Interviewer: What
do you mean by functional complexity?
Schützenberger: It
is impossible to grasp the phenomenon of life without that concept, the two
words each expressing a crucial idea. The laboratory biologists’ normal and unforced
vernacular is almost always couched in functional terms: the function of an
eye, the function of an enzyme, or a ribosome, or the fruit fly’s antennae.
Functional language matches up perfectly with biological reality. Physiologists
see this better than anyone else. Within their world, everything is a matter of
function, the various systems that they study [are] all characterized
in…functional terms. At the level of molecular biology, functionality may seem
to pose certain conceptual problems, perhaps because the very notion of an
organ has disappeared when biological relationships are specified in
biochemical terms. But appearances are misleading. Certain functions remain even in the absence of an organ or
organ systems. Complexity is also a crucial concept. Even among unicellular
organisms, [there] are processes of unbelievable complexity and
subtlety. Organisms present themselves to us as a complex ensemble of
functional interrelationships.
The simplicity
and tidiness of the mechanistic worldview has proved ideal for textbooks and an
ever-increasing number of publications written for laypeople, a genre with the
unfortunate name “pop science” (short
for “popular science”). In the not-too-distant past, serious scientists were
discouraged from publishing their findings outside of respected scholarly
journals. Not only is this no longer the case, but some scientists forego
publishing their findings in technical journals and present them in book form,
using language accessible to laymen. The result has been a tremendous leap in
the scientific literacy of an interested and voraciously curious public. Likewise,
modern science writers routinely cite other popular works in their
bibliographies. By explaining complicated matters in clear, non-technical
language and simplifying challenging material, cutting-edge scientific topics
are made available to the masses as never before.
No author
consciously intends to restrict readers’ awareness of nature’s complexities
(which, indeed, usually require at least some
explanatory simplification for the sake of intelligibility). Still, widely read
books on an array of biological topics often portray not only the more esoteric
but “normal” life processes in an overly simplistic fashion, glossing over
subtleties or skipping complicated explanations. This is often necessary to preserve
narrative flow; it is altogether too easy to get diverted or bogged down in
details. But the sort of oversimplification I wish to draw attention to does
not always benefit a technically fluent audience. Then again, in many cases
this tendency toward simplification and generalization may be an unavoidable
consequence of trying to reach readers with broad ranges of knowledge.
In truth:
without exception, everything relating
to living matter is staggeringly
complicated. Educators abridge descriptions of life-processes to bring such
matters within intellectual reach. Often, this abbreviation is just a matter of
condensing large amounts of information into manageable form. But an author who
promotes the idea that nature operates by “simple” rules is, consciously or
otherwise, advancing a mechanistic stance—one that aims to smooth out nature’s
often tortuous pathways.
Take any
generalized written account of, say, mitosis. Readers will often be fore-warned
that the subject of cellular division is both extremely involved and highly
technical. Following this brief disclaimer, multiple layers of mentally numbing
intricacy are not merely be downplayed—typically, they will not even be alluded
to again. Nor will the collective causal effects conferred by such complexity
even be touched upon as a gentle reminder that can impart valuable perspective.
Incurious readers seldom think to ask tough questions, having (literally) been
schooled to assume that the entire train of events takes place automatically
and is not particularly noteworthy to begin with.
Another
important issue is the habitual time lag in imparting the latest information.
When fresh data or exciting findings appear—information that might bring to
light new details and add nuance to some biological model—there is typically a
lengthy delay in their conveyance. Many people still rely on books and
magazines as their preferred choice when it comes to learning about things.
Especially for lay audiences, the imparting of important new information in
printed form can sometimes be held back for years. (Indeed, presenting up to
date facts and ideas that readers may not have heard about is a major impetus
behind this work.) Another obstacle in providing the public with advanced information
can be traced to textbooks; many are revised repeatedly and distributed as new
editions without antiquated details being checked for truthfulness and retired
when appropriate; a good deal of superseded or downright false material is disseminated
in this fashion.[2]
Finally, the broad range of factual veracity found online has created a real
impediment to finding accurate, reliable information. Hopefully, this serious
problem will somehow be mitigated in coming years.
Long after it
should have become universally recognized that cells are far more complicated
than was previously imagined, they continue to depicted in ways that make light of their extraordinary intricacy.
Researchers continue to unravel our most tangled riddles and many biologists
believe that, sooner or later, various lingering unknowns will be settled.
Meanwhile, thanks to the wondrous qualities of what I call acute bio-complexity seldom receiving a
fitting level of emphasis in textbooks and works of pop science, our “scientifically
engaged” public has ended up with a flawed and inadequate view of how living
things operate. (This, partly a result of a tendency to deliberately dumb-down
media and internet renderings.) The true wonders of nature merit highlighting
when appropriate; acute bio-complexity is an attribute of life that deserves to be kept in mind continuously.
Here
are two passages from an excellent book about the cell and current (circa 1996)
biochemical research by Boyce Rensberger—at that time, science writer for The Washington Post—which are
illustrative of this effectively trivialized approach:
The discovery of
self-assembly explains many events in cells that once seemed utterly
mysterious. It is akin to learning that the steel skeleton of a building will
assemble spontaneously once a load of girders is dumped at a construction site.
The genes cause a load of protein molecules to be synthesized in the cell, but
the proteins, needing no further control, spontaneously assemble themselves
into larger structures. The plan of the final result is implicit in the
structure of the components.
To back up
this assertion, he then cites two classic examples of structural self-assembly:
the case of microtubules (which spontaneously form when molecules of
tubulin—a protein synthesized in all
cells—join together in a uniform spiral pattern) and the self-ordering of
phospholipids into the bilayer membranes common to all eukaryotic cells.
Rensberger promotes a sense that such auto-assemblage is marvelous, yes, but simply the result of an opportune coincidence
of chemical properties.
Still,
Rensberger’s descriptions are a bit misleading (given that the two key
processes are far from entirely automatic and, additionally, the components
have to first be fabricated within the cell). As for microtubules: a number of
specialized protein machines assist with the construction of new (and
degradation of old) tubules along with their attachment to organelles or the
cell wall. In the case of lipid bilayers, thanks to the powerful chemical
self-attraction of lipids in an aqueous solution, they readily assemble into
sheets or vesicles. However, cellular membranes are actually constructed
piecemeal by the endoplasmic reticulum, then further processed in the golgi
and, finally, are transported in vesicular form to fuse with some targeted
portion of the membrane.
In the second
excerpt, Rensberger again de-emphasizes complexity in favor of fostering an
impression of straightforward simplicity:
Amazingly enough, some of
the regulatory DNA sequences are not situated near the gene they control. They
may be hundreds or tens of thousands of bases away. And yet, if the right
regulatory proteins don’t bind to them, the gene won’t be expressed. How can
this be? How can the gene or the RNA polymerase “know” whether certain proteins
have grabbed onto the DNA strand…? Simple. DNA is flexible. It simply forms a
loop in itself, bringing the distant regulatory protein into contact with other
proteins on the promoter. In the case of the beta hemoglobin gene, there are
several regulators…that speed up the gene-activation rate to varying degrees
and some that slow it down to varying degrees. Somehow they work it out among
themselves how often the gene should be allowed to express itself.
My intention
is not to denigrate Rensberger’s excellent book—still one of the best overall
accounts of cellular life. These two examples are merely representative of the
cavalier language and rhetoric sometimes used to explain such phenomena. Many
contemporary books about these types of subjects are peppered with similar
instances; when some involved process requiring multiple steps and coordinated
assistance is described, the whole affair is frequently put across in a fashion
that deftly underplays its elaborate nature. (A later chapter will examine this
issue in more detail.) What Rensberger has just described here describes only
one step in a remarkably complex process involving thousands of molecular
helpers. And there is nothing simple about any of it.
Unquestionably,
individual molecular interactions are events involving straight-forward
chemical and electrical attractions (or repulsions). The occasional use of superlatives
like “amazing” and “wondrous” in books like Rensberger’s Life Itself (or any biology
textbook) merely allude to the uncanny ways in which inanimate molecules behave. The reader is routinely assured that
such things happen automatically and according to the types of rationally
ordered but non-intentional activity under discussion here. (Often times this
disclaimer is accompanied by a comment reminding the reader that there are no
mysterious agencies involved, so strange can these happenings seem to
non-scientists). Unquestionably, some of the complicated issues discussed here
have by now been explained in some measure. Some have not. But answers to many
of my own pointed questions are not to be found in typical popular science
books. The kind of information I seek is more likely located in the plethora of
scholarly literature found in scientific journals (published at a rate of some thousands per day).
One thing I
have observed while reading technical papers—a noticeable pattern: various
molecular participants arrive on the scene of some reaction to play a part in a
key process with no word of where they came from, how they were manufactured,
or what regulatory agency was involved in their appearance. Such tangential
information may have been deemed non-essential or beyond the subject matter’s
scope. Perhaps it is unknown. But the absence often strikes me as intentional;
things simply “show up.”
And show up
they do…. In their frenetic comings and goings, molecules display a sort of
purposefulness that only higher-level organisms are thought to enjoy. Are their coordinated actions, taken
together, purely mechanical? Microbiologist James Shapiro writes about “the
growing realization that cells have molecular computing networks which process
information about internal operations and about the external environment to
make decisions controlling growth, movement, and differentiation”:
Bacterial and yeast cells
have molecules that monitor the status of the genome and activate cellular
responses when damaged DNA accumulates. The surveillance molecules do this by
modifying transcription factors so that appropriate repair functions are
synthesized. These inducible DNA damage response systems…include so-called
“checkpoint” functions that act to arrest cell division until the repair
process has been completed…. One can characterize this surveillance/inducible
repair/checkpoint system as a molecular computation network demonstrating
biologically useful properties of self-awareness and decision-making.
This is not a
conventional portrayal of mindless molecules at work. Recall that, in the
second excerpt from Life Itself,
Rensberger wrote of these regulatory enzymes: “Somehow they work it out among
themselves.” Obviously, Rensberger did not intend to allege truly purposive action being
displayed in using this offhand way of explaining the solution to an arcane
problem, but simply sought to carry on with his narrative. In the course of my research,
though, never have I seen so much as a hint of there being anything out of the
ordinary about the way protein machines bustle about in what are described as resolute teams, with individual members making crucial decisions.
Returning to
my original statement regarding the nature of life: it possesses its own form of intelligence and a quality of
self-directedness that is displayed by all organisms—even manifesting at the
molecular level. It would be a mistake to equate this kind of willful discernment
with its human analogue. Nonetheless, these traits are called to mind as it
becomes ever more obvious that living things operate according to singular
types of molecular organization—with involvements that go well beyond the
ordinary chaotic collisions that cause things to proceed in cell-world. And
behind all such activity there is often an element suggestive of intent.
In fact,
enzymes display intelligence-mimicking behavior in the form of a functional
property called allostery, made
possible by an enzyme’s capacity to change shape such that an active site can
no longer bind with its substrate (as discussed in Chapter 5.)
Say a
particular enzyme’s job is to catalyze a reaction that produces a chemical
whose concentration causes problems, maybe even a fatal toxicity, when
exceeding certain limits. How does it “know” when to stop? Answer: the
catalyzed reaction’s product (or, if the reaction results in more than one
product, one of them) also serves as a control
molecule. When this product’s concentration reaches a certain level, it
begins binding to a second active site on the enzyme, changing the enzyme’s
shape so that the substrate is no longer able to dock, thus halting production
of the chemical in question. This is what is known as a negative feedback loop,[3]
a vital feature exhibited throughout nature from the nano-scale to the
planetary (where, for instance, forms of self-correcting regulation are seen at
work in the carbon and hydrological cycles).
Allostery
forms the basis of regulation in cells. Physicist-turned-microbiologist Peter
Hoffman adds extra perspective on the intricacy of these regulatory systems:
There are more complicated
schemes that involve vast networks of interacting enzymes. The product of one
enzyme may act as the control molecule for another enzyme, either enhancing or
inhibiting its activity. The product of this second enzyme may again control
the first enzyme, forming a two-enzyme feedback loop…or the product may
influence a third enzyme, which influences a fourth, and so on. Complicated
schemes of feedback loops and mutual enhancement or inhibition provide the
computing power that makes living cells seem intelligent.
This
dual-functionality of proteins—their ability to both carry out reactions and
adjust results to some necessary end—is a crucial feature in the regulation of
cellular metabolism. Allosteric enzyme activity is essential to prevent the
chemical chaos that would result if not delicately tuned to a cell’s strict
requirements. Jacques Monod, who discovered the phenomenon in Paris in the
early 1960s while working with François Jacob on bacterial cell metabolism,
felt the significance of allostery to be so indispensable that called it “the
second secret of life.” (The “first” being the genetic code itself.) Horace
Judson, in The Eighth Day of Creation,
offers this:
Allosteric proteins were
relays, mediating interactions between compounds which themselves had no
chemical affinity, and by that regulating the flux of energy and materials
through the major system, while themselves requiring little energy. The
gratuity [“the freedom from any chemical or structural necessity in the relation
between the substrate of an enzyme and the other small molecules that prompted
or inhibited its activity”] of allosteric reactions all but transcended
chemistry, to give molecular evolution a practically limitless field for
biological elaboration.
These are all
attributes whose subtlety deserves more emphasis whenever cellular functions
are under discussion. Instead, we find a marked tendency to de-emphasize the sophistication
of features such as auto-regulation. By the same token, it is not only the
subtlety and phenomenally clever quality of all these things that boggles and
bewilders, but the way (despite their being completely entangled) these
activities are so precisely coordinated. This “higher order” of interaction is
what has such weighty implications: this is
where the impression of intelligence and intentionality is grounded.
Whenever I
read descriptions of highly involved matters such as allosteric feedback loops
imediately followed by assurances of their simply resulting from predictable, ordinary molecular
interactions, such guarantees sound hollow and forced. This leaves me
further convinced that life’s
creative impetus is the agency behind such beyond-belief sophistication. While
attempting to always keep in mind the risky proposition of relying on an
emotional response to things one finds intellectually difficult to accept, I continually
find myself dubious and forever questioning accepted narratives. For an example
of my thought-train: regarding mitosis, How
do all the molecular players involved gather and position themselves at the
outset? Is there an overall strategy? How do they know exactly when to perform
their assignments, avoid interfering with other teammates, and recognize when
to cease and desist? How do they all make it to the game on time? What “master
gene” calls them to their tasks? What controls those master genes? How did such
an elaborate system come to be in the first place?
And I hear the
committed materialist’s answer: Yes, yes,
yes…we know how each of these things take place: it’s all by gene-controlled
chemical signals…markers, couriers, vesicular transport. Regulatory genes.
Allosteric proteins. The subtlest details are being worked out even now; these
automatic processes are well-understood, at least in general outline. It’s all
chemistry!
About those
“upper-echelon proteins:” whether self-regulating or controlled by genes—the
ones that initiate and direct the actions of whole assemblages of nano-scale machines—how
do they discharge their responsibilities? What orders them up and accounts for all the functions carried out during
their vital, higher-level tasks? How are the actions of allosteric enzymes
coordinated with those of genes, when neither has controlling influence over
the other?
And now, one
last example that underscores yet another aspect of these profound, multifaceted
interactions. During the various stages of mitosis, including DNA replication,
genes remain dormant. (In the case of Homo
sapiens, for some hours.) Hence, all instructions relevant to cell division
have to be issued beforehand; all the suites of enzymes and protein machinery
involved have to be synthesized, tagged for recognition, and somehow programmed
in advance. Many of these will need to be repaired or replaced—perhaps several
times—while they wait. Once provided with final marching orders, though, all
these soldierly nanomachines rejoin other troops careening about the cell,
killing time until a molecular bugler sounds the call.
Andreas
Wagner, specialist in the new field of computational biology, provides an answer (of sorts) to all
these quandries and seeming bottlenecks. (This elucidation is likely about as
straightforward as can be achieved using plain language.) He writes:
The answer lies in
regulation…. And what regulates the regulators? Simple: more regulators…. And
what about these regulators, how are they regulated? Through other regulators.
All these regulators often form daisy chains, regulation cascades….[This] would
seem enough complexity…but alas, regulation can get much more complicated: Regulators form not just linear chains but
complex…circuits where regulators
regulate each other…. Each [activates or represses] a gene [and] can twiddle
the knobs of other genes—up to hundreds—outside the circuit…. Inside a cell
these influences create a symphony of mutual activation and repression, where
each instrument in the orchestra of genes responds to the melodic cues of
others with its own notes, until the circuit reaches an equilibrium—like a
polyphonic closing chord—where the expression of circuit genes no longer changes and their
mutual influences have reached a balance.[4]
Wagner’s
portrayal of symphonic regulation provides an apt context for the asking of
three Big Questions that draw near the heart of what I have termed Natural Design:
At what point do all these circles close? What is the nature of these highest
levels of organization and control? Can
something be identified that, ultimately, is “in charge”? Whatever it is,
whatever might be considered the “conductor,” appears to operate by way of a
multilayered complexity that is beyond normal means of description. Or is
perhaps not within reach of our imagination. This…thing…is rooted in the underlying character of life. An overarching executive “directing principle” need not
operate by way of some centralized agency, after all. This, a natural way for
humans to conceptualize the matter, simply reflects our limited intellectual and
imaginative capabilities.
Immanuel Kant,
whose thoughts on these particular concerns are still pertinent, believed the
whole subject inaccessible to causal explanation. As he urged, we might be
better served by simply taking life’s
nature as a given and let biology proceed from that starting point. There is,
after all, precedence for his stance: this being essentially the way physicists
treat matter, time, and the elemental forces—core principles matter not subject
to further elucidation. For instance, there is no point in even asking why protons and electrons bear
charge. They just do. Case closed.
But, given
what we now know about cellular regulation, it is feasible to conceive that life and all its processes in their
entirety are synchronized, modulated, and controlled by one colossal network of
self-regulating feedback loops. There is no conductor; while biologists have
long known this, it is a only in recent years that we finally have the means
and proper framework to finally begin to piece together scenarios that can
encompass systems of the sort of complexity found throughout nature.
One matter
that probably should have been addressed earlier in this discourse: the
functionality, the “behavior,” of atoms and molecules—though amazing—is always
straightforward and wholly foreseeable. Every electron in the universe is
absolutely identical. (The same is true of all the subatomic particles.) Atoms
of specific elements vary in the number of neutrons and electrons they carry
but individuals of the different
forms are identical. Each form has distinct properties and acts upon other
atoms in ways that may vary with conditions, but each form is eternally the
same. In this sense there is no mystery whatsoever in the way chemical
substances interact; indeed, few things are more predictable. The speed and
fidelity of enzyme/substrate interactions, for instance, is automatic and
unvarying. Mistakes made during the replication of DNA are remarkably rare because of the reliability and constancy
of the participants’ actions. It is this level of uniform consistency that
makes life possible…and its
possibility so extraordinary. What I doggedly contend to be beyond normal
chemistry is the essential nature of those myriad interactive systems and their
extreme degrees of coordination.
Protein form is yet another issue, each specific
type having presumably evolved step by step in Darwinian fashion (based on
selection for functionality). It is known that individual amino acids can be
substituted through time with no adverse effect on the protein’s performance.
On the other hand, a single missing or misplaced amino acid can be
catastrophic, resulting in sickness or death. Their crucial folding process, as
discussed previously, is based on particular properties belonging to the
different amino acids and takes place semi-automatically (though often
requiring assistance from chaperones) depending on the charge of the different
species or their chemical rapport with water molecules. They vary tremendously
in size: hormones like glucagon,
which has only 29 amino acids, to huge proteins like titin, which has over 34,000.
In any case,
we would benefit from there being a suite of exclusive descriptive words to
capture different aspects of nature’s daunting complexity, this being one of
its most distinctive and fundamental characteristics. While it should be
standard custom throughout the study of nature to routinely reference this
complexity as a subtending biological theme, this would only result in
excessive qualification. Which, unfortunately, would serve to further burden
the communication of information that is already terribly involved at the
outset. In fact, the exacting approach required in describing multifaceted
natural processes has always presented conceptual and descriptive challenges,
given that the capacity to sustain awareness of many things interacting
simultaneously is a gift few are endowed with. Still, such awareness—even an
approximation—is crucial in the effort to understand life at its deepest levels.
Fortunately, sophisticated digital visual aids are proving to be a tremendous
tool and will only improve over time.
At present,
though, many individuals (including leading experts in their fields) often
create an impression of not being fully awake to this crucial truth: in
biological systems, at all scales and each level of organization, different
types of the attribute Marcel-Paul Schützenberger termed functional complexity are in operation. And at each organizational
stratum, new structures or regularities appear: that property known as emergence. Each stratum employs its own
logic. And each calls for its own manner of describing relationships between
parts or processes that often are not even present at levels above or below. In fact, life could be said to be an emergent property arising from a
consortium of emergent properties.
After
some reflection, few people would likely find anything smacking of falsehood in
these claims. Recognizing emergentism as an essential feature of all life
processes has become accepted truth. Still, I continually observe in others an
apparent inability to grasp the subtext beneath nature’s profound intricacy.
There is perhaps an unconscious resistance to the idea that this ineffable
quality has pivotal meaning on its own. Acute biological complexity is rooted
in one of life’s most distinguishing
traits: the capacity of its productions to be both self-governed and
harmoniously organized. This shadowy, indefinable quality fails to explain things but provides support for
collectively reassessing emergent properties—a movement already well underway.
©2018
by Tim Forsell
[1] Marcel-Paul Schützenberger (1920–1996) was a member of
the French Academy of Sciences, a medical doctor, mathematician, and according
one contributor to a memoriam in The
Electronic Journal of Combinatorics (Volume 3, Issue 1), Herbert Wilf,
Schützenberger “was interested in (and therefore passionately interested in)
the many flaws in the Darwinian theory as it is commonly presented…. [He]
became one of the first distinguished scientists in the world to point out that
a theory of evolution that depends on uniformly randomly occurring mutations
cannot be the truth because the number of mutations needed to create the speciation
that we observe, and the time that would be needed for those mutations to have
happened by chance, exceed by thousands of orders of magnitude the time that
has been available.”
[2] Paleontologist Simon Conway Morris referred to such
information being “still routinely cited…in that zoo of good intentions, the
undergraduate textbook.” A classic example is the formerly ubiquitous embryo
drawings by Ernst Haeckel illustrating his long-discredited “biogenic law” with
its tongue-twisting axiom, “ontogeny recapitulates phylogeny,” found in
generation after generation of biology texts. Only 30 years after Haeckel
produced the compelling drawings (around the turn of the twentieth century) his biogenic law had been refuted, yet they continued to be reprinted
for decades.
[3] Negative
feedback occurs in a
system or process when some function of its output is “fed back” in such a way
as to reduce the effect of perturbations
and help maintain a state of equilibrium. The classic example is the effect of
a heater’s thermostat.
[4] While remaining true in spirit, this excerpt is a
significant reduction of Wagner’s much lengthier account.
