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and it's my very very special pleasure
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to introduce our today speaker the
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speaker of the anniversary event here
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Alfonso Martinez Arias Alfonso is is an
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old friend and colleague
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a long-term friend and colleague sorry
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a well-established friend and calling no
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and he's been here 10 years ago
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and he has opened the entire Series so
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I'm super happy that he could be
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convinced to come here again
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and tell us his story 10 years later of
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what you need to know about Alfonso is I
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think he
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he was a superstar in genetics in flies
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but he had a question that went beyond
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that
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and then completely abandoned I don't
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know whether completely but in in terms
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of Publications almost completely
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abandoned flies and moved to an entirely
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new thing and he simply was interested
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and and thrilled by the question
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what does it take for a single cell I
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don't want to give you a talk what it
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does it take for a single cell to
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develop rather than divide
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and that's something that wasn't easily
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addressable in flies but was addressable
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in vertebrate systems and I'm pretty
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sure we will hear more about the power
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of cells
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and I think for me he's he's really a
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role model you should follow your ideas
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and it should not just stick to
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something where you've been successful
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at
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I think that is something for your life
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do you think you need to know what you
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have to do in your next step next 10
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years 20 30 50 no way
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you will find out every day in you
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and that's the way
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you will hopefully enjoy your life and
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you will be successful and make
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important discoveries at least for
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yourself maybe for the world as we will
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see here with Alfonso Alfonso thanks a
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lot for being here again and we're
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looking forward to your presentation
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thank you
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[Applause]
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Deutsche
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foreign
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foreign
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in this Herald's Ford and then weld in
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the v11 representation
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shaft this is
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burden
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foreign
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East
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in English
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expressions
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[Applause]
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[Music]
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[Applause]
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so I'll try to speak slowly which as
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your friend knows is very difficult for
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me
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so um I don't know whether you've ever
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wondered how we are made how many of you
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have ever wondered where do we come from
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how we are made
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foreign
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you don't have to raise a hand if you've
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never asked that question
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and how many of you think just out of
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curiosity because we live in a certain
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time that we are made by our genes that
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everything that we are is in our genes
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how many of you believe that
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fascinating so what else is there to do
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what else is there to do other than
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genes so this question have been asked
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by many people over the years and you
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can see that here where there have been
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many answers over over the years about
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this some people think religiously this
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is a beautiful sculpture by by August
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Rodan which is representing the creation
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out of the hand of God there goes Edam
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and Eve Leonardo tried to Leonardo da
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Vinci try to find this out I don't know
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why this is not working but oh no
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sorry about this but Leonardo da Vinci
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tried to try to
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um represent them and try to figure out
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what was inside the room but people
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today is very normal for all of you to
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to to know that we come from inside the
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womb of our of our mother in in some
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mysterious way and that mysterious way
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was represented Us in this um in those
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things on the on the on the left ideas
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more clear ideas about how we were made
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how we were functioned appeared in the
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17th century because of this treaty that
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was published in France in the in the
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1800s called The Man machine the man
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machine was an idea because at that time
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the physicists had discovered the loss
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of nature people were starting to
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construct devices based on mechanics so
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they started to see that perhaps human
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beings organisms acted like machines and
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and this is one inside there were a lot
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of machines and they LED people to start
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some clever people to start making up
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copies of ourselves as if we are
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machines and one of the most remarkable
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ones if you ever go to Switzerland is
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this Trio of people by a very famous
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Swiss watchmaker corpia Jacques dross
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who built these three which are still in
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neutral exactly as you see them there
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there is a scribe that is a draftman and
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there is a harpsichordist the the
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draftsman it's an amazing piece of work
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because as as you as you can see here it
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moves the eyes it writes it can write up
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to 10 different texts it will erase the
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text when it's wrong and and it's
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probably the first programmable you can
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see there in the back of thing I mean
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trees are very good at making these
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precisions instruments and this was a
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very very remarkable object and that's
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the way people people made this
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similarity they thought that we were
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made of of some natural copy of of metal
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and wires and plates this really got to
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to a very interesting this this notion
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of the man as a machine got to a
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fantastic view by this man who many of
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you don't know called Fritz can he
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worked in Berlin and over a number of
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years he published his work The Mensch
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else industrial palast I mean it's a
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very fascinating set of drawings which
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he put out in in the form of booklets
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over a number of years and and
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represented the the human being as he
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says as an industrial Palace I I learned
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that somebody had made a movie putting
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putting right I mean putting into into
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motion what Fritz can this and you can
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see it here and I hope that it will work
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foreign
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we are breathing that that's the lungs
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now we focus on the heart the Palm that
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is pumping
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I think this is my favorite beat what
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happens if you are an industrial Palace
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when you eat there is a bar of chocolate
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there it goes
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and your throat
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I like this bit it goes into the the
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stomach and you can see they're throwing
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all the acids everything to dissolve the
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food there is a man with a liver waiting
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for everything to accumulate
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and then when everything is ready he
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will pull the lever and there it goes
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into the intestine
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and there the goodies are separated from
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the crap
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you see there the goodies are floating
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about and they're going to be insane
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somewhere else
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and the rest is going to the waist
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and then we can get back that's where
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the liver the pancreas is taking all the
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goodies and translating them into into
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something interesting remarkable it's
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fun
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there is a wee-wee going out
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after you've separated the wings
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and you know the goodies go one way
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remarkable
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so in many ways this idea of the man as
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a machine
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is the is the the the progenitor the
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precursor of all these Prosthetics that
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we know about and and really a lot of
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things some of those are wishful
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thinking but but some are real and you
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know that many valves of the heart and
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many other pieces of our body are made
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mechanically out of this notion that
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human beings there is something mechanic
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about about the way we work however if
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we look if you look at your skin I mean
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today we know that this is not the way
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we're our components is not whether a
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metal our components are are other
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elements that that we can watch if we
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get deep into our body in the 60s there
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was this movie that called The Fantastic
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Voyage which they made it it's an
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American movie which they take people
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and make them really really small and
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they make this little vehicle and then
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they inject them into the blood of the
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organism and they start navigating over
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over the in this machine and what they
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see it's it's it sells I mean there goes
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the people it's it's a very classic
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movie that has been made and people
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navigate through the blood system and
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they get into dangers in the different
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organs and and so what they see is cells
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because indeed
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if we look beyond the
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the surface if we get a bit deeper that
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that's there you have a situation of the
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uh that's the yeah there is a delay
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that's my problem with the with the I
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can see now so there you have the layers
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of the skin that's but I mean we go even
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deeper and nicer we can see this Majesty
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of the cells because that's what we are
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made of and as I will show you in a
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minute it is the cells that make us in a
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very interesting manner you can see here
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one of Johan's favorite organs which is
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the variety of eyes I mean the
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creativity of the Celsius and armors
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because if we look beyond that initial
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surface we will see cells everywhere
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look at the variety of cells
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and I'd like you to think I mean if you
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hear about it you are hearing me because
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again these cells arrange in this
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fantastic and these beautiful Palisades
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which are essential for your hearing and
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and to distinguish all the sounds so
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wherever you look it sells because cells
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have a variety of shape a variety of
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form a variety of creativity that if you
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think about DNA and you've seen some of
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the pictures these mornings that some of
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you have put DNA is very boring it's
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just the same thing it doesn't have this
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this kind of creativity or ability and
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it surprises me and this is a theme that
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I'd like to share with you why we have
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fallen into the Trap that we are are
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represented in our genes in some form
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when actually we are represented in our
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cell
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in your body
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you have 440
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000 trillion cells 40 000 trillion cells
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that's what your body is and what is
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remarkable is that those cells are
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changing all the time
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so for example those numbers that are
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giving you there are absolutely true you
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are making two million red blood cells
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per second each of you is making your
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bone marrow is making two million think
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about it every second
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I mean every time I see this number I
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achieve it it's absolutely remarkable
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and what is interesting is that Johan
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knows that and I is forever but not the
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rest of your body in fact everything in
278
00:14:11,940 --> 00:14:16,079
your body except your heart maybe and
279
00:14:13,860 --> 00:14:17,879
certainly your eyes is turning over all
280
00:14:16,078 --> 00:14:20,278
the time
281
00:14:17,879 --> 00:14:22,799
you know sometimes you know the your
282
00:14:20,278 --> 00:14:24,539
skin you get a new skin every every
283
00:14:22,799 --> 00:14:26,219
month so to speak you get a new
284
00:14:24,539 --> 00:14:28,019
intestine every two or three every part
285
00:14:26,220 --> 00:14:29,759
of your body is turning over
286
00:14:28,019 --> 00:14:31,379
in fact you are not going to be the same
287
00:14:29,759 --> 00:14:32,939
in 10 years time
288
00:14:31,379 --> 00:14:35,399
one of the things that excites me is
289
00:14:32,940 --> 00:14:37,980
that your skeleton will change every 10
290
00:14:35,399 --> 00:14:39,179
years it will be completely renewed well
291
00:14:37,980 --> 00:14:40,920
that's because you know when my clothes
292
00:14:39,179 --> 00:14:43,919
don't feed me it's because my skeleton
293
00:14:40,919 --> 00:14:45,899
changes nothing else changes in my body
294
00:14:43,919 --> 00:14:47,578
so I think I think that you have to you
295
00:14:45,899 --> 00:14:50,639
have to appreciate that that you are
296
00:14:47,578 --> 00:14:52,859
changing you are a work in progress of
297
00:14:50,639 --> 00:14:55,860
yourselves that throughout your body who
298
00:14:52,860 --> 00:14:58,320
you are in terms physically changes and
299
00:14:55,860 --> 00:15:01,139
I find that very remarkable a lot of
300
00:14:58,320 --> 00:15:03,420
that work is due to the fact that in
301
00:15:01,139 --> 00:15:05,399
every organ of your body there is a very
302
00:15:03,419 --> 00:15:07,979
special population of cells which are
303
00:15:05,399 --> 00:15:10,860
called stem cells whose job is to do
304
00:15:07,980 --> 00:15:13,139
this renewal I mean we think because we
305
00:15:10,860 --> 00:15:14,579
see ourselves we tend to think that we
306
00:15:13,139 --> 00:15:16,259
are something static that we are
307
00:15:14,578 --> 00:15:18,239
something but actually there is a lot
308
00:15:16,259 --> 00:15:20,939
going on we're just fleeting structures
309
00:15:18,240 --> 00:15:21,839
fitting creations of ourselves this is
310
00:15:20,940 --> 00:15:24,779
why
311
00:15:21,839 --> 00:15:26,880
I find very remarkable that that today
312
00:15:24,778 --> 00:15:29,039
everybody is saying that you're gonna
313
00:15:26,879 --> 00:15:31,379
find who you are when you're gonna leave
314
00:15:29,039 --> 00:15:33,899
when you're gonna die what all in the
315
00:15:31,379 --> 00:15:36,059
DNA I could spend and maybe we can talk
316
00:15:33,899 --> 00:15:38,820
later many examples in which that is not
317
00:15:36,059 --> 00:15:41,039
the case you cannot pin down much of
318
00:15:38,820 --> 00:15:43,500
what we are into and the problem is and
319
00:15:41,039 --> 00:15:45,360
that's for you to to solve in the next
320
00:15:43,500 --> 00:15:47,698
few years that is the cell because it is
321
00:15:45,360 --> 00:15:49,980
all there is in the DNA all that it's in
322
00:15:47,698 --> 00:15:52,198
the DNA is instruction to to make Nano
323
00:15:49,980 --> 00:15:55,259
machines proteins and the protein
324
00:15:52,198 --> 00:15:57,778
complexes are Nano machines
325
00:15:55,259 --> 00:16:00,958
and those are in an aggregate in this
326
00:15:57,778 --> 00:16:03,360
sort of milieu of lipids and sugars and
327
00:16:00,958 --> 00:16:05,039
they create cells and in the cells
328
00:16:03,360 --> 00:16:07,440
everything once you get a cell the cell
329
00:16:05,039 --> 00:16:09,000
controls everything so it's not that the
330
00:16:07,440 --> 00:16:11,220
genes make the cells once you create a
331
00:16:09,000 --> 00:16:13,259
cell a cell controls everything think of
332
00:16:11,220 --> 00:16:15,300
your nervous system it's not your genes
333
00:16:13,259 --> 00:16:17,159
that is letting you listen that is
334
00:16:15,299 --> 00:16:19,078
letting you think it is the interactions
335
00:16:17,159 --> 00:16:20,698
between those cells the genes are just
336
00:16:19,078 --> 00:16:24,059
providing the tools
337
00:16:20,698 --> 00:16:26,219
and indeed inside the cells
338
00:16:24,059 --> 00:16:29,838
there is a lot of Nano machines and you
339
00:16:26,220 --> 00:16:29,839
can see that in the next movie
340
00:16:31,259 --> 00:16:36,059
besides I mean there are machines this
341
00:16:33,958 --> 00:16:38,099
is this is a representation
342
00:16:36,059 --> 00:16:40,018
but that's um
343
00:16:38,100 --> 00:16:41,579
as Johan knows a few years ago I was
344
00:16:40,019 --> 00:16:43,440
very interested and I'm still in noise
345
00:16:41,578 --> 00:16:45,899
how can we listen to the noise of the
346
00:16:43,440 --> 00:16:48,420
cells there you have
347
00:16:45,899 --> 00:16:51,480
very remarkable and really all these we
348
00:16:48,419 --> 00:16:54,899
have gleaned over the last 50 years and
349
00:16:51,480 --> 00:16:56,940
everybody and many colleagues have
350
00:16:54,899 --> 00:16:58,679
contributed we think this is not a bad
351
00:16:56,940 --> 00:17:00,480
representation of what is going on in
352
00:16:58,679 --> 00:17:02,159
the cell so not only your cells are
353
00:17:00,480 --> 00:17:04,019
changing all the time but your cells are
354
00:17:02,159 --> 00:17:05,818
a constant
355
00:17:04,019 --> 00:17:07,558
sea of activity
356
00:17:05,818 --> 00:17:09,779
and you know we are going now out of the
357
00:17:07,558 --> 00:17:11,399
nucleus you will see some of our
358
00:17:09,779 --> 00:17:13,558
favorite molecules and some of you have
359
00:17:11,400 --> 00:17:15,298
seen them today there is the nucleus
360
00:17:13,558 --> 00:17:17,099
that you can see mitochondria floating
361
00:17:15,298 --> 00:17:18,379
there you see the Golgi apparatus and
362
00:17:17,099 --> 00:17:20,938
many of you this morning in the
363
00:17:18,380 --> 00:17:23,819
cytoskeleton is a remarkable thing which
364
00:17:20,939 --> 00:17:26,160
shows this Fleet in nature of everything
365
00:17:23,818 --> 00:17:28,438
in us because here you have there are
366
00:17:26,160 --> 00:17:30,720
cables that are scaffolding this is what
367
00:17:28,439 --> 00:17:31,679
is the tubulin we we saw and you know
368
00:17:30,720 --> 00:17:33,480
there are those things they actually
369
00:17:31,679 --> 00:17:35,220
move like that they actually move like
370
00:17:33,480 --> 00:17:37,558
that okay this has been shown and this
371
00:17:35,220 --> 00:17:41,600
has been seen they have legs some of
372
00:17:37,558 --> 00:17:41,599
them they carry they carry cargos
373
00:17:44,279 --> 00:17:48,178
remarkable
374
00:17:46,019 --> 00:17:49,980
and all this has has been today you can
375
00:17:48,179 --> 00:17:52,019
see these things at the single molecule
376
00:17:49,980 --> 00:17:54,779
level is like that has been the great
377
00:17:52,019 --> 00:17:56,460
revolution in biology the ability to to
378
00:17:54,779 --> 00:17:58,379
see these things
379
00:17:56,460 --> 00:17:59,819
and you know these micro cubicles that
380
00:17:58,380 --> 00:18:03,120
some of you they are constantly making
381
00:17:59,819 --> 00:18:05,700
and unmaking they are constantly so all
382
00:18:03,119 --> 00:18:07,619
this stability that we see all these
383
00:18:05,700 --> 00:18:09,360
being being there sitting that I see
384
00:18:07,619 --> 00:18:11,038
there is a lot going on not only at the
385
00:18:09,359 --> 00:18:14,119
level of yourselves turning over but at
386
00:18:11,038 --> 00:18:14,119
the level of the molecules
387
00:18:15,058 --> 00:18:18,500
I don't know where they made that noise
388
00:18:21,660 --> 00:18:26,779
is the acting that some you know when
389
00:18:23,400 --> 00:18:26,780
cells explore those things
390
00:18:31,079 --> 00:18:35,099
there's machines we know that there is
391
00:18:32,940 --> 00:18:36,900
so that's what the genes do the genes
392
00:18:35,099 --> 00:18:38,279
code for the parts of these Nano
393
00:18:36,900 --> 00:18:41,160
machines and when these machines
394
00:18:38,279 --> 00:18:43,319
assembled they start doing things that
395
00:18:41,160 --> 00:18:46,880
genes cannot dream of but that's a
396
00:18:43,319 --> 00:18:46,879
muscle contraction when you're running
397
00:18:50,099 --> 00:18:54,839
so this is this is I want you to get
398
00:18:52,140 --> 00:18:58,140
this idea that that cells are hubs of
399
00:18:54,839 --> 00:19:00,839
activity and that that that not only
400
00:18:58,140 --> 00:19:03,120
sells a hubs of activity but but we are
401
00:19:00,839 --> 00:19:06,599
also hubs of activity of ourselves this
402
00:19:03,119 --> 00:19:09,000
idea now this structure these remarkable
403
00:19:06,599 --> 00:19:10,139
structure that is the cell how did it
404
00:19:09,000 --> 00:19:12,839
come about
405
00:19:10,140 --> 00:19:14,520
there are two kinds of cells there oh no
406
00:19:12,839 --> 00:19:16,019
now it starts well that's not what I
407
00:19:14,519 --> 00:19:18,000
wanted
408
00:19:16,019 --> 00:19:20,639
I should have done it before
409
00:19:18,000 --> 00:19:23,460
the magic that I made made reference to
410
00:19:20,640 --> 00:19:25,380
Magic happens all the time so there are
411
00:19:23,460 --> 00:19:26,819
two kinds of cells there are two kinds
412
00:19:25,380 --> 00:19:28,980
of cells that you probably have learned
413
00:19:26,819 --> 00:19:31,200
in school there are the prokaryotes and
414
00:19:28,980 --> 00:19:32,519
there are eukaryotes the prokaryotes are
415
00:19:31,200 --> 00:19:34,558
they very simple they don't have a
416
00:19:32,519 --> 00:19:36,538
nucleus they have some DNA wrapped in
417
00:19:34,558 --> 00:19:38,160
the middle they are simple cells but
418
00:19:36,538 --> 00:19:40,679
don't be fooled by simpleness because
419
00:19:38,160 --> 00:19:42,419
they've been here way before we arrived
420
00:19:40,679 --> 00:19:44,759
and they will be here long after we are
421
00:19:42,419 --> 00:19:47,520
gone so that that's very important and
422
00:19:44,759 --> 00:19:49,319
very humbling to to have and then there
423
00:19:47,519 --> 00:19:51,000
is a eukaryotic cells which are very
424
00:19:49,319 --> 00:19:52,918
complicated they have all the so
425
00:19:51,000 --> 00:19:55,319
bacteria that don't have all those
426
00:19:52,919 --> 00:19:57,360
complexities that that you that I've
427
00:19:55,319 --> 00:19:59,460
shown you there so how these very
428
00:19:57,359 --> 00:20:01,558
complex structure how did it come about
429
00:19:59,460 --> 00:20:03,960
how did it come about
430
00:20:01,558 --> 00:20:06,000
um there was a woman called Lynne
431
00:20:03,960 --> 00:20:08,819
Margolis who many years ago when when
432
00:20:06,000 --> 00:20:10,919
she was a young woman she had a great
433
00:20:08,819 --> 00:20:12,960
idea she noticed something very strange
434
00:20:10,919 --> 00:20:14,340
you all know about mitochondria
435
00:20:12,960 --> 00:20:16,259
and she had the thought that
436
00:20:14,339 --> 00:20:19,500
mitochondria looked very very much like
437
00:20:16,259 --> 00:20:21,419
bacteria so he had the idea that perhaps
438
00:20:19,500 --> 00:20:24,119
what happened in the course of evolution
439
00:20:21,419 --> 00:20:26,160
is that the way a eukaryotic cell arose
440
00:20:24,119 --> 00:20:28,379
is at a certain point that there were
441
00:20:26,160 --> 00:20:30,720
many different kinds of bacteria
442
00:20:28,380 --> 00:20:33,000
unicellular organisms they were eating
443
00:20:30,720 --> 00:20:36,179
each other all the time and in one of
444
00:20:33,000 --> 00:20:37,980
those eating situations some bacteria
445
00:20:36,179 --> 00:20:40,740
that perform the same function as the
446
00:20:37,980 --> 00:20:42,599
mitochondria were eaten by another type
447
00:20:40,740 --> 00:20:44,759
of cell and they started to cooperate
448
00:20:42,599 --> 00:20:46,918
they figured out things to cooperate and
449
00:20:44,759 --> 00:20:49,319
that she thinks is the way that the that
450
00:20:46,919 --> 00:20:51,600
the in this merger in this merger this
451
00:20:49,319 --> 00:20:53,099
is the way the eukaryotic cell arose in
452
00:20:51,599 --> 00:20:56,459
fact there must have been many of these
453
00:20:53,099 --> 00:20:58,199
mergers because when the the bacteria
454
00:20:56,460 --> 00:21:01,259
that were eaten by one of the cells were
455
00:20:58,200 --> 00:21:03,000
able to fix oxygen and were able to that
456
00:21:01,259 --> 00:21:04,798
that gave rise there is all these
457
00:21:03,000 --> 00:21:06,900
bacteria which are called cyanobacteria
458
00:21:04,798 --> 00:21:09,119
a cell that ate one of those became the
459
00:21:06,900 --> 00:21:11,460
plants and cells that ate other other
460
00:21:09,119 --> 00:21:13,619
bacteria that were better better doing
461
00:21:11,460 --> 00:21:15,298
not not able to fix oxygen that they
462
00:21:13,619 --> 00:21:18,899
were fixing other things they gave rise
463
00:21:15,298 --> 00:21:22,079
to the animals so this single cell
464
00:21:18,900 --> 00:21:23,940
complicated organisms they they sort of
465
00:21:22,079 --> 00:21:26,759
come you can see here the branch that
466
00:21:23,940 --> 00:21:28,620
goes to the goes to the to the to the
467
00:21:26,759 --> 00:21:30,359
plants and these other plants goes to
468
00:21:28,619 --> 00:21:32,699
animal-like structures which are called
469
00:21:30,359 --> 00:21:35,219
protista these protists are very very
470
00:21:32,700 --> 00:21:37,798
remarkable uh this this is a drawing
471
00:21:35,220 --> 00:21:39,960
from a very famous German scientist very
472
00:21:37,798 --> 00:21:41,940
great artist also called Ernst Heckle
473
00:21:39,960 --> 00:21:44,100
who was very interested by this world
474
00:21:41,940 --> 00:21:46,080
and look at this remarkably a lot of
475
00:21:44,099 --> 00:21:48,058
those are single cell organists those
476
00:21:46,079 --> 00:21:49,918
are single cell organisms look at the
477
00:21:48,058 --> 00:21:51,839
Variety that there are and some of them
478
00:21:49,919 --> 00:21:53,759
are absolutely very very beautiful this
479
00:21:51,839 --> 00:21:55,558
is some staining with some antibodies to
480
00:21:53,759 --> 00:21:57,960
reveal the internal structure that's
481
00:21:55,558 --> 00:22:00,359
called a stentor it's a very interesting
482
00:21:57,960 --> 00:22:02,159
and intelligent animals I have a good
483
00:22:00,359 --> 00:22:04,798
friend in Harvard who is interested in
484
00:22:02,159 --> 00:22:06,480
the behavior of this simple cell in fact
485
00:22:04,798 --> 00:22:09,000
this is a very it has a very good story
486
00:22:06,480 --> 00:22:10,620
this this has fascinated the the
487
00:22:09,000 --> 00:22:13,079
scientists for a long time so this this
488
00:22:10,619 --> 00:22:14,819
thing called the center sits on the
489
00:22:13,079 --> 00:22:16,859
floor and it's waiting there and if you
490
00:22:14,819 --> 00:22:18,899
go and put a little bit of Ink on it a
491
00:22:16,859 --> 00:22:21,719
little bit of it it will move like this
492
00:22:18,900 --> 00:22:23,280
to try to get away all those drops if
493
00:22:21,720 --> 00:22:25,259
you start pouring more it gets very
494
00:22:23,279 --> 00:22:27,359
agitated and it starts agitating even
495
00:22:25,259 --> 00:22:29,099
more and if you put even more what it
496
00:22:27,359 --> 00:22:31,139
will do it gets so agitated that it
497
00:22:29,099 --> 00:22:33,058
lifts itself off the ground and moves
498
00:22:31,140 --> 00:22:34,799
somewhere else away from the ink so that
499
00:22:33,058 --> 00:22:37,019
says that he's thinking even a single
500
00:22:34,798 --> 00:22:39,658
cell can do that okay so that's very
501
00:22:37,019 --> 00:22:42,720
remarkable and it is here somewhere here
502
00:22:39,659 --> 00:22:46,559
that the ancestors of the animals lie in
503
00:22:42,720 --> 00:22:48,779
this world of the protista of the of the
504
00:22:46,558 --> 00:22:50,759
Single Cell prokaryotes something very
505
00:22:48,779 --> 00:22:52,259
mysterious and I was talking to Stefan
506
00:22:50,759 --> 00:22:54,000
this morning about that something very
507
00:22:52,259 --> 00:22:56,220
mysterious must have happened here and
508
00:22:54,000 --> 00:22:58,140
this is this is one of the great
509
00:22:56,220 --> 00:22:59,579
mysteries of Life how do you go from
510
00:22:58,140 --> 00:23:02,700
from this there is actually a whole
511
00:22:59,579 --> 00:23:04,079
group of of animals like here of organic
512
00:23:02,700 --> 00:23:06,419
sorry I should say organisms which are
513
00:23:04,079 --> 00:23:08,279
not animals but but they they behave in
514
00:23:06,419 --> 00:23:10,799
funny way they are much more complex
515
00:23:08,279 --> 00:23:12,899
than these but they are not animals yet
516
00:23:10,798 --> 00:23:14,819
an animal is a multicellular organism
517
00:23:12,900 --> 00:23:17,220
and something must have happened at some
518
00:23:14,819 --> 00:23:18,538
point you can see here some these very
519
00:23:17,220 --> 00:23:20,700
interesting organisms that are not
520
00:23:18,538 --> 00:23:22,619
animals they try to form colonies they
521
00:23:20,700 --> 00:23:24,900
try to interact with each other but they
522
00:23:22,619 --> 00:23:27,359
don't form these structures these
523
00:23:24,900 --> 00:23:30,900
compact structures that are that are
524
00:23:27,359 --> 00:23:33,119
animals at some point about 600 million
525
00:23:30,900 --> 00:23:35,940
years ago I know it's an amazing numbers
526
00:23:33,119 --> 00:23:39,119
I'm throwing numbers of you you know 40
527
00:23:35,940 --> 00:23:40,558
000 trillion cells 500 million years I
528
00:23:39,119 --> 00:23:42,298
mean when a physicist tells you about
529
00:23:40,558 --> 00:23:44,158
stars and how many stars are in the
530
00:23:42,298 --> 00:23:45,720
universe you can laugh because there is
531
00:23:44,159 --> 00:23:47,640
more cells in the world than there are
532
00:23:45,720 --> 00:23:49,200
stars in the universe at this very
533
00:23:47,640 --> 00:23:50,700
moment so that's something that that
534
00:23:49,200 --> 00:23:52,679
should humble and the physicists are
535
00:23:50,700 --> 00:23:55,080
very afraid of biology by the way
536
00:23:52,679 --> 00:23:56,940
should take very good we are very
537
00:23:55,079 --> 00:23:58,619
impressed by the physicists but they are
538
00:23:56,940 --> 00:24:00,900
very afraid of biology this is something
539
00:23:58,619 --> 00:24:03,359
for you to think about ask them to
540
00:24:00,900 --> 00:24:05,759
explain life to you okay in case there
541
00:24:03,359 --> 00:24:07,439
is any Ephesus in the audience
542
00:24:05,759 --> 00:24:10,558
but but you can see this very
543
00:24:07,440 --> 00:24:12,080
interesting animals which uh sorry
544
00:24:10,558 --> 00:24:14,399
organisms
545
00:24:12,079 --> 00:24:16,980
this organisms are at the interface
546
00:24:14,400 --> 00:24:19,679
between the the protista this single
547
00:24:16,980 --> 00:24:21,900
cell organisms and the and the animals
548
00:24:19,679 --> 00:24:23,460
and the first animals that appear there
549
00:24:21,900 --> 00:24:25,259
seems to be a gap here all of a sudden
550
00:24:23,460 --> 00:24:27,298
you start seeing when you look at
551
00:24:25,259 --> 00:24:29,279
fossils you start seeing disorganisms
552
00:24:27,298 --> 00:24:30,839
you just as in the sponges esponjias are
553
00:24:29,279 --> 00:24:33,178
the first animals and we know that they
554
00:24:30,839 --> 00:24:34,019
are animals do you also get these
555
00:24:33,179 --> 00:24:37,200
beautiful
556
00:24:34,019 --> 00:24:38,700
um medallions this is Hydra that some of
557
00:24:37,200 --> 00:24:41,038
you know and of course there is a lot of
558
00:24:38,700 --> 00:24:44,960
work going on here in in Heidelberg on
559
00:24:41,038 --> 00:24:44,960
Hydra and this is another another
560
00:24:45,859 --> 00:24:50,038
they're absolutely beautiful these are
561
00:24:48,240 --> 00:24:52,200
the first experiments I mean what we are
562
00:24:50,038 --> 00:24:53,879
looking is the remnants of experiments
563
00:24:52,200 --> 00:24:56,400
that nature has done
564
00:24:53,880 --> 00:24:58,679
these are not quite like us but they
565
00:24:56,400 --> 00:25:01,380
obviously occupied the Earth for a for a
566
00:24:58,679 --> 00:25:04,620
very long time when mostly was uh
567
00:25:01,380 --> 00:25:07,080
submerged in in water and then
568
00:25:04,619 --> 00:25:09,000
500 million years ago something
569
00:25:07,079 --> 00:25:11,158
remarkable happened
570
00:25:09,000 --> 00:25:13,500
it's called the Cambrian explosions
571
00:25:11,159 --> 00:25:15,960
because all of a sudden this was
572
00:25:13,500 --> 00:25:18,480
discovered in in a little Shale in in
573
00:25:15,960 --> 00:25:20,579
Canada called the Burgess Shale and all
574
00:25:18,480 --> 00:25:22,860
of a sudden out of this what you see
575
00:25:20,579 --> 00:25:24,418
before is this boring organ not a great
576
00:25:22,859 --> 00:25:27,178
variety of them and all of a sudden
577
00:25:24,419 --> 00:25:29,159
about 500 million years ago you get a
578
00:25:27,179 --> 00:25:31,080
huge explosion a huge experiment in
579
00:25:29,159 --> 00:25:32,940
animal form you get a lot of weird
580
00:25:31,079 --> 00:25:35,220
things I mean this famous biologist
581
00:25:32,940 --> 00:25:37,019
Stephen J Gould has written a book
582
00:25:35,220 --> 00:25:39,240
called this wonderful life about about
583
00:25:37,019 --> 00:25:41,400
this this explosion they found all these
584
00:25:39,240 --> 00:25:43,859
fossils with animals that some of them
585
00:25:41,400 --> 00:25:45,419
resemble some of what we are today I
586
00:25:43,859 --> 00:25:47,699
mean they they have what they call we
587
00:25:45,419 --> 00:25:49,559
call bilateral symmetry they had to hit
588
00:25:47,700 --> 00:25:52,080
any tail there are others that are very
589
00:25:49,558 --> 00:25:54,000
very weird but it's clearly nature
590
00:25:52,079 --> 00:25:56,759
experimenting
591
00:25:54,000 --> 00:25:58,380
nature is experimenting here with form
592
00:25:56,759 --> 00:26:01,140
and of course
593
00:25:58,380 --> 00:26:02,820
it's not DNA that is experimenting it is
594
00:26:01,140 --> 00:26:05,220
the cells that are experimenting with
595
00:26:02,819 --> 00:26:07,859
configurations with activities with
596
00:26:05,220 --> 00:26:10,500
things that that will fool them and out
597
00:26:07,859 --> 00:26:12,839
of these Cambrian explosion
598
00:26:10,500 --> 00:26:15,480
we got something that starts looking we
599
00:26:12,839 --> 00:26:17,699
get Evolution going big time and you can
600
00:26:15,480 --> 00:26:20,099
see here I mean you know initially uh
601
00:26:17,700 --> 00:26:22,380
that's a tree of what happens I mean
602
00:26:20,099 --> 00:26:24,778
what we what we are today it's a
603
00:26:22,380 --> 00:26:27,120
consequence of this all of a sudden it
604
00:26:24,778 --> 00:26:29,339
accelerates that once you invent cells
605
00:26:27,119 --> 00:26:31,379
one one you get eukaryotic cells they
606
00:26:29,339 --> 00:26:33,119
start exploring a very wide space
607
00:26:31,380 --> 00:26:35,039
they're still being creative this is
608
00:26:33,119 --> 00:26:38,158
this is what I find and indeed you know
609
00:26:35,038 --> 00:26:39,960
cells are incredibly creative I mean it
610
00:26:38,159 --> 00:26:42,480
is all down to the cells and they create
611
00:26:39,960 --> 00:26:44,519
the structures like this here I mean
612
00:26:42,480 --> 00:26:46,980
some of you talked about plants this
613
00:26:44,519 --> 00:26:49,079
morning I mean this is the eye of a
614
00:26:46,980 --> 00:26:50,819
flight you can see here on the left this
615
00:26:49,079 --> 00:26:52,019
is one of my favorite structures that
616
00:26:50,819 --> 00:26:54,058
you can see here so but you can see
617
00:26:52,019 --> 00:26:56,519
there is a paramecium on the this is a
618
00:26:54,058 --> 00:26:59,879
unicellular organism and that's 200
619
00:26:56,519 --> 00:27:02,759
microns 200 microns a fifth of a
620
00:26:59,880 --> 00:27:05,760
millimeter that is a fly that is not a
621
00:27:02,759 --> 00:27:07,798
fake there is a fly which is about 200
622
00:27:05,759 --> 00:27:10,019
microns and it has a nervous system and
623
00:27:07,798 --> 00:27:10,940
it has eyes and it has wings and the
624
00:27:10,019 --> 00:27:13,019
length of that
625
00:27:10,940 --> 00:27:14,700
you will not be surprised that this
626
00:27:13,019 --> 00:27:16,579
nervous system has thrown out all the
627
00:27:14,700 --> 00:27:19,500
nuclei
628
00:27:16,579 --> 00:27:22,319
that little fly is called Tinker Bella
629
00:27:19,500 --> 00:27:24,480
Nana from Tinkerbell in Peter Pan so
630
00:27:22,319 --> 00:27:26,759
because it's really like Tinkerbell in
631
00:27:24,480 --> 00:27:28,860
many many different ways but you also
632
00:27:26,759 --> 00:27:30,359
get the the the the Beautiful the beauty
633
00:27:28,859 --> 00:27:32,939
of the I mean it's just it's just the
634
00:27:30,359 --> 00:27:36,000
creativity of of cells it excels
635
00:27:32,940 --> 00:27:39,600
anything that an artist can do and those
636
00:27:36,000 --> 00:27:42,900
patterns and those shapes and everything
637
00:27:39,599 --> 00:27:45,418
so how does all these come about well
638
00:27:42,900 --> 00:27:47,940
because we are one cell one cell becomes
639
00:27:45,419 --> 00:27:49,440
two two becomes four and so on and then
640
00:27:47,940 --> 00:27:51,659
we become many
641
00:27:49,440 --> 00:27:54,840
what you see in this movie here is
642
00:27:51,659 --> 00:27:57,480
actually a human fertilized egg
643
00:27:54,839 --> 00:28:00,599
now in in vitro fertilization clinics
644
00:27:57,480 --> 00:28:02,339
people are giving movies of the eggs
645
00:28:00,599 --> 00:28:04,558
that have been successfully fertilized
646
00:28:02,339 --> 00:28:07,259
and they like to think that this is the
647
00:28:04,558 --> 00:28:10,399
child we can discuss that later but but
648
00:28:07,259 --> 00:28:10,400
they give them the movies
649
00:28:10,619 --> 00:28:14,879
yeah yeah I can see that so there you go
650
00:28:12,960 --> 00:28:16,740
you know a cell becomes two to become
651
00:28:14,880 --> 00:28:18,840
and in the process of seven days what
652
00:28:16,740 --> 00:28:21,179
you're seeing there is the first week of
653
00:28:18,839 --> 00:28:23,959
the life of someone that that that's
654
00:28:21,179 --> 00:28:23,960
what it is foreign
655
00:28:27,419 --> 00:28:31,799
that's the important thing first and
656
00:28:29,640 --> 00:28:33,299
then when there are millions and in the
657
00:28:31,798 --> 00:28:35,519
process of being Millions the cells
658
00:28:33,298 --> 00:28:37,558
start becoming different from each other
659
00:28:35,519 --> 00:28:39,298
and doing things this by the way is from
660
00:28:37,558 --> 00:28:40,980
a very wonderful book that we've had at
661
00:28:39,298 --> 00:28:43,859
home for many years called cell Saras
662
00:28:40,980 --> 00:28:46,200
which is the title of the talk really
663
00:28:43,859 --> 00:28:48,599
because in a way to me
664
00:28:46,200 --> 00:28:49,919
as you can see here the development of
665
00:28:48,599 --> 00:28:52,379
an organ is that's what we are talking
666
00:28:49,919 --> 00:28:54,600
about you often said I mean a fly of
667
00:28:52,380 --> 00:28:56,520
course come also from a single cell but
668
00:28:54,599 --> 00:28:58,500
but it's a dictatorship the fly is a
669
00:28:56,519 --> 00:29:00,418
dictatorship this is a democracy the way
670
00:28:58,500 --> 00:29:02,880
a vertebrate vertebrate develops it's a
671
00:29:00,419 --> 00:29:04,919
democracy and and and you know it's it's
672
00:29:02,880 --> 00:29:06,778
about cells it's turning is in terms of
673
00:29:04,919 --> 00:29:09,059
a mapping genes into cells it's about
674
00:29:06,778 --> 00:29:11,339
cells mapping into space and time and
675
00:29:09,058 --> 00:29:13,019
genes are just instructions to make the
676
00:29:11,339 --> 00:29:15,058
component of the cells and you can see
677
00:29:13,019 --> 00:29:17,220
the beauty of development in in these
678
00:29:15,058 --> 00:29:20,220
movies that just took a couple of random
679
00:29:17,220 --> 00:29:23,399
ones here you have a drosophila embryo
680
00:29:20,220 --> 00:29:25,740
the ones at the top are are zebrafish
681
00:29:23,398 --> 00:29:27,719
Johan never gives me a movie of medaka
682
00:29:25,740 --> 00:29:29,880
so one day maybe he will and I can put
683
00:29:27,720 --> 00:29:31,798
it in the in the gallery and there you
684
00:29:29,880 --> 00:29:34,799
have a chicken making making the Soma
685
00:29:31,798 --> 00:29:36,480
it's absolutely absolutely amazing
686
00:29:34,798 --> 00:29:38,819
um the first thing that the embryo does
687
00:29:36,480 --> 00:29:40,740
or or this cell when it amplifies itself
688
00:29:38,819 --> 00:29:43,619
now you get a whole bowl of cells that
689
00:29:40,740 --> 00:29:45,419
are all the same and then it's gonna go
690
00:29:43,619 --> 00:29:48,359
through this process called gastrulation
691
00:29:45,419 --> 00:29:50,340
which very famous biologies that that
692
00:29:48,359 --> 00:29:52,379
unfortunately passed away two years ago
693
00:29:50,339 --> 00:29:55,019
Lou is well predefined in that manner
694
00:29:52,380 --> 00:29:57,419
the most important event in your life is
695
00:29:55,019 --> 00:29:59,460
not birth or marriage or death but
696
00:29:57,419 --> 00:30:01,140
gastrulation
697
00:29:59,460 --> 00:30:02,038
you didn't know that but you know that
698
00:30:01,140 --> 00:30:04,679
now
699
00:30:02,038 --> 00:30:05,759
and why is that the case and why is that
700
00:30:04,679 --> 00:30:07,679
the case
701
00:30:05,759 --> 00:30:09,359
because that's the moment that that ball
702
00:30:07,679 --> 00:30:11,720
of cells
703
00:30:09,359 --> 00:30:15,119
that is the outcome of the fertilization
704
00:30:11,720 --> 00:30:17,460
engages into a choreography a cell
705
00:30:15,119 --> 00:30:19,558
origami game which transforms that into
706
00:30:17,460 --> 00:30:21,720
an organ this is a very famous xenobus
707
00:30:19,558 --> 00:30:23,339
movie I know there is a friend of mine
708
00:30:21,720 --> 00:30:25,380
in the audience I will be very happy to
709
00:30:23,339 --> 00:30:27,240
see to see this movie and there you have
710
00:30:25,380 --> 00:30:28,380
you know you have a lot of cells that
711
00:30:27,240 --> 00:30:30,960
are all the same and all of a sudden
712
00:30:28,380 --> 00:30:33,240
this choreography starts and out of that
713
00:30:30,960 --> 00:30:35,100
choreography you get something that
714
00:30:33,240 --> 00:30:37,500
looks like an embryo you can see why I
715
00:30:35,099 --> 00:30:39,000
say there is self origami or it is a
716
00:30:37,500 --> 00:30:40,980
choreography in fact the cells are
717
00:30:39,000 --> 00:30:43,019
moving in very defined ways it's a very
718
00:30:40,980 --> 00:30:45,058
this is a drawings of a scientist on
719
00:30:43,019 --> 00:30:46,500
that something that that you can see
720
00:30:45,058 --> 00:30:48,298
there you know some cells are going
721
00:30:46,500 --> 00:30:50,278
inside and you can see how from
722
00:30:48,298 --> 00:30:51,599
posterior to anterior you get you get
723
00:30:50,278 --> 00:30:53,759
the nervous system which is outside
724
00:30:51,599 --> 00:30:55,199
inside there are the muscles now I'll
725
00:30:53,759 --> 00:30:57,599
tell you how you are never going to
726
00:30:55,200 --> 00:30:59,220
forget what gastrulation is which is a
727
00:30:57,599 --> 00:31:01,740
sentence not mine but of that famous
728
00:30:59,220 --> 00:31:03,720
scientist called Ray Keller castrolation
729
00:31:01,740 --> 00:31:05,399
is the act whereby you separate the
730
00:31:03,720 --> 00:31:08,038
from the brain
731
00:31:05,398 --> 00:31:10,739
that's what it is and in fact that
732
00:31:08,038 --> 00:31:11,819
little hole that little halter which now
733
00:31:10,740 --> 00:31:13,558
you're never going to forget gas
734
00:31:11,819 --> 00:31:15,658
relation is the most important moment in
735
00:31:13,558 --> 00:31:18,298
your life and is the one whereby you
736
00:31:15,659 --> 00:31:20,399
separate the from the brain
737
00:31:18,298 --> 00:31:23,639
and as we all know many people don't
738
00:31:20,398 --> 00:31:26,819
achieve that separation very well
739
00:31:23,640 --> 00:31:29,299
so that's very good
740
00:31:26,819 --> 00:31:29,298
so
741
00:31:31,859 --> 00:31:36,139
sorry I don't know I don't know why do
742
00:31:33,720 --> 00:31:36,140
you know any
743
00:31:36,240 --> 00:31:39,720
anyway
744
00:31:38,099 --> 00:31:42,500
um
745
00:31:39,720 --> 00:31:42,500
not sorry
746
00:31:44,038 --> 00:31:50,339
um so but the question here is um how do
747
00:31:48,058 --> 00:31:52,678
we how do we so we've gone these bionics
748
00:31:50,339 --> 00:31:54,658
you know it's very good but if the cells
749
00:31:52,679 --> 00:31:57,480
are all this creativity can we actually
750
00:31:54,659 --> 00:31:59,399
change this bionic into something that
751
00:31:57,480 --> 00:32:01,620
we can make with cells can we start
752
00:31:59,398 --> 00:32:04,259
working instead of with wire and and and
753
00:32:01,619 --> 00:32:07,079
metal can we actually
754
00:32:04,259 --> 00:32:09,058
um use it to to build the can we use
755
00:32:07,079 --> 00:32:11,398
cells how can we do that I told you
756
00:32:09,058 --> 00:32:13,558
before that there are these stem cells
757
00:32:11,398 --> 00:32:15,959
that are in every in every organ of ours
758
00:32:13,558 --> 00:32:18,298
but there is a very special kind of stem
759
00:32:15,960 --> 00:32:20,700
cell that doesn't really exist we've
760
00:32:18,298 --> 00:32:23,099
managed to to get it in a plate out of
761
00:32:20,700 --> 00:32:25,200
very early embryos and it's called the
762
00:32:23,099 --> 00:32:27,898
embryonic stem cell okay this is the
763
00:32:25,200 --> 00:32:30,120
embryonic stem cell oh sorry and the
764
00:32:27,898 --> 00:32:33,479
embryonic stem cell I hope
765
00:32:30,119 --> 00:32:35,579
can stay there it passes by
766
00:32:33,480 --> 00:32:37,919
um I'm gonna try to to freeze it here I
767
00:32:35,579 --> 00:32:39,839
I think I'm sorry about that well these
768
00:32:37,919 --> 00:32:42,360
embryonic stem cells we get them out of
769
00:32:39,839 --> 00:32:45,538
embryos we can culture them in a dish
770
00:32:42,359 --> 00:32:48,240
for a very very very long time and and
771
00:32:45,538 --> 00:32:50,339
they keep this ability to generate the
772
00:32:48,240 --> 00:32:52,259
organism while they are on the plate and
773
00:32:50,339 --> 00:32:54,058
it's very remarkable how do we know that
774
00:32:52,259 --> 00:32:56,460
because if we put it back in an embryo
775
00:32:54,058 --> 00:33:00,058
they will generate a mouse
776
00:32:56,460 --> 00:33:02,519
okay and this is very important now many
777
00:33:00,058 --> 00:33:04,139
years ago a scientists in Cambridge
778
00:33:02,519 --> 00:33:05,940
called in Oxford at the time called
779
00:33:04,140 --> 00:33:07,620
young Garden did an experiment that led
780
00:33:05,940 --> 00:33:09,240
to this other experiments many years
781
00:33:07,619 --> 00:33:10,918
later which is that you can take any
782
00:33:09,240 --> 00:33:13,259
cell of your body
783
00:33:10,919 --> 00:33:16,620
and actually get it back to the first
784
00:33:13,259 --> 00:33:19,319
cell that was in the embryo you can turn
785
00:33:16,619 --> 00:33:21,418
back the clock of the cells and this was
786
00:33:19,319 --> 00:33:23,639
exploited by this person's senior
787
00:33:21,419 --> 00:33:25,559
jamanaka younger than work with frog
788
00:33:23,640 --> 00:33:28,259
shinia jamanaka work with with human
789
00:33:25,558 --> 00:33:30,119
cells and with and and and what he did
790
00:33:28,259 --> 00:33:32,519
is this kind of reprogramming which as
791
00:33:30,119 --> 00:33:34,918
you can see here you take cells from
792
00:33:32,519 --> 00:33:37,319
skin cells and using a cocktail of
793
00:33:34,919 --> 00:33:39,059
transcription factors of molecules you
794
00:33:37,319 --> 00:33:40,918
can turn them back into embryonic stem
795
00:33:39,058 --> 00:33:43,139
cells we then you can differentiate
796
00:33:40,919 --> 00:33:45,720
that's what stem cells do into any cell
797
00:33:43,140 --> 00:33:48,059
tissue of the organ and now the idea is
798
00:33:45,720 --> 00:33:50,038
people are working on this very actively
799
00:33:48,058 --> 00:33:51,720
now you should be able to take these
800
00:33:50,038 --> 00:33:54,240
cells and use them as the source of
801
00:33:51,720 --> 00:33:56,100
those tissues and repair and and that's
802
00:33:54,240 --> 00:33:57,960
really what's being done these days in
803
00:33:56,099 --> 00:34:00,000
in terms of the of the engineering I
804
00:33:57,960 --> 00:34:02,038
mean a lot of work is being done these
805
00:34:00,000 --> 00:34:05,460
days precisely about about turning these
806
00:34:02,038 --> 00:34:08,159
cells into the into the
807
00:34:05,460 --> 00:34:10,378
in the the the different parts of the
808
00:34:08,159 --> 00:34:12,119
organs of the organisms we already know
809
00:34:10,378 --> 00:34:15,480
for example these cells if you don't do
810
00:34:12,119 --> 00:34:17,338
anything to them I don't know it is he's
811
00:34:15,480 --> 00:34:19,559
taking there is very little we can do I
812
00:34:17,338 --> 00:34:21,599
know but but if you turn them you can
813
00:34:19,559 --> 00:34:23,219
turn them into brains for example you
814
00:34:21,599 --> 00:34:25,139
can turn them into levers you can turn
815
00:34:23,219 --> 00:34:27,118
them into ice it's it's a very um we
816
00:34:25,139 --> 00:34:29,220
know we are not sure it's a bit of an
817
00:34:27,119 --> 00:34:31,379
Alchemy it's something that happens and
818
00:34:29,219 --> 00:34:33,719
indeed this reminds me that the lecture
819
00:34:31,378 --> 00:34:36,179
that I gave 10 years ago sort of had
820
00:34:33,719 --> 00:34:38,098
very big references to Harry Potter and
821
00:34:36,179 --> 00:34:39,838
I looked at it and I say that I was
822
00:34:38,099 --> 00:34:42,359
talking about the alchemy that that we
823
00:34:39,838 --> 00:34:44,219
can do to get cells to do that so using
824
00:34:42,358 --> 00:34:46,500
embryonic stem cells in the case of the
825
00:34:44,219 --> 00:34:48,658
mouse we have been managed many together
826
00:34:46,500 --> 00:34:51,000
with other people to reproduce the very
827
00:34:48,659 --> 00:34:52,500
earliest stages of development and I put
828
00:34:51,000 --> 00:34:54,599
Harry Potter there because there is a
829
00:34:52,500 --> 00:34:57,300
lot of magic it is for you guys who are
830
00:34:54,599 --> 00:34:59,760
interested in this to explain to us what
831
00:34:57,300 --> 00:35:01,980
is that is going on after all let's not
832
00:34:59,760 --> 00:35:04,260
look down into Alchemy because Alchemy
833
00:35:01,980 --> 00:35:06,838
is is the progenitor is what gives rise
834
00:35:04,260 --> 00:35:09,480
to chemistry so the Alchemy is not bad
835
00:35:06,838 --> 00:35:10,619
it's just very early chemistry so using
836
00:35:09,480 --> 00:35:12,960
this um
837
00:35:10,619 --> 00:35:14,519
these kind of tricks with those stem
838
00:35:12,960 --> 00:35:16,858
cells we've managed to reproduce the
839
00:35:14,519 --> 00:35:18,300
very early stages of development but we
840
00:35:16,858 --> 00:35:20,098
were wondering about whether we could
841
00:35:18,300 --> 00:35:21,780
reproduce gastrulation which is that
842
00:35:20,099 --> 00:35:24,000
moment in which we're going to change
843
00:35:21,780 --> 00:35:26,579
the the the whole mass of cells into
844
00:35:24,000 --> 00:35:28,440
something that that shapes us and and we
845
00:35:26,579 --> 00:35:30,599
did that in the lab and you don't need
846
00:35:28,440 --> 00:35:32,220
to worry about the details we we call
847
00:35:30,599 --> 00:35:34,800
these things gastroits and you can see
848
00:35:32,219 --> 00:35:36,539
we put a very small number of cells and
849
00:35:34,800 --> 00:35:38,339
the cells seem to know how many they are
850
00:35:36,539 --> 00:35:39,779
and if we put the right number of cells
851
00:35:38,338 --> 00:35:42,000
and they all get together in the right
852
00:35:39,780 --> 00:35:43,560
time you actually you start getting for
853
00:35:42,000 --> 00:35:45,480
example you will see now a gene there
854
00:35:43,559 --> 00:35:47,460
that is starting to be expressed and it
855
00:35:45,480 --> 00:35:49,619
becomes restricted we start with about
856
00:35:47,460 --> 00:35:52,440
two three hundred cells and as you can
857
00:35:49,619 --> 00:35:55,440
see here those 300 cells become these
858
00:35:52,440 --> 00:35:58,139
very um is very very remarkable objects
859
00:35:55,440 --> 00:35:59,940
that elongate and and when we look at
860
00:35:58,139 --> 00:36:02,578
the genes that they are expressing there
861
00:35:59,940 --> 00:36:04,440
we see that they seem to have the same
862
00:36:02,579 --> 00:36:07,079
organization in gene expression as an
863
00:36:04,440 --> 00:36:09,900
embryo in fact as you can see here these
864
00:36:07,079 --> 00:36:11,820
things are quite a coordinate system in
865
00:36:09,900 --> 00:36:13,500
which in which you you have the three
866
00:36:11,820 --> 00:36:15,359
coordinates you have the enteroposterior
867
00:36:13,500 --> 00:36:17,699
the doors of ventral and the left right
868
00:36:15,358 --> 00:36:19,799
this is in vitro this is in a dish so
869
00:36:17,699 --> 00:36:21,719
these cells have an ability to to make
870
00:36:19,800 --> 00:36:23,579
to make something that very much
871
00:36:21,719 --> 00:36:24,659
resembles the organization of an embryo
872
00:36:23,579 --> 00:36:26,579
you don't need to worry about these
873
00:36:24,659 --> 00:36:28,139
pictures it's just to show you that the
874
00:36:26,579 --> 00:36:29,760
organization of the cells in this
875
00:36:28,139 --> 00:36:31,618
structures is very much that of the
876
00:36:29,760 --> 00:36:33,599
embryo and that they follow Paths of
877
00:36:31,619 --> 00:36:35,820
differentiation there is a very special
878
00:36:33,599 --> 00:36:38,099
class of genes called the oxygens that
879
00:36:35,820 --> 00:36:40,140
we all have which seem to act as a ruler
880
00:36:38,099 --> 00:36:41,640
about what the different parts of the
881
00:36:40,139 --> 00:36:44,338
body have to do from anterior to
882
00:36:41,639 --> 00:36:45,900
posterior so they are very special genes
883
00:36:44,338 --> 00:36:47,759
because they are very conserved they are
884
00:36:45,900 --> 00:36:50,039
always expressing like a Russian doll
885
00:36:47,760 --> 00:36:51,780
kind of pattern and indeed in these
886
00:36:50,039 --> 00:36:53,699
structures that we call Gastrology they
887
00:36:51,780 --> 00:36:55,079
have the same expression pattern you can
888
00:36:53,699 --> 00:36:57,419
see that they have this nested
889
00:36:55,079 --> 00:36:58,700
expression so these these structures are
890
00:36:57,420 --> 00:37:01,320
very intriguing
891
00:36:58,699 --> 00:37:03,539
and and we can we can follow in them
892
00:37:01,320 --> 00:37:05,039
that that's the cells we can follow all
893
00:37:03,539 --> 00:37:07,019
the different parts of the of the earth
894
00:37:05,039 --> 00:37:09,358
we can make in every systems we can make
895
00:37:07,019 --> 00:37:11,280
muscles we can make guts we can make
896
00:37:09,358 --> 00:37:13,920
blood we can make a heart but you don't
897
00:37:11,280 --> 00:37:15,599
need so but this is all integrated this
898
00:37:13,920 --> 00:37:17,519
is this is really like an embryo but
899
00:37:15,599 --> 00:37:19,380
some of you might have realized that
900
00:37:17,519 --> 00:37:21,480
this is not this does not look like an
901
00:37:19,380 --> 00:37:23,820
embryo although it has all the genes
902
00:37:21,480 --> 00:37:24,719
perfectly organized it's lacking
903
00:37:23,820 --> 00:37:27,240
something
904
00:37:24,719 --> 00:37:29,159
and that's something probably is some
905
00:37:27,239 --> 00:37:31,739
interactions between cells that are
906
00:37:29,159 --> 00:37:33,899
going to shape that into something that
907
00:37:31,739 --> 00:37:35,819
looks more like an embryo because an
908
00:37:33,900 --> 00:37:37,619
embryo an organism is not just a
909
00:37:35,820 --> 00:37:39,300
collection of genes it's also a
910
00:37:37,619 --> 00:37:43,800
collection of cell interactions and in
911
00:37:39,300 --> 00:37:47,099
this lab culture system you have you're
912
00:37:43,800 --> 00:37:49,740
missing that that component of input it
913
00:37:47,099 --> 00:37:52,320
is this is a very famous set of drawings
914
00:37:49,739 --> 00:37:54,179
from Picasso what we are we're picking
915
00:37:52,320 --> 00:37:56,160
up is the essence of the organism it
916
00:37:54,179 --> 00:37:57,899
doesn't look like a bull but it has many
917
00:37:56,159 --> 00:37:59,759
of the elements of a bull and and you
918
00:37:57,900 --> 00:38:02,579
can recognize that as a structure of a
919
00:37:59,760 --> 00:38:04,260
bull all this work was done with mice so
920
00:38:02,579 --> 00:38:06,780
we wonder what would happen if we could
921
00:38:04,260 --> 00:38:09,660
do it with with humans and and try to
922
00:38:06,780 --> 00:38:11,280
see what what the anardo did and indeed
923
00:38:09,659 --> 00:38:13,739
I mean we managed to create these
924
00:38:11,280 --> 00:38:16,079
structures which We call gastruloids we
925
00:38:13,739 --> 00:38:18,959
they they are this is from from human
926
00:38:16,079 --> 00:38:20,579
cells and they look very much like the
927
00:38:18,960 --> 00:38:22,559
same of the mouse they have this very
928
00:38:20,579 --> 00:38:24,119
beautiful organization of gene
929
00:38:22,559 --> 00:38:26,460
expression they are very reproducible
930
00:38:24,119 --> 00:38:28,500
they have been very very efficiently and
931
00:38:26,460 --> 00:38:30,838
all you need to know we we get them to
932
00:38:28,500 --> 00:38:32,400
to do all sorts of things and we can do
933
00:38:30,838 --> 00:38:35,460
all sorts of analysis that you don't
934
00:38:32,400 --> 00:38:37,320
need to to worry about and when we look
935
00:38:35,460 --> 00:38:39,960
because there are ways that we can say
936
00:38:37,320 --> 00:38:42,059
how old what what stage of embryo
937
00:38:39,960 --> 00:38:45,599
Genesis of the development of a human
938
00:38:42,059 --> 00:38:47,460
being these structures re resemble and
939
00:38:45,599 --> 00:38:49,740
we realize that we have managed to reach
940
00:38:47,460 --> 00:38:50,880
about 21 days which is at the end of
941
00:38:49,739 --> 00:38:54,659
gastrulation
942
00:38:50,880 --> 00:38:56,460
so we are able to reproduce or well not
943
00:38:54,659 --> 00:38:58,679
we use the cells we've managed to
944
00:38:56,460 --> 00:39:00,720
communicate with the cells in a manner
945
00:38:58,679 --> 00:39:02,159
that we've encouraged them to reproduce
946
00:39:00,719 --> 00:39:03,480
the very early stages of human
947
00:39:02,159 --> 00:39:05,279
development
948
00:39:03,480 --> 00:39:07,679
this is very important why it's very
949
00:39:05,280 --> 00:39:09,839
important because there is no way of
950
00:39:07,679 --> 00:39:12,239
studying human development we can study
951
00:39:09,838 --> 00:39:14,039
animals we can study mice we can study
952
00:39:12,239 --> 00:39:16,379
fish but we cannot study humans because
953
00:39:14,039 --> 00:39:18,358
we cannot do experiments with humans so
954
00:39:16,380 --> 00:39:21,480
the fact that with cells we've managed
955
00:39:18,358 --> 00:39:22,799
to create a system that reproduces many
956
00:39:21,480 --> 00:39:24,900
of the earliest stages of human
957
00:39:22,800 --> 00:39:27,000
development is going to allow us to
958
00:39:24,900 --> 00:39:29,519
create and learn something about the the
959
00:39:27,000 --> 00:39:31,619
how the basic body plan the basic
960
00:39:29,519 --> 00:39:33,900
structure that we are coming to being
961
00:39:31,619 --> 00:39:35,940
and for example we're producing this
962
00:39:33,900 --> 00:39:39,119
system various special processes here
963
00:39:35,940 --> 00:39:40,858
you have a very a very famous process
964
00:39:39,119 --> 00:39:42,720
which is called sometogenesis is
965
00:39:40,858 --> 00:39:44,880
basically we are segmented and we grow
966
00:39:42,719 --> 00:39:46,618
from anterior to posterior and during
967
00:39:44,880 --> 00:39:48,300
this time in the embryo you lay down
968
00:39:46,619 --> 00:39:50,220
these masses of cells which are called
969
00:39:48,300 --> 00:39:52,740
somites which will give rise to your
970
00:39:50,219 --> 00:39:55,019
ribs to the muscles of your thorax and
971
00:39:52,739 --> 00:39:57,118
we managed to reproduce this image you
972
00:39:55,019 --> 00:39:58,739
can see there how this is one of these
973
00:39:57,119 --> 00:40:00,960
gastroes and you can see how they are
974
00:39:58,739 --> 00:40:02,459
they are doing that and what you can see
975
00:40:00,960 --> 00:40:05,579
here in this movie
976
00:40:02,460 --> 00:40:08,039
you can see that over time there is one
977
00:40:05,579 --> 00:40:09,480
more segment attached there is one more
978
00:40:08,039 --> 00:40:11,279
segment the way this is growing is
979
00:40:09,480 --> 00:40:13,260
because these segments are going that's
980
00:40:11,280 --> 00:40:14,820
associated with rhythmic gene expression
981
00:40:13,260 --> 00:40:17,940
that we haven't seen in humans before
982
00:40:14,820 --> 00:40:19,619
and I think it should work here there
983
00:40:17,940 --> 00:40:21,599
you go and you can see as the thing
984
00:40:19,619 --> 00:40:24,059
elongates you get this gene expression
985
00:40:21,599 --> 00:40:26,338
being being pattern and we can reproduce
986
00:40:24,059 --> 00:40:28,559
this in the in the in the dish
987
00:40:26,338 --> 00:40:30,838
so I think that this is going to be very
988
00:40:28,559 --> 00:40:33,179
useful to study and we are collaborating
989
00:40:30,838 --> 00:40:34,980
with a group in in with a colleague to
990
00:40:33,179 --> 00:40:37,440
try to use this to study the origin of
991
00:40:34,980 --> 00:40:39,838
many spinal cord malformations and many
992
00:40:37,440 --> 00:40:41,579
spinal cord things and there is other
993
00:40:39,838 --> 00:40:43,858
people that are using this system to
994
00:40:41,579 --> 00:40:45,359
generate hearts hearts are not just a
995
00:40:43,858 --> 00:40:47,098
group of cells that come and give rise
996
00:40:45,358 --> 00:40:49,920
to the heart it requires the integration
997
00:40:47,099 --> 00:40:52,380
of many different cell types and cell
998
00:40:49,920 --> 00:40:55,079
signals that that are that are very
999
00:40:52,380 --> 00:40:56,820
difficult to generate simply by by
1000
00:40:55,079 --> 00:40:59,640
trying to steal everything to make a
1001
00:40:56,820 --> 00:41:02,099
harder hard is the cooperation of many
1002
00:40:59,639 --> 00:41:04,019
different cell types and and there are
1003
00:41:02,099 --> 00:41:05,940
these are called organoids but but they
1004
00:41:04,019 --> 00:41:08,099
come from embryonic cells and from
1005
00:41:05,940 --> 00:41:09,900
creating this little blueprint of the
1006
00:41:08,099 --> 00:41:13,140
organism that allows the cells to
1007
00:41:09,900 --> 00:41:14,940
interact and to and to generate the the
1008
00:41:13,139 --> 00:41:17,639
the heart
1009
00:41:14,940 --> 00:41:19,858
ten years ago I did give the I mean I
1010
00:41:17,639 --> 00:41:21,838
looked at this and and I was very funny
1011
00:41:19,858 --> 00:41:23,279
I think that's maybe Joachim will
1012
00:41:21,838 --> 00:41:24,960
remember that was the title of the
1013
00:41:23,280 --> 00:41:27,480
lecture genetic Alchemy and the making
1014
00:41:24,960 --> 00:41:30,000
of animal embryos and the last is light
1015
00:41:27,480 --> 00:41:31,679
of that lecture was this that cells are
1016
00:41:30,000 --> 00:41:33,000
the link between the molecules of the
1017
00:41:31,679 --> 00:41:35,399
organism they are the ultimate
1018
00:41:33,000 --> 00:41:37,559
Alchemists I think 10 years later we
1019
00:41:35,400 --> 00:41:39,960
have a lot more evidence that this is
1020
00:41:37,559 --> 00:41:42,119
absolutely the case and that indeed I
1021
00:41:39,960 --> 00:41:44,039
mean you know the the the the the
1022
00:41:42,119 --> 00:41:46,680
elements the cells are the ones that
1023
00:41:44,039 --> 00:41:48,539
integrate all these elements and make a
1024
00:41:46,679 --> 00:41:50,039
a
1025
00:41:48,539 --> 00:41:52,500
an organism
1026
00:41:50,039 --> 00:41:55,320
and I'd like to to finish coming to the
1027
00:41:52,500 --> 00:41:58,019
end with this I like always fantastic
1028
00:41:55,320 --> 00:42:00,660
quotation from Stephen J Gould which
1029
00:41:58,019 --> 00:42:03,719
which to me it says I think it's there
1030
00:42:00,659 --> 00:42:07,098
and it's Aus Reiner of Reagan Uber
1031
00:42:03,719 --> 00:42:07,098
Thrift the evolutions
1032
00:42:21,989 --> 00:42:26,909
[Music]
1033
00:42:23,940 --> 00:42:29,989
foreign
1034
00:42:26,909 --> 00:42:29,989
[Music]
1035
00:42:42,559 --> 00:42:47,880
and with that and reminding that it's
1036
00:42:45,599 --> 00:42:49,800
not just Alchemy I just want to thank
1037
00:42:47,880 --> 00:42:51,130
you for listening to me and I look
1038
00:42:49,800 --> 00:42:51,580
forward to talking with you later
1039
00:42:51,130 --> 00:42:54,889
[Applause]
1040
00:42:51,579 --> 00:42:54,889
[Music]
1041
00:42:55,130 --> 00:43:09,700
[Applause]
77710
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