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Our future, our universe, and other weighty topics


Monday, October 5, 2020

No, We Were Not Built by Software

 Ever since DNA was discovered, some biologists have been making a claim as phony as a three dollar bill. This claim (which I call the Great DNA Myth) is the false assertion that DNA is some kind of blueprint or recipe for making an organism.  It has been incorrectly asserted countless times that an incredibly complicated structure such as a human body arises because some specification of the human body is read from DNA.  No such specification exists in DNA. DNA merely specifies low-level chemical information, such as which amino acids make up the polypeptide chains that are the starting points of protein molecules. DNA does not have any high-level specification of the human body, does not have a specification of any organ in the human body, and does not even have any specification of any of the 200 types of cells used by the human body.  Besides not having any specification of such things (in the sense of anything like a blueprint), DNA also does not have anything like a set of instructions for assembling cells or organs or bodies.  In DNA there is no program or recipe for building organisms or any of their visible parts. 

Many biology experts (such as more than 15 I quote at the end of this post) have confessed that the myth of DNA as a blueprint or recipe for the human form is untrue. So it's kind of like a situation where biology's left hand is writing one thing, and biology's right hand is writing an entirely different thing that contradicts what the left hand is writing. 

A recent article in The Scientist backs away from some of the old mythology claiming our bodies arise from DNA blueprints or DNA recipes, commendably telling us "genomes are not a blueprint for anatomy."  But while the article has some moments of candor, it sadly veers into some replacement rhetoric that may leave us with an erroneous idea.

The article by Michael Levin (a director of a biology lab) has a title mentioning something that is not actually explained in the article.   That title is "How Groups of Cells Cooperate to Build Organs and Organisms."  The article gives us no real sign that Levin understands any such thing.  In fact, in the text Levin refers to "the deep puzzle of how competent agents such as cells work together to pursue goals such as building, remodeling, or repairing a complex organ to a predetermined spec," without telling how any such specification has been found anywhere, and without clarifying this strange idea of a mere cell pursuing a goal.  Elsewhere he asks, "What if we solved the mystery of how groups of cells cooperate to construct specific multicellular bodies during embryogenesis and regeneration?" These two statements certainly do not sound like the words of someone who has any great understanding of "how groups of cells cooperate to build organs and organisms,"  something no one actually understands. 

But I can at least applaud the candid humility of both of these statements, both of which suggest the real truth, that biologists have no understanding at all of how a speck-sized egg is able to progress to become a large organism such as a 10-pound baby.  The problem is that Levin does not stick to such humility. Elsewhere in his article, he rather seems to veer away from such humility, and begins to speak as if he has some kind of idea about how incredibly complex large organisms arise.  He tries to suggest that organisms such as you and I are built by software

Levin states, "The software of life, which exploits the laws of physics and computation, is enabled by chemical, mechanical, and electrical signaling across cellular networks."  He refers to "the logic of the software—implemented by chemical, mechanical, and electrical signaling among cells—that controls large-scale outcomes and enables remodeling to stop when a specific morphology has been achieved." He refers to "anatomical software." "Software" is just a figurative term Levin has carelessly chosen to use for mere signaling going on between cells. But signaling isn't software. When I use my remote control to change the channel on my TV, that's a signal, but it isn't software. If I use a hand signal to summon a cab to the curb, that's a signal, but it isn't software. When a cell sends out some chemical, that may be a signal, but it isn't software.  Software is intelligently designed information characterized by things such as very precise and highly organized complex instructions, iterative loops, variable assignment and if/then logic. Mere signals between cells are not such a thing.  No one has actually discovered any such thing as "anatomical software" in the human body. 

At one point in his article, Levin makes a vaunting claim. He states, "We were able to create novel living machines, artificial bodies with morphologies and behaviors completely different from the default anatomy of the frog species (Xenopus laevis) whose cells we used." Wow, you might think from such a statement that Levin and his colleagues have achieved some kind of titantic success in which they have been able to design novel new organisms. But if you follow the link he provides, you will be very disappointed. The link leads to an article (in The Scientist) with a very misleading title, "Algorithm Designs Robots Using Frog Cells." The article merely describes a most unimpressive little formless clump of cells.  It seems that The Scientist has been infected by the clickbait epidemic that has spread to so many science sites, so that it now sometimes has sensational-sounding article titles that do not match the content of the article. 

We can never explain the origin of large incredibly complicated  biological organisms by some mere idea of cell signaling. First, while networks of cell signals are fantastically complicated, an individual cell signal is a low-information thing like a traffic light signal or a TV remote control signal, not a high-information thing like a radio signal that can transmit precise and very detailed instructions. So cell signals cannot explain how cells organize into incredibly complicated functional structures. For example, there is no cell signal that can tell a cell to take a particular position in three dimensional space or a particular position in the body or a particular position in an organ. Second, signals between cells cannot explain how different types of cells originate, such as 200 types of fantastically complicated human cells that are capable of such incredibly sophisticated signaling effects.  

Cell signaling includes a host of situations where one cell has a signal receiver that precisely meshes with a single reception area in another cell, rather like a key exactly fitting a lock. How could there be so many such situations, when the structures of cells aren't even specified in DNA?   

Do a Google image search for "cell signaling" or "signal transduction," and you will see many an extremely complicated biochemistry diagram, none of which comes anywhere close to fully explaining the myriad complexities of cell signaling. The immensely complicated chart here shows some of these signal pathways. The science paper "The complexity of complexes in signal transduction" gives us a taste of the vast complexities involved in cell signaling:

"Many activities of cells are controlled by cell-surface receptors, which in response to ligands, trigger intracellular signaling reactions that elicit cellular responses. A hallmark of these signaling reactions is the reversible nucleation of multicomponent complexes, which typically begin to assemble when ligand-receptor binding allows an enzyme, often a kinase, to create docking sites for signaling molecules through chemical modifications, such as tyrosine phosphorylation. One function of such docking sites is the co-localization of enzymes with their substrates, which can enhance both enzyme activity and specificity. The directed assembly of complexes can also influence the sensitivity of cellular responses to ligand-receptor binding kinetics and determine whether a cellular response is up- or downregulated in response to a ligand stimulus. The full functional implications of ligand-stimulated complex formation are difficult to discern intuitively. Complex formation is governed by conditional interactions among multivalent signaling molecules and influenced by quantitative properties of both the components in a system and the system itself. Even a simple list of the complexes that can potentially form in response to a ligand stimulus is problematic because of the number of ways signaling molecules can be modified and combined."

If you dive down to study all the innumerable enormous intricacies of cell structure and cell signaling, you will feel like someone studying the electronic intricacies of a digital computer, and will be left more puzzled rather than less puzzled by how such purposeful fine-tuned intricacy could have arisen. I borrow this term "fine-tuned" from a science paper that refers to the "fine-tuned communication between different cells."  These matters are a hundred miles over the heads of our scientists, two of which made the general observation in one paper that "we still lack an explicit analysis of complexity in a specific system at molecular level."  Referring to a crucial aspect of morphogenesis, a page of a Yale lab confesses, "The process by which stem cells differentiate into various tissues is largely unknown due to the enormous complexity of signals, both chemical and mechanical."  Trying to say that the growth of an organism is merely caused by cell signals is rather like some first-grader saying he understands how TV shows arrive on his TV set, because he knows it's all "just energy moving around." 

Were our scientists to describe accurately their lack of knowledge of how a speck-sized egg progresses to become a full-sized human, and if they were to describe accurately the failure of all neural explanations for human mental phenomena such as consciousness, thinking, imagination, instantaneous memory recall, and 50-year memory preservation, our scientists would have to confess that while they understand how a woman becomes pregnant, they do not actually understand the origin of any single human being.  But such a confession is not made by them, because it would conflict with their unfounded boast that they understand the origin of the human race.  Similarly, once a child has boasted that he understands the game of baseball, he cannot then confess that he does not understand what a homerun or a base hit is.  And once a child has boasted that he knows how movies are made, he cannot then confess that he does not understand how images get on the frames of a film. 

8 comments:

  1. Always interesting to read you.... Thanks for making the effort to warn us from the current overhypes in the media.
    As to the issue with memory formations in the brain I wonder what your take is on these recent findings?
    https://www.psychologytoday.com/gb/blog/the-athletes-way/202010/the-mystery-how-memories-form-just-got-less-mysterious
    https://www.nature.com/articles/s41593-020-00717-0#citeas

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  2. Thanks very much for the kind comments, Marco. As for the Nature article, it is behind a paywall, so I am limited in the extent to which I can access. Certainly the abstract does not mention any observations justifying a claim that an engram (a stored memory) has actually been found in a mouse. Previous papers making such claims have suffered from a variety of flaws that I discuss in my post below:
    https://headtruth.blogspot.com/2019/11/the-lack-of-evidence-for-engram-cells.html
    I see that the Nature paper you linked to suffers from at least one of those flaws: a sample size so small that no robust evidence for an effect has been provided. As a rough rule of thumb, no experimental study involving animals is even moderately reliable unless it involves at least 15 animals per study group. But I see in the supplemental information of the "seriously underpowered" Nature paper you mentioned that it used only FOUR animals or THREE animals in its study groups. No robust evidence is provided by such skimpy study groups. As for the Psychology Today article, it simply mentions the same Nature paper that doesn't prove anything because it used less than 30% of the sample size it should have used to get a reliable result.

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    1. Yes, unfortunately behind a paywall. Maybe the MIT press releases gives more info: https://news.mit.edu/2020/engram-memories-form-1005
      Will read your post on engrams. It will need some time to digest since I'm not a biologist (but as a physicist believe to know how statistics has to be applied). Actually determined to find out what the truth of the matter is on memory, or at least, to know how far up to date research can tell us about its physicality (or not). Will eventually turn back to this. Thanks so far.

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    2. Your original comment has led me to write a full post on the topic of the new MIT paper, which is below:

      https://headtruth.blogspot.com/2020/10/engrams-are-touted-like-phlogiston-was.html

      The paper in question is mainly citing groups of 4 mice, and it is hard to tell whether such a number is a study group size or a number (4 out of 15 or 4 out of 30) from a larger sample. In any case, when I mainly get an "n=4 mice" in the paper when trying to find the numbers used, I don't find the results robust.

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    3. Thank you for the detailed answer with an entire post. The title says it all! :)) Will go through it... Meanwhile I got the paper from Asaf Marco through Researchgate. I even don't begin to read it because it is an article of 34 pages full of technicalities I wouldn't understand anyway. I sent it to you via email.

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  3. Let's say that there is some top-down principle by which organisms acquire their forms from some non-material library of forms. How do you think this interacts with the postulate of energy conservation ? Is energy not conserved in biological organisms ? Can this be highlighted in metabolic experiments ?

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  4. A very good question. I don't see any problem involving energy conservation in morphogenesis. There's plenty of energy and matter available from the mother. The problem is in explaining all of the many levels of enormous organization. How much energy does it take to tremendously organize some unit of matter? That's hard to quantify, but it's not necessarily all that great. It's not clear that there's any gigantic spike of energy during morphogenesis, so I see no obvious need to say that energy is not conserved.

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    1. The thing is that in order to put an atom in a specific position in the body you need to change its natural linear trajectory, so you modify its energy and momentum.

      My take on these is that anyway, energy is just a concept that works to describe only simple physical systems, and it looses its meaning in biological systems. I think we need some top-down holistic approach to science, of which physics would turn out to be just a particular case for simple systems.

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