WEBVTT

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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.

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But others can do the exact opposite --
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.

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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.

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The woman had a knee injury,
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.

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Unfortunately for her,

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the bacteria causing the infection
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

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to stop the infection
from spreading further.

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Now, my father-in-law was desperate
for a different kind of solution,

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and he applied for an experimental,
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,

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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.

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And I actually quit my job last year
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.

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And that means what we see on the screen
is in reality extremely tiny.

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The grainy thing in the middle
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

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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.

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And your hand, just like
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.

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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.

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Typically, a phage will only infect
a single bacterial species.

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So in this rendering here,
the phage that you see

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hunts for a bacterium
called Staphylococcus aureus,

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which is known as MRSA
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,

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on the lookout for the right surface
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

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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.

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At this point, the phage
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.

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Once around 50-100 phages have accumulated
within the bacteria cell,

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the phages are then able
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

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and go on the hunt again
for a new bacteria to infect.

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Now, I'm sorry, this probably
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 --

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that make them so interesting
from a medical point of view.

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The other part that I find
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.

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And yet, today I would tell you
they are part of a natural principle.

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Phages and bacteria go back
to the earliest days of evolution.

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They have always existed in tandem,
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,

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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.

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So even before we continue
talking about their medical potential,

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I think everybody should know
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,

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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?

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The simple answer is: no one
has developed this kind of a drug yet,

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at least not one that conforms
to the Western regulatory standards

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that set the norm
for so much of the world.

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To understand why,
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.

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Except, when he discovered them
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,

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which is a bacterial infection
that causes severe diarrhea,

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and back then, was actually
killing a lot of people,

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because after all, no cure for bacterial
infections had been invented.

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He was looking at samples from patients
who had survived this illness.

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And he found that something
weird was going on.

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Something in the sample
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.

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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,

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and then took a tiny drop and added it
to freshly cultivated bacteria.

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And he observed
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,

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adding it to the next batch
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.

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First of all, the obvious one:
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,

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because a tiny drop was sufficient
to have a huge impact.

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He called the agent he had found
an "invisible microbe"

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and gave it the name "bacteriophage,"

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which, literally translated,
means "bacteria eater."

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And by the way, this is one
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 --

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in genomic editing,
but also in other fields.

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And just today, the Nobel Prize
in chemistry was announced

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for two scientists who work with phages
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.

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After all, albeit invisible,

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you had something
that reliably was killing bacteria.

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Companies that still exist today,
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,

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it's very difficult to get
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

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you want to give to patients.

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So when chemical antibiotics
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

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of the first antibiotic, penicillin.

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And antibiotics really work
very differently than phages.

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For the most part, they inhibit
the growth of the bacteria,

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and they don't care so much
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.

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Compare that to phages,
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.

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You had a patient
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

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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,

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they, rightly so, became the first-line
therapy for bacterial infections.

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And by the way, they have contributed
tremendously to our life expectancy.

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We are only able to do
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

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from the bacterial infection that he might
contract during the operation.

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So we started to forget about phages,
especially in Western medicine.

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And to a certain extent, even when
I was growing up, the notion was:

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we have solved bacterial infections;
we have antibiotics.

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Of course, today,
we know that this is wrong.

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Today, most of you
will have heard about superbugs.

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Those are bacteria
that have become resistant

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to many, if not all, of the antibiotics
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.

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As we started using
antibiotics everywhere --

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in hospitals, to treat and prevent;
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,

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those bacteria survived
that were best able to adapt.

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Today, we call these
"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,

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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.

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Compare that to eight million deaths
from cancer per year today,

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and you can see
that this is a scary number.

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But the good news is,
phages have stuck around.

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And let me tell you, they are not
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.

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And they've also stayed selective,
which today is really a good thing.

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Today, we are able to reliably identify
a bacterial pathogen

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that's causing an infection
in many settings.

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And their selectivity will help us
avoid some of the side effects

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that are commonly associated
with broad-spectrum antibiotics.

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But maybe the best news of all is:
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.

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And that's what's happening
around the globe.

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More than 10 biotech companies,
including our own company,

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are developing human-phage applications
to treat bacterial infections.

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A number of clinical trials
are getting underway in Europe and the US.

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So I'm convinced
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.

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(Laughter)

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To me, phages are the superheroes
that we have been waiting for

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in our fight against
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.

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Thank you.

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(Applause)