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foreign
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good morning everybody lovely to see you all um we are here to discuss the gene
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machine my name is Ganesh Taylor I'm your host and I'm not going to be doing very much because of these two gentlemen on either side of me
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so with no further Ado dawkins's selfish Gene has been hugely influential both
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within evolutionary biology and The Wider public sphere it is a beautiful simple story that
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genes and not organisms Drive evolutionary change but critics argue the story is
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simplistic the effect of a gene is not always the same and is dependent on its host and
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the cell environment Dennis Noble a pioneer of systems bio biology goes further arguing that the
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organism and not genes are in fact in charge
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so Dennis as you probably already know anyway is a is a world-renowned biologist and professor emeritus of
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cardiovascular physiology at the University of Oxford he's famous for developing the first ever mathematical
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model of cardiac cells in 1960 his most groundbreaking book the music of life
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was the first work in the field of systems biology to my left of course is Richard Dawkins
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who is a biologist and best-selling author he is one of the most famous scientists in the world but you don't
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need me to tell you that anyway with good reason his 1976 work the selfish Gene was the first ever real Blockbuster
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Popular Science book shaping how we have all understood Evolution and where we come from and since then of course he's
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written numerous other bestsellers including the blind watchmaker The God Delusion and climbing Mount improbable
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so I'm going to sit back and let you two take it away I I approach this with some trepidation
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because um Dennis Noble was actually my doctoral examiner [Laughter]
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Richard we're in the chair again so I'm somewhat nervous I hope I pass
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today [Laughter] um I would like to ask you to ignore all
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that was said about the selfish Gene to me the argument today is about one
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paragraph in Dennis's excellent book dance to the tune of life which is a
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wonderful book um except that it's wrong [Laughter]
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um the the sentence well the paragraph concerned is is this book will show that
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there are no genes for anything living organisms have functions which use genes
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to make the molecules they need genes are used they are not active
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causes now I think that's a wonderful sentence because although it's wrong
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it's clear it's absolutely clear and open and articulate and that makes my
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job relatively easy um because I want to show the exact
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opposite is true um the truth is is opposite genes use
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individuals use organisms as tools for their own propagation if Dennis is right
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then I've been wrong for 50 years and so have actually most of the people now
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working in the field um studying animals in Africa and where
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the the kind of assumption is that organisms are working to propagate the
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genes that uh that drive them now I'm I'm not saying for a moment that other
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things in the organism are unimportant the the rhetoric of Dennis's book I
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think is wonderful I mean it's it's a it's a beautiful evocation of the
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um the unity of the organism the fact that all the parts are working together as a system
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um what is wrong however is the view that genes are used
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in a way he's implying that
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when this cell needs to make a protein it goes into the nucleus and consults
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the library which is the genome and takes down the volume
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relevant to the enzyme that's needed absolutely uh and this is the this is
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the one we need we need to make this protein let's get the relevant Gene out and use it
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um that that that is Dennis's view he's nodding vigorously
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um and um absolutely I have no problem with that as a
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physiologist and this is a physiologist I was an embryologist for that matter that is indeed what happens but as an
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evolutionist what matters is that genes are causal agents contradicting Dennis's
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statement um they are not active causes they are active causes in the following well she
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has a better shut up and let should I sort of um
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how how do we ever recognize a Cause well I think the answer is this
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we do an experiment we manipulate you cannot show that something's a cause unless you manipulate and it's a very
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trivial example suppose you have a hypothesis that a crows every
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time a church clock um told So You observe a correlation that the
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the the the clock tolls and the and the crows
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is it causal the only way to be sure is to do an experiment climb up into the
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Clock Tower and change the clock or manipulate the clock ideally make the
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clock till at random and then if the crows uh then
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you've shown a causal link in the case of genes we know that if you
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if you mutate a gene then it will change the phenotype
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more importantly for an evolutionist that change Will Go On to the Next Generation and the next and the next and
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the next and potentially forever um whereas if you change anything else
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no matter how important it may be causally in the embryology of the animal if you break a leg
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circumcise a penis do anything else it will not be transmitted into future
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generations and that's the crucial difference genes are causal in the sense
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that a change in a gene a mutation has a statistical consequence
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in in an indefinite number of future Generations now the reason that matters
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is that natural selection chooses between Alternatives and the
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choice between Alternatives only matters if it is potentially Immortal or at least
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if it goes on for a very large number of generations darwinian
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Theory which Dennis has a lot of criticism of in his in his book is a theory of differential survival of
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genes in gene pools and that only matters if the genes are
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potentially able to survive in the gene pool for a very long time the ones that do survive are the ones that are that
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have a beneficial causal influence on everybody in which they find themselves
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successive Generations the genes find themselves in bodies again and again the
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ones that survived over many generations will be the ones that have a causal influence on a long succession of what
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is the now shut up amazing yes well I I love that introduction Richard because
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30 years ago I did precisely that experiment let's go through it carefully because I
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think the experiment is important and this was work done with my colleague from Italy daru di Francesco and what we
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discovered in that work about 30 years ago was that a particular protein and
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therefore the gene it's an hcn protein so it's an hcn Gene that was responsible
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for the great majority of the cardiac Rhythm actually can be knocked out all
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the protein blocked and hardly any change in rhythm
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now I'll tell you something else that I think is very important to this debate that's what the great majority of genome
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sequencing and genome Association Studies have shown the association
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levels between the Crow and the the Bell or whatever it was I've forgotten
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now and the association levels are actually generally with a few outlier genes that are very clearly terribly
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important to the organism they can be overridden by the rest of the organism you see and that's exactly what was
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happening in our cardiac pacemaker work what we showed is the the Rhythm goes
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like that that's what's happening in your heart now and it goes with a
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particular frequency let's give it 80 80 beats per minute you block this particular component which we know as a
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matter of physiology contributes 80 percent of the rhythm-generating electric current you knock it out
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there's hardly any change in free can see now I think what is happening is that organisms are terribly robust they
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know how to manage with whatever genes they happen to have so what I think is happening there is simply that another
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network is operating we actually have identified that Network too so we've done all of those experiments already
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and I think the genome-wide association study people have done this endlessly
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During the period in which for what is it now about 20 years of genome sequencing and what we find is that the
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actual Association levels are quite low and that I think is also important as a
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practical consequence because that's the reason why we don't have all the medications that were promised when the
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first human genome sequence was announced in great fanfares on both sides of the Atlantic and around 2000
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with great nature paper of 2001 and that takes me on to another thing that I'd
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like to put to Richard which is this I think the evidence that as you put it
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the organism has gone in and changed its genes is evident in that 2001 nature
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paper on the human genome sequencing if you will want to look it up on your
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mobile phones it's figure 42. and what figure 42 shows is very interesting
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indeed they looked at the sequences for two major groups of proteins the
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chromatins and and transcription factors and what they found was astonishing
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when you look at the domains obviously you can look at it either as a genome sequence or as protein domains that are
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coded for by those genome sequences what you find is that whole domains have been
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pulled apart and put back together and slowly as an accretion of these domains
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now I think you Richard did the best calculation on this many years ago I
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think it was in was the watchmaker the watchmaker blind um very good book incidentally I full of
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Praise of your writing too and the you did the calculations that show how
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improbable it would be that for example the sentence me thinks it is like a
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weasel would arise by pure charms and what you think you I think you did there was to show beautifully with the
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mathematical model that if you held the various bits that had been shown to be
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correct you would get there very quickly and I think that's what organisms have been doing with their genes you see I
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think they do go in I think later on in the discussion I'll explain the mechanism by which they do exactly what
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you're asking for how do they go in to the nucleus and tell the nucleus what to
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do I love the way you put that Richard you see so I think you were absolutely right but probably for the wrong reasons
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yes well now Dennis you're talking about something very interesting which is the robustness of this organisms and the
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ability to um as it well manipulate and change things and that is a wonderful fact from an
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embryological point of view from an epigenetic point of view um but nevertheless
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in the long run as an evolutionist in the long run as the generations go by no
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matter how clever even if organisms do do change what effect genes have and I'm
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sure they do nevertheless in the long run what matters is changes in gene
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frequencies in populations and I'm talking as an evolutionist now not as a
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physiologist or as an embryologist perhaps we could say that genes do two quite different things
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in embryology what they do is influence phenotypes in highly complicated ways
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including the ways you've just enunciated but from an evolutionary point of view
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what matters is the ones that are still here Ten Thousand Years hence
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you actually use the the rather rather Vivid um image I think you said somewhere yes 10 000 years to keep a
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genome that's right if you were to put a genome so if you put Dennis's genome in
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a Petri dish that's right yes um and and keep it um going for for ten thousand
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years well it wouldn't keep going it would Decay as you as you rightly say however the information
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it could be preserved on paper you could actually write it down on a on a in a
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book on a you could carve the ATC and G um
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codons in Granite and and keep it for 10 000 years and then in 10 000 years
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type it into a sequencing machine which we already have and it would recreate an
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identical twin of Dennis Noble no I don't think it would you don't think it
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would no no uh why not well it would he would need one it would need a an egg
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cell oh of course it would yes yes I think we need yeah
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in 10 000 years they will they will have the technology oh I see okay well I now
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definitely need to follow up on a a different issue there and if I may Richard yes
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um because you see what it would need to be is a good self-replicator and you
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won't be surprised that I disagree with you on self-replication because I think that's a central feature because I think
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without the self-replicator I'm not quite sure that I understand what the selfish Gene idea really means now let
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me just explain briefly why it can't be a self-replicator
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the the way in which that arose goes way back to the quantum mechanics Pioneer uh
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in Schrodinger who in 1942 gave lectures in uh the university what not the
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university the Institute of advanced studies in Dublin he published it and what he said in that book is very
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insightful it was that whatever the genetic material was with his DNA
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protein or whatever it would be found to be a highly accurately reproduced
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molecular sequence and he called that an aperiodic Crystal
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the word crystal matters there because you see what you say Richard in your
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books is that it replicates much as Crystal does now I think that's partly
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true but unfortunately not sufficiently true is what exactly happens let's just
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go through it and there's got to be technical for about 20 seconds or so
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um what actually happens is as we all know the double helix discovered by
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Watson and Crick and Rosalind Franklin you remember those images that were
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produced I I see all the women and a few men clapping yes anyway what Rosalind
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was working on very interesting fact was not a crystal
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her work in that critical working out of the double helix was actually on the
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flexible thread that actually is the DNA in a Cell you can crystallize DNA that
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was done much later but not in a living cell otherwise you can never read it now why is the crystal metaphor accurate to
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some degree but not to sufficient degree and it's worth just going through the figures because they're very important
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what happens is the double helix unwinds is a c finds its mate because it
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naturally likes the other one that it likes to come in and link to it and the
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same applies to the T and and the G and so on so every one of them has a mate that's fine
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now that is a pure chemistry thing and you could say that's almost like a
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crystal forming itself because what crystals do is that the other molecules
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that are in solution like to in a lock and key fashion go into the crystal that's all fine so in the same kind of
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way and I think this is the reason why people like Richard say it is a self-replicator and rely on the
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molecular biology to say that they're quite right up to a point now the question is up to what point in all
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chemical reactions there's an energy a formation and breakage and from that you know how frequently it
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will go wrong it's about in the case of the nucleotides it's about one in ten
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thousand nucleotides now you might think that's fine if you wrote a scientific article
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of 10 000 words and you had only one word as a typo you would be very pleased
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but the trouble is that suffices for small viruses like Coronavirus
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because as a mutation rate of one in ten thousand each time it's copied would be
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acceptable if you've only got say 10 or 20 or 30 000 as a genome length we have
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got three billion and the difference is around a million
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fold now how accurate is DNA replication
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obviously that first stage which is Crystal like and I accept the metaphor
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there is accurate up to about 1 in 10 to the four what is the accuracy when the
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cell actually divides and provides two new cells it's one in ten to the ten
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hardly a single that's rather like a proofreader of 10 000 books going
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through ten thousand books and making sure there's not a single error in the whole ten thousand books
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how is that achieved it's utterly amazing it's achieved by the living cell because what then happens as the problem
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of the breakages as we might call them in the DNA formation from the double
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helix and it's Unwound what then happens is the whole Army of enzymes go in and
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literally proofread the mistakes and I only know and that's
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why I say you'd have to put my genome in 10 000 years hence in into a living cell
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to do it now the question is which living cell and because you see that
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will provide all the material initially to enable it to be reproduced so what
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I'm saying is that it cannot be a faithful replicator except in the presence of its vehicle which is the
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living cell so I don't think there can be a neat separation between the replicator and the vehicle
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proofreading is of course very important and that that is one of the ways in
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which true that self-replication happens what matters from an evolutionary point
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of view is that certain genes survive in the gene pool
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and others don't now the proofreading is very important that helps the thing along but what
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matters from The evolutionary point of view is the survival or non-survival in
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the gene pool of successful genes versus unsuccessful genes
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successful genes are the ones which statistically have a positive effect on their own
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Survival through Gene pools and the way they do that is via their phenotypic
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effects their effects Upon A succession of bodies in any particular body we have a
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combination of good genes and bad genes successful and unsuccessful and the body will die or not depending upon all sorts
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of factors that may get struck by lightning it may be eaten by a lion and wasn't looking and so on but on average
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if a gene is successful that what that means is that it has a beneficial effect
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upon a large number of bodies in which it in which it finds itself
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very often it will find itself in the company of bad genes and it'll die
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anyway but statistically on average certain genes will get through the 10
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000 year time of the of more than ten thousand years millions of years will get through uh all those Generations
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because of its average statistical effect upon a whole lot of bodies and
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others will not get through because of their average statistical effect upon a whole lot of bodies that is natural
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selection that is why animals are so good at what they do it's
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why birds are so good at flying it's why moles are so good at digging it's why fish are so good at swimming it's
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because of the average statistical effects of a whole lot of genes working together in concert with one another
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to make good phenotypes and so all the complications of what's
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going on inside the body in embryology all the proofreading all the
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interactions all the things that Dennis described so wonderfully in his book are
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completely irrelevant if what you care about is the survival over many generations of
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certain genes rather than rather than other genes yes I I fully understand
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what you're saying Richard but I don't think you really answered my point because you see I was saying that none
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of that would happen without the cooperation at the least and I would say
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the very active cooperation of the living cell because as I said it's only a living cell that can reproduce
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accurately yes now I think what what we need to do here is to get another
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element into this because I think what you're really worried about is how can
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it be that the body can actually change the genome and that's the big question
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now the reason we know that it can is that we know it controls it that's the
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first step so let's see first of all how that can be done I have two very important colleagues
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have done the work I'm going to describe so I'm going to credit them dick Chen
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worked with me as a graduate student way back in the 1960s and is now working at
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the New York University of New York and has done part of the experiments I'm
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going to describe an event for rec who is a physiologist in the same Department
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as me in Oxford and what they've done is absolutely beautiful they've asked the
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question you see it's the relevant question that I think Richard is asking how can it be that the surface of the
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body or of a cell it might be that it's a unicellular organism then it would be the surface of the organism how can it
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know how can its nucleus know that there is a need to change
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and we now know how that can be done what they've shown
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is best described by imagining first of all that a single nucleotide is about
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the size of my fist and it said it's situated in the nucleus let's put that in the center of the cell
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if we did that on that scale the surface membrane of that cell would
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be way up in Scotland how on Earth can it be that a signal
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through a receptor on the surface can influence the nucleus and we now
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know how that can be done what they both found doing different experiments in different cells was that
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calcium coming through protein channels in that surface membrane using the same
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metaphor way way up up there in Scotland creates a calcium concentration in a
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small Subspace underneath the membrane and that high calcium triggers a
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chemical reaction that produces a messenger and that messenger gets attached to some
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extremely important proteins in the cell those proteins are called tubulins and
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the name suggests what they do they form tubes literally they're a tube trains in
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cells and I'm not joking because what happens is those tubulins run all the
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way through from one edge of the cell to another they have little motors on them little molecular Motors and they can attach a
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messenger molecule to the motor and what then happens is phenomenal they
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literally walk along the tubulin it takes just a few seconds to go from that surface
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imagine on this scale way up there in Scotland to the nucleus what does it do
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in those experiments it changes the gene expression levels in the relevant genes
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that matter for that particular function now the only thing that's missing here
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and I'm sure Richard will pick this up very quickly so I'll say it myself is that those are very recent
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experiments done in 2016 and more recently 2018 I think it was anyway the
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important point is that we don't yet know how that induces genome change and I
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really mean actual change in DNA and yet we know also that those
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processes must be able to do that because we can show that let's take a tumor developing your body
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and it's a bad situation you're beginning to get metastasis so the
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doctors get out the radiotherapy and the chemotherapy they attack it and try to destroy it what happens
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the tumor cells themselves tell the genome to increase the mutation rate how
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can they do that precisely by the kinds of mechanisms I've just described because the mutation rate is under the
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control of what is happening in the body as a whole what then happens is
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phenomenal it happens in your immune system all the time it happens in bacteria all the time
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because they change their genomes in response to antibiotics and what they do
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is very simple you remember that difference between 1 in 10 to the four and one in 10 to the 10
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that depends as I said on the cell having these repair mechanisms the
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proofreading mechanisms but you see they can be down regulated that process can be down regulated and what that does is
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to produce literally millions of new DNA sequences that can then be selected now
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the selection and I agree there is a kind of natural selection here within the organism now the question is very
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simple do those new new sequences get to the germline you bet they do
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and that I'm afraid is where I think the big hole in the theory lies because once
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you can do that you can get what for example Zhang and his colleagues have shown in a paper published in 2018 I can
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send all these references to anybody who sends me an email so if you're worried about whether I'm telling the truth just
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send an email and I will send you the reference what they showed was that a small non-coding RNA that's a little bit
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of Technology but a new a new sequence generated by the organism can pass to
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the germline cells which become eventually of course the eggs and the sperm and what that will do is then tell
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the Next Generation to inherit the metabolic characteristics that were
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conveyed by that I'm I'm sorry to say this because I know this is a dirty word amongst mostly
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evolutionary biologists but Landmark is back very simple all right
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right by the way the um the the the the walking mechanism is simply beautiful it
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is absolutely films absolutely uncanny
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um at one point Dennis I thought you were confusing um gene expression which of course is
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obvious I mean yeah no it didn't confuse them we don't
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um I that's why we I went on to explain how those changes can then be communicated um because that that's an
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extremely important distinction indeed yeah there's there's no no dispute whatever about certain G is being turned
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on in some cells and others in other cells that's that's what embryology is all about however what Dennis went on to
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say is that there's evidence that it actually gets into the germline and um Lamarck is back uh well if
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Lamarck is back um in if we're an indefinite number of generations I'm impressed
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um if it's only for a couple of generations I'm not um but let's suppose that it is for a
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larger number of generations if that's true then I would have to revise
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what I say to include any change in the germline then now now becomes admitted
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into the charm circle of replicators and that's fine
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um I doubt it um but but I I don't want to be dogmatic
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about saying that the the the DNA in the existing germline is all there ever was
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if on some other planet and maybe on this planet it's true the germline can
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be altered then that's fine we Inc we the the broad Church of The Selfish Gene
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can Embrace that um as I say I doubt it yes okay yes but
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look I think the one thing to to perhaps make clear to the audience is this is
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happening in everybody in this room because we had the pandemic that arrived
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with coronavirus now of course we've fortunately developed vaccines against
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the virus and that's been our great saving uh Grace but what would have
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happened anyway with a lot of people dying of course would have been that our immune systems would have done exactly
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what we're describing that is they would have used that mechanism for hypermutating at his mutating extremely
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quickly to produce millions of new DNA sequences and then that is used to be
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what then it gives you the immunity the acquired immunity obviously now what
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Richard is questioning is okay maybe that can occasionally be passed to the
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journal line we don't know that yet whether an immune response can be passed
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to the journal line and I would readily say we don't know that yet but what is
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important is Rich's point about how temporary it is now it's very important
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indeed and I agree with Richard about the importance of temperiness or permanence because it seems to me that
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what these mechanisms give is the option for The evolutionary process to as it
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were try it out if there's an environmental change that makes it very
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difficult to survive and all organisms are under stress and they alter their genomes and pass some of that even
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temporarily onto the next Generations what the next Generations can do is to
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find out whether they do experience that change environment or not if they don't then it's great that it's temporary
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you don't have to alter the main genome if it is more or less permanent and goes
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on for many generations then how can it get assimilated in the genome Conrad Waddington showed how to do that way
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back in the 1950s incidentally his book the strategy of the genes has been
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rightly republished in 2014 so you you can buy it again it was published in
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1957. he did beautiful experiments on fruit flies he induced changes with very
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tiny gentle persuasion as it were from either heat or ether or some other
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experimental techniques in which he could as he would persuade a few of the fries to show a new characteristic and
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he actually determined how many generations would you have to continue to do that in order for it to become
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assimilated into the genome it's about 14. it's not very long
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now what he was showing is what he called genetic assimilation I think it was a great mistake that Waddington was
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ignored by The evolutionary biologist and that's a shame the Waddington effect was actually
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selection I mean it it was not by him well
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the the flies that didn't respond correctly to the heat shock yeah died
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yes that's right so it was selection I'm agreeing with you it only looked like numbers maybe the only point in the
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evening where we totally agree that was selection yes I absolutely agree I'm
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agreeing with you what Waddington was doing it was a simulation of a lamarckian experiment for quite a
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different reason and I think it comes back to your opening question to to me
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do you still hold to the idea that it's agency that organisms have rather than a
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DNA now I do because you see I think what organisms are doing is partly
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through their social choices effectively choosing which genes they will allow to
36:32
survive that's what what insisters social selection yes oh I mean well who
36:40
you mate with for example we're back to Darwin's idea of sexual selection well we are as a social selection so ideas
36:47
why why drag the mark in then I think that's the markian because it's
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part of the use within the social context you see what what landmark was
37:00
insisting on um was the idea that use and disuse was itself something that could be inherited
37:07
and I think this is something of course it starts culturally but it becomes something that can be inherited through
37:14
the fact that you are as organisms choosing the characteristics that you
37:20
want to survive in the later generations why do we marry anybody isn't that why we do it
37:27
I mean this this is perfectly darwinian what you're talking about yes absolutely
37:33
I agree and darwinian Darwin was a lamakian
37:39
I'm not joking no you're not no in 1868 he published his theory of generals
37:46
which is precisely the thing we've now discovered as their extracellular vesicles today so I absolutely totally
37:52
agree with you Richard Darwin was indeed a landmark and I'm a good darwinian
37:58
you're a sixth edition Darwin um Darwin in the sixth edition of the
38:05
original species did uh flirt with lamarchism that is true um that's a historical fact but it's not
38:12
a very important biological fact oh I think it's extremely important okay well
38:17
um no seriously Richard because he he he collaborated with this is not very well
38:23
known he collaborated with physiologists in the last 20 years of his life between 1872 and 1882 he collaborated with my
38:31
predecessor as the chair of physiology um Burton Sanderson and he collaborated
38:37
with his student George romanes in a very simple set of experiments because you see took lamarcianism so seriously
38:45
that he invented this theory of genules and I better just very briefly explain what that is he realized as Richard is
38:52
beautifully explained that you've got to explain how it can be that the body can
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in its changes due to use and disuse communicate any of that to the germline
39:03
otherwise all of that information is Richard beautifully expressed it earlier on would be lost so how can that be
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communicated he couldn't see what could possibly do that so he invented an idea and he admitted it was an idea which was
39:17
that tiny particles put out by the cells themselves which he
39:23
called genules would be able perhaps to pass through the bloodstream down to the
39:28
germline that was his way of explaining there could be Soma to germline expression but he readily admitted at
39:35
the time this is just a hypothesis because he couldn't see them now with 19th century microscopy indeed you could
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not the 20th century microscopy and 21st century microscopy even better we've
39:48
been able to do so and it's the experiments are simply beautiful just go online and ask to look at extracellular
39:55
vesicles made evident by labeling molecules
40:01
fluorescently so they literally glow green yellow red or whatever it might be
40:07
enables you know this is this particular RNA this is this particular DNA and so on and that escapes the limits of light
40:15
microscopy you can actually resolve down to a very tiny particles indeed they're
40:21
called extracellular vesicles those have been shown experimentally to be passed
40:26
to the germline that's how the rnas and dnas the new rnas and dnas get to the
40:32
germline so I think that if he was alive today I
40:38
think Charles Darwin would be praising and cheering the discovery of extra cellular vesicles they are his generals
40:46
and they carry out the function that Darwin proposed now why did you spend the last 20 years of his life
40:52
collaborating with George romanis is because he actually thought this must be right
40:57
so I don't think it's trivial that Darwin was a lamakian okay I think I do think this is actually
41:03
quite misleading um what Darwin's generals was supposed to
41:09
be about was investigating the the current state
41:14
of the body and passing it on to the next Generation so the generals were going all around the body and they were
41:21
um detecting changes in the body um the sort of classic Lamarque and
41:26
examples like the blacksmith's arms getting muscular and the giraffe's neck stretching and things like that
41:32
um Lamarck thought that those were inherited Darwin in his later years thought they were too uh and um the
41:41
general Darwin's generals were going around the body in the bloodstream and picking up information about the current
41:48
state of the body the modifies date of the body the acquired state of the body and going to the germline going to the
41:55
gonads and imprinting the information into the germline now that is a very
42:01
radical idea that's precisely what the exocellular vesicles are doing well yes but but they're not
42:07
it's nothing to do with blacksmith's arms it's it's it's it's them they may be doing something if you're right about
42:13
the immune system you know you seem to be suggesting that what happens is that when when the immune immune system
42:21
uh reacts to an infection like covid and
42:27
um and we become immune to it that immunity gets passed on no I know I
42:32
deliberately said we're not yet sure about that I know you did and I'm glad we are sure about is that other things
42:38
are passed on metabolic disorders are passed on and sexual preference are
42:44
passed off the racial preferences in what in what way it passed on it's passed on in planarians and that's been
42:51
demonstrated again all of these references I'm very happy for people to email me and ask for them but that's
42:58
been shown very recently by Toca and his collaborators in work in Israel and I
43:03
think that is actually a 2021 and how many generations
43:08
well what they're showing okay come back to the point I made about temporary and
43:14
permanent because you see temporary is actually an advantage if you don't yet
43:20
know from an evolutionary perspective whether the change is valuable or not I think it's great you see that epigenetic
43:27
changes and and temporary alterations of the germline are not necessarily passed
43:35
on through many many thousands of generations because if the change in the environment is is really temporary you
43:42
don't want a permanent response so I can see the evolutionary logic of doing it
43:47
in that kind of way you keep it soft until it needs to become hard and then
43:52
you let it become hard you let it then become assimilated into the genome
43:58
well that's fine I mean that that's coming back to the Warrington effect in a way to some extent yeah yes I think
44:04
this is why I said that Waddington was um badly ignored or or sometimes called
44:10
the Baldwin effect sometimes called um yes
44:15
but I think what what's happened today is that we actually now know the precise mechanisms by which it can happen we
44:21
know the molecular biology we know the cellular biology of it so what I'm saying is it's time for evolutionary
44:28
biology to catch up I mean yeah if I may ask in that case how long would it need to be I mean you've asked a few times
44:34
I'm really taken by this sort of temporal thing how long would it need to be to have an effect
44:39
do you think in order to be evolutionarily interesting then it it needs to be
44:46
something that we we see as a change in the gene pool
44:51
um and uh changing the gene pool would be would be I mean I can't put an actual number of Generations on it but but it's
44:59
it's it's it's it's not a proper darwinian change if it's just
45:05
um uh for example the the there's evidence that starvation effects
45:11
yes and these are um uh as it were I mean
45:17
epigenetic effects are are changes in the as the embryo develops
45:24
changes in the expression of genes in different parts of the body so in liver
45:30
cells certain genes are turned on in kidney cells are the genes Eternal muscle cells and other genes eternalism
45:35
those are epigenetic effects now there is some evidence that those epigenetic changes can be
45:42
inherited into the Next Generation and possibly the grandchild generation that's not a a proper gene pool change
45:49
yeah I think Richard is right on that but what we would need to do is to look at the effects after billions of years
45:57
and that's exactly what the Human Genome Project did in its nature paper of 2001.
46:03
remember I've heard to figure 42 of that paper you see there the evidence that
46:08
those genomes were changed by moving great chunks around in the genome
46:15
not time I guess to go through the detail of that but unfortunately that's fairly clear evidence that it must have
46:22
happened during evolutionary time scale fascinating it's obviously also important to say that increasingly with
46:28
modern Technologies people are starting to look at sort of the genomes of um other humanoid species indeed and
46:35
looking into the past to sort of get more information on on perhaps what our more recent ancestors look like and it
46:41
might be quite interesting to sort of see whether or not that those pieces of data can can add to to this conversation
46:48
in in due course what bothers me is is Dennis is saying Lamarck is bad because
46:54
because in order for Lamarck to be back it seems to me we wouldn't need to have something more like the blacksmith's
47:00
arms effect where where an adaptation and I mean the plenty of adaptations that happen in lifetime you your muscles
47:08
develop when you when you use them it will be wonderful maybe on some other planet it happens that when your muscles
47:14
develop when you're you get a suntan when you when you all sorts of adaptive
47:19
changes like that get inherited and that's what Lamar was suggesting and I
47:26
think to say that Lamarck is back is is going to give a misleading impression because people will think you're saying
47:32
that something like the giraffe effect the blacksmith be very precise it is
47:38
that the inheritance of use and disuse is now evident that's the way I would
47:43
well well yes is it I mean you're not going to go out and say that that
47:50
adaptation as we see it in the field as as animals develop camouflage as animals
47:56
develop stronger bones as they as they use them stronger muscles as they use them that
48:02
would be a proper lamakian effect that would be a real adaptive change as a
48:07
consequence and reduce and disuse when we know that the rnas that communicate
48:12
all of that can be transmitted to the germline oh my gosh so we've got part of the evidence that obviously I mean what
48:19
I would want to say on this is this is open field for experimentation in the future that's what we need we need to be
48:26
open to those possibilities on that delightful note please can we take a moment to appreciate the Civility and
48:32
eloquence with which these two gentlemen have debated and disagreed this moment
48:39
can you sign my book Dennis oh my gosh
48:44
look at this oh this is fantastic look at this
48:51
and that is how it's done fabulous