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Introduction to Systems Biology
This will be a review of Denis Noble's paper ...
Quote
Claude Bernard, the first systems biologist, and the future of physiology

Authors
Denis Noble
First published: 18 December 2007Full publication history
DOI: 10.1113/expphysiol.2007.038695  View/save citation
Cited by (CrossRef): 91 articles Check for updates Citation tools
Article has an altmetric score of 19
This article is based on the Paton Lecture delivered with the same title to the Life Sciences 2007 meeting in Glasgow in July 2007.
Corresponding author D. Noble: Department of Physiology, Anatomy and Genetics, Parks Road, Oxford OX1 3PT, UK. denis.noble@dpag.ox.ac.uk

Abstract
The first systems analysis of the functioning of an organism was Claude Bernard's concept of the constancy of the internal environment (le milieu intérieur), since it implied the existence of control processes to achieve this. He can be regarded, therefore, as the first systems biologist. The new vogue for systems biology today is an important development, since it is time to complement reductionist molecular biology by integrative approaches.
...
Many other discoveries of this kind (Finar, 1964) led to the idea that life itself could be reduced to chemistry and physics.   This was the challenge that physiologists such as Claude Bernard faced. His answer was precise. Neither vitalism nor chemical reductionism characterized living organisms.

...

The principles of systems biology
First principle: biological functionality is multilevel I start with this principle because it is obviously true, all the other principles can be shown to follow from it, and it is therefore the basis on which a physiological understanding of the phenomenon of life must be based.
...
It is hard to think of a more important overall systems property than the one Bernard first identified.  Yet, the language of modern reductionist biology often seems to deny this obvious truth.

...

Second principle: transmission of information is not one way The central dogma of molecular biology (Crick, 1970) is that information flows from DNA to RNA, from RNA to proteins, which can then form protein networks, and so on up through the biological levels to that of the whole organism. Information does not flow the other way.
...
Moreover, the DNA code itself is marked by the organism. This is the focus of the rapidly growing field of epigenetics (Qiu, 2006). At least two such mechanisms are now known at the molecular level: methylation of cytosine bases and control by interaction with the tails of histones around which the DNA is wound. Both of these processes modulate gene expression.
...
There is nothing new in the idea that such feedback control of gene expression must exist. It is, after all, the basis of cell differentiation. All nucleated cells in the body contain exactly the same genome (with the exception of course of the germ cells, with only half the DNA). Yet the expression pattern of a cardiac cell is completely different from, say, a hepatic or bone cell. Moreover, whatever is determining those expression levels is accurately inherited during cell division. This cellular inheritance process is robust; it depends on some form of gene marking. It is this information on relative gene expression levels that is critical in determining each cell type.

By what principle could we possibly say that this is not relevant information? In the processes of differentiation and growth it is just as relevant as the raw DNA sequences. Yet, it is clear that this information does travel 'the other way'. The genes are told by the cells and tissues what to do, how frequently they should be transcribed and when to stop. There is 'downward causation' (Noble, 2006; chapter 4) from those higher levels that determines how the genome is 'played' in each cell (Fig. 2). Moreover, the possible number of combinations that could arise from so many gene components is so large (Feytmans et al. 2005) that there wouldn't be enough material in the whole universe for nature to have tried more than a small fraction of the possible combinations even over the billions of years of evolution (Noble, 2006; chapter 2).

...

Third principle: DNA is not the sole transmitter of inheritance The defenders of the original version of the central dogma would argue that, while my conclusions regarding the second principle are correct, what happens when information is transmitted to the next generation through the germ-line nevertheless involves wiping the slate clean of epigenetic effects. Methylation of cytosine bases and other forms of genome marking are removed. The genome is reset so that 'Lamarckism' is impossible.

But this is to put the matter the wrong way round. We need to explain why the genome (usually) reverts to an unmarked state. We don't explain that by appealing to the central dogma, for that dogma is simply a restatement of the same idea.

...

Fourth principle: the theory of biological relativity; there is no privileged level of causality

Fifth principle: gene ontology will fail without higher-level insight

Sixth principle: there is no genetic program

Seventh principle: there are no programs at any other level

Eighth principle: there are no programs in the brain

Ninth principle: the self is not an object

onclusions
Tenth principle: there are many more to be discovered; a genuine 'theory of biology' does not yet exist. Well, of course, choosing just 10 principles was too limiting. This last one points the way to many others of whose existence we have only vague ideas. We do not yet have a genuine theory of biology. The Theory of Evolution is not a theory in the sense in which I am using the term. It is more an historical account, itself standing in need of explanation. We don't even know yet whether it consists of events that are difficult, if not impossible, to analyse fully from a scientific perspective, or whether it was a process that would have homed in to the organisms we have, regardless of the conditions. My own suspicion is that it is most unlikely that, if we could turn the clock right back and let the process run again, we would end up with anything like the range of species we have today on earth (Gould, 2002).

http://onlinelibrary.wiley.com/doi/10.1113/expphysiol.2007.038695/full

  • Martin.au
  • Thingyologist
Re: Introduction to Systems Biology
Reply #1
Given your propensity for 'failing to read', how are you going to write a review?
"That which can be asserted with evidence can also be dismissed without evidence." (Dave Hawkins)

  • Photon
  • I interfere with myself
Re: Introduction to Systems Biology
Reply #2
As usual, he'll just insert what he thinks the author meant to say, which uncannily will just happen to agree with whatever ridiculous misinterpretation he's peddling at the time.  The actual written words are nearly irrelevant to this process.

  • Pingu
Re: Introduction to Systems Biology
Reply #3
Nice to see you finally taking up my recommendation to read Denis Noble, Dave!  I told you you would like him.

Quote from: Pingu 12-13-2009, 10:33 AM
I'm just reading a very nice book-length essay by Denis Noble called The Music of Life.  Anyone else read it?

Socrates, Supersport, Clast, Dave, you might enjoy it.




Quote from:  author=Pingu 07-11-2010, 12:44 AM
Oh, and Dave, read this very nice article by Denis Noble:

http://www.musicoflife.co.uk/pdfs/GenesandCausation.pdf

It's beautifully written, and you'll probably like it.



Quote from: Pingu 08-24-2010, 05:32 PM
Quote from: Dave Hawkins;1066983
Quote from: Febble;1065891
Dave, I've asked you before - have you read Denis Noble's book, The Music of Life?  I think you'd like it.

It's an interesting counter-take on Dawkins' view of The Selfish Gene.

And that's an interesting article by Shapiro.  Thanks.
You're welcome.  You should also read his second one I linked about bacteria being small but not stupid.  Because bacteria are so highly sophisticated, it sort of puts a big question mark over that whole idea of bacteria somehow being a simple organism from which all of life descended.

Dave, I'll say this for the gazillionth time: nobody thinks that all life descended from a modern bacterium.

Do you understand what that means?  A modern bacterium is just as evolved as we are - more so if anything, because there have been more generations in their line than in ours.

Both modern bacteria and humans descended from a common ancestor that was not only far simpler than us, but far simpler than a modern bacterium.

Pointing to the complexities of a modern bacterium and saying - hey, look, that's thing we are supposed to have descended from, is plain silly.

Please don't say it again.

Oh, and read that Dennis Noble book, or failing that, the website I linked to.

Quote
Tell me ... why do you think it's reasonable to believe that copying errors evolved a system of proofreading to prevent copying errors?  That seems like a really weird belief to me.

Of course.  It's not a belief anyway, it's a reasonable proposition.  If too many errors causes populations to go extinct from "mutational meltdown" and two few cause populations to go extinct because of failure to adapt, the ones that don't go extinct will tend to be those in which the mutational rates are at some optimal rate.  That may well be a result of counterbalancing processes that tend to maintain fidelity despite factors that reduce it.

A lot of your problem in understanding Dave, seems to arise from your difficult with comprehending the notion of an optimum, or a medium.  You seem to live in a black and white world in which some=all and few = none.

The universe doesn't tend to work that way.  Check out the [WIKI]Central limit theorem.[/WIKI]

Quote from: Pingu 06-28-2014, 02:51 PM
Quote from: Dave Hawkins;2381009
Quote from: Pingu;2381005
Quote from: Dave Hawkins;2380997
My patience is wearing thin trying to get willfully blind people to see.  Pretty soon it might be time to just join the 3W people in simply putting you out of business.

So the fact that I was trying to get you to read Denis Noble for years counts for nothing, eh, Dave?

Note that my patience did not wear thin, and finally you decided that the "3W people" had something to offer.

At which point you turn round and accuse us of being "wilfully blind".
Yes, because you don't accept any of the really obvious stuff they say.

Although oddly enough, Noble thinks I do:

Quote from: Denis Noble, to Pingu, by email
I came across some of your remarks on one of the blog sites concerned with my Experimental Physiology article.
 

I just wanted to say that I enjoyed what you wrote. You have a very good feel for what I was saying.



Quote from: Pingu 08-01-2014, 10:48 AM
Dave, try Denis Noble's Music of Life.

If you don't want to shell out for the book, you can watch his lecture on the same material here:




http://videolectures.net/eccs07_noble_psb/

There's an article here:

http://ep.physoc.org/content/98/8/1235.full.pdf+html

With a FAQ here:

http://musicoflife.co.uk/Answers-menu.html

In fact - start with the FAQ, Dave.

I guess my patience was finally rewarded!
I have a Darwin-debased mind.

  • Pingu
Re: Introduction to Systems Biology
Reply #4
So when can we expect your review, Dave?
I have a Darwin-debased mind.

Re: Introduction to Systems Biology
Reply #5
I don't have the impression that you were the one that introduced me to Noble. I think I ran across him because of my interest in Shapiro which goes back a long time. I guess we should call him Saint Shapiro now. You guys may not recognize him as such but I have for a long time and one of the reasons I'm all of a sudden more interested in Denis Noble is because it appears that Denis Noble also seems to regard him as Saint Shapiro.

So I think rather than me thanking you for introducing me to Noble, you should probably be thanking me for introducing you to the whole Third Way movement via Shapiro. And yes, Denis Noble seems to be a prominent Third Wayer that we should listen to.

  • Photon
  • I interfere with myself
Re: Introduction to Systems Biology
Reply #6
I don't have the impression that you were the one that introduced me to Noble. I think I ran across him because of my interest in Shapiro which goes back a long time. I guess we should call him Saint Shapiro now. You guys may not recognize him as such but I have for a long time and one of the reasons I'm all of a sudden more interested in Denis Noble is because it appears that Denis Noble also seems to regard him as Saint Shapiro.

So I think rather than me thanking you for introducing me to Noble, you should probably be thanking me for introducing you to the whole Third Way movement via Shapiro. And yes, Denis Noble seems to be a prominent Third Wayer that we should listen to.
Dave would have run into that school, even without a weapon, to take on that shooter.

Casting yourself as the hero doesn't work with historical revisionism any better than self-aggrandizing hypotheticals.

  • Pingu
Re: Introduction to Systems Biology
Reply #7
I don't have the impression that you were the one that introduced me to Noble.

No, you probably don't, as you routinely ignore my posts, even when they are direct replies to you. But as you can see, I did.


I think I ran across him because of my interest in Shapiro which goes back a long time. I guess we should call him Saint Shapiro now. You guys may not recognize him as such

No, we don't recognise people as saints, Dave, not most of us. and not qua scientists.

but I have for a long time and one of the reasons I'm all of a sudden more interested in Denis Noble is because it appears that Denis Noble also seems to regard him as Saint Shapiro.

Well, it makes more sense that you would become interested in him because he acknowledged Shapiro than that I recommended him to you.

So I think rather than me thanking you for introducing me to Noble, you should probably be thanking me for introducing you to the whole Third Way movement via Shapiro. And yes, Denis Noble seems to be a prominent Third Wayer that we should listen to.

Well, no, you didn't. And, as VoxRat has told you, he's been teaching Shapiro's work for years.

You aren't as brilliant as you think you are, you know, Dave.
I have a Darwin-debased mind.

  • Pingu
Re: Introduction to Systems Biology
Reply #8
And I don't think you've even read Shapiro's book, or any of his papers. 

Just his blog articles amirite?
I have a Darwin-debased mind.

Re: Introduction to Systems Biology
Reply #9
That's right. I don't read someone's book until I am sold on the idea that I should read it for whatever reason. Life is too short.

  • Pingu
Re: Introduction to Systems Biology
Reply #10
That's right. I don't read someone's book until I am sold on the idea that I should read it for whatever reason. Life is too short.

And you aren't yet sold on the idea of reading Shapiro's book? Even though you think he's a saint?

I have a Darwin-debased mind.

  • VoxRat
  • wtactualf
Re: Introduction to Systems Biology
Reply #11
Great "review" shaping up here!  :thumbsup:
"I understand Donald Trump better than many people because I really am a lot like him." - Dave Hawkins

  • VoxRat
  • wtactualf
Re: Introduction to Systems Biology
Reply #12
That's right. I don't read someone's book until I am sold on the idea that I should read it for whatever reason. Life is too short.
Remember that time you claimed to have read Darwin's Origin of Species, cover to cover?

"I understand Donald Trump better than many people because I really am a lot like him." - Dave Hawkins

  • Pingu
Re: Introduction to Systems Biology
Reply #13
*click* *click* *click* *click* *click*

aw still no review  :sadcheer:
I have a Darwin-debased mind.

  • Photon
  • I interfere with myself
Re: Introduction to Systems Biology
Reply #14
*click* *click* *click* *click* *click*

aw still no review  :sadcheer:
Franoogling takes time.

  • VoxRat
  • wtactualf
Re: Introduction to Systems Biology
Reply #15
I think Hawkins already summed up Denis Noble's whole point here:

Genomes have everything they need already. Nothing non genetic from the outside is needed.

:rofl:
:rofl::rofl:
:rofl::rofl::rofl:
:rofl::rofl::rofl::rofl:
:rofl::rofl::rofl::rofl::rofl:

"I understand Donald Trump better than many people because I really am a lot like him." - Dave Hawkins

  • Pingu
Re: Introduction to Systems Biology
Reply #16
This is nicely put:

Quote from: Denis Noble
Ninth principle: the self is not an object In brief, the mind is not a separate object competing for activity and influence with the molecules of the body. Thinking in that way was originally the mistake of the dualists, such as Sherrington and Eccles, led by the philosophy of Descartes. Modern biologists have abandoned the separate substance idea, but many still cling to a materialist version of the same mistake (Bennett & Hacker, 2003), based on the idea that somewhere in the brain the self is to be found as some neuronal process. The reason why that level of integration is too low is that the brain, and the rest of our bodies which are essential for attributes such as consciousness to make sense (Noble, 2006; chapter 9), are tools (back to the database idea again) in an integrative process that occurs at a higher level involving social interactions. We cannot attribute the concept of self-ness to ourselves without also doing so to others (Strawson, 1959). Contrary to Crick's view, therefore, our selves are indeed much 'more than the behaviour of a vast assembly of nerve cells and their associated molecules' precisely because the social interactions are essential even to understanding what something like an intention might be. I analyse an example of this point in much more detail in chapter 9 of The Music of Life. This philosophical point is easier to understand when we take a systems view of biology, since it is in many ways an extension of that view to the highest level of integration in the organism.

One of the big drivers of systems neuroscience has been the discovery that the brain is a network rather than a set of modules. Which makes a lot more sense than the hyper-regionalism of the nineties.  There was even a plug-in for one of the major brain imaging software packages called "what does this bit do?" - when you clicked on a brain region you'd get links to all the functional imaging papers that referenced that region.  It was quite clever, but also reveallingly silly.
I have a Darwin-debased mind.

Re: Introduction to Systems Biology
Reply #17
That's right. I don't read someone's book until I am sold on the idea that I should read it for whatever reason. Life is too short.

And you aren't yet sold on the idea of reading Shapiro's book? Even though you think he's a saint?
Getting closer, thanks to Denis Noble's video yesterday.

  • borealis
  • Administrator
Re: Introduction to Systems Biology
Reply #18
TR: ...Shapiro?
DAVE: New guru, who dis?

  • JonF
Re: Introduction to Systems Biology
Reply #19
TR: ...Shapiro?
DAVE: New guru, who dis?
Shapiro's been a Davie guru for years.  IIRC there was a thread on the old TR in which Pingu and Vox eviscerated Dave's misunderstandings of Shapiro.
"I would never consider my evaluation of his work to be fair minded unless I had actually read his own words." - Dave Hawkins

  • VoxRat
  • wtactualf
Re: Introduction to Systems Biology
Reply #20

One of the big drivers of systems neuroscience has been the discovery that the brain is a network rather than a set of modules. Which makes a lot more sense than the hyper-regionalism of the nineties.  There was even a plug-in for one of the major brain imaging software packages called "what does this bit do?" - when you clicked on a brain region you'd get links to all the functional imaging papers that referenced that region.  It was quite clever, but also reveallingly silly.
Surprisingly - in retrospect - this "network" idea was the takeaway (I took away, anyway) from an undergraduate physiological psychology course I took in the early 1970's.  The text - inasmuch as there was one - was Karl Pribram's Languages of the Brain.
"I understand Donald Trump better than many people because I really am a lot like him." - Dave Hawkins

  • Pingu
Re: Introduction to Systems Biology
Reply #21

One of the big drivers of systems neuroscience has been the discovery that the brain is a network rather than a set of modules. Which makes a lot more sense than the hyper-regionalism of the nineties.  There was even a plug-in for one of the major brain imaging software packages called "what does this bit do?" - when you clicked on a brain region you'd get links to all the functional imaging papers that referenced that region.  It was quite clever, but also reveallingly silly.
Surprisingly - in retrospect - this "network" idea was the takeaway (I took away, anyway) from an undergraduate physiological psychology course I took in the early 1970's.  The text - inasmuch as there was one - was Karl Pribram's Languages of the Brain.

Yes.  I mean I don't think anyone expected regionalism, but then some lesion studies seemed to suggest it, and there was the old grandmother neuron thing.  But the thing about following the data is that sometimes the data seems to contradict your theoretical expectations!

So the network discoveries have been pretty cool.  Overblown, but still cool.  Basically, it turned out that most of the regional stuff was noise and the actual signal was from a relatively small number of discrete networks.  Only they probably aren't discrete, and their discovery is in part due to the actual limitations of fMRI.  They are remarkably hard to find in MEG!  Well, we can find networks, but they don't behave the same way, and they overlap differently.
I have a Darwin-debased mind.

  • Pingu
Re: Introduction to Systems Biology
Reply #22
That's right. I don't read someone's book until I am sold on the idea that I should read it for whatever reason. Life is too short.

And you aren't yet sold on the idea of reading Shapiro's book? Even though you think he's a saint?
Getting closer, thanks to Denis Noble's video yesterday.

So you went all in for Noble because he agreed with your assessment of Shapiro as a "saint".  And yet that assessment was based on NOT reading Shapiro's actual book or papers???

wtf Dave?

What made you adopt Shapiro as your saint in the first place if you still aren't "sold" on him enough to even read his book?  And if you still aren't sold on him enough to read his book, whay should Noble's approval of Shapiro's book make you think that Noble is worth reading?

Not that you have, yet, apparently.

When is your review going to be posted?
I have a Darwin-debased mind.

Re: Introduction to Systems Biology
Reply #23
My own suspicion is that it is most unlikely that, if we could turn the clock right back and let the process run again, we would end up with anything like the range of species we have today on earth (Gould, 2002).
Here's a sentence ripe for Davining. On my plain reading of it, it looks like he is saying exactly what Dave does not want him to be saying: that there is plenty of "randomness" (at least in the sense of unpredictability) inherent in evolutionary processes. My prediction, however, is that Dave will home in on the word "unlikely" and try to argue that Noble is making some sort of teleological argument here.

  • Pingu
Re: Introduction to Systems Biology
Reply #24
Also, canonising Shapiro seems a bit unfair on McClintock  :sadcheer:
I have a Darwin-debased mind.