about superbugs.
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Those are bacteria
that have become resistant
that have become resistant
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to many, if not all, of the antibiotics
that we have developed
that we have developed
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to treat this infection.
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How did we get here?
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Well, we weren't as smart
as we thought we were.
as we thought we were.
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As we started using
antibiotics everywhere --
antibiotics everywhere --
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in hospitals, to treat and prevent;
at home, for simple colds;
at home, for simple colds;
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on farms, to keep animals healthy --
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the bacteria evolved.
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In the onslaught of antibiotics
that were all around them,
that were all around them,
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those bacteria survived
that were best able to adapt.
that were best able to adapt.
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Today, we call these
"multidrug-resistant bacteria."
"multidrug-resistant bacteria."
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And let me put a scary number out there.
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In a recent study commissioned
by the UK government,
by the UK government,
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it was estimated that by 2050,
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ten million people could die every year
from multidrug-resistant infections.
from multidrug-resistant infections.
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Compare that to eight million deaths
from cancer per year today,
from cancer per year today,
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and you can see
that this is a scary number.
that this is a scary number.
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But the good news is,
phages have stuck around.
phages have stuck around.
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And let me tell you, they are not
impressed by multidrug resistance.
impressed by multidrug resistance.
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(Laughter)
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They are just as happily killing
and hunting bacteria all around us.
and hunting bacteria all around us.
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And they've also stayed selective,
which today is really a good thing.
which today is really a good thing.
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Today, we are able to reliably identify
a bacterial pathogen
a bacterial pathogen
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that's causing an infection
in many settings.
in many settings.
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And their selectivity will help us
avoid some of the side effects
avoid some of the side effects
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that are commonly associated
with broad-spectrum antibiotics.
with broad-spectrum antibiotics.
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But maybe the best news of all is:
they are no longer an invisible microbe.
they are no longer an invisible microbe.
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We can look at them.
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And we did so together before.
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We can sequence their DNA.
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We understand how they replicate.
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And we understand the limitations.
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We are in a great place
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to now develop strong and reliable
phage-based pharmaceuticals.
phage-based pharmaceuticals.
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And that's what's happening
around the globe.
around the globe.
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More than 10 biotech companies,
including our own company,
including our own company,
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are developing human-phage applications
to treat bacterial infections.
to treat bacterial infections.
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A number of clinical trials
are getting underway in Europe and the US.
are getting underway in Europe and the US.
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So I'm convinced
that we're standing on the verge
that we're standing on the verge
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of a renaissance of phage therapy.
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And to me, the correct way to depict
the phage is something like this.
the phage is something like this.
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(Laughter)
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To me, phages are the superheroes
that we have been waiting for
that we have been waiting for
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in our fight against
multidrug-resistant infections.
multidrug-resistant infections.
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So the next time you think about a virus,
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keep this image in mind.
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After all, a phage might
one day save your life.
one day save your life.
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Thank you.
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(Applause)
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ABOUT THE SPEAKER
Alexander Belcredi - Biotech entrepreneurAlexander Belcredi studies how viruses can help in the fight against superbugs.
Why you should listen
Alexander Belcredi has been working in the pharmaceutical space for over a decade. He spent nine years at BCG where he was part of the global health care team, focusing on pharma and medtech. While at BCG, Belcredi became acutely aware of the urgent need to develop alternatives to antibiotics and was fascinated by the role that phage therapy can play. In 2017, he co-founded PhagoMed Biopharma GmbH, a biotech company developing phage-based pharmaceuticals to treat bacterial infections, where he is now the CEO. Belcredi holds an MA in Modern History and Economics from the University of St. Andrews as well as an MBA from INSEAD.
Alexander Belcredi | Speaker | TED.com