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


The second half of the last century
was completely defined by a technological revolution: the software revolution. The ability to program electrons
on a material called silicon made possible technologies,
companies and industries that were at one point
unimaginable to many of us, but which have now fundamentally changed
the way the world works. The first half of this century, though, is going to be transformed
by a new software revolution: the living software revolution. And this will be powered by the ability
to program biochemistry on a material called biology. And doing so will enable us to harness
the properties of biology to generate new kinds of therapies, to repair damaged tissue, to reprogram faulty cells or even build programmable
operating systems out of biochemistry. If we can realize this —
and we do need to realize it — its impact will be so enormous that it will make the first
software revolution pale in comparison. And that’s because living software
would transform the entirety of medicine, agriculture and energy, and these are sectors that dwarf
those dominated by IT. Imagine programmable plants
that fix nitrogen more effectively or resist emerging fungal pathogens, or even programming crops
to be perennial rather than annual so you could double
your crop yields each year. That would transform agriculture and how we’ll keep our growing
and global population fed. Or imagine programmable immunity, designing and harnessing molecular devices
that guide your immune system to detect, eradicate
or even prevent disease. This would transform medicine and how we’ll keep our growing
and aging population healthy. We already have many of the tools
that will make living software a reality. We can precisely edit genes with CRISPR. We can rewrite the genetic code
one base at a time. We can even build functioning
synthetic circuits out of DNA. But figuring out how and when
to wield these tools is still a process of trial and error. It needs deep expertise,
years of specialization. And experimental protocols
are difficult to discover and all too often, difficult to reproduce. And, you know, we have a tendency
in biology to focus a lot on the parts, but we all know that something like flying
wouldn’t be understood by only studying feathers. So programming biology is not yet
as simple as programming your computer. And then to make matters worse, living systems largely bear no resemblance
to the engineered systems that you and I program every day. In contrast to engineered systems,
living systems self-generate, they self-organize, they operate at molecular scales. And these molecular-level interactions lead generally to robust
macro-scale output. They can even self-repair. Consider, for example,
the humble household plant, like that one sat
on your mantelpiece at home that you keep forgetting to water. Every day, despite your neglect,
that plant has to wake up and figure out how
to allocate its resources. Will it grow, photosynthesize,
produce seeds, or flower? And that’s a decision that has to be made
at the level of the whole organism. But a plant doesn’t have a brain
to figure all of that out. It has to make do
with the cells on its leaves. They have to respond to the environment and make the decisions
that affect the whole plant. So somehow there must be a program
running inside these cells, a program that responds
to input signals and cues and shapes what that cell will do. And then those programs must operate
in a distributed way across individual cells, so that they can coordinate
and that plant can grow and flourish. If we could understand
these biological programs, if we could understand
biological computation, it would transform our ability
to understand how and why cells do what they do. Because, if we understood these programs, we could debug them when things go wrong. Or we could learn from them how to design
the kind of synthetic circuits that truly exploit
the computational power of biochemistry. My passion about this idea
led me to a career in research at the interface of maths,
computer science and biology. And in my work, I focus on the concept
of biology as computation. And that means asking
what do cells compute, and how can we uncover
these biological programs? And I started to ask these questions
together with some brilliant collaborators at Microsoft Research
and the University of Cambridge, where together we wanted to understand the biological program
running inside a unique type of cell: an embryonic stem cell. These cells are unique
because they’re totally naïve. They can become anything they want: a brain cell, a heart cell,
a bone cell, a lung cell, any adult cell type. This naïvety, it sets them apart, but it also ignited the imagination
of the scientific community, who realized, if we could
tap into that potential, we would have a powerful
tool for medicine. If we could figure out
how these cells make the decision to become one cell type or another, we might be able to harness them to generate cells that we need
to repair diseased or damaged tissue. But realizing that vision
is not without its challenges, not least because these particular cells, they emerge just six days
after conception. And then within a day or so, they’re gone. They have set off down the different paths that form all the structures
and organs of your adult body. But it turns out that cell fates
are a lot more plastic than we might have imagined. About 13 years ago, some scientists
showed something truly revolutionary. By inserting just a handful of genes
into an adult cell, like one of your skin cells, you can transform that cell
back to the naïve state. And it’s a process that’s actually
known as “reprogramming,” and it allows us to imagine
a kind of stem cell utopia, the ability to take a sample
of a patient’s own cells, transform them back to the naïve state and use those cells to make
whatever that patient might need, whether it’s brain cells or heart cells. But over the last decade or so, figuring out how to change cell fate, it’s still a process of trial and error. Even in cases where we’ve uncovered
successful experimental protocols, they’re still inefficient, and we lack a fundamental understanding
of how and why they work. If you figured out how to change
a stem cell into a heart cell, that hasn’t got any way of telling you
how to change a stem cell into a brain cell. So we wanted to understand
the biological program running inside an embryonic stem cell, and understanding the computation
performed by a living system starts with asking
a devastatingly simple question: What is it that system actually has to do? Now, computer science actually
has a set of strategies for dealing with what it is the software
and hardware are meant to do. When you write a program,
you code a piece of software, you want that software to run correctly. You want performance, functionality. You want to prevent bugs. They can cost you a lot. So when a developer writes a program, they could write down
a set of specifications. These are what your program should do. Maybe it should compare
the size of two numbers or order numbers by increasing size. Technology exists that allows us
automatically to check whether our specifications are satisfied, whether that program
does what it should do. And so our idea was that in the same way, experimental observations,
things we measure in the lab, they correspond to specifications
of what the biological program should do. So we just needed to figure out a way to encode this new type of specification. So let’s say you’ve been busy in the lab
and you’ve been measuring your genes and you’ve found that if Gene A is active, then Gene B or Gene C seems to be active. We can write that observation down
as a mathematical expression if we can use the language of logic: If A, then B or C. Now, this is a very simple example, OK. It’s just to illustrate the point. We can encode truly rich expressions that actually capture the behavior
of multiple genes or proteins over time across multiple different experiments. And so by translating our observations into mathematical expression in this way, it becomes possible to test whether
or not those observations can emerge from a program of genetic interactions. And we developed a tool to do just this. We were able to use this tool
to encode observations as mathematical expressions, and then that tool would allow us
to uncover the genetic program that could explain them all. And we then apply this approach to uncover the genetic program
running inside embryonic stem cells to see if we could understand
how to induce that naïve state. And this tool was actually built on a solver that’s deployed
routinely around the world for conventional software verification. So we started with a set
of nearly 50 different specifications that we generated from experimental
observations of embryonic stem cells. And by encoding these
observations in this tool, we were able to uncover
the first molecular program that could explain all of them. Now, that’s kind of a feat
in and of itself, right? Being able to reconcile
all of these different observations is not the kind of thing
you can do on the back of an envelope, even if you have a really big envelope. 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 in conditions we hadn’t yet tested. We could probe the program in silico. And so we did just that: we generated predictions
that we tested in the lab, and we found that this program
was highly predictive. It told us how we could
accelerate progress back to the naïve state
quickly and efficiently. It told us which genes
to target to do that, which genes might even
hinder that process. We even found the program predicted
the order in which genes would switch on. So this approach really allowed us
to uncover the dynamics of what the cells are doing. What we’ve developed, it’s not a method
that’s specific to stem cell biology. Rather, it allows us to make sense
of the computation being carried out by the cell in the context of genetic interactions. So really, it’s just one building block. The field urgently needs
to develop new approaches to understand biological
computation more broadly and at different levels, from DNA right through
to the flow of information between cells. Only this kind of
transformative understanding will enable us to harness biology
in ways that are predictable and reliable. But to program biology,
we will also need to develop the kinds of tools and languages that allow both experimentalists
and computational scientists to design biological function and have those designs compile down
to the machine code of the cell, its biochemistry, so that we could then
build those structures. Now, that’s something akin
to a living software compiler, and I’m proud to be
part of a team at Microsoft that’s working to develop one. Though to say it’s a grand challenge
is kind of an understatement, but if it’s realized, it would be the final bridge
between software and wetware. More broadly, though, programming biology
is only going to be possible if we can transform the field
into being truly interdisciplinary. It needs us to bridge
the physical and the life sciences, and scientists from
each of these disciplines need to be able to work together
with common languages and to have shared scientific questions. In the long term, it’s worth remembering
that many of the giant software companies 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. And if we start now to think about
the potential for technology enabled by computational biology, we’ll see some of the steps
that we need to take along the way to make that a reality. Now, there is the sobering thought
that this kind of technology could be open to misuse. If we’re willing to talk
about the potential for programming immune cells, we should also be thinking
about the potential of bacteria engineered to evade them. There might be people willing to do that. Now, one reassuring thought in this is that — well, less so
for the scientists — is that biology is
a fragile thing to work with. So programming biology
is not going to be something you’ll be doing in your garden shed. But because we’re at the outset of this, we can move forward
with our eyes wide open. We can ask the difficult
questions up front, we can put in place
the necessary safeguards and, as part of that,
we’ll have to think about our ethics. We’ll have to think about putting bounds
on the implementation of biological function. So as part of this, research in bioethics
will have to be a priority. It can’t be relegated to second place in the excitement
of scientific innovation. But the ultimate prize,
the ultimate destination on this journey, would be breakthrough applications
and breakthrough industries in areas from agriculture and medicine
to energy and materials and even computing itself. Imagine, one day we could be powering
the planet sustainably on the ultimate green energy if we could mimic something
that plants figured out millennia ago: how to harness the sun’s energy
with an efficiency that is unparalleled by our current solar cells. If we understood that program
of quantum interactions that allow plants to absorb
sunlight so efficiently, we might be able to translate that
into building synthetic DNA circuits that offer the material
for better solar cells. There are teams and scientists working
on the fundamentals of this right now, so perhaps if it got the right attention
and the right investment, it could be realized in 10 or 15 years. So we are at the beginning
of a technological revolution. Understanding this ancient type
of biological computation is the critical first step. 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)

100 thoughts on “The next software revolution: programming biological cells | Sara-Jane Dunn

  1. Some take-aways : 1 Math is the language to uncover and understand patterns; 2. Everything can ultimately be reduced to physics; 3 System dynamics is far more useful than its typical application in engineering.

  2. I was thinking: maybe a group will split off from society and say "We will live in our own communities without adopting this new technology." And this made me think of the Amish.

  3. Great talk, but why the incorrect information about biomass solar efficiency? Plants collect sunlight at 2 – 6% efficiency. The current record for human-made solar cells is 46%. Lot's of great applications but learning from high-efficiency plant photosynthesis is not among them… =

  4. Between the computational power of Quantum Computing, the threat of AI, and now Biological Programing it's very clear that the world is about to be more divided that ever. Get wealthy! Lol.

  5. Microsoft please focus on creating public education and genetic protective systems. I removed my other comments. I still think this video should be removed. I presented very negatively towards the risks of this exposure. I do believe wholeheartedly this tech is necessary for an incredibly awesome future, though until then, things are going to get incredibly volatile.

  6. Fascinating and a bit scary too but as with any frontier of knowledge it’s well worth pursuing – we must be very aware of the risks tho’.

  7. Seems like a technology with more negative outcomes than positive ones ( new bio weapons , engineered babies with unknown outcomes) .

  8. ~~~ sturdy knowledge of Osiris is beyond human sight but able to be felt and trained by the third eye questionnaire of parabola timeline for UR DREAM LIFE in workouts and job apply creative force is frozen in your sin simulation tumbler angel investors are molecular mechanisms THE COURSEWORK OR COURSE IS ALL AROUND U REAP EXACTLY HOW AND WHAT N WHY ~~~

  9. Insight : Biology is like kids, you have to dominate it carefully with care, nurture it, guide it without being harsh. Plus, you and your intentions have to be very pure, like parents approach towards kids. Then only Biology will work in your favour, otherwise adversely. Domination should be enchanting, not brutal. Also, Biology works as a team, this should be considered too. One literally has to use emotions to program Biology.
    Edit: scope of Biology could be beyond cell level to global level, like a global consciousness or emergence. This is because of millions of years of evolution and connections at quantum level. This needs to be considered too. As of now it behaves like grumpy kid locally.

  10. This is how women in science get recognition. By being amazing at their job and presentation. Not through SJW bullshit.

  11. If you have a belly, you shouldn't put yellow trousers over it. Common sense is not that common?…I'm scared of her programming anything.

  12. Give me photosynthesis gene my cell can activate it and my cell can assimilate any gene as my own specially plant genes. I don't want the poisonous one.

  13. She's naming all these positive things when in all reality it's all lies because they will never use this for the good of the people. They want population control and this would literally put it right in their hands. The crap they spray in the air is already changing our DNA wait till 5G rolls out completely that's going to mutate our DNA not to mention all the other harmful crap it does. Don't get me started on their vaccines. God programmed me just fine and my DNA is what it's meant to be

  14. I am a software engineer by profession such project will lead to the degradation of human and make us vulnerable to man 👨

  15. I like to think of the genome, or dna, as a long ribbon, with codes along the ribbon being utilized from birth (start of genome, start of code) to death (end of genome, end of code)…. 2,500,000,000 genes is approximately 1 gene being executed each second.

  16. A beautiful aspiration that will unfortunately be disfigured by profits and greed and technological suppression………..prove me wrong?

  17. Its amazing that every cell in you is replaced and only your conscious stays the same.
    This could be that through water somehow it transfers the information or might actually be on the quantum level.

  18. You know I am waiting for biological evolution from 2010. It has been 9 years now but no groundbreaking evolution in biology 😣😥😢.

  19. Dare I say, what a beautiful (extraordinary) explanation, and presentation.
    It's been long since having the pleasure of experiencing such intellect, and expert articulation. And that, in parallel. Inspiring. Thank you for sharing Sarah-Jane.

  20. This woman sounds like she has read "This mortal coil" from Emily Suvada a tad too often and took it too seriously.

    …I like where these things are going!😈

  21. They mean the "exposure" of the new revolution. The normalization and marketing of affronts to Creation in the never ending attempt to avoid genetic annihilation! When they stop lying to themselves and their children, they will stop taking guns to school. Until then, #cognitivedissonance in segregation! #mgunzulies TRANSLATION= How can I manufacture melanin? ANSWER= You cant!

  22. one thing human race is most known for is "</Misuse./ …
    Programmable kids, thoughts and sexual mate….Capitalism live long

  23. There is no limitations
    What can be done, will be done. who will represent the outcome of whats right or wrong. The present day mentality, which is based on the past. War heads stand locked and loaded. To determine whats right, and whats wrong. The growth in your belly, cut out, or naturally birthed. Bagged and Dispose of . We see reality through the screen of programs ,opinions and propaganda, the narrative your values and insights define what is. To defy truth for reason. The old saying, you can be anything you want to be. Well,perhaps we can.

  24. It is decades now that we are told about the coming age of genetic engineering but the expectations have never been met. What should make us believe that this time things will turn out to be otherwise? I bet that in 10, 20, 30 years we will again see other TED talks that will promise us a bright future that has still to come. It looks to me more and more a genetic-self-delusion. At any rate… good luck.

  25. I found her discussion illuminating and intelligible to the lay person. However, despite this, I am disturbed by her casual optimism with regard to "bio-ethics" . Is she completely blind to current events? Did she fail to recognize climate change? Is she oblivious to the immense divide that exists economically between nations and within nations? Is she ignoring the political and social divides that are destabilizing the world? Who is going to benefit from this technology? The pitchforks are at the doors of the governments and corporations of this planet! Good luck, lady!!

  26. Fascinating, but the implications go so far beyond a YouTube comment, and fact that is so very obvious, that I am tempted to believe there is no point even in commenting….
    Oh, sorry. I just wasted 10 seconds of your life.

  27. I don't want big tech or big pharma near any of this stuff. This is what will be the end of life as we know it….handing over the programming of biology to people who only care about making money. Not me. I'll be out fishing, hiking, swimming, and enjoying life as a human being and not Frankensteins and their creators.

  28. Just a simple story about regenerative medicine or bioengineering.
    I expected something about a fusion of IT and biology from title…

  29. 6:00,,couple of videos ago, They were talking about interfacing AI with the neurotransmitters of the human brain,,,talk about regulating

  30. Sara said something which I have been suspecting for awhile now: DNA is holographic, running under quantum principals. If so, that would explain the incredible entanglement of the helix it's self. Which hints to the reason why our brain is so crevassed, and as one becomes more intelligent, more so it becomes.
    Being said, that would give rise to truly living, functional, "Created" beings as such as we are, but being silicon instead of a carbon based entity. . ?
    Knock-knock. . . "Good to see you friend!. . Come in, come in!.. Welcome to dinner! Would you like a bowl of sand with a glass of some hot, freshly squeezed D.I. water? Maybe an arsenic biscuit too??"

  31. A multidisciplinary group at UC Berkeley and an institute in China have been researching biological computation since the 1970's. Read "The Body Electric" by Dr. Robert Becker to understand the interface with the living creature.

  32. So……Let us declare aging a disease. The issues you are talking about after the fact are secondary and related to different "causes" or silos. As David Sinclair calls this "whack a mole" health, the underlying cause of all these diseases ignored. You are dealing with this but in an exclusive domain of funding. As a before the disease treatment of the yet to emerge malady an anti-aging approach would come into the domain of public health and save the funding of band-aid solution treating symptoms. This would avert the hegemony of Microsoft and make research in this direction public funding.

  33. The only problem of human science is that there are allowed to work only morons and freaks of nature and for normal guys this is restricted area

  34. My friends .. there is still a prophecy to be fulfilled in the Bible that describes the following …

    "And that day they sought death, but they did not find it, death fled from them …" any coincidence ??

    They will probably achieve this supposed defeat of death, but they will bring great harm to their lives.

  35. This a revolutionary, highly challenging idea that may help

    The difference is that any living cells exist by creation, hence its perfect. perfectly understanding the working of it might not be possible. Secondly there should be zero error in its implementation since it's dealing with life of a beaing.

    Software engineers generally are unable even to get a zero bug computer program. Then how is this going to be logical

    But I think it may help to fix certen level of biological issues , if succeeded

  36. I'm curious as to how CRISPR would be part of what she's trying to do, once after the labour of forming mathematical models of cellular mechanisms has been done.

  37. you only need to remove pain. Mental and physical. I just ended suffering for most humans if this ever becomes plausable.

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