How a long-forgotten virus could help us solve the antibiotics crisis | Alexander Belcredi

328,276 views ・ 2018-12-07

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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)
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