2024-02-23 16:27:38 +01:00
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\chapter{A Deal with Life}
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2024-02-25 20:54:47 +01:00
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\begin{refsection}[bib/sivanov-dblp-mod.bib,bib/sivanov-extra.bib,bib/dealb.bib]
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2024-02-23 16:27:38 +01:00
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Life is one of the most beautiful things in the universe. Arguably,
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it is because we humans belong to the kingdom of Life that it
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fascinates us so. Beyond its intrinsic beauty to which our sensory
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organs are attuned, it also deeply attracts us because of the
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self-referentiality of its contemplation: when thinking about Life, we
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often think about our interactions with it, and ultimately
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about ourselves.
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Self-referentiality is also a hurdle: it is intrinsically difficult to
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conceive of oneself. Even though theoretical computer science is no
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substitute for philosophy, I enjoy taking Gödel's incompleteness
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theorems\footnote{\url{https://en.wikipedia.org/wiki/Gödel's_incompleteness_theorems}}
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and especially Hilbert's
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\emph{Entscheidungsproblem}\footnote{\url{https://en.wikipedia.org/wiki/Entscheidungsproblem}}
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and the halting
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problem\footnote{\url{https://en.wikipedia.org/wiki/Halting_problem}}
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as vivid examples: Turing's famous proof states that a Turing machine
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cannot generally decide whether another Turing machine will ever halt.
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Since abstract computing devices can be seen as distant
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mathematizations of the human brain, this formal result hints that
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entirely conceiving of our mind---and by extension of Life itself---is
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borderline intractable.
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The difficulty of self-referiantiality is also deeply disturbing,
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especially because understanding how our bodies function within their
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environments has so many essential implications: dealing with the
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climate crisis, tackling diseases, improving the quality of life, to
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only cite the foremost ones. To avoid the worry of looking into the
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mirror for too long, one can brutally build a wall between oneself and
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``the rest'' of Life, and adopt what may be called the Engineer's
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position: a living organism is a machine constituted out of mechanical
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pieces, whilst the human disassembles, adjusts, and reassembles them
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again, improved.
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Modern biology, medicine, biotechnology illustrate the high
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performance of the Engineer's approach, and this text is not
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a criticism of mechanicism per se. Nevertheless, its efficiency does
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not entail total truthfulness, nor even exclusivity about truth.
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In other words, mechanistic views allowing for impressive technical
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achievements does not mean that these views fully reflect reality, nor
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that mechanicism is the final stop on our journey to understanding
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Life. In my research, I aim for exploring different approaches to
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Life and tools supporting such approaches. I take particular
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enthusiasm in thinking about striking \emph{a deal with Life}:
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establishing \emph{mutually beneficial} interactions with living
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systems.
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Concluding deals as opposed to taking the Engineer's position resets
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the power balance in our relationship with Life: instead of seeking to
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control, hack, or otherwise dominate living organisms, the goal is to
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further take into account their well-being. I believe that
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approaching Life from this viewpoint is essential if we are after true
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solutions to fundamental problems such as the climate crisis or
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complex diseases. On a more philosophical note, the framework of
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mutually beneficial interactions should remind us that our
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intelligence in no way warrants an extraction of the human being into
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an exceptional superior stance---we are part of Life, and we ought to
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think and act accordingly.
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2024-02-25 20:54:47 +01:00
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\newpage
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2024-02-25 21:20:55 +01:00
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\section{Mechanicism: Where engineering meets biology}
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\label{sec:mechanicism}
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2024-02-25 20:54:47 +01:00
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In the 20th century, biology was dramatically affected by physics and
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engineering, and this has brought revolutionary advances in
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understanding Life and interaction with
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it~\cite{CornishBowdenCLSA2007,Glade22,Nicholson2019,Woese2004}.
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Grounding the function of biological structures in the physical
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reality allowed for convergence of worldview between physics and
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biology, thereby conferring to the latter the gravitas of a ``real''
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science. A remarkable tool physics and engineering brought to biology
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is reductionism---to understand a system, decompose it into parts,
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understand each of the parts, and understand the interactions between
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the parts to get back to the big picture. Reductionism in turn
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fostered the emergence of mechanicism, the modern proponents of which
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``conceive of the cell as an intricate piece of machinery whose
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organization reflects a pre-existing design, whose structure is wholly
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intelligible in reductionistic terms, and whose operation is governed
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by deterministic laws, rendering its behaviour predictable and
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controllable—at least in principle.''\cite{Nicholson2019}
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With all due recognition of the major advances yielded by reductionism
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and mechanicism, it appears hard to believe that this is the final
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stop on the way to understanding Life. I recall first of all the
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discussion in~\cite[page~2]{Woese2004} of reductionism as an
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operational tool allowing to tackle complexity (empirical
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reductionism), as opposed to the belief that it actually corresponds
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to the organization of the living matter (fundamental reductionism).
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Fundamental reductionism makes therefore an additional strong
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assumption, which impacts the ``sense of what is important'':
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molecular biology established the molecular level as fundamental, and
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demoted the status of larger structures---e.g. organisms, ecosystems,
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etc. These are deemed emergent, and therefore less important,
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secondary, directly derivable from more fundamental matters.
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While the notion of emergence in natural sciences is fraught, and its
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objective qualities can be debated (e.g.~\cite{RonaldSC99}), it has
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the merit of putting in focus the hierarchy of scales. It is
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a hierarchy in the sense that, while physics teaches us that the whole
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is always necessarily the sum of its parts (plus the interactions), it
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is often irrelevant to put the whole away, and only peer at the
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components. It is therefore important to not always fall through to
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the underlying levels, and specifically to avoid Laplace's daemon
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abuse: the Laplace's daemon\footnote{Laplace's daemon is a thought
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experiment introducing an imaginary creature which knows exactly the
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positions and momenta of every atom in the universe. The original
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conclusion conceived by of Pierre-Simon Laplace in 1814 is that this
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absolute knowledge should entail full knowledge of past and future
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positions of these particles~\cite{wikiLaplace}. In modern days,
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Laplace's daemon is often used as a metaphor for absolute knowledge
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of the minutae of a complex system, down to its elementary
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particles.} cannot practically exist, but should it exist, it would
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in no way have any influence on the fact that we as humans find it
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extremely useful to operate with concepts situated at higher
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scales\footnote{An informal inspiration for these observations comes
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from~\cite{Carroll}.}. It is physics again, and statistical
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mechanics in particular, that recalls this saliently by deeply relying
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upon thinking about systems such as gasses in terms of macrostates
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(volume, pressure, temperature) and microstates (positions and momenta
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of all particles)~\cite{SusskindCourse,wikiEntropy}. In other words,
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while one might argue that microstates are more ``fundamental'' in
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some way, it is of little practical importance, and addressing
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multiple scales is still pertinent.
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Fundamental reductionism as a belief is strongly related to
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engineering, and specifically the practice of constructing complex
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structures and mechanisms out of simpler building blocks.
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The multiple ways in which engineering has been durably changing our
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lives and our surroundings naturally fuels extending its reach beyond
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human creation, onto living matter. A spectacular manifestation is
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the Machine Conception of the Cell (MCC) as introduced
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in~\cite{Nicholson2019}: the cell is seen as an intricate machine,
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somewhat similar to a computer, which makes it appropriate to use
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engineering terms to designate the cellular components visible by
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microscopy: molecular motors, Golgi apparatus, genetic program, pumps,
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locks, keys, gates, circuitry, etc. The choice of terms is in
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principle contingent, and it is natural to use words evoking familiar
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structures, but in practice this reinforces the belief in the
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truthfulness of the engineering approach. Indeed, scientific papers
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ubiquitously summarize knowledge in the form of circuits or maps.
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As stated in~\cite[page~6]{Mayer2009}, ``the typical ‘cartoons’ of
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signaling pathways, with their reassuring arrows and limited number of
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states [...] could be the real villain of the piece.'' The Wikipedia
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page on molecular motors literally starts with the sentence
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``Molecular motors are [...] molecular
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\emph{machines}''\cite{wikiMotors} (the emphasis is mine), and
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features several animations which would look appropriate in a book on
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the construction of mechanical toys. The last illustration---and
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probably the most verbose---of the relationship between reductionism
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and the Engineer's work I bring here is the very term
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``biological engineering''.
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In fact, widely admitted considerations easily uncover some flaws in
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the belief in the fundamental nature of the MCC~\cite{Nicholson2019}.
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To cite two of the most salient ones, the cell is a milieu which is
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better described as liquid, rather than solid. It is densely packed
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with various molecules, which do not always strictly respect a certain
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conformation, but rather continuously evolve across a spectrum of
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shapes. It being impossible for a human to observe the cellular
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processes with the naked eye, the researcher is tempted to follow the
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mindset suggested by the available technology conceived for conceiving
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of and observing microscopic machines~\cite{Glade22}, a mindset which
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also happens to be mainstream. Unsurprisingly, if one looks for
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machines, one finds machines, as the animation ``The Inner Life of the
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Cell'' conveniently illustrates~\cite{lifeOfTheCell}.
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Avoiding conceptual frameworks other than fundamental reductionism and
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mechanicism not only forces our thinking into a certain box which
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partially corresponds to reality, but also biases our methodology of
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interactions with Life. When one imagines the cell as a machine, one
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expects mechanistic explanations, building upon strong causality.
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When the computer screen shows a picture or a car modifies its
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trajectory, it is always possible to indicate a satisfactory set of
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causes. This is because the engineers who built the device had
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a specific intention in mind, which can be relatively easily unpacked.
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Biological systems originated from spontaneous evolution, without
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anyone human baking in specific goals, implying that causality is much
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harder to establish convincingly. Yet, reductionism and mechanicism
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tempt the researches to only look for correlations which may be
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interpreted as causal: ``It is much easier to write and publish
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a paper suggesting Protein X is necessary for transmitting a signal
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from A to B, than one showing that Protein X is one of many potential
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components of a heterogeneous ensemble of signaling complexes that
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together couple A to B.''~\cite{Mayer2009}.
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While the Machine Conception of the Cell and similar mechanistic
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points of view are not oblivious to the intrinsic noise of the
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respective biological systems, seeing them as machines invites to
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treating noise as a nuisance which the biological systems manage to
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successfully combat in every moment of their existence. However,
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multiple indications exist that noise plays an essential role, as
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a matter of fact making some processes possible. We cite as an
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example the Brownian ratchet model of intracellular transport, which
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has been gaining considerable traction recently~\cite{Nicholson2019},
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and which essentially consists in hypothesising that molecular motors
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feature two distinct conformations of the energy landscape---a flat
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one and a saw-toothed one. By periodically switching between the two,
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the motor buffeted by thermal fluctuations will tend to advance along
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the cytoskeletal track it is attached to
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(Figure~\ref{fig:ratchet-motor}).
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\begin{figure}
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\centering
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\tikzstyle axis=[->]
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\tikzstyle movement=[-{Latex[width=1.2mm]},semithick]
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\tikzstyle landscape=[very thick,cap=round]
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\tikzstyle motor=[draw,circle,thick,minimum size=3.5mm]
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\tikzstyle motorFlip=[motor]
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\tikzstyle motorFlop=[motor,fill=black!40]
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\tikzstyle motorGhost=[motor,densely dotted]
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\newcommand{\landscapeXOff}{.2mm}
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\newcommand{\landscapeYOff}{1mm}
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\newcommand{\xLength}{56mm}
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\newcommand{\yLength}{11mm}
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\newcommand{\graphSkip}{\vspace{-3mm}}
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\newcommand{\stepLabOff}{-7mm}
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\begin{tikzpicture}
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\draw[axis] (0,0) --
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node[midway,xshift=\stepLabOff,minimum width=7mm] {\small (1)}
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(0,\yLength)
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node[xshift=3mm] {$U$};
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\draw[axis] (0,0) -- (\xLength, 0) node[yshift=-2mm,xshift=-1mm] {$x$};
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\draw[landscape] (\landscapeXOff,\landscapeYOff) -- +(52mm,0);
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\node[motorFlip] (motor) at (11mm,3mm) {};
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\node[motorGhost] at ($(motor)-(3.5mm,0)$) {};
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\node[motorGhost] at ($(motor)-(6mm,0)$) {};
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\node[motorGhost] at ($(motor)+(3.5mm,0)$) {};
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\node[motorGhost] at ($(motor)+(6mm,0)$) {};
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\coordinate[above=2mm of motor] (arrowAnchor);
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\draw[movement] ($(arrowAnchor)-(2mm,0)$) -- +(-6mm,0);
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\draw[movement] ($(arrowAnchor)+(2mm,0)$) -- +(6mm,0);
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\end{tikzpicture}
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\graphSkip
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\begin{tikzpicture}
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\draw[axis] (0,0) --
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node[midway,xshift=\stepLabOff,minimum width=7mm] {\small (2)}
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(0,\yLength)
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node[xshift=3mm] {$U$};
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\draw[axis] (0,0) -- (\xLength, 0) node[yshift=-2mm,xshift=-1mm] {$x$};
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\draw[landscape] (\landscapeXOff,\landscapeYOff)
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-- ++(2mm,5mm) -- ++(11mm,-5mm)
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-- ++(2mm,5mm) -- ++(11mm,-5mm)
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-- ++(2mm,5mm) -- ++(11mm,-5mm)
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-- ++(2mm,5mm) -- ++(11mm,-5mm);
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\node[motorFlop] (motor) at (25.2mm,3.7mm) {};
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\coordinate[above=2mm of motor] (arrowAnchor);
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\draw[movement] ($(arrowAnchor)-(2mm,0)$) -- +(-4.5mm,0);
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\draw[movement] ($(arrowAnchor)+(2mm,0)$) -- +(9mm,0);
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\end{tikzpicture}
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\graphSkip
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\begin{tikzpicture}
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\draw[axis] (0,0) --
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node[midway,xshift=\stepLabOff,minimum width=7mm] {\small (3)}
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(0,\yLength)
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node[xshift=3mm] {$U$};
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\draw[axis] (0,0) -- (\xLength, 0) node[yshift=-2mm,xshift=-1mm] {$x$};
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\draw[landscape] (\landscapeXOff,\landscapeYOff) -- +(52mm,0);
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\node[motorFlip] (motor) at (25.2mm,3mm) {};
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\node[motorGhost] at ($(motor)-(3.5mm,0)$) {};
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\node[motorGhost] at ($(motor)-(6mm,0)$) {};
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\node[motorGhost] at ($(motor)+(3.5mm,0)$) {};
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\node[motorGhost] at ($(motor)+(6mm,0)$) {};
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\coordinate[above=2mm of motor] (arrowAnchor);
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\draw[movement] ($(arrowAnchor)-(2mm,0)$) -- +(-6mm,0);
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\draw[movement] ($(arrowAnchor)+(2mm,0)$) -- +(6mm,0);
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\end{tikzpicture}
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\graphSkip
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\begin{tikzpicture}
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\draw[axis] (0,0) --
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node[midway,xshift=\stepLabOff,minimum width=7mm] {\small (4)}
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(0,\yLength)
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node[xshift=3mm] {$U$};
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\draw[axis] (0,0) -- (\xLength, 0) node[yshift=-2mm,xshift=-1mm] {$x$};
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\draw[landscape] (\landscapeXOff,\landscapeYOff)
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-- ++(2mm,5mm) -- ++(11mm,-5mm)
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-- ++(2mm,5mm) -- ++(11mm,-5mm)
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-- ++(2mm,5mm) -- ++(11mm,-5mm)
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-- ++(2mm,5mm) -- ++(11mm,-5mm);
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\node[motorFlop] (motor) at (38.2mm,3.7mm) {};
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\coordinate[above=2mm of motor] (arrowAnchor);
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\draw[movement] ($(arrowAnchor)-(2mm,0)$) -- +(-4.5mm,0);
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\draw[movement] ($(arrowAnchor)+(2mm,0)$) -- +(9mm,0);
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\end{tikzpicture}
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\caption{A schematic illustration of the Brownian ratchet model of
|
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|
molecular motors. A motor is shown as a circle
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(\protect\tikz[baseline,yshift=1.2mm]\protect\node[motorFlip,minimum
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size=2.5mm]{}; or
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\protect\tikz[baseline,yshift=1.2mm]\protect\node[motorFlop,minimum
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size=2.5mm]{};), and its energy landscape is shown as a thick line
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\protect\tikz[baseline,yshift=.2em]\protect\draw[landscape]
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(0,0) -- (2ex,0);. The horizontal axis $x$ represents the motor's
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position on the cytoskeletal track, while the vertical axis $U$
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illustrates the motor's free energy. The motor is hypothesized to
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feature two distinct potential energy landscapes, depending on its
|
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conformational state. In the flip conformation
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\protect\tikz[baseline,yshift=1.2mm]\protect\node[motorFlip,minimum
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size=2.5mm]{};, the energy landscape is flat so the protein may
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slide freely in one of the two directions, with equal probability
|
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for both directions. In the flop conformation
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\protect\tikz[baseline,yshift=1.2mm]\protect\node[motorFlop,minimum
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size=2.5mm]{};, the saw-tooth shape of the landscape favors the
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motor moving to the right, illustrated by a longer arrow pointing
|
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|
to the right. When cycles of ATP hydrolysis make the motor
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|
periodically switch between the two conformations, thermal
|
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|
|
fluctuations will tend to push it to the right. (The original
|
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|
figure is~\cite[Figure~4]{Nicholson2019}, itself a reproduction
|
|
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|
from~\cite{Kurakin2006}.)}
|
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|
\label{fig:ratchet-motor}
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|
\end{figure}
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|
2024-02-27 15:30:02 +01:00
|
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|
\section{The Deal: Mutually beneficial interactions}
|
2024-02-25 21:20:55 +01:00
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|
\label{sec:deals}
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|
2024-02-25 20:54:47 +01:00
|
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|
Seeing Life as an ensemble of machines biases how we expect to collect
|
|
|
|
|
profit from acting on it. Machine means control: we are constantly
|
|
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|
|
looking for knobs which we could turn this or that way, and which
|
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|
|
could modify the behavior of the system to fit our needs and
|
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|
|
|
expectations. This can be seen both at the very practical level,
|
|
|
|
|
where bioengineers seek to modify bacteria to produce chemicals,
|
|
|
|
|
e.g.~\cite{berkleyBio}, and also at the theoretical level, where
|
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|
|
|
researchers develop methodologies to support looking for the coveted
|
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|
|
|
knobs, e.g.~\cite{PardoID21,Vogel2008,Zanudo2015}. If we admit that
|
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|
the reductionistic and mechanistic approach is not globally true, we
|
2024-02-25 21:28:35 +01:00
|
|
|
|
must accept that these knobs may not necessarily have a definitive
|
|
|
|
|
shape, but rather be a complex assemblage of factors, affecting the
|
|
|
|
|
trajectory of the system in multiple non-trivial ways, and possibly
|
|
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|
|
shifting in time. Finally, this control mindset introduces an
|
|
|
|
|
asymmetric relationship between the controller and the controlled,
|
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|
which is unnatural biological context because both the controller and
|
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|
|
the controlled are made out of the same kind of matter, and are
|
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|
|
ultimately embedded in the same environment.
|
2024-02-27 15:30:02 +01:00
|
|
|
|
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|
|
This chapter outlines a conceptual framework putting symmetry back
|
|
|
|
|
into the picture, \emph{the Deal with Life}: instead of
|
|
|
|
|
surreptitiously lifting the human above and out of the living matter
|
|
|
|
|
by self-designating ourselves as superior Engineers, I propose to
|
|
|
|
|
account for the fact that we act \emph{within} Life and its complex
|
|
|
|
|
feedback loops by looking to organize \emph{mutually beneficial
|
|
|
|
|
interactions} with the living systems, as opposed to trying to
|
|
|
|
|
control, hack, or engineer them. Since we are talking about the
|
|
|
|
|
general mindset, the choice of words in not contingent: controlling,
|
|
|
|
|
hacking, and engineering impose a vertical power relationship, while
|
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|
|
|
thinking in terms of mutual benefit admits that our target system has
|
|
|
|
|
a trajectory of its own, which we would like to preserve it to some
|
|
|
|
|
degree. Playing with words and summarizing the control-hack-engineer
|
|
|
|
|
mindset as ``We control, Life obeys'' makes the power imbalance even
|
|
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|
|
more striking.
|
|
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|
|
Today, the most obvious inspiration for considering mutual benefit
|
|
|
|
|
comes from the climate crisis: for centuries, we have acted on the
|
|
|
|
|
environment expecting it to behave like a heat bath, i.e., to absorb
|
|
|
|
|
whatever we throw at it without essentially changing its state.
|
|
|
|
|
Besides brandishing a certain naïveté, this point of view is so
|
|
|
|
|
difficult to abandon that is has become the epitome of science denial
|
|
|
|
|
according to certain studies,
|
|
|
|
|
e.g.~\cite{BjornbergKGH2017,ONeillB2010,wikiClimate}, as well
|
|
|
|
|
as~\cite[page~155]{DryzekNS2011}. As these references and multiple
|
|
|
|
|
others show, refusing to admit human cause as central to the climate
|
|
|
|
|
crisis has been invariably and strongly supported by the fossil fuel
|
|
|
|
|
industry. I suspect nevertheless that one of the reasons for the
|
|
|
|
|
resilience of the denialist mindset is the deeply anchored feeling
|
|
|
|
|
that we are engineers and the environment a mere tool. My own
|
|
|
|
|
inspiration for the Deal with Life comes from theoretical biology
|
|
|
|
|
discussions with Nicolas \textsc{Glade} at the TIMC lab in
|
|
|
|
|
Grenoble\footnote{\url{https://www.timc.fr/}}, and specifically from
|
|
|
|
|
the remarks outlined in Section~\ref{sec:mechanicism} above concerning
|
|
|
|
|
the dominance of the engineering mindset in modern biology, especially
|
|
|
|
|
in molecular biology, and the ruts it forces our thinking in.
|
|
|
|
|
|
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|
|
Thinking about mutual benefit in dealing with Life unpacks multiple
|
|
|
|
|
different levels of caring about the destiny of the system of
|
|
|
|
|
interest:
|
|
|
|
|
\begin{itemize}
|
|
|
|
|
\item \emph{Level 0}: This is the Engineer's mindset: fundamental
|
|
|
|
|
reductionism and mechanicism---we control, Life obeys. At this
|
|
|
|
|
level, we do not conceive of any kind of benefit to the
|
|
|
|
|
target system.
|
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|
|
\item \emph{Level 1}: We aim to preserve the destiny of the target
|
|
|
|
|
system to a certain degree. If it is a yeast population, we may
|
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|
|
|
want to not allow its size below a certain threshold, or if it is
|
|
|
|
|
a farm animal, we may want to ensure a certain quality of life
|
|
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|
|
according to a set of measures.
|
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|
|
\item \emph{Level 2}: We aim to benefit the target system to a certain
|
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|
|
|
degree, while also extracting our own profit from the interaction.
|
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|
In the case of a farm animal, we may want to ensure that its the
|
|
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|
|
state of well-being be \emph{improved} in the context of its
|
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|
|
interaction with respect to a life without any human intervention.
|
|
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|
|
\end{itemize}
|
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|
|
All three levels of this hierarchy of mutual benefit are in fact
|
|
|
|
|
already present in our interactions with living organisms.
|
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|
|
Respecting Level 1 is almost ubiquitously needed, since otherwise we
|
|
|
|
|
may kill the system of interest before it is capable of producing the
|
|
|
|
|
deliverable we are after. Level~2 manifests itself to different
|
|
|
|
|
degrees in interactions with domesticated animals, especially in the
|
|
|
|
|
context of increased awareness of the conditions to which livestock
|
|
|
|
|
are typically treated in modern agriculture. Levels 1 and 2 are also
|
|
|
|
|
progressively making their way to prominence in dealing with
|
|
|
|
|
ecosystems: cutting down forests brings about various kinds of
|
|
|
|
|
catastrophes, so it is now laudable to curb deforestation, and even to
|
|
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|
|
conduct reforestation campaigns.
|
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|
|
It would seem on the other hand that biomedical research is stubbornly
|
|
|
|
|
fond of ignoring Levels~1 and 2, and instead focuses on proudly
|
|
|
|
|
brandishing the Engineer's Level 0, claiming that if something does
|
|
|
|
|
not work out today, it will certainly work out tomorrow, provided that
|
|
|
|
|
tomorrow brings around more energy, more computing power, more
|
|
|
|
|
workforce, more data. Yet again, in no way do I aim to deny or
|
|
|
|
|
minimize the benefits of mechanicism and reductionism in
|
|
|
|
|
biology---which has been instrumental in multiple groundbreaking
|
|
|
|
|
achievements over the 20th century and beyond. I insist nevertheless
|
|
|
|
|
that exclusively sticking to Level 0 of the hierarchy of mutual
|
|
|
|
|
benefit is a fundamental limitation of thought. Lifting this
|
|
|
|
|
limitation will undoubtedly open up a multitude of new approaches and
|
|
|
|
|
solutions, as this chapter attempts to outline.
|
|
|
|
|
|
|
|
|
|
A final argument for taking into consideration the destiny of the
|
|
|
|
|
system of interest which has been lurking around the corner the whole
|
|
|
|
|
time is that we as humans do not often have a choice on this matter:
|
|
|
|
|
the living system serving as a target is often required to survive our
|
|
|
|
|
intervention, and sometimes to maintain the majority of the functions
|
|
|
|
|
it had before the intervention. That biomedical research is reluctant
|
|
|
|
|
to go from accepting this obvious constraint to taking more holistic
|
|
|
|
|
approaches including mutual benefit is possibly due to the complexity
|
|
|
|
|
that awaits us on the very threshold of the comfortable Engineer's
|
|
|
|
|
mindset. In other words, it is much easier to see the disease as
|
|
|
|
|
separate from the carrying organism, and imagine curative strategies
|
|
|
|
|
tightly focused on a well defined set of diseased structures than to
|
|
|
|
|
admit that the onset of the disease is a consequence of a complex
|
|
|
|
|
interplay of multiple factors. Indeed, conceiving of diseases from
|
|
|
|
|
this more holistic viewpoint is often prohibitively complex with the
|
|
|
|
|
currently available data and knowledge, all while the reductionist
|
|
|
|
|
approach gives at least some solutions. I claim however that this is
|
|
|
|
|
no way should hinder our motivation to tackle the complexity of the
|
|
|
|
|
more holistic approach.
|
|
|
|
|
|
|
|
|
|
Finally, the way I employ the terms ``deal'' and ``mutual benefit''
|
|
|
|
|
corroborates no particular social ideology. The Deal with Life simply
|
|
|
|
|
calls for including the potential benefit of the target system into
|
|
|
|
|
the picture by establishing a measure of it. It is up to the
|
|
|
|
|
protagonists of the concrete context, problem, or practical
|
|
|
|
|
application to decide whether, how much, and in which way to
|
|
|
|
|
prioritize this benefit over the profit we humans are expecting
|
|
|
|
|
to extract.
|
2024-02-25 20:54:47 +01:00
|
|
|
|
|
2024-03-30 10:49:05 +01:00
|
|
|
|
\section{The Deal: A conceptual maquette}
|
|
|
|
|
\label{sec:maquette}
|
|
|
|
|
|
|
|
|
|
This section aims to provide an overview of the Deal with Life
|
|
|
|
|
framework for thinking about mutually beneficial interactions with
|
|
|
|
|
living systems, without focusing on the formal details.
|
|
|
|
|
Properly formalizing the ideas exposed in this section is
|
|
|
|
|
a significant part of my future research.
|
|
|
|
|
|
|
|
|
|
A formalization of the Deal with Life is structured into two stages:
|
|
|
|
|
\begin{enumerate}
|
|
|
|
|
\item abstract general framework,
|
|
|
|
|
\item concrete implementations.
|
|
|
|
|
\end{enumerate}
|
|
|
|
|
The abstract general framework rigorously defines the main concepts:
|
|
|
|
|
the interacting systems, their benefits, etc., while concrete
|
|
|
|
|
implementations instantiate these definitions for concrete systems,
|
|
|
|
|
supplying additional concepts and tools applicable to the concrete
|
|
|
|
|
case. Concrete implementations in their own turn occur on two levels:
|
|
|
|
|
concrete formal dynamical systems---e.g., membrane systems, Boolean
|
|
|
|
|
networks, string rewriting systems\footnote{The subsequent chapters of
|
|
|
|
|
this manuscript describe these formal dynamical systems in more
|
|
|
|
|
detail.}---and concrete biological systems---e.g., a human,
|
|
|
|
|
population of yeasts, a plant, an ecosystem, etc. Note that while the
|
|
|
|
|
introductory discourse heavily focuses on how we as humans interact
|
|
|
|
|
with Life, the Deal with Life framework can be adapted to
|
|
|
|
|
characterizing and evaluating the interactions between other living
|
|
|
|
|
systems, not necessarily involving the human.
|
|
|
|
|
|
2024-03-30 10:49:44 +01:00
|
|
|
|
\subsection{Dynamical systems}
|
|
|
|
|
\label{sec:ds}
|
|
|
|
|
|
|
|
|
|
Following the spirit of~\cite{Thom1974,Zeeman1976}, I propose to use
|
|
|
|
|
the language of abstract dynamical systems for the general framework
|
|
|
|
|
of the Deal. In this subsection I quickly recall the main notions,
|
|
|
|
|
and I refer to sources like~\cite{Brown2018,wikiDS} for more general
|
|
|
|
|
and more detailed definitions.
|
|
|
|
|
|
|
|
|
|
An \emph{abstract dynamical system} over the state space $X$ and time
|
|
|
|
|
$T$ is a (partial) function $\Phi : X \times T \to X$ assigning to
|
|
|
|
|
a state $s \in X$ the new state $\Phi(s, t)$ in which the system will
|
|
|
|
|
be after time $t \in T$. The function $\Phi$ satisfies the following
|
|
|
|
|
two natural properties:
|
|
|
|
|
\begin{enumerate}
|
|
|
|
|
\item $\Phi(s, 0) = s$: the system does not change its state in
|
|
|
|
|
0 time,
|
|
|
|
|
\item $\Phi(\Phi(s, t_1), t_2) = \Phi(s, t_1 + t_2)$: evolving the
|
|
|
|
|
system for time $t_1$, then for time $t_2$ leads to the same state
|
|
|
|
|
as evolving the systems for time $t_1 + t_2$.
|
|
|
|
|
\end{enumerate}
|
|
|
|
|
|
|
|
|
|
A common shape for a state is an $n$-vector of real parameters of
|
|
|
|
|
a system---in which case $X \subseteq \mathbb{R}^n$---but no
|
|
|
|
|
particular restrictions are imposed: $X$ may be a more a general
|
|
|
|
|
algebraic object. In the most general setting, $T$ is a monoid, but
|
|
|
|
|
it is rather customary for the time domain to be a contiguous infinite
|
|
|
|
|
subset of either $\mathbb{Z}$ or $\mathbb{R}$. In the first case,
|
|
|
|
|
$\Phi$ is usually called a discrete-time dynamical system, and in the
|
|
|
|
|
second case $\Phi$ is called a continuous-time dynamical system.
|
|
|
|
|
If additionally the state space $X$ of a discrete-time dynamical
|
|
|
|
|
system $\Phi : X \times T \to T$ with $T \subseteq \mathbb{Z}$ is
|
|
|
|
|
discrete (countable), then $\Phi$ is called a discrete dynamical
|
|
|
|
|
system. Finally, if $X$ is a finite set, then $\Phi$ is called
|
|
|
|
|
a finite dynamical system.
|
|
|
|
|
|
|
|
|
|
In the case of discrete-time dynamical systems, the time variable can
|
|
|
|
|
be interpreted as the number of evolution steps. More concretely, for
|
|
|
|
|
a $t > 0$, $\Phi(s, t)$ can be seen as the state of the system after
|
|
|
|
|
$t$ steps, while $\Phi(s, -t)$ can be seen as the state the system
|
|
|
|
|
\emph{was in} $t$ steps ago. When $T = \mathbb{N}$, it is customary
|
|
|
|
|
to see the discrete-time dynamical systems as the function
|
|
|
|
|
$F : X \to X$, giving the state to which the dynamical system
|
|
|
|
|
transitions from state $s \in X$: $F(s) = \Phi(s, 1)$
|
2024-04-09 09:00:29 +02:00
|
|
|
|
(e.g,~\cite[Chapter~1]{Riva22}). $F$~generates the possibly infinite
|
|
|
|
|
state graph of the discrete-time dynamical system, whose nodes are the
|
|
|
|
|
states, and there is a directed edge from state $s_1$ to state $s_2$
|
|
|
|
|
if $s_2 = F(s_1)$.
|
2024-03-30 10:49:44 +01:00
|
|
|
|
|
|
|
|
|
Given a dynamical system $\Phi : X \times T \to X$ and a state
|
|
|
|
|
$s \in X$, it is possible to construct the restricted function
|
|
|
|
|
$\Phi_s : T \to X$, $\Phi_s(t) = \Phi(s, t)$, determining the
|
|
|
|
|
\emph{trajectory} of $\Phi$ through $s$.
|
|
|
|
|
$\Ima \Phi_s = \{\Phi(s, t) \mid t\in T\}$. If $T = \mathbb{Z}$ or
|
|
|
|
|
$T = \mathbb{R}$, then the trajectory $\Ima \Phi_s$ can be interpreted
|
2024-04-29 15:02:52 +02:00
|
|
|
|
as the sequence of all states through which $\Phi$ goes before and after
|
2024-03-30 10:49:44 +01:00
|
|
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reaching $s$. If $T = \mathbb{N}$, then the trajectory through $s$ is
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the iteration of $F$: $\{F^k(s) \mid k \in \mathbb{N}\}$, where
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$F^0(s) = s$, $F^1(s) = F(s)$, $F^2(s) = F(F(s))$, etc.
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2024-04-09 14:20:54 +02:00
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While I will give most of the general definitions for abstract
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2024-04-12 14:50:46 +02:00
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dynamical systems, I will rely on discrete-time dynamical systems with
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$T = \mathbb{N}$ later on in the manuscript, for the following
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reasons:
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2024-04-09 14:20:54 +02:00
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\begin{enumerate}
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\item discrete time yields simpler formal systems, which can capture
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a wider range of features before becoming too complex to comprehend,
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\item discrete time is sufficient to represent the majority of
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time-related concepts, e.g., event ordering, situating measurements
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in time, etc.
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\end{enumerate}
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Last but not least, this choice is motivated by my own expertise as
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a computer scientist lying in the field of discrete dynamical systems.
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2024-04-24 14:44:23 +02:00
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\subsection{Determinism, reversibility, stochasticity}
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\label{sec:det-rever-stoch}
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The type of the function $\Phi$ as shown in the previous section
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imposes \emph{deterministic} behavior: for any time interval $t\in T$,
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$\Phi : X \times T \to X$ assigns to every state $s \in X$ exactly one
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state $\Phi(s, t)$. Furthermore, when $T = \mathbb{Z}$ or
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$T = \mathbb{R}$, the system is \emph{reversible}: to any state $s$
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and any time interval $t > 0$, $\Phi$ associates exactly one state
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$\Phi(s, -t)$. In the case $T = \mathbb{Z}$, this implies that every
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state $s \in X$ has exactly one preimage under the function $F$:
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$|F^{-1}(s)| = 1$.
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While it is true that any non-deterministic Turing machine
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$\mathcal{N}$ can be simulated by a deterministic Turing machine which
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explores all non-deterministic branches of the computations of
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$\mathcal{N}$, and Bennett showed in~\cite{Bennett1973} how any Turing
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machine can be made reversible, determinism and reversibility are
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quite strong restrictions. In particular, for discrete-time dynamical
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systems, the state graph generated by $F$ is a set of
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chains~\cite{DotyKLOSW2023}, i.e., it can be represented in the plane
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as a set of linear parallel non-intersecting oriented paths.
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Despite the fact that non-determinism and reversibility do not
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increase the computational power of Turing machines, these
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restrictions may have a significant impact in weaker models of
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computation. On the other hand, non-determinism and irreversibility
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are useful ingredients to have for practical reasons when building
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models of reality: indeed, our intuitive perception is that many
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phenomena in the world around us are non-deterministic, and most of
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them appear irreversible\footnote{Here, I will only point the reader
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to~\cite{CarrollArrowFAQ2007} for an entry point into the
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fascinating discussion of the irreversibility observed in the
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macroscopic world as opposed to the reversibility of the microscopic
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world.}.
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A general way to capture the fact that a phenomenon may go different
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ways at some point are stochastic processes, which can be defined as
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sequences of random variables, each of which describes the possible
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outcomes at a given moment of time~\cite{wikiStochastic}. In general,
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stochastic processes can also describe irreversible processes, e.g.,
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because the total number of possible outcomes may decrease over time.
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In the case of discrete-time dynamical systems with $T = \mathbb{N}$,
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non-determinism can be represented in an arguably simpler way by
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modifying the type of $F$ to be $F : X \to 2^X$, meaning that for
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a state $s$, $F(s) \subseteq X$ represents the set of possible next
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states. The notion of the state graph can be naturally extended by
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defining it as graph whose set of nodes is $X$ and which contains an
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edge from $s_1 \in X$ to $s_2 \in X$ if $s_2 \in F(s_1)$.
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Modifying the type of $F$ in this way enriches the state graph in two
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ways:
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\begin{enumerate}
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\item a state $s \in X$ may have no successor states, i.e.,
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$F(s) = \emptyset$,
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\item they may be multiple edges originating at the same state
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$s \in X$ if $|F(s)| > 1$.
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\end{enumerate}
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It is further possible to enrich the structure of $F$ by annotating
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the next states in $F(s)$ with probabilities. More concretely, the
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type of $F$ can be further extended to
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$F : X \to 2^{X \times \mathbb{R}}$, thus making $F$ produce sets of
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pairs (state, probability), with the normalization condition that for
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every $s$ for which $F(s) \neq \emptyset$ the probabilities of the
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next states amount to 1: $\sum_{(s', p) \in F(s)} p = 1$.
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In the rest of the manuscript I use the following terminology for
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designating different types of discrete-time dynamical systems with
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$T = \mathbb{N}$, depending on the type of $F$:
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\begin{itemize}
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\item $F : X \to X$: \emph{deterministic} discrete-time dynamical
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system, or deterministic DDS;
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\item $F : X \to 2^X$: \emph{non-deterministic} discrete-time
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dynamical system, or non-deterministic DDS;
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\item $F : X \to 2^{X \times \mathbb{R}}$ with the normalization
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condition from the previous paragraph: \emph{stochastic}
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discrete-time dynamical system, or stochastic DDS.
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\end{itemize}
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Note how understanding discrete-time dynamical systems as a function
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assigning states to states (i.e., of one of the types above) allows
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separating non-determinism from stochasticity. Indeed, according to
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the preceding discussion, non-determinism describes the possibility of
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a state to have more than one successor state, while stochasticity
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means that, in addition, a probability distribution is defined on the
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set of successor states. Transposing this separation between
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non-determinism and stochasticity to general dynamical systems defined
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as $\Phi : X \times T \to X$ seems at least syntactically cumbersome,
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and the traditional way of capturing non-determinism via stochastic
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processes as sequences of random variables includes probability
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distributions from the start.
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The definition of a trajectory in the case of non-deterministic and
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irreversible dynamical systems depends on the choice of formalism, but
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any definition should respect the intuition that a trajectory is a set
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|
of states the dynamical system may traverse. In the case of
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non-deterministic DDS defined as above, a trajectory is a sequence of
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states $(s_i)_{i \in T}$ such that $s_{i+1} \in F(s_i)$. Similarly,
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in the case of stochastic DDS, a trajectory is a sequence of state
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$(s_i)_{i \in T}$ such that there exists a probability $p$ yielding
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the pair $(s_{i+1}, p) \in F(s_i)$.
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2024-02-25 20:54:47 +01:00
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\printbibliography[heading=subbibliography]
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\end{refsection}
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2024-02-23 16:27:38 +01:00
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%%% Local Variables:
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%%% TeX-engine: luatex
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%%% TeX-master: "hdr"
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2024-03-30 10:49:44 +01:00
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%%% reftex-default-bibliography: ("bib/dealb.bib" "bib/sivanov-dblp-mod.bib" "bib/sivanov-extra.bib")
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2024-02-23 16:27:38 +01:00
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%%% End:
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