Copy part of and slightly amend the introduction of the Deal draft.

deal.tex

@@ -1,4 +1,5 @@
 \chapter{A Deal with Life}
+\begin{refsection}[bib/sivanov-dblp-mod.bib,bib/sivanov-extra.bib,bib/dealb.bib]
 
 Life is one of the most beautiful things in the universe.  Arguably,
 it is because we humans belong to the kingdom of Life that it
@@ -59,6 +60,307 @@ intelligence in no way warrants an extraction of the human being into
 an exceptional superior stance---we are part of Life, and we ought to
 think and act accordingly.
 
+\newpage
+
+\section{A short glance on reductionism and mechanicism}
+\label{sec:mecha}
+
+In the 20th century, biology was dramatically affected by physics and
+engineering, and this has brought revolutionary advances in
+understanding Life and interaction with
+it~\cite{CornishBowdenCLSA2007,Glade22,Nicholson2019,Woese2004}.
+Grounding the function of biological structures in the physical
+reality allowed for convergence of worldview between physics and
+biology, thereby conferring to the latter the gravitas of a ``real''
+science.  A remarkable tool physics and engineering brought to biology
+is reductionism---to understand a system, decompose it into parts,
+understand each of the parts, and understand the interactions between
+the parts to get back to the big picture.  Reductionism in turn
+fostered the emergence of mechanicism, the modern proponents of which
+``conceive of the cell as an intricate piece of machinery whose
+organization reflects a pre-existing design, whose structure is wholly
+intelligible in reductionistic terms, and whose operation is governed
+by deterministic laws, rendering its behaviour predictable and
+controllable—at least in principle.''\cite{Nicholson2019}
+
+With all due recognition of the major advances yielded by reductionism
+and mechanicism, it appears hard to believe that this is the final
+stop on the way to understanding Life.  I recall first of all the
+discussion in~\cite[page~2]{Woese2004} of reductionism as an
+operational tool allowing to tackle complexity (empirical
+reductionism), as opposed to the belief that it actually corresponds
+to the organization of the living matter (fundamental reductionism).
+Fundamental reductionism makes therefore an additional strong
+assumption, which impacts the ``sense of what is important'':
+molecular biology established the molecular level as fundamental, and
+demoted the status of larger structures---e.g. organisms, ecosystems,
+etc.  These are deemed emergent, and therefore less important,
+secondary, directly derivable from more fundamental matters.
+
+While the notion of emergence in natural sciences is fraught, and its
+objective qualities can be debated (e.g.~\cite{RonaldSC99}), it has
+the merit of putting in focus the hierarchy of scales.  It is
+a hierarchy in the sense that, while physics teaches us that the whole
+is always necessarily the sum of its parts (plus the interactions), it
+is often irrelevant to put the whole away, and only peer at the
+components.  It is therefore important to not always fall through to
+the underlying levels, and specifically to avoid Laplace's daemon
+abuse: the Laplace's daemon\footnote{Laplace's daemon is a thought
+  experiment introducing an imaginary creature which knows exactly the
+  positions and momenta of every atom in the universe.  The original
+  conclusion conceived by of Pierre-Simon Laplace in 1814 is that this
+  absolute knowledge should entail full knowledge of past and future
+  positions of these particles~\cite{wikiLaplace}.  In modern days,
+  Laplace's daemon is often used as a metaphor for absolute knowledge
+  of the minutae of a complex system, down to its elementary
+  particles.} cannot practically exist, but should it exist, it would
+in no way have any influence on the fact that we as humans find it
+extremely useful to operate with concepts situated at higher
+scales\footnote{An informal inspiration for these observations comes
+  from~\cite{Carroll}.}.  It is physics again, and statistical
+mechanics in particular, that recalls this saliently by deeply relying
+upon thinking about systems such as gasses in terms of macrostates
+(volume, pressure, temperature) and microstates (positions and momenta
+of all particles)~\cite{SusskindCourse,wikiEntropy}.  In other words,
+while one might argue that microstates are more ``fundamental'' in
+some way, it is of little practical importance, and addressing
+multiple scales is still pertinent.
+
+Fundamental reductionism as a belief is strongly related to
+engineering, and specifically the practice of constructing complex
+structures and mechanisms out of simpler building blocks.
+The multiple ways in which engineering has been durably changing our
+lives and our surroundings naturally fuels extending its reach beyond
+human creation, onto living matter.  A spectacular manifestation is
+the Machine Conception of the Cell (MCC) as introduced
+in~\cite{Nicholson2019}: the cell is seen as an intricate machine,
+somewhat similar to a computer, which makes it appropriate to use
+engineering terms to designate the cellular components visible by
+microscopy: molecular motors, Golgi apparatus, genetic program, pumps,
+locks, keys, gates, circuitry, etc.  The choice of terms is in
+principle contingent, and it is natural to use words evoking familiar
+structures, but in practice this reinforces the belief in the
+truthfulness of the engineering approach.  Indeed, scientific papers
+ubiquitously summarize knowledge in the form of circuits or maps.
+As stated in~\cite[page~6]{Mayer2009}, ``the typical ‘cartoons’ of
+signaling pathways, with their reassuring arrows and limited number of
+states [...] could be the real villain of the piece.'' The Wikipedia
+page on molecular motors literally starts with the sentence
+``Molecular motors are [...] molecular
+\emph{machines}''\cite{wikiMotors} (the emphasis is mine), and
+features several animations which would look appropriate in a book on
+the construction of mechanical toys.  The last illustration---and
+probably the most verbose---of the relationship between reductionism
+and the Engineer's work I bring here is the very term
+``biological engineering''.
+
+In fact, widely admitted considerations easily uncover some flaws in
+the belief in the fundamental nature of the MCC~\cite{Nicholson2019}.
+To cite two of the most salient ones, the cell is a milieu which is
+better described as liquid, rather than solid.  It is densely packed
+with various molecules, which do not always strictly respect a certain
+conformation, but rather continuously evolve across a spectrum of
+shapes.  It being impossible for a human to observe the cellular
+processes with the naked eye, the researcher is tempted to follow the
+mindset suggested by the available technology conceived for conceiving
+of and observing microscopic machines~\cite{Glade22}, a mindset which
+also happens to be mainstream.  Unsurprisingly, if one looks for
+machines, one finds machines, as the animation ``The Inner Life of the
+Cell'' conveniently illustrates~\cite{lifeOfTheCell}.
+
+Avoiding conceptual frameworks other than fundamental reductionism and
+mechanicism not only forces our thinking into a certain box which
+partially corresponds to reality, but also biases our methodology of
+interactions with Life.  When one imagines the cell as a machine, one
+expects mechanistic explanations, building upon strong causality.
+When the computer screen shows a picture or a car modifies its
+trajectory, it is always possible to indicate a satisfactory set of
+causes.  This is because the engineers who built the device had
+a specific intention in mind, which can be relatively easily unpacked.
+Biological systems originated from spontaneous evolution, without
+anyone human baking in specific goals, implying that causality is much
+harder to establish convincingly.  Yet, reductionism and mechanicism
+tempt the researches to only look for correlations which may be
+interpreted as causal: ``It is much easier to write and publish
+a paper suggesting Protein X is necessary for transmitting a signal
+from A to B, than one showing that Protein X is one of many potential
+components of a heterogeneous ensemble of signaling complexes that
+together couple A to B.''~\cite{Mayer2009}.
+
+While the Machine Conception of the Cell and similar mechanistic
+points of view are not oblivious to the intrinsic noise of the
+respective biological systems, seeing them as machines invites to
+treating noise as a nuisance which the biological systems manage to
+successfully combat in every moment of their existence.  However,
+multiple indications exist that noise plays an essential role, as
+a matter of fact making some processes possible.  We cite as an
+example the Brownian ratchet model of intracellular transport, which
+has been gaining considerable traction recently~\cite{Nicholson2019},
+and which essentially consists in hypothesising that molecular motors
+feature two distinct conformations of the energy landscape---a flat
+one and a saw-toothed one.  By periodically switching between the two,
+the motor buffeted by thermal fluctuations will tend to advance along
+the cytoskeletal track it is attached to
+(Figure~\ref{fig:ratchet-motor}).
+
+\begin{figure}
+  \centering
+
+  \tikzstyle axis=[->]
+  \tikzstyle movement=[-{Latex[width=1.2mm]},semithick]
+  \tikzstyle landscape=[very thick,cap=round]
+  \tikzstyle motor=[draw,circle,thick,minimum size=3.5mm]
+  \tikzstyle motorFlip=[motor]
+  \tikzstyle motorFlop=[motor,fill=black!40]
+  \tikzstyle motorGhost=[motor,densely dotted]
+  \newcommand{\landscapeXOff}{.2mm}
+  \newcommand{\landscapeYOff}{1mm}
+  \newcommand{\xLength}{56mm}
+  \newcommand{\yLength}{11mm}
+  \newcommand{\graphSkip}{\vspace{-3mm}}
+  \newcommand{\stepLabOff}{-7mm}
+  \begin{tikzpicture}
+    \draw[axis] (0,0) --
+    node[midway,xshift=\stepLabOff,minimum width=7mm] {\small (1)}
+    (0,\yLength)
+    node[xshift=3mm] {$U$};
+    \draw[axis] (0,0) -- (\xLength, 0) node[yshift=-2mm,xshift=-1mm] {$x$};
+    \draw[landscape] (\landscapeXOff,\landscapeYOff) -- +(52mm,0);
+
+    \node[motorFlip] (motor) at (11mm,3mm) {};
+    \node[motorGhost] at ($(motor)-(3.5mm,0)$) {};
+    \node[motorGhost] at ($(motor)-(6mm,0)$) {};
+    \node[motorGhost] at ($(motor)+(3.5mm,0)$) {};
+    \node[motorGhost] at ($(motor)+(6mm,0)$) {};
+
+    \coordinate[above=2mm of motor] (arrowAnchor);
+    \draw[movement] ($(arrowAnchor)-(2mm,0)$) -- +(-6mm,0);
+    \draw[movement] ($(arrowAnchor)+(2mm,0)$) -- +(6mm,0);
+  \end{tikzpicture}
+
+  \graphSkip
+
+  \begin{tikzpicture}
+    \draw[axis] (0,0) --
+    node[midway,xshift=\stepLabOff,minimum width=7mm] {\small (2)}
+    (0,\yLength)
+    node[xshift=3mm] {$U$};
+    \draw[axis] (0,0) -- (\xLength, 0) node[yshift=-2mm,xshift=-1mm] {$x$};
+    \draw[landscape] (\landscapeXOff,\landscapeYOff)
+    -- ++(2mm,5mm) -- ++(11mm,-5mm)
+    -- ++(2mm,5mm) -- ++(11mm,-5mm)
+    -- ++(2mm,5mm) -- ++(11mm,-5mm)
+    -- ++(2mm,5mm) -- ++(11mm,-5mm);
+
+    \node[motorFlop] (motor) at (25.2mm,3.7mm) {};
+    \coordinate[above=2mm of motor] (arrowAnchor);
+    \draw[movement] ($(arrowAnchor)-(2mm,0)$) -- +(-4.5mm,0);
+    \draw[movement] ($(arrowAnchor)+(2mm,0)$) -- +(9mm,0);
+  \end{tikzpicture}
+
+  \graphSkip
+
+  \begin{tikzpicture}
+    \draw[axis] (0,0) --
+    node[midway,xshift=\stepLabOff,minimum width=7mm] {\small (3)}
+    (0,\yLength)
+    node[xshift=3mm] {$U$};
+    \draw[axis] (0,0) -- (\xLength, 0) node[yshift=-2mm,xshift=-1mm] {$x$};
+    \draw[landscape] (\landscapeXOff,\landscapeYOff) -- +(52mm,0);
+
+    \node[motorFlip] (motor) at (25.2mm,3mm) {};
+    \node[motorGhost] at ($(motor)-(3.5mm,0)$) {};
+    \node[motorGhost] at ($(motor)-(6mm,0)$) {};
+    \node[motorGhost] at ($(motor)+(3.5mm,0)$) {};
+    \node[motorGhost] at ($(motor)+(6mm,0)$) {};
+
+    \coordinate[above=2mm of motor] (arrowAnchor);
+    \draw[movement] ($(arrowAnchor)-(2mm,0)$) -- +(-6mm,0);
+    \draw[movement] ($(arrowAnchor)+(2mm,0)$) -- +(6mm,0);
+  \end{tikzpicture}
+
+  \graphSkip
+
+  \begin{tikzpicture}
+    \draw[axis] (0,0) --
+    node[midway,xshift=\stepLabOff,minimum width=7mm] {\small (4)}
+    (0,\yLength)
+    node[xshift=3mm] {$U$};
+    \draw[axis] (0,0) -- (\xLength, 0) node[yshift=-2mm,xshift=-1mm] {$x$};
+    \draw[landscape] (\landscapeXOff,\landscapeYOff)
+    -- ++(2mm,5mm) -- ++(11mm,-5mm)
+    -- ++(2mm,5mm) -- ++(11mm,-5mm)
+    -- ++(2mm,5mm) -- ++(11mm,-5mm)
+    -- ++(2mm,5mm) -- ++(11mm,-5mm);
+
+    \node[motorFlop] (motor) at (38.2mm,3.7mm) {};
+    \coordinate[above=2mm of motor] (arrowAnchor);
+    \draw[movement] ($(arrowAnchor)-(2mm,0)$) -- +(-4.5mm,0);
+    \draw[movement] ($(arrowAnchor)+(2mm,0)$) -- +(9mm,0);
+  \end{tikzpicture}
+
+  \caption{A schematic illustration of the Brownian ratchet model of
+    molecular motors.  A motor is shown as a circle
+    (\protect\tikz[baseline,yshift=1.2mm]\protect\node[motorFlip,minimum
+    size=2.5mm]{}; or
+    \protect\tikz[baseline,yshift=1.2mm]\protect\node[motorFlop,minimum
+    size=2.5mm]{};), and its energy landscape is shown as a thick line
+    \protect\tikz[baseline,yshift=.2em]\protect\draw[landscape]
+    (0,0) -- (2ex,0);.  The horizontal axis $x$ represents the motor's
+    position on the cytoskeletal track, while the vertical axis $U$
+    illustrates the motor's free energy.  The motor is hypothesized to
+    feature two distinct potential energy landscapes, depending on its
+    conformational state.  In the flip conformation
+    \protect\tikz[baseline,yshift=1.2mm]\protect\node[motorFlip,minimum
+    size=2.5mm]{};, the energy landscape is flat so the protein may
+    slide freely in one of the two directions, with equal probability
+    for both directions.  In the flop conformation
+    \protect\tikz[baseline,yshift=1.2mm]\protect\node[motorFlop,minimum
+    size=2.5mm]{};, the saw-tooth shape of the landscape favors the
+    motor moving to the right, illustrated by a longer arrow pointing
+    to the right.  When cycles of ATP hydrolysis make the motor
+    periodically switch between the two conformations, thermal
+    fluctuations will tend to push it to the right.  (The original
+    figure is~\cite[Figure~4]{Nicholson2019}, itself a reproduction
+    from~\cite{Kurakin2006}.)}
+  \label{fig:ratchet-motor}
+\end{figure}
+
+Seeing Life as an ensemble of machines biases how we expect to collect
+profit from acting on it.  Machine means control: we are constantly
+looking for knobs which we could turn this or that way, and which
+could modify the behavior of the system to fit our needs and
+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
+researchers develop methodologies to support looking for the coveted
+knobs, e.g.~\cite{PardoID21,Vogel2008,Zanudo2015}.  If we admit that
+the reductionistic and mechanistic approach is not globally true, we
+must therefore 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 shifting in time.  Finally, this control mindset
+introduces an asymmetric relationship between the controller and the
+controlled, which is unnatural biological context because both the
+controller and the controlled are made out of the same kind of matter,
+and are ultimately embedded in the same environment.
+
+In this chapter, I introduce the Deal with Life: instead of looking to
+impact biological systems asymmetrically, surreptitiously lifting
+ourselves above the living matter, I propose to account for the fact
+that we act within complex feedback loops, which sometimes end up
+imposing the consequences of the actions on the actors.  The principle
+of a Deal with Life is to render the interactions \emph{mutually
+  beneficial}: ideally, both systems engaging in the interaction
+should benefit from it.  In practice, this should be translated into
+joint maximization of a pair of functions measuring the utility of the
+interaction for both parties, possibly with one of the two functions
+being prioritized over the other.
+
+\printbibliography[heading=subbibliography]
+
+\end{refsection}
+
 %%% Local Variables:
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hdr.tex

@@ -82,7 +82,7 @@
 }
 
 \graphicspath{{pics/}}
-\usetikzlibrary{calc}
+\usetikzlibrary{calc,positioning,arrows.meta}
 
 \newif\ifentiredoc
 \entiredoctrue % Use this if you want to compile the entire document.
@@ -127,6 +127,8 @@
 
 \changelocaltocdepth{2}
 
+\input{deal}
+
 \fi
 \end{document}