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

Translator: Anne Hessellund Reviewer: Jette Thrane

Take a moment

Brug et øjeblik

and think about a virus.

og tænk på en virus.

What comes to your mind?

Hvad er din første tanke?

An illness?

En sygdom?

A fear?

En frygt?

Probably something really unpleasant.

Sandsynligvis noget meget ubehageligt.

And yet, viruses are not all the same.

Men virus er forskellige.

It's true, some of them cause devastating disease.

Nogle er basis for dødbringende sygdomme.

But others can do the exact opposite -- they can cure disease.

Men andre kan rent faktisk kurere sygdomme.

These viruses are called "phages."

Disse virus kaldes "bakteriofager".

Now, the first time I heard about phages was back in 2013.

Den første gang jeg hørte om bakteriofager var tilbage i 2013.

My father-in-law, who's a surgeon,

Min svigerfar, som er kirurg,

was telling me about a woman he was treating.

fortalte mig om en kvinde, som han behandlede.

The woman had a knee injury, required multiple surgeries,

Kvinden havde en knæskade, som krævede gentagne operationer,

and over the course of these,

og i den periode

developed a chronic bacterial infection in her leg.

udvikledes en kronisk bakteriel infektion i hendes ben.

Unfortunately for her,

Uheldigvis for hende,

the bacteria causing the infection also did not respond

var bakterien, som var årsag til infektionen immun

to any antibiotic that was available.

overfor alle de antibiotika, der var tilgængelige.

So at this point, typically, the only option left is to amputate the leg

På dette tidspunkt er det normalt eneste mulighed at amputere benet,

to stop the infection from spreading further.

for at stoppe infektionens yderligere spredning.

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

Min svigerfar var desperat efter at finde en anden løsning,

and he applied for an experimental, last-resort treatment using phages.

og som sidste udvej ansøgte han om forsøgs-behandling med bakteriofager.

And guess what? It worked.

Og gæt engang. Det virkede.

Within three weeks of applying the phages, the chronic infection had healed up,

Efter 3 ugers behandling med bakterio- fager, var den kroniske infektion væk.

where before, no antibiotic was working.

hvor ingen antibiotika virkede.

I was fascinated by this weird conception:

Jeg blev fascineret af dette lidt skøre koncept:

viruses curing an infection.

virus kurerer en infektion.

To this day, I am fascinated by the medical potential of phages.

Jeg er stadig fascineret over bakteriofagernes medicinske potentiale.

And I actually quit my job last year to build a company in this space.

Jeg opsagde faktisk mit job sidste år, for at lave et firma i denne branche

Now, what is a phage?

Men, hvad er en bakteriofag?

The image that you see here was taken by an electron microscope.

Billedet, som du kan se her blev taget med et elektron-mikroskop.

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

Og det betyder, at det du kan se på skærmen i virkeligheden er meget lille.

The grainy thing in the middle with the head, the long body

Den kornede ting i midten, med hovedet og den lange krop

and a number of feet --

og et antal fødder,

this is the image of a prototypical phage.

det er billedet af en prototype af en bakteriofag.

It's kind of cute.

Den er lidt sød.

(Laughter)

(Latter)

Now, take a look at your hand.

Kig nu på din hånd.

In our team, we've estimated that you have more than 10 billion phages

I vores team, har vi estimeret at du har mere end 10 billioner bakteriofager

on each of your hands.

på hver af dine hænder.

What are they doing there?

Hvad skal de dog der?

(Laughter)

(Latter)

Well, viruses are good at infecting cells.

Ja, virus er gode til at inficere celler.

And phages are great at infecting bacteria.

Bakteriofager er gode til at inficere bakterier.

And your hand, just like so much of our body,

Og din hånd, såvel som resten af din krop,

is a hotbed of bacterial activity,

er et arnested for bakteriel aktivitet,

making it an ideal hunting ground for phages.

som gør det til et ideelt jagtområde for bakteriofager.

Because after all, phages hunt bacteria.

For bakteriofager jagter bakterier.

It's also important to know that phages are extremely selective hunters.

Det er også vigtigt at bakteriofager er meget selektive jægere.

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

Typisk, så kan en bakteriofag kun inficere en enkelt bakterieart.

So in this rendering here, the phage that you see

Den bakteriofag, som du ser her

hunts for a bacterium called Staphylococcus aureus,

jager efter en bakterie, som kaldes Staphylococcus aureus.

which is known as MRSA in its drug-resistant form.

hvilket er kendt som MRSA i sin antibiotika resistente form.

It causes skin or wound infections.

Den forårsager hud- eller sårinfektioner.

The way the phage hunts is with its feet.

Den måde bakteriofagen jager er med sine fødder.

The feet are actually extremely sensitive receptors,

Fødderne er nogle meget følsomme receptorer,

on the lookout for the right surface on a bacterial cell.

som leder efter den rigtige overflade på en bakterie celle.

Once it finds it,

Når den finder det,

the phage will latch on to the bacterial cell wall

vil bakteriofagen hæge sig fast på bakteriens cellevæg

and then inject its DNA.

og indsprøjte sit DNA.

DNA sits in the head of the phage

DNA'et er i hovedet af bakteriofagen.

and travels into the bacteria through the long body.

og bevæger sig ind i bakterien gennem den lange krop.

At this point, the phage reprograms the bacteria

Nu vil bakteriofagen omprogrammere bakterien

into producing lots of new phages.

til at producere mange nye bakteriofager.

The bacteria, in effect, becomes a phage factory.

Bakterien bliver i virkeligheden en bakteriofag fabrik.

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

Når 50-100 bakteriofager er produceret inde i bakteriecellen,

the phages are then able to release a protein

frigør bakteriofagerne et protein,

that disrupts the bacteria cell wall.

som gennemtrænger bakteriens celle væg.

As the bacteria bursts, the phages move out

Mens bakterien brister, flytter bakteriofagerne ud

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

og går på jagt efter nye bakterier, de kan inficere.

Now, I'm sorry, this probably sounded like a scary virus again.

Undskyld, dette lød nok lidt som en skræmme virus igen.

But it's exactly this ability of phages --

Men det er præcis den egenskab ved bakteriofager --

to multiply within the bacteria and then kill them --

at opformere sig indeni bakterien og så dræbe den, --

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

som gør dem så interessante fra et medicinsk synspunkt.

The other part that I find extremely interesting

Den andet, som jeg finder yderst interessant

is the scale at which this is going on.

er den skala, hvormed dette foregår.

Now, just five years ago, I really had no clue about phages.

For blot fem år siden, vidste jeg virkelig intet om bakteriofager.

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

Og i dag kan jeg fortælle dig, at de er et naturligt fundament.

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

Bakteriofager og bakterier er begge organismer fra den tidligste evolution.

They have always existed in tandem, keeping each other in check.

De har altid eksisteret side om side og holdt hinanden i skak.

So this is really the story of yin and yang, of the hunter and the prey,

Så dette er virkelig historien om Yin og Yang, om jægeren og byttet

at a microscopic level.

på et mikroskopisk niveau.

Some scientists have even estimated

Nogle forskere har endda beregnet

that phages are the most abundant organism on our planet.

at bakteriofager er den mest talrige organisme på vores planet.

So even before we continue talking about their medical potential,

Så inden vi taler videre om deres medicinske potentiale,

I think everybody should know about phages and their role on earth:

synes jeg, alle bør kende til bakteriofager og deres rolle på jorden:

they hunt, infect and kill bacteria.

de jager, inficerer og dræber bakterier.

Now, how come we have something that works so well in nature,

Hvordan kan det så være, at vi har noget, der virker så godt i naturen,

every day, everywhere around us,

hver dag, overalt omkring os,

and yet, in most parts of the world,

og dog har vi, i det meste af verden,

we do not have a single drug on the market

ikke et eneste lægemiddel på markedet

that uses this principle to combat bacterial infections?

som benytter dette princip til at bekæmpe bakterielle infektioner?

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

Det simple svar er: ingen har endnu udviklet sådan et lægemiddel.

at least not one that conforms to the Western regulatory standards

ihvertfald ikke et, der lever op til de vestlige regulatoriske standarder,

that set the norm for so much of the world.

som sætter reglerne for en stor del af verden.

To understand why, we need to move back in time.

For at forstå hvorfor, skal vi tilbage i tiden.

This is a picture of Félix d'Herelle.

Dette er et billede af Félix d'Herelle.

He is one of the two scientists credited with discovering phages.

Han er en af de to forskere, anerkendt for opdagelsen af bakteriofager.

Except, when he discovered them back in 1917, he had no clue

Men, da han opdagede dem tilbage i 1917 havde han ingen idé om

what he had discovered.

hvad han havde opdaget.

He was interested in a disease called bacillary dysentery,

Han var interesseret i en sygdom, som kaldes bacille dysenteri,

which is a bacterial infection that causes severe diarrhea,

som er en bakteriel infektion, der forårsager alvorlig diarré,

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

og som dengang, dræbte mange mennesker,

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

fordi man ikke havde en behandling for bakterielle infektioner.

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

Han tog prøver fra patienter, som havde overlevet denne sygdom.

And he found that something weird was going on.

Og han opdagede at der skete noget skørt.

Something in the sample was killing the bacteria

Et eller andet i prøverne dræbte de bakterier,

that were supposed to cause the disease.

som man mente forårsagede sygdommen.

To find out what was going on, he did an ingenious experiment.

For at undersøge hvad der skete, udførte han et genialt forsøg.

He took the sample, filtered it

Han tog en prøve og filtrerede den,

until he was sure that only something very small could have remained,

indtil han var sikker på, at kun noget meget småt kunne restere,

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

så udtog han en lille dråbe, som han tilsatte til nogle opformerede bakterier.

And he observed that within a number of hours,

Og han observerede at indenfor nogen timer,

the bacteria had been killed.

var bakterierne blevet dræbt.

He then repeated this, again filtering, taking a tiny drop,

Han gentog så forsøget, filtrerede og udtog en lille dråbe,

adding it to the next batch of fresh bacteria.

og tilsatte den til næste batch af friske bakterier.

He did this in sequence 50 times,

Han gentog dette 50 gange efter hinanden,

always observing the same effect.

hver gang med den samme effekt.

And at this point, he made two conclusions.

Og på dette tidspunkt, lavede han to konklusioner.

First of all, the obvious one: yes, something was killing the bacteria,

Den første og selvfølgelige: Ja, noget dræbte bakterierne

and it was in that liquid.

og det var ikke væsken.

The other one: it had to be biologic in nature,

Den næste: Det måtte være af biologisk oprindelse,

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

fordi så lille en dråbe var tilstrækkelig til at have en så stor effekt.

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

Han kaldte det, han havde fundet for: "en usynlig mikroorganisme",

and gave it the name "bacteriophage,"

og gav den navnet: "Bakteriofag",

which, literally translated, means "bacteria eater."

som direkte oversat betyder: "bakterie spiser".

And by the way, this is one of the most fundamental discoveries

Og forresten, dette er en af de mest fundamentale opdagelser

of modern microbiology.

af moderne mikrobiologi.

So many modern techniques go back to our understanding of how phages work --

Mange moderne teknikker bygger på forståelsen af bakteriofagers arbejde --

in genomic editing, but also in other fields.

i gen-modificering men også på andre områder.

And just today, the Nobel Prize in chemistry was announced

Og netop i dag blev Nobel prisen i kemi bekendtgjort

for two scientists who work with phages and develop drugs based on that.

for to forskere, som arbejder med bakteriofager og udvikler medicin deraf.

Now, back in the 1920s and 1930s,

Men tilbage i 1920'erne og 1930'erne,

people also immediately saw the medical potential of phages.

så man også potentialet for lægemidler med bakteriofager.

After all, albeit invisible,

Omend stadig usynlig,

you had something that reliably was killing bacteria.

du har fundet noget, som virkelig dræber bakterier.

Companies that still exist today, such as Abbott, Squibb or Lilly,

Firmaer som eksisterer i dag, såsom Abbott, Squibb eller Lilly,

sold phage preparations.

solgte medicin med bakteriofager

But the reality is, if you're starting with an invisible microbe,

Men realiteten er, at når du starter med en usynlig mikroorganisme

it's very difficult to get to a reliable drug.

så er det svært at nå frem til et pålideligt lægemiddel.

Just imagine going to the FDA today

Forestil dig blot at gå til FDA i dag

and telling them all about that invisible virus

for at fortælle dem alt om den usynlige virus,

you want to give to patients.

som du vil give til patienter.

So when chemical antibiotics emerged in the 1940s,

Så, da kemiske antibiotika dukkede op i 1940'erne,

they completely changed the game.

ændrede de fuldstændigt billedet.

And this guy played a major role.

Og denne fyr spillede en stor rolle.

This is Alexander Fleming.

Det er Alexander Fleming.

He won the Nobel Prize in medicine

Han vandt Nobel prisen i medicin

for his work contributing to the development

for sit arbejde som bidrog til udviklingen

of the first antibiotic, penicillin.

af det første antibiotika, penicillin.

And antibiotics really work very differently than phages.

Og antibiotika virker virkelig på en helt anden måde end bakteriofager.

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

Størstedelen, hæmmer væksten af bakterier,

and they don't care so much which kind of bacteria are present.

og de er lidt ligeglade med hvilke bakterier, der er tilstede.

The ones that we call broad-spectrum

Dem vi kalder bredspektrede antibiotika

will even work against a whole bunch of bacteria out there.

vil endda kæmpe mod en hel bunke af bakterier derude.

Compare that to phages, which work extremely narrowly

Sammenlignet med bakteriofager som er meget specifikke,

against one bacterial species,

mod en bakterieart,

and you can see the obvious advantage.

viser dig en klar fordel.

Now, back then, this must have felt like a dream come true.

Men, dengang, må det have været som en drøm der blev til virkelighed.

You had a patient with a suspected bacterial infection,

Du havde en patient med en formodet bakteriel infektion,

you gave him the antibiotic,

du gav ham antibiotika,

and without really needing to know anything else about the bacteria

og uden rigtig at behøve at vide noget om bakterien,

causing the disease,

som var årsagen,

many of the patients recovered.

ville mange af patienterne komme sig.

And so as we developed more and more antibiotics,

Og efterhånden som vi udviklede flere antibiotika,

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

blev de, første-valgs-behandling for bakterielle infektioner.

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

De har øget vores forventede levetid betragteligt.

We are only able to do complex medical interventions

Når vi i dag kan udføre kompleks medicinsk behandling

and medical surgeries today

og kirurgi, så er det

because we have antibiotics,

fordi vi har antibiotika,

and we don't risk the patient dying the very next day

og fordi vi ikke risikerer at patienten dør næste dag

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

af en bakteriel infektion, som han kan være smittet med under operationen.

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

Derfor glemte vi alt om bakteriofager specielt i vestlige landes medicin.

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

Og selv da jeg voksede op var det til en vis grad forestillingen at:

we have solved bacterial infections; we have antibiotics.

vi har løst problemet med bakterielle infektioner for vi har antibiotika.

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

I dag ved vi selvfølgelig, at det er forkert.

Today, most of you will have heard about superbugs.

De fleste af jer har hørt om superbakterier.

Those are bacteria that have become resistant

Det er bakterier som er blevet immune

to many, if not all, of the antibiotics that we have developed

overfor mange, hvis ikke overfor alle, af de antibiotika vi har udviklet

to treat this infection.

til at behandle infektioner

How did we get here?

Hvordan skete det?

Well, we weren't as smart as we thought we were.

Ja, vi var ikke helt så smarte, som vi troede.

As we started using antibiotics everywhere --

Da vi startede med at bruge antibiotika overalt --

in hospitals, to treat and prevent; at home, for simple colds;

for at forebygge og behandle på hospitalerne; for forkølelser hjemme;

on farms, to keep animals healthy --

for at holde dyrene raske på gårdene --

the bacteria evolved.

udviklede bakterierne sig.

In the onslaught of antibiotics that were all around them,

I det angreb af antibiotika der var rundt om dem,

those bacteria survived that were best able to adapt.

var det de bakterier, der bedst tilpassede sig, der overlevede.

Today, we call these "multidrug-resistant bacteria."

I dag, kalder vi dem "multi-resistente bakterier".

And let me put a scary number out there.

Og lad mig give jer et skræmmende tal.

In a recent study commissioned by the UK government,

I et nyligt studie bestilt af UK regeringen,

it was estimated that by 2050,

blev det estimeret at i 2050,

ten million people could die every year from multidrug-resistant infections.

kan 10 millioner mennesker dø hvert år af multi-resistente infektioner.

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

Sammenlign det med at der i dag dør 8 millioner af cancer hvert år

and you can see that this is a scary number.

og du vil se, at det er et skræmmende tal.

But the good news is, phages have stuck around.

Men den gode nyhed er, bakteriofager er her stadig.

And let me tell you, they are not impressed by multidrug resistance.

Og de er ikke imponeret af multi-resistens.

(Laughter)

(Latter)

They are just as happily killing and hunting bacteria all around us.

De jager og dræber gladeligt enhver bakterie

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

Og de er forblevet selektive, hvilket i dag er en god egenskab.

Today, we are able to reliably identify a bacterial pathogen

Vi kan i dag pålideligt identificere en bakteriel patogen,

that's causing an infection in many settings.

som forårsager en infektion i forskellige omgivelser.

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

Og selektiviteten kan hjælpe til at vi mindsker de bivirkninger

that are commonly associated with broad-spectrum antibiotics.

som normalt er forbundet med bred-spektret antibiotika.

But maybe the best news of all is: they are no longer an invisible microbe.

Men, den allerbedste nyhed er, at de ikke længere er usynlige mikroorganismer.

We can look at them.

Vi kan se på dem.

And we did so together before.

Og det gjorde vi lige før.

We can sequence their DNA.

Vi kan sekvensere deres DNA

We understand how they replicate.

Forstår hvordan de replikerer,

And we understand the limitations.

og deres begrænsninger.

We are in a great place

Vi er nu i stand til

to now develop strong and reliable phage-based pharmaceuticals.

at udvikle stærke og sikre bakteriofag-baserede lægemidler.

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

Og det er i gang overalt i verden

More than 10 biotech companies, including our own company,

Mere end 10 biotek firmaer inklusiv vores eget,

are developing human-phage applications to treat bacterial infections.

udvikler bakteriofager til behandling af infektioner

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

Et antal kliniske forsøg er på vej i Europa og i USA.

So I'm convinced that we're standing on the verge

Jeg er sikker på der kommer et paradigmeskifte

of a renaissance of phage therapy.

og renæssance for fag behandlinger.

And to me, the correct way to depict the phage is something like this.

Jeg beskriver bakteriofagen på denne måde.

(Laughter)

(Latter)

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

Bakteriofager er de superhelte vi har ventet på

in our fight against multidrug-resistant infections.

i kampen mod multi-resistente infektioner.

So the next time you think about a virus,

Så næste gang du tænker på en virus,

keep this image in mind.

så husk dette billede.

After all, a phage might one day save your life.

Det kan blive en bakteriofag, der redder dit liv en dag.

Thank you.

Tak.

(Applause)

(Klapsalve)