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<p class="MsoNormal"><span style="font-family:"Arial",sans-serif">Dear Colleagues -  I look forward to your valuable comments.<o:p></o:p></span></p>
<p class="MsoNormal"><span style="font-family:"Arial",sans-serif"><o:p> </o:p></span></p>
<p align="center" style="margin:0cm;text-align:center;background:white"><a name="_Hlk116426332"><b><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">G</span></b></a><span style="mso-bookmark:_Hlk116426332"><span style="font-size:11.0pt;color:black">ö<b><span style="border:none windowtext 1.0pt;padding:0cm">delian
 Self-Referential Genomic Information Processing: Complex Self-Other Interactions and Novelty Production</span></b></span></span><span style="mso-bookmark:_Hlk116426332"><b><span style="font-size:11.0pt;border:none windowtext 1.0pt;padding:0cm"><o:p></o:p></span></b></span></p>
<p style="margin:0cm;background:white"><span style="mso-bookmark:_Hlk116426332"><b><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm"><o:p> </o:p></span></b></span></p>
<p style="margin:0cm;background:white"><span style="mso-bookmark:_Hlk116426332"><b><i><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">Overview for Foundations of Information Science Discussion –
<o:p></o:p></span></i></b></span></p>
<p style="margin:0cm;background:white"><span style="mso-bookmark:_Hlk116426332"><b><i><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">Sheri Markose         25-10-2022<o:p></o:p></span></i></b></span></p>
<ol style="margin-top:0cm" start="1" type="1">
<li style="margin-top:0cm;margin-bottom:0cm;mso-list:l0 level1 lfo1;background:white">
<span style="mso-bookmark:_Hlk116426332"><b><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">Background
</span></b></span><span style="mso-bookmark:_Hlk116426332"><b><span style="font-size:11.0pt;border:none windowtext 1.0pt;padding:0cm"><o:p></o:p></span></b></span></li></ol>
<p style="margin:0cm;background:white"><span style="mso-bookmark:_Hlk116426332"><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">Complexity, evolvability, novelty production and ‘thinking outside the box’ in biology and humans
 have for most part relied on models of randomness or on statistical white noise error terms.  
</span></span><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm"><o:p></o:p></span></p>
<p style="margin:0cm;background:white"><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">                  The digitization of inheritable information in the genome encoded in a near universal alphabet  (A,T,C,G/U) has been
 called the ‘algorithmic takeover of biology’ by Walker and Davis (2013).  The Faustian pact at the genesis of life colourfully portrayed by Freeman Dyson  as ‘ the takeover of a replicative digital virus of an analogue metabolism’ accords with the perspective
 of Forterre, Zimmer, Villareal, Koonin and others.  </span><span style="font-size:11.0pt;color:black">This underpins the remarkable fact that in nature only life and biology as we know it and the artifacts of genomic intelligence (GI) thereof are explicitly
 code based digital systems.  </span><span style="font-size:11.0pt"><o:p></o:p></span></p>
<p class="MsoBodyText2" style="line-height:normal"><span style="font-size:11.0pt">                     Genomic intelligence is a concept introduced in
<a href="https://urldefense.com/v3/__https://doi.org/10.3390/e23040405__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqV3O-kDY$">Markose (2021)</a> specifically to characterize the Gödelization of code-based information processing in genomic systems with the distinctive self-referential conditions of Gödel Incompleteness results that appear
 to have been acquired for complexification over the course of evolution of multicellular eukaryote life,
<a href="https://urldefense.com/v3/__https://doi.org/10.1016/j.biosystems.2022.104718__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqPn2Rp5k$">Markose (2022)</a>.  <a name="bbib59">
To explain the latter in contrast to the relative stasis of prokaryotes, which has remain unchanged since inception,
</a></span><span style="mso-bookmark:bbib59"></span><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib10__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqdTKw3lg$"><span style="mso-bookmark:bbib59"><span style="font-size:11.0pt;color:#0C7DBB">Barbieri (2012</span></span><span style="mso-bookmark:bbib59"></span></a><span style="mso-bookmark:bbib59"><span style="font-size:11.0pt;color:#2E2E2E">; </span></span><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib13__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq0lIhVMs$"><span style="mso-bookmark:bbib59"><span style="font-size:11.0pt;color:#0C7DBB">2018)</span></span><span style="mso-bookmark:bbib59"></span></a><span style="mso-bookmark:bbib59"><span style="font-size:11.0pt">,for
 instance, has resorted to Code Biology and Codeopoiesis, viz. biotic code based explanations to complement  the more popular thermodynamic explanations of self-organization and
</span></span><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/topics/mathematics/autopoiesis__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqDFaksjk$" title="Learn more about autopoiesis from ScienceDirect's AI-generated Topic Pages"><span style="mso-bookmark:bbib59"><span style="font-size:11.0pt;color:#2E2E2E">autopoiesis</span></span><span style="mso-bookmark:bbib59"></span></a><span style="mso-bookmark:bbib59"><span style="font-size:11.0pt;color:#2E2E2E">.
</span></span><span style="mso-bookmark:bbib59"></span><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib59__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqIQhnjCw$"><span style="mso-bookmark:bbib59"><span style="font-size:11.0pt;color:#0C7DBB">Igamberdiev (2021)</span></span><span style="mso-bookmark:bbib59"></span></a><span style="mso-bookmark:bbib59"></span><span style="font-size:11.0pt;color:#2E2E2E"> gives
 general principles, but no concrete evidence, for why “living systems during evolution continuously realize the proof of Gödel's theorems (1931).” <o:p></o:p></span></p>
<p style="margin:0cm;background:white"><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">                   Significantly, while debunking the idea that the primary source of evolutionary changes arise from random transcription/replication
 errors, t</span><span style="font-size:11.0pt;color:black;background:white">he epochal discovery by Nobel Laureate
<a name="bbib88">Barbara </a></span><span style="mso-bookmark:bbib88"></span><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib88__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqajIC2C4$"><span style="mso-bookmark:bbib88"><span style="font-size:11.0pt;color:#0C7DBB">McClintock (1984)</span></span><span style="mso-bookmark:bbib88"></span></a><span style="mso-bookmark:bbib88"></span><span style="font-size:11.0pt;color:black;background:white">
 of viral transposable elements that conduct cut-paste (transposons) and copy-paste (retrotransposon) gives a code based explanation  for genomic evolvability, brain plasticity and novel phenotype primarily in eukaryotes.  This underscores the truism that primarily
 only software can change software and also that viral hacking by such internal and external biotic malware is the Achilles heel of genomic digital systems.<span style="background:yellow;mso-highlight:yellow">
</span>  </span><span style="font-size:11.0pt;background:white"><o:p></o:p></span></p>
<ol style="margin-top:0cm" start="2" type="1">
<li style="margin-top:0cm;margin-bottom:0cm;mso-list:l0 level1 lfo1;background:white">
<b><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">Unpacking the Evidence</span></b><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">
<b>for </b></span><b><span style="font-size:11.0pt;color:black">Gödelization of Biology</span></b><span style="font-size:11.0pt;color:black">
</span><b><span style="font-size:11.0pt;border:none windowtext 1.0pt;padding:0cm"><o:p></o:p></span></b></li></ol>
<p style="margin:0cm;background:white"><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">                        While operations on encoded information fall under the purview of Computation Theory and Recursion Function Theory
 (<b>RFT</b>), till recently there was no evidence for how this and </span><span style="font-size:11.0pt;color:#2E2E2E">Gödel's theorems apply to</span><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm"> biology.  Markose (</span><span style="font-size:11.0pt;color:black"><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib61__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq6qlj9z0$"><span style="border:none windowtext 1.0pt;padding:0cm">2022</span></a><span style="border:none windowtext 1.0pt;padding:0cm">)
 unpacks the recent breakthroughs here. </span></span><span style="font-size:11.0pt;border:none windowtext 1.0pt;padding:0cm"><o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt">                     Gödelization of information processing starts, firstly, with unique identifiers or Gödel numbers for digital entities well known in the digital economy and taking the form of bio-peptide
 unique identifiers including ‘zip codes’ in organisms as discovered in the Nobel prize winning work of Blobel (2009). It appears all signalling in bio-ICT relies on peptide identifiers from transcription factors to neuron-neuron links. 
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt">                     Two other
<span style="color:black;border:none windowtext 1.0pt;padding:0cm;background:white">
distinctive </span>Gödelian<span style="color:black;border:none windowtext 1.0pt;padding:0cm;background:white"> features found in genomic intelligence, using epithets from Hofstadter (1999) are self-reference (<b>Self-Ref</b>) or the online machine execution
 involving the Diagonal operator and offline virtual self-representation (<b>Self-Rep</b>) of the former. 
</span>The breakthrough on the significance of these staples of <b>RFT</b> found in textbooks such as Rogers (1967) and Cutland (1980), starts with the insight from Gershenfeld (<a name="bbib48"></a><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib48__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqGSrl56A$"><span style="mso-bookmark:bbib48"><span style="color:#0C7DBB">2012</span></span><span style="mso-bookmark:bbib48"></span></a><span style="mso-bookmark:bbib48"></span><span style="color:#2E2E2E">, </span><a name="bbib49"></a><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib49__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqpGCiPPQ$"><span style="mso-bookmark:bbib49"><span style="color:#0C7DBB">2017</span></span><span style="mso-bookmark:bbib49"></span></a><span style="mso-bookmark:bbib49"></span><span style="color:#2E2E2E"> Chapter
 3 p. 109</span></span><span style="font-size:11.0pt;font-family:"Georgia",serif;color:#2E2E2E">)</span><span style="font-size:11.0pt"> as to what the self-referential/Diagonal operator means for biology, where a program
<i>g </i>builds<i> </i>machine </span><i><span style="font-size:11.0pt;font-family:Symbol">f
</span></i><span style="font-size:11.0pt">to run <i>g </i>(typically denoted as </span>
<i><span style="font-size:11.0pt;font-family:Symbol">f</span></i><i><sub><span style="font-size:11.0pt">g</span></sub></i><i><span style="font-size:11.0pt">(g)</span></i><span style="font-size:11.0pt">). Gershenfeld (</span><span style="font-size:11.0pt"><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib48__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqGSrl56A$"><span style="color:#0C7DBB">2012</span></a>)
 says what 21 century digital fabrication is trying to achieve is something biology solved 3.7 billion years ago with the self-assembly programs associated with the ribosome and other transcriptase machinery involved in gene expression for the morphology, somatic
 identity and regulatory control of the organism. <o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt">                      Despite the central role assigned to self-reference for the sentient self in advanced organisms (<a href="https://urldefense.com/v3/__https://scholar.google.se/citations?view_op=view_citation&hl=sv&user=ZW8RWdAAAAAJ&citation_for_view=ZW8RWdAAAAAJ:Y0pCki6q_DkC__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqclXIy_8$">Gardenfors 
 2003</a>, <a href="https://urldefense.com/v3/__https://doi.org/10.1016/j.neuroimage.2005.12.002__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqKaUbmro$">Northoff et. al, 2006</a> ,
<a name="bbib94"></a><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib94__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqkgZx_Ng$"><span style="mso-bookmark:bbib94"><span style="color:#0C7DBB">Newen (2018)</span></span><span style="mso-bookmark:bbib94"></span></a><span style="mso-bookmark:bbib94"></span>
 , <a href="https://urldefense.com/v3/__https://doi.org/10.1016/j.pbiomolbio.2018.10.002__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqM9CMK80$">Miller et.al., 2018</a> , etc) only
<a name="bbib114"></a><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib114__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqPf630Ss$"><span style="mso-bookmark:bbib114"><span style="color:#0C7DBB">Tsuda (2014)</span></span><span style="mso-bookmark:bbib114"></span></a><span style="mso-bookmark:bbib114"></span><span style="color:#2E2E2E"> </span>and
 Markose (2017, 2021,2022) have noted how the evolutionary development of <b>Self-Rep</b> mirror structures as in
<span style="color:black;border:none windowtext 1.0pt;padding:0cm;background:white">
the</span> Gödel Meta-Representation Theorem (Rogers,1967) is necessary for biotic elements to make statements about themselves, first having self-assembled themselves.  This
<i>offline</i> embodied <b>Self-Rep</b>, which contrasts with no such structures in prokaryotes, was a paradigm shift
<span style="color:black;border:none windowtext 1.0pt;padding:0cm;background:white">
in the Adaptive Immune System (AIS) some 500 million years ago in the lineage of jawed fish, called the Big Bang of Immunology, Janeway et. al (2005).  This latterly appears as Mirror Neuron System (MNS) mostly in primate brains first discovered by the Parma
 Group of neuroscientists. <o:p></o:p></span></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm;background:white">                   </span><span style="font-size:11.0pt">The
<b><span style="color:black;border:none windowtext 1.0pt;padding:0cm;background:white">AIS</span></b><span style="color:black;border:none windowtext 1.0pt;padding:0cm;background:white"> demonstrates virtual offline mirrored self-representation (<b>Self-Rep</b>)
 in the MHC1 T cell receptors of ~85 % of expressed genes viz. <i>halted </i>machine executions of genomic self-assembly codes that determine the somatic and phenotype identity for the organism.  As will be seen, these Self-Repped gene codes in the Thymus,
 called the <i>Thymic Self </i> (</span><a href="https://urldefense.com/v3/__https://www.frontiersin.org/articles/10.3389/fpsyt.2020.540676/full__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqRtkoQzk$"><span style="border:none windowtext 1.0pt;padding:0cm;background:white">Ramon and Faure, 2021</span></a><span style="color:black;border:none windowtext 1.0pt;padding:0cm;background:white">)
 or ‘the science of self’ (</span><a href="https://urldefense.com/v3/__https://link.springer.com/article/10.1007/s00281-020-00831-y__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq71KRW4U$"><span style="border:none windowtext 1.0pt;padding:0cm;background:white">Greenen, 2021</span></a><span style="color:black;border:none windowtext 1.0pt;padding:0cm;background:white">)
 are primarily used to identify the hostile other, viz. negation function operators of non-self antigens.  In turn, the Mirror Neuron System (<b>MNS</b>) reuses codes of self-actions from the sensory-motor cortex for social cognition and inference regarding
 conspecifics via virtual simulations in the <b>MNS</b> (</span><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib35__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqek3WNP4$"><span style="color:#0C7DBB">Fadiga et al. (1995)</span></a><span style="color:#2E2E2E">; </span><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib46__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqHLWVVsM$"><span style="color:#0C7DBB">Gallese
 et al. (1996)</span></a><span style="color:#2E2E2E">; </span><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/science/article/pii/S0303264722001022*bib102__;Iw!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqmxeFzqA$"><span style="color:#0C7DBB">Rizzolatti et al. (1996)</span></a>). 
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt">                 It is conjectured that an identical
<b>RFT</b> machinery is involved in the self-other nexus in both the <b>AIS</b> and
<b>MNS</b>.  The graphics for <b>Self-Rep</b> Mirror Mapping in the <b>AIS</b> and
<b>MNS</b> is given in <a href="https://urldefense.com/v3/__https://www.mdpi.com/1099-4300/23/4/405__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq8Rs91D0$">Figure 1 in Markose (2021)</a>.<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt;background:lime;mso-highlight:lime"><o:p> </o:p></span></p>
<ol style="margin-top:0cm" start="3" type="1">
<li class="MsoListParagraph" style="margin-bottom:0cm;margin-left:0cm;mso-add-space:auto;line-height:normal;mso-list:l0 level1 lfo1">
<b><span style="font-family:"Times New Roman",serif">Detection of Non-Self Antigen in AIS: N</span></b><b><span style="font-family:"Times New Roman",serif">ew Diversity-Selector Model and Gödel Sentence in Genomic Blockchain Distributed Ledger (BCDL)
<o:p></o:p></span></b></li></ol>
<p class="MsoFootnoteText"><b><span style="font-size:11.0pt;font-family:Symbol">                     </span></b><span style="font-size:11.0pt">The most significant of all breakthroughs here is the one made by the game theorist Binmore (1987) who raised the
 ‘spectre of Gödel (1931)’ in the form of Gödel’s Liar who will negate or falsify what can be computed/predicted. Binmore effectively mooted the adversarial digital game which is co-extensive with life itself (Markose, 2017, 2021). This constitutes the
<i>fourth</i> condition of Gödel systems and involves an adversarial agent in the form of a virus or a hacker whose actions cannot be constrained in anyway.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt">                The Gödel Incompleteness result that generates the Gödel Sentence permits a code qua biotic element to self-report  “I’m under attack”, when it has been hacked/negated by a novel malware.
 This marks an endogenous exit from listable sets, a necessary condition for novelty and the production of novel antibodies, to avoid the irrational state of logical inconsistency of formal systems (<a href="https://urldefense.com/v3/__https://www.jstor.org/stable/j.ctt1b7x7ww__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqtrLoY_E$">Smullyan,1961</a>). 
 The genomic Gödel Sentence in terms of 21 century nomenclature is a <i>hash</i> that helps demonstrate endogenously that the outputs of expressed genes have been maliciously altered. Note,
</span>that halting self-assembly gene codes, <i>g</i> <span style="font-family:Symbol">
Î</span><span style="font-family:Symbol"> </span><b>G </b>that create the organism are theorems of the genomic system
<span style="font-size:11.0pt">theorems and is disjoint from known non-theorems or what the immunologist Burnett (1958) famously called ‘forbidden codes’ if allowed to run will ‘negate’ the theorems and cause harm.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt">                Indeed, how the
<b>AIS</b> identifies novel software attacks on own gene codes, <i>g</i> , by malware/parasite negating functions
<i>f<sub>p</sub></i><sup>¬ !</sup> , which belongs to an uncountable infinite set that cannot be mechanically listed, is stupendous case of uber bio-cybersecurity.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt">              <span style="color:black;border:none windowtext 1.0pt;padding:0cm;background:white">The AIS implements ‘out of the box’ astronomic anticipative search for novel non-self antigens necessary
 for </span>novel anti-body production and cognition <span style="color:black;background:white">
in humans manifests unbounded proteanism for novel extended phenotypes, Dawkins (1987), in the form of artifacts outside of ourselves</span>. 
<span style="color:black;background:white">This facility found only in the <b>AIS</b> relying on the Recombination Activator genes (<b>RAG</b> 1 and 2) and in the human brain for neural receptor diversity runs into orders of magnitude of 10<sup>20</sup> – 10<sup>30</sup> that
 exceed the pre-scripted germline genome size many times over.    </span><span style="background:white"><o:p></o:p></span></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt;color:#555555;background:white">               </span><span style="font-size:11.0pt"> The Rogers (1967) fixed point indexes for yet to happen
<i>f<sub>p</sub></i><sup>¬ !</sup> attacks by the non-self antigens are generated in the
<b>AIS</b>  in most ingenious fashion: a large number of codes/indexes purported to be of different
<a name="_Hlk117013984"><i>f<sub>p</sub></i><sup>¬ !</sup> </a>on each <b>self-repped</b>
<i> g </i>are generated in the T-Cell Receptors. This is the most spectacular case of predictive coding. Suppose that the g.n for the specific tuple {<i> f<sub>p</sub></i><sup>¬
</sup>, <i>g<sub>n</sub></i> } denoted by <i>g<sup>¬</sup></i>. When the attack by
<i>f<sub>p</sub></i><sup>¬ !</sup>  takes place in real time in the periphery involving the said pair {<i> f<sub>p</sub></i><sup>¬
</sup>, <i>g<sub>n</sub></i> }, the experientially driven peripheral MHC1 receptor must record this and if this ‘syncs’ with the one that was speculatively generated in the thymic MHC1 receptors, two parts of the fixed point come together to construct a genomic
 Gödel Sentence.   <i> </i><o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt">               This molecular genomic diversity-selector model follows a unique self-referential blockchain distributed ledger that is different, in terms of the self-referential design, from man-made
<b>BCDLs</b> first invented circa 2009.  <span style="color:black;border:none windowtext 1.0pt;padding:0cm">
The genomic </span><b>BCDL </b><span style="color:black;border:none windowtext 1.0pt;padding:0cm">manifests secure digital and decentralized record keeping where no internal or external bio-malware can compromise the immutability of the life’s building blocks
 and no novel blocks can be added that is not consistent with extant blocks. <o:p>
</o:p></span></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">                    There are no doubt
</span><span style="font-size:11.0pt;color:black;background:white">macroscopic environmental and population level pressures of the Neo-Darwinian style natural selection arising from conspecific or multi-species competition for survival in terms of those which
 reproduce more and those which die out. There is growing evidence that at level of bio-digital smart controls of the eukaryote genome and homeostasis, selective pressures are based on the principles of a unique self-referential
</span><b><span style="font-size:11.0pt;color:black;border:none windowtext 1.0pt;padding:0cm">BCDL</span></b><span style="font-size:11.0pt;color:black;background:white">
</span><span style="font-size:11.0pt;background:white"><o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt;color:black;background:white">                    In conclusion, genomic intelligence in vertebrates that has reached its apogee in humans is highly empathic as the conspecific/other is the projection
 of self; greatly Machiavellian having co-evolved with adversarial viral agents; geared toward unbounded proteanism from the get-go starting with transposon based diversity of
<b>RAG</b> genes in the immune system and stringently self-regulated by a <b>BCD</b>L driven by the principle of autonomy of the life of the organism and an agenda to be hack-free.        
</span><span style="font-size:11.0pt;background:white"><o:p></o:p></span></p>
<p class="MsoNormal"><span style="font-family:"Arial",sans-serif"><o:p> </o:p></span></p>
<p class="MsoFootnoteText"><b><span style="font-size:11.0pt">Points for discussion and areas where I would like collaborators and those I can learn from as in my day job I’m an economist
<o:p></o:p></span></b></p>
<p class="MsoFootnoteText"><b><span style="font-size:11.0pt">#1</span></b><span style="font-size:11.0pt"> I fully concur with the latter part of
</span><span style="font-size:11.0pt"><a href="https://urldefense.com/v3/__https://doi.org/10.1016/j.pbiomolbio.2018.10.002__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqM9CMK80$">Miller/Torday (2018)</a> statement :
<o:p></o:p></span></p>
<p style="margin:0cm;background:white"><span style="font-size:11.0pt;color:#2E2E2E">“As self-referential cognition is demonstrated by all living organisms, life can be equated with the sustenance of cellular </span><span style="font-size:11.0pt;color:black"><a href="https://urldefense.com/v3/__https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/homeostasis__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq8F9h1Jc$" title="Learn more about homeostasis from ScienceDirect's AI-generated Topic Pages"><span style="color:#2E2E2E">homeostasis</span></a></span><span style="font-size:11.0pt;color:#2E2E2E"> in
 the continuous defence of 'self'.” </span><span style="font-size:11.0pt;color:black">However, Miller/Torday do not use any of the code based
<b>RFT</b> Gödel style <b>Self-Ref</b> mirror structures for genomic information processing.</span><span style="font-size:11.0pt"><o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt">                No doubt prokaryote CRISPR based identification of non-self antigens is highly sophisticated and so are the innate immune system strategies which primarily entail analog defences of
</span><span style="font-size:11.0pt">setting up barriers, toxicity, raising temperature by inflammation and ingestion by phagocytes. Prokaryotes distinctively do not have the mirror
<b>Self-Rep </b>offline structures of self as in the Rogers (1967) <b>RFT</b> fixed point theorems which permit bio-molecules to self-report changes to their own codes.  My take on homeostasis in eukaryotes post jawed fish is that bio software data security
 and hence the autonomy of self was taken to the next level: the design of how codes can self-report they have been changed by bio malware by utilizing hashes like the Gödel Sentence.
<o:p></o:p></span></p>
<p class="MsoFootnoteText"><span style="font-size:11.0pt">                It will be interesting to compare the bacteria-phage arms race in prokaryotes with the one in the
<b>AIS</b> antibody production outlined above. I have reached out to John Mattick and Silvia Sanchez Ramon on these issues.
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<p class="MsoFootnoteText"><span style="font-size:11.0pt"><o:p> </o:p></span></p>
<p class="MsoFootnoteText"><b><span style="font-size:11.0pt">#2.</span></b><span style="font-size:11.0pt">  In Markose (2021) I indicate that the generation of genomic Gödel Sentences for detection of novel the non-self antigen is necessary for novel antibody
 production is a testable hypothesis. Those who died of Covid 19 were found not to be capable of antibody production and instead were subjected by a cytokine storm brought about by the analog defences of toxicity and inflammation of the innate immune system.
<o:p></o:p></span></p>
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<p class="MsoFootnoteText"><b><span style="font-size:11.0pt"># 3</span></b><span style="font-size:11.0pt"> A common
<b>Self-Rep</b> mirror <b>RFT</b> machinery for self-other recognition in the <b>
AIS </b>and social cognition following from the Mirror Neuron Systems in primates has been conjectured. Similar conjectures have been made at least since Irun Cohen, but without any
<b>RFT</b> to guide the discussions.  </span><span style="font-size:11.0pt"><a href="https://urldefense.com/v3/__https://www.mdpi.com/1099-4300/23/4/405__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSq8Rs91D0$">Figure 1 in Markose (2021)</a> shows how a knock-out of the circuitry for self’s updates on non-self activity vis-ŕ-vis self (the RHS
 entry in the <i>offline</i> <b>Self-Rep</b> </span><span style="font-size:11.0pt;font-family:Symbol">s</span><span style="font-size:11.0pt">(g,g) operator ) known to be controlled by interferon gamma as in
<a href="https://urldefense.com/v3/__https://www.nature.com/articles/nature18626__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqF1KRYvk$">Jonathan Kipnis Group 2016</a> experiment on rats, could lead to loss of immune capabilities as well as their sociability.  Note, the Markose
<b>RFT</b> machinery for the self-other nexus is a different explanation to the evo-devo one given by Kipnis et.al.
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<p class="MsoFootnoteText"><span style="font-size:11.0pt"><o:p> </o:p></span></p>
<p class="MsoFootnoteText"><b><span style="font-size:11.0pt">#4</span></b><span style="font-size:11.0pt"> Finally, it is a matter of incredulity that over 90 years have passed since Gödel (1931) for evidence  to be found that the staples of
<b>Self-Ref</b> and <b>Self-Rep</b> and the Gödel Sentence are ubiquitous in Biology.  A number of factors can be adduced. Even those who espouse that code-based operations are relevant in cognition such as in the Computational Theory of Mind never mention
<b>Self-Ref</b> and <b>Self-Rep</b>, let alone that the Gödel Sentence is like a </span>
<i><span style="font-size:11.0pt">hash </span></i><span style="font-size:11.0pt">which permits a software document to endogenously self-report it has been hacked.  There is a strong anti-machine view which overlooks the encoded basis of the genome and biology
 and claims that biology is a non-digital natural process that is creative in some vitalistic way.
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<p class="MsoFootnoteText"><span style="font-size:11.0pt"><o:p> </o:p></span></p>
<p class="MsoNormal"><b><span style="font-family:"Times New Roman",serif">References
<o:p></o:p></span></b></p>
<p class="MsoNormal"><b><span style="font-family:"Times New Roman",serif">#Blog on University of Essex Website:
<i>How we became smart – a journey of discovery through the world of game theory and genomic intelligence</i>
<a href="https://urldefense.com/v3/__https://www.essex.ac.uk/blog/posts/2021/10/26/how-we-became-smart__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqVgSsoLo$">https://www.essex.ac.uk/blog/posts/2021/10/26/how-we-became-smart</a> 
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<p class="MsoNormal"><b><span style="font-family:"Times New Roman",serif"><br>
#</span></b><span style="font-family:"Times New Roman",serif">Markose, S.M, 2022,
</span><span style="font-family:"Times New Roman",serif;color:#505050;mso-fareast-language:EN-GB">Complexification of eukaryote phenotype: Adaptive immuno-cognitive systems as unique Gödelian blockchain distributed ledger,
</span><span style="font-family:"Times New Roman",serif;color:#323232;mso-fareast-language:EN-GB">Biosystems, ISSN: 0303-2647, Vol: 220,
</span><a href="https://urldefense.com/v3/__https://doi.org/10.1016/j.biosystems.2022.104718__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqPn2Rp5k$" target="_blank" title="Persistent link using digital object identifier"><span style="font-family:"Times New Roman",serif;color:#0C7DBB">https://doi.org/10.1016/j.biosystems.2022.104718</span></a><span class="MsoHyperlink"><span style="font-family:"Times New Roman",serif;color:#0C7DBB">
<o:p></o:p></span></span></p>
<p class="MsoNormal"><u><span style="font-family:"Times New Roman",serif;color:#0C7DBB"><br>
<span class="MsoHyperlink"><span style="color:#0C7DBB">#</span></span></span></u><span style="font-family:"Times New Roman",serif;color:black;background:white">Markose, S.M, 2021, </span><a href="https://urldefense.com/v3/__https://doi.org/10.3390/e23040405__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqV3O-kDY$"><span style="font-family:"Times New Roman",serif;color:#70B85D;border:none windowtext 1.0pt;padding:0cm;background:white">“Genomic
 Intelligence as Über Bio-Cybersecurity: The Gödel Sentence in Immuno-Cognitive Systems”</span></a><span style="font-family:"Times New Roman",serif;color:black;background:white">, </span><em><span style="font-family:"Calibri",sans-serif;color:black;border:none windowtext 1.0pt;padding:0cm;background:white">Entropy. </span></em><span style="font-family:"Times New Roman",serif;color:black;background:white">23(4),
 405; ttps://doi.org/10.3390/e23040405   <o:p></o:p></span></p>
<p class="MsoNormal"><span class="info"><span style="font-family:"Times New Roman",serif;color:black;border:none windowtext 1.0pt;padding:0cm;background:white"><br>
Markose, S.M, 2017, Complex type 4 structure changing dynamics of digital agents: Nash equilibria or a game with arms race in innovations. </span></span><span class="info"><i><span style="font-family:"Times New Roman",serif;color:black;border:none windowtext 1.0pt;padding:0cm">Journal
 of Dynamics & Games</span></i></span><span class="info"><span style="font-family:"Times New Roman",serif;color:black;border:none windowtext 1.0pt;padding:0cm;background:white">, 2017, 4 (3) : 255-284. doi: </span></span><a href="https://urldefense.com/v3/__http://dx.doi.org/10.3934/jdg.2017015__;!!D9dNQwwGXtA!RRmmHQCs_Cav9UXiPz27dODNI-Kke3ky-PhpVLOvgOETwB-s3hTK7egkhJHf5AFKr0UuxLxzixSqC_UOvRc$"><span style="font-family:"Times New Roman",serif;color:#70B85D;border:none windowtext 1.0pt;padding:0cm">10.3934/jdg.2017015</span></a><span style="font-family:"Times New Roman",serif;color:black;background:white">  
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<p class="MsoNormal"><span style="font-size:10.0pt;font-family:"Arial",sans-serif">-------------------<o:p></o:p></span></p>
<p class="MsoNormal"><span style="font-size:10.0pt;font-family:"Arial",sans-serif">Professor Sheri Markose<o:p></o:p></span></p>
<p class="MsoNormal"><span style="font-size:10.0pt;font-family:"Arial",sans-serif">Economics Department<o:p></o:p></span></p>
<p class="MsoNormal"><span style="font-size:10.0pt;font-family:"Arial",sans-serif">University of Essex<o:p></o:p></span></p>
<p class="MsoNormal"><span style="font-size:10.0pt;font-family:"Arial",sans-serif">UK
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