Gary Marcus: Making the Mind Why we’ve misunderstood the nature-nurture debate 2004
In the assembly of the brain, as in the assembly of other organs, one of the most important ideas is that of a cascade, one gene influencing another, which influences another, which influences another, and so on. Rather than acting in absolute isolation, most genes act as parts of elaborate networks in which the expression of one gene is a precondition for the expression of the next. The THEN of one gene can satisfy the IF of another and thus induce it to turn on. Regulatory proteins are proteins (themselves the product of genes) that control the expression of other genes and thus tie the whole genetic system together. A single regulatory gene at the top of a complex network can indirectly launch a cascade of hundreds or thousands of other genes leading to, for example, the development of an eye or a limb.
In the words of Swiss biologist Walter Gehring, such genes can serve as “master control genes” and exert enormous power on a growing system. PAX6, for example, is a regulatory protein that plays a role in eye development, and Gehring has shown that artificially activating it in the right spot on a fruit fly’s antenna can lead to an extra eye, right there on the antenna—thus, a simple regulatory gene leads directly and indirectly to the expression of approximately 2,500 other genes. What is true for the fly’s eye is also true for its brain—and also for the human brain: by compounding and coordinating their effects, genes can exert enormous influence on biological structure.
Imagine a book containing blueprints: specified, complex, instructional, codified assembly information, to make a specific machine, a programmable robot made and composed of several interlocked parts. The book contains information to specify each subpart of the robot, and there is a manual/information on how to take each subunit and assemble the robot. That robot is a tiny part of an assembly line of several robots, that work together to produce a subunit of a complex machine. The book also contains information on how to join the several robots, to make the assembly line. There are 20 thousand books instructing how to make 20 thousand assembly lines like this. There are other books, written in at least 45 different languages, that instruct and inform how to connect the 20 thousand assembly lines. The product is a factory that self reproduces, and makes other factories, similar, but not exactly the same. They reproduce, self replicate, and in about 20 years, they do so 37 trillion times to make the most perfect, the most efficient, and the best-constructed machine ever devised.
To create all this, the following is necessary:
1. Inventing languages, codes, software, and translation programs, and using them to write blueprints.
2. Creating the hardware, the storage mediums of the information to store all the information, the blueprints
3. Creating all the 20 thousand books, containing part of the information needed to create the end product, our best-constructed machine ever devised
4. Bring all the 20 thousand books together to one place and store them. The library.
5. Create a library index system to know when, and where to extract the information.
6. Create a robotic network, capable, based on the information from the library index system, to go and pick the right book on the shelf and bring it to the processing machinery.
7. Creating machines/robots to process, that is transcribe and translate the information in each book, that is encoding, sending, and decoding it.
8. Mechanisms to use the information to produce the end products, machines, robots production lines, energy, computers.
9. Networks that operate based on signals, informing how to direct the made robots/machine products to be installed in the right places in the factory
10. And finally, that creates a factory that self replicates and the end product is the best-constructed machine ever devised.
11. Mechanisms that monitor, error check the entire process, and repair machines, and sensors, that cut and either discard or recycle defective parts.
Above is an analogy to what we see in the cell.
1. The language, code, software, and translation program, is the genetic code. It is used to write the genetic information.
2. The hardware is the DNA molecule that stores the information, and messenger RNA is the information transmission device.
3. The 20 thousand books, are the 20 thousand genes
4. Together, they compose the human genome.
5. The library index program is the information stored through the genomic regulatory code, and at least 45 different epigenetic codes, stored for example through glycoproteins, or histone tails
6. Epigenetic information directs the gene regulatory network based on signaling networks.
7. RNA polymerases transcribe DNA to mRNA, and ribosome translates mRNA
8. The ribosome produces molecular machines, proteins
9. Epigenetic information directs molecular taxis, like kinesin motor proteins, to carry proteins to be transported on molecular highways, tubulins, to where they need to be employed in the cell factory.
10. That creates self-replicating cell factories, that do so about 37 trillion times in 20 years, creating the best-constructed machine ever devised: the human body.
11. Several error-check and repair mechanisms monitor the processes in the cell, and mistranslated molecules are either recycled or discarded.
The above process is based on and requires intelligence to implement various informational systems which are based on hardware and software:
The interdependent and irreducible structures required to make proteins
1. High information content (or specified complexity), irreducible complexity, and the setup of exquisitely integrated circuits, which by significant alterations are inevitably damaged or destroy the function, constitute strong indicators or hallmarks of (past) intelligent design.
2. The high information content and biological irreducible gene regulatory networks which also require regulation and are structured in a cascade manner, similar to electronic circuit boards, utilizing proteins and enzymes that manifest by themself irreducible complexity, constitute strong indicators or hallmarks of (past) creation through intelligent intervention, and design.
3. Naturalistic mechanisms or undirected causes do not suffice to explain the origin of information (instructed complex information), irreducible complexity, and the setup of complex circuits with little tolerance of change.
4. Therefore, intelligent design constitutes the best explanation for the origin of information and irreducible complexity in metabolic biological circuits.
1. Complex multicellular lifeforms depend on gene regulatory networks (dGRN's) which are a collection of molecular regulators that interact with each other and with other substances in the cell to orchestrate the expression of DNA.
2. dGRN's operate based on logic gates and their networks process chemical input signals similar to computers. These encoded instructions are based on boolean logic.
3. Logic depends on reason. Reason depends on intelligence. Only an intelligent mind can think rationally, and implement a system based on conceptual laws of logic. Therefore, the best and most reasonable explanation for the existence of complex gene regulatory networks based on boolean logic, essential for the making of complex multicellular organisms, is the creative action of a powerful, transcendent, intelligent Creator.
1. The setup of functional Information retrieval systems, like a library classification system, is always tracked back to intelligence
2. The gene regulatory network is a fully automated, pre-programmed, ultra-complex gene information extraction system
3. Therefore, its origin is best explained through the intelligent setup
All multicellular organisms are composed of various cell types. The different cell types in a multicellular organism differ dramatically in both structure and function.
If we compare a mammalian neuron with a liver cell, for example,
the differences are so extreme that it is difficult to imagine that the two cells contain the same genome.
In the human body, there are about 200 different cells. From kidney cells to neurons, blood cells, bone cells and so on. The development of multicellular organisms composed of different cell types requires mechanisms for turning gene expression on and off in specific cells at particular times during development.
The development of an organism — from a fertilized egg, through embryonic and juvenile stages, to adulthood — requires the coordinated expression of sets of genes at the proper times and in the proper places. A hierarchically structured development program is responsible for controlling and directing the formation and patterning of the developing embryo, axes, organs, and other major features.
A blueprint is the instruction manual to make for example a mansion. An architect draws the project, informs all sizes, materials etc, and upon that blueprint, the house is built. DNA is a molecule, equal to a computer hard disc, storing a blueprint. The instructional information to make an organism. You, for example.
DNA is a set of instructions for how to build a baby. It’s more like a recipe for making a cake. Or like a computer program whose instructions are obeyed in order: first do this, then do that, then if so-and-so is true do … otherwise do … and so on for thousands of instructions. A computer program is like a very long recipe, complicated by branch points. A recipe is like a very short program, with only a dozen or so instructions.
Genes are equal to a blueprint or an instruction manual. They encode or instruct how to make proteins and proteins dictate and control cell function.
The genetic sequence of made of nucleotides is transcribed into messenger RNA, and the ribosome translates the RNA information into a sequence of amino acids, which form a polypeptide chain, which, once completed folds into 3D form.
We can compare a gene to a book, containing the instruction manual to make a protein, a specific molecular machine.
While each book contains the instructions to make just one or a few proteins which are eventually complementary, forming a chemical production line, the genome can be compared to a library, full of books, each with different instructions to make different molecular machines, which in its entirety form a factory, the biological Cell.
The human genome contains about 20000 genes, which can be compared to 20000 books in a library.
A factory must be built in the right sequence and order. First the protecting walls, then the compartments, then the production lines, the machines must be placed right and interconnected and so forth. The workers follow the precise pre-established instructions from the engineers who conceptualized the factory.
That information must be pre-existent before starting the construction process. Analogously, the instructions to build a living cell must be fully extant, stored in the genome. But the genome is just a storage device, like a library full of books that can't do anything on its own.
It has to be known where the books are stored, and when they have to be taken out from the library, copied and the copy sent to the factory workers, and once the information has been extracted from the book, it has to be stored again in the shelf at the right place in order to be found again, and the process repeated with all books until all information has been provided.
Every library has a book index system that permits to find any book or other information mediums like newspapers, manuscripts, films, documents, DVDs, quickly. It permits to know the direction to go to the right shelf, and immediately find the book.
Let's suppose there would be a company, that intends to produce very complex products, which require an entire library to store the information, required to produce the products. But everything would have to be invented from scratch, starting even with the language and codes permitting the storage, transmission, and retrieval of information.
Following would be necessary:
1. Inventing languages and codes, and writing books and software programs
2. Creating a library
3. Disposal of information contained in books
4. Using the books of the library containing blueprints to produce machines, and finally, a factory that makes the products
The above process is based and requires intelligence to implement various informational systems which are based on hardware and software:
Inventing languages and codes, writing books and software programs, and its distribution requires:
1. The invention of a language, and an alphabet or software program code using symbols to convey and produce codified information
2. Inventing the storage medium, paper, ink, hard disks, DVD's, etc.
3. This permits Intelligent minds to record, store, transmit and retrieve created and invented information.
4. Engineers need to know how to invent a factory that prints books or produces computer hardware and hard disks.
5. Employees of a publishing company need to learn and know how to use printing machines, factories that make CD's, invent and create a distribution network, and then know how to distribute the books or other mediums containing information.
Creating a library requires:
1. To decide the target public, topics of the books and which language. The library of Harvard Business school will dispose of books academic educational books in English, while Tokyo's Library of Children's Literature Children books in Japanese.
2. To know how to invent the organization and order of the physical library space, the line-up of the shelves and tagging them, and so the books so that each can be found.
3. Software engineers know how to invent software languages and programs which can be used to create a library index program and then create the program.
4. Librarians that learn how to operate the index software program, and use it to organize and provide the input, store the information of where to find each book.
Dispose of books in a library requires:
1. know how to use the library software program, searching for book titles, finding the index of each book, the tag of each shelf, and knowing the tag of the books.
2. to know the physical location of the shelf and the location of the book on the shelf, how to go and take the book from the shelf.
3. Now, one is able to extract the book's information.
4. Afterward, the book can be returned to the library.
Using the books of the library, containing blueprints, to produce machines, and finally, a factory
1. The instructional information of the book is transcribed, copied, and transmitted to a translator
2. The information is translated into another language, and simultaneously, upon that translated information, the subunit of a complex machine is built.
3. The subunit, once made, is error-checked and in case of errors, destroyed, then tagged, and transported to its final assembly destination.
4. The process is repeated until all subunits are made, transported to the final destination for final assembly.
5. All subunits are assembled by other machines into a functional machine.
6. The completed machine is interconnected with other machines to form an assembly line, and starting its operation in a factory, producing things of higher complexity.
as a comparison, and analogously, the cell has to perform the same action, orchestrating gene expression, through the gene regulatory network. But before that can occur, the invention of the following is required:
The creation of biological codes and information storage mechanisms, and its distribution:
1. creating the Genetic Code, and at least 23 different epigenetic codes and languages
2. creating the DNA molecule, and glycoproteins to store the glycan code, histone tails to store the histone code, and over 20 different information storage mechanisms
3. this permits to store, transmit and retrieve biological information
4. the creation of metabolic and catabolic pathways to produce the basic molecules that serve as information storage ( DNA, amino acids - glycoproteins) and transmission ( mRNA) devices, and receive/translate information ( ribosomes)
5. the creation of DNA replicating mechanisms
Creating a gene regulatory network requires:
1. The pre-existence of genes, the genetic code, and the genetic information containing information to produce proteins, and the information which orchestrates the expression of genes itself, and all regulatory elements, like transcription factors, start and stop signs of each gene, etc.
2. the creation of the gene regulatory network itself, logic gates, and its organization for the organism that has to be built.
3. The mechanisms that orchestrate gene expression at the right time, depending on internal and external signaling inputs
4. Mechanisms within the gene regulatory network, which permit the binding of transcription factors at the right place in DNA, and so gene expression at the right time.
The interplay of genes with the gene regulatory network (dGRN) permits:
1. the dGRN to orchestrate organismal development by expressing the genes at the right time, transcription factors to bind at the right place
2. recognize the sequences of the gene, where to bind.
3. the transcription of the genetic information into messenger RNA (mRNA)
4. Replicate the DNA molecule
Using genetic information, containing instructional information to produce molecular machines, and finally, cell factories:
1. The instructional information stored in DNA is transcribed by RNA polymerase machines, transmitted through messenger RNA, and translated by the ribosome
2. The product of the ribosome is polymerization of amino acids to make protein molecular machines
3. When the amino acids strings leave the Ribosome factory, error checking is performed and in case of errors, the product is recycled, or the protein is tagged and transported to its final destination.
4. The process is repeated until all subunits are made, transported to the final destination for final assembly.
5. All subunits are assembled by other protein machines into a functional machine.
6. The completed protein molecular machine is interconnected with other protein molecular machines to form assembly lines, and starting its operation in the cell factory, producing self replication, and the perpetuation of life.
1. The Genomic regulatory Code
2. The Genetic Code
3. Genetic information
2. the DNA molecules
3. the Gene regulatory network
4. transcription factors
5. cis-regulatory elements
6. RNA polymerase nanomachines
7. Epigenetic systems like histones in an interplay with epigenetic languages
The genome of an organism contains the instructions to make all different cells, Cell differentiation is driven by developmental gene regulatory networks. The expression of either a neuron cell or liver cell can be regulated at many of the steps in the pathway from DNA to RNA to Protein.
A librarian, informed by the customer what book he wants to borrow, will be able to recognize the book in the shelf of the library based on the title or tag on the book cover, take the book off the shelf and borrow it to the customer.
Analogously, cells need to direct and orchestrate when a particular gene has to be transcribed. To recognize the right gene, a chromosome has promoters or cis-regulatory elements nearby of the gene that has to be expressed and transcription factor proteins are able to recognize and bind to them. That, as a consequence, will recruit the RNA polymerase machine, transcribing the gene.
Transcription factor proteins ( in the picturer, named GATA1) after recognition of the promoter region, bind to it. It is most commonly located near to the actual coding region.
The outside of the double helix is studded with DNA sequence information that transcription regulators recognize: the edge of each base pair presents a distinctive pattern of hydrogen-bond donors, hydrogen-bond acceptors, and hydrophobic patches in both the major and minor grooves. The 20 or so contacts that are typically formed at the protein–DNA interface add together to ensure that the interaction is both highly specific and very strong.
Gene regulatory networks interplay tightly to activate or repress de expression of genes. The right execution of this molecular choreography is fundamental to all life forms and essential for orderly animal development, thus play a key role to explain animal diversity.
Gene regulatory networks guide the organism’s response to changes in their environment
The architecture of the body plan depends, amongst other factors, on the structure of developmental gene regulatory networks.
Davidson is refuting Darwinian evolution with these words: Neo-Darwinian evolution is uniformitarian in that it assumes that all process works the same way, so that evolution of enzymes or flower colors can be used as current proxies for study of evolution of the body plan.
It erroneously assumes that change in protein-coding sequence is the basic cause of change in developmental program; and it erroneously assumes that evolutionary change in body plan morphology occurs by a continuous process. All of these assumptions are basically counterfactual.
Cis-regulatory elements (CREs) have essential roles in development, and their divergence is a common cause of evolutionary change. Over 40 years ago, mutations affecting the regulation of gene expression were predicted to be a common source of evolutionary change1–3. Since this time, and most rapidly during the past 5 to 10 years, empirical evidence has accumulated showing this prediction to be true.
Last edited by Otangelo on Thu Jun 23, 2022 8:37 am; edited 1 time in total