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[Music]

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our second keynote speaker of the

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conference holds the Chancellor's

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distinguished profession professorship

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in physics at UCSD he's a theoretical

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physicist whose work is wide-ranging and

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whose Twitter bio says I'm interested in

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everything

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before joining UCSD he was at the

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University of Illinois at

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Urbana-Champaign for over 30 years where

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he led the biocomplexity group within

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the Carl R woes Institute for genomic

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biology and where he both founded and

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directed the NASA astrobiology Institute

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for Universal biology his research has

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been highly multidisciplinary ranging

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from condensed matter and hydrodynamics

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to the ecology and evolution of living

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systems among his many accolades Nigel

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received the 2020 leop kadenoff prize

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from the American physical Society for

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quote profound contributions to the

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fields of superconductivity fluid

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turbulence and dynamical pattern

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formation it's been a pleasure to have

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him as a professor and it's a pleasure

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to have him with us here today please

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birthday

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[Applause]

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thank you very much for the kind and

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invitation to speak at Brad Khan I love

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this conference I've sent my students to

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it I've been in it before I think it's

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absolutely wonderful and I was really

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thrilled to see that NASA is still

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supporting it and even to uh to uh to

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catch up with an old friend and

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acquaintance from my days at the NASA

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astrobiology Institute hi Mike so I'm

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going to talk about something that uh

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that by All rights shouldn't exist and I

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don't mean life itself and I mean uh

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Universal aspects of living systems I'm

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a physicist as you heard from the

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introduction and so my approach to

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anything is is ridiculously as simple

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and is almost surely destined for

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failure but we try to fail in a in a

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grand way and at least see what we can

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learn from our attempts to understand uh

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the physical principles that govern uh

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life so I'm going to talk about

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Universal biology the genetic code in

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the first billion years of life on Earth

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and I have uh collaborators my first

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collaborate I want to mention is a Carl

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woes who will feature in this story and

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many of you may know Carl woes he

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discovered the Arca he was a very famous

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evolutionary biologist and he was my

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mentor when I started doing biology

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about 20 years ago

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I was one of my graduate students who

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did a fantastic work on the generic code

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and was in fact also at the University

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of Wisconsin where Alex was as a as a

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student before

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um uh Apache Jaffa is now uh as a in in

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the Netherlands and tomato bianchalani

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is now working in a genotech here in

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California all right so I'm going to

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tell you about work that was done uh

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over the last uh uh 10 or 10 or 15 years

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or so

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through the NASA astrobiology Institute

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and I hope you're going to find it

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interesting if you have any questions

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feel free to interrupt during the during

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the talk especially if it's a

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clarification and I'll be of course be

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happy to take questions as as we go

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through to the end so the thing I want

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to understand is what are the sorts of

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evolutionary transitions that life most

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inevitably pass through this is part of

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a program that the NASA uh discussed in

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The Marvelous astrobiology roadmap from

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about 15 years ago

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trying to understand a universal biology

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and look for Universal characteristics

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of life and the idea is if we can

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understand what features of life on

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Earth are not idiosyncratic but actually

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just something that we should expect

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from another planet and understanding

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these processes understanding these

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transitions may help us to come up with

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uh biosignatures and we'll see that in

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fact there are some prospects for that

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so I want to understand basically can we

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understand some features of Life

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Universal features which you may say may

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not exist but we'll see we'll see it's

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the country and can we understand from

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general dynamical principles without

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necessarily having to worry about all

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the chemical details

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so I'm going to talk about two things in

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this talk I'm going to talk about uh the

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canonical genetic code and that's going

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to be most the most of my talk I will

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talk about biological homochiality

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because it is important as a as a bio

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signature it's been assumed to be a

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biosignature but um but actually we'll

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see in this talk that actually there are

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dynamical reasons for thinking that

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homocolity isn't inevitable outcome of

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living systems

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so I want to first start off though by

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talking about are there any universal

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features in biology and and how should

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we think about them so I'm a physicist

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so I start off by asking is there

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universality in physics so here's an

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example this is thermal conductivity or

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various uh glassy materials this is raw

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data and then when we process it in a

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certain way the data from different

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materials all collapse onto one uh

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Universal curve except for this regime

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over here and so that's something that

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we try to understand if we want to

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understand glassly and glassy materials

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here's another example which is a much

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better one this example is looking at

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the magnetic field or the magnetization

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in a magnet exposed to an external

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magnetic field H at temperature t as you

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go through the ferromagnetic phase

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transition the transition that makes

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stuff be magnetic at low temperatures

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and not magnetic at high temperatures

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and you the data you take from a

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different external magnetic fields

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different uh temperatures and then if

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you process the data in the right way

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all these data from five different

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materials none of which are look

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anything alike all fall onto one

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universal curve and the prediction for

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that curve is the solid line which goes

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embarrassingly close to all the data and

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it has no adjustable parameters

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so that's another example of of scaling

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and universality in physics and you

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might say well this is this is really

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great because what did the physicists do

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they made a model of a magnetic system

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and then they took that model worked out

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its consequences did some calculations

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and then showed that it gave a precise

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prediction in agreement with experiments

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that's what physicists usually do in

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fact it's nothing like that at all but

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actually it is it's a model of a model

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of a model of a model of a model and

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that that does all the work the first

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model is a model of quantum chemistry

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then there's a model of electronic

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structure then there's a model of the

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dipole moment on the electronic spins

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that uses quantum mechanics and then you

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say well quantum mechanics is too hard

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so let's get rid of quantum mechanics

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and then you have a classical and you

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still can't do it and only make some

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sort of approximation that position to

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call Landau Theory and then you you get

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the results that I showed you

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and the thing you want I want you to

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understand the reason why I'm uh

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tormenting you with this physics stuff

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is because every step along the way here

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is a non-systematic approximation you

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cannot justify these approximations

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starting from first principles from the

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Schrodinger equation or whatever else it

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is so the point is here is an example of

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how a ludicrously simple model that has

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no right to actually be able to describe

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reality actually describes it precisely

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and we know in this case why it works it

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works in this case because of a thing

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called renormalization group Theory

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which Ken Wilson won the Nobel Prize for

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inventing in the 1980s and so we

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understand how all these approximations

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that we made throw away stuff that

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really doesn't matter for the thing that

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we were trying to calculate

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so that's the uh so that that tells you

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that it is not impossible to make

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ludicrously simple models and still have

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some understanding of how the system

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actually behaves

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okay so but we're going to of course

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apply that type of modeling philosophy

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uh to biology but first of all let's ask

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another question so for me as a

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physicist I want to know do we learn new

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physics when we study biology or is it

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just insanely complicated Material

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Science are they Universal phenomena do

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they reveal anything important and what

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do we miss by not understanding

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Universal phenomena okay I'm going to

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show you that the high Universal

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phenomena some of you will be very

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surprised at the examples I'm going to

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show you I'm also going to show you that

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if we don't understand these Universal

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phenomena not only can we not understand

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how life started at all and how it

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evolved we certainly can't understand

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how to do things like respond to a

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pandemic or deal with antibiotic

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resistance or herbicide doesn't or

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Cancer all of these things depend on

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understanding Evolution and these

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Universal properties

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okay so let's talk about Universal

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biology so so uh let me give you an

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example here

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so this was uh this was a headline on

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the NASA website at some point uh 2013

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about 10 years ago mystery of the

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missing waves on Titan so basically

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people knew that from looking at the uh

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at uh the flow mechanics and and the

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atmosphere of Titan that there should be

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uh waves on on the surface of Titan

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um and uh and uh so there was a mystery

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they weren't there we couldn't see them

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nobody knew why and then about a year

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later uh Cassini Spies The wind-rippled

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Waves uh on Titan so so suddenly sign of

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relief thank goodness you you can sleep

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at night we found the waves on the

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surface of the oceans of Titan okay so

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that's a real real headline okay here's

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what here's one that you have Okay so I

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just forget I forgot this we know the

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waves on the ocean of Titan are missing

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because there's a general theory of

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two-phase fluid flow interfaces but

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predict waves and the dispersion

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characteristics so we knew what to look

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for okay here's a headline that you

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didn't see

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mystery of the missing life on Titan and

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then definitely not this one Cassini

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Spies The long-sort Life on Titan okay

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anybody seen that headline it never

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occurred okay and it's a joke right

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because it's a joke because we don't

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know if there's a missing life because

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we don't have a theory that predicts the

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existence of Life as a physical

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phenomena so that's the first thing why

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does life as a phenomenon exist and we

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certainly don't understand what sort of

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Life can exist in different uh

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environments

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so so

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back to Cassini Cassini May indeed have

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00:10:57,410 --> 00:10:55,740
actually seen life

279
00:10:59,650 --> 00:10:57,420
but not on Titan

280
00:11:02,150 --> 00:10:59,660
it may have seen life

281
00:11:04,310 --> 00:11:02,160
okay so how many people here know about

282
00:11:07,250 --> 00:11:04,320
Enceladus

283
00:11:08,990 --> 00:11:07,260
great a lot more a lot more people than

284
00:11:11,870 --> 00:11:09,000
word as a typical physics colloquium

285
00:11:15,170 --> 00:11:11,880
right so so good so so as you know

286
00:11:17,150 --> 00:11:15,180
insolidos is a is an isolated World

287
00:11:20,769 --> 00:11:17,160
orbiting Saturn

288
00:11:23,329 --> 00:11:20,779
um it has a global ocean of liquid water

289
00:11:25,730 --> 00:11:23,339
underneath the ice and we know that

290
00:11:27,530 --> 00:11:25,740
because we can see how it wobbles and

291
00:11:29,170 --> 00:11:27,540
because of the way it wobbles we can

292
00:11:32,030 --> 00:11:29,180
detect there must be life underneath

293
00:11:34,970 --> 00:11:32,040
there must be water underneath and it

294
00:11:37,310 --> 00:11:34,980
also obligingly has a crack in the ice

295
00:11:38,990 --> 00:11:37,320
lots of cracks and so water squirts out

296
00:11:40,610 --> 00:11:39,000
through the cracks and so you've got a

297
00:11:42,710 --> 00:11:40,620
fountain a huge fountain and you can fly

298
00:11:45,470 --> 00:11:42,720
satellites through the fountain and you

299
00:11:46,670 --> 00:11:45,480
can look at the water that you uh that

300
00:11:49,370 --> 00:11:46,680
you pick up

301
00:11:51,470 --> 00:11:49,380
and that water you can analyze it's

302
00:11:53,329 --> 00:11:51,480
chemistry and its chemistry looks very

303
00:11:55,610 --> 00:11:53,339
similar to what we might see as an

304
00:11:58,910 --> 00:11:55,620
alkaline hydrothermal vent here on Earth

305
00:12:01,670 --> 00:11:58,920
so we Cassini wasn't instrumented for

306
00:12:04,550 --> 00:12:01,680
looking at life but we may have seen

307
00:12:07,069 --> 00:12:04,560
some signatures of life through that

308
00:12:12,530 --> 00:12:09,769
so what is what is also biology well

309
00:12:14,389 --> 00:12:12,540
Universal biology is the idea that we

310
00:12:16,550 --> 00:12:14,399
are interested in general principles and

311
00:12:18,829 --> 00:12:16,560
not specific carbon chemistry details

312
00:12:20,449 --> 00:12:18,839
and so we want to develop a theory of

313
00:12:22,730 --> 00:12:20,459
universal biology divorced from

314
00:12:25,130 --> 00:12:22,740
idiosyncratic details of the actual

315
00:12:27,970 --> 00:12:25,140
chemistry and the and the geological

316
00:12:31,250 --> 00:12:27,980
context and so on and this will involve

317
00:12:33,710 --> 00:12:31,260
abstractions and and we use abstractions

318
00:12:36,530 --> 00:12:33,720
all the time in in biology and we'll

319
00:12:39,170 --> 00:12:36,540
talk about one of those in a minute

320
00:12:40,910 --> 00:12:39,180
so this slide is pretty much all we know

321
00:12:43,790 --> 00:12:40,920
about Universal biology

322
00:12:46,910 --> 00:12:43,800
so are you looking at it carefully

323
00:12:49,190 --> 00:12:46,920
there's not much there so let's talk

324
00:12:51,530 --> 00:12:49,200
instead about something where we do have

325
00:12:52,730 --> 00:12:51,540
an understanding and that is universal

326
00:12:54,889 --> 00:12:52,740
computation

327
00:12:57,230 --> 00:12:54,899
so I want to tell you now about what we

328
00:12:59,829 --> 00:12:57,240
what a universal biology would look like

329
00:13:03,230 --> 00:12:59,839
if we could do it and we use as a Model

330
00:13:04,610 --> 00:13:03,240
A computer so here is a picture of my

331
00:13:05,690 --> 00:13:04,620
computer or something close to my

332
00:13:10,970 --> 00:13:05,700
computer

333
00:13:12,530 --> 00:13:10,980
see a few hundred miles up the road at

334
00:13:15,170 --> 00:13:12,540
the Museum of computation in Mountain

335
00:13:17,269 --> 00:13:15,180
View or in my case I saw it at the

336
00:13:19,069 --> 00:13:17,279
science museum in London this is a

337
00:13:21,710 --> 00:13:19,079
computer made out of COG wheels and

338
00:13:24,470 --> 00:13:21,720
springs designed and partially built by

339
00:13:28,490 --> 00:13:24,480
George Babbage in the 1900s it is the

340
00:13:30,590 --> 00:13:28,500
authentic steampunk artifact

341
00:13:33,590 --> 00:13:30,600
these two things are the same

342
00:13:36,530 --> 00:13:33,600
they're the same algorithmically this

343
00:13:38,930 --> 00:13:36,540
thing over here the left hand side is a

344
00:13:41,629 --> 00:13:38,940
computer and you know that it's uh not

345
00:13:43,850 --> 00:13:41,639
uh just a shiny chunk of glass plastic

346
00:13:45,050 --> 00:13:43,860
and silicon it's actually a universal

347
00:13:47,210 --> 00:13:45,060
turing machine

348
00:13:48,889 --> 00:13:47,220
the thing on the right is also a turing

349
00:13:51,050 --> 00:13:48,899
machine because it has conditional

350
00:13:52,550 --> 00:13:51,060
branching in its instruction set and so

351
00:13:55,490 --> 00:13:52,560
it can be shown that it can be mapped

352
00:13:56,769 --> 00:13:55,500
onto a universal turing machine so in

353
00:13:58,970 --> 00:13:56,779
fact the two things are the same

354
00:14:00,530 --> 00:13:58,980
although one of them is at many times

355
00:14:02,090 --> 00:14:00,540
faster than the other

356
00:14:04,430 --> 00:14:02,100
so the turing machine with an online

357
00:14:06,650 --> 00:14:04,440
architecture is really what a computer

358
00:14:10,009 --> 00:14:06,660
is and we have Hardware to instantiate

359
00:14:12,590 --> 00:14:10,019
uh that uh that algorithm so the medium

360
00:14:14,930 --> 00:14:12,600
is not the message here is John Von

361
00:14:16,970 --> 00:14:14,940
Neumann standing in front of another

362
00:14:19,610 --> 00:14:16,980
computer that he built at The Institute

363
00:14:21,470 --> 00:14:19,620
for advanced study in the 1950s in this

364
00:14:24,710 --> 00:14:21,480
computer it's built out of thermionic

365
00:14:27,110 --> 00:14:24,720
valves it's built out of relays and

366
00:14:28,910 --> 00:14:27,120
switches and so neither this nor this

367
00:14:31,910 --> 00:14:28,920
we're seeing here the evolution of

368
00:14:33,710 --> 00:14:31,920
computational Hardware but in all of

369
00:14:35,210 --> 00:14:33,720
these machines they all do the same

370
00:14:37,250 --> 00:14:35,220
thing they're all Universal Turing

371
00:14:39,290 --> 00:14:37,260
machines and so we're looking at life we

372
00:14:42,050 --> 00:14:39,300
should be thinking about life as making

373
00:14:45,050 --> 00:14:42,060
a progression as you see over here but

374
00:14:46,550 --> 00:14:45,060
executing the same sort of algorithmic

375
00:14:49,250 --> 00:14:46,560
processes

376
00:14:51,829 --> 00:14:49,260
now these are new physical laws in in

377
00:14:53,269 --> 00:14:51,839
biology well uh Schrodinger and Dell

378
00:14:55,610 --> 00:14:53,279
Brooke were the first physicists to work

379
00:14:57,650 --> 00:14:55,620
in biology and their partial motivation

380
00:14:59,389 --> 00:14:57,660
was to find new physical laws they were

381
00:15:02,030 --> 00:14:59,399
thinking about quantum mechanics in the

382
00:15:03,590 --> 00:15:02,040
1930s as they might see some deviations

383
00:15:07,730 --> 00:15:03,600
from quantum mechanics or something like

384
00:15:09,110 --> 00:15:07,740
that but today we not many people well

385
00:15:12,410 --> 00:15:09,120
some people think that could be still

386
00:15:14,329 --> 00:15:12,420
true but most of us think that uh

387
00:15:16,189 --> 00:15:14,339
big question is trying to understand

388
00:15:19,129 --> 00:15:16,199
emergence and the existence of life

389
00:15:22,210 --> 00:15:19,139
itself how is it that matter at

390
00:15:25,189 --> 00:15:22,220
molecules and atoms are self-organize

391
00:15:27,470 --> 00:15:25,199
hierarchically create replicating and

392
00:15:30,170 --> 00:15:27,480
evolvable structures we don't have a

393
00:15:32,389 --> 00:15:30,180
clue about how that happens how do

394
00:15:33,949 --> 00:15:32,399
molecules come to life so if you want to

395
00:15:36,050 --> 00:15:33,959
understand biology in the same way that

396
00:15:38,329 --> 00:15:36,060
we understand physical phenomena we need

397
00:15:40,970 --> 00:15:38,339
to understand the existence and not just

398
00:15:42,530 --> 00:15:40,980
the specific realization of of living

399
00:15:44,269 --> 00:15:42,540
systems

400
00:15:46,910 --> 00:15:44,279
and I'm going to take the perspective

401
00:15:49,129 --> 00:15:46,920
here that living systems are dynamical

402
00:15:50,210 --> 00:15:49,139
systems that are able to reprogram

403
00:15:52,009 --> 00:15:50,220
themselves

404
00:15:54,590 --> 00:15:52,019
so let's think about that

405
00:15:56,870 --> 00:15:54,600
so here is the uh here is the fortune

406
00:15:59,090 --> 00:15:56,880
cookie the program is the data the data

407
00:16:01,970 --> 00:15:59,100
is the program okay this is Niels

408
00:16:04,370 --> 00:16:01,980
barricelli who was uh the first person

409
00:16:06,889 --> 00:16:04,380
to write a computer virus he was working

410
00:16:09,050 --> 00:16:06,899
at The Institute for advanced study and

411
00:16:10,910 --> 00:16:09,060
in the day while John Von Neumann was

412
00:16:13,730 --> 00:16:10,920
using the computer one of the first

413
00:16:16,310 --> 00:16:13,740
computers to uh solve the equations of

414
00:16:18,889 --> 00:16:16,320
hydrodynamics to design uh hydrogen

415
00:16:21,430 --> 00:16:18,899
bombs uh Niels banacelli went in at

416
00:16:24,110 --> 00:16:21,440
night and made a

417
00:16:26,990 --> 00:16:24,120
computer viruses and then had them

418
00:16:29,689 --> 00:16:27,000
compete and and evolve with each other

419
00:16:32,269 --> 00:16:29,699
inside a fixed ecosystem which was the

420
00:16:34,670 --> 00:16:32,279
memory of the of the computer

421
00:16:37,910 --> 00:16:34,680
and here he understood what he was

422
00:16:40,090 --> 00:16:37,920
seeing here was uh was actually being of

423
00:16:43,189 --> 00:16:40,100
the phenomena that we see in evolving

424
00:16:45,650 --> 00:16:43,199
evolvable ecosystems

425
00:16:47,749 --> 00:16:45,660
so what do self-programming systems uh

426
00:16:50,389 --> 00:16:47,759
can do well living systems have the

427
00:16:52,910 --> 00:16:50,399
capacity to evolve and evolving systems

428
00:16:55,249 --> 00:16:52,920
can reprogram themselves so they're able

429
00:16:57,889 --> 00:16:55,259
to respond to perturbations by creating

430
00:17:00,350 --> 00:16:57,899
new functionality that is the defining

431
00:17:01,610 --> 00:17:00,360
characteristic of living systems and

432
00:17:03,829 --> 00:17:01,620
this is very different from physical

433
00:17:06,470 --> 00:17:03,839
systems or engineered systems which are

434
00:17:09,470 --> 00:17:06,480
by a fixed or predetermined uh equation

435
00:17:11,390 --> 00:17:09,480
of motion or or behavior so the future

436
00:17:14,150 --> 00:17:11,400
state of an evolvable system is

437
00:17:15,710 --> 00:17:14,160
inherently unpredictable and never maybe

438
00:17:18,470 --> 00:17:15,720
girdle undecidable don't worry about

439
00:17:20,449 --> 00:17:18,480
that and so this this uh this this

440
00:17:23,270 --> 00:17:20,459
feature means that it's very difficult

441
00:17:25,549 --> 00:17:23,280
to control evolving systems and we'll

442
00:17:27,230 --> 00:17:25,559
come to that we'll turn to that at the

443
00:17:30,169 --> 00:17:27,240
end of The Talk

444
00:17:33,049 --> 00:17:30,179
now what do most biologists do well most

445
00:17:34,850 --> 00:17:33,059
biologists uh do something rather

446
00:17:36,890 --> 00:17:34,860
strange you could call it the inverse

447
00:17:40,010 --> 00:17:36,900
problem imagine that you came down from

448
00:17:42,350 --> 00:17:40,020
Mars and I gave you my computer and you

449
00:17:45,110 --> 00:17:42,360
had no idea what this thing was what

450
00:17:47,270 --> 00:17:45,120
would you be able to do to figure out

451
00:17:49,490 --> 00:17:47,280
that this thing is not just a an

452
00:17:50,630 --> 00:17:49,500
expensive door stop but actually as a

453
00:17:52,310 --> 00:17:50,640
universal turing machine with a

454
00:17:54,049 --> 00:17:52,320
vulnerable human architecture it would

455
00:17:56,810 --> 00:17:54,059
be very very different very very

456
00:17:59,029 --> 00:17:56,820
difficult to figure out from the

457
00:18:01,190 --> 00:17:59,039
electronic circuits and the hardware and

458
00:18:04,070 --> 00:18:01,200
so on but that's what the thing actually

459
00:18:06,169 --> 00:18:04,080
did and so what we want to do in biology

460
00:18:08,330 --> 00:18:06,179
is we have the inverse problem the

461
00:18:10,370 --> 00:18:08,340
biology is already created and we want

462
00:18:13,310 --> 00:18:10,380
to understand one is the abstract theory

463
00:18:14,810 --> 00:18:13,320
of which it is an instantiation and that

464
00:18:16,730 --> 00:18:14,820
abstract Theory would underline all

465
00:18:19,310 --> 00:18:16,740
systems that exhibit the characteristics

466
00:18:21,169 --> 00:18:19,320
of life so could you could you if you

467
00:18:22,730 --> 00:18:21,179
didn't know about the universal Turing

468
00:18:25,789 --> 00:18:22,740
machines with a Von Neumann architecture

469
00:18:28,850 --> 00:18:25,799
could you deduce a theoretical framework

470
00:18:31,250 --> 00:18:28,860
just by somebody giving you to a highly

471
00:18:33,289 --> 00:18:31,260
evolved computer

472
00:18:35,210 --> 00:18:33,299
okay we've talked about abstraction so

473
00:18:37,549 --> 00:18:35,220
now let's get down to a real abstraction

474
00:18:40,909 --> 00:18:37,559
so I want to talk about the genetic code

475
00:18:43,490 --> 00:18:40,919
and I figuratively find that people from

476
00:18:45,049 --> 00:18:43,500
various wide-ranging audiences don't

477
00:18:47,270 --> 00:18:45,059
quite know what I mean when I talk about

478
00:18:50,750 --> 00:18:47,280
the genetic code so let's just take a

479
00:18:54,230 --> 00:18:50,760
pause to uh to go through that so in the

480
00:18:56,750 --> 00:18:54,240
modern world as you know DNA contains

481
00:19:00,789 --> 00:18:56,760
our genome and the DNA is built from

482
00:19:04,250 --> 00:19:00,799
four nucleotide bases RNA polymerase

483
00:19:07,549 --> 00:19:04,260
reads the the gene coding segments some

484
00:19:09,770 --> 00:19:07,559
spits out mRNA that's also built from

485
00:19:12,350 --> 00:19:09,780
four nucleotide bases and then the

486
00:19:14,690 --> 00:19:12,360
ribosomes go along with the MRNA and

487
00:19:17,150 --> 00:19:14,700
they spit out the proteins and they

488
00:19:18,610 --> 00:19:17,160
choose which proteins should go into the

489
00:19:21,169 --> 00:19:18,620
protein

490
00:19:23,750 --> 00:19:21,179
the issues which amino acids should go

491
00:19:25,970 --> 00:19:23,760
into the proteins from the code that

492
00:19:28,430 --> 00:19:25,980
they're reading from the from the MRNA

493
00:19:31,029 --> 00:19:28,440
and the way they read that code is they

494
00:19:33,950 --> 00:19:31,039
read it in triplets so

495
00:19:36,890 --> 00:19:33,960
a-u-g-a-c-a GGG and so on these are

496
00:19:39,830 --> 00:19:36,900
codon Triplets of of

497
00:19:42,049 --> 00:19:39,840
of nucleotide bases and the genetic code

498
00:19:46,850 --> 00:19:42,059
it tells you if you read this thing here

499
00:19:48,830 --> 00:19:46,860
what amino acid is going to go into the

500
00:19:51,169 --> 00:19:48,840
into the protein that you're building

501
00:19:53,450 --> 00:19:51,179
and so this is a sort of cartoon here of

502
00:19:54,850 --> 00:19:53,460
the whole translation process and you're

503
00:19:58,789 --> 00:19:54,860
supposed to think of this huge machine

504
00:20:01,010 --> 00:19:58,799
uh moving along like so

505
00:20:03,470 --> 00:20:01,020
so just to summarize what the genetic

506
00:20:05,210 --> 00:20:03,480
code is it's a map it's a map used by

507
00:20:08,450 --> 00:20:05,220
the ribosome to translate the message

508
00:20:11,570 --> 00:20:08,460
from n1a Triplets of four bases into the

509
00:20:14,810 --> 00:20:11,580
20 amino acids of life and uh and and

510
00:20:18,590 --> 00:20:14,820
we're going to discuss uh how that code

511
00:20:21,289 --> 00:20:18,600
evolved now this is Carl woes sitting uh

512
00:20:23,150 --> 00:20:21,299
in his office on and on the New York

513
00:20:27,890 --> 00:20:23,160
Times front page Thursday November the

514
00:20:29,870 --> 00:20:27,900
3rd 1977. why is he there well it says

515
00:20:32,990 --> 00:20:29,880
here scientists discover a form of life

516
00:20:35,090 --> 00:20:33,000
that predates higher organisms and I

517
00:20:37,370 --> 00:20:35,100
guess fake news is not just a new

518
00:20:39,169 --> 00:20:37,380
invention it happened uh it happened

519
00:20:42,049 --> 00:20:39,179
back in the 70s as well this is

520
00:20:44,210 --> 00:20:42,059
partially true not not not not quite

521
00:20:47,930 --> 00:20:44,220
true but in any case he had discovered

522
00:20:50,630 --> 00:20:47,940
uh the uh the archaea so let me just

523
00:20:53,029 --> 00:20:50,640
tell you uh what he had discovered so

524
00:20:56,210 --> 00:20:53,039
this is the tree of life this is from a

525
00:20:58,310 --> 00:20:56,220
paper by Norm Pace in 97

526
00:21:01,610 --> 00:20:58,320
now you can see here there are three

527
00:21:05,090 --> 00:21:01,620
domains the bacteria the archaea and the

528
00:21:08,270 --> 00:21:05,100
eukaryotes you are over here virtually

529
00:21:10,370 --> 00:21:08,280
everything else here is is microbial and

530
00:21:12,650 --> 00:21:10,380
uh the and this this this phylogenetic

531
00:21:14,930 --> 00:21:12,660
tree is a kind of map it's built it's

532
00:21:17,330 --> 00:21:14,940
been elaborated on by now and there's

533
00:21:19,490 --> 00:21:17,340
there's uh it's it's out of date and

534
00:21:21,650 --> 00:21:19,500
there's uh some debates about whether

535
00:21:23,330 --> 00:21:21,660
there's two domains or three domains and

536
00:21:25,970 --> 00:21:23,340
so on and so forth but fundamentally

537
00:21:27,950 --> 00:21:25,980
this is what uh what he discovered now

538
00:21:31,190 --> 00:21:27,960
how did he uh how did he discover this

539
00:21:34,909 --> 00:21:31,200
well what he did was looked for patterns

540
00:21:37,549 --> 00:21:34,919
in uh in in molecular sequences from

541
00:21:39,710 --> 00:21:37,559
parts of the ribosome the 16s small

542
00:21:42,110 --> 00:21:39,720
subunit of the ribosome and by looking

543
00:21:44,510 --> 00:21:42,120
at those sequences was able to look at

544
00:21:46,909 --> 00:21:44,520
do the what what today would call

545
00:21:48,830 --> 00:21:46,919
comparative genomics and map out uh the

546
00:21:51,350 --> 00:21:48,840
the this tree of life

547
00:21:53,510 --> 00:21:51,360
and some around here is uh the last

548
00:21:56,570 --> 00:21:53,520
Universal common ancestor or the last

549
00:21:58,310 --> 00:21:56,580
Universal common ancestral community

550
00:22:02,510 --> 00:21:58,320
so this is the paper that they wrote in

551
00:22:04,549 --> 00:22:02,520
in 1977 and uh the the mystery that this

552
00:22:07,549 --> 00:22:04,559
uh this this work

553
00:22:09,830 --> 00:22:07,559
um uh left us with is the following we

554
00:22:11,510 --> 00:22:09,840
know that the planet is about 4.6

555
00:22:14,690 --> 00:22:11,520
billion years old

556
00:22:17,990 --> 00:22:14,700
we know that the the last Universal

557
00:22:19,850 --> 00:22:18,000
common ancestor even then was uh was

558
00:22:22,430 --> 00:22:19,860
dated to at least three billion years

559
00:22:24,470 --> 00:22:22,440
today we think it's about 3.6 3.8

560
00:22:27,890 --> 00:22:24,480
billion years depending on who you're

561
00:22:28,549 --> 00:22:27,900
talking to based on uh static

562
00:22:37,730 --> 00:22:28,559
um

563
00:22:40,490 --> 00:22:37,740
you know if they're various geological

564
00:22:41,330 --> 00:22:40,500
evidence and and so on for matalites and

565
00:22:43,610 --> 00:22:41,340
so on

566
00:22:46,669 --> 00:22:43,620
um so so basically but something like

567
00:22:49,549 --> 00:22:46,679
this but but the point that that woes

568
00:22:51,710 --> 00:22:49,559
and fox were making is that a lot of the

569
00:22:53,570 --> 00:22:51,720
of the time the planet was inhospitable

570
00:22:57,049 --> 00:22:53,580
to life you had less than a billion

571
00:22:58,730 --> 00:22:57,059
years in which life could evolve and it

572
00:23:01,310 --> 00:22:58,740
evolved the complexity of something like

573
00:23:03,350 --> 00:23:01,320
the modern cell in less than a billion

574
00:23:05,090 --> 00:23:03,360
years and then after that there wasn't

575
00:23:07,370 --> 00:23:05,100
very much cellular Evolution maybe

576
00:23:08,930 --> 00:23:07,380
dinosaurs or multicellularity and things

577
00:23:10,789 --> 00:23:08,940
like that but from a point of view of

578
00:23:12,289 --> 00:23:10,799
the architecture of the cell uh very

579
00:23:16,070 --> 00:23:12,299
little

580
00:23:17,750 --> 00:23:16,080
so so what uh What uh uh woes and fox uh

581
00:23:20,630 --> 00:23:17,760
here's some pictures of them doing their

582
00:23:24,169 --> 00:23:20,640
work at the time uh what they what they

583
00:23:27,049 --> 00:23:24,179
uh what they wrote was that uh that it

584
00:23:29,450 --> 00:23:27,059
wasn't that the evolution speeded up at

585
00:23:31,970 --> 00:23:29,460
the beginning and then slowed down uh

586
00:23:33,830 --> 00:23:31,980
the last Universal common ancestor what

587
00:23:37,070 --> 00:23:33,840
they wrote was that actually maybe

588
00:23:38,750 --> 00:23:37,080
Evolution had a different character

589
00:23:41,090 --> 00:23:38,760
um in its early phases and we're going

590
00:23:43,370 --> 00:23:41,100
to see that there is evidence for that

591
00:23:45,289 --> 00:23:43,380
now what kind of different mode could

592
00:23:48,049 --> 00:23:45,299
there be of evolution

593
00:23:50,390 --> 00:23:48,059
well most of us when you think about

594
00:23:52,970 --> 00:23:50,400
Evolution you think about what is really

595
00:23:55,190 --> 00:23:52,980
called vertical Evolution that is you

596
00:23:56,810 --> 00:23:55,200
have your genes you give your genes to

597
00:23:58,610 --> 00:23:56,820
your children they give their genes to

598
00:24:01,430 --> 00:23:58,620
their children and so on and so forth

599
00:24:04,070 --> 00:24:01,440
and so there's a a transfer of genetic

600
00:24:05,930 --> 00:24:04,080
material of genes through the

601
00:24:08,690 --> 00:24:05,940
generations

602
00:24:11,210 --> 00:24:08,700
horizontal Gene transfer is a different

603
00:24:13,909 --> 00:24:11,220
thing altogether horizontal Gene

604
00:24:16,250 --> 00:24:13,919
transfer is the transfer of genes from

605
00:24:19,250 --> 00:24:16,260
one organism to another that it is not

606
00:24:22,909 --> 00:24:19,260
related to and I and this is uh this is

607
00:24:24,770 --> 00:24:22,919
what happens uh in in bacteria there's

608
00:24:27,409 --> 00:24:24,780
three ways that this can are known to

609
00:24:29,450 --> 00:24:27,419
happen here on Earth genes can be

610
00:24:31,970 --> 00:24:29,460
transmitted through viruses through

611
00:24:34,070 --> 00:24:31,980
direct contact or through uptake of free

612
00:24:37,730 --> 00:24:34,080
DNA from the environment so the question

613
00:24:40,190 --> 00:24:37,740
is what happens when all the all the

614
00:24:42,649 --> 00:24:40,200
microbes in the world do this what

615
00:24:45,590 --> 00:24:42,659
happens when all of early life is able

616
00:24:47,450 --> 00:24:45,600
to uh to transfer genes

617
00:24:50,950 --> 00:24:47,460
okay let me just give you two quick uh

618
00:24:53,690 --> 00:24:50,960
anecdotes about that so this here is a

619
00:24:56,630 --> 00:24:53,700
cyanophage it's a it's a phage that's in

620
00:24:58,270 --> 00:24:56,640
in facts uh prochlorococcus one of the

621
00:25:01,789 --> 00:24:58,280
most abundant organisms of the planet

622
00:25:04,669 --> 00:25:01,799
and uh and and this here is a is a

623
00:25:07,610 --> 00:25:04,679
phylogenetic tree of the of a gene that

624
00:25:10,909 --> 00:25:07,620
is involved in the in photosystem too

625
00:25:12,049 --> 00:25:10,919
and if you can read phylogenetic trees

626
00:25:14,330 --> 00:25:12,059
it doesn't matter if you can't but if

627
00:25:16,850 --> 00:25:14,340
you can read them what this shows you is

628
00:25:19,669 --> 00:25:16,860
that this Gene was transferred back and

629
00:25:23,990 --> 00:25:19,679
forth between a virus and the bacterial

630
00:25:26,450 --> 00:25:24,000
host multiple times during evolution

631
00:25:28,430 --> 00:25:26,460
and in fact the the the group that

632
00:25:31,310 --> 00:25:28,440
discovered this solid metal in

633
00:25:34,070 --> 00:25:31,320
planetism's lab they wrote that to host

634
00:25:35,630 --> 00:25:34,080
like genes acquired by phages undergo a

635
00:25:38,090 --> 00:25:35,640
period of diversification and phase

636
00:25:40,909 --> 00:25:38,100
genomes and serve as a genetic reservoir

637
00:25:43,370 --> 00:25:40,919
for their hosts so the idea is I have a

638
00:25:46,730 --> 00:25:43,380
gene that is a photosynthesis Gene that

639
00:25:49,070 --> 00:25:46,740
that Gene helps in photosynthesis that

640
00:25:50,990 --> 00:25:49,080
Gene gets transferred by a viral attack

641
00:25:54,529 --> 00:25:51,000
to phage

642
00:25:57,529 --> 00:25:54,539
in phage that Gene can evolve much more

643
00:25:59,149 --> 00:25:57,539
rapidly because there are less proof

644
00:26:02,570 --> 00:25:59,159
readings and things like this that go on

645
00:26:06,049 --> 00:26:02,580
in Phase replication so as a result the

646
00:26:08,090 --> 00:26:06,059
bacteria are get infected by new genes

647
00:26:09,710 --> 00:26:08,100
from the phage but those genes have

648
00:26:11,990 --> 00:26:09,720
evolved much more rapidly in the phase

649
00:26:14,090 --> 00:26:12,000
than the wooden bacteria and so there's

650
00:26:17,810 --> 00:26:14,100
a there's a mechanism by which you could

651
00:26:20,210 --> 00:26:17,820
have rapid evolutionary change mediated

652
00:26:21,950 --> 00:26:20,220
by phage or by other mechanisms of

653
00:26:23,870 --> 00:26:21,960
horizontal Gene transfer and because

654
00:26:26,330 --> 00:26:23,880
that is a network effect it's

655
00:26:29,149 --> 00:26:26,340
extraordinarily efficient

656
00:26:30,890 --> 00:26:29,159
and uh and um I'm not going to have time

657
00:26:33,289 --> 00:26:30,900
to show you work that we did actually

658
00:26:36,049 --> 00:26:33,299
modeling that that whole process

659
00:26:38,390 --> 00:26:36,059
now this is the uh the uh with that

660
00:26:40,490 --> 00:26:38,400
having said that and told you about an

661
00:26:42,710 --> 00:26:40,500
other mode of transfer let me now tell

662
00:26:45,110 --> 00:26:42,720
you about the genetic code so here is

663
00:26:48,470 --> 00:26:45,120
the genetic code so the way you read it

664
00:26:50,450 --> 00:26:48,480
is like this you you and then the First

665
00:26:52,669 --> 00:26:50,460
Column up here so that brings you to

666
00:26:54,049 --> 00:26:52,679
this cell that's phenylalanyl in and you

667
00:26:56,990 --> 00:26:54,059
can do the same thing for all of these

668
00:27:00,169 --> 00:26:57,000
of course it's a it's a it's a code of

669
00:27:02,090 --> 00:27:00,179
triplets of for a nucleotide basis an

670
00:27:03,590 --> 00:27:02,100
alphabet of four so in principle there

671
00:27:05,990 --> 00:27:03,600
are 64 things you could code for but

672
00:27:09,230 --> 00:27:06,000
there's only 20 amino acids so the code

673
00:27:11,810 --> 00:27:09,240
is redundant and uh but it's not just

674
00:27:13,310 --> 00:27:11,820
redundant it also has structure so if

675
00:27:15,169 --> 00:27:13,320
you look here these are the most

676
00:27:16,970 --> 00:27:15,179
hydrophobic amino acids these are the

677
00:27:18,289 --> 00:27:16,980
most hydrophilic ones and you can see

678
00:27:20,930 --> 00:27:18,299
that in the way that this code is

679
00:27:25,549 --> 00:27:20,940
written there is structure here

680
00:27:28,070 --> 00:27:25,559
the amino acids have are segmented in

681
00:27:28,850 --> 00:27:28,080
this in this uh in this genetic code

682
00:27:31,130 --> 00:27:28,860
table

683
00:27:34,730 --> 00:27:31,140
so one of the things that Carl was did

684
00:27:36,049 --> 00:27:34,740
back in the 1960s was to measure a

685
00:27:38,330 --> 00:27:36,059
quantity that he called polar

686
00:27:39,830 --> 00:27:38,340
acquirement which measured this balance

687
00:27:42,409 --> 00:27:39,840
between hydrophobicity and

688
00:27:45,289 --> 00:27:42,419
hydrophilicity and gave a single number

689
00:27:48,169 --> 00:27:45,299
which is small upper over here and large

690
00:27:51,710 --> 00:27:48,179
over here and and so he was able to

691
00:27:54,529 --> 00:27:51,720
quantify that chemical difference

692
00:27:56,870 --> 00:27:54,539
now you all know that the genetic code

693
00:27:58,130 --> 00:27:56,880
is pretty much Universal it's not

694
00:27:59,870 --> 00:27:58,140
exactly Universal there's small

695
00:28:01,850 --> 00:27:59,880
variations and stop codons but it's

696
00:28:02,930 --> 00:28:01,860
basically Universal but what I want to

697
00:28:04,549 --> 00:28:02,940
tell you now is something that you may

698
00:28:07,730 --> 00:28:04,559
not know about and that is that the

699
00:28:09,830 --> 00:28:07,740
genetic code is pretty much optimal in

700
00:28:12,049 --> 00:28:09,840
minimizing errors

701
00:28:14,510 --> 00:28:12,059
okay so let's let's uh let's discuss

702
00:28:16,190 --> 00:28:14,520
what we mean by that so let's suppose

703
00:28:18,769 --> 00:28:16,200
that you were given the task of of

704
00:28:21,769 --> 00:28:18,779
Designing intelligently a genetic code

705
00:28:23,930 --> 00:28:21,779
okay well you might say well translation

706
00:28:25,789 --> 00:28:23,940
is fundamentally important to a cellular

707
00:28:28,310 --> 00:28:25,799
operation so we want to make sure that

708
00:28:31,909 --> 00:28:28,320
any any mistakes any mutations or any

709
00:28:33,529 --> 00:28:31,919
misreadings give you an amino acid which

710
00:28:35,690 --> 00:28:33,539
is pretty close in chemical properties

711
00:28:37,190 --> 00:28:35,700
to the one that you should have got and

712
00:28:40,010 --> 00:28:37,200
if you could design a code like that

713
00:28:42,950 --> 00:28:40,020
then then that would be great okay it

714
00:28:46,310 --> 00:28:42,960
would be robust to errors so the

715
00:28:49,010 --> 00:28:46,320
question is is our genetic code like

716
00:28:51,529 --> 00:28:49,020
that I'm going to show you that it is

717
00:28:53,090 --> 00:28:51,539
so here's the actual genetic code so

718
00:28:55,669 --> 00:28:53,100
what you can do is you can make in the

719
00:28:58,130 --> 00:28:55,679
computer alternative genetic codes just

720
00:28:59,990 --> 00:28:58,140
by permuting the labels so here I'm

721
00:29:02,149 --> 00:29:00,000
permuting the label so I get new codes

722
00:29:04,310 --> 00:29:02,159
I'll be it with the same pattern of

723
00:29:06,890 --> 00:29:04,320
degeneracy there's 20 factorial which is

724
00:29:08,930 --> 00:29:06,900
about 10 to the 18 possible genetic code

725
00:29:11,090 --> 00:29:08,940
that you could have in the computer

726
00:29:14,930 --> 00:29:11,100
okay so now I can say all right I've

727
00:29:17,269 --> 00:29:14,940
made this whole Suite of genetic codes

728
00:29:20,389 --> 00:29:17,279
how good are they at minimizing errors

729
00:29:22,970 --> 00:29:20,399
and uh and there's a way that you can

730
00:29:25,430 --> 00:29:22,980
you can compute that and I'm not going

731
00:29:27,049 --> 00:29:25,440
to go into the exact metric that one

732
00:29:29,210 --> 00:29:27,059
uses

733
00:29:31,669 --> 00:29:29,220
so there's a way that one can do that so

734
00:29:34,430 --> 00:29:31,679
then one can ask well what should be the

735
00:29:35,889 --> 00:29:34,440
output if we take all our genetic codes

736
00:29:38,210 --> 00:29:35,899
that we've constructed in the computer

737
00:29:40,070 --> 00:29:38,220
measure how good they are at minimizing

738
00:29:42,830 --> 00:29:40,080
errors and then plot the probability

739
00:29:44,810 --> 00:29:42,840
distribution how many times we see a

740
00:29:47,450 --> 00:29:44,820
particular code with a particular score

741
00:29:49,610 --> 00:29:47,460
and minimizing errors and the smaller

742
00:29:51,649 --> 00:29:49,620
the the number here is on the horizontal

743
00:29:53,149 --> 00:29:51,659
axis the better the code is at

744
00:29:55,370 --> 00:29:53,159
minimizing error

745
00:29:57,230 --> 00:29:55,380
okay so one possibility that you could

746
00:29:59,810 --> 00:29:57,240
have is something like this you've got

747
00:30:02,269 --> 00:29:59,820
some you know Bells roughly bell-shaped

748
00:30:03,950 --> 00:30:02,279
curve and uh and then you that's what

749
00:30:05,570 --> 00:30:03,960
you would get for any random genetic

750
00:30:07,250 --> 00:30:05,580
code and then you look at the actual

751
00:30:09,289 --> 00:30:07,260
genetic code it happens to be here in

752
00:30:11,330 --> 00:30:09,299
the middle in this uh in this sketch and

753
00:30:14,210 --> 00:30:11,340
so you would say okay well if that's

754
00:30:16,549 --> 00:30:14,220
what happens then that means that the

755
00:30:19,730 --> 00:30:16,559
current genetic code is just a frozen

756
00:30:21,289 --> 00:30:19,740
accident there were some ancestral

757
00:30:23,750 --> 00:30:21,299
organism

758
00:30:25,190 --> 00:30:23,760
it by accident it happens to be the one

759
00:30:28,430 --> 00:30:25,200
that we're all descended from all life

760
00:30:30,470 --> 00:30:28,440
on Earth it had some genetic code we all

761
00:30:32,389 --> 00:30:30,480
have the same genetic code as it because

762
00:30:36,289 --> 00:30:32,399
if we had a different genetic code then

763
00:30:37,789 --> 00:30:36,299
we'd be mistranslating our genomes we'd

764
00:30:39,350 --> 00:30:37,799
be getting the long amino acids and the

765
00:30:42,529 --> 00:30:39,360
wrong proteins and so we wouldn't

766
00:30:45,409 --> 00:30:42,539
survive and so the code must be what

767
00:30:47,750 --> 00:30:45,419
Francis Crick in 1968 called a frozen

768
00:30:49,549 --> 00:30:47,760
accident it's an accident because it

769
00:30:51,710 --> 00:30:49,559
just comes from whatever was the last

770
00:30:54,289 --> 00:30:51,720
Universal common ancestor and it's

771
00:30:57,710 --> 00:30:54,299
frozen because if it evolves the changes

772
00:31:00,830 --> 00:30:57,720
that it would happen would be deadly

773
00:31:02,990 --> 00:31:00,840
well the other option is something like

774
00:31:05,029 --> 00:31:03,000
this you've got a bell-shaped curve like

775
00:31:06,830 --> 00:31:05,039
this and then the attribution of the

776
00:31:09,529 --> 00:31:06,840
code is somewhere down here in the Tails

777
00:31:11,690 --> 00:31:09,539
and if that's true then that says heck

778
00:31:13,970 --> 00:31:11,700
the genetic code that we have is not a

779
00:31:17,210 --> 00:31:13,980
frozen accident it had to have have

780
00:31:19,010 --> 00:31:17,220
evolved so here are the data this was a

781
00:31:22,669 --> 00:31:19,020
these data taken from an experiment that

782
00:31:25,190 --> 00:31:22,679
was done by freelance Hearst in 1998 so

783
00:31:27,110 --> 00:31:25,200
they they generated 1 million genetic

784
00:31:29,029 --> 00:31:27,120
codes and they scored them in a way

785
00:31:31,010 --> 00:31:29,039
they're like I'm not going to go into in

786
00:31:33,950 --> 00:31:31,020
detail and the actual genetic code is

787
00:31:35,810 --> 00:31:33,960
way way down here in the tail so all

788
00:31:38,149 --> 00:31:35,820
these random codes look nothing like

789
00:31:41,149 --> 00:31:38,159
this actual universal genetic code the

790
00:31:43,070 --> 00:31:41,159
canonical genetic code and so the title

791
00:31:44,750 --> 00:31:43,080
of their paper was the genetic code is

792
00:31:47,090 --> 00:31:44,760
one in a million

793
00:31:49,909 --> 00:31:47,100
can you generate a million genetic codes

794
00:31:52,310 --> 00:31:49,919
and and they're all worse than the one

795
00:31:54,049 --> 00:31:52,320
that we actually have at minimizing

796
00:31:55,549 --> 00:31:54,059
translation hours

797
00:31:57,230 --> 00:31:55,559
actually we know that actually it's

798
00:32:00,169 --> 00:31:57,240
actually more more like a hundred times

799
00:32:02,389 --> 00:32:00,179
uh better than that

800
00:32:04,970 --> 00:32:02,399
okay so now we have to ask the question

801
00:32:06,649 --> 00:32:04,980
how did the genetic code get like this

802
00:32:09,049 --> 00:32:06,659
how is it possible for the code to

803
00:32:11,330 --> 00:32:09,059
evolve because Florence is quick already

804
00:32:13,310 --> 00:32:11,340
told us that it can't evolve if you so

805
00:32:14,870 --> 00:32:13,320
if you change the genetic code you're

806
00:32:16,490 --> 00:32:14,880
going to start making the wrong amino

807
00:32:18,769 --> 00:32:16,500
acids you make your own amino acids you

808
00:32:20,750 --> 00:32:18,779
make the wrong proteins everything dies

809
00:32:24,409 --> 00:32:20,760
so we have to figure out how to do it

810
00:32:26,810 --> 00:32:24,419
and and this is what we did uh in in

811
00:32:28,490 --> 00:32:26,820
this paper over here and I want to walk

812
00:32:31,190 --> 00:32:28,500
you through not I'm not going to go into

813
00:32:33,350 --> 00:32:31,200
any of the the modeling and the math and

814
00:32:35,870 --> 00:32:33,360
so on I want to give you a feel of how

815
00:32:38,990 --> 00:32:35,880
we can understand how it is possible for

816
00:32:40,310 --> 00:32:39,000
a code to evolve

817
00:32:41,930 --> 00:32:40,320
okay so we're going to do a thought

818
00:32:44,990 --> 00:32:41,940
experiment and we're going to do the

819
00:32:48,169 --> 00:32:45,000
thought experiment by involving in our

820
00:32:54,049 --> 00:32:48,179
little story here the experts on codes

821
00:33:00,830 --> 00:32:57,529
spies you're right

822
00:33:04,490 --> 00:33:00,840
these characters from from from bad and

823
00:33:05,870 --> 00:33:04,500
possibly sexist 1960s TV shows

824
00:33:08,389 --> 00:33:05,880
all right so we're going to do an

825
00:33:10,549 --> 00:33:08,399
experiment that involves uh these spies

826
00:33:12,409 --> 00:33:10,559
and we're going to imagine that the

827
00:33:13,430 --> 00:33:12,419
spies of course have their secret code

828
00:33:18,409 --> 00:33:13,440
book

829
00:33:20,149 --> 00:33:18,419
are trying to communicate with uh one

830
00:33:22,070 --> 00:33:20,159
disreputable member of their Community

831
00:33:23,269 --> 00:33:22,080
shown here on the right and so we're

832
00:33:25,789 --> 00:33:23,279
going to do a thought experiment about

833
00:33:27,529 --> 00:33:25,799
what can happen when one spy tries to

834
00:33:30,049 --> 00:33:27,539
talk to to the other

835
00:33:32,630 --> 00:33:30,059
so let's start off with a with a message

836
00:33:35,149 --> 00:33:32,640
which is emitted over here so this is

837
00:33:38,570 --> 00:33:35,159
the message that she wants to send

838
00:33:41,029 --> 00:33:38,580
that is a received by by uh the the

839
00:33:44,029 --> 00:33:41,039
person on the right uses their code

840
00:33:47,570 --> 00:33:44,039
block and they correctly decode it as as

841
00:33:50,210 --> 00:33:47,580
uh as that sequence of uh of amino acids

842
00:33:52,070 --> 00:33:50,220
so so far everything is good there's

843
00:33:55,190 --> 00:33:52,080
only a single message that you can

844
00:33:57,409 --> 00:33:55,200
deduce from this signal that you receive

845
00:33:58,490 --> 00:33:57,419
okay so this is the standard operating

846
00:34:01,130 --> 00:33:58,500
procedure

847
00:34:03,590 --> 00:34:01,140
but the person on the right was chosen

848
00:34:06,769 --> 00:34:03,600
not just for their for their glamorous

849
00:34:08,450 --> 00:34:06,779
sartorial style but for the fact that

850
00:34:10,849 --> 00:34:08,460
they're very uh

851
00:34:13,190 --> 00:34:10,859
um incompetent and so I want you to

852
00:34:14,990 --> 00:34:13,200
imagine that this person has lost half

853
00:34:19,070 --> 00:34:15,000
the code book

854
00:34:20,869 --> 00:34:19,080
and so the code has now been uh changed

855
00:34:23,450 --> 00:34:20,879
because you've missed half the code book

856
00:34:25,369 --> 00:34:23,460
and so now he translates it as equals m

857
00:34:27,589 --> 00:34:25,379
c squared which means nothing to him but

858
00:34:28,909 --> 00:34:27,599
it may mean something to to you and so

859
00:34:31,369 --> 00:34:28,919
what we've learned from this is that if

860
00:34:33,230 --> 00:34:31,379
you evolve or change the code

861
00:34:36,129 --> 00:34:33,240
in this case by losing half the code

862
00:34:39,050 --> 00:34:36,139
book the message gets garbled so so far

863
00:34:40,909 --> 00:34:39,060
Crick was right

864
00:34:43,790 --> 00:34:40,919
suppose however

865
00:34:45,409 --> 00:34:43,800
that we have a statistical code book not

866
00:34:47,690 --> 00:34:45,419
a code book that gives you one message

867
00:34:49,010 --> 00:34:47,700
but a code book that gives you an

868
00:34:51,169 --> 00:34:49,020
ensemble of messages

869
00:34:52,970 --> 00:34:51,179
and from those messages you look at them

870
00:34:54,430 --> 00:34:52,980
and you say oh that makes no sense that

871
00:34:57,530 --> 00:34:54,440
makes no sense that makes it says oh

872
00:34:59,570 --> 00:34:57,540
phenylalum okay great perfect this must

873
00:35:03,109 --> 00:34:59,580
be what they what they meant if you have

874
00:35:04,730 --> 00:35:03,119
a code plus it's context then if you if

875
00:35:07,070 --> 00:35:04,740
you just have a probabilistic code book

876
00:35:08,690 --> 00:35:07,080
you have a chance of being able to

877
00:35:10,849 --> 00:35:08,700
interpret the message

878
00:35:12,829 --> 00:35:10,859
so the idea then was that if you have a

879
00:35:15,130 --> 00:35:12,839
polar ballistic code book then that

880
00:35:17,870 --> 00:35:15,140
means that you may you may need to have

881
00:35:19,790 --> 00:35:17,880
statistical proteins a process of

882
00:35:22,910 --> 00:35:19,800
translation that doesn't Just Produce

883
00:35:24,829 --> 00:35:22,920
one protein but produces many

884
00:35:27,710 --> 00:35:24,839
and this would make complete sense

885
00:35:30,050 --> 00:35:27,720
because think about early life think

886
00:35:32,870 --> 00:35:30,060
about early life which we know was a was

887
00:35:35,030 --> 00:35:32,880
a dominated by endosymbiosis and all

888
00:35:37,190 --> 00:35:35,040
sorts of events like that which of

889
00:35:40,130 --> 00:35:37,200
course led to many of the structures

890
00:35:42,650 --> 00:35:40,140
that we see in in modern cells uh like

891
00:35:45,589 --> 00:35:42,660
mitochondria and chloroplasts and so on

892
00:35:48,770 --> 00:35:45,599
so we can imagine that early life was a

893
00:35:51,230 --> 00:35:48,780
bit like early automobiles okay remember

894
00:35:52,930 --> 00:35:51,240
how early automobiles were they a

895
00:35:54,829 --> 00:35:52,940
hundred years ago a bit more than that

896
00:35:57,470 --> 00:35:54,839
automobiles did not look like they do

897
00:35:58,970 --> 00:35:57,480
today they were rickety old things they

898
00:36:01,250 --> 00:35:58,980
were sort of held together by string

899
00:36:04,010 --> 00:36:01,260
ceiling wax and if I drove over to one

900
00:36:05,930 --> 00:36:04,020
of my friends in my car and uh and then

901
00:36:07,849 --> 00:36:05,940
the wheel fell off

902
00:36:09,589 --> 00:36:07,859
you know she would just say well no

903
00:36:11,270 --> 00:36:09,599
problem I've got an old bicycle in the

904
00:36:13,370 --> 00:36:11,280
garage here we'll just screw on the

905
00:36:16,430 --> 00:36:13,380
wheel of that old bicycle onto your car

906
00:36:18,230 --> 00:36:16,440
and you'll go you're good to go

907
00:36:20,030 --> 00:36:18,240
that you could do you could mix and

908
00:36:22,730 --> 00:36:20,040
match parts

909
00:36:23,750 --> 00:36:22,740
100 years ago 120 years ago in the early

910
00:36:26,690 --> 00:36:23,760
class

911
00:36:29,450 --> 00:36:26,700
try to try doing that today to a to a

912
00:36:31,010 --> 00:36:29,460
Toyota Corolla right to taking a bicycle

913
00:36:32,990 --> 00:36:31,020
wheel and sticking it on when you've got

914
00:36:35,630 --> 00:36:33,000
a flat tire that's not going to work at

915
00:36:38,030 --> 00:36:35,640
all modern cars are more highly evolved

916
00:36:40,370 --> 00:36:38,040
and so they're very intolerant of

917
00:36:42,770 --> 00:36:40,380
anything that is not exactly right

918
00:36:46,130 --> 00:36:42,780
and so we get the idea that evolved

919
00:36:49,490 --> 00:36:46,140
systems become very intolerant of any

920
00:36:51,349 --> 00:36:49,500
kind of ambiguity in what's present but

921
00:36:54,109 --> 00:36:51,359
systems that are very early on are very

922
00:36:57,410 --> 00:36:54,119
simple are able to tolerate ambiguity

923
00:36:59,870 --> 00:36:57,420
and uh and and and so uh you can have

924
00:37:01,730 --> 00:36:59,880
this idea that the codes are floppy that

925
00:37:03,710 --> 00:37:01,740
the statistical proteins that have been

926
00:37:07,130 --> 00:37:03,720
made are not always the same proteins

927
00:37:09,650 --> 00:37:07,140
and then somehow the messages uh can can

928
00:37:12,410 --> 00:37:09,660
be interpreted so in other words what

929
00:37:15,890 --> 00:37:12,420
I'm saying is that the code book and the

930
00:37:18,530 --> 00:37:15,900
message can co-evolve as the organisms

931
00:37:21,109 --> 00:37:18,540
become more and more complex you get a

932
00:37:23,450 --> 00:37:21,119
probability distribution of codes that

933
00:37:24,770 --> 00:37:23,460
can be the outcome of translation and as

934
00:37:27,530 --> 00:37:24,780
the organisms become more and more

935
00:37:30,410 --> 00:37:27,540
complex that distribution gets narrower

936
00:37:32,270 --> 00:37:30,420
and narrower and very intolerant of any

937
00:37:34,849 --> 00:37:32,280
kind of element

938
00:37:36,410 --> 00:37:34,859
now you might ask yourself well wait

939
00:37:38,050 --> 00:37:36,420
this doesn't make any sense

940
00:37:41,930 --> 00:37:38,060
selection pressure

941
00:37:43,069 --> 00:37:41,940
acts on the phenotype it doesn't act on

942
00:37:44,630 --> 00:37:43,079
the code

943
00:37:47,210 --> 00:37:44,640
but I want to show you that it acts on

944
00:37:49,250 --> 00:37:47,220
the code too okay so here is a thought

945
00:37:51,530 --> 00:37:49,260
experiment but for me it was an actual

946
00:37:53,030 --> 00:37:51,540
experiment so I'm a physicist so I like

947
00:37:55,730 --> 00:37:53,040
to write papers with mathematical

948
00:37:59,089 --> 00:37:55,740
equations and so when I write a paper or

949
00:38:01,849 --> 00:37:59,099
a grant proposal I write it in a Thing

950
00:38:04,250 --> 00:38:01,859
Called Tech a type setting program that

951
00:38:07,190 --> 00:38:04,260
enables you to write equations my

952
00:38:14,510 --> 00:38:07,200
biological colleagues of course use a

953
00:38:20,990 --> 00:38:17,030
I guess the age of satire is not over

954
00:38:22,910 --> 00:38:21,000
yet and so uh so you can imagine the

955
00:38:24,470 --> 00:38:22,920
situation where I have sitting with my

956
00:38:26,089 --> 00:38:24,480
friends and the institute for genomic

957
00:38:28,609 --> 00:38:26,099
biology and I'm saying hey let's write

958
00:38:30,069 --> 00:38:28,619
this proposal together and they say sure

959
00:38:33,650 --> 00:38:30,079
about so we're going to write it in in

960
00:38:35,510 --> 00:38:33,660
word and hasten the my stuff in Tech and

961
00:38:38,030 --> 00:38:35,520
of course you know it's it's a complete

962
00:38:40,550 --> 00:38:38,040
disaster and uh and uh and what happens

963
00:38:42,710 --> 00:38:40,560
is the uh our proposal never actually

964
00:38:45,890 --> 00:38:42,720
gets written it never gets submitted and

965
00:38:47,870 --> 00:38:45,900
so it never gets funded meanwhile down

966
00:38:50,569 --> 00:38:47,880
the corridor another person is

967
00:38:53,450 --> 00:38:50,579
collaborating with their co-workers they

968
00:38:54,770 --> 00:38:53,460
just write it in word no problems and

969
00:38:57,770 --> 00:38:54,780
even if their proposal was less good

970
00:38:59,630 --> 00:38:57,780
than ours it's still uh it still has a

971
00:39:02,569 --> 00:38:59,640
chance of being funded so the code

972
00:39:04,970 --> 00:39:02,579
actually uh does matter

973
00:39:07,069 --> 00:39:04,980
now what is the basic way that the

974
00:39:08,089 --> 00:39:07,079
genetic code evolves in terms of its

975
00:39:10,910 --> 00:39:08,099
context

976
00:39:13,550 --> 00:39:10,920
so here's our here's a um an interesting

977
00:39:16,849 --> 00:39:13,560
uh factoid and this this slide is now

978
00:39:18,349 --> 00:39:16,859
quite old but uh this is uh this you may

979
00:39:20,870 --> 00:39:18,359
not recognize this person this is Bill

980
00:39:23,569 --> 00:39:20,880
Gates uh this is the late uh Steve Jobs

981
00:39:25,609 --> 00:39:23,579
both of them with examples of their of

982
00:39:28,370 --> 00:39:25,619
their of their companies or computers

983
00:39:30,650 --> 00:39:28,380
and uh actually uh my computer is a

984
00:39:33,530 --> 00:39:30,660
Windows computer but many people like

985
00:39:35,030 --> 00:39:33,540
her like the Apple computers and and the

986
00:39:37,849 --> 00:39:35,040
reason that um

987
00:39:39,290 --> 00:39:37,859
you know the the reason I use a Windows

988
00:39:41,770 --> 00:39:39,300
computer well I mean everybody does

989
00:39:44,270 --> 00:39:41,780
right like 96 of all the world's

990
00:39:47,630 --> 00:39:44,280
computers run their windows in a very

991
00:39:49,490 --> 00:39:47,640
small fashion run uh the the Mac

992
00:39:51,530 --> 00:39:49,500
operating system and the reason is that

993
00:39:53,270 --> 00:39:51,540
the Windows operating system is much

994
00:39:57,710 --> 00:39:53,280
better than

995
00:40:03,349 --> 00:40:00,530
well that's a very inopportune time to

996
00:40:05,870 --> 00:40:03,359
have a blue screen of death

997
00:40:09,589 --> 00:40:05,880
there's operating system is to put it

998
00:40:12,710 --> 00:40:09,599
mildly uh rubbish uh it has all sorts of

999
00:40:14,030 --> 00:40:12,720
things like this but the reason why it

1000
00:40:15,950 --> 00:40:14,040
is so popular

1001
00:40:20,150 --> 00:40:15,960
is not because it is the best computer

1002
00:40:23,450 --> 00:40:20,160
system it's because any program that you

1003
00:40:25,430 --> 00:40:23,460
want to run you can find it on Windows

1004
00:40:28,069 --> 00:40:25,440
but you may not be able to find it on

1005
00:40:30,470 --> 00:40:28,079
the Macos that may not be so true today

1006
00:40:32,510 --> 00:40:30,480
but it was certainly true uh suddenly 10

1007
00:40:34,790 --> 00:40:32,520
10 years ago and so what you learn from

1008
00:40:37,550 --> 00:40:34,800
this is that the community with access

1009
00:40:39,410 --> 00:40:37,560
to the broadest range of Innovations has

1010
00:40:41,930 --> 00:40:39,420
an evolutionary Advantage anything that

1011
00:40:43,910 --> 00:40:41,940
you want to do you can find a gadget in

1012
00:40:46,430 --> 00:40:43,920
that operating system that does it and

1013
00:40:48,890 --> 00:40:46,440
so what's important for platforms for

1014
00:40:51,290 --> 00:40:48,900
operating systems for processes that are

1015
00:40:54,650 --> 00:40:51,300
fundamental to cells like the like

1016
00:40:56,450 --> 00:40:54,660
translation is that is that you have the

1017
00:40:59,030 --> 00:40:56,460
broadest reach

1018
00:41:00,589 --> 00:40:59,040
so what we did in our in our

1019
00:41:02,870 --> 00:41:00,599
mathematical model which I'm not going

1020
00:41:05,329 --> 00:41:02,880
to go into in detail was we we are

1021
00:41:07,550 --> 00:41:05,339
considered a simulation a digital life

1022
00:41:09,170 --> 00:41:07,560
simulation just like the computer virus

1023
00:41:10,730 --> 00:41:09,180
once that I showed you at the beginning

1024
00:41:13,430 --> 00:41:10,740
of the call at the beginning of the uh

1025
00:41:15,109 --> 00:41:13,440
of the of the talk the ones uh run by

1026
00:41:17,390 --> 00:41:15,119
Niels Barry Charlie at The Institute for

1027
00:41:19,190 --> 00:41:17,400
advanced study so we have an asexual

1028
00:41:21,589 --> 00:41:19,200
population of evolving reproducing

1029
00:41:24,349 --> 00:41:21,599
digital organisms like computer viruses

1030
00:41:27,950 --> 00:41:24,359
the phenotype is a function of their

1031
00:41:29,990 --> 00:41:27,960
proteins and the proteins are obtained

1032
00:41:32,150 --> 00:41:30,000
by translating the genome with a code

1033
00:41:33,650 --> 00:41:32,160
but with uh with errors the individual

1034
00:41:35,630 --> 00:41:33,660
reproduction rate is a function of

1035
00:41:38,810 --> 00:41:35,640
fitness and the messages change are

1036
00:41:42,230 --> 00:41:38,820
faster than codes and so so forth and so

1037
00:41:45,170 --> 00:41:42,240
everything that's in this system allows

1038
00:41:47,329 --> 00:41:45,180
codes to evolve due to selection of the

1039
00:41:48,770 --> 00:41:47,339
phenotype through the mechanism that I

1040
00:41:50,390 --> 00:41:48,780
was showing you so now what we're doing

1041
00:41:52,010 --> 00:41:50,400
is simulating a whole population of

1042
00:41:54,890 --> 00:41:52,020
different organisms which have different

1043
00:41:57,230 --> 00:41:54,900
codes another question is which code is

1044
00:41:58,970 --> 00:41:57,240
the one that wins

1045
00:42:00,829 --> 00:41:58,980
all right so let's imagine that we've

1046
00:42:02,630 --> 00:42:00,839
done this experiment

1047
00:42:03,710 --> 00:42:02,640
so I started with a bunch of organisms

1048
00:42:05,630 --> 00:42:03,720
all of which have slightly different

1049
00:42:07,310 --> 00:42:05,640
genetic codes and they all co-evolve and

1050
00:42:09,470 --> 00:42:07,320
they're trying to deal with the

1051
00:42:12,589 --> 00:42:09,480
environment that they are they're in and

1052
00:42:14,390 --> 00:42:12,599
we watch how they evolve in time now we

1053
00:42:16,370 --> 00:42:14,400
did two experiments here

1054
00:42:17,569 --> 00:42:16,380
well I'm going to show you this graph

1055
00:42:20,030 --> 00:42:17,579
and I'm going to show another one

1056
00:42:22,190 --> 00:42:20,040
similar to it in the next slide this on

1057
00:42:24,770 --> 00:42:22,200
the vertical axis is the quality of the

1058
00:42:27,890 --> 00:42:24,780
code it's how good the genetic code is

1059
00:42:30,710 --> 00:42:27,900
of those organisms minimizing ever and

1060
00:42:32,630 --> 00:42:30,720
this is time over here and here's what

1061
00:42:34,550 --> 00:42:32,640
happens when you do this with regular

1062
00:42:36,410 --> 00:42:34,560
vertical darwinian Evolution that you're

1063
00:42:39,290 --> 00:42:36,420
used to and you can see that what

1064
00:42:40,970 --> 00:42:39,300
happens is that is as I as I evolve the

1065
00:42:44,089 --> 00:42:40,980
system

1066
00:42:46,670 --> 00:42:44,099
the uh the um the codes get better

1067
00:42:48,589 --> 00:42:46,680
smaller is better and then eventually it

1068
00:42:50,750 --> 00:42:48,599
stops and it just stays constant in time

1069
00:42:52,430 --> 00:42:50,760
and maybe if we waited like 100 times

1070
00:42:53,990 --> 00:42:52,440
longer maybe there'd be some other

1071
00:42:55,670 --> 00:42:54,000
change down here or something like this

1072
00:42:57,530 --> 00:42:55,680
and you run it again and for this one

1073
00:43:00,470 --> 00:42:57,540
you get something like this and you run

1074
00:43:02,630 --> 00:43:00,480
it again you get something like this

1075
00:43:05,690 --> 00:43:02,640
and if you ask

1076
00:43:07,130 --> 00:43:05,700
I've got a whole distribution

1077
00:43:08,750 --> 00:43:07,140
codes here

1078
00:43:10,550 --> 00:43:08,760
um what would I have got at random when

1079
00:43:12,109 --> 00:43:10,560
you can work that out and it would be

1080
00:43:14,569 --> 00:43:12,119
something like this and so what I've

1081
00:43:17,030 --> 00:43:14,579
learned is that without uh in this

1082
00:43:20,750 --> 00:43:17,040
experiment with vertical Evolution only

1083
00:43:23,030 --> 00:43:20,760
I evolve organisms that have codes that

1084
00:43:25,069 --> 00:43:23,040
are indistinguishable from random codes

1085
00:43:26,450 --> 00:43:25,079
and they're not unique and they're

1086
00:43:28,550 --> 00:43:26,460
certainly not optimal

1087
00:43:30,950 --> 00:43:28,560
but if I switch on horizontal Gene

1088
00:43:33,950 --> 00:43:30,960
transfer then what happens is the codes

1089
00:43:36,829 --> 00:43:33,960
follow this blue trajectory here and as

1090
00:43:40,190 --> 00:43:36,839
you can see end up uh with uh with a

1091
00:43:42,530 --> 00:43:40,200
very optimal code and one which is very

1092
00:43:44,809 --> 00:43:42,540
far from what you would get at random

1093
00:43:46,730 --> 00:43:44,819
and so once you've learned from this is

1094
00:43:49,089 --> 00:43:46,740
that the process of horizontal Gene to

1095
00:43:52,250 --> 00:43:49,099
transfer as an evolutionary process

1096
00:43:53,930 --> 00:43:52,260
leads to optimality of the uh of the

1097
00:43:57,109 --> 00:43:53,940
genetic code

1098
00:43:59,690 --> 00:43:57,119
now if we look at uh at uh how many

1099
00:44:02,150 --> 00:43:59,700
codes we have in our system now that's

1100
00:44:04,849 --> 00:44:02,160
shown shown here and again the same

1101
00:44:07,730 --> 00:44:04,859
thing is true that if you just use a

1102
00:44:10,910 --> 00:44:07,740
vertical Evolution uh you have you don't

1103
00:44:12,470 --> 00:44:10,920
get much uh selection of the genetic

1104
00:44:14,690 --> 00:44:12,480
codes as we saw on the previous slide

1105
00:44:17,270 --> 00:44:14,700
and but if you switch on horizontal Gene

1106
00:44:18,050 --> 00:44:17,280
transfer you get a universal genetic

1107
00:44:20,329 --> 00:44:18,060
code

1108
00:44:23,150 --> 00:44:20,339
and so what we've learned from this is

1109
00:44:25,730 --> 00:44:23,160
that the the the phase diagram of Life

1110
00:44:27,770 --> 00:44:25,740
must have looked something like this so

1111
00:44:30,609 --> 00:44:27,780
we're somewhere up here where in that

1112
00:44:34,790 --> 00:44:30,619
blob over here early on

1113
00:44:37,670 --> 00:44:34,800
the evolution was a network process

1114
00:44:40,010 --> 00:44:37,680
shown schematically over here

1115
00:44:41,690 --> 00:44:40,020
rapid Evolution and then over here we

1116
00:44:44,510 --> 00:44:41,700
have the vertical Evolution which we saw

1117
00:44:46,730 --> 00:44:44,520
was incredibly slow and that's the

1118
00:44:49,069 --> 00:44:46,740
process that we are in today and the

1119
00:44:50,870 --> 00:44:49,079
summary over here was a transition that

1120
00:44:53,150 --> 00:44:50,880
uh that Carl was like to call the

1121
00:44:55,849 --> 00:44:53,160
darwinian transition a claimed of a

1122
00:44:58,069 --> 00:44:55,859
phase transition uh between a collective

1123
00:45:01,670 --> 00:44:58,079
Network phase of life and a transition

1124
00:45:05,270 --> 00:45:01,680
to a life where organismal identity and

1125
00:45:10,370 --> 00:45:05,280
individuality becomes more important

1126
00:45:12,950 --> 00:45:10,380
all right so so I I I I'm going to uh

1127
00:45:15,470 --> 00:45:12,960
skip my section on Homer care housing so

1128
00:45:17,990 --> 00:45:15,480
I'm just going to skip through that and

1129
00:45:19,309 --> 00:45:18,000
uh and I wanted to tell you about some

1130
00:45:21,770 --> 00:45:19,319
of the things there's a universal in

1131
00:45:23,930 --> 00:45:21,780
biology so anyway the bottom line of

1132
00:45:26,530 --> 00:45:23,940
this is that uh we made a mathematical

1133
00:45:28,210 --> 00:45:26,540
model of the evolution of of of of of

1134
00:45:31,130 --> 00:45:28,220
Kyle

1135
00:45:33,470 --> 00:45:31,140
autocatalytic self-replicators and we

1136
00:45:37,490 --> 00:45:33,480
could show that uh you ultimately end up

1137
00:45:39,890 --> 00:45:37,500
with with broken 100 are broken uh

1138
00:45:42,290 --> 00:45:39,900
chirality not just you get sun

1139
00:45:44,150 --> 00:45:42,300
right-handed or sun left-handed but 100

1140
00:45:46,250 --> 00:45:44,160
effect and that's the thing that we

1141
00:45:49,130 --> 00:45:46,260
observe in biology and that's the thing

1142
00:45:51,650 --> 00:45:49,140
that was difficult to explain and and we

1143
00:45:54,470 --> 00:45:51,660
have made a theory for that

1144
00:45:55,309 --> 00:45:54,480
okay so um let me just very quickly show

1145
00:45:58,670 --> 00:45:55,319
you

1146
00:46:00,710 --> 00:45:58,680
um some examples of universality in

1147
00:46:02,569 --> 00:46:00,720
Modern Biology even today there are

1148
00:46:04,309 --> 00:46:02,579
things that are Universal not just the

1149
00:46:05,510 --> 00:46:04,319
evolutionary processes of say the

1150
00:46:07,910 --> 00:46:05,520
genetic code which may have happened

1151
00:46:10,849 --> 00:46:07,920
billions of years ago but other things

1152
00:46:12,770 --> 00:46:10,859
too so one example of this is the

1153
00:46:15,290 --> 00:46:12,780
universal statistics of gene expression

1154
00:46:18,109 --> 00:46:15,300
so if I have a genetically identical

1155
00:46:19,910 --> 00:46:18,119
cells they can exhibit different protein

1156
00:46:21,770 --> 00:46:19,920
copy numbers that's something that we've

1157
00:46:23,870 --> 00:46:21,780
known for about 20 years that's called

1158
00:46:26,210 --> 00:46:23,880
stochastic gene expression the whole

1159
00:46:28,970 --> 00:46:26,220
process of of expressing genes is a

1160
00:46:31,670 --> 00:46:28,980
random process and so the protein copy

1161
00:46:34,069 --> 00:46:31,680
numbers are not thermodynamically large

1162
00:46:36,770 --> 00:46:34,079
and so what happens is you have large

1163
00:46:39,349 --> 00:46:36,780
fluctuations in protein copy numbers in

1164
00:46:41,630 --> 00:46:39,359
in cells and here are experimental data

1165
00:46:45,109 --> 00:46:41,640
are showing you for a variety of

1166
00:46:46,609 --> 00:46:45,119
different uh of different uh cells here

1167
00:46:48,650 --> 00:46:46,619
I'm looking to go through the through

1168
00:46:51,710 --> 00:46:48,660
the details showing you that there's a

1169
00:46:54,050 --> 00:46:51,720
universal distribution for the protein

1170
00:46:55,790 --> 00:46:54,060
copy number now which is all these data

1171
00:46:58,730 --> 00:46:55,800
are collapsing onto one universal curve

1172
00:47:01,250 --> 00:46:58,740
can be predicted this is very much like

1173
00:47:02,809 --> 00:47:01,260
the universality I showed you in the

1174
00:47:05,030 --> 00:47:02,819
magnetic system at the beginning of the

1175
00:47:08,690 --> 00:47:06,349
um here's another one which is

1176
00:47:10,849 --> 00:47:08,700
absolutely fantastic and is still not

1177
00:47:13,609 --> 00:47:10,859
understood and that is universal

1178
00:47:15,589 --> 00:47:13,619
metabolism so here's the experiment so

1179
00:47:17,690 --> 00:47:15,599
what you do is you go into the lab and

1180
00:47:19,430 --> 00:47:17,700
uh you get some paper and some mud and

1181
00:47:21,770 --> 00:47:19,440
bits of egg and water and stuff like

1182
00:47:23,210 --> 00:47:21,780
this and you throw in some microbes and

1183
00:47:25,010 --> 00:47:23,220
then you make a bioreactor and the

1184
00:47:27,770 --> 00:47:25,020
bioreactor is producing that same

1185
00:47:31,849 --> 00:47:27,780
methane okay and so you get this thing

1186
00:47:34,430 --> 00:47:31,859
running and the bioreactor is uh your

1187
00:47:36,950 --> 00:47:34,440
measuring is producing a fixed rate of

1188
00:47:39,589 --> 00:47:36,960
methane coming out if you're feeding the

1189
00:47:42,410 --> 00:47:39,599
bioreactor and the rate of uh methane

1190
00:47:45,109 --> 00:47:42,420
coming out is a constant so you say well

1191
00:47:47,089 --> 00:47:45,119
that's great I wonder what's in my

1192
00:47:50,390 --> 00:47:47,099
bioreactor what's in my chemostat

1193
00:47:54,349 --> 00:47:50,400
so you go and do a Melody genomic survey

1194
00:47:56,990 --> 00:47:54,359
and and what you find is that even

1195
00:47:58,370 --> 00:47:57,000
though the methane that is coming out is

1196
00:48:01,010 --> 00:47:58,380
constant

1197
00:48:02,990 --> 00:48:01,020
when you look at the community structure

1198
00:48:05,569 --> 00:48:03,000
that you see and here I'm showing you

1199
00:48:08,990 --> 00:48:05,579
examples these are real data from from

1200
00:48:11,690 --> 00:48:09,000
different uh from a reactor what do you

1201
00:48:14,510 --> 00:48:11,700
find is that you know let's say day 900

1202
00:48:17,089 --> 00:48:14,520
you go and draw a pie chart showing you

1203
00:48:19,430 --> 00:48:17,099
the different uh uh operational

1204
00:48:21,470 --> 00:48:19,440
taxonomic units that are present in your

1205
00:48:24,410 --> 00:48:21,480
system and you say now until I'm done

1206
00:48:26,210 --> 00:48:24,420
and then you know your advisor says aha

1207
00:48:28,010 --> 00:48:26,220
you're not done wait two years and do

1208
00:48:29,210 --> 00:48:28,020
the experiment again so you've trigger

1209
00:48:30,890 --> 00:48:29,220
your thumb for two years and do the

1210
00:48:33,349 --> 00:48:30,900
experiment again and then what you find

1211
00:48:35,809 --> 00:48:33,359
is a completely different uh set of

1212
00:48:37,870 --> 00:48:35,819
organisms that are in the back in the

1213
00:48:40,370 --> 00:48:37,880
bioreactor but they're still producing

1214
00:48:41,270 --> 00:48:40,380
methane is exactly the rate that it was

1215
00:48:43,490 --> 00:48:41,280
before

1216
00:48:48,109 --> 00:48:43,500
hey this experiment was actually done by

1217
00:48:51,530 --> 00:48:48,119
Anna Fernandez and uh and in 1999 and

1218
00:48:54,650 --> 00:48:51,540
her advisor basically said this can't be

1219
00:48:56,150 --> 00:48:54,660
true we can't publish this the the we

1220
00:48:58,670 --> 00:48:56,160
can't publish these data but they

1221
00:49:01,910 --> 00:48:58,680
publish it in any case and and this has

1222
00:49:03,530 --> 00:49:01,920
been replicated many times since so what

1223
00:49:06,710 --> 00:49:03,540
we've learned then is that the

1224
00:49:09,710 --> 00:49:06,720
functional properties of a community are

1225
00:49:12,589 --> 00:49:09,720
insensitive to taxonomic fluctuations

1226
00:49:17,930 --> 00:49:12,599
here's a here's another example this is

1227
00:49:21,050 --> 00:49:17,940
from uh Luca and and durbly uh and uh

1228
00:49:23,329 --> 00:49:21,060
partly uh this is decoupling function

1229
00:49:25,730 --> 00:49:23,339
and taxonomy in the global ocean

1230
00:49:28,270 --> 00:49:25,740
microbiome and basically the same the

1231
00:49:30,470 --> 00:49:28,280
same story but despite the constant

1232
00:49:33,530 --> 00:49:30,480
metabolic function of the ocean

1233
00:49:35,569 --> 00:49:33,540
microbiome there were large taxonomic

1234
00:49:38,569 --> 00:49:35,579
fluctuations and we don't have any idea

1235
00:49:40,910 --> 00:49:38,579
of why this is happening

1236
00:49:42,589 --> 00:49:40,920
okay so these are examples of universal

1237
00:49:44,210 --> 00:49:42,599
things that are going on right now and

1238
00:49:45,170 --> 00:49:44,220
they need to be understood and they're

1239
00:49:47,089 --> 00:49:45,180
telling us something about the

1240
00:49:49,190 --> 00:49:47,099
collective properties of microbial

1241
00:49:51,410 --> 00:49:49,200
communities now

1242
00:49:53,930 --> 00:49:51,420
if the NASA astral Biology Institute was

1243
00:49:55,849 --> 00:49:53,940
still still a thing in existence and I

1244
00:49:57,349 --> 00:49:55,859
hadn't moved from Illinois to hear and

1245
00:49:59,089 --> 00:49:57,359
so on one of the things that I would be

1246
00:50:01,550 --> 00:49:59,099
thinking about doing is exploiting this

1247
00:50:03,470 --> 00:50:01,560
for example suppose I want to know what

1248
00:50:07,430 --> 00:50:03,480
are going to be the bio signatures of

1249
00:50:09,650 --> 00:50:07,440
say life that lives under the uh the ice

1250
00:50:12,410 --> 00:50:09,660
of encelados

1251
00:50:14,210 --> 00:50:12,420
well it turns out

1252
00:50:16,130 --> 00:50:14,220
that the metabolic output of microbial

1253
00:50:18,589 --> 00:50:16,140
communities doesn't depend sensitively

1254
00:50:21,050 --> 00:50:18,599
on what organisms are there so if I have

1255
00:50:23,809 --> 00:50:21,060
some knowledge of the geochemistry I can

1256
00:50:25,670 --> 00:50:23,819
then exploit this this uh this

1257
00:50:28,750 --> 00:50:25,680
functional redundancy to be able to make

1258
00:50:31,370 --> 00:50:28,760
predictions about what a metabolic

1259
00:50:33,710 --> 00:50:31,380
biosignatures I might find

1260
00:50:36,349 --> 00:50:33,720
okay so let's end with a discussing

1261
00:50:42,890 --> 00:50:36,359
about whether or not a universality is

1262
00:50:47,150 --> 00:50:45,829
so here is an example of another uh

1263
00:50:55,490 --> 00:50:47,160
scaling law

1264
00:50:58,549 --> 00:50:55,500
been known since the 1850s in England uh

1265
00:51:00,650 --> 00:50:58,559
these are data taking taken from bird

1266
00:51:03,250 --> 00:51:00,660
lovers actually not bird lovers these

1267
00:51:06,410 --> 00:51:03,260
are plants never mind these are plants

1268
00:51:08,870 --> 00:51:06,420
people in England like two things or

1269
00:51:11,270 --> 00:51:08,880
actually three things they like plants

1270
00:51:12,710 --> 00:51:11,280
they're like birds and they like beer or

1271
00:51:14,270 --> 00:51:12,720
like stink any pie or they're like

1272
00:51:15,950 --> 00:51:14,280
football or whatever you want but they

1273
00:51:17,510 --> 00:51:15,960
like plants and they're like and they

1274
00:51:21,890 --> 00:51:17,520
like birds and so there's a lot of data

1275
00:51:23,510 --> 00:51:21,900
going back uh you know 150 years

1276
00:51:26,329 --> 00:51:23,520
um and and here is showing you the

1277
00:51:29,270 --> 00:51:26,339
number of species as a function of the

1278
00:51:31,730 --> 00:51:29,280
area of the of the of the habitat and

1279
00:51:34,250 --> 00:51:31,740
what you can see from these data is that

1280
00:51:36,170 --> 00:51:34,260
the number of species uh scales like the

1281
00:51:38,569 --> 00:51:36,180
area to the one quarter power

1282
00:51:40,730 --> 00:51:38,579
so you might say here's a field count

1283
00:51:42,049 --> 00:51:40,740
all the bugs in the field count all the

1284
00:51:44,390 --> 00:51:42,059
plants in the field

1285
00:51:46,190 --> 00:51:44,400
double the size of the field count how

1286
00:51:47,569 --> 00:51:46,200
many they're in there then you might say

1287
00:51:50,329 --> 00:51:47,579
okay remember species are going to

1288
00:51:53,210 --> 00:51:50,339
double not true it goes like roughly

1289
00:51:56,089 --> 00:51:53,220
like the area to the one quarter power

1290
00:51:59,210 --> 00:51:56,099
not not the area itself so this is a

1291
00:52:02,329 --> 00:51:59,220
very important law because we can use it

1292
00:52:05,210 --> 00:52:02,339
to make extrapolations for example if we

1293
00:52:08,030 --> 00:52:05,220
know how much deforestation happened

1294
00:52:09,470 --> 00:52:08,040
today in the Amazon let's say when we

1295
00:52:12,890 --> 00:52:09,480
can figure out how many species might

1296
00:52:16,190 --> 00:52:12,900
have got uh affected by that

1297
00:52:17,990 --> 00:52:16,200
so that says these universal laws are

1298
00:52:19,790 --> 00:52:18,000
useful there's an argument that says

1299
00:52:21,530 --> 00:52:19,800
they're not useful

1300
00:52:23,329 --> 00:52:21,540
so here's an experiment that was

1301
00:52:24,670 --> 00:52:23,339
actually done this is Battle at Colorado

1302
00:52:28,849 --> 00:52:24,680
Island

1303
00:52:31,190 --> 00:52:28,859
in Panama and this is a an island which

1304
00:52:33,829 --> 00:52:31,200
is beloved by ecologists because it has

1305
00:52:35,450 --> 00:52:33,839
lots of trees and plants and we know

1306
00:52:38,089 --> 00:52:35,460
every single tree and every plant on

1307
00:52:39,890 --> 00:52:38,099
that island it's heavily studded okay

1308
00:52:42,710 --> 00:52:39,900
so you might ask yourself the following

1309
00:52:44,630 --> 00:52:42,720
question on this island what is the

1310
00:52:47,030 --> 00:52:44,640
number of species fraction of species

1311
00:52:49,549 --> 00:52:47,040
with a given number of individuals okay

1312
00:52:51,170 --> 00:52:49,559
how many species have 100 individuals

1313
00:52:52,609 --> 00:52:51,180
how many species have a thousand

1314
00:52:55,069 --> 00:52:52,619
individuals how many species have four

1315
00:52:59,450 --> 00:52:55,079
individuals in salt okay so you can

1316
00:53:02,210 --> 00:52:59,460
produce a species abundance curve and um

1317
00:53:03,589 --> 00:53:02,220
and then you and you get data that looks

1318
00:53:05,569 --> 00:53:03,599
like one of these curves here I don't

1319
00:53:07,849 --> 00:53:05,579
even remember which one it is so that

1320
00:53:09,589 --> 00:53:07,859
would be uh that would be a measurement

1321
00:53:11,450 --> 00:53:09,599
and you could make a theory for that

1322
00:53:13,430 --> 00:53:11,460
because you could say well we have to

1323
00:53:14,690 --> 00:53:13,440
look at the soil we have to look at the

1324
00:53:16,309 --> 00:53:14,700
weather we have to look at the

1325
00:53:18,410 --> 00:53:16,319
interactions between the trees the

1326
00:53:20,630 --> 00:53:18,420
canopy and so on and so forth and if we

1327
00:53:24,290 --> 00:53:20,640
had a detailed model we could probably

1328
00:53:25,790 --> 00:53:24,300
predict uh this this this curve

1329
00:53:28,069 --> 00:53:25,800
but there's another way to think about

1330
00:53:29,450 --> 00:53:28,079
it which is just to say well let's just

1331
00:53:31,430 --> 00:53:29,460
close it's just a random process

1332
00:53:34,130 --> 00:53:31,440
something has to be the most abundant

1333
00:53:36,770 --> 00:53:34,140
organism okay so what I've read is

1334
00:53:38,150 --> 00:53:36,780
that's it what its name is but then

1335
00:53:40,130 --> 00:53:38,160
something else has to be the next most

1336
00:53:41,809 --> 00:53:40,140
abundant and you can work out a theory

1337
00:53:44,150 --> 00:53:41,819
that looks like the general statistics

1338
00:53:46,370 --> 00:53:44,160
that you would expect for abundance just

1339
00:53:47,690 --> 00:53:46,380
like the central limit theorem in in

1340
00:53:50,510 --> 00:53:47,700
statistics

1341
00:53:52,069 --> 00:53:50,520
and so in in a neutral Theory the

1342
00:53:54,230 --> 00:53:52,079
species are functionally equivalent

1343
00:53:56,630 --> 00:53:54,240
they're not different they don't occupy

1344
00:53:58,970 --> 00:53:56,640
different uh geochemical or biological

1345
00:54:01,910 --> 00:53:58,980
niches metabolic niches so you've got

1346
00:54:04,250 --> 00:54:01,920
these two completely different theories

1347
00:54:05,750 --> 00:54:04,260
and one of them gives the black curve

1348
00:54:08,150 --> 00:54:05,760
one of them gives the green curve they

1349
00:54:10,609 --> 00:54:08,160
both explain the data equally well

1350
00:54:13,309 --> 00:54:10,619
so this is uh again

1351
00:54:15,470 --> 00:54:13,319
not not helpful so the upside of

1352
00:54:17,089 --> 00:54:15,480
universality is that you can make

1353
00:54:18,650 --> 00:54:17,099
predictions based on the minimal model

1354
00:54:21,230 --> 00:54:18,660
and that's a good thing

1355
00:54:23,450 --> 00:54:21,240
like trying to predict the metabolic

1356
00:54:26,569 --> 00:54:23,460
signature or putative life under the

1357
00:54:28,849 --> 00:54:26,579
under the ice cap of encels the downside

1358
00:54:30,890 --> 00:54:28,859
of universality is that statistically

1359
00:54:32,870 --> 00:54:30,900
similar results can be obtained from

1360
00:54:34,609 --> 00:54:32,880
microscopic models that are completely

1361
00:54:36,410 --> 00:54:34,619
different in their assumptions

1362
00:54:38,690 --> 00:54:36,420
and so if you have something Universal

1363
00:54:40,370 --> 00:54:38,700
at a high level of description that

1364
00:54:43,069 --> 00:54:40,380
means you can't understand the actual

1365
00:54:45,349 --> 00:54:43,079
processes that went on that caused the

1366
00:54:48,770 --> 00:54:45,359
thing in the first place

1367
00:54:50,870 --> 00:54:48,780
okay I want to end by asking what do we

1368
00:54:53,990 --> 00:54:50,880
miss if we don't understand Universal

1369
00:54:56,809 --> 00:54:54,000
phenomena and I'm going to talk about an

1370
00:54:59,089 --> 00:54:56,819
example uh that that may not be

1371
00:55:01,250 --> 00:54:59,099
meaningful to to some of you or many of

1372
00:55:04,069 --> 00:55:01,260
you even but it doesn't matter I want

1373
00:55:05,510 --> 00:55:04,079
you to just understand the the point so

1374
00:55:08,450 --> 00:55:05,520
this is about something in in

1375
00:55:10,730 --> 00:55:08,460
superconductivity and uh and there's a

1376
00:55:12,530 --> 00:55:10,740
couple of students here from my class on

1377
00:55:14,690 --> 00:55:12,540
emerging states of matter so they'll be

1378
00:55:17,270 --> 00:55:14,700
familiar with these examples so what is

1379
00:55:20,150 --> 00:55:17,280
superconductivity it's the it's the fact

1380
00:55:21,829 --> 00:55:20,160
that you can have a current flowing

1381
00:55:23,750 --> 00:55:21,839
through a material and there is no

1382
00:55:26,030 --> 00:55:23,760
electrical resistance and no heat that

1383
00:55:28,130 --> 00:55:26,040
comes out so that's that's the that's

1384
00:55:29,990 --> 00:55:28,140
the idea of superconductivity it's just

1385
00:55:32,870 --> 00:55:30,000
superconductor if you have it you can

1386
00:55:35,210 --> 00:55:32,880
make levitating trains and and transmit

1387
00:55:37,130 --> 00:55:35,220
power over long distances and solve all

1388
00:55:39,849 --> 00:55:37,140
the world's problems

1389
00:55:43,849 --> 00:55:39,859
that was discovered in 1911

1390
00:55:46,130 --> 00:55:43,859
1903 1933 it was also discovered that

1391
00:55:48,890 --> 00:55:46,140
superconductors don't just have a a

1392
00:55:50,690 --> 00:55:48,900
current that lasts forever and also go

1393
00:55:53,329 --> 00:55:50,700
round and round Forever by petrol motion

1394
00:55:56,150 --> 00:55:53,339
they also expel magnetic fields okay

1395
00:55:58,549 --> 00:55:56,160
don't ask why it doesn't matter

1396
00:55:59,990 --> 00:55:58,559
20 years later after that it was

1397
00:56:01,490 --> 00:56:00,000
discovered that actually nope it's not

1398
00:56:04,010 --> 00:56:01,500
true they don't expel magnetic fields

1399
00:56:06,230 --> 00:56:04,020
well some do but some don't some allow

1400
00:56:08,990 --> 00:56:06,240
magnetic fields to penetrate a

1401
00:56:11,329 --> 00:56:09,000
superconductor but in a lattice of

1402
00:56:12,410 --> 00:56:11,339
so-called vortices or flux tubes in a

1403
00:56:14,150 --> 00:56:12,420
way that is

1404
00:56:16,490 --> 00:56:14,160
you know I'm not going to I'm not going

1405
00:56:19,069 --> 00:56:16,500
to go into but that that can happen and

1406
00:56:21,650 --> 00:56:19,079
then finally oops wrong thing then

1407
00:56:24,109 --> 00:56:21,660
finally uh about 10 years or so after

1408
00:56:26,690 --> 00:56:24,119
that something called the judicial

1409
00:56:27,770 --> 00:56:26,700
effect was discovered the idea that I

1410
00:56:30,890 --> 00:56:27,780
can have

1411
00:56:34,190 --> 00:56:30,900
um a current uh flowing

1412
00:56:36,349 --> 00:56:34,200
um which which will will be uh um

1413
00:56:39,410 --> 00:56:36,359
oscillating with a frequency that is

1414
00:56:41,089 --> 00:56:39,420
just determined by quantum mechanics and

1415
00:56:43,010 --> 00:56:41,099
doesn't depend on the material or

1416
00:56:46,250 --> 00:56:43,020
anything like that so you can use this

1417
00:56:48,710 --> 00:56:46,260
to create a universal standard of

1418
00:56:50,930 --> 00:56:48,720
voltage and and of time okay so this

1419
00:56:53,809 --> 00:56:50,940
this is a complicated quantum mechanical

1420
00:56:56,510 --> 00:56:53,819
effect and it took 50 years and and most

1421
00:56:57,890 --> 00:56:56,520
of the people on on this who discovered

1422
00:56:59,630 --> 00:56:57,900
these things ends up getting Nobel

1423
00:57:01,910 --> 00:56:59,640
prizes these were very important things

1424
00:57:04,130 --> 00:57:01,920
scientifically and technically and the

1425
00:57:05,510 --> 00:57:04,140
question is why did it take so long to

1426
00:57:08,569 --> 00:57:05,520
make these discoveries are physicists

1427
00:57:10,609 --> 00:57:08,579
stupid well maybe but uh but the thing

1428
00:57:13,250 --> 00:57:10,619
is this it's even worse because in my

1429
00:57:15,230 --> 00:57:13,260
class I derive all of these things in in

1430
00:57:16,750 --> 00:57:15,240
basically one lecture in a few lines of

1431
00:57:20,030 --> 00:57:16,760
algebra for

1432
00:57:22,430 --> 00:57:20,040
jumbo that's written down here okay so

1433
00:57:24,829 --> 00:57:22,440
what was going wrong what was going

1434
00:57:28,130 --> 00:57:24,839
wrong was that people were focusing on

1435
00:57:29,390 --> 00:57:28,140
the wrong level of description and I

1436
00:57:30,829 --> 00:57:29,400
want to explain to you what I mean by

1437
00:57:34,250 --> 00:57:30,839
that

1438
00:57:36,230 --> 00:57:34,260
okay so in world of superconductivity

1439
00:57:37,670 --> 00:57:36,240
you have to make a superconductor so

1440
00:57:39,950 --> 00:57:37,680
that's a problem in quantum chemistry

1441
00:57:42,950 --> 00:57:39,960
and Material Science there's a theory

1442
00:57:45,230 --> 00:57:42,960
that applies to at least the classic

1443
00:57:46,730 --> 00:57:45,240
superconductors but not the ones that

1444
00:57:48,530 --> 00:57:46,740
everybody's excited about for the last

1445
00:57:50,630 --> 00:57:48,540
30 years the high temperature

1446
00:57:52,490 --> 00:57:50,640
superconductors so there's a theory of

1447
00:57:54,410 --> 00:57:52,500
that which is which is very nice and so

1448
00:57:56,630 --> 00:57:54,420
on and then lastly there's a theory

1449
00:57:59,089 --> 00:57:56,640
which I which I've given by this name

1450
00:58:01,730 --> 00:57:59,099
here is basically a theory that looks at

1451
00:58:04,190 --> 00:58:01,740
the quantum mechanical symmetries of

1452
00:58:07,490 --> 00:58:04,200
Superman actors now when we talk about

1453
00:58:10,549 --> 00:58:07,500
biology we have another set of levels of

1454
00:58:12,530 --> 00:58:10,559
description so so this level is quantum

1455
00:58:14,630 --> 00:58:12,540
chemistry this is electrons moving

1456
00:58:17,930 --> 00:58:14,640
around and this is looking at Symmetry

1457
00:58:19,790 --> 00:58:17,940
and and wave functions all right here in

1458
00:58:21,349 --> 00:58:19,800
biology we start off with the lowest

1459
00:58:22,370 --> 00:58:21,359
level of description with atoms and

1460
00:58:23,809 --> 00:58:22,380
molecules

1461
00:58:25,790 --> 00:58:23,819
there's an intermediate level of

1462
00:58:27,470 --> 00:58:25,800
description where we you know we talked

1463
00:58:29,750 --> 00:58:27,480
about with translation we look at our

1464
00:58:31,609 --> 00:58:29,760
DNA we look at how elastic it is and how

1465
00:58:33,410 --> 00:58:31,619
proteins fold and things like this we

1466
00:58:35,390 --> 00:58:33,420
look at a liquid liquid intracellular

1467
00:58:36,410 --> 00:58:35,400
complexes and things like that in cell

1468
00:58:38,809 --> 00:58:36,420
biology

1469
00:58:41,750 --> 00:58:38,819
and then finally on the LA on the larger

1470
00:58:43,789 --> 00:58:41,760
scale I talked about the Dynamics of how

1471
00:58:46,130 --> 00:58:43,799
systems evolved the Dynamics of evolving

1472
00:58:48,710 --> 00:58:46,140
systems like the genetic code

1473
00:58:50,930 --> 00:58:48,720
so those are levels of description these

1474
00:58:54,589 --> 00:58:50,940
levels of description answer different

1475
00:58:56,690 --> 00:58:54,599
questions so in superconductivity well

1476
00:58:59,809 --> 00:58:56,700
quantum chemistry of Material Science

1477
00:59:01,730 --> 00:58:59,819
says how do you make a stuff what's the

1478
00:59:03,349 --> 00:59:01,740
specific recipe of putting the atoms

1479
00:59:05,329 --> 00:59:03,359
together in such a way that you make a

1480
00:59:08,089 --> 00:59:05,339
particular superconductor

1481
00:59:10,789 --> 00:59:08,099
this uh this uh this intermediate level

1482
00:59:13,789 --> 00:59:10,799
of description tells you about what is

1483
00:59:15,410 --> 00:59:13,799
the basic mechanism by which uh you know

1484
00:59:17,150 --> 00:59:15,420
electrons form what's called a Cooper

1485
00:59:18,589 --> 00:59:17,160
pair a composite bows on the inside a

1486
00:59:20,809 --> 00:59:18,599
superconductor and then do something

1487
00:59:23,390 --> 00:59:20,819
called Bose condensation so this is a

1488
00:59:25,309 --> 00:59:23,400
sort of more detailed uh description

1489
00:59:27,710 --> 00:59:25,319
that applies to um to many different

1490
00:59:30,170 --> 00:59:27,720
superconductors and this level of

1491
00:59:32,990 --> 00:59:30,180
description this symmetry wave function

1492
00:59:34,430 --> 00:59:33,000
quantum mechanical Theory describes why

1493
00:59:36,710 --> 00:59:34,440
the phenomenon of superconductivity

1494
00:59:38,630 --> 00:59:36,720
exists at all how you can get all the

1495
00:59:40,789 --> 00:59:38,640
phenomenon of superconductivity just

1496
00:59:42,289 --> 00:59:40,799
from one very simple and mathematical

1497
00:59:45,470 --> 00:59:42,299
description

1498
00:59:47,329 --> 00:59:45,480
now in the in the world of biology atoms

1499
00:59:50,870 --> 00:59:47,339
and molecules tells us something about

1500
00:59:53,030 --> 00:59:50,880
how specific biopolymers interact and

1501
00:59:54,829 --> 00:59:53,040
fold undergo template-directed synthesis

1502
00:59:56,510 --> 00:59:54,839
and so on and so forth if you want to

1503
00:59:58,130 --> 00:59:56,520
understand those questions you have to

1504
00:59:59,390 --> 00:59:58,140
deal with atoms and molecules there's no

1505
01:00:01,670 --> 00:59:59,400
way around it

1506
01:00:03,589 --> 01:00:01,680
if you want to understand

1507
01:00:05,870 --> 01:00:03,599
um the you know the basic functional

1508
01:00:08,150 --> 01:00:05,880
cellular processes you don't need to

1509
01:00:10,730 --> 01:00:08,160
have such a detailed description you can

1510
01:00:13,250 --> 01:00:10,740
just think about uh you know face

1511
01:00:15,289 --> 01:00:13,260
separation inside cells and and sort of

1512
01:00:17,390 --> 01:00:15,299
bending rigidity of cell membranes and

1513
01:00:19,490 --> 01:00:17,400
DNA and so on and so forth

1514
01:00:21,770 --> 01:00:19,500
and if you want to understand why the

1515
01:00:23,630 --> 01:00:21,780
phenomenon of Life exists at all well

1516
01:00:25,849 --> 01:00:23,640
that's surely a question that would be

1517
01:00:28,609 --> 01:00:25,859
answered if we understood more about the

1518
01:00:31,730 --> 01:00:28,619
Dynamics of evolving systems

1519
01:00:34,490 --> 01:00:31,740
different levels of description apply to

1520
01:00:36,890 --> 01:00:34,500
different levels of universality so if I

1521
01:00:38,750 --> 01:00:36,900
look in in the quantum chemistry of

1522
01:00:40,430 --> 01:00:38,760
material science that tells us something

1523
01:00:42,109 --> 01:00:40,440
about very specific materials like

1524
01:00:44,390 --> 01:00:42,119
Atrium barium and copper oxide or

1525
01:00:46,549 --> 01:00:44,400
something like this if I want to look at

1526
01:00:48,289 --> 01:00:46,559
this level of description it tells us

1527
01:00:50,569 --> 01:00:48,299
something about what are called weak

1528
01:00:53,270 --> 01:00:50,579
coupling superconductors and finally

1529
01:00:55,549 --> 01:00:53,280
this level of description uh this

1530
01:00:57,470 --> 01:00:55,559
symmetry wave function Theory tells us

1531
01:00:59,450 --> 01:00:57,480
about all superconductors whether

1532
01:01:01,730 --> 01:00:59,460
they're made in a material science lab

1533
01:01:05,150 --> 01:01:01,740
or whether they occur in the in the

1534
01:01:08,049 --> 01:01:05,160
heart of a of a neutron star

1535
01:01:11,510 --> 01:01:08,059
in biology this level of description

1536
01:01:13,250 --> 01:01:11,520
applies effort to uh very specific

1537
01:01:15,710 --> 01:01:13,260
biopolymers you know those chemical

1538
01:01:17,349 --> 01:01:15,720
structure of RNA or DNA or some

1539
01:01:21,349 --> 01:01:17,359
particular protein

1540
01:01:23,089 --> 01:01:21,359
the elasticity theory for DNA and so on

1541
01:01:26,510 --> 01:01:23,099
and so forth tells you about the physics

1542
01:01:28,130 --> 01:01:26,520
of subcellular components and the

1543
01:01:30,470 --> 01:01:28,140
Dynamics of evolving systems would have

1544
01:01:32,809 --> 01:01:30,480
would be applying to all life and just

1545
01:01:34,370 --> 01:01:32,819
in the same way that a universal turing

1546
01:01:36,289 --> 01:01:34,380
machine with a Von Neumann architecture

1547
01:01:38,450 --> 01:01:36,299
applies to all things that we call

1548
01:01:40,970 --> 01:01:38,460
computers

1549
01:01:44,390 --> 01:01:40,980
now why do we need this Universal level

1550
01:01:47,390 --> 01:01:44,400
this top level description of of of of

1551
01:01:50,390 --> 01:01:47,400
stuff well if I have a superconductor

1552
01:01:52,490 --> 01:01:50,400
and I want to understand uh this level

1553
01:01:54,650 --> 01:01:52,500
of description not only does it tell me

1554
01:01:55,849 --> 01:01:54,660
that superconductors exist but it also

1555
01:01:58,069 --> 01:01:55,859
tells me everything that a

1556
01:01:59,870 --> 01:01:58,079
superconductor can do it tells me the

1557
01:02:02,450 --> 01:01:59,880
myosin effect the vortex lattice the

1558
01:02:03,770 --> 01:02:02,460
josen effects it tells me how a

1559
01:02:06,410 --> 01:02:03,780
superconductor responds to

1560
01:02:08,089 --> 01:02:06,420
electromagnetic fields so if I don't

1561
01:02:10,130 --> 01:02:08,099
have this

1562
01:02:12,049 --> 01:02:10,140
I can't predict how a superconductor

1563
01:02:15,289 --> 01:02:12,059
responds to an electromagnetic field and

1564
01:02:19,250 --> 01:02:17,270
by regarding superconductors as

1565
01:02:21,710 --> 01:02:19,260
collections of atoms

1566
01:02:23,809 --> 01:02:21,720
we are missing the emergent laws that

1567
01:02:25,670 --> 01:02:23,819
act at the system scale and govern the

1568
01:02:28,549 --> 01:02:25,680
large-scale response to electromagnetic

1569
01:02:31,190 --> 01:02:28,559
fields just like

1570
01:02:34,130 --> 01:02:31,200
when we were looking at our bioreactor

1571
01:02:37,549 --> 01:02:34,140
it produces methane at a constant rate

1572
01:02:39,410 --> 01:02:37,559
if we just focus on the on the on the uh

1573
01:02:41,329 --> 01:02:39,420
on the bacteria that are in there we

1574
01:02:43,069 --> 01:02:41,339
won't be able to understand that we need

1575
01:02:46,010 --> 01:02:43,079
to understand how metabolism can be

1576
01:02:47,930 --> 01:02:46,020
emergent in a community this problem we

1577
01:02:49,970 --> 01:02:47,940
know how to solve it took us 50 years to

1578
01:02:51,289 --> 01:02:49,980
do it and we had to rejigger the way we

1579
01:02:54,230 --> 01:02:51,299
think about physics

1580
01:02:56,210 --> 01:02:54,240
for living systems we know that this

1581
01:02:58,309 --> 01:02:56,220
level of description would apply to all

1582
01:03:00,950 --> 01:02:58,319
of life and what happens if we don't

1583
01:03:02,450 --> 01:03:00,960
have it we can't predict the response of

1584
01:03:04,730 --> 01:03:02,460
living systems to selective

1585
01:03:07,430 --> 01:03:04,740
perturbations we can't tell what happens

1586
01:03:09,770 --> 01:03:07,440
when you play antibiotics or herbicides

1587
01:03:12,950 --> 01:03:09,780
or insecticides or chemotherapy to

1588
01:03:14,210 --> 01:03:12,960
somebody with cancer okay and and we

1589
01:03:16,849 --> 01:03:14,220
know what happens in the real world

1590
01:03:18,650 --> 01:03:16,859
whenever we do these interventions and

1591
01:03:19,910 --> 01:03:18,660
treat living systems as engineered

1592
01:03:22,309 --> 01:03:19,920
systems

1593
01:03:24,890 --> 01:03:22,319
what happens is they fight back they

1594
01:03:26,630 --> 01:03:24,900
evolve the cancer tumor evolves and you

1595
01:03:29,329 --> 01:03:26,640
and you and you and the chemotherapy

1596
01:03:30,789 --> 01:03:29,339
stops being effective Roundup stops

1597
01:03:32,930 --> 01:03:30,799
being effective against weeds

1598
01:03:35,089 --> 01:03:32,940
antibiotics stop being effective against

1599
01:03:36,530 --> 01:03:35,099
bacterial infections and so on and so

1600
01:03:38,569 --> 01:03:36,540
forth

1601
01:03:40,849 --> 01:03:38,579
by regarding biology as complicated

1602
01:03:42,230 --> 01:03:40,859
physical systems we are missing the

1603
01:03:44,150 --> 01:03:42,240
emerging laws that act on the system

1604
01:03:46,549 --> 01:03:44,160
scale and govern the large-scale

1605
01:03:51,049 --> 01:03:46,559
response to control perturbations and we

1606
01:03:54,230 --> 01:03:52,849
all right if you if you want to read

1607
01:03:56,589 --> 01:03:54,240
about any of these things that I've been

1608
01:03:59,990 --> 01:03:56,599
talking about there is a article I wrote

1609
01:04:02,450 --> 01:04:00,000
uh called life is physics with uh with

1610
01:04:04,789 --> 01:04:02,460
Carl wos and another one on the

1611
01:04:08,210 --> 01:04:04,799
statistical mechanics of early life in

1612
01:04:10,549 --> 01:04:08,220
Phil transa this one was called life is

1613
01:04:12,230 --> 01:04:10,559
physics for the following reason

1614
01:04:14,690 --> 01:04:12,240
when I used to go to astrobiology

1615
01:04:16,490 --> 01:04:14,700
conferences on the first day somebody

1616
01:04:19,190 --> 01:04:16,500
would get up and show some extremely

1617
01:04:21,170 --> 01:04:19,200
complicated chemical pathway that they

1618
01:04:23,390 --> 01:04:21,180
thought might have existed in the RNA

1619
01:04:25,430 --> 01:04:23,400
world or the sugar world or lipid world

1620
01:04:27,349 --> 01:04:25,440
or whatever will be was the fat all the

1621
01:04:28,670 --> 01:04:27,359
time and they would say life is

1622
01:04:32,990 --> 01:04:28,680
chemistry

1623
01:04:34,250 --> 01:04:33,000
doesn't it doesn't matter it does matter

1624
01:04:36,109 --> 01:04:34,260
you can't build a superconductor with

1625
01:04:37,910 --> 01:04:36,119
our atoms and molecules but you have to

1626
01:04:40,549 --> 01:04:37,920
understand the emergent physical laws as

1627
01:04:42,530 --> 01:04:40,559
well the dynamical processes that go on

1628
01:04:44,690 --> 01:04:42,540
and so that's why we talk about this as

1629
01:04:46,670 --> 01:04:44,700
life as physics

1630
01:04:48,650 --> 01:04:46,680
all right so did we learn new physics

1631
01:04:51,890 --> 01:04:48,660
when we study biological biological

1632
01:04:53,210 --> 01:04:51,900
systems uh yes we do we we realize that

1633
01:04:55,609 --> 01:04:53,220
they actually do things that physical

1634
01:04:58,390 --> 01:04:55,619
systems don't are they Universal

1635
01:05:00,770 --> 01:04:58,400
phenomena in biology yes genetic code

1636
01:05:03,289 --> 01:05:00,780
gene expression distribution of species

1637
01:05:05,569 --> 01:05:03,299
metabolism and so on do they reveal

1638
01:05:07,789 --> 01:05:05,579
things that are important well yes they

1639
01:05:09,470 --> 01:05:07,799
tell us about the phase diagram of life

1640
01:05:11,690 --> 01:05:09,480
because about cell structure and

1641
01:05:13,010 --> 01:05:11,700
principles of how things evolve and what

1642
01:05:15,410 --> 01:05:13,020
do we miss by not understanding

1643
01:05:17,870 --> 01:05:15,420
Universal phenomena we've we don't

1644
01:05:19,789 --> 01:05:17,880
understand why life exists at all and we

1645
01:05:23,270 --> 01:05:19,799
don't understand how to how biological

1646
01:05:26,510 --> 01:05:23,280
systems respond to control perturbations

1647
01:05:28,490 --> 01:05:26,520
so so here is uh here is the the history

1648
01:05:30,829 --> 01:05:28,500
of life we know that some around here

1649
01:05:32,990 --> 01:05:30,839
was a homoclimal transition in the

1650
01:05:35,690 --> 01:05:33,000
genetic code the darwinian transition

1651
01:05:38,030 --> 01:05:35,700
and finally 3.8 billion years ago last

1652
01:05:39,829 --> 01:05:38,040
Universal common ancestor all of this

1653
01:05:43,069 --> 01:05:39,839
happens super fast because it was

1654
01:05:45,349 --> 01:05:43,079
dominated by Network effects and while

1655
01:05:48,130 --> 01:05:45,359
and what I didn't tell you about this in

1656
01:05:50,870 --> 01:05:48,140
detail or the catalysis leads to 100

1657
01:05:53,150 --> 01:05:50,880
homicorality horizontal Gene transfer

1658
01:05:55,130 --> 01:05:53,160
networks Drive the evolution of the

1659
01:05:56,750 --> 01:05:55,140
unique optimal genetic code and

1660
01:05:58,789 --> 01:05:56,760
horizontal Gene transfer eventually

1661
01:06:01,309 --> 01:05:58,799
becomes ineffective compared to Vertical

1662
01:06:03,410 --> 01:06:01,319
selection and you get this transition to

1663
01:06:05,450 --> 01:06:03,420
the vertical phase of life that we are

1664
01:06:08,630 --> 01:06:05,460
in today

1665
01:06:11,329 --> 01:06:08,640
I want to end with a quote a since I'm a

1666
01:06:13,789 --> 01:06:11,339
physicist I study biology I'm not

1667
01:06:16,730 --> 01:06:13,799
because I love biology I have a sort of

1668
01:06:19,130 --> 01:06:16,740
hate relationship with Biology but

1669
01:06:21,589 --> 01:06:19,140
but because it teaches me things that

1670
01:06:23,569 --> 01:06:21,599
are that expands the scope of physics so

1671
01:06:25,910 --> 01:06:23,579
ask not what physics can do for biology

1672
01:06:27,950 --> 01:06:25,920
build you a better microscope build your

1673
01:06:31,270 --> 01:06:27,960
build a computer simulation understand

1674
01:06:33,410 --> 01:06:31,280
the uh the structure of some protein

1675
01:06:34,970 --> 01:06:33,420
asking instead of what biology can do

1676
01:06:37,530 --> 01:06:34,980
for physics it can teach us wonderful

1677
01:06:51,130 --> 01:06:37,540
things thank you very much

1678
01:06:51,140 --> 01:06:55,849
all right

1679
01:07:01,010 --> 01:06:58,609
so I'm very recently coming to

1680
01:07:02,809 --> 01:07:01,020
appreciate this the importance of this

1681
01:07:05,230 --> 01:07:02,819
horizontal Gene transfer but

1682
01:07:08,329 --> 01:07:05,240
mechanistically I don't understand

1683
01:07:10,789 --> 01:07:08,339
how like why this trade-off is tied to

1684
01:07:12,190 --> 01:07:10,799
optimizing the genetic code well you

1685
01:07:14,450 --> 01:07:12,200
don't understand why what

1686
01:07:17,510 --> 01:07:14,460
mechanistically I don't understand why

1687
01:07:23,470 --> 01:07:17,520
it's massive Advantage is tied to having

1688
01:07:29,870 --> 01:07:28,010
so the question is uh why why why is if

1689
01:07:32,089 --> 01:07:29,880
I understand why why is horizontal Gene

1690
01:07:34,130 --> 01:07:32,099
transfer

1691
01:07:35,510 --> 01:07:34,140
um important in in evolving these

1692
01:07:38,930 --> 01:07:35,520
genetic code is that what you're asking

1693
01:07:40,670 --> 01:07:38,940
yeah yeah yeah so so the fundamental

1694
01:07:42,470 --> 01:07:40,680
reason is this well I showed you in the

1695
01:07:44,450 --> 01:07:42,480
in the simulations

1696
01:07:47,450 --> 01:07:44,460
um was that if you if you just have

1697
01:07:48,650 --> 01:07:47,460
vertical Evolution which I explained to

1698
01:07:50,029 --> 01:07:48,660
you what it is

1699
01:07:51,470 --> 01:07:50,039
um you kind of get trapped in local

1700
01:07:54,049 --> 01:07:51,480
Minima

1701
01:07:56,270 --> 01:07:54,059
okay so horizontal Gene transfer is a

1702
01:07:58,910 --> 01:07:56,280
very non-local shuffling of genes that

1703
01:08:00,829 --> 01:07:58,920
wouldn't otherwise happen and so it's a

1704
01:08:03,410 --> 01:08:00,839
much faster way of exploring the space

1705
01:08:06,890 --> 01:08:03,420
of possibilities and so what happened in

1706
01:08:10,609 --> 01:08:06,900
early life is organisms were very porous

1707
01:08:12,890 --> 01:08:10,619
there's a lot of endosymbiosis so you

1708
01:08:14,630 --> 01:08:12,900
know today we we only you know you and I

1709
01:08:17,870 --> 01:08:14,640
are not horizontally transferring genes

1710
01:08:20,209 --> 01:08:17,880
the bacteria in our guts are but in

1711
01:08:22,010 --> 01:08:20,219
early life organisms would sort of Pulp

1712
01:08:24,709 --> 01:08:22,020
go through each other and Collide and

1713
01:08:26,329 --> 01:08:24,719
and subsume each other and so on and so

1714
01:08:28,490 --> 01:08:26,339
there was a very natural built-in

1715
01:08:29,990 --> 01:08:28,500
mechanism for genes to be horizontally

1716
01:08:34,130 --> 01:08:30,000
transferred

1717
01:08:36,769 --> 01:08:34,140
and so when we when we model that in our

1718
01:08:38,689 --> 01:08:36,779
in our simulations what we see is that

1719
01:08:40,249 --> 01:08:38,699
is enormously effective in accelerating

1720
01:08:43,189 --> 01:08:40,259
the evolution rate

1721
01:08:44,689 --> 01:08:43,199
so so bottom line is horizontal Gene

1722
01:08:45,890 --> 01:08:44,699
transfer is just one way to accelerate

1723
01:08:47,870 --> 01:08:45,900
evolution

1724
01:08:49,789 --> 01:08:47,880
and if you accelerate Evolution you

1725
01:08:51,410 --> 01:08:49,799
don't get stuck in local Minima if you

1726
01:08:54,229 --> 01:08:51,420
don't get stuck in local minimum as it

1727
01:08:56,510 --> 01:08:54,239
were you'd then find the true

1728
01:08:58,490 --> 01:08:56,520
dust code or the best whatever it is

1729
01:09:00,950 --> 01:08:58,500
that you're optimizing and and that's

1730
01:09:03,349 --> 01:09:00,960
why that's why it works so did I answer

1731
01:09:05,329 --> 01:09:03,359
your question what was the bit what was

1732
01:09:08,570 --> 01:09:05,339
the bit that I hadn't explained that

1733
01:09:12,410 --> 01:09:10,550
I I saw it empirically that it was true

1734
01:09:15,590 --> 01:09:12,420
but the mechanism oh okay so I explained

1735
01:09:19,189 --> 01:09:15,600
it yeah go ahead thank you okay yeah hi

1736
01:09:21,470 --> 01:09:19,199
there hi uh I'm Maddie from um MIT

1737
01:09:23,510 --> 01:09:21,480
um great talk I was kind of interested

1738
01:09:26,390 --> 01:09:23,520
based on your like um idea of evolution

1739
01:09:28,370 --> 01:09:26,400
of this like Pro Geno like horizontal

1740
01:09:30,110 --> 01:09:28,380
Gene transfer dominated system evolving

1741
01:09:31,729 --> 01:09:30,120
to this darwinian phase where do you

1742
01:09:33,650 --> 01:09:31,739
think kind of the universality of like

1743
01:09:34,910 --> 01:09:33,660
essential Dogma kind of starts to evolve

1744
01:09:37,130 --> 01:09:34,920
when we think of like the genetic code

1745
01:09:38,510 --> 01:09:37,140
of like codons to proteins and DNA like

1746
01:09:40,970 --> 01:09:38,520
is that something that might have

1747
01:09:42,470 --> 01:09:40,980
existed with like this pre-state or

1748
01:09:44,570 --> 01:09:42,480
would this be something we only see with

1749
01:09:47,150 --> 01:09:44,580
like the rise of like I don't think the

1750
01:09:49,849 --> 01:09:47,160
central dogma even exists today

1751
01:09:51,709 --> 01:09:49,859
okay we we know we know that that's we

1752
01:09:54,530 --> 01:09:51,719
know that that's not true we know that

1753
01:09:56,270 --> 01:09:54,540
there are there are ways that um that

1754
01:09:58,189 --> 01:09:56,280
there can be you know post-translational

1755
01:10:00,290 --> 01:09:58,199
modifications you have a virtual

1756
01:10:03,950 --> 01:10:00,300
transcription and so on and so forth so

1757
01:10:07,490 --> 01:10:03,960
so organisms uh even today can rewrite

1758
01:10:09,950 --> 01:10:07,500
their their genome and so

1759
01:10:12,590 --> 01:10:09,960
um you know when when did the you know

1760
01:10:14,630 --> 01:10:12,600
of course we we you know we

1761
01:10:17,209 --> 01:10:14,640
the first people didn't

1762
01:10:19,910 --> 01:10:17,219
you know didn't know about that Crick

1763
01:10:21,470 --> 01:10:19,920
called it the central dogma as a joke

1764
01:10:23,750 --> 01:10:21,480
um but today we know that you know

1765
01:10:26,270 --> 01:10:23,760
viruses are doing this or all the time

1766
01:10:29,630 --> 01:10:26,280
so we have lots of endogenous retro bio

1767
01:10:33,709 --> 01:10:29,640
DNA in our own genomes so so I'm not so

1768
01:10:36,169 --> 01:10:33,719
convinced that um that the um the

1769
01:10:38,870 --> 01:10:36,179
central dogma world as it were

1770
01:10:41,930 --> 01:10:38,880
ever existed or at least even exists uh

1771
01:10:44,630 --> 01:10:41,940
even exists exists now but the extent to

1772
01:10:47,750 --> 01:10:44,640
which you know genome editing

1773
01:10:49,250 --> 01:10:47,760
self-genome editing um evolved in time

1774
01:10:50,689 --> 01:10:49,260
that's not something that I've looked at

1775
01:10:52,430 --> 01:10:50,699
but you certainly could you could you

1776
01:10:54,890 --> 01:10:52,440
could imagine it uh suddenly being

1777
01:10:58,490 --> 01:10:54,900
accelerated during the progenya for

1778
01:11:00,410 --> 01:10:58,500
example but it's going on today so so

1779
01:11:02,810 --> 01:11:00,420
um so um

1780
01:11:04,189 --> 01:11:02,820
and did I answer your question or did I

1781
01:11:06,290 --> 01:11:04,199
just dismiss the premise of the question

1782
01:11:08,030 --> 01:11:06,300
and so it swept it under the rug that

1783
01:11:09,830 --> 01:11:08,040
way no it's very fascinating fascinating

1784
01:11:11,930 --> 01:11:09,840
answer I would say biologists would have

1785
01:11:13,370 --> 01:11:11,940
a lot to discussion I would say

1786
01:11:14,870 --> 01:11:13,380
biologists have a lot to discuss with

1787
01:11:16,669 --> 01:11:14,880
you about um the idea of the central

1788
01:11:19,189 --> 01:11:16,679
dogma but I think that is a fascinating

1789
01:11:21,530 --> 01:11:19,199
way to think about it yeah no no I mean

1790
01:11:23,090 --> 01:11:21,540
I mean I mean you know it may be it may

1791
01:11:25,970 --> 01:11:23,100
be broadly true but there's certainly

1792
01:11:27,950 --> 01:11:25,980
lots of exceptions to it and and so uh

1793
01:11:30,530 --> 01:11:27,960
and that's why I say it's not like it

1794
01:11:34,010 --> 01:11:30,540
really has to happen it's it's just you

1795
01:11:36,729 --> 01:11:34,020
know the balance of you know okay mostly

1796
01:11:40,310 --> 01:11:36,739
these things work but the fact um

1797
01:11:42,350 --> 01:11:40,320
they're not forbidden by any symmetry or

1798
01:11:45,950 --> 01:11:42,360
any law laws of physics or anything like

1799
01:11:48,350 --> 01:11:45,960
this so so how you know fundamentally I

1800
01:11:51,350 --> 01:11:48,360
I think the the main principle of trying

1801
01:11:53,810 --> 01:11:51,360
to underlie genome uh genome stability

1802
01:11:55,970 --> 01:11:53,820
is essentially reproducibility in other

1803
01:11:57,649 --> 01:11:55,980
words you know if everything is

1804
01:11:59,390 --> 01:11:57,659
fluctuating too much

1805
01:12:01,189 --> 01:11:59,400
then you're making too many

1806
01:12:02,330 --> 01:12:01,199
possibilities and and then you you're

1807
01:12:04,070 --> 01:12:02,340
getting

1808
01:12:05,810 --> 01:12:04,080
um generalists as well but not new

1809
01:12:08,330 --> 01:12:05,820
Specialists and so it's really tied up

1810
01:12:09,950 --> 01:12:08,340
with you know whether the organisms are

1811
01:12:12,290 --> 01:12:09,960
optimized for their particular

1812
01:12:14,870 --> 01:12:12,300
environment and for the for you know for

1813
01:12:16,130 --> 01:12:14,880
their niches in in the ecosystem so I

1814
01:12:17,450 --> 01:12:16,140
think these these things are balanced

1815
01:12:22,310 --> 01:12:17,460
like that

1816
01:12:26,090 --> 01:12:23,930
so I'm very excited to see you here

1817
01:12:27,950 --> 01:12:26,100
because I'm also physicist by training

1818
01:12:29,450 --> 01:12:27,960
and I have two questions for you so

1819
01:12:31,250 --> 01:12:29,460
first of all can there be nuclear

1820
01:12:33,590 --> 01:12:31,260
signatures for life

1821
01:12:35,270 --> 01:12:33,600
and second question is we just can

1822
01:12:37,310 --> 01:12:35,280
observe five percent of our universe the

1823
01:12:40,970 --> 01:12:37,320
rest of the universe is dark energy dark

1824
01:12:44,149 --> 01:12:40,980
matter can there be dark matter life

1825
01:12:45,770 --> 01:12:44,159
um okay I so the question is are there

1826
01:12:47,630 --> 01:12:45,780
nuclear signatures of life when you say

1827
01:12:49,430 --> 01:12:47,640
nuclear what do you mean by that at the

1828
01:12:51,350 --> 01:12:49,440
nuclear level like we talk about

1829
01:12:57,290 --> 01:12:51,360
biosignatures of Life can there be

1830
01:13:02,209 --> 01:12:59,570
do I don't understand what you mean

1831
01:13:04,130 --> 01:13:02,219
sorry like uh can there be Nuclear

1832
01:13:11,689 --> 01:13:04,140
Physics going on which can lead to life

1833
01:13:17,689 --> 01:13:13,149
I don't know about

1834
01:13:19,850 --> 01:13:17,699
nuclear certainly Atomic I mean there's

1835
01:13:21,590 --> 01:13:19,860
um I don't really I don't know the

1836
01:13:24,649 --> 01:13:21,600
answer to your question but but I'll

1837
01:13:27,410 --> 01:13:24,659
give you an example there's um there is

1838
01:13:28,070 --> 01:13:27,420
a particular excitation

1839
01:13:32,570 --> 01:13:28,080
um

1840
01:13:34,790 --> 01:13:32,580
in carbon the the oil excitation and and

1841
01:13:36,590 --> 01:13:34,800
it's probably the the first or maybe

1842
01:13:39,410 --> 01:13:36,600
only successful application of the

1843
01:13:40,669 --> 01:13:39,420
anthropic principle uh where he guessed

1844
01:13:42,649 --> 01:13:40,679
that there had to be such an excitation

1845
01:13:44,630 --> 01:13:42,659
for some process to occur that was

1846
01:13:46,370 --> 01:13:44,640
essential for life and indeed it was

1847
01:13:47,750 --> 01:13:46,380
later discovered to be true

1848
01:13:49,430 --> 01:13:47,760
so

1849
01:13:51,470 --> 01:13:49,440
I don't really know the answer to your

1850
01:13:54,590 --> 01:13:51,480
question it's not impossible because

1851
01:13:56,270 --> 01:13:54,600
this whole example is is a sort of very

1852
01:13:58,310 --> 01:13:56,280
strange one it's obviously something

1853
01:13:59,209 --> 01:13:58,320
that if you take those sort of

1854
01:14:02,390 --> 01:13:59,219
perspective that you should be looking

1855
01:14:03,830 --> 01:14:02,400
at large scales of systems you would

1856
01:14:05,630 --> 01:14:03,840
never think that there would be this

1857
01:14:07,209 --> 01:14:05,640
kind of thing happening but we also know

1858
01:14:10,010 --> 01:14:07,219
in physics that there was a scale

1859
01:14:11,450 --> 01:14:10,020
interference and that small uh

1860
01:14:13,550 --> 01:14:11,460
negligible effects kind of large

1861
01:14:16,910 --> 01:14:13,560
consequences I have a whole other talk

1862
01:14:19,130 --> 01:14:16,920
about about that in trying to understand

1863
01:14:21,649 --> 01:14:19,140
um the the the tree-like evolution of

1864
01:14:24,950 --> 01:14:21,659
Life which I'm not going to talk about

1865
01:14:26,450 --> 01:14:24,960
um so so I don't I don't really know

1866
01:14:28,250 --> 01:14:26,460
um there was a second question a second

1867
01:14:29,810 --> 01:14:28,260
question was we can only observe five

1868
01:14:32,209 --> 01:14:29,820
percent of our universe because the rest

1869
01:14:33,830 --> 01:14:32,219
of the universe is large right so can

1870
01:14:35,390 --> 01:14:33,840
there be dark matter can there be dark

1871
01:14:43,030 --> 01:14:35,400
matter and can you have can you have

1872
01:14:51,189 --> 01:14:45,590
is very very enthusiastically ready to

1873
01:14:57,169 --> 01:14:55,070
so I I think that the life is you know

1874
01:14:58,729 --> 01:14:57,179
is essentially an inexorable consequence

1875
01:15:00,470 --> 01:14:58,739
of the laws of physics I don't think

1876
01:15:02,930 --> 01:15:00,480
it's Unique or an accident

1877
01:15:05,570 --> 01:15:02,940
so yes that's my answer but I have no

1878
01:15:07,430 --> 01:15:05,580
scientific reason for for answering your

1879
01:15:09,410 --> 01:15:07,440
question in the affirmative

1880
01:15:10,189 --> 01:15:09,420
yes please go ahead yes hello Professor

1881
01:15:14,510 --> 01:15:10,199
like

1882
01:15:16,490 --> 01:15:14,520
am after your talk so thank you thank

1883
01:15:20,510 --> 01:15:16,500
you so much actually I have the similar

1884
01:15:22,550 --> 01:15:20,520
notion like uh I the like uh

1885
01:15:24,350 --> 01:15:22,560
like whatever you have presented here

1886
01:15:25,910 --> 01:15:24,360
like I'm I'm literally feeling we share

1887
01:15:28,490 --> 01:15:25,920
the similar Vibe actually I'm the second

1888
01:15:32,810 --> 01:15:28,500
year PhD student in astronomy and I have

1889
01:15:34,610 --> 01:15:32,820
a degree in physics and so like I'm

1890
01:15:40,010 --> 01:15:34,620
sorry I'm a little nervous but I have I

1891
01:15:47,149 --> 01:15:43,250
so uh yeah I I want to ask like uh What

1892
01:15:49,430 --> 01:15:47,159
uh since uh yeah like I also like

1893
01:15:51,709 --> 01:15:49,440
the earth-centric like investigation of

1894
01:15:53,990 --> 01:15:51,719
life it it it really doesn't convince me

1895
01:15:57,709 --> 01:15:54,000
to for like to to see the life outside

1896
01:15:59,870 --> 01:15:57,719
the universe and so like I'm really

1897
01:16:01,910 --> 01:15:59,880
interested to study the like uh physical

1898
01:16:04,250 --> 01:16:01,920
Evolution like how how we can study the

1899
01:16:07,189 --> 01:16:04,260
life like after the universe like and

1900
01:16:10,370 --> 01:16:07,199
and it is true that uh we should have a

1901
01:16:12,830 --> 01:16:10,380
generic uh like generic definition how

1902
01:16:13,790 --> 01:16:12,840
should life look like so that's why I'm

1903
01:16:15,890 --> 01:16:13,800
very much interested in the

1904
01:16:17,689 --> 01:16:15,900
thermodynamic evolution of life so I

1905
01:16:20,030 --> 01:16:17,699
just want to know like what are your

1906
01:16:21,830 --> 01:16:20,040
thoughts about like what do you what do

1907
01:16:23,930 --> 01:16:21,840
you think about like because there are

1908
01:16:25,490 --> 01:16:23,940
many uh researchers who are doing uh

1909
01:16:27,530 --> 01:16:25,500
great work on that the on the

1910
01:16:29,930 --> 01:16:27,540
thermodynamic evolution of life so I

1911
01:16:32,750 --> 01:16:29,940
just want to know your thoughts on that

1912
01:16:35,750 --> 01:16:32,760
and I'm like I'm super excited to work

1913
01:16:38,270 --> 01:16:35,760
on on this field and uh yeah like even

1914
01:16:40,070 --> 01:16:38,280
uh I'm in second year and I like I have

1915
01:16:41,689 --> 01:16:40,080
already decided I want my second PhD in

1916
01:16:44,030 --> 01:16:41,699
my physics and I want to study the

1917
01:16:45,830 --> 01:16:44,040
thermodynamic evolution of Life So yeah

1918
01:16:50,990 --> 01:16:45,840
thank you

1919
01:16:52,250 --> 01:16:51,000
kind words and um now I don't I don't

1920
01:16:56,750 --> 01:16:52,260
quite understand what is the question

1921
01:17:03,649 --> 01:16:58,850
the microphone is next

1922
01:17:07,130 --> 01:17:03,659
yeah so uh there is uh let the the the

1923
01:17:09,830 --> 01:17:07,140
Third Law of like uh thermodynamics yeah

1924
01:17:11,030 --> 01:17:09,840
the thermo uh yeah the entropy so it it

1925
01:17:13,610 --> 01:17:11,040
says like

1926
01:17:16,669 --> 01:17:13,620
um every natural uh laws in the world

1927
01:17:19,910 --> 01:17:16,679
they have a particular direction and it

1928
01:17:22,550 --> 01:17:19,920
find this is It's that's that's if if we

1929
01:17:25,430 --> 01:17:22,560
think about that that's that's itself is

1930
01:17:28,729 --> 01:17:25,440
a is a very great like itself is a very

1931
01:17:30,110 --> 01:17:28,739
great it tells like every natural you

1932
01:17:32,630 --> 01:17:30,120
know process in the world they have a

1933
01:17:34,610 --> 01:17:32,640
specific Direction and what I feel like

1934
01:17:37,430 --> 01:17:34,620
yeah what I what I feel like that's

1935
01:17:40,130 --> 01:17:37,440
that's my hypothesis like that life is

1936
01:17:42,410 --> 01:17:40,140
not the you know the the most like the

1937
01:17:45,649 --> 01:17:42,420
the most probable state of state of the

1938
01:17:48,110 --> 01:17:45,659
of the nature nature doesn't want right

1939
01:17:50,330 --> 01:17:48,120
that's what I think and I want to study

1940
01:17:52,490 --> 01:17:50,340
this uh with uh like thermodynamic

1941
01:17:54,410 --> 01:17:52,500
evolution of life that's why uh yeah I

1942
01:17:56,510 --> 01:17:54,420
want to study that so I wanted to know

1943
01:17:59,030 --> 01:17:56,520
your uh okay so I think I think I I

1944
01:18:01,070 --> 01:17:59,040
think I'm sorry I was so long

1945
01:18:03,530 --> 01:18:01,080
I think I can paraphrase your your

1946
01:18:05,590 --> 01:18:03,540
question so tell me if this is a

1947
01:18:10,250 --> 01:18:05,600
reasonable paraphrasing of your question

1948
01:18:13,070 --> 01:18:10,260
why why the why does life inexorably

1949
01:18:16,790 --> 01:18:13,080
become more and more complex

1950
01:18:19,130 --> 01:18:16,800
I I and I think that is a very important

1951
01:18:21,050 --> 01:18:19,140
foundational question because you might

1952
01:18:23,870 --> 01:18:21,060
say okay let's suppose you believed in

1953
01:18:26,090 --> 01:18:23,880
the only World which I actually as it

1954
01:18:28,070 --> 01:18:26,100
happens I I don't believe in it but but

1955
01:18:30,530 --> 01:18:28,080
let's suppose you did then you might say

1956
01:18:34,070 --> 01:18:30,540
well okay so I get these uh these uh

1957
01:18:37,130 --> 01:18:34,080
these all the catalytic uh replicators I

1958
01:18:40,250 --> 01:18:37,140
have RNA doing all the functions of of

1959
01:18:42,590 --> 01:18:40,260
Life uh why isn't the world just you

1960
01:18:45,169 --> 01:18:42,600
know knee-deep in uh self-replicating

1961
01:18:47,390 --> 01:18:45,179
RNA molecules you know why do we have

1962
01:18:49,729 --> 01:18:47,400
arts and elephants and and blue whales

1963
01:18:51,250 --> 01:18:49,739
and things like this and so so I think

1964
01:18:54,830 --> 01:18:51,260
the the you know the the

1965
01:18:57,590 --> 01:18:54,840
fundamental question is why do you have

1966
01:19:00,530 --> 01:18:57,600
this uh Evolution to greater and greater

1967
01:19:01,790 --> 01:19:00,540
complexity and I think that's a

1968
01:19:04,130 --> 01:19:01,800
um that's a question that we don't have

1969
01:19:05,570 --> 01:19:04,140
a good answer for now I'll tell you what

1970
01:19:07,250 --> 01:19:05,580
happens when we try to model living

1971
01:19:12,169 --> 01:19:07,260
systems

1972
01:19:14,270 --> 01:19:12,179
say in a computer you make an artificial

1973
01:19:17,030 --> 01:19:14,280
ecosystem lots of things interacting

1974
01:19:19,189 --> 01:19:17,040
with each other and you run it and what

1975
01:19:21,350 --> 01:19:19,199
happens is it does evolve in complexity

1976
01:19:22,370 --> 01:19:21,360
just a little bit and then it just stops

1977
01:19:24,590 --> 01:19:22,380
evolving

1978
01:19:26,930 --> 01:19:24,600
it just stay it stays constantly and it

1979
01:19:29,330 --> 01:19:26,940
really the simulation does not involve

1980
01:19:33,530 --> 01:19:29,340
more and more arbitrarily complex Life

1981
01:19:36,830 --> 01:19:33,540
As Time proceeds so we try to figure out

1982
01:19:39,229 --> 01:19:36,840
uh what is the fundamental mechanisms

1983
01:19:41,930 --> 01:19:39,239
genetic mechanisms that could enable

1984
01:19:45,890 --> 01:19:41,940
this increase to give you as you put it

1985
01:19:48,110 --> 01:19:45,900
this directionality of life and what we

1986
01:19:50,570 --> 01:19:48,120
discovered was this and it relates to

1987
01:19:53,149 --> 01:19:50,580
things I emphasize in the talk

1988
01:19:54,470 --> 01:19:53,159
mostly when we think about Evolution you

1989
01:19:57,050 --> 01:19:54,480
know you read the newspapers you think

1990
01:19:59,270 --> 01:19:57,060
about uh mutations and point mutations

1991
01:20:01,550 --> 01:19:59,280
and things like this I don't think those

1992
01:20:03,290 --> 01:20:01,560
things are very important at all for

1993
01:20:06,169 --> 01:20:03,300
evolution on the large scale what we

1994
01:20:08,689 --> 01:20:06,179
discovered in computer simulations was

1995
01:20:11,209 --> 01:20:08,699
that there's two things that cause life

1996
01:20:13,189 --> 01:20:11,219
to inexorably get more and more complex

1997
01:20:16,090 --> 01:20:13,199
and that is first of all you have

1998
01:20:18,830 --> 01:20:16,100
horizontal Gene transfer so you have

1999
01:20:19,669 --> 01:20:18,840
mechanisms that enable

2000
01:20:22,130 --> 01:20:19,679
um

2001
01:20:24,470 --> 01:20:22,140
essentially an evolving system to really

2002
01:20:27,110 --> 01:20:24,480
find its its local maximum or local

2003
01:20:28,430 --> 01:20:27,120
minimum Optimum and the other is Gene

2004
01:20:32,630 --> 01:20:28,440
duplication

2005
01:20:34,430 --> 01:20:32,640
because you make a copy of a gene and

2006
01:20:35,810 --> 01:20:34,440
then one copy goes off and Carries On

2007
01:20:37,689 --> 01:20:35,820
doing what it was supposed to be doing

2008
01:20:40,610 --> 01:20:37,699
the other one can evolve without

2009
01:20:42,050 --> 01:20:40,620
deleterious effect on the organism and

2010
01:20:44,830 --> 01:20:42,060
when you look in in The evolutionary

2011
01:20:47,510 --> 01:20:44,840
history of of life and you look at uh

2012
01:20:49,310 --> 01:20:47,520
genomes you see throughout this

2013
01:20:52,189 --> 01:20:49,320
pervasive influence of horizontal Gene

2014
01:20:55,550 --> 01:20:52,199
transversely in microbial organisms and

2015
01:20:58,550 --> 01:20:55,560
um and and and Gene duplication and you

2016
01:20:59,689 --> 01:20:58,560
see Gene duplication in all branches of

2017
01:21:02,030 --> 01:20:59,699
life

2018
01:21:04,790 --> 01:21:02,040
um so so I think what you have to try to

2019
01:21:05,990 --> 01:21:04,800
understand is the the interplay between

2020
01:21:09,110 --> 01:21:06,000
these different

2021
01:21:11,030 --> 01:21:09,120
our processes at the genetic level then

2022
01:21:14,450 --> 01:21:11,040
have consequences for the large-scale

2023
01:21:18,350 --> 01:21:14,460
complexity of organisms so we we built

2024
01:21:22,610 --> 01:21:19,850
um computer model of an evolving

2025
01:21:25,510 --> 01:21:22,620
ecosystem which has continual growth of

2026
01:21:28,610 --> 01:21:25,520
complexity due to those particular

2027
01:21:30,590 --> 01:21:28,620
genetic operators and it's not a very

2028
01:21:32,810 --> 01:21:30,600
realistic model and the model and the

2029
01:21:35,330 --> 01:21:32,820
method of the the way we measured

2030
01:21:37,250 --> 01:21:35,340
complexity was completely unrealistic

2031
01:21:39,410 --> 01:21:37,260
and we measured it by the length of the

2032
01:21:41,209 --> 01:21:39,420
genome as opposed to something like

2033
01:21:44,030 --> 01:21:41,219
common golf complexity or some other

2034
01:21:47,770 --> 01:21:44,040
algorithmic complexity measure but um

2035
01:21:51,649 --> 01:21:47,780
but it it does show you that certain

2036
01:21:52,910 --> 01:21:51,659
genetic processes can give rise when

2037
01:21:54,530 --> 01:21:52,920
they interact with the environment and

2038
01:21:57,410 --> 01:21:54,540
that was important in our in our

2039
01:21:59,750 --> 01:21:57,420
calculation I can give rise to this

2040
01:22:01,370 --> 01:21:59,760
direction of life this ever increasing

2041
01:22:02,990 --> 01:22:01,380
growth of complexity

2042
01:22:05,810 --> 01:22:03,000
so that's the best I can do in answering

2043
01:22:07,370 --> 01:22:05,820
your question is that helpful

2044
01:22:08,930 --> 01:22:07,380
okay unfortunately run out of time for

2045
01:22:10,550 --> 01:22:08,940
questions hopefully you can find Nigel

2046
01:22:15,380 --> 01:22:10,560
at the dinner but let's thank our