Jay Bradner: Open-source cancer research

Translator: Eulalia Baroja Reviewer: Xosé María Moreno

Mudeime de Chicago a Boston hai 10 anos,

I moved to Boston 10 years ago from Chicago,

with an interest in cancer and in chemistry.

interesado no cancro e na química.

You might know that chemistry is the science of making molecules

Pode que xa saibades que a química é a ciencia que fabrica moléculas,

or, to my taste,

ou no meu caso, novos fármacos para o cancro.

new drugs for cancer.

And you might also know that, for science and medicine,

E pode que tamén saibades, que para a ciencia e a medicina,

Boston is a bit of a candy store.

Boston é coma unha tenda de lambetadas.

You can't roll a stop sign in Cambridge without hitting a graduate student.

Non podes pasar un stop en Cambridge

sen dar cun estudante universitario.

The bar is called the Miracle of Science.

Ó bar chámanlle "o milagre da ciencia".

The billboards say "Lab Space Available."

A maioría dos anuncios falan de "Laboratorios dispoñibles".

And it's fair to say that in these 10 years,

E poderiamos dicir que dende hai uns 10 anos

we've witnessed absolutely the start of a scientific revolution --

estamos a presenciar a comezo

dunha revolución científica: a medicina xenómica.

that of genome medicine.

Sabemos máis dos pacientes que entran nas nosas clínicas

We know more about the patients that enter our clinic now

do que nunca soubemos.

than ever before.

And we're able, finally, to answer the question

E podemos, por fin, responder á pregunta

que nos ten urxido durante tantos anos:

that's been so pressing for so many years:

Why do I have cancer?

por que temos cancro?

This information is also pretty staggering.

Esta información é bastante sorprendente.

Pode que xa saibades que,

You might know that, so far, in just the dawn of this revolution,

por agora, nos comezos desta revolución,

we know that there are perhaps 40,000 unique mutations

sabemos que hai coma unhas 40.000 mutacións

que afectan a máis de 10.000 xenes;

affecting more than 10,000 genes,

and that there are 500 of these genes that are bona-fide drivers,

e que 500 deses xenes,

dan lugar a cancros,

causes of cancer.

de forma contrastada.

Pero en cambio,

Yet comparatively,

we have about a dozen targeted medications.

temos coma unha ducia de medicamentos dirixidos.

And this inadequacy of cancer medicine

E esta falta de eficiencia no tratamento do cancro

really hit home when my father was diagnosed with pancreatic cancer.

afectoume moito cando lle diagnosticaron

cancro de páncreas ó meu pai.

Non o trouxemos a Boston.

We didn't fly him to Boston.

We didn't sequence his genome.

Nin secuenciamos o seu xenoma.

It's been known for decades what causes this malignancy.

Hai décadas que se sabe

que é o que causa estes tumores.

Son tres proteínas:

It's three proteins: ras, myc, p53.

Ras, MIC e p53.

This is old information we've known since about the 80s,

Sabemos esta información xa dende os anos 70,

yet there's no medicine I can prescribe

pero aínda non se pode recetar unha menciña

to a patient with this or any of the numerous solid tumors

a un paciente con este

ou calquera dos outros tumores

caused by these three ...

que causan estes tres xinetes

Horsemen of the Apocalypse that is cancer.

do apocalipsis que chamamos cancro.

There's no ras, no myc, no p53 drug.

Non hai tratamento para a Ras, MIC ou p53.

And you might fairly ask: Why is that?

E con toda razón vos preguntaredes: por que?

A resposta, científica, pero non por iso menos decepcionante

And the very unsatisfying yet scientific answer is:

é que é moi difícil.

it's too hard.

That for whatever reason,

Por algunha razón

these three proteins have entered a space, in the language of our field,

estas tres proteínas están nunha área do campo científico

that's called the undruggable genome --

que chamamos "o xenoma intratable".

which is like calling a computer unsurfable

Que é como chamar a un ordenador inexplorable,

ou á lúa impaseable.

or the Moon unwalkable.

It's a horrible term of trade.

Vaia, un estarrecedor termo do gremio.

But what it means

O que significa

is that we've failed to identify a greasy pocket in these proteins,

é que non damos atopado ningún buraco nestas proteínas

no que poder, coma se fósemos cerralleiros,

into which we, like molecular locksmiths,

can fashion an active, small, organic molecule or drug substance.

introducir algunha pequena molécula ou substancia

orgánica activa.

Namentres estudaba medicina clínica,

Now, as I was training in clinical medicine

hematoloxía e oncoloxía,

and hematology and oncology and stem-cell transplantation,

e transplantes con células nai,

what we had instead,

o que atopábamos en troques

cascading through the regulatory network at the FDA,

no Regulamento da Axencia de Drogas e Alimentos

eran estas substancias:

were these substances:

arsenic,

arsénico, talidomida

thalidomide,

e este derivado químico

and this chemical derivative of nitrogen mustard gas.

do gas mostaza nitroxenado.

And this is the 21st century.

E isto é o século XXI.

And so, I guess you'd say,

E así, como vostedes dirían, insatisfeito

dissatisfied with the performance and quality of these medicines,

co rendemento e calidade destes medicamentos,

I went back to school, in chemistry,

volvín a estudar químicas.

Pensaba que

with the idea that perhaps by learning the trade of discovery chemistry

quizais aprendendo o oficio dos descubrimentos químicos

and approaching it in the context of this brave new world

e dende o contexto deste novo e descoñecido mundo

of the open source,

que é o do código aberto,

o código-compartido,

the crowd source,

the collaborative network that we have access to within academia,

a rede colaborativa á que temos acceso no ámbito académico,

that we might more quickly bring powerful and targeted therapies

quizais atopariamos terapias

máis potentes e dirixidas ós pacientes

con máis rapidez.

to our patients.

And so, please consider this a work in progress,

Entendede que aínda é un proxecto en curso,

pero gustaríame contarvos unha historia

but I'd like to tell you today a story

sobre un cancro pouco común,

about a very rare cancer called midline carcinoma,

o das estruturas da liña media,

sobre o transporte de proteínas,

about the undruggable protein target that causes this cancer,

o transporte de proteínas intratable que causan este cancro,

chamadas BRD4,

called BRD4,

and about a molecule developed at my lab at Dana-Farber Cancer Institute,

e sobre unha molécla

elaborada no meu laboratorio no Instituto para o Cancro Dana Farber

called JQ1,

chamada JQ1, chamada así por Jun Qi,

which we affectionately named for Jun Qi,

o químico que a fabricou.

the chemist that made this molecule.

Now, BRD4 is an interesting protein.

A BRD4 é unha proteína interesante.

You might ask: with all the things cancer's trying to do to kill our patient,

Quizais vos preguntedes, con todo o que fai o cancro para tratar de matar ós pacientes,

como se acorda de que é un cancro?

how does it remember it's cancer?

Cando enrola o seu xenoma,

When it winds up its genome,

divides into two cells and unwinds again,

se divide en dúas células e se desenrola de novo,

why does it not turn into an eye, into a liver,

por que non se convirte nun ollo, ou nun fígado?

Ten os xenes necesarios para facelo.

as it has all the genes necessary to do this?

It remembers that it's cancer.

Pero sempre lembra que é un cancro.

And the reason is that cancer, like every cell in the body,

A razón é que o cancro, igual ca outras células do corpo,

coloca unhas pequenas marcas moleculares,

places little molecular bookmarks,

coma un Post-it,

little Post-it notes,

that remind the cell, "I'm cancer; I should keep growing."

que lle recorda: "Son un cancro, teño que seguir crecendo."

E estas notas inclúen

And those Post-it notes involve this and other proteins of its class --

esa e outras proteínas do mesmo tipo;

os chamados bromodominios.

so-called bromodomains.

So we developed an idea, a rationale,

Nós elaboramos unha idea, unha base lóxica:

that perhaps if we made a molecule

quizais se fabricásemos unha molécula

that prevented the Post-it note from sticking

que previse que se pegase esa nota

entrando no buratiño

by entering into the little pocket

at the base of this spinning protein,

da base desta proteína xiratoria,

then maybe we could convince cancer cells,

quizais poderiamos convencer as células canceríxenas,

certainly those addicted to this BRD4 protein,

a esas adictas ás proteínas BRD4,

that they're not cancer.

de que non son un cancro.

And so we started to work on this problem.

Así comezamos a traballar neste problema.

We developed libraries of compounds

Elaboramos unha cantidade importante de compostos

e finalmente chegamos á JQ1 e outras

and eventually arrived at this and similar substances

substancias similares.

called JQ1.

Now, not being a drug company,

Como non somos unha famacéutica,

we could do certain things, we had certain flexibilities,

tiñamos varias opcións, tiñamos flexibilidade,

that I respect that a pharmaceutical industry doesn't have.

que entendo que a industria farmacéutica non ten.

We just started mailing it to our friends.

Así que enviamos a JQ1 ós nosos amigos.

Eu teño un pequeno laboratorio.

I have a small lab.

We thought we'd just send it to people and see how the molecule behaves.

Así que pensamos enviala e ver cómo se comportaba a molécula.

Mandámola a Oxford, en Inglaterra,

We sent it to Oxford, England,

onde un grupo de destacados cristalógrafos xeraron esta imaxe,

where a group of talented crystallographers provided this picture,

que nos axudou a comprender

which helped us understand exactly how this molecule is so potent

como a molécula era tan útil para transporte de proteínas.

for this protein target.

It's what we call a perfect fit of shape complementarity,

É o que chamamos un axuste perfecto,

unha forma complementaria, un feito a medida.

or hand in glove.

Este cancro é moi pouco común,

Now, this is a very rare cancer,

este cancro adicto á BRD4

this BRD4-addicted cancer.

Traballamos entón con mostras de material

And so we worked with samples of material

that were collected by young pathologists at Brigham and Women's Hospital.

recollido por patólogos novos do Hospital Brigham para mulleres.

E namentres tratabamos estas células coa molécula,

And as we treated these cells with this molecule,

we observed something really striking.

observamos algo moi asombroso.

As células canceríxenas,

The cancer cells --

small, round and rapidly dividing,

pequenas, redondas, que se dividen rápido,

grew these arms and extensions.

facían uns brazos e prolongacións.

They were changing shape.

Estaban a cambiar de forma.

In effect,

De feito, a célula canceríxena

the cancer cell was forgetting it was cancer

estaba esquecendo que era un cancro

e convertíase nunha célula normal.

and becoming a normal cell.

Estabamos entusiasmados.

This got us very excited.

O seguinte paso era inocular a molécula en ratos.

The next step would be to put this molecule into mice.

The only problem was there's no mouse model of this rare cancer.

Pero non hai modelos deste tipo de cancro para ratos.

Mentras levabamos a cabo esta investigación,

And so at the time we were doing this research,

I was caring for a 29-year-old firefighter from Connecticut

eu estaba tratando a un bombeiro de 29 anos

que estaba case no final da súa vida

who was very much at the end of life

with this incurable cancer.

a causa deste tipo de cancro.

This BRD4-addicted cancer was growing throughout his left lung.

Este cancro adicto á BRD4

estaba crecendo no seu pulmón esquerdo.

And he had a chest tube in that was draining little bits of debris.

Tiña un tubo torácico que drenaba pequenos restos do cancro

que se tiraban

And every nursing shift, we would throw this material out.

en cada quenda das enfermeiras.

And so we approached this patient

Así que nos achegamos a este paciente

and asked if he would collaborate with us.

e lle pedimos que colaborase con nós.

Could we take this precious and rare cancerous material

Queriamos coller ese material canceríxeno raro e valioso

from this chest tube

do tubo torácico,

and drive it across town and put it into mice

levalo ó laboratorio e inxectárlleo ós ratos

and try to do a clinical trial at a stage that with a prototype drug,

para tratar de facer un ensaio clínico

e probar o prototipo de tratamento.

well, that would be, of course, impossible

Sería imposible e, a dicir verdade, ilegal facelo en persoas.

and, rightly, illegal to do in humans.

Axudounos.

And he obliged us.

At the Lurie Family Center for Animal Imaging,

E no Centro de Imaxe da Familia Lurie,

our colleague, Andrew Kung, grew this cancer successfully in mice

o meu compañeiro Andrew Kung fixo crecer con éxito

este cancro nos ratos.

without ever touching plastic.

And you can see this PET scan of a mouse -- what we call a pet PET.

Podedes ver nesta tomografía de positróns dun rato

como crece o cancro,

The cancer is growing

as this red, huge mass in the hind limb of this animal.

esa masa grande e vermella nas patas traseiras do animal.

Cando o tratamos co noso composto,

And as we treat it with our compound,

a adicción,

this addiction to sugar,

o crecemento, parou.

this rapid growth, faded.

And on the animal on the right,

No animal da dereita

you see that the cancer was responding.

vese como respondeu o cancro.

We've completed, now, clinical trials

Xa completamos ensaios clínicos

en ratos con catro modelos da enfermidade

in four mouse models of this disease.

e sempre obtemos o mesmo resultado:

And every time, we see the same thing.

The mice with this cancer that get the drug live,

os ratos ós que inxectamos o fármaco sobreviven;

os outros morren con rapidez.

and the ones that don't rapidly perish.

Comezamos entón a preguntarnos

So we started to wonder,

what would a drug company do at this point?

que faría unha farmacéutica no noso caso.

Well, they probably would keep this a secret

Seguramente o manterían en segredo

until they turn the prototype drug

ata obter un principio activo

into an active pharmaceutical substance.

a partir do prototipo.

Pero nós fixemos o contrario.

So we did just the opposite.

Publicamos un artigo

We published a paper that described this finding

que describía os achados

at the earliest prototype stage.

na fase do prototipo.

We gave the world the chemical identity of this molecule,

Demos ó mundo a fórmula química da molécula,

typically a secret in our discipline.

o que sería xeralmente un segredo na nosa especialidade.

We told people exactly how to make it.

Explicamos con exactitude cómo fabricala,

e proporcionamos a nosa dirección

We gave them our email address,

suggesting that if they write us,

ofrecéndonos a enviar unha molécula

we'll send them a free molecule.

de forma gratuita se nola pedían.

(Laughter)

Basicamente tratamos de crear

We basically tried to create the most competitive environment

un entorno cooperativo para o noso laboratorio o máis competivo posible.

for our lab as possible.

E tivo éxito, por desgracia.

And this was, unfortunately, successful.

(Risos)

(Laughter)

Because now, we've shared this molecule,

Porque agora que xa compartimos a molécula,

just since December of last year,

en decembro do ano pasado,

with 40 laboratories in the United States

con 40 laboratorios nos EEUU

e outros 30 en Europa,

and 30 more in Europe --

moitos deles de empresas farmacéuticas

many of them pharmaceutical companies,

seeking now to enter this space,

procuran agora entrar neste espazo,

to target this rare cancer that, thankfully right now,

en investigar sobre este cancro;

agora, por fortuna,

is quite desirable to study in that industry.

resulta interesante tratar o tema na industria.

Pero a ciencia que retorna de todos eses laboratorios

But the science that's coming back from all of these laboratories

sobre o uso da molécula

about the use of this molecule

proporcionounos ideas

has provided us insights we might not have had on our own.

que por nós mesmos nos obteriamos.

Leukemia cells treated with this compound

As células con leucemia que se tratan con ela

turn into normal white blood cells.

vólvense glóbulos brancos normais.

Mice with multiple myeloma,

Os ratos con mielomas múltiples,

an incurable malignancy of the bone marrow,

unha enfermidade incurable da médula ósea,

respond dramatically

responden de forma espectacular

to the treatment with this drug.

ó tratamento con este fármaco.

You might know that fat has memory.

Pode que saibades que a graxa ten memoria.

É interesante poder demostralo.

I'll nicely demonstrate that for you.

(Laughter)

In fact, this molecule

E de feito, esta molécula

prevents this adipocyte, this fat stem cell,

evita que eses adipocitos, esas células nai graxas,

from remembering how to make fat,

recorden como facer graxa.

such that mice on a high-fat diet,

Así, ratos cunha dieta con moita graxa,

like the folks in my hometown of Chicago --

coma a da xente do meu pobo natal,

(Laughter)

non acaban cun fígado graxo,

fail to develop fatty liver,

un problema médico bastante grave.

which is a major medical problem.

O que este estudo nos ensinou;

What this research taught us --

not just my lab, but our institute,

non só ó meu laboratorio, senón tamén

ó noso instituto e á Facultade de Medicina de Harvard;

and Harvard Medical School more generally --

é que no ámbito académico temos recursos excepcionais

is that we have unique resources in academia

para descubrir fármacos,

for drug discovery;

that our center, which has tested perhaps more cancer molecules

que o noso centro

que ten feito máis probas ca ningún outro con moléculas

in a scientific way

relacionadas con cancro,

than any other,

never made one of its own.

nunca fixo ningunha en solitario.

For all the reasons you see listed here,

Por todo o que temos dito ata agora,

we think there's a great opportunity for academic centers

pensamos que é unha boa oportunidade para que os centros académicos

to participate in this earliest, conceptually tricky

participen nesta disciplina, nova, creativa

e conceptualmente complicada,

and creative discipline

of prototype drug discovery.

que é a descuberta de prototipos farmacéuticos.

E agora que?

So what next?

We have this molecule, but it's not a pill yet.

Temos unha molécula, pero non pílulas.

Non hai unha forma de toma oral.

It's not orally bioavailable.

We need to fix it so we can deliver it to our patients.

Temos que conseguir que chegue ós pacientes.

And everyone in the lab,

Todos no laboratorio,

especially following the interaction with these patients,

especialmente os que máis interaccionan cos pacientes,

séntense bastente obrigados

feels quite compelled to deliver a drug substance

a produciren un fármaco a partir desta molécula.

based on this molecule.

It's here where I'd say

Agora é cando

that we could use your help and your insights,

pido a vosa colaboración,

your collaborative participation.

axuda e ideas.

Unlike a drug company, we don't have a pipeline

A diferenza dunha empresa farmacéutica,

non temos unha liña de distribución onde colocar as moléculas.

that we can deposit these molecules into.

Non temos un equipo de vendedores e comerciantes

We don't have a team of salespeople and marketeers

to tell us how to position this drug against the other.

que nos digan como colocar o fármaco fronte ó resto.

What we do have is the flexibility of an academic center

O que si temos é a flexibilidade de ser un centro académico,

onde traballa xente competente, motivada e

to work with competent, motivated,

enthusiastic, hopefully well-funded people

entusiasta, e esperamos que con fondos,

to carry these molecules forward into the clinic

para levarmos estas moléculas cara o paso clínico

while preserving our ability to share the prototype drug worldwide.

á vez que preservan a nosa capacidade

para compartir o prototipo co resto do mundo.

This molecule will soon leave our benches

A molécula pronto deixará o noso laboratorio

para trasladarse a unha nova pequena compañía

and go into a small start-up company called Tensha Therapeutics.

chamada Tensha Therapeutics.

And, really, this is the fourth of these molecules

En realidade é a cuarta destas moléculas

to kind of "graduate" from our little pipeline

que se "gradúa" no noso laboratorio de descubrimentos.

of drug discovery,

Dúas delas, un fármaco tópico

two of which -- a topical drug for lymphoma of the skin

para o linfoma de pel,

and an oral substance for the treatment of multiple myeloma --

unha substancia oral para tratar o mieloma múltiple,

will actually come to the bedside for the first clinical trial

están a piques de comezar

o seu primeiro ensaio clínico, en xullo deste ano.

in July of this year -- for us, a major and exciting milestone.

Para nós é un gran e estimulante fito.

I want to leave you with just two ideas.

Quero deixarvos dúas ideas.

The first is: if anything is unique about this research,

En primeiro lugar,

o excepcional da nosa investigación:

it's less the science than the strategy.

non foi tanto a ciencia, senón a estratexia;

This, for us, was a social experiment --

isto foi para nós un experimento social.

Queriamos comprobar que pasaría

an experiment in "What would happen if we were as open and honest

se fósemos tan abertos e honestos

at the earliest phase of discovery chemistry research

nas primeiras fases da investigación química

as we could be?"

como puidésemos.

This string of letters and numbers

Esta cadea de letras, números,

and symbols and parentheses

símbolos e parénteses

that can be texted, I suppose,

que se pode mandar nun SMS,

or Twittered worldwide,

ou twittear mundialmente,

é a fórmula química do noso composto.

is the chemical identity of our pro compound.

It's the information that we most need from pharmaceutical companies,

É a información que precisamos

das compañías farmacéuticas,

the information on how these early prototype drugs might work.

a información

de cómo estes prototipos poderían funcionar.

Yet this information is largely a secret.

Pero esta información é xeralmente secreta.

And so we seek, really, to download

Así que nós esperamos

sacar partido dos abraiantes éxitos

from the amazing successes of the computer-science industry,

da industria científica informática, dous principios:

two principles -- that of open source and that of crowdsourcing --

o código aberto e o "crowdsourcing",

para acelerar de maneira

to quickly, responsibly accelerate the delivery of targeted therapeutics

responsable e rápida o acceso dos pacientes

to patients with cancer.

ás terapias dirixidas.

Now, the business model involves all of you.

Agora o modelo empresarial inclúevos a todos vós.

This research is funded by the public.

Esta investigación finánciaa o público.

It's funded by foundations.

Finánciana fundacións.

And one thing I've learned in Boston

E unha cousa que aprendín en Boston

is that you people will do anything for cancer, and I love that.

é que a xente de aquí faría calquera cousa polo cancro, e é algo que adoro.

Recorrer o estado en bicicleta, subir e baixar o río...

You bike across the state, you walk up and down the river.

(Risos)

(Laughter)

En ningunha outra parte teño visto

I've never seen, really, anywhere,

un apoio semellante

this unique support for cancer research.

para o estudo do cancro.

And so I want to thank you

Así que quero dárvos as grazas

for your participation, your collaboration

pola vosa participación, colaboración

and most of all,

e sobre todo pola vosa confianza nas nosas ideas.

for your confidence in our ideas.

(Aplausos)

(Applause)