What Is the Problem of Form?
This is a preliminary draft of one chapter of a book-in-progress
tentatively entitled, “Evolution As It Was Meant To Be — And the Living Narratives That Tell Its Story”.
You will find
a fairly lengthy article serving as a kind of extended abstract of major
parts of the book. This material is part of the
Biology Worthy of Life
Project. Copyright 2017-2021
The Nature Institute.
All rights reserved. Original publication: May 28, 2020.
Last revision: May 31, 2020.
It is well known that amphibians such as frogs and salamanders have a
remarkable ability to regenerate severed limbs. What may not be so
commonly realized is that, if you graft the tail bud of a salamander onto
the flank of a frog tadpole at the place where a limb would normally form
— and also near the time when metamorphosis of the tadpole into a frog
will occur — the grafted organ first grows into a salamander-like tail,
and then, in some cases, more or less completely transforms into a limb,
albeit a dysfunctional one. Among other changes, the tip of the tail
turns into a set of fingers
The experiment can remind us, in passing, how biologists commonly try to
learn about life by severely disrupting it. But the current thing to note
is that, in this particular experiment, the transformation of the tail
into an approximate limb cannot be the result of local causes, since the
local environment of the fingers-to-be is a tail, not a limb. The power
of transformation is, in a puzzling manner, holistic. The part is caught
up within the whole and moves toward its new identity based, not merely on
local determinants, but also on the form and character of a whole that is
not yet physically all there.
In a rather different vein, Harvard biologist Richard Lewontin once
described how you can excise the developing limb bud from an amphibian
embryo, shake the cells loose from each other, allow them to reaggregate
into a random lump, and then replace the lump in the embryo. A normal leg
develops. Somehow the currently unrealized form of the limb as a whole is
the ruling factor, redefining the parts according to the larger,
developing pattern. Lewontin went on to remark:
Unlike a machine whose totality is created by the juxtaposition of bits
and pieces with different functions and properties, the bits and pieces of
a developing organism seem to come into existence as a consequence of
their spatial position at critical moments in the embryo’s development.
But how can this be? How can spatial position within a not yet fully
realized form physically determine not only the future and proper
sculpting of that form, but also the identity of its parts?
In one way or another, the problem is universal. A key feature of
holistic, end-directed, living processes is that the end plays a role in
shaping the means. (See many of the preceding chapters, and especially
Tadpoles with faces engineered to be highly abnormal “nevertheless largely
become normal [adult] frogs: the craniofacial organs move in abnormal
paths until a proper frog face morphology is achieved”
In other words, the means are modified, even becoming entirely
unprecedented if necessary, in order to achieve a characteristic result.
We find the same principle when we look at cascades of gene expression,
such as the sequential expression of the various genes that have been said
to “determine” left-right asymmetry of the vertebrate body. The normal
expectation would be that if one blocks or changes the expression of
earlier genes in the sequence, the disorder should accumulate and be
magnified, perhaps explosively, in downstream gene expression, since
proper cues for the later steps are missing. But
Surprisingly, this is not actually what occurs: each subsequent step has
fewer errors than the previous step, suggesting that the classic linear
pathway picture is importantly incomplete. Embryos recognize
transcriptional deviations from the correct pattern and repair them over
time … The existence of corrective pathways in embryogenesis and
regeneration raises profound questions about the nearly ubiquitous stories
our textbooks and “models” tell about the molecular explanations for
All this may remind us of E. S. Russell’s remark that in biology “the
end-state is more constant than the method of reaching it”
We also see here the principle that cell biologist Paul Weiss enunciated
so clearly at mid-twentieth century, when he pointed out that the whole
“is infinitely less variant from moment to moment than are the
momentary activities of its parts”. At the lowest level of biological
activity, molecules in the watery medium of a cell have degrees of freedom
(possibilities of movement and interaction) that would spell utter chaos
at higher levels if it were not for the fact that the lower-level activity
is “disciplined” from
One further example. During development, the lens of an amphibian eye
derives from the outer layer of cells in the developing head, at the point
where an outgrowth of the brain comes into contact with the epidermal
cells. But if an already developed lens is removed from one of these
animals, something truly remarkable happens: a new lens forms from the
upper edge of the iris, a structure that has nothing to do with lens
formation in normal development. The procedure runs like this
(Gilbert 1994, p. 40):
Cells from the upper part of the iris — cells that have already reached an
endpoint of differentiation — begin multiplying;
these multiplying cells then proceed to dedifferentiate — that is, to lose
their specialized character, including the pigmentation that gives the
iris its color;
the newly multiplied, iris-derived cells migrate so as to form a globe
tissue in the proper location for a lens; and finally,
they start producing the differentiated products of lens cells,
crystallin proteins, and are thereby transformed into transparent lens
cells — all in
the nuanced spatial pattern required for the formation of a proper lens.
And so, lacking the usual resources and the usual context for formation of
a lens, the animal follows an altogether novel path toward the restoration
of normal form and function.
It is impossible to believe that these complex and intricately coordinated
responses to the loss of the lens were somehow already physically
determined or programmed or otherwise specified in the animal’s one-celled
zygote. Nor is it easy to imagine how there could ever have been a
sustained and large population of lens-injured amphibians with otherwise
functional eyes — a population large enough, that is, to enable a
supposedly mindless process of natural selection to evolve a specific,
novel solution to the problem of lens regeneration.
The problem of form exists
even at the molecular level
The problem of form has long been central to biology, where each creature
so notably reproduces after its own kind and according to its own form.
“It is hardly too much to say”, wrote geneticist C. H. Waddington, “that
the whole science of biology has its origin in the study of form”. In
both their descriptive and theoretical activity, biologists "have been
immersed in a lore of form and spatial configuration”
(Waddington 1951, p. 43).
“Immersed in a lore of form” is, however, an oddly mild way of putting it.
“Hopelessly adrift upon a fathomless sea of mystery” might be more
fitting. An observer surveying the biological disciplines today (some
seventy years after Waddington’s comment), can hardly help noticing that
every organism’s stunning achievement of form has become an enigma so
profound, and so threatening to the prevailing style of biological
explanation, that few biologists dare to focus for long on the substance
of the problem.
The Miracle of Wound Healing
Here is a description offered by English biologist Brian Ford
“Surgery is war. It is impossible to envisage the sheer complexity of
what happens within a surgical wound. It is a microscopical scene of
devastation. Muscle cells have been crudely crushed, nerves ripped
asunder; the scalpel blade has slashed and separated close communities of
tissues, rupturing long-established networks of blood vessels. After the
operation, broken and cut tissues are crushed together by the surgeon’s
crude clamps. There is no circulation of blood or lymph across the
“Yet within seconds of the assault, the single cells are stirred into
action. They use unimaginable senses to detect what has happened and
start to respond. Stem cells specialize to become the spiky-looking cells
of the stratum spinosum [one of the lower layers of the epidermis]; the
shattered capillaries are meticulously repaired, new cells form layers of
smooth muscle in the blood-vessel walls and neat endothelium; nerve fibres
extend towards the site of the suture to restore the tactile senses
“These phenomena require individual cells to work out what they need to
do. And the ingenious restoration of the blood-vessel network reveals
that there is an over-arching sense of the structure of the whole area in
which this remarkable repair takes place. So too does the restoration of
the skin. Cells that carry out the repair are subtly coordinated so that
the skin surface, the contour of which they cannot surely detect, is
restored in a form that is close to perfect.”
We will find it necessary in our further discussion to keep in mind that
the mystery is at least as apparent on the microscopic (and even the
molecular) level as it is at more easily recognizable levels. We have
already seen this in earlier chapters. For example, in
we heard the English neurophysiologist, Sir Charles Scott Sherrington,
describing how a severed motor nerve in some animals manages to grow back,
through many obstacles, toward the far-distant muscle it was originally
Somehow the minuscule nerve “knows” where it is within the vast
three-dimensionality of the animal’s body — knows its own place in
contradistinction to that of all the other nerves in different parts of
the body. It likewise “senses” where it needs to get to in the local
context, and how to find its way there. It’s as if it had a detailed map
of the terrain.
When we consider the more general case of wound healing described in
we find ourselves watching how the nerves, blood vessels, muscles, and all
the diverse, mangled tissues in a wound sort themselves out. It is all
somehow governed by what the description’s author calls “an over-arching
sense of the structure of the whole area in which [the] repair takes
place.” The original form is restored as far as possible. But what is
being sensed? how is it sensed? and “who” is doing the sensing? — these
most basic questions remain unanswered.
We saw in
that a similar problem faces us when we look at the several hundred
molecules engaged in the intricate molecular “surgery” known as RNA
splicing. We know that all the complex, carefully sequenced, splicing
interactions respect every bit of physical and chemical understanding we
have amassed, and so we can explain them in that sense. But a
biological understanding — an understanding of the effective,
flexible, context-dependent coordination of physical events toward a
desirable result — remains to be attained.
And so the problem of form, even when we try to approach it at the
molecular level, seems intractable from the standpoint of conventional
biology. In the case of RNA splicing, we can ask how each of the several
hundred molecules cooperating in the activity of splicing is synthesized
in the right amount; how each particular molecule is brought to the right
place for splicing, and at the right time; how it manages to interact with
properly selected molecules among all the other potential partners in the
operation, doing so in a carefully choreographed sequence; how the overall
cooperation among all the molecules is achieved; and how this cooperation
is properly aligned with the needs of the cell at a particular time
— a time when one form of the spliced RNA rather than another happens to
be called for, requiring the surgery to be performed with unique
Need is not a term of physical science. Further, all this occurs
in a fluid or highly plastic medium, with no crucial and precisely
machined channels of communication such as those carved in silicon chips
at our high-tech factories. The essential mechanistic constraints, such
as those required for the operation of our machines, simply are not there
in the organism.
Of course, researchers have traced all sorts of molecular syntheses,
movements, and interactions. We can be sure that everything in the entire
picture proceeds lawfully, and in this very constricted sense every local
event looks necessary. And yet we can find no combination of physical
laws capable of “enforcing” the proper form of all the different parts of
the body of this or that animal. In the case of a wound, there is no
purely physical necessity to achieve a given form in the face of
In other words, the mere fact of physical lawfulness does not explain the
coordination of events along an extended timeline in the
of healing, from infliction of the wound to the final restoration of
normalcy. Nor does it explain the narrative of RNA splicing, from the
occurrence of an RNA molecule in need of reconfiguration, to the final
product of those hundreds of participating molecular “surgeons”. We can
“watch” the molecules performing in a way that gives expression to the
overall sense, or meaning, of the activity, but we do not have even the
barest beginnings of a purely physical explanation for their commitment to
Michael Levin: Revolutionary
Michael Levin is an enthusiastic, prolific, hyper-achieving researcher who
appears to represent at least part of the future of biology. As the
Vannevar Bush Professor at Tufts University near Boston, Levin is
principal investigator of the Levin Lab there, director of the Tufts
Center for Regenerative and Developmental Biology, and team leader of the
Allen Discovery Center at Tufts. He also holds positions at Harvard and
MIT. The wide-ranging work under his supervision includes pioneering
explorations of the role of electrical fields in the production of
biological form. (See
Electricity in the Developing Tadpole
In the summer of 2011 a team of researchers at Tufts University produced a
startling, time-lapse video of a developing tadpole
Due to the use of special dyes reporting the electric potentials across
cell membranes, areas of the embryonic surface successively lit up
brightly and then went dark. For a few seconds of the time-lapse film
(representing the events of several hours), the featureless part of the
embryo that would eventually become the animal’s head flashed the image of
a tadpole face.
But no actual face had yet developed. Nevertheless, the electrical
pattern did “signal” where key elements of the tadpole’s face, such as its
eyes, would eventually appear. Regional changes in electric potential,
these scientists concluded, “regulate expression of genes involved in
According to Michael Levin, head of the laboratory where the tadpole
research was performed, “Ion flows and the resulting [membrane voltage]
changes are components of long-range conversations that orchestrate
cellular activities during embryonic development, regeneration, and
… tumor suppression”. He adds that “bioelectric cues are
increasingly being found to be an important regulator of cell behavior”,
controlling the proliferation and death of cells, their migration and
orientation, and their differentiation into different cell types.
“We are”, he wrote further, “just beginning to scratch the surface of the
bioelectric code — the mapping between voltage properties and patterning
outcomes, akin to the genetic, epigenetic, and perhaps other codes
remaining to be discovered”
Levin’s team quickly went on to manipulate the distribution of membrane
voltages in developing embryos so as to provoke the generation of eyes in
decidedly unexpected places — for example, on the back and tail, and even
in the gut, of a frog embryo. The results were fragmentary and rather
chaotic — the ectopic (“out of place”) eyes were partial or deformed — but
the result was nevertheless as startling as it was monstrous
(Pai et al. 2012).
But what is perhaps most impressive about Levin is his willingness at
least to make a start at acknowledging certain extraordinarily difficult
questions biologists must raise if they want to face organisms squarely,
as we actually observe them. Chief among these is the problem of organic
Levin is particularly explicit about this problem in a paper entitled “The
Biophysics of Regenerative Repair Suggests New Perspectives on Biological
Causation”, published in Bioessays
We will now give particular attention to this paper, which will be the
source of all quotations unless otherwise indicated.
The way in which tissue voltage patterns prefigure the developing form of
embryos has been central to Levin’s thinking
This prefiguring, he emphasizes, is not in the first instance a genetic
event, but “a [much higher-level] physiological event … causally
responsible for a given patterning outcome” — and therefore also a cause
of the gene expression required for that outcome.
In other words — and this is where Levin particularly sees himself
offering something new — there is a kind of causation, somehow active in
the larger pattern, that we cannot understand by adding together the
causal action of molecular-level entities upon each other. The
tissue-wide electric potentials can fairly be said to play a decisive role
in stimulating cascades of gene expression on the way toward formation of
entire organs. But, in the reverse direction, genes cannot be said to
cause, or explain, the patterns of electric
Similarly with the examples in the opening section of this chapter. They
all raise the problem of causation from whole to part — and (although this
is not a point Levin raises) they all vex our efforts at strictly physical
understanding. The question we need to ask ourselves is this: “How can
the physical body of a relatively undeveloped organism — a body already
exhibiting coordinated physical processes perfectly adapted to the
organism’s present state — redirect and transform those well-adapted
physical processes so as to conform to a different and more “mature”
pattern that is not yet there?”
Whole-part, future-oriented causation
Why does holistic causation refuse strictly physical understanding? A key
difficulty, as I have been emphasizing, lies in the observation that every
embryo seems, in its holistic manner, to be reliably guided toward
a future state. It is as if that future state were somehow present and
influential along the entire path of its own material realization — as if
the developing embryo were expressing from the very beginning its own
telos, or the essential idea of its ultimate maturity and
wholeness, as a very real and present power.
In a moment we will have to ask to what degree Levin clearly recognizes
how thoroughly the problem of causation running from whole to part and
directed toward the future disrupts conventional thinking. He is, in any
case, fascinated by what he often refers to as “top-down causation” — “an
important distinct type of causation” in which ”a future state …
guides the behavior of the system”. He recognizes the “incredibly tangled
details underlying system-level outcomes in biological systems”, and
instead of immediately pivoting away from the challenge of
future-directed, higher-level causation in order to resume the analysis of
microstates, he questions the wisdom of such a strategy:
Embryonic patterning, remodeling, and regeneration achieve invariant
anatomical outcomes despite external interventions. Linear “developmental
pathways” are often inadequate explanations for dynamic large-scale
pattern regulation, even when they accurately capture relationships
between molecular components.
That is, even in the face of the researcher’s deranging intrusions, the
embryo does its best to re-organize itself in the light of a
characteristic outcome yet to be fully realized — all in a way that does
not seem to be explained by the activity of lower-level entities.
The common expectation, which dominated twentieth-century molecular
biology, had been that we would learn to track every microstate in every
cell and organism, and in doing this we would gain all the understanding
of biological processes we could ask for. Levin wonders whether this
expectation isn’t having the unfortunate effect of “delaying the
development of higher-level laws” that could advance our interests more
So, then: what might he mean by “higher-level laws”?
Michael Levin: Counter-revolutionary
Unfortunately, and despite Levin’s desire to frame a new paradigm of
causation in living beings, his work testifies to the deeply engrained
power of conventional biological thinking. In fact, he seems drawn to the
most abstract and least biological aspects of this thinking.
Counter to what you might have thought based on the preceding
descriptions, Levin’s interests center emphatically on machine-like
models, control, and prediction. (I count forty-eight
occurrences of the word “control” in the main body of his article.) He
repeatedly expresses his confidence in explanatory models based on
“top-down” techniques already “exploited very successfully by control
theory, cybernetics, computer science, and engineering of autonomous
robotics” — and is also impressed by “new developments in information
theory that help to rigorously identify and quantify tractable macrostates
with maximal causal power”. These top-down tools of control could now
“enable transformative advances in biomedicine”.
By “top-down” Levin typically means: driven by a computer-like program
somehow embodied in things like circuits and switches. The new in
his “new paradigm” consists largely of the fact that the program is
thought to be distributed throughout tissues and organs, rather than
encoded in the tight “logic” of the DNA sequence.
Even the bioelectric features of tissues
become, for Levin, the manifestations of digital devices. When he looks
at these features, he sees circuits, biolectric networks that serve as “a
rich computational medium”, and feedback loops “equivalent to transistors
— fundamental building blocks of logic circuits and decision-making
And so, he is convinced, appropriate machine models present a wonderful
opportunity: we may gain “predictive control in regenerative medicine and
synthetic biology”. All that is required is a high-level focus on
“control mechanisms that harness cell behavior toward specific organ-level
outcomes”. His complaint about microstates as presumptive causes is that
they do not enable us “to make quantitatively accurate predictions with
respect to the complex final outcome … which is the key property we
require from a purported explanation of a biological process”.
One might have thought that at least one key thing we want from biological
explanations is an understanding of the unique ways of being
distinguishing the life of one organism from another — for example, the
zebra from the lion
The narrow interest in “quantitatively accurate predictions”, on the other
hand, stems from the long-running commitment of science to the discovery
of clear and unambiguous causes of a certain sort — reliable causal
factors that, within carefully controlled systems, consistently make
specific things happen, and therefore can be used technologically.
Certainly we do want a maximally effective medicine, just as we
want a maximally effective political or educational system. But this does
not mean we can healthily understand political or educational processes by
grounding ourselves in machine models of causation. And the same goes for
medicine. Our understanding in such domains arises not so much from
technological manipulation, as from our taking up a meaningful role of our
own within the never fully predictable context of an organism’s unfolding
Our hope is to become part of an informative, worthwhile, and mutual
The main problem we have in following Levin is that we arrive at neither a
revolution nor a new paradigm for causation merely by changing our level
of observation from microstates to macrostates — from molecules to tissues
and organs. As long as we remain committed to the same physical and
mechanistic notion of causation that has dominated biology for the past
few centuries, we can hardly claim to have arrived at a profoundly new
understanding of biological causation.
I believe Levin has glimpsed the fact that something radically changes
when one begins to talk about top-down causation — especially if one
realizes that, in organisms, we are looking not only at causes running
from the whole toward the parts, but also at a kind of future-oriented
causation. But he has compromised whatever insight he had by forcibly
marrying it to tired, machine-based habits of explanation that represent
nothing but the old paradigm.
Of course, he might well object to this. His references to cybernetics,
control theory, and computational neuroscience show that he sees himself
focusing on a distinct type of machine — namely, those operating
under some form of programmed control and feedback. Don’t we see in these
machines a kind of top-down and purposive causation that seems to match
that of organisms? The inadequacy of current thinking about biological
causation, he is suggesting, lies in biologists’ failure to exploit the
analogies between living beings, on one hand, and machines of this
particular sort, on the other.
He is right — and importantly so — about biologists’ failure to take
seriously the fact of purposive, or telos-realizing, biological
causation. But does he himself acknowledge causation that is genuinely
purposive? Or does he instead think in terms of causation that only
looks, rather illusorily, “as if” it were purposive? And do
programmed machines point us toward a useful understanding of biological
In what sense are machines end-directed?
In his paper, Levin addresses the idea of “setpoints as causes”.
Setpoints, he says, are not-yet-existing “future states” that somehow
“guide the behavior of the system” toward a realization of those future
states. As it stands — and in relation to living beings — the assertion
is as vague as it is radical. But Levin makes clear the kind of thing he
has in mind: it is illustrated above all by the kind of feedback and
control systems we routinely rely upon in devices we use daily.
In such systems, the setpoint is embodied in a mechanism or controller
that can be set to some value. In a very simple case, this could be a
thermostat set to a particular temperature. That temperature is the
setpoint, and the thermostat uses it to control a heating system, such as
the one in many homes.
A more complex case would be a computer taking input from buttons you may
have on your automobile’s steering wheel, where the input represents a
desired cruise control speed. Or think of a cruise missile flexibly
seeking out a specified target with the help of “sensing” instruments and
a complex, computerized guidance system. The target (set point) must, in
one way or another, be entered into the computer.
It is obvious that we can say, abstractly and analogically, that organisms
pursuing their own purposes have “setpoints”. The lion (in some sense)
races “like” a cruise missile toward the antelope, adjusting its course as
the antelope turns this way and that. And, likewise, the lion embryo
flexibly pursues a reliable “trajectory” toward its mature form. But —
although Levin often seems to forget the fact — such remote analogies fail
to show that the lion can in any meaningful sense be explained as the
functioning of a programmed machine. This would have to be demonstrated.
Surely (to change the image) it is difficult to find much commonality
between the transformation of a single zygotic cell into a mature eagle,
on one hand, and the “development” of a missile, on the other. If, before
venturing upon its flight, the missile were to “mature” from a single
transistor (or circuit board) into the totality of a functioning, deadly
efficient vehicle; and if, during its flight, all its physical
constituents were metabolizing and metamorphosing as an essential part of
the overall operation; and if, instead of a single “setpoint”, there were
a massively interwoven and nearly infinite collection of “setpoints”
governing each of the missile’s “organs”, each “cell”, the entire missile
as a whole, and all its environmental relations — well, as you can see,
taking the comparison with living beings seriously could get silly fast.
But the decisive issue is not difficult to grasp. Cruise missiles — and,
for that matter, kitchen blenders, electric hand drills, and textile looms
— consist of materials we articulate together for use as tools in
accomplishing our own tasks. The “top-down” ideas guiding assembly are
ours; they do not come to expression through holistically active
developmental processes in which all the parts being assembled
participate. Our ideas are not native to the collection of parts.
Our ideas are not active at the very root of material manifestation in the
way that physical laws and biological principles are inseparable from the
substance in which they work. We merely rearrange, in an external manner,
materials already given to us. We cannot penetrate to the inherent
lawfulness of physical materials with the force of our wills, except in
moving our own bodies. (And even there, the doing is currently
inaccessible to our
When we want to explain the operation of a kitchen blender (or a missile),
we require no reference to its intentions, or to any striving toward a
future state. When we do make such reference, we are really talking about
our own purposes in structuring the device for employment in service of
our interests. Removing our intentions from the picture leaves nothing
missing in a strictly physical, non-intentional, and non-end-directed
characterization of the device. There is no more a physically inherent
end-directness in a cruise missile than in a blender.
By contrast, a developing organism’s living “trajectory” results from its
growing directionally into its mature functioning. We never see a
designing power or force that assembles an organism in anything like the
way we build tools and machines. Whatever is at work expresses itself at
the foundations of material manifestation. Organisms are not designed
and tinkered with from without, but rather are enlivened from within.
The wisdom we find at play in them is intrinsic; it is their own in a
sense wholly untrue of the external intelligence with which our mechanical
inventions are structured.
Does this not make a great difference for our thinking about causation in
organisms and machines? The act of structuring and programming a physical
device such as a cruise missile is our own. The missile itself has no
intentions, and is not “aiming at” anything, no matter how great our role
as inventors and builders. In this regard it is simply a more complex
kitchen blender. We may have gotten more sophisticated in shaping tools
to our own ends, but that is our development, not the machine’s.
A deep issue, unaddressed
I have several times mentioned in these pages that all biologists do
recognize the agency — the telos-realizing, purposive,
(narrative) activity — of organisms. Biological research is structured by
our interest in the things organisms do and accomplish so differently from
what rocks “do” and “accomplish”, from gene expression, to DNA replication
and cell division, to growth and development, to behavior.
But, as I have also mentioned, this awareness of agency remains, for most
and therefore does not make its way into biological theory and
explanation, or even into the biologist’s own clear consciousness. Levin
therefore provides a valuable service by encouraging a more general
awareness of what he occasionally refers to as the “teleological”
dimension of biology.
I do regret, however, that despite his extraordinarily wide-ranging
familiarity with the technical literature, he shows no evidence of having
mined the rich wisdom in the works of the organicist biologists of the
twentieth century — figures such as E. S. Russell and John Scott Haldane
(not to be confused with his son, J. B. S. Haldane) in Britain, and Paul
These prominent and well-respected researchers had already grasped the
centrality for biology of the coordinating (“top-down”) agency at work in
organisms seen as wholes.
A familiarity with this earlier work might have prodded Levin to take a
more critical approach to the machine models he so insistently applies to
organisms. As it is, he makes no very apparent effort to justify a
substantive comparison of living activity to humanly designed machine
operation. He does, however, assure us that, with respect to developing
organisms, “work is ongoing to understand the molecular nature of the
processes that measure the [current] state, maintain the setpoint, and
implement the means-ends process to achieve the target morphology”.
But, in the work he cites, I see nothing to suggest answers to the most
obvious questions. Where might the setpoint be physically embodied —
where might it even conceivably be embodied — so as to represent
the entire, infinitely detailed and intricately interwoven morphology of a
given animal? Once found, how might this setpoint actually direct and
coordinate all the animal’s
activity over a lifetime — or over a single healing episode such as
And where do we find evidence that an organism’s fundamental activity of
growth, striving, and self-transformation can be
understood on the model of our technological devices?
Much of the work Levin draws upon to illustrate machine-based theorizing
about the top-down performance of organisms comes from neuroscience, and
especially computational neuroscience. The naivete expressed in this work
can be startling. This is illustrated by how quickly, in the dawning
computer age, neuroscientists decided that neurons (the only cells in the
brain taken with any seriousness at the time) were essentially binary,
on-or-off devices more or less like transistors. Even today that basic
mind-set seems entrenched, despite the inevitable complicating factors
emerging year after year.
It all reminds me of the prominently honored theoretical neuroscientist,
Larry Abbott, who, in a genuine attempt to support the prevailing mindset,
wrote a book chapter about the brain entitled “Where Are the Switches on
There turns out to be no obvious answer.
Beyond neuroscience, it seems that if anyone anywhere has applied a
machine model to biological problems, and if the machine model
incorporates a top-down aspect, as in cybernetic devices, this seems
enough for Levin to claim an applicability to organisms and a confirmation
of top-down living activity. But why the need for such confirmation in
machine-based models, when the most obvious route to it is simply to
look at organisms, as eminent biologists have already done — and as
all biologists do, at least unconsciously? The problem of
telos-realizing activity is universally recognized, even if nearly
all biologists assume it has somehow been explained away by natural
An unquestioned model
The machine model seems so deeply embedded in Levin’s thinking that one
can only surmise he has never thought of questioning it. He seems to
think it inevitable that any analogy between an organism and a machine,
however abstract, means the organism must work the way the machine works.
He is properly struck by the remarkable achievements of development and
regeneration we mentioned earlier in this chapter. But when he looks at
these achievements, he immediately, and without further question, sees in
them “extensive proof-of-principle of control circuits that enable
efficient self-repair and dynamic control of multicellular, large-scale
(Pezzulo and Levin 2015).
In other words, the fact that we see the organism developmentally
transforming itself and healing wounds — and doing so as a coherent whole
— is already proof for him that we are dealing with large-scale “control
circuits”. Certainly there is a physical activity through which
the organism’s transformation and healing is realized. But nowhere in the
physical lawfulness of this activity do we find the requisite principles
of coordination and control. The fact that we can build machines with
certain kinds of controls does not show that organisms function causally
in the manner of these machines.
As for the predictability in which Levin sees evidence of top-down
controls, his prime illustrations are the achievement of his laboratory in
stimulating the development of eyes on the tails (or in the guts) of
tadpoles, and in producing two-headed flatworms — all by means of
bioelectric manipulations. It is true enough that when we forcibly
intervene in an animal’s life, giving it biological signals that would not
normally occur, it can only take the signals as reality and respond
holistically as best it can. Presumably, if we intervene to keep
experimental conditions constant, we might (more or less predictably)
expect similar insults to produce similar responses.
But it isn’t clear how “throwing a wrench into the works” by deranging an
animal’s normal developmental processes, thereby causing the formation of
dysfunctional eyes and supernumerary heads, constitutes the kind of
predictability we would want from an understanding of the true
nature of an organism. And, in any case, none of this testifies to
the machine-like nature of the processes by which an organism carries out
even deranged living activities.
It is precisely because every organism is, in a holistic sense, an
agent, that it can respond to violent interventions in a meaningful and
creative manner. This holistic response is what seems to entrance Levin.
He wants other biologists to recognize the organism’s top-down
performance. But not only does he fail to reckon with the work of earlier
biologists who both described such holistic agency and denied the
machine interpretation; he sees no need to make his own case for that
interpretation. He just takes it for granted.
Given his promise as a biologist, I could dearly wish that Levin would
consider something like the process of RNA splicing described in
or DNA replication and damage repair, or cell division, or just about any
other sustained biochemical or physiological activity in living beings.
And then I would love to see him view this activity in light of the
observation by Paul Weiss we heard above: “The behavior of the whole “is
infinitely less variant from moment to moment than are the momentary
activities of its parts”. Where are the machine models that can
meaningfully elucidate the overall coherence of these largely fluid
I am sure Levin would be pleased to see how Weiss’ work thoroughly
supports his own interest in top-down causation. But Weiss would have
wanted no part of Levin’s machine-based explanation.
Where are we now?
Organic Form and Machine Models
(“All Science Must Be Rooted in Experience”) we saw that scientific
knowledge arises through a marriage of sense and thought. When my own
thinking becomes one with and inseparable from the thinking in some
particular phenomenon — I could almost say, “When the phenomenon thinks in
me” — then I can, with reason, be confident of my understanding.
We understand a machine, too, by participating with our minds in the
thinking that constitutes it as the kind of thing it is. The part of this
thinking that is most obviously relevant to living beings is,
unsurprisingly, the thinking originally contributed by ourselves, as we
imagined and assembled the machine according to our own purposes. This
thinking, which occurred in the past, is reflected, or imprinted
upon, the device’s form, and also reflected in our intentions as we employ
the device. By contrast, the present thinking at work in the
materials of the machine is nothing other than what we discover in the
non-living world generally. This includes the ideas we formulate as
So here’s where we are. We have been introduced to the problem of form —
the problem Michael Levin so eloquently brings to the biologist’s
attention. How does an organism move in a persistent, adaptive, and
sometimes strikingly novel way toward the realization of a living shape
and functioning that are in some sense “given in advance”? At this point
— based on the present chapter as well as the preceding ones — we have
only the negative conclusion that machine ideas are neither revolutionary
nor particularly helpful for our approach to this question.
we will look at a more conventional take on the problem of form — the one
offered by evolutionary developmental biologist Sean Carroll in his book,
Endless Forms Most Beautiful. This will enable us to get at a
rather unexpected conclusion: form is not something we should be feeling a
need to explain, least of all to explain with our familiar mechanistic
notions. Once we rise above those notions, we may be able to glimpse that
the proper apprehension of form is itself the understanding we were really
seeking all along.
Weiss 1962, p. 6. Emphasis in original.
Weiss’ point is that, whatever the level we analyze, from macromolecular
complexes, to organelles, to cells, to tissues, to individual organs, to
the organism as a whole, we find the same principle: we cannot reconstruct
the pattern at any level of activity by starting from the parts and
interactions at that level. There are always organizing principles
that must be seen working from a larger whole into the parts.
Weiss expressed this truth in a significant formula:
Σ(va + vb + vc + . . .
That is, if you take a given fraction, A, of an organic complex such as a
cell, and if you measure all the fluctuations of its physical and chemical
parameters over a period of time, summing them as va, and if
you do the same with all the other fractions, B, C … and if,
finally, you record all the measurable features of the total complex, S,
as a whole, along with their variations, then you reach this conclusion:
the total variance of all the subprocesses within a cell (jumping up a
level, you could also say: “the total variance of all the cells in a
tissue”) is less than the sum of all the variances of the individual
subprocesses (or separate cells in the tissue). “The formula represents
an ‘operational’ description of what it is that makes the cell as a unit
‘more than the sum of its parts’”
(Weiss 1963, pp. 395-6).
In other words, despite the countless processes going on in the cell, and
despite the fact that each process might be expected to “go its own way”
according to the myriad factors impinging on it from all directions, the
actual result is quite different. Rather than becoming progressively
disordered in their mutual relations (as indeed happens after death, when
the whole dissolves into separate fragments), the processes hold together
in a larger unity.
We might say that a given type of cell (or tissue, or organ, or organism)
insists upon maintaining its own recognizable identity with “unreasonable”
It turns out, then, with a touch of irony, that less change is what
shows the whole cell to be more than the sum of its parts. It’s as
if there were an active, coordinating agency subsuming all the
part-processes and disciplining their separate variabilities so that they
remain informed by the greater unity. The coordination, the ordering, the
continual overcoming of otherwise disordering impacts from the environment
so as to retain for the whole a particular character or organized way of
being, expressively unique and different from other creatures — this is
the “more” of the organism that cannot be had from the mere summing of
discrete parts. The center holds, and this ordering center — this whole
that is more than the sum of its parts — cannot itself be just one or some
of those parts it is holding together. When the organism dies, the parts
are all still there, but the whole is not.
(See also the brief discussion of Weiss in
Vandenberg et al. 2011.
As of April, 2020, the video was available
The point is that
bioelectric fields across tissues are the result of physiological
processes at a considerable remove from gene expression. While genes are
certainly required for the production of the
ion-transporting proteins that help produce electric fields, these genes
can hardly be said to control the subsequent activity of these proteins.
This activity includes the elaborate and sensitively shifting play of
bioelectric signaling of the sort involved in craniofacial patterning of
We may also bring materials into contact with each other so that
they can undergo the chemical transformations expressing their own
inherent potentials. These transformations, such as the (sometimes
explosive) reaction of gaseous oxygen and hydrogen to produce water, remain
almost a complete mystery to us at the qualitative, phenomenal level,
despite our ability to map forces and create models of (falsely imagined)
“entities” at the atomic and molecular levels.
See, for example,
Interestingly, I have lately happened upon a web page where Levin cites
“Scientists who have inspired me”.
Paul Weiss is one of those listed. But I have found no reference to
Weiss’ work in Levin’s scientific papers, although I could well have
missed something. Curiously, one of the four books Levin attributes to
Weiss, entitled First Considerations, is actually a work by the
American philosopher, Paul Weiss (1900–2002), known for writings in
metaphysics, epistemology, and cosmology. In any case, it remains true
that the biologist Weiss’ skepticism about machine-based models of living
processes is a badly needed addition to Levin’s scientific perspective.
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Steve Talbott :: What Is the Problem of Form?