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

Translator: Alberte Regueira López Reviewer: Serv. de Norm. Lingüística U. de Santiago de Compostela

Take a moment

Detédevos un momento,

and think about a virus.

e pensade nun virus.

What comes to your mind?

Que vos vén á cabeza?

An illness?

Unha doenza?

A fear?

Medo?

Probably something really unpleasant.

De seguro algo moi desagradable.

And yet, viruses are not all the same.

Porén, non todos os virus son iguais.

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

É certo, algúns deles causan doenzas devastadoras.

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

Pero outros poden facer xusto o contrario: curar doenzas

These viruses are called "phages."

Estes virus chámanse "fagos".

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

A primeira vez que oín falar dos fagos foi no 2013.

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

Meu sogro, que é cirurxián,

was telling me about a woman he was treating.

faloume sobre unha muller á que estaba tratando.

The woman had a knee injury, required multiple surgeries,

Tiña unha ferida no xeonllo que precisou múltiples operacións,

and over the course of these,

e durante o proceso

developed a chronic bacterial infection in her leg.

desenvolveu na perna unha infección bacteriana crónica.

Unfortunately for her,

Por desgraza, as bacterias causantes da infección non respondían

the bacteria causing the infection also did not respond

to any antibiotic that was available.

a ningún antibiótico dispoñible.

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

Chegados a este punto, a única opción que quedaba era amputar a perna

to stop the infection from spreading further.

para evitar que a infección se espallase máis.

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

Meu sogro buscaba desesperadamente outra solución

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

e optou por un tratamento experimental empregando fagos como último recurso.

And guess what? It worked.

E adiviñade o que pasou. Funcionou.

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

Tres semanas despois de empregar os fagos, a infección crónica curou,

where before, no antibiotic was working.

aínda cando ningún antibiótico funcionara.

I was fascinated by this weird conception:

Fascinoume esta peculiar idea:

viruses curing an infection.

un virus que cura unha infección.

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

Ata hoxe, sigo abraiado coas posibilidades médicas dos fagos.

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

E de feito o ano pasado deixei o traballo para crear unha empresa neste ámbito.

Now, what is a phage?

Agora ben, que é un fago?

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

A imaxe que vedes aquí foi tomada cun microscopio electrónico.

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

Iso significa que o que se ve en pantalla é en realidade extremadamente minúsculo.

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

Esa cousa granulada do medio cunha cabeza, un corpo longo

and a number of feet --

e uns cantos pés

this is the image of a prototypical phage.

é a imaxe dun fago prototípico.

It's kind of cute.

A que é riquiño?

(Laughter)

(Risos)

Now, take a look at your hand.

Agora, ollade a vosa man.

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

No noso equipo, estimamos que tedes máis de 10 mil millóns de fagos

on each of your hands.

en cada unha das mans.

What are they doing there?

Que están facendo aí?

(Laughter)

(Risos)

Well, viruses are good at infecting cells.

Pois ben, os virus son bos infectando células

And phages are great at infecting bacteria.

E os fagos dedícanse a infectar bacterias.

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

A vosa man, como a maior parte do voso corpo,

is a hotbed of bacterial activity,

é un fervedoiro de actividade bacteriana,

making it an ideal hunting ground for phages.

o que a fai un lugar perfecto de caza para os fagos.

Because after all, phages hunt bacteria.

Xa que ó fin e ó cabo, os fagos cazan bacterias.

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

Tamén é importante saber que son cazadores moi selectivos.

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

Normalmente un fago só pode infectar unha especie bacteriana.

So in this rendering here, the phage that you see

O fago que vedes aquí nesta representación,

hunts for a bacterium called Staphylococcus aureus,

caza unha bacteria chamada Staphylococcus aureus,

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

que se coñece como SARM na súa forma resistente ós antibióticos.

It causes skin or wound infections.

Causa infeccións na pel ou en feridas.

The way the phage hunts is with its feet.

Os fagos cazan cos pés

The feet are actually extremely sensitive receptors,

En realidade, os pés son receptores extremadamente sensibles,

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

que buscan unha superficie en particular nas células bacterianas.

Once it finds it,

Unha vez atopada,

the phage will latch on to the bacterial cell wall

o fago acóplase á parede celular da bacteria

and then inject its DNA.

e despois inxecta o seu ADN.

DNA sits in the head of the phage

O ADN atópase na cabeza do fago

and travels into the bacteria through the long body.

e viaxa ata a bacteria a través do corpo longo.

At this point, the phage reprograms the bacteria

Neste intre, o fago reprograma a bacteria

into producing lots of new phages.

para producir unha morea de novos fagos.

The bacteria, in effect, becomes a phage factory.

Deste xeito, a bacteria convértese nunha fábrica de fagos.

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

Cando se acumulan entre 50 e 100 fagos dentro da célula bacteriana

the phages are then able to release a protein

estes xa son capaces de liberar unha proteína

that disrupts the bacteria cell wall.

que rompe a parede celular da bacteria.

As the bacteria bursts, the phages move out

Ó estalar a bacteria libéranse os fagos

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

e van de caza outra vez para infectar unha nova bacteria.

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

Síntoo, se cadra isto tamén semella un arrepiante virus.

But it's exactly this ability of phages --

Pero esta capacidade específica dos fagos,

to multiply within the bacteria and then kill them --

a de multiplicárense dentro de bacterias e despois matalas,

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

é a que os fai tan interesantes dende un punto de vista médico.

The other part that I find extremely interesting

O outro aspecto que considero de sumo interese

is the scale at which this is going on.

é a escala a que isto acontece.

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

Hai cinco anos non tiña nin idea sobre fagos

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

Pero hoxe podo afirmar que son parte dun principio natural.

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

Os fagos e as bacterias remóntanse ós primeiros días da evolución.

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

Sempre existiron conxuntamente controlándose entre si.

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

De feito, é a historia do yin e o yang, a do o cazador e a presa,

at a microscopic level.

a nivel microscópico.

Some scientists have even estimated

Algúns científicos ata consideran

that phages are the most abundant organism on our planet.

que os fagos son os organismos máis abundantes do planeta.

So even before we continue talking about their medical potential,

Así que antes de seguir falando do seu potencial médico,

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

penso que todos deberíamos coñecer os fagos e o seu papel na Terra:

they hunt, infect and kill bacteria.

cazan, infectan e destrúen bacterias.

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

Como é que temos algo que funciona tan ben na natureza,

every day, everywhere around us,

todo o tempo, en calquera lugar,

and yet, in most parts of the world,

e aínda así na maior parte do mundo

we do not have a single drug on the market

non hai unha menciña no mercado

that uses this principle to combat bacterial infections?

que empregue este principio para combater infeccións bacterianas?

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

A resposta sinxela é: non se desenvolveu aínda unha menciña deste tipo,

at least not one that conforms to the Western regulatory standards

polo menos unha que cumpra cos estándares de regulación occidentais,

that set the norm for so much of the world.

que serven de referencia para a maioría do mundo.

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

Para enterdermos o porqué, é preciso mirarmos cara ao pasado.

This is a picture of Félix d'Herelle.

Esta é unha foto de Félix d'Herelle.

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

É un dos dous científicos ós que se atribúe o descubrimento dos fagos.

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

Aínda que cando os descubriu en 1917 non tiña idea

what he had discovered.

do que acababa de descubrir.

He was interested in a disease called bacillary dysentery,

Estaba interesado nunha enfermidade chamada disentería bacilar,

which is a bacterial infection that causes severe diarrhea,

unha infección bacteriana que provoca diarrea aguda

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

e que estaba matando unha morea de xente,

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

xa que daquela aínda non había cura para as infeccións bacterianas.

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

Estaba observando mostras de pacientes que sobreviviran a esta enfermidade.

And he found that something weird was going on.

E atopou que algo estraño estaba pasando.

Something in the sample was killing the bacteria

Algo nas mostras estaba matando as bacterias

that were supposed to cause the disease.

que supostamente causaban a enfermidade.

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

Para saber o que estaba pasando, realizou un experimento ben enxeñoso.

He took the sample, filtered it

Colleu unha mostra, filtrouna

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

ata que estaba seguro de que só podía quedar algo minúsculo,

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

e despois engadiu unha pinguiña a cultivos de bacterias novos.

And he observed that within a number of hours,

E observou que nunhas horas

the bacteria had been killed.

as bacterias morreran.

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

Repetiu entón o experimento, filtrou outra vez a mostra, colleu unha pinguiña

adding it to the next batch of fresh bacteria.

e engadiuna á seguinte quenda de bacterias frescas.

He did this in sequence 50 times,

Fixo isto en cadea 50 veces,

always observing the same effect.

e sempre obtivo o mesmo resultado.

And at this point, he made two conclusions.

E chegado a este punto, concluíu dúas cousas.

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

En primeiro lugar, a máis obvia: si, algo estaba matando as bacterias

and it was in that liquid.

e estaba nese líquido.

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

A outra: tiña que ser algo de natureza biolóxica,

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

xa que unha pinguiña de nada era abondo para provocar un gran impacto.

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

Ó axente que atopou chamoulle "microbio invisible"

and gave it the name "bacteriophage,"

e denominouno "bacteriófago",

which, literally translated, means "bacteria eater."

que literalmente significa "que come bacterias".

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

E por certo, este foi un dos descubrimentos máis importantes

of modern microbiology.

da microbioloxía moderna.

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

Unha chea de técnicas modernas baséanse no coñecemento sobre os fagos

in genomic editing, but also in other fields.

na edición xenómica e noutras áreas.

And just today, the Nobel Prize in chemistry was announced

E precisamente hoxe, outorgouse o premio Nobel de Química

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

a dous científicos que traballan con fagos e que desenvolven menciñas baseadas neles.

Now, back in the 1920s and 1930s,

Nos anos 20 e 30 do século pasado,

people also immediately saw the medical potential of phages.

viuse inmediatamente o potencial médico dos fagos.

After all, albeit invisible,

Á fin e ao cabo, aínda que invisibles,

you had something that reliably was killing bacteria.

había algo que mataba bacterias cunha alta efectividade.

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

Empresas que aínda hoxe existen, como Abbott, Squibb ou Lilly,

sold phage preparations.

vendían preparados de fagos.

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

Pero a verdade é que se partes dun microbio invisible

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

é moi difícil obter unha menciña fiable.

Just imagine going to the FDA today

Imaxinade como sería ir hoxe en día á FDA

and telling them all about that invisible virus

e falarlles dun virus invisible

you want to give to patients.

que lle queres dar ós pacientes.

So when chemical antibiotics emerged in the 1940s,

Cando os antibióticos químicos apareceron nos anos 40,

they completely changed the game.

cambiaron as regras do xogo por completo.

And this guy played a major role.

E este tipo tivo un papel moi importante.

This is Alexander Fleming.

É Alexander Fleming.

He won the Nobel Prize in medicine

Gañou o Premio Nobel de Medicina

for his work contributing to the development

polas súas contribucións ó desenvolvemento

do primeiro antibiótico: a penicilina.

of the first antibiotic, penicillin.

And antibiotics really work very differently than phages.

Os antibióticos funcionan dun xeito moi distinto ós fagos.

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

A maioría deles inhiben o crecemento das bacterias

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

e non lles importa moito que tipo de bacteria sexa.

The ones that we call broad-spectrum

Os que se denominan de amplo espectro

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

son efectivos para unha morea de bacterias.

Compare that to phages, which work extremely narrowly

Comparados cos fagos, que son extremadamente precisos

against one bacterial species,

contra unha especie bacteriana,

and you can see the obvious advantage.

a vantaxe é evidente.

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

No seu día, isto tivo que ser como un soño feito realidade.

You had a patient with a suspected bacterial infection,

Tiñas un paciente sospeitoso de ter unha infección bacteriana

you gave him the antibiotic,

dábaslle o antibiótico,

and without really needing to know anything else about the bacteria

e sen ter que saber nada sobre a bacteria causante da enfermidade

causing the disease,

many of the patients recovered.

a maioría dos pacientes recuperábanse.

And so as we developed more and more antibiotics,

E axiña que se desenvolveron máis e máis antibióticos

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

convertéronse con razón na principal terapia para as infeccións bacterianas.

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

E por certo, contribuíron enormemente á nosa esperanza de vida.

We are only able to do complex medical interventions

Hoxe en día é posible realizar intervencións complexas

and medical surgeries today

e cirurxías médicas

because we have antibiotics,

porque hai antibióticos,

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

e non nos arriscamos a que o paciente morra ó día seguinte

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

por unha infección bacteriana que puido contraer durante a operación.

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

Así que comezamos a esquecernos dos fagos, en especial na medicina occidental.

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

E ata certo punto, cando era novo, a crenza era:

we have solved bacterial infections; we have antibiotics.

o problema das infeccións bacterianas está resolto, hai antibióticos.

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

Hoxe sabemos que isto non é certo, claro.

Today, most of you will have heard about superbugs.

Hoxe, a maioría oiriades falar das superbacterias.

Those are bacteria that have become resistant

Son bacterias que se tornaron resistentes

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

á maioría dos antibióticos que levamos desenvolvidos

to treat this infection.

para tratar unha infección.

How did we get here?

Como chegamos ata aquí?

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

Non eramos tan listos como pensabamos.

As we started using antibiotics everywhere --

Ó empezar a usar antibióticos en todas partes,

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

nos hospitais para tratar e previr, na casa para un catarro común,

on farms, to keep animals healthy --

nas granxas, para manter os animais sans,

the bacteria evolved.

as bacterias evolucionaron.

In the onslaught of antibiotics that were all around them,

Na arremetida de antibióticos á que se viron sometidas,

those bacteria survived that were best able to adapt.

as bacterias que mellor souberon adaptarse sobreviviron.

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

Agora chamámoslles "bacterias multirresistentes".

And let me put a scary number out there.

Deixádeme que vos dea un dato preocupante.

In a recent study commissioned by the UK government,

Nun estudo recente encargado polo goberno británico,

it was estimated that by 2050,

estimouse que para o ano 2050,

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

poden morrer dez millóns de persoas ó ano por infeccións resistentes ás menciñas.

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

Comparado coas oito millóns de mortes anuais por cancro actuais

and you can see that this is a scary number.

podedes ver que é un dato que mete medo.

But the good news is, phages have stuck around.

Pero as boas novas son que aínda contamos cos fagos.

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

E deixádeme dicirvos, non lle teñen medo á resistencia ós antibióticos.

(Laughter)

(Risos)

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

Seguen cazando e matando bacterias ó noso redor coma se nada.

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

E aínda por riba son selectivos, o que é algo moi bo actualmente.

Today, we are able to reliably identify a bacterial pathogen

Hoxe, somos quen de identificar con certeza un patóxeno bacteriano

that's causing an infection in many settings.

que causa unha infección en distintos contornos.

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

A súa selectividade axudaranos a evitar algúns efectos secundarios

that are commonly associated with broad-spectrum antibiotics.

comunmente asociados ós antibióticos de amplo espectro.

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

Pero quizais a mellor noticia é que xa non son microbios invisibles.

We can look at them.

Podemos miralos.

And we did so together before.

Fixémolo xuntos hai un intre.

We can sequence their DNA.

Podemos secuenciar o seu ADN,

We understand how they replicate.

entendemos como se replican

And we understand the limitations.

e comprendemos as súas limitacións.

We are in a great place

Estamos nun excelente momento

to now develop strong and reliable phage-based pharmaceuticals.

para desenvolver menciñas efectivas e fiables baseadas en fagos.

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

E xusto iso é o que está pasando no mundo.

More than 10 biotech companies, including our own company,

Máis de 10 empresas biotecnolóxicas, incluída a nosa,

están desenvolvendo fagoterapias para tratar infeccións bacterianas en humanos.

are developing human-phage applications to treat bacterial infections.

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

Estanse a realizar ensaios clínicos en Europa e nos EE. UU.

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

Estou convencido de que nos atopamos ás portas

of a renaissance of phage therapy.

do rexurdimento da terapia con fagos.

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

E, para min, a maneira axeitada de representar un fago é algo tal que así.

(Laughter)

(Risos)

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

Para min, os fagos son os superheroes que levamos tempo agardando

in our fight against multidrug-resistant infections.

na nosa loita contra as infeccións resistentes ós antibióticos.

So the next time you think about a virus,

Así que a próxima vez que pensedes nun virus,

keep this image in mind.

lembrade esta imaxe.

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

Despois de todo, nunca saberedes cando un fago vos pode salvar a vida.

Thank you.

Grazas.

(Applause)

(Aplausos)