The next software revolution: programming biological cells | Sara-Jane Dunn

Translator: Carlos Calo Romeu Reviewer: Servizo de Normalización Lingüística

A segunda metade do século XX estivo marcada

por unha revolución tecnolóxica:

a revolución do software.

The second half of the last century was completely defined

A capacidade de programar electróns nun material chamado silicio

by a technological revolution:

fixo posible tecnoloxías, empresas e industrias

the software revolution.

que eran, en certo punto, inimaxinables para moitos de nós,

The ability to program electrons on a material called silicon

pero que agora cambiaron de raíz a forma na que o mundo funciona.

made possible technologies, companies and industries

that were at one point unimaginable to many of us,

Porén, na primeira metade do século XXI

vai acontecer unha nova revolución do software:

but which have now fundamentally changed the way the world works.

a revolución do software vivente,

The first half of this century, though,

que se baseará na capacidade de programar a bioquímica

is going to be transformed by a new software revolution:

nun material chamado bioloxía.

the living software revolution.

Lograr isto permitiranos aproveitar as propiedades da bioloxía

And this will be powered by the ability to program biochemistry

parar xerar novos tipos de terapias,

on a material called biology.

para reparar tecido danado,

And doing so will enable us to harness the properties of biology

para reprogramar células defectuosas

ou incluso crear sistemas operativos programables a partir da bioquímica.

to generate new kinds of therapies,

to repair damaged tissue,

Se conseguimos logralo, e temos que conseguilo,

to reprogram faulty cells

or even build programmable operating systems out of biochemistry.

o seu impacto será tan grande

que a primeira revolución será insignificante en comparación.

If we can realize this -- and we do need to realize it --

Iso débese a que o soporte lóxico vivente transformaría por completo a medicina,

its impact will be so enormous

a agricultura e a enerxía,

that it will make the first software revolution pale in comparison.

sectores que eclipsan os dominados pola informática.

And that's because living software would transform the entirety of medicine,

Imaxinade plantas programadas para que fixen mellor o nitróxeno

agriculture and energy,

and these are sectors that dwarf those dominated by IT.

ou resistan novos patóxenos fúnxicos,

ou cultivos programados para ser perennes en lugar de anuais

Imagine programmable plants that fix nitrogen more effectively

e duplicar así as colleitas cada ano.

or resist emerging fungal pathogens,

Transformaría a agricultura

or even programming crops to be perennial rather than annual

e permitiría seguir alimentando un planeta cada vez máis habitado.

so you could double your crop yields each year.

Imaxinade tamén inmunidade programable,

That would transform agriculture

deseñar e controlar moléculas que axuden ao noso sistema inmunitario

and how we'll keep our growing and global population fed.

a detectar, erradicar ou previr enfermidades.

Or imagine programmable immunity,

Transformaría a medicina

designing and harnessing molecular devices that guide your immune system

e permitiría seguir coidando dunha poboación cada vez máis envellecida.

to detect, eradicate or even prevent disease.

Xa contamos con moitas das ferramentas que permitirían facer isto unha realidade.

This would transform medicine

and how we'll keep our growing and aging population healthy.

Podemos editar xenes con CRISPR.

Podemos reescribir o código xenético base a base.

We already have many of the tools that will make living software a reality.

Incluso podemos construír circuítos biolóxicos sintéticos con ADN.

We can precisely edit genes with CRISPR.

Pero descubrir como e cando usar estas ferramentas

We can rewrite the genetic code one base at a time.

aínda é ensaio e erro.

We can even build functioning synthetic circuits out of DNA.

Precisa de moita experiencia, anos de especialización

But figuring out how and when to wield these tools

e experimentos que son tan difíciles de descubrir como de reproducir.

is still a process of trial and error.

It needs deep expertise, years of specialization.

Na bioloxía, somos propensos a centrarnos nas partes,

And experimental protocols are difficult to discover

pero todo o mundo sabe que non se pode comprender algo que voa

and all too often, difficult to reproduce.

só estudando plumas.

And, you know, we have a tendency in biology to focus a lot on the parts,

Hoxe, programar a bioloxía non é tan sinxelo como o é un ordenador.

but we all know that something like flying wouldn't be understood

Para empeorar a situación,

by only studying feathers.

os sistemas vivos non se parecen case nada aos programas que desenvolvemos.

So programming biology is not yet as simple as programming your computer.

And then to make matters worse,

A diferenza dos programas de ordenador,

living systems largely bear no resemblance to the engineered systems

os sistemas vivos xéranse e organízanse independentemente,

funcionan a escala molecular e as súas interaccións

that you and I program every day.

In contrast to engineered systems, living systems self-generate,

adoitan conseguir un rendemento forte a gran escala.

they self-organize,

Ata poden repararse eles mesmos.

they operate at molecular scales.

And these molecular-level interactions

Pensade, por exemplo, na típica planta doméstica,

lead generally to robust macro-scale output.

como a que colocas enriba da cheminea

They can even self-repair.

e sempre te esqueces de regar.

Pese ao teu despiste, a planta ten que espertar todos os días

Consider, for example, the humble household plant,

e pensar en que vai gastar os recursos dos que dispón.

like that one sat on your mantelpiece at home

that you keep forgetting to water.

Crecerá, realizará a fotosíntese, producirá sementes ou florecerá?

Every day, despite your neglect, that plant has to wake up

Esa decisión correspóndelle ao organismo por completo.

and figure out how to allocate its resources.

Pero a planta non ten un cerebro para pensar en todo iso.

Will it grow, photosynthesize, produce seeds, or flower?

Ten que amañarse coas células das súas follas.

And that's a decision that has to be made at the level of the whole organism.

Estas teñen que interactuar co ambiente

But a plant doesn't have a brain to figure all of that out.

e tomar decisións que afectan a toda a planta.

Ten que haber un programa executándose nestas células,

It has to make do with the cells on its leaves.

They have to respond to the environment

un programa que responde aos diferentes sinais de entrada

and make the decisions that affect the whole plant.

e controla as accións da célula.

So somehow there must be a program running inside these cells,

Estes programas teñen que operar de maneira distribuída en cada célula

a program that responds to input signals and cues

para que poidan coordinarse e a planta creza e floreza.

and shapes what that cell will do.

And then those programs must operate in a distributed way

Se conseguísemos entender estes programas biolóxicos

across individual cells,

so that they can coordinate and that plant can grow and flourish.

e como opera a bioloxía,

transformaría a nosa capacidade para entender como e por que

If we could understand these biological programs,

actúan as células.

if we could understand biological computation,

Se entendésemos estes programas,

poderiamos depuralos cando algo vaia mal,

it would transform our ability to understand how and why

ou aprender deles como deseñar o tipo de circuítos sintéticos

cells do what they do.

Because, if we understood these programs,

que aproveitan de verdade o poder computacional da bioquímica.

we could debug them when things go wrong.

Or we could learn from them how to design the kind of synthetic circuits

A miña paixón por isto levoume por unha liña de investigación

that truly exploit the computational power of biochemistry.

relacionada coas matemáticas, a informática e a bioloxía,

na que centro o meu esforzo na bioloxía como computación,

My passion about this idea led me to a career in research

at the interface of maths, computer science and biology.

preguntándome que calculan as células

e como podemos descubrir estes programas biolóxicos.

And in my work, I focus on the concept of biology as computation.

Empecei a facerme estas preguntas con algúns dos meus compañeiros

And that means asking what do cells compute,

and how can we uncover these biological programs?

en Microsoft Research, na Universidade de Cambridge,

xa que queriamos comprender

And I started to ask these questions together with some brilliant collaborators

o programa biolóxico que se executa nun tipo de células en concreto:

at Microsoft Research and the University of Cambridge,

as células nai embrionarias.

where together we wanted to understand

Estas células son especiais porque son pluripotentes.

the biological program running inside a unique type of cell:

Poden converterse en calquera célula:

do cerebro, do corazón, dos ósos, dos pulmóns ou en calquera outra.

an embryonic stem cell.

These cells are unique because they're totally naïve.

Esta pluripotencia fainas únicas

They can become anything they want:

e foi a chispa que alimentou a imaxinación dos investigadores,

a brain cell, a heart cell, a bone cell, a lung cell,

pois déronse conta de que, se puidésemos aproveitala,

any adult cell type.

a medicina gañaría unha ferramenta poderosísima.

This naïvety, it sets them apart,

but it also ignited the imagination of the scientific community,

Se podemos descubrir como escollen estas células en cales converterse,

who realized, if we could tap into that potential,

poderiamos facer uso delas

we would have a powerful tool for medicine.

para xerar as células que necesitamos para reparar tecido morto ou danado.

If we could figure out how these cells make the decision

to become one cell type or another,

Lograr isto non será doado,

we might be able to harness them

to generate cells that we need to repair diseased or damaged tissue.

e menos con estas células en particular,

pois aparecen seis días despois da concepción

But realizing that vision is not without its challenges,

e nun par de días máis, desaparecen.

not least because these particular cells,

Xa decidiron o seu futuro

e convertéronse nas células que formarán os órganos do corpo.

they emerge just six days after conception.

And then within a day or so, they're gone.

Aínda así, estas decisións son menos firmes

They have set off down the different paths

that form all the structures and organs of your adult body.

do que se imaxinaba.

Hai 13 anos, uns científicos descubriron algo revolucionario.

But it turns out that cell fates are a lot more plastic

Inserindo uns poucos xenes nunha célula adulta,

than we might have imagined.

About 13 years ago, some scientists showed something truly revolutionary.

como as da pel,

pódese facer que esa célula volva ao estado de pluripotencia.

By inserting just a handful of genes into an adult cell,

Este proceso recibe o nome de “reprogramación”,

like one of your skin cells,

e permítenos imaxinar unha especie de utopía de células nai

you can transform that cell back to the naïve state.

na que podemos extraer células do propio paciente,

And it's a process that's actually known as "reprogramming,"

facelas pluripotentes outra vez

and it allows us to imagine a kind of stem cell utopia,

e empregalas para crear as células que o paciente precise,

the ability to take a sample of a patient's own cells,

xa sexan para o cerebro ou o corazón.

transform them back to the naïve state

Durante a última década,

intentar cambiar o destino das células nai

and use those cells to make whatever that patient might need,

aínda se rexe por ensaio e erro.

whether it's brain cells or heart cells.

Incluso nos casos nos que xa existen protocolos experimentais que funcionan,

But over the last decade or so,

figuring out how to change cell fate,

son ineficientes,

it's still a process of trial and error.

e descoñecemos como e por que funcionan.

Even in cases where we've uncovered successful experimental protocols,

Aínda que saibas converter unha célula nai nunha do corazón,

they're still inefficient,

and we lack a fundamental understanding of how and why they work.

non tes porque saber convertela nunha célula cerebral.

If you figured out how to change a stem cell into a heart cell,

O obxectivo é comprender o programa biolóxico

that hasn't got any way of telling you how to change a stem cell

que se executa nas células nai embrionarias,

e para entender os cálculos que realiza un organismo vivo

into a brain cell.

So we wanted to understand the biological program

empézase facendo unha pregunta moi simple:

running inside an embryonic stem cell,

Que é o que ten que facer ese organismo?

and understanding the computation performed by a living system

starts with asking a devastatingly simple question:

A informática conta cun conxunto de estratexias

para saber cales son as funcións do software e o hardware.

What is it that system actually has to do?

Ao desenvolver un programa ou implementar un código,

Now, computer science actually has a set of strategies

queres que se execute correctamente,

for dealing with what it is the software and hardware are meant to do.

que sexa rápido, teña moitas funcións

e estea libre de erros, pois corrixilos é caro.

When you write a program, you code a piece of software,

Cando un desenvolvedor crea un programa,

you want that software to run correctly.

pode especificar unha serie de requisitos.

You want performance, functionality.

Estes indican que fai o programa.

You want to prevent bugs.

Por exemplo, comparar dous números e ordenalos de menor a maior.

They can cost you a lot.

So when a developer writes a program,

they could write down a set of specifications.

Existen programas que nos permiten comprobar automaticamente

These are what your program should do.

Maybe it should compare the size of two numbers

se estes requisitos se cumpren e o programa fai o que ten que facer.

or order numbers by increasing size.

Technology exists that allows us automatically to check

Do mesmo xeito, a nosa idea é que os experimentos que se fan no laboratorio

whether our specifications are satisfied,

whether that program does what it should do.

teñen asociados certos requisitos que describen un programa biolóxico.

And so our idea was that in the same way,

experimental observations, things we measure in the lab,

Só temos que descubrir como codificar esta serie de requisitos.

they correspond to specifications of what the biological program should do.

Imaxinade que un laboratorio que traballa con xenes descubre

So we just needed to figure out a way

to encode this new type of specification.

que se un xene A se activa,

entón un xene B ou un xene C actívanse.

So let's say you've been busy in the lab and you've been measuring your genes

Podemos anotalo como unha expresión matemática

and you've found that if Gene A is active,

usando a linguaxe lóxica:

then Gene B or Gene C seems to be active.

Se A, entón B ou C.

We can write that observation down as a mathematical expression

Este é un caso moi sinxelo só para poñer un exemplo.

if we can use the language of logic:

Podemos codificar expresións complexas

If A, then B or C.

que conteñan o comportamento de xenes ou proteínas ao longo do tempo

Now, this is a very simple example, OK.

It's just to illustrate the point.

entre múltiples experimentos.

We can encode truly rich expressions

Ao traducir estas observacións a expresións matemáticas,

that actually capture the behavior of multiple genes or proteins over time

pódense realizar probas para saber se as ditas observacións poden xurdir

across multiple different experiments.

And so by translating our observations

dun programa de interaccións xenéticas.

into mathematical expression in this way,

it becomes possible to test whether or not those observations can emerge

Creamos un programa con isto en mente.

Podemos usar esta ferramenta para codificar observacións

from a program of genetic interactions.

como expresións matemáticas,

e a ferramenta permitiranos descubrir o programa xenético

And we developed a tool to do just this.

We were able to use this tool to encode observations

que as relaciona.

Aplicamos este método

as mathematical expressions,

and then that tool would allow us to uncover the genetic program

para descubrir o programa xenético que se executa nas células nai embrionarias

that could explain them all.

e intentar comprender o procedemento de recuperación da pluripotencia.

And we then apply this approach

to uncover the genetic program running inside embryonic stem cells

Esta ferramenta construíuse

a partir dun programa recoñecido de verificación de requisitos.

to see if we could understand how to induce that naïve state.

Comezamos cun conxunto duns 50 requisitos

And this tool was actually built

on a solver that's deployed routinely around the world

que obtivemos de experimentar con células nai embrionarias.

for conventional software verification.

So we started with a set of nearly 50 different specifications

Despois de codificalos na ferramenta,

puidemos descubrir o primeiro programa molecular

that we generated from experimental observations of embryonic stem cells.

que os relaciona a todos.

And by encoding these observations in this tool,

Un fito importante de seu.

we were able to uncover the first molecular program

Ser capaz de relacionar todas estas observacións

that could explain all of them.

non é algo que se poida facer da noite á mañá,

Now, that's kind of a feat in and of itself, right?

aínda que sexa unha noite moi longa.

Being able to reconcile all of these different observations

Sabendo todo isto, podemos ir máis alá.

is not the kind of thing you can do on the back of an envelope,

Con esta ferramenta, poderiamos predicir as accións dunha célula

even if you have a really big envelope.

en situacións descoñecidas, e simulalas nun ordenador.

Because we've got this kind of understanding,

we could go one step further.

We could use this program to predict what this cell might do

Fixémolo:

xeramos predicións a partir dos experimentos que realizamos

in conditions we hadn't yet tested.

e achamos que o programa das células nai é moi previsible.

We could probe the program in silico.

Ensinounos como devolver a pluripotencia ás células nai

And so we did just that:

we generated predictions that we tested in the lab,

dun xeito rápido e eficiente.

and we found that this program was highly predictive.

Indicounos os xenes nos que centrarse para logralo

It told us how we could accelerate progress

e aqueles que hai que evitar.

back to the naïve state quickly and efficiently.

A simulación incluso predixo a orde de activación dos xenes.

It told us which genes to target to do that,

which genes might even hinder that process.

Este método foi de grande axuda para descubrir máis

We even found the program predicted the order in which genes would switch on.

sobre como actúan estas células.

Este programa non é exclusivo para as células nai embrionarias.

So this approach really allowed us to uncover the dynamics

Permítenos coñecer máis sobre os cálculos que realizan as células

of what the cells are doing.

What we've developed, it's not a method that's specific to stem cell biology.

en relación coas interaccións xenéticas.

En esencia, unha compoñente máis.

Rather, it allows us to make sense of the computation

Precísanse atopar novos métodos

being carried out by the cell

in the context of genetic interactions.

para comprender mellor, e a diferentes niveis,

a computación biolóxica,

So really, it's just one building block.

desde o ADN e ata o paso de información entre células.

The field urgently needs to develop new approaches

to understand biological computation more broadly

Só cando poidamos entender isto

and at different levels,

seremos capaces de aproveitar a bioloxía con métodos previsibles e de confianza.

from DNA right through to the flow of information between cells.

Only this kind of transformative understanding

Para programar a bioloxía, hai que crear

will enable us to harness biology in ways that are predictable and reliable.

novas ferramentas e linguaxes

que permitirán tanto aos científicos coma aos enxeñeiros informáticos

But to program biology, we will also need to develop

deseñar as funcións biolóxicas

e traducilas á linguaxe máquina da célula,

the kinds of tools and languages

that allow both experimentalists and computational scientists

a súa bioquímica,

para logo poder construír esas estruturas.

to design biological function

Sería algo parecido a un compilador de software vivente,

and have those designs compile down to the machine code of the cell,

algo no que estou orgullosa de traballar como parte dun equipo en Microsoft.

its biochemistry,

so that we could then build those structures.

Dicir que é un gran desafío queda curto,

Now, that's something akin to a living software compiler,

pero se o logramos,

and I'm proud to be part of a team at Microsoft

sería o último paso para poder implementar software en organismos vivos.

that's working to develop one.

Though to say it's a grand challenge is kind of an understatement,

Programar a bioloxía só será posible

but if it's realized,

it would be the final bridge between software and wetware.

se a podemos converter nun campo interdisciplinario.

Debemos superar a barreira entre a física e as ciencias da vida

More broadly, though, programming biology is only going to be possible

e os profesionais de cada disciplina teñen que poder traballar xuntos

if we can transform the field into being truly interdisciplinary.

compartindo linguaxes e preguntas.

It needs us to bridge the physical and the life sciences,

and scientists from each of these disciplines

É importante recordar que moitas das grandes empresas tecnolóxicas,

need to be able to work together with common languages

and to have shared scientific questions.

ou das tecnoloxías que empregamos cada día

non se poderían imaxinar

cando se comezaba a programar en microchips de silicio.

In the long term, it's worth remembering that many of the giant software companies

Se empezamos a pensar agora nos posibles usos da bioloxía computacional,

and the technology that you and I work with every day

could hardly have been imagined

at the time we first started programming on silicon microchips.

veremos algúns dos pasos que teremos que tomar

And if we start now to think about the potential for technology

para facelo unha realidade.

É posible pensar que se podería facer un mal uso desta tecnoloxía.

enabled by computational biology,

we'll see some of the steps that we need to take along the way

Se estamos a pensar en programar células inmunitarias,

to make that a reality.

Now, there is the sobering thought that this kind of technology

tamén teriamos que ter en conta as bacterias programadas para evitalas.

could be open to misuse.

If we're willing to talk about the potential

Pode haber xente que queira facelo.

for programming immune cells,

we should also be thinking about the potential of bacteria

Menos para os científicos, un pensamento tranquilizador

engineered to evade them.

é que traballar coa bioloxía é moi delicado.

There might be people willing to do that.

Programar a bioloxía non será algo que se poida facer en calquera sitio.

Now, one reassuring thought in this

is that -- well, less so for the scientists --

is that biology is a fragile thing to work with.

Como aínda acabamos de empezar,

podemos avanzar con precaución.

So programming biology is not going to be something

Se nos facemos xa as preguntas difíciles,

you'll be doing in your garden shed.

podemos implementar as salvagardas necesarias

But because we're at the outset of this,

we can move forward with our eyes wide open.

ademais de pensar en temas éticos.

We can ask the difficult questions up front,

Hai que pensar onde poñer os límites á hora de alterar a bioloxía.

we can put in place the necessary safeguards

and, as part of that, we'll have to think about our ethics.

A bioética será o aspecto de maior importancia.

We'll have to think about putting bounds on the implementation

Non se pode deixar en segundo plano co gallo do avance científico.

of biological function.

So as part of this, research in bioethics will have to be a priority.

A recompensa de completar esta investigación

It can't be relegated to second place

será a de conseguir novas aplicacións e industrias innovadoras

in the excitement of scientific innovation.

en campos como a agricultura, a medicina, a enerxía, os materiais

But the ultimate prize, the ultimate destination on this journey,

e incluso na informática.

would be breakthrough applications and breakthrough industries

No futuro, poderiamos subministrar ao planeta

in areas from agriculture and medicine to energy and materials

coa enerxía renovable definitiva

and even computing itself.

se lográsemos imitar as plantas en algo que descubriron hai millóns de anos:

Imagine, one day we could be powering the planet sustainably

como aproveitar a enerxía do sol cunha eficiencia incomparable

on the ultimate green energy

á dos nosos paneis solares.

if we could mimic something that plants figured out millennia ago:

Se entendésemos o programa das interaccións cuánticas

how to harness the sun's energy with an efficiency that is unparalleled

que permiten ás plantas absorber luz solar tan eficientemente,

by our current solar cells.

poderiamos ser capaces de construír circuítos sintéticos de ADN

If we understood that program of quantum interactions

cos que crear mellores paneis solares.

that allow plants to absorb sunlight so efficiently,

Xa hai científicos traballando nos pilares desta tecnoloxía,

we might be able to translate that into building synthetic DNA circuits

conque se se conseguisen a atención e os fondos necesarios,

that offer the material for better solar cells.

podería ser unha realidade en 10 ou 15 anos.

There are teams and scientists working on the fundamentals of this right now,

Estamos ante o comezo dunha revolución tecnolóxica.

so perhaps if it got the right attention and the right investment,

Comprender este tipo de computación biolóxica

it could be realized in 10 or 15 years.

é un paso crítico.

So we are at the beginning of a technological revolution.

E se podemos logralo,

entrariamos na era dos sistemas operativos

Understanding this ancient type of biological computation

que executan programas vivos.

is the critical first step.

Moitas grazas.

(Aplausos)

And if we can realize this,

we would enter in the era of an operating system

that runs living software.

Thank you very much.

(Applause)