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Monday, November 7, 2022

Developmental Biologists Can't Get Their Story Straight

Developmental biology is the branch of biology studying the process by which an organism progresses from a speck-sized state of a newly fertilized zygote to a full adult state that is vastly more organized and much larger. A recent Quanta Magazine article here tries to give us some sound bites suggesting that developmental biologists are making progress. But inadvertently the article is rather much a portrait of developmental biology in disarray, not getting much of anywhere, without any convincing story to tell for how marvels of biological organization occur. There's a little halfhearted mention of chemicals, a little halfhearted mention of physics, and nothing that adds up to a hundredth of an explanation of how vastly organized human bodies could arise from the tiny speck-sized simplicity of a newly fertilized zygote.  

Over the past few decades we have seen these common elements in these types of articles and the papers of developmental biologists:

(1) Again and again, words will be carefully chosen to try to make the problem of morphogenesis sound a billion times simpler than it is. For example, someone will talk about a problem of the origin of "form" or "shape." The problem is vastly bigger than that. It is the problem of explaining why fantastically organized structures appear, with so many levels of very high organization. That is a problem almost infinitely bigger than the problem of explaining how human-shaped bodies arise.

(2) Again and again, appeals are made to "patterns," as if an organism's body was a mere pattern. A human body is something almost infinitely more impressive than some mere pattern. 

(3) Again and again, dubious claims are made that some tiny little thing has been explained, often with some kind of mention of physics or chemistry. Almost all of the claims fail to be well-replicated scientific results.  An example is the unfounded claim that there are "morphogen gradient" chemicals that tell cells where to go to. For a long discussion of why this claim has no real explanatory value and is also not well grounded in observations, see my post here

(4) The explanatory sound bites given made are ever-changing. For decades  biologists told us the bogus story line that the human body arises because of a blueprint in DNA (despite the lack of any such anatomical blueprint in DNA). But the Quanta Magazine article ends with this statement, which sings a different tune:

“ 'We used to think if we just studied the genome with more and more depth and rigor, all of this would be clear,' Shyer said, but 'the answers to the important questions might not be at the level of the genome.' Once it seemed that developmental decisions were made through the interplay of genes and their products within cells, but the emerging truth is that 'the decision-making can be happening outside of the cell, through the physical interactions of cells with each other.' ” 

You do not explain how cells know where to go in the developing body or how to progress by using the vague wooly phrase "the physical interactions of cells with each other." If we don't understand how cells are able to go to the right places in the body (as if they had some knowledge they should not have), we do not explain such a thing by imagining such cells are interacting with other cells that also should not have such knowledge of the proper destinations of cells. And you don't get "decision-making" from "physical interactions"; you get decision-making from a mind. 

(5) There is an abundant use of imprecise wooly phrases and poorly defined terms, such as "morphogens" (a term defined in many different ways) and "the physical interactions of cells with each other." 

(6) Again and again, we will read the use of spurious action verbs in which it is unreasonably claimed that mindless information-free things "guide" or "direct" things.  An example is when the Quanta Magazine article claims that "physical tensions within an embryo set up patterns that guide growth."  

(7) Again and again, we hear about meaningless unimpressive experiments that are described in glowing terms, as if some great insight was gained. An example may be found in the Quanta Magazine article here when we read about some silly experiment in which scientists "removed the skin from a chicken embryo and disintegrated the tissue to pull apart the cells," putting the cells into a petri dish, and adding some chemical. They then observed the cells form a shape that is described as a ring shape (even though it does not look like a ring at all). This unimpressive result is described in the most glowing terms in the Quanta Magazine article, as if it provides some great insight. We see three pictures, and the third picture hardly looks any more organized than the first. But the result is described glowingly as evidence for "self-organization." Scientists are deluding themselves if they get excited about such results. 

Another example of this is the Quanta Magazine article here. Besides the unsolved problem of how cells end up in the correct positions in the body (not at all solved by the socially constructed myth of morphogen gradients), there is the problem of how simple stem cells turn into 200 types of cells in the human body, most of which are many, many times more organized and complex than such stem cells.  The Quanta Magazine article above offers no answer to this great mystery. It merely discusses scientists fooling around with artificial methods of making cells change their color.  

Quanta Magazine typically assigns its online articles about developmental biology (involving riddles a thousand miles over the heads of PhD's) to writers who lack even a bachelor's degree in biology. Any generalizations you read in such articles should be treated with great suspicion, and when PhD's in developmental biology are quoted, their statements should be treated with only somewhat less suspicion. Almost every biology origins claim you hear from a developmental biologist should be regarded with suspicion, and you should not take for granted the truth of any origins generalization they make. We should remember that many developmental biologists told us for so many years the fictional story that the human body arises from the reading of a DNA blueprint, a fiction many such biologists continue to assert (even though many other scientists have denied it). DNA contains no such blueprint for human anatomy, but merely low-level chemical information. 

The article on developmental biology in the Stanford Encyclopedia of Philosophy makes the following interesting comment, noting a lack of any guiding theory in developmental biology:

"Although it is common in philosophy to associate sciences with theories, such that the individuation of a science is dependent on a constitutive theory or group of models, it is uncommon to find presentations of developmental biology that make reference to a theory of development (see discussion in Minelli and Pradeu 2014). Instead, we find references to families of approaches (developmental genetics, experimental embryology, cell biology, and molecular biology) or catalogues of 'key molecular components' (transcription factor families, inducing factor families, cytoskeleton or cell adhesion molecules, and extracellular matrix components). No standard theory or group of models provides theoretical scaffolding in the major textbooks (e.g., Slack 2013; Wolpert et al. 2010; Gilbert 2010). The absence of any reference to a constitutive theory of development or some set of core explanatory models is prima facie puzzling." 


biological complexity

A very recent paper on morphogenesis rather much hints at how our scientists are pretty much empty-handed in their explanations on this topic. The paper is entitled "Closing the Loop on Morphogenesis: A Mathematical Model of Morphogenesis by Closed-Loop Reaction-Diffusion." We have a paper that tries to explain a little by some speculative model involving what is called a cellular automaton. A cellular automaton is some little piece of software whereby each individual two-dimensional cell on a flat grid (roughly comparable to a checker on a checkerboard) behaves according to some rule that requires it to know about the states of all other cells on the two-dimensional grid (kind of like a checker that moves in some way after pondering the positions of all other checkers on the checkerboard).  What is wrong here? Three big things: first, cells don't have a two-dimensional arrangement, but a three-dimensional arrangement; second, a cell can't be aware of the states of all the cells that are nearby; third, cells don't seem to be microscopic computers capable of doing such calculations.  Using the term "in silico" to mean "occurring only within a computer," the authors confess, "This work is purely in silico; we have yet no evidence that this particular cellular automaton exists in nature."  Why would scientists be "grasping at straws" in this way by suggesting explanations so lame and implausible? Because they are pretty much "empty handed" in regard to explaining morphogenesis; and when you're empty-handed, you grasp at straws.   

Studying the topic of systems referred to as molecular machines, you may get an idea of the explanatory shortfalls of developmental biologists, their almost total failure to credibly explain the arising of stratospheric heights of organization in a human body. Below from page 137 of a PhD thesis is a list of biological systems described as if they were very impressive machinery:


Subcellular assembly

Sample of ‘molecular machine’ language

Source reference

Ribosome

probably the most sophisticated machine ever made”

Garrett (1999)

Proteasome

a molecular machine designed for controlled proteolysis”

Voges et al. (1999)

Glideosome

a molecular machine powering motility”

Keeley et al. (2003)

Spliceosome

among the most complex macromolecular machines known”

Nilsen (2003)

Blood clotting system

a typical example of a molecular machine”

Spronk et al. (2003)

Photosynthetic system

the most elaborate nanoscale biological machine in nature”

Imahori (2004)

Bacterial flagellum

an exquisitely engineered chemi-osmotic nanomachine”

Pallen et al. (2005)

Myosin filament

a complicated machine of many moving parts”

Ohki et al. (2006

RNA degradasome

a supramolecular machine dedicated to RNA processing”

Marcaida et al. (2006)

RNA Polymerase

a multifunctional molecular machine”

Haag et al. (2007). For details on the vast complexity of the RNA Polymerase III protein complex, consisting of more than 3000 well-arranged amino acids existing in more than a dozen proteins coded by genes scattered across more than 10 different chromosomes, see here.

An article by scientists discusses molecular machines in the human body:

"A molecular machine (or ‘nanomachine’) is a mechanical device that is measured in nanometers (millionths of a millimeter, or units of 10-9 meter; on the scale of a single molecule) and converts chemical, electrical or optical energy to controlled mechanical work [1,2]. The human body can be viewed as a complex ensemble of nanomachines [3,4]. These tiny machines are responsible for the directed transport of macromolecules, membranes or chromosomes within the cytoplasm. They play a critical role in virtually every biological process (e.g., muscle contraction, cell division, intracellular transport, ATP production and genomic transcription)...Myosin, kinesin and their relatives are linear motors that convert the energy of ATP hydrolysis into mechanical work."

Humans are not machines, largely because humans have minds and lives and understanding that no machine has. But within our bodies are many types of extremely complex functional systems that can reasonably be described as molecular machinery. How does machinery so complex and purposeful arise in a growing human body long after the appearance of a speck-sized zygote? Our developmental biologists have no credible explanation. Trying to explain such wonders of origination,  without resorting to the lie that a DNA blueprint for building humans is read, our developmental biologists do little more than mutter unimpressive sound bites about "patterns," "shapes," "cellular interactions" and "physical forces." Similarly, when trying to explain such basic mental phenomena as learning and recollection, our neuroscientists do little more than mutter unimpressive and implausible sound bites such as "synapse strengthening," "circuit reactivation," and "connection patterns."

Very strangely, philosophers of mind tend to pay no attention at all to the unsolved mystery of morphogenesis, the problem of how a speck-sized zygote is able to progress into the vastly more organized state of the human body, consisting of trillions of well-organized cells of about 200 different types.  So, for example, in David Chalmer's book The Conscious Mind: In Search of a Theory of Conscious Experience, we have 1362 uses of the word "consciousness," but no substantive references to morphogenesis or developmental biology.  It is senseless for philosophers of mind to ignore the mystery of morphogenesis, for that mystery offers us a profound clue that seems to point us in the right direction when trying to explain minds: that both the physical origin of a human body and the origin of a human mind are probably in some very large sense top-down affairs, rather than merely bottom-up affairs that can be explained mechanistically.   

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