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

Prevodilac: Kristina Radosavljević Lektor: Ivana Krivokuća

Take a moment

Zastanite malo

and think about a virus.

i razmislite o virusima.

What comes to your mind?

Šta vam prvo pada na pamet?

An illness?

Bolest?

A fear?

Strah?

Probably something really unpleasant.

Verovatno nešto jako neprijatno.

And yet, viruses are not all the same.

A ipak, nisu svi virusi isti.

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

Istina, neki od njih izazivaju razorne bolesti.

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

Ali drugi mogu učiniti potpuno suprotno - mogu izlečiti bolest.

These viruses are called "phages."

Ovi virusi se zovu „fagi“.

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

Prvi put sam čuo za fage 2013. godine.

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

Moj tast, hirurg,

was telling me about a woman he was treating.

mi je pričao o ženi koju je lečio.

The woman had a knee injury, required multiple surgeries,

Žena je imala povredu kolena koja je zahtevala nekoliko operacija,

and over the course of these,

zbog kojih joj se razvila hronična bakterijska infekcija u nozi.

developed a chronic bacterial infection in her leg.

Unfortunately for her,

Na njenu žalost,

the bacteria causing the infection also did not respond

bakterija koja je izazivala infekciju

nije reagovala ni na jedan antibiotik koji je bio dostupan.

to any antibiotic that was available.

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

Tako da je u tom momentu, obično, jedina opcija amputacija noge

to stop the infection from spreading further.

kako bi se sprečilo širenje infekcije.

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

Moj tast je očajnički pokušavao da pronađe drugo rešenje,

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

i primenio je eksperimentalni, najnoviji tretman koristeći fage.

And guess what? It worked.

I znate šta se desilo? Uspelo je.

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

U roku od tri nedelje od primene faga, hronična infekcija je bila izlečena,

where before, no antibiotic was working.

tamo gde nijedan antibiotik nije uspeo.

I was fascinated by this weird conception:

Ovaj čudni koncept je bio fascinantan za mene:

viruses curing an infection.

virusi leče infekciju.

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

Do današnjeg dana, fasciniran sam medicinskim potencijalom faga.

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

U stvari, dao sam otkaz prošle godine da bih osnovao kompaniju u ovoj sferi.

Now, what is a phage?

Šta je fag?

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

Slika koju ovde vidite je napravljena elektronskim mikroskopom.

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

Što znači da je ono što vidimo na ekranu u stvarnosti izuzetno sićušno.

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

Ova zrnasta stvar u sredini sa glavom, dugačkim telom

and a number of feet --

i više stopala -

this is the image of a prototypical phage.

to je slika prototipa faga.

It's kind of cute.

Sladak je, na neki način.

(Laughter)

(Smeh)

Now, take a look at your hand.

Sad, pogledajmo vaše ruke.

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

Naš tim je procenio da imate više od 10 milijardi faga

on each of your hands.

na svakoj ruci.

What are they doing there?

Šta rade tu?

(Laughter)

(Smeh)

Well, viruses are good at infecting cells.

Pa, virusi su dobri u inficiranju ćelija.

And phages are great at infecting bacteria.

A fagi su dobri u inficiranju bakterija.

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

A vaša ruka je, kao i ostatak vašeg tela,

is a hotbed of bacterial activity,

leglo bakterijske aktivnosti,

making it an ideal hunting ground for phages.

što je čini idealnim lovištem za fage.

Because after all, phages hunt bacteria.

Zato što, na kraju krajeva, fagi love bakterije.

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

Takođe je veoma važno znati da su fagi veoma selektivni lovci.

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

Obično, fag će inficirati samo jednu vrstu bakterija.

So in this rendering here, the phage that you see

Dakle, na ovom prikazu ovde, fag koga vidite

hunts for a bacterium called Staphylococcus aureus,

lovi bakteriju koja se zove zlatni stafilokok,

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

poznatu kao MRSA, u svom obliku otpornom na antibiotike.

It causes skin or wound infections.

Izaziva infekcije kože ili rana.

The way the phage hunts is with its feet.

Fagi love svojim stopalima.

The feet are actually extremely sensitive receptors,

Stopala su u stvari izuzetno osetljivi receptori,

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

u potrazi za pravom površinom bakterijske ćelije.

Once it finds it,

Jednom kada je nađe,

the phage will latch on to the bacterial cell wall

fag će se prikovati za zid bakterijske ćelije

and then inject its DNA.

i ubaciti svoj DNK.

DNA sits in the head of the phage

DNK se nalazi u glavi faga

and travels into the bacteria through the long body.

i putuje u bakteriju kroz dugačko telo.

At this point, the phage reprograms the bacteria

U ovom trenutku, fag reprogramira bakteriju

into producing lots of new phages.

da proizvodi mnogo novih faga.

The bacteria, in effect, becomes a phage factory.

Tako bakterija postaje fabrika faga.

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

Kada se 50-100 faga nakupe unutar ćelije,

the phages are then able to release a protein

fagi su tad u mogućnosti da oslobode protein

that disrupts the bacteria cell wall.

koji slabi ćelijski zid bakterije.

As the bacteria bursts, the phages move out

Kako bakterija pukne, fagi se iseljavaju

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

i idu ponovo u potragu za novom bakterijom koju će inficirati.

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

Izvinjavam se, ovo je verovatno ponovo zvučalo kao strašni virus.

But it's exactly this ability of phages --

Ali upravo ova sposobnost faga -

to multiply within the bacteria and then kill them --

da se razmnože u bakteriji i onda ih ubiju -

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

ih čini izuzetno interesantnim sa medicinske tačke gledišta.

The other part that I find extremely interesting

Drugi deo koji je meni izuzetno interesantan

is the scale at which this is going on.

je obim u kojem se to odvija.

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

Pre samo pet godina, nisam imao pojma o fagima.

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

A ipak, danas bih mogao da vam kažem da su oni deo prirodnog principa.

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

Fagi i bakterije postoje od najranijih dana evolucije.

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

I uvek su živeli u tandemu, držeći pod kontrolom jedni druge.

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

Dakle, ovo je u suštini priča o jinu i jangu, o lovcu i plenu,

at a microscopic level.

na mikroskopskom nivou.

Some scientists have even estimated

Neki naučnici su čak procenili

that phages are the most abundant organism on our planet.

da su fagi najrasprostranjeniji organizmi na našoj planeti.

So even before we continue talking about their medical potential,

Tako da, pre nego što nastavimo priču o njihovom medicinskom potencijalu,

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

mislim da bi svi trebalo da znaju šta su fagi i koja je njihova uloga na zemlji:

they hunt, infect and kill bacteria.

oni love, inficiraju i ubijaju bakterije.

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

Pa, kako to da imamo nešto što tako dobro funkcioniše u prirodi,

every day, everywhere around us,

svakodnevno, svuda oko nas,

and yet, in most parts of the world,

a ipak, u većem delu sveta,

we do not have a single drug on the market

nemamo nijedan lek na tržištu

that uses this principle to combat bacterial infections?

koji koristi ovaj princip u borbi protiv bakterijskih infekcija?

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

Jednostavan odgovor je: niko još nije razvio ovakvu vrstu leka,

at least not one that conforms to the Western regulatory standards

bar ne takvog koji odgovara standardima zapadne kontrole

that set the norm for so much of the world.

koja je postavila pravila u većem delu sveta.

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

Da bismo otkrili zašto, moramo se malo vratiti kroz vreme.

This is a picture of Félix d'Herelle.

Ovo je slika Feliksa De Herela.

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

On je jedan od dva naučnika zaslužnih za otkriće faga.

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

Samo, kad ih je otkrio, 1917. godine,

nije imao predstavu šta je otkrio.

what he had discovered.

He was interested in a disease called bacillary dysentery,

Zanimala ga je bolest zvana bacilarna dizenterija,

which is a bacterial infection that causes severe diarrhea,

bakterijska infekcija koja izaziva tešku dijareju,

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

i u to vreme je ubijala dosta ljudi,

zato što, na kraju krajeva, nije postojao lek za bakterijsku infekciju.

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

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

On je posmatrao uzorke pacijenata koji su preživeli bolest.

And he found that something weird was going on.

I otkrio je da se nešto čudno dešavalo.

Something in the sample was killing the bacteria

Nešto u uzorku je ubijalo bakterije

that were supposed to cause the disease.

koje je trebalo da izazovu bolest.

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

Da bi saznao šta se dešava, napravio je genijalan eksperiment.

He took the sample, filtered it

Uzeo je uzorak, filtrirao ga

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

dok nije bio siguran da je ostalo jako malo,

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

a potom je uzeo malu kap i dodao je sveže uzgojenim bakterijama.

And he observed that within a number of hours,

Onda je video da su u roku od nekoliko sati

the bacteria had been killed.

bakterije bile ubijene.

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

Onda je on ponovio ovo, ponovo filtrirao, uzeo malu kap,

adding it to the next batch of fresh bacteria.

dodao je u sledeću seriju svežih bakterija.

He did this in sequence 50 times,

Ovo je ponovio 50 puta,

always observing the same effect.

uvek gledajući isti efekat.

And at this point, he made two conclusions.

U tom momentu, zaključio je dve stvari.

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

Pre svega, što je očigledno, da, nešto je ubijalo bakterije,

and it was in that liquid.

i to nešto je bilo u tečnosti.

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

Drugo: to je moralo biti nešto biološke prirode,

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

zato što je bila dovoljna samo mala kap da napravi tako veliki učinak.

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

On je ovaj agens koji je pronašao nazvao „nevidljivi mikrob“

and gave it the name "bacteriophage,"

i dao mu naziv „bakterofag“,

which, literally translated, means "bacteria eater."

što u bukvalnom prevodu znači „žderač bakterija“.

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

A inače, ovo je jedno od osnovnih otkrića

of modern microbiology.

moderne mikrobiologije.

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

Mnoge moderne tehnike se vraćaju proučavanju toga kako fagi funkcionišu -

in genomic editing, but also in other fields.

u menjanju genoma, ali takođe i na drugim poljima.

And just today, the Nobel Prize in chemistry was announced

Upravo danas je najavljena dodela Nobelove nagrade iz hemije

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

za dva naučnika koja su radila sa fagima i razvila lek na bazi njih.

Now, back in the 1920s and 1930s,

U 1920-im i 1930-im,

people also immediately saw the medical potential of phages.

ljudi su takođe odmah uočili medicinski potencijal faga.

After all, albeit invisible,

Na kraju krajeva, iako nevidiljivo,

you had something that reliably was killing bacteria.

imali ste nešto što pouzdano ubija bakterije.

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

Kompanije koje postoje i danas, kao što su Abot, Skvib i Lili,

sold phage preparations.

su prodavale pripremu faga.

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

Ali u stvarnosti, ako počinjete sa nevidljivim mikrobima,

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

veoma je teško dobiti pouzdan lek.

Just imagine going to the FDA today

Zamislite da idete danas u Upravu za hranu i lekove

and telling them all about that invisible virus

i govorite im o nevidljivom virusu

you want to give to patients.

koji želite da date pacijentu.

So when chemical antibiotics emerged in the 1940s,

Kada su se hemijski antibiotici pojavili 1940-ih,

they completely changed the game.

potpuno su promenili igru.

And this guy played a major role.

A ovaj lik je odigrao važnu ulogu.

This is Alexander Fleming.

To je Aleksandar Fleming.

He won the Nobel Prize in medicine

Dobio je Nobelovu nagradu za medicinu

for his work contributing to the development

zbog svog rada koji je doprineo razvoju

prvog antibiotika, penicilina.

of the first antibiotic, penicillin.

And antibiotics really work very differently than phages.

A antibiotici su stvarno delovali veoma drugačije od faga.

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

Većinom, oni sprečavaju rast bakterija,

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

i nije ih mnogo briga koja je vrsta bakterija prisutna.

The ones that we call broad-spectrum

Takozvani antibiotik širokog spektra

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

će raditi protiv čitavog niza bakterija.

Compare that to phages, which work extremely narrowly

U poređenju sa fagima, čije je delovanje prilično suženo

against one bacterial species,

protiv određene bakterijske vrste,

and you can see the obvious advantage.

možete videti očiglednu prednost.

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

Tada je to verovatno izgledalo kao san koji se ostvaruje.

You had a patient with a suspected bacterial infection,

Imali ste pacijenta kod koga se sumnja na bakterijsku infekciju,

you gave him the antibiotic,

dali ste mu antibiotik,

and without really needing to know anything else about the bacteria

i bez ikakve potrebe da znate bilo šta o bakteriji

koja je izazvala bolest,

causing the disease,

many of the patients recovered.

mnogi pacijenti su se oporavili.

And so as we developed more and more antibiotics,

Tako smo razvili još antibiotika,

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

koji su, s pravom, postali prvi izbor za terapiju protiv bakterijskih infekcija.

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

Uzgred, oni su veoma doprineli produžetku životnog veka.

We are only able to do complex medical interventions

Danas možemo da izvršimo kompleksne medicinske intervencije

and medical surgeries today

i operacije

because we have antibiotics,

samo zahvaljujući antibioticima,

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

bez rizika da će pacijent umreti sledećeg dana

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

od bakterijske infekcije sa kojom je možda došao u kontakt tokom operacije.

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

Tako smo počeli da zaboravljamo na fage, pogotovo zapadna medicina.

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

I u određenoj meri, čak i dok sam ja odrastao, važio je koncept

we have solved bacterial infections; we have antibiotics.

da smo rešili problem bakterijskih infekcija

jer imamo antibiotike.

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

Naravno, danas znamo da je to pogrešno.

Today, most of you will have heard about superbugs.

Danas je većina vas verovatno čula za superbakterije.

Those are bacteria that have become resistant

To su one bakterije koje su postale otporne

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

na mnoge, ako ne na sve, antibiotike koje smo razvili

to treat this infection.

da bismo lečili infekciju.

How did we get here?

Kako smo dospeli dovde?

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

Pa, nismo bili toliko pametni koliko smo mislili da jesmo.

As we started using antibiotics everywhere --

Počeli smo koristiti antibiotike svuda -

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

u bolnicama, za lečenje i prevenciju; kod kuće, za najobičnije prehlade;

on farms, to keep animals healthy --

na farmama, da bi životinje ostale zdrave -

the bacteria evolved.

bakterije su evoluirale.

In the onslaught of antibiotics that were all around them,

U najezdi antibiotika koji su bili oko njih,

those bacteria survived that were best able to adapt.

bakterije koje su preživele su one koje su najbolje mogle da se prilagode.

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

Danas, njih zovemo „bakterije otporne na lekove“.

And let me put a scary number out there.

Dozvolite mi da iznesem jedan zastrašujući broj.

In a recent study commissioned by the UK government,

U nedavnom istraživanju koje je sprovela britanska vlada,

it was estimated that by 2050,

procenjeno je da bi do 2050. godine

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

deset miliona ljudi godišnje moglo umreti od infekcija otpornih na lekove.

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

Uporedite to sa osam miliona godišnje smrtnih ishoda od raka danas,

and you can see that this is a scary number.

i videćete da je to zastrašujući broj.

But the good news is, phages have stuck around.

Ali, dobra vest je da su fagi još uvek tu.

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

I da vam kažem, uopšte nisu impresionirani otpornošću na lekove.

(Laughter)

(Smeh)

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

I dalje srećno ubijaju i love bakterije oko nas.

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

A i dalje su ostali selektivni, što je danas jako dobra stvar.

Danas smo u mogućnosti da identifikujemo bakterijski patogen

Today, we are able to reliably identify a bacterial pathogen

that's causing an infection in many settings.

koji izaziva infekciju u mnogim prilikama.

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

A njihova selektivnost će nam pomoći da izbegnemo neke nuspojave

that are commonly associated with broad-spectrum antibiotics.

koje često prate antibiotike širokog spektra.

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

Ali možda je najbolja vest od svih to da više nisu nevidljivi mikrobi.

We can look at them.

Možemo ih videti.

And we did so together before.

I to smo i uradili zajedno.

We can sequence their DNA.

Možemo analizirati njihov DNK.

We understand how they replicate.

Shvatili smo kako se razmnožavaju.

And we understand the limitations.

I znamo njihova ograničenja.

We are in a great place

Nalazimo se na idealnoj poziciji

to now develop strong and reliable phage-based pharmaceuticals.

da sada razvijemo jaku i pouzdanu farmakologiju baziranu na fagima.

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

I to se dešava širom sveta.

More than 10 biotech companies, including our own company,

Preko 10 biotehničkih kompanija, uključujući i našu,

are developing human-phage applications to treat bacterial infections.

razvijaju primenu ljudskih faga u borbi protiv bakterijskih infekcija.

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

Broj kliničkih ispitivanja se odvija u Evropi i SAD.

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

Tako da sam uveren da stojimo na pragu

of a renaissance of phage therapy.

renesanse terapije fagima.

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

A za mene, najbolji način da se opiše fag je nešto ovako.

(Laughter)

(Smeh)

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

Za mene, fagi su superheroji koje smo čekali

in our fight against multidrug-resistant infections.

u našoj borbi protiv infekcija otpornih na lekove.

So the next time you think about a virus,

Dakle, sledeći put kada pomislite na viruse,

keep this image in mind.

imajte ovu sliku na umu.

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

Na kraju krajeva, fag vam jednog dana može spasiti život.

Thank you.

Hvala vam.

(Applause)

(Aplauz)