> profoundly misleading.<p>> Watson’s reductive and erroneous presentation.<p>These descriptions are silly, and a huge exaggeration. The traditional succinct formulation (from Watson) DNA => RNA => Protein is used in an educational context (whether of the general public or students). As such it does a great job! If students can get and retain that idea, then the educator is winning.<p>And if the student goes further into molecular biology they may discover that reverse transcription exists. Great.<p>But simple-to-understand formulations that capture the key idea are pedagogically essential, and the attacks in this article are completely unnecessary. It's easy to wonder whether they are irrational, i.e. sociopolitically motivated by (perfectly reasonable) distaste for Watson's (deeply unpleasant) comments made later in life, and they lessen the attraction of the author's forthcoming biography of Crick.
Unfortunate nomenclature aside, this issue highlights the difference between models and reality in science and how students can take these models too literally and thus easily conflate the two in pedagogy. Here's an embarrassing story for me: I didn't realize (or at least didn't internalize) that not all cells in the human body conform to to the canonical image of the cell that we see in Biology textbooks (<a href="https://en.wikipedia.org/wiki/Cell_(biology)#/media/File:Celltypes.svg" rel="nofollow">https://en.wikipedia.org/wiki/Cell_(biology)#/media/File:Cel...</a>) until I finished oncology and embryology class in my senior year back in 2015. For example, erythrocytes (RBCs) don't have nucleus and mitochondria. Some hepatocytes even have more than 1 nucleus (polyploidy).<p>I still don't know how I went through my cell biology class in sophomore year without understanding this. Maybe I missed the forest for the trees (curse you clathrin mediated endocytosis!)
Muscles also have more than one nucleus per cell, if you have strength trained. You can fast and diet and waste away all the protein and shrink them down, but the nuclei remain. Go in to a surge of calories, protein, (and optional androgenic hormone signaling) and the nuclei effectively parallel process transcription of mRNA in the ribosomes for regeneration of the proteins from amino acids and re-bulking up of the cells and your strength.<p>This, (along with neural adaption) is what we are taking about when we reference “muscle memory”. It’s a steep hill to
train the first time and multiply the nuclei, but once you have them, you have them for life, and subsequent re-strengthening efforts will be far easier.<p>I’ve gone through this myself and it’s pretty shocking. It took me X years to achieve Y kilograms barbell whatever movement. A diet or lack of training for a year and I can only do Y/2. But if I eat a ton, I can be back to Y or higher in a few months.
It’s always refreshing for me to hear share what they did _not_ know, especially when it’s seems like “something obvious” that they absolutely “should” have known. Thanks for being honest and open - I can personally really relate to this anecdote, and also in the context of biology, genetics, etc.
I re-listened to Malcolm Gladwell's podcast episode about Nobel prize winning Howard Temin on the weekend. According to his student:<p>> “At one point, Howard Temin wrote Francis Crick, Sir Francis Crick, Nobel Prize winner of Watson and Crick, the co-discoverers of DNA, the authors of the central dogma itself. Temin writes Crick a letter, gently suggesting that an amendment to the central dogma might be in order. Crick writes back: "I'm sure you think this is true, but you must realize you are wrong".<p><a href="https://www.pushkin.fm/podcasts/revisionist-history/the-obscure-virus-club" rel="nofollow">https://www.pushkin.fm/podcasts/revisionist-history/the-obsc...</a>
> The most significant part of Crick’s idea — and the part that Watson ignored in his oversimplification — was that there are three flows of information that cannot occur, due both to lack of experimental evidence and any plausible biochemical mechanisms. These were protein → protein, protein → RNA and, above all, protein → DNA.<p>These are categorically untrue. Post translational modification of proteins (by proteins) is a thing. Post transcriptional modification of RNAs (by proteins) is a thing. Transposition of DNA sequences (by proteins) is a thing.
> Post translational modification of proteins (by proteins) is a thing.<p>Yes prions are real but the article points out that prions modify the way other, already-existing proteins fold. Prions do not create new proteins nor do they change the amino acid sequences of other proteins, which means prions don't violate the dogma.<p>The article addresses your other points as well.
Folding is clearly a form of information transfer though (and proteins are deeply involved in folding other proteins, even outside of the prion case). As stated in the screenshot it is fine "information here means the sequence of amino acid residues..." but that's a much narrower definition than is commonly communicated.<p>Proteins also do change the amino acid sequences of other proteins - they cleave them! The results of the cleavage are then important for cell biology, and although it seems plausible that the the results could have traditional "protein" style functions, e.g. as an enzyme, I not sure this is ever actually the case. But the end result is still that the rule has to be understood very narrowly.
I take these points to be correct, but they seem tangential to what is (at least according to the article) the main issue at stake: can proteins modify the information passed on to descendants? If this were the case, there would be a mechanism whereby Lamarckian evolution could, at least in theory, occur.<p>In that regard, I feel this is particularly relevant:<p><i>"During an organism’s life, environmental conditions cause certain genes to get switched on or off. This often occurs through a process known as methylation, in which the cell adds a methyl group to a cytosine base in a DNA sequence. As a result, the cell no longer transcribes the gene.</i><p><i>"These effects occur most frequently in somatic cells — the cells that make up the body of the organism. If epigenetic marks occur in sex cells [however], they are wiped clean prior to egg and sperm formation. Then, once the sperm and eggs have fully formed, methylation patterns are re-established in each type of cell, meaning that the acquired genetic regulation is reset to baseline in the offspring."</i>
In the diagram/text description it is specifically referring to replication, in the sense of transmitting genetic information to daughter cells. In that sense there is no protein-protein transfer; no means of copying one protein or rebuilding nucleic acids from the amino acid sequence.
These exceptions covered toward the end of the article. The core claim by Crick boils down to “no reverse translation”.
Isn't this about the same as using a compiler to produce binary code from a high-level language?<p>The code in the high-level language determines the binary executable code output. But the binary output cannot produce the code in the high-level language.<p>Of course we can build "de-assmeblers" etc. that do somehing like that for us, but nature does nto have de-assmebhlers.
Proteins can cause DNA alterations via chromosomal translocations.<p>If these occur in germ cells, the new sequences may transmit permanently to future generations.<p>Depending on the definition of "information transfer" and the willingness to consider methylation as information transfer, how would the Central Dogma view protein-induced chromosomal translocations?
I don’t understand how “Crick’s attempt to break the central dogma” … “relied upon the fact that the genetic code is redundant.”<p>The article doesn’t seem to present any explanation of how his argument supposedly relied on that.
what Crick means, I believe, is that since multiple codons can code for a single amino acid the information or entropy in that set of codons is larger than the information transferred to the protein creating a many-to-one interaction. This means that you could, in principle, create an RNA sequence 'A' that codes for the same protein as another sequence 'B', but they are discretely different implying that this difference could be exploited to send different information back from proteins to this different RNA sequence. Kinda a reach in my opinion and not really important as proving you could do that doesn't bring us any closer to understanding what nature actually does. I guess the most interesting result with this research is analyzing the thermodynamics of this reverse interaction as an argument as to why nature has not evolved a way to do this.
Codons for the same amino acid can have very different efficiencies due to use of different tRNAs. And tRNA abundance varies across organelles (mitochondria), cells, and organs. It is not just protein sequence but also protein abundance and translational progressivity/speed/efficiency and completeness. Reverse translation would not recover these aspects.
I think it was a bad argument, perhaps due to weakness in Crick's knowledge of information science.<p>The argument goes like this;<p>Suppose you built a library of chemical reactions, to generate a DNA codon from
an amino acid, and did this for all of the different amino acids.
Since two different DNA sequences comple to the same protein, you could take sequence A, perform transcription and generate a protein P, and then construct a different DNA sequence B.<p>Thus we have "genetic information" extracted from a protein and stored in DNA, violating the Dogma... in an extremely cheesy way, since it's obviously the same "information" you had at the start, just encoded differently, and also it's not different in any meaningful sense from doing the same reverse engineering on non-logically-redundant DNA.
I think the idea is that this different codon sequence "may" be able to be used by the biological organism in a as yet to be discovered way. So, it wouldn't be useful in producing more proteins but may be able to affect the cell in some other way. I've never heard of anything like that though and the redundant codons is probably just the most thermodynamically efficient route to protein production. Interesting thought though
That still makes no sense to me.<p>Same protein P is coded by two different sequences, A and B. The "redundancy" observation is just saying that when you find some P molecules in the organism, you can't tell which were coded by A and which by B - that information is, <i>literally, lost in translation</i>. Yes, it's not really lost - it's smeared over the "global state", as DNA sequences are physical objects and A and B have slightly different resource costs, but that's still far from being able to modify DNA based on information from proteins.<p>FWIW, "redundancy" does have some different interesting functions in nature. Sequences like "AAAA" "ABAB" and "BBBB" are (in this example) equivalent under normal read, but if you shift the reading window one nucleotide to the left or right, those two sequences could code for something else entirely. AFAIK some bacteria exploit that. But again, this is still not a protein->DNA information transfer.
Here is an argument against the CD. We know that DNA changes overtime due indirectly from environmental conditions through evolutionary natural selection. So, why is this not an argument for the reversed direction of information?
Because having a vague, highly indirect, unpredictable and generally unreliable influence on genetic information is not the same as transmitting or copying it in day to day operation. Not even close, not even comparable for the purpose of answering measurable questions. The CD is not, and was never intended to be, an all-encompassing metaphysical invariant, it's an observation about biochemistry.
The proteins don't directly change the DNA via information transfer, that's not how natural selection works.
Not directly, but in a very long round about way they do. Like if I have a mutation that is evolutionarily positive, the only way that helps me pass on my DNA is through the expression of the proteins, without them I could not do anything. The proteins, and their interactions with the environment, creates new information that indirectly results in a evolutionary pressure on the DNA and at a population level can change it.<p>How can DNA 'get' more information if not from the proteins interactions with its environment?
not a biologist, but if we have a bunch of redundant dna (aka genes) that get activated/deactivated based on our environment, would that "state" be transferred to children? or do children get a blank slate of parental dna?<p>also, what causes genes to activate or deactivate? if proteins have any impact on this then there is information flow in the reverse direction, no?
I think there are multiple mechanisms by which genes "activate" and "deactivate", but one of them is methylation, which can to some extent be passed to offspring: this is studied as part of "epigenetics".
To answer the second question, the Central Dogma is interested in permanent changes at each stage, so the proteins can change the way DNA is expressed, but it cannot change the DNA sequence itself.
Surely prion diseases are an example of protein to protein, which the article specifically says was part of the CD?<p>I’m not unhappy with the tone of the article suggesting that Watson, yet again, vastly misunderstood the work of his betters while taking credit for it.
The “dogma” is “information flow from proteins back to genetic material does not occur” not that proteins can’t transfer information. Regardless of considering “shape” as information or not, the transfer is not violating that statement, the information is fully trapped in the protein and not flowed back to DNA.
As the first figure says:<p>> Information here means the sequence of the amino acid residues, or other sequences related to it.<p>Prions do not transfer sequence information between proteins, so this is in keeping with Crick's idea.<p>I've always assumed that Watson understood Crick's idea perfectly well, but used the simpler formulation because it was easier to communicate, while still being mostly accurate.
Yes, that is highly likely. Most causality flows in the same direct—from DNA variants through RNA variants, through protein variance to differences in phenotypes.<p>Many many exceptions, but this is the main causal flow.
I think if prions were considered violations of CD then enzymes or at least ribosomes would be considered to violate CD as well.
It seems the articles purpose is less about what could best be described as dunking on what 10th graders are taught about molecular biology for simplicity’s sake, and more about discrediting Watson by reframing the past, and chipping away at his legacy because of… well, you know.
What?
Hanging your name on things has always been a double-edged sword in any context, but science is actively held back by cults of personality. Your contributions might be foundational, but your legacy is harmful.
>...Specifically, prion proteins do not change the sequence of amino acids; they instead transmit their pathological shape to otherwise “healthy” proteins, causing them to misfold in the same way. Prion diseases do not alter the validity of the Central Dogma because they don’t alter any genetic sequences.<p>...did you read it?
> Watson, yet again, vastly misunderstood the work of his betters while taking credit for it.<p>Is this regarding Rosalind Franklin's data?
...well <i>that</i> makes a lot more sense now. Flashing back to my undergrad biology class, I honestly never understood what was so important about the "central dogma" or why it was so important to spend so much time on. Now, reading its origin story, it is immediately apparent why it's interesting and such an important feature of life to understand. (Tangent: anyone who complained about mRNA vaccines "corrupting your DNA" fell afoul of exactly what the central dogma is about.)<p>More broadly, it is fascinating to see how often this happens. So many ideas that are spread or taught in their "modern form" are trite or difficult or just disconnected. And then you see them in their original place, often in the original discoverer's words... and it's immediately obvious what they really mean and why they're so important. (Another example: Einstein's (special) theory of relativity. Read his original papers! They're short and explain everything!) I'd suggest the solution is just reading more primary source material, but unfortunately the opposite is also true: plenty of stuff is illegible in its original form, too. (Maxwell's formulation of Maxwell's equations comes to mind here.)
One way to look at it is that most college textbooks are bad. They are written by one person, who has limited time, and limited understanding. And then you have a teacher who knows even less than the textbook, trying to explain the textbook.<p>In contrast, Wikipedia editors have all the time they care to spend on the subject (which is a lot!). They often reproduce the original discoverer's words, when appropriate. E.g., <a href="https://en.wikipedia.org/wiki/Central_dogma_of_molecular_biology" rel="nofollow">https://en.wikipedia.org/wiki/Central_dogma_of_molecular_bio...</a> uses Crick's words. Whereas in the case of Maxwell, the formulation "is credited to Oliver Heaviside". Long story short: Wikipedia has the best explanations, and if you don't think so then fix it!
It is difficult to entirely avoid contamination by DNA. <a href="https://x.com/p_j_buckhaults/status/1861083163868672204" rel="nofollow">https://x.com/p_j_buckhaults/status/1861083163868672204</a>
> anyone who complained about mRNA vaccines "corrupting your DNA" fell afoul of exactly what the central dogma is about<p>I don't understand how you arrive at this — while it's true they almost certainly do not "corrupt your DNA", the reasons have nothing to do with the central dogma as Crick conceived it, since information flow from RNA to DNA is not addressed by it.