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| GÖDEL, ESCHER, BACH (1988) |
"As development of an organism takes place, can it be said that the information is being "pulled out" of its DNA? Is that where all of the information about the organism's structure reside;
DNA and the Necessity of Chemical Context
In one sense, the answer seems to be yes, thanks to experiments li Avery's [1]. But in another sense, the answer seems to be no, because so much of the pulling-out process depends on extraordinarily complicated cellular chemical processes, which are not coded for in the DNA itself. The DNA relies on the fact that they will happen, but does not seem to contain a code which brings them about. Thus we have two conflicting views on the nature of the information in a genotype. One view says that so much of the information is outside the DNA that it is not reasonable to look upon the DNA as anything more than a very intricate set of triggers, like a sequence of buttons to be pushed on a jukebox; another view says that the information is all there, but in a very implicit form.
Now it might seem that these are just two ways of saying the same thing, but that is not necessarily so. One view says that the DNA is quite meaningless out of context; the other says that even if it were taken out context, a molecule of DNA from a living being has such a compelling inner logic to its structure that its message could be deduced anyway. To put it as succinctly as possible, one view says that in order for DNA to have meaning, chemical context is necessary; the other view says that only intelligence is necessary to reveal the "intrinsic meaning" of a strand of DNA."
Quote from chapter 6 'The Location of Meaning'.
My copy of Douglas Hofstadter's famous book 'Gödel, Escher, Bach' (Dutch translation, 1985) stood gathering dust on my bookshelf for some 30 years. A few days ago when I was searching for artwork of M. C. Escher in Hofstadter's book, I unexpectedly came across arguments against the 'DNA-centric view' of life. I have blogged about DNA-centrism many times over the past several months. It is extraordinary to find the same ideas you have been developing in a book that was written 47 years ago. As far as I can see, Hofstadter was not participating in an ongoing discussion among biologists about DNA-centrism. He wrote his ideas as part of an investigation of formal languages. DNA was an example of such a language. Probably the two mutually exclusive points of view –'DNA-centric' and 'cell-centric'– did not exist at the time. Likely, mainstream biology was DNA-centric. For example, Hofstadter writes: "Gunther Stent has characterized the nucleus as the 'throne room' of the cell, with DNA acting as the ruler." (page 509). Hofstadter wrote this in passing and without further comment! Stunning remark! If this isn't DNA-centrism, then I don't know what is! Hofstadter accepts it as if it were merely a neutral description of what DNA is. Probably it reflects mainstream scientific thinking at the time.
Hofstadter is a computer scientist and investigated coded messages, and the concept of information and meaning. It appears he had a detailed knowledge of what DNA is and how it functions. In chapter 16 Hofstadter gives detailed description of the structure of DNA, the Genetic code [2], transcription, translation, proteins, Transfer RNA and Ribosomes. Furthermore, he understood that knowing the Genetic Code, that is how a particular DNA sequence is translated in to a protein, is far from sufficient to understand how a genotype is translated in to a phenotype [1]. This truth still holds today!
An important question for Hofstadter was:
Where is the meaning of a coded message located?
Applied to DNA, attempts to answer this question yield important insights. Interestingly, he proposed two possible answers: the intrinsic and extrinsic view of meaning. The intrinsic view means that DNA has 'a compelling inner logic' that enables an intelligent (extraterrestrial) investigator to decode the DNA message. This sounds rather vague. Hofstadter doesn't explain what 'inner logic' means [4], [5]. The extrinsic view is that the meaning of DNA is not stored in DNA itself, but that "extraordinarily complicated cellular chemical processes" are required.
Although he never rejects the intrinsic meaning hypothesis explicitly, I conclude from his statement "extraordinarily complicated cellular chemical processes, which are not coded for in the DNA itself", that he favours the extrinsic view. This is further confirmed by the heading "DNA and the Necessity of Chemical Context" and this (charming!) statement:
"they [an extraterrestrial civilization] might to try to deduce from its chemical structure what kind of chemical environment it seemed to want, and then supply such an environment." (under the section heading How Universal Is DNA's Message?). (page 183).
Another wonderful statement:
"On the other hand, DNA is itself a passive molecule which undergoes manipulation at the hands of various kinds of enzymes; in this sense, a DNA molecule is exactly like a long piece of data, as well." (page 542) (my emphasis). I love this. This is exactly what I argued on several previous blogs. And: "But most of the 'living' in a cell goes on outside of the nucleus, namely in the cytoplasm..." (page 512). Well said! I fully agree. In other words: DNA is dead, the cell is alive! However, Hofstadter does not note there is a certain degree of contradiction between DNA 'sitting on a throne' and being dead.
Bootstrap problem
Continuing with the intrinsic and extrinsic point of view. There is a problem with the distinction. The tRNAs contain the translation key of DNA to protein. Since the information for producing tRNAs is stored in DNA (necessarily, because it must be inherited), one could say that the meaning of DNA is intrinsic to DNA. That's OK. However, in order for that information in DNA to be used, it must first be read by cellular machinery. Hofstadter is aware of the problem [3]: "... there is no way for the DNA to hoist itself by its own bootstraps. Some amount of knowledge of the Genetic Code must already be present in the cell beforehand." (page 519) (my italics). Excellent remark! Remarkable insight! However, it appears that the concepts intrinsic and extrinsic meaning are ambiguous. In one sense, DNA has an intrinsic meaning because DNA encodes for tRNAs, but on the other hand the meaning is extrinsic because machinery outside DNA is necessary to get the whole process started. In other words: a bootstrap problem [6]. The information is there, but one can not get it out!
Think about this: 47 years ago a smart computer scientist clearly understood that a DNA 'message' is meaningless without its cellular context! So, the cell-centric view is certainly not a modern invention. It was kept alive in the fringes of science. Hofstadter did not fully realize that his anti DNA-centric views contradicted the prevailing view of DNA as 'the Ruler on the throne'. Since Watson and Crick (1953) DNA-centrism has experienced stormy growth. Today, more and more scientists reject the DNA-centric view of life.
Notes
- My note: Avery (1944) was the first to demonstrate that DNA and not protein was the vehicle of heredity.
-
The Genetic Code table is on page 515. Furthermore: "The curious
fact is that the Genetic Code is stored-where else?-in the DNA itself." (page 517). -
quote: "(Warning: Understanding this "language" would not at all be the same
as cracking the Genetic Code, something which took place in the early
1960s. ... The cracking of the Genetic Code was a vital step on the
way to extracting the meaning of DNA strands, but it was only the first on a long path which is yet to be trodden.)" page 168. - An argument against the intrinsic meaning of DNA is: the genetic code is a rather arbitrary association of 61 base triplets with 20 Amino Acids and 3 base triplets with STOP signals. Hofstadter did not mention this in this book. But 3 years later, in his 1982 Scientific American "Metamagical Themas" column, titled "Is the genetic code an arbitrary one, or would another code work as well?" Hofstadter argued that the genetic code is not fundamentally dictated by chemical necessity, suggesting that many other codes could theoretically work. (answer by Google AI!). The conclusion must be: there is no compelling logic in DNA.
- A further problem with 'intrinsic meaning': how to find the translation keys in a code script with the length of billions of symbols? The code for the tRNAs are scattered all around DNA and there are many duplicate keys. In other words: how to locate the meaning of DNA?! That's the fundamental question.
Sources
The paperback edition is still available on Amazon. The PDF of the book can be found on several websites, such as this one. I discovered the Dutch translation of the book at my bookshelves, which so it appears was a birthday present.
Previous blogs
- If the blueprint of the embryo is not in DNA, then where is it? Alfonso Martinez Arias. A very convincing argument for the cell-centric view of life 14 March 2026
- Richard Dawkins admits: DNA is *not* a blueprint! But Dawkins still got another metaphor wrong! 16 February 2026
- Think about this: 09 February 2026
- Gene-centrism is bad biology. Here is why. 17 December 2025
- What is DNA-centrism? Why is it wrong? 10 November 2025
Dr Korthof, thanks for this update! Almost forgotten.....
ReplyDeleteThe subject of this blogpost is very interesting, but the question posed is somewhat reminiscent of the chicken-and-egg problem. DNA only has meaning within the cell and supposedly has no intrinsic meaning of its own.
ReplyDeleteIt is interesting to think and philosophize about this, but the chicken and its egg evolved together, as we know from animals (fish) that laid eggs, and so on back in time to the first gametes.
Proteins most likely originated together with RNA in the RNA-protein world. Some authors (Patrick Forterre) hypothesize that the first protocells were infected by DNA viruses that replaced the RNA in these protocells with DNA, a more stable molecule. The meaning of the code in DNA evolved with the emergence of ribozymes and tRNA, which carry the amino acids.
Within this context, DNA has meaning. It is possible that extraterrestrial intelligence can also give it meaning and 'read' and decipher somehow its code. It is not without reason that humanity sent the Arecibo radio message into space with the nucleotides and a graphical representation of the helix structure.
I tried to read Hofstadter some decennia ago, but was not able to understand him then. Maybe it's worth to try it again.
Vrolijk Pasen Gert
Interesting things you found in Godel, Escher and Bach, Gert
ReplyDeleteA difficult book, I assume you were not the only one who was not able to understand the book of Hofstadter, then and now. I tried to understand a bit of it, not easy. His discussion of the relationship between genotype en phenotype is intruiging.
Marleen, Rolie & others, at the time I did not read the whole book, I browsed through it, but probably did not understand much of it. Now, I read chapter 6 'The Location of Meaning', there is the interesting stuff. It contains some really amazing visionary statements. All the best!
ReplyDeleteDear dr Korthof
ReplyDeleteI’d say that no compelling logic in the chemistry of DNA is not the same as no compelling logic in DNA
Dear Dr Anonymous, please could you explain what you mean by that? I am not sure what your intention is. In the spirit of Douglas Hofstadter: could an extraterrestrial civilization understand the meaning of a DNA molecule? could they suspect it has any meaning at all? could they understand that DNA is meant to code for proteins? etc.
ReplyDeleteDear Dr Korthof
ReplyDeleteWhen it comes to the question of whether there is ‘chemical necessity’ or even ‘compelling logic’ in the genetic code, I don't think that thought experiments (i.e. speculations without observations) can get us much further.
Take f.e. the fact that different codons can code for the same amino acid. This has often been viewed as simple redundancy, possible consequence of the arbitrariness of the code, or say, lack of ‘chemical necessity’ or ‘compelling logic’.
But it turns out that synonymous codons are not truly equal. Recent research, Science, 2026; DOI: 10.1126/science.adw0288 , shows that some codons (1)make mRNA molecules more stable and (2) easier for cells to translate into proteins, making them (3) more efficient.
The findings “reveal a *direct molecular link* between synonymous codon choice and the control of gene expression in human cells" : DHX29 recruits the GIGYF2•4EHP protein complex. This complex acts to *selectively suppress* mRNAs that contain non-optimal codons, *effectively reducing* the production of *inefficient genetic* messages.
So, it seems that our terrestrial intelligence understands the 'meaning of DNA molecules' increasingly better - whatever 'chemical necessity' or 'compelling logic' may mean.
Or in the words of the projectleader Osamu Takeuchi (an endorsement of your previous blogs):
"We have long been fascinated by how cells *interpret* the hidden layer of information embedded within the genetic code, so discovering the *molecular factor* that allows human cells to read and respond to this hidden code has been particularly rewarding” (emphasis added).
Dear Dr. Anonymous, thanks for the link to the Science article. I fully agree that all scientific questions must be answered by experiments and not by speculation. What Hofstadter was doing however is proposing two alternatives from a theoretical perspective: external and internal logic. If these alternatives are not on the table, there are no questions to ask in the first place!
ReplyDeleteI like the cell-centric way how Osamu Takeuchi expresses his views :
- "how cells interpret the hidden layer of information embedded within the genetic code..."
- "human cells to read and respond to this hidden code"
Clearly the cells are the active partner doing the reading, the DNA code is the passive partner being read. This is indeed the theme of my latest blogs!
Dear Dr Korthof,
ReplyDeletePlease note that the GIGYF2.4EHP complex also is an answer to your fundamental question, at least partly, because it doesn’t locate *the meaning* of DNA, but certainly some meaning.
Dear dr Anonymous, the function of the GIGYF2.4EHP complex is highly technical biochemical subject which requires specialised biochemical knowledge. In general: Nonsense-mediated mRNA decay recognizes premature stop codons, which on its own is a remarkable fact. This can be interpreted as an example of the cell deciding which mRNA are translated or destroyed: the primacy of the cellular machinery.
ReplyDeleteAnother example that the cell controls DNA: X-chromosome inactivation. It is a random process: early in development, each cell independently chooses one X chromosome to inactivate, typically resulting in about 50% of cells inactivating the paternal X and 50% the maternal X. Note: a complete chromosome is silenced!
ReplyDeletedear Dr Korthof
ReplyDeletethanks for the examples of the primacy of the cellular machinery
Maybe we shouldn't forget the cell's 'little helpers' after all- although, of course, they are nowhere on their own!
Gradients of signaling molecules act like directional cues, helping cells move and develop in the correct locations.
the CaV2.1 channel, the most common calcium ion channel in the brain can take almost 200 different shapes depending on the strength and duration of an electrical signal.
Piezo1 among other things, acts as a sensor that converts mechanical signals from the environment into cellular responses.
dear Dr Anonymous, if the same CaV2.1 protein "can take almost 200 different shapes depending on the strength and duration of an electrical signal", then the actual 3D properties are dependent on physical forces, since the protein has only one amino acid sequence encoded by DNA. So, the DNA code for the protein assumes that those physical forces are present. Electricity, mechanical forces, etc. are not encoded in DNA. They are external to DNA itself.
ReplyDeletedear Dr. Korthof
ReplyDeleteI never implied that these little helpers themselves in turn weren't helped- f.e. by mechanical forces, like Piezo1, which plays an extremely important role in neurogenesis as a powerful link between the brain’s physical environment and how its wiring is built: indeed *completely* external to DNA itself: Nat. Mater. 25, 687–697 (2026). https://doi.org/10.1038/s41563-025-02463-9
As I said: of course, [these helpers] are nowhere on their own!"
So we just very much agree.
Dear Dr. Anonymous, I tried to interpret your comment. It was not a criticism!
ReplyDeleteA quote from the interesting article you mentioned: "...mechanical stresses, environmental stiffness, and cell or tissue geometry profoundly affect cell proliferation, migration and fate specification..."
"... the nervous system, for example, mechanical forces regulate development and various physiological processes,..."
Precisely! These forces are all external to the DNA code. They are assumed. Maybe we could say the brain (in fact the whole of development from egg to adult) is an emergent property of all forces taken together. On this planet this works. On another planet (bigger/smaller, etc. etc.) the enzymes need to be adapted to the physical circumstances of the planet.
PS I have to add that I have no expertise whatsoever of the workings of the brain!
Very interesting discussion. Mechanical and electro-magnetic forces play also an important, if not decisive role in embryonal development.
ReplyDeleteFind more by seeking "mechanochemical" developement.
@Gert: you wrote: "On this planet this works. On another planet (bigger/smaller, etc. etc.) the enzymes need to be adapted to the physical circumstances of the planet."
The most important influences are the chemical environment, not the size of a planet as such.
Dear Dr Korthof
ReplyDeleteThere is still a lot we don’t know about the workings of the brain.
Neurons are the largest and the most morphologically complex of all (x different types, functions, and still counting) with subcellular compartmentation, and long-distant transport of gene products, signalling molecules, and above all different activity-dependent gene expression: this so-called neuroplasticity, i.e. the coordinated activity of large neural networks during behavior, substantiates your main point even more than you might think. See also the so called 4th law of behavioral genetics.
Rolie: you are right, the chemical environment is the primary factor. On the level of (DNA) chemistry physical characteristics of the planet are not important. But at development from egg to embryo in general the strength of gravity could influence proper development. (NASA research on the effect of zero gravity or microgravity on fertilization and embryo development).
ReplyDeleteDr Anonymous: I agree. The 4th law of behavioral genetics shows that "This law highlights that complex traits (intelligence, personality, mental health) are polygenic, shaped by thousands of variants with tiny individual effects, rather than a few major genes."
So, should we interpret this as an argument against or pro DNA-centric view? Electricity, the movement of electrons, is a physical law, as such not caused or influenced by DNA, but maybe guided/channelled by protein structures.