[Fis] Fis Digest, Vol 85, Issue 16--CLOSING

[Jerry LR Chandler]

Youri, Pedro, List:

Perhaps a short footnote to the discussion.

The remarkable success of linear mathematics is not to be denied.  We are all aware of its massive impact on our daily lives and the work that we do.

That being said, the questions turn to evaluation of the ’net value’ of information theory/linear mathematics on the direction of social and cultural values.  In particular, the role of the individual has changed so dramatically.

It seems to me that the nature of informational successes is wildly overestimated.  As Youri alludes, only small categories of issues and challenges can be addressed.  As Youri’s work illustrates, the widely issues of the extreme perplexity of nature remain unapproachable through linear mathematics.  And non-mathematics remains bound to a few variables, not the tens of thousands of factors that are operating in ribosomal information processing during molecular transcription and translations.  

One issue of deep concern is the very limitation of linguistic communication itself.  How many factors can one communicate in a sentence?  How many quantities can one compare to describe a biological object?  To me, this is a very very serious problem. 

How serious is this limitation of expressibility within human languages?  How much meaning can one compress into a few propositional terms?

Beyond the limitations of any one language looms the larger issue of scientific meta-languages, several semeiotic versions used to describe singular natural processes. This also is a very serious challenge.  COVID has opened this issue to the general public and the public has sharply rejected “scientific wisdom”.

Spring is only a few weeks away; I am looking forward to the pleasures of working my garden!

Cheers
Jerry 

> On Feb 1, 2022, at 2:12 PM, Pedro C. Marijuán <pedroc.marijuan at gmail.com> wrote:
> 
> Dear Youri and FIS Colleagues,
> 
> Many thanks for all your personal reflections. It is a great closing of the New Year Lecture.
> What a pity you have been sequestered these weeks by the guardians of orthodoxy!
> 
> For those interested in biological information, the sober realization is that there is a whole world of phenomena to analyze, reinterpret, and cohere. 
> Almost anything in the "received wisdom" about biomolecular phenomena looks partial, biased, insufficient--notwithstanding all the great experimental achievements accumulated. Youri is very eloquent about that in his ribosome research. Something similar seems to be occurring in the neurosciences, also dumbfounded under the sheer accumulation of facts. We lack clarity, concision, coherence in all bio-info arenas. We might say the received wisdom (sequencing, structure/function, Darwinian selection, input/output) at least maintains a "floating line" that gives a shared coherence to international research programs--that at the same time work hard to stifle new thought. A genuine thinking bureaucracy.
> 
> There is also a "mass bureaucracy" in the control and administration of research. All this surrounding bureaucracy has been engrossed by two new factors, presumably. One, not new actually, is the approximate duplication of scientific effort every 30 years or so; for each passing generation after the industrial revolution has doubled the scientific/technological workforce on average. Like in the evolution of central nervous systems we seem to have crossed a threshold in this engrossment of science practitioners. It is an ad hoc industry now, deprived more and more of vocational drivers and subject to a multilayered political/administrative command. There seems to be more than 10 million scientists in the world nowadays (from UNESCO report), and every year another 300,000 would be joining. They need institutions, labs, career development, journals, publications, etc. "Publish or perish"...No wonder a mammoth pseudo-publication system has taken off, degrading the whole system as a way to communicate new research and new thought. And the other factor would relate to the information technologies themselves. Their many advantages have also serious collateral damages for our scientific endeavor. The e-bureaucracy has become larger and larger, and insatiable, a painful sink of our research time. The new ways of e-thinking, influenced by the new communication tools, are superficial and lacking reflection, and at the same time plainly caught into the "identitary fragmentation." Less (serious) scientific books are written, and even less are read. "We students do not read books!", they say nonchalantly... But perhaps more than journals, books have been the fundamental vehicle of scientific thought. 
> 
> It is curious, but somehow these are also social "informational problems." 
> 
> Anyhow, I was motivated by Youri reflections. Hope having not been too rambling.
> And now we have to continue our FIS discussions--in a few days I will send the received proposals so far.
> 
> Best wishes to all, and I join Gordana's greetings to our Chinese Colleagues for their Spring Festival & New Year.
> 
> --Pedro
> 
> El 31/01/2022 a las 11:42, Youri Timsit escribió:
>> about Information, Editors, Humour and Life Metaphors
>> 
>> 
>> Dear all,
>> 
>>  
>> Thanks again to Pedro for allowing these interesting exchanges and thanks
>> to all for
>> your comments around the new year lecture.
>> 
>>  
>> First of all, I would like to point out that I am not an information
>> specialist at all,
>> nor am I a mathematician: I look modestly at the structure of biological
>> macromolecules. And by chance, I simply observed protein networks in the
>> ribosome that were analogous to neural networks. By transitivity, I
>> wondered if
>> these networks could also transmit signals and integrate them, like neural
>> networks: is it information? I don't know Š.
>> 
>>  
>> But that¹s how I came to ask the question, can the architecture of the
>> networks tell us
>> what they do? Can we deduce the 'function' of a network by the way it is
>> connected? If you look through the literature, you can find, for example,
>> these
>> famous "small world networks", the "scale-free" networks,
>> Uri Alon's FFL motifs, but if you look a little deeper, you can see that
>> it's
>> not that simple... the answer is not clear.
>> 
>> I also asked myself a stupid question: is there a kind of
>> 'proportionality' between the difficulty of
>> the tasks to be accomplished and the complexity of the networks that are
>> supposed to process them? If we look at the nervous system, from the
>> simplest
>> organisms to the most complex (which Cajal has started to do), we can see
>> that
>> the more complex the behaviour of organisms is, the more complex their
>> nervous
>> system is... but is there a simple law to describe this phenomenon? and do
>> things start from the ribosome, from LUCA (last universal common ancestor)?
>> 
>>  
>> This is why I called on my mathematical colleagues Daniel Bennequin, who
>> is also a nervous
>> system specialist, and his student Grégoire Sergeant-Perthuis. Ribosome
>> networks
>> and their properties have been described but, of course, this does not
>> allow us
>> to understand how they work. The famous 'structure-function relationships'
>> that
>> serve as the scaffolding for all modern biology have serious limitations.
>> 
>>  
>> And to answer Jerry's question, normally, if we knew the properties of
>> atoms and
>> molecules perfectly, the crystallographic structure of a bacterial ribosome
>> (take for example pdb code: 4y4p which contains 3 tRNAs and is very high
>> resolution): normally, this structure which contains "all the
>> information" should allow us to understand the ribosome completely... But
>> this is not the case. It also requires thousands of tedious biochemical
>> studies, the design of hundreds of mutants in various areas of the rRNA and
>> ribosomal proteins to test their 'functional' roles. And with all this work
>> over half a century, we have painfully arrived at a very mechanistic view
>> of
>> the ribosome and the whole of life... and the essentials still elude us.
>> The
>> conclusion of a recent review by one of the leading experts in the field
>> (Harry
>> Noller) on ribosome dynamics is: "an important unanswered question is: how
>> are intersubunit and head rotations coordinated with all of the other
>> dynamic
>> events of the ribosome during translocation?" (Noller et al., 2017,
>> https://doi.org/10.1017/S0033583517000117 <https://doi.org/10.1017/S0033583517000117>).
>> 
>>  
>> Thus, a purely mechanistic vision does not allow us to understand either
>> the ribosome
>> or living organisms in their entirety and misses entirely the "information
>> flow" that Pedro talks about.
>> 
>> When we see that the entire human genome has been sequenced, that the PDB
>> is filled
>> with hundreds of thousands of macromolecule structures, that the
>> pharmaceutical
>> industry 'excels' in the design of targeted medicines and the belief in the
>> effectiveness of drug design, and that on the other hand, a tiny
>> coronavirus or
>> even an ebola virus containing only 6 genes can wipe out the whole of
>> mankind,
>> we have the right to ask ourselves whether we are not missing something
>> essential in our understanding of living organisms?
>>  
>> 
>> In my opinion, this is where the crucial question of living metaphors,
>> humour,
>> seriousness and aggressiveness of scientific editors comes in...
>>  
>> It seems to me that certain forms of thought, and in particular the choice
>> of metaphors,
>> are more conducive to poetry, humour, and that humour, art and poetry, can
>> often mitigate the aggressive impulses, war and, among other things, the
>> implacable authority of scientific editors (this is in response to the
>> editor's
>> comments on Joe's article). I think S. Freud would not contradict me...
>> sublimation in art, is the last bastion against barbarism...
>>  
>> 
>> In biology, for the moment, it is very comfortable for the community of
>> biologists (and the
>> pharmaceutical industry that controls it) to compare living beings to
>> machines:
>> the whole edifice of molecular biology is based on this reductive analogy
>> that
>> simplifies living beings and their constituents to a mechanistic
>> functioning
>> drawn from analogies with engineering and industry. Genetic 'codes and
>> programmes',
>> and the notions of the famous 'structure/function' relationships that have
>> structured biological thinking since the death of Stalin, Prokofiev in
>> 1953 and
>> the concomitant publication of the structure of the DNA double helix. Each
>> molecule has a specific function and its structure is responsible for it!
>> Of
>> course, there is some truth in this paradigm, but it is not so simple...
>> But
>> one prefers this simple system of thought to wandering in still ill-defined
>> spheres... wandering is very badly tolerated by science although it is its
>> deepest essence....
>>  
>> 
>> If we look at the literature on antibiotics, for example, we realise that
>> many
>> "antimicrobial molecules" are also neuromodulators ... ! We also
>> realise that proteins can have multiple functions, that others have no
>> structure.... etc: there is a huge task to be carried out in biology:
>> redefine
>> the notion of function!
>>  
>> 
>> On the subject of seriousness in science, there are few philosophical
>> works that
>> address this question: what is really serious? It is, however, a serious
>> question... Nietzche had already asked himself about humour and philosophy
>> when
>> he published his "gai savoir"... more recently, we find "en
>> quête du sérieux" by J.LH. Thomas. Rare are the philosophers and
>> scientists who question the seriousness of their approaches... is
>> sequencing
>> the entire human genome really serious? (this question is provocative... I
>> am aware of it) but one can ask the question in
>> view of what this project has really brought?
>> 
>> In this respect, I have the impression that an epistemological perspective
>> on one's own activity is more conducive to a form of humour,
>> relativity and makes people less rigid and therefore less aggressive ?
>> 
>> About competition between living beings (and researchers) ... the famous
>> "struggle for life"..., there are other systems of thought which are
>> still very much in the minority... see "la manifestation de soi" by
>> Jacques Dewitte (édition la découverte..; I don't know if it's translated
>> into
>> English?). Despite the dominant view, we know that ecosystems are based on
>> many
>> other laws than the prey/predator relationship... You only have to look at
>> how
>> a large whale can protect penguins, sea lions and its calf under its fins
>> against the attack of orcas.
>> 
>>  
>> This machine metaphor and all the simplifying ideology about living beings
>> that goes with it
>> is nevertheless dominant and authoritarian today: in my opinion, it
>> guarantees
>> the functioning of a biology at the mercy of the pharmaceutical industry,
>> which
>> wants to reduce living beings to obedient objects.
>> 
>> It is based on a misunderstood Darwinian vision that exalts the survival
>> of the strongest
>> and the best adapted... see the "Darwinian programme for French
>> science" proposed by the president of the CNRS, A. Petit: we are not far
>> from the notion of degenerate art that was hunted down not so long ago by
>> certain regimes.
>>  
>> 
>> In short,there is a whole arsenal of concepts that are the pillars of a
>> neo-liberal
>> reductionist ideology, which, instead of understanding and contemplating
>> the
>> living, seeks to exploit it, if not destroy it. With the machine metaphor,
>> we
>> are not joking, there is no room for humour, we are 'efficient' and
>> 'performing' and we assimilate ourselves to our object of study... we
>> ourselves
>> become machines for producing scientific facts... and multiple guardians
>> ambush
>> everywhere, making sure that this gigantic machine called science works
>> well...
>> That's why it took me a while to answer you, I was transformed for several
>> weeks into a machine asking for money to be able to do science...
>>  
>> 
>> Like any authoritarian system, it comes with a repressive apparatus to
>> enforce it, and
>> I'm taking the risk of proposing here that the main inquisitors are the
>> "scientific editors" and also a large part of our colleagues who
>> "know" where "right and wrong", "true and false",
>> lie on the basis of a supposed rationality.
>>  
>> 
>> One can imagine that showing Chaplin's film "Modern Times", having the
>> Milgram test or
>> listening to a Bach fugue to the editors of major scientific journals could
>> help them better understand the limits of the machine metaphor, understand
>> the
>> immeasurable complexity of life and its information flows and make
>> relations
>> between researchers more harmonious....
>>  
>>  
>>  
>>  
>> 
>> 
>> all the best
>> 
>> Youri
>> 
>> 
>> 
>> Le 27/01/2022 12:00, « fis-bounces at listas.unizar.es <mailto:fis-bounces at listas.unizar.es> on behalf of
>> fis-request at listas.unizar.es <mailto:fis-request at listas.unizar.es> » <fis-bounces at listas.unizar.es on behalf of
>> fis-request at listas.unizar.es> <mailto:fis-bounces at listas.unizar.esonbehalfoffis-request@listas.unizar.es> a écrit :
>> 
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>>> Today's Topics:
>>> 
>>>   1. Fwd:  NEW YEAR LECTURE--from Jerry Chandler (Pedro C. Mariju?n)
>>>   2. Test Message No Content (Jerry LR Chandler)
>>> 
>>> 
>>> ----------------------------------------------------------------------
>>> 
>>> Message: 1
>>> Date: Wed, 26 Jan 2022 13:45:57 +0100
>>> From: Pedro C. Mariju?n <pedroc.marijuan at gmail.com> <mailto:pedroc.marijuan at gmail.com>
>>> To: "'fis'" <fis at listas.unizar.es> <mailto:fis at listas.unizar.es>
>>> Subject: [Fis] Fwd:  NEW YEAR LECTURE--from Jerry Chandler
>>> Message-ID: <54419d99-ed1b-3da4-384e-845765c1917e at gmail.com> <mailto:54419d99-ed1b-3da4-384e-845765c1917e at gmail.com>
>>> Content-Type: text/plain; charset="utf-8"; Format="flowed"
>>> 
>>> _Mssg. from Jerry Chandler_
>>> 
>>> List, Pedro, Youri,
>>> 
>>>> On Jan 19, 2022, at 12:55 PM, Pedro C. Mariju?n
>>>> <pedroc.marijuan at gmail.com <mailto:pedroc.marijuan at gmail.com> <mailto:pedroc.marijuan at gmail.com> <mailto:pedroc.marijuan at gmail.com>> wrote:
>>>> 
>>>> So, my contention is that a new filed like bio-chemistry or
>>>> bio-physics would be needed concerning the biological-informational
>>>> themes, a bio-information discipline comparable to those just
>>>> mentioned. According to several authors? (me included), the
>>>> prokaryotic cell should be considered as the fundamental, basic unit
>>>> of biological cognition. Thereafter, there would be different ways to
>>>> characterize its informational processes, particularly along the
>>>> "information flow" conceptualization... interested parties may go to
>>>> the recent contribution of Jorge Navarro and
>>>> mine:https://www.mdpi.com/1422-0067/22/21/11965 <https://www.mdpi.com/1422-0067/22/21/11965>, it is in the special
>>>> issue coordinated by Youri.? I also discuss that the from the
>>>> informational thinking one could find the ways and means to renew the
>>>> outdated Modern Synthesis.
>>>> 
>>>> Otherwise, without a clearer disciplinary framework, am afraid the new
>>>> biology will be reduced to bioinformatics and experimental "omic"
>>>> disciplines. Just another (advanced, "very advanced") technology.
>>> Pedro: ?Your comments are often intriguing and these sentences are no
>>> exception.
>>> I do not grasp what either your scientific or personal objectives are.
>>> ?One consistent theme in somehow tied to expectations about ?biologic
>>> codes? in relation to forms of communication. ?Can you be more explicit
>>> about what sorts of meaning you are seeking to understand?
>>> Youri has presented the FIS with an encoded diagram of one of the
>>> central apparati of all living organisms. ?Roughly speaking, the role of
>>> the ribosome is well-understood although finer structuring of the
>>> apparatus and its dynamics will continue to be studied ad infinitum. The
>>> logical role of the ribosome in transducing information into alternative
>>> dynamic forms has been clear for more than 40 years.
>>> 
>>> ?This encoded diagram is based on the epistemology of the chemical code
>>> of life, the physical codes of mass and electricity and the mathematical
>>> codes of permutation groups, space groups, number theory, and so forth.
>>> Is it not clear that Youri?s work generates a diagram that is a logical
>>> constant of form?
>>> 
>>> Somehow, I suspect that the epistemic gaps between mathematics and
>>> physics and chemistry lie at the root of your search for biological
>>> codes. ?Perhaps the effort is guided by a believe that the genesis of
>>> living dynamics, involving thousands of variables and literally hundreds
>>> of millions of *_unique_* biochemical reactions must necessarily be
>>> expressible in simplistic and other scientific, syntactical symbol
>>> systems? ?(Hundreds of millions of reactions BECAUSE every DNA base
>>> occupies a logically unique sequential position and undergoes unique
>>> reactions during transcription and duplication.)
>>> 
>>> ?Is the concern semantics or semeoius? ?The syntax of Youri?s work is
>>> not seriously questioned, is it? ?Is the problem that Youri?s work does
>>> not fit into alternative theories of ?information? that can not be
>>> distorted to fit the biological codes?
>>> 
>>> Youri - Can you refer to a data source that lists the physical-chemical
>>> data of an E coli ribosome in terms of the parts of the whole? ?(I am
>>> not referring x-ray data, just the chemical parameters used to compute
>>> the structure.). As time allows, I may do a few calculations to
>>> unconceal aspects of the scientific information content of a ribosome.
>>> 
>>> Cheers
>>> 
>>> Jerry
>>> 
>>> 
>>> 
>>> 
>>> 
>>> -- 
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