Sunday, March 13, 2016

Paradigm shifting

I was reading up on non-coding RNAs and came across this recent paper.
Bhartiya, D., and Scaria, V. (2016) Genomic variations in non-coding RNAs: Structure, function and regulation. Genomics 107:59-68. [doi: 10.1016/j.ygeno.2016.01.005]

Abstract: The last decade has seen tremendous improvements in the understanding of human variations and their association with human traits and diseases. The availability of high-resolution map of the human transcriptome and the discovery of a large number of non-protein coding RNA genes has created a paradigm shift in the understanding of functional variations in non-coding RNAs. Several groups in recent years have reported functional variations and trait or disease associated variations mapping to non-coding RNAs including microRNAs, small nucleolar RNAs and long non-coding RNAs. The understanding of the functional consequences of variations in non-coding RNAs has been largely restricted by the limitations in understanding the functionalities of the non-coding RNAs. In this short review, we outline the current state-of-the-art of the field with emphasis on providing a conceptual outline as on how variations could modulate changes in the sequence, structure, and thereby the functionality of non-coding RNAs.
The concept of a scientific paradigm and a "paradigm shift" was promoted by Thomas Kuhn. His most popular work was The Structure of Scientific Revolutions, published in 1962.

One of the ideas expressed in that book is that scientists operate on a day-to-day basis with a common set of assumptions about their discipline. Those "assumptions" are like a model—they are supported by a large amount of data and/or theoretical studies so that the average scientist in the field doesn't question the model. Most of the work in the discipline is devoted to discoveries within the "paradigm" and not to overthrowing it.

Gradually, evidence may accumulate that questions or challenges the existing model. Usually that data is set aside and counted as anomalous, an exception, or an artifact. In other words, the model resists change in contrast to the "nasty, ugly, little fact"1 view of science mentioned by T.H. Huxley.

This is a simplistic view of Kuhn's thesis, to be sure, but I'm going to talk about "paradigm shifting" in the colloquial sense, so bear with me.

This is a good time to note that many (most?) philosophers of science disagree with Kuhn's view of how scientists operate. I think that's largely because Kuhn was writing about the sociology of the scientific community and not epistemology. No doubt some philosophers will weigh in. So far, they have not been very effective in preventing the abuse of the word "paradigm" whether they believe in it or not.

I sympathize with Stephen Jay Gould who wrote about this in "A Foot Soldier for Evolution," one of the essays in the anthology Eight Little Piggies. Gould was a friend of Thomas Kuhn and he agreed with the general thrust of the argument in The Structure of Scientific Revolutions. In the following excerpt he's referring to the idea that a nasty, ugly, fact could kill a beautiful theory. Gould says,
Some beliefs may be subject to such instant, brutal and unambiguous rejection. For example: no left-coiling periwinkle has ever been found among millions of snails examined. If I happen to find one during my walk on Nobska beach tomorrow morning, a century of well nurtured negative evidence will collapse in an instant.

This Huxleyan vision of clean refutation buttresses one of our worst stereotypes about science. We tend to view science as a truth-seeking machine, driven by two forces that winnow error: the new discovery and the crucial experiment—prime generators of those nasty,ugly, little facts. Science does, of course, seek truth, and even succeeds reasonably often, so far as we can tell. But science, like all of life, is filled with rich and complex ambiguity, The path to truth is rarely straight, marked by a gate of entry that sorts applicants by such relatively simple criteria as age and height. (When I was a kid, you could get into Yankee Stadium for half price if your head didn't reach a line prominently drawn on the entrance gate about four feet above the ground. You could scrunch down, but they checked. One nasty, ugly, day, I started to pay full price, and that was that.)

Little facts rarely undo big theories all by themselves—the myth of David and Goliath notwithstanding. Such facts can refute little, highly specific theories, like my conjecture about lefty periwinkles, but they rarely slay grand and comprehensive views of nature. No single, pristine fact taught us that the earth revolves around the sun or that evolution produced similarities among organisms. Overarching theories are much bigger than single facts, ...

Instead, little facts are assimilated into large theories. They may reside there uncomfortably, bothering the honorable proponents. Large numbers of little facts may eventually combine with other social and intellectual forces to topple a grand theory.
What did Bhartiya and Scaria mean when they mentioned "paradigm shift" in their abstract? What "paradigm" got shifted and what were the facts that caused such a shift?

We get some clues in the introduction where they write,
One of the major discoveries that have come up in the last decade, with comprehensive maps of genome diversity, transcriptome and epigenome at hand, was the discovery of pervasive transcription in the human genome.
The references they give are to two reviews with a common author, Alain Jacquier of the Pasteur Institute in Paris (France) (Jacquier, 2009; Jensen et al., 2013).

I'm assuming that the idea of pervasive transcription is new to Bhartiya & Scaria and I'm assuming they're fans of the hypothesis that most of these RNAs have a function. But just because some idea is new to you, doesn't mean that it conflicts with the prevailing model of the experts. So Bhartica & Scaria checked the literature and found two recent reviews published in high quality journals. Both of them emphasized the "revolutionary" idea of pervasive transcription and the likely functions of all those transcripts.

If it's true that large complex genomes have many more genes for functional RNAs than for proteins then this really is a big change in our understanding, especially if most of those RNAs are required for the sophisticated regulation of the protein-coding genes. This conflict with the worldview (paradigm) of a messy genome full of junk and the view that our old understanding of gene regulation by transcription factors is basically correct.

If that's the case, then a paradigm shift is under way.

However, the idea of pervasive transcription is not new to everyone since it has been known for 45 years. If many of the real experts in the subject knew about pervasive transcription long before publication of the human genome sequence then where is the paradigm? I submit that the word "paradigm" should only be used to describe the dominant worldview among experts in the field and by "dominant" I mean overwhelming.

There are lots and lots of scientists (I am one) whose model of how biology works at the molecular level hasn't changed substantially in 30-35 years. They've known for a long time that there are many different kinds of genes including protein-coding genes and a variety of different genes for RNAs. Those genes include genes for regulatory RNAs (discovered in the late 19070s).

They've known for a long time that most of the genome is transcribed but the transcripts from intergenic regions tends to be of very low abundance. This knowledge dates from hybridization studies in the early 1970s. They know that promoters and transcription factor binding sites occur frequently in large genomes by accident so that there MUST be spurious binding as a consequence of the properties of DNA binding proteins. Where there's spurious binding there will be spurious transcription. It's a logical consequence of the properties of DNA and large genomes.

They've known from molecular studies of Drosophila, yeast, and C. elgans development that large phenotypic changes happen with small changes to regulatory sites that control expression of developmental genes. This is the contribution of evo-devo in the 1980s. It means that most animals, for example, will have pretty much the same complement of genes.

They've known that most of the DNA in large complex genomes is junk. They've known that this is consistent with modern evolutionary theory ever since the revival of random genetic drift and nearly-neutral theory over 45 years ago.

All of these ideas were confirmed by the publication of the human genome sequence. The only significant change in the past few decades—beginning about 1990—is that there are more genes for small RNAs than most of us expected but the differences aren't huge. There may be 5000 such genes in the human genome2 wheres if you had asked me in 1990 I would have said there were only a few hundred. This change is easily accommodated into my worldview (paradigm) and those of other scientists.

It's true that there were many scientists who assumed an entirely different model. I'm convinced that critics who complain about the word "gene" are correct in one sense, most scientists thought and acted as though all genes encoded proteins. It's certainly true that the majority of textbook writers and teachers thought this way.

But if a large number of scientists and teachers believe in a model that's demonstrably false, it this a scientific "paradigm"? I don't think that's what Kuhn had in mind. If something happens to correct those false ideas, is that a "paradigm shift"? I don't think so although I'll readily admit that it's a revolution of some sort.

Let's summarize the argument so far—I apologize for rambling on about this.
  1. Bhartiya & Scaria believe that the prevailing model in 2000 was that most (all?) genes encoded proteins and these genes made up only a small percentage of the genome. This was the prevailing paradigm, in their view.
  2. Bhartiya & Scaria believe that pervasive transcription was only discovered about 10 years ago and this led to the realization that there are huge numbers of genes for non-coding RNAs covering almost all of the genome.
  3. These new discoveries have overthrown the prevailing paradigm leading to a paradigm shift.
The logic here is correct but there's something deeply flawed with this view of genomics. Bhartiya & Scaria are wrong about the prevailing paradigm. They're wrong about the discovery of pervasive transcription. And they're wrong to claim that most of those transcripts are functional.

There is no paradigm shift and that phrase should not have been used in a review published in a reputable journal. The reviewers of the journal Genomics should have exercised better judgement.

I'm working my way through Suzan Mazur's book The Paradigm Shifters. It's a series of light-weight interviews with scientists who view themselves on the leading edge of a revolution in the way we think about evolution.

The funniest thing about this group is that they're all "shifting" in different directions! The saddest thing is that they're all fighting a "paradigm" that only exists in their own imaginations. It's a backward, outdated view of evolution that dates back to the nineteenth century. Most of them missed the real revolution that took place with the development of modern population genetics.

Like so much of the rhetoric about paradigm shifting, they are doubly wrong. They don't understand the "paradigm" and their "shifts" are either incorrect or insignificant.

Stop using the word "paradigm." It doesn't mean what you think it means. Stop claiming that a revolution is under way unless you can show that your facts are correct and the views of the experts are changing. Most challenges to the prevailing model are bound to fail. That's how the system works and that's a good thing.

Is it possible to recognize a real paradigm shift when it is under way? I think not, especially in the early stages where, by definition, scientists are skeptical of the new results.

Are there any good examples of "paradigm shifts" in biochemistry and molecular biology? I don't think there are very many. Chemiosmotic Theory is the best example I can think of [Nobel Laureate: Peter D. Mitchell]. Most other new discoveries were easily incorporated into existing models (e.g. introns and splicing).

1. "A beautiful theory, killed by a nasty, ugly, little fact." Thomas Henry Huxley speaking to Herbert Spencer as reported by Francis Galton.

2. My money is on less than 1000.

Jacquier, A. (2009) The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nature Reviews Genetics, 10:833-844. [doi: 10.1038/nrg2683]

Jensen, T.H., Jacquier, A., and Libri, D. (2013) Dealing with pervasive transcription. Molecular cell, 52:473-484. [doi: 10.1016/j.molcel.2013.10.032]


  1. There is no paradigm anymore.....pretty much all of 20th century evolutionary biology has turned out to be a pathetic lie and a massive waste of time and money....the predictions were wrong.(junk dna, "random" variation, the molecular clock, the Central Dogma, Weismann's Barrier, the prediction that HGT is rare and only happens between members of the same species...the prediction that we'd have up to a million genes to code for traits......the lack of any expectation of the power of epigenetics...etc) ....The whole Neo-Darwinist, selectionist paradigm was and is complete crap..the 20th century was nothing but a giant lie passed off as "science."........but finally we have a new crop of scientists who finally got sick enough of the lies to boldly throw up their hands and form The Third Way. Only when the dinosaurs of the past century finally die off will any real science start getting done, which would be to subject real, live organisms to real environmental challenges and then testing their capacity to generate genetic and phenotypic traits. The days of cutting the living, interactive, dynamic organism out of science should be over. But science has managed to scam society out of its money by convincing them that all the answers could be had merely by analyzing animals' genomes....what a laugh. crooks...frauds....

    1. I doubt that you understand what evolution is.

  2. Not many commenters manage to spout so much bullshit in so little space in a single comment. Quite an accomplishment, of a sort.

    Junk DNA -- real

    Random variation -- random with respect to the organisms needs (the intended meaning of "random" in the context of evolutionary biology) though sometimes more frequent in some parts of the genome than others.

    Molecular clock -- messy, but true.

    Central Dogma -- not a prediction of evolutionary biology. True in its original meaning though often misinterpreted.

    Weismann's Barrier -- true for animals that have separate germline and somatic cells, but pathetically animal-centric. Irrelevant to plants and fungi.

    Did anyone actually predict that HGT only happens between members of the same species???? And how would we detect it if it did?

    HGT is more common than was sometimes thought, especially in prokaryotes, but not really common, especially in multicellular eukaryotes.

    Did anyone who knew much about genetics predict that we'd have up to a million genes to code for traits [in one species]? If so they seem to be wrong, though one can weasel around a lot with the slippery term "trait."

    People shocked by the power of epigenetics seriously misunderstand how powerful epigenetics is (or isn't).

    No reason to let a few mere facts stand in the way of your rant, of course. But I do have one last comment. We can learn a lot from analyzing animals' genomes, but nobody with half a brain thinks we can learn all the answers about animals merely from analyzing their genomes. Not to mention the answers about plants, fungi, etc.

    And now back to the work I'm having fun avoiding. :-)

  3. The Third Way gang accept pretty much all of mainstream evolutionary theory.

    1. Really? Can you show me evidence that Denis Noble now understands population genetics, Neutral Theory, and random genetic drift? He didn't when I talked to him a year ago.

      How about Raju Pookottil or Evelyn Fox Keller,

    2. I have to agree with Larry on this least to a degree.

      The Third Way gang are why beyond what Larry had already been preaching way passed the Neo-Darwinian bs.

      However, Larry thinks or possibly even believes that HIS modern evolutionary theory will "save the world" and somehow fill in the gaps of thousands if not tens of thousands of useless bs papers "published" or hyper-popularized by people like Coyne, PZ. Myers, Dawkins, and my favorite the proud judge Dan Grour.

      Larry; you need to face more than "truth" you want it to be... How can you tackle it? Can you?

    3. Can you show me evidence that Denis Noble now understands population genetics, Neutral Theory, and random genetic drift? He didn't when I talked to him a year ago.

      To be fair, Jon Fleming didn't say they understand evolutionary theory, only that they "accept" it. Creationists "accept" all sorts of things they don't understand. Why can't the 3rd Way gang?

    4. Yeah, acceptance and understanding are a different kettle of horses of another color.

  4. alright I'll bite....bwilson...there is no such thing as random (unbiased in the direction of fitness) when it comes to the generation of adaptive traits. If you think otherwise, prove me your best example in multicellular organisms....I can give you a whole host of traits derived by controlled mechanisms (epigenetics/HGT/developmental plasticity, etc)....can you actually show any adaptive traits coming about by random mutation/natural selection in a population of animals? (you must prove the randomness aspect of the said mutation) good luck.

    1. HGT is a "controlled mechanism" among multicellular organisms?

      Could you perhaps produce some evidence that HGT is being systematically "controlled" by a multicellular organism to produce adaptive change?

    2. Sigh. Are recipient cells reading the DNA and discerning its function before making decisions about what genetic material to uptake from the environment and incorporate into the genome?

      I'm not sure how some people manage to use terms like HGT, epigenetics, and random mutation in sentences, yet seem to absolutely lack any understanding of the associated processes and mechanisms or of genome biology and evolution.

    3. Well, virtually everyone here knows what Unknown is about except, possibly, Unknown himself.

      So, for Unknown’s benefit: Unknown thinks that phenomena like HGT and epigenetics are new concepts. They aren’t of course, they have been known about and studied for several decades and were first discovered by (how else?) scientists doing scientific research (no other “ways of knowing” played even the slightest role).

      But anyway, Unknown, thinking they are new concepts, thinks that this means they therefore automatically upset the “evolution theory applecart”.

      But, alas, he doesn’t understand anything about a) the scientific process or b) molecular mechanisms in general or as they relate to evolution or c) evolutionary theory itself.

      He therefore doesn’t understand that these concepts do not pose the slightest threat to the concept of evolution or how fundamentally nonsensical it would be to make such a claim in the first place.

      And, finally, all of this is an extremely strong predictor of the facts that Unknown a) gets all of his scientific information from the internet and b) likely has no more than a high school education (or if more, in a non-biology field) and most-tellingly c) is religious.

      So his interests aren’t really about biological mechanisms at all despite his pretensions – but merely about religious apologetics.

      Recognize yourself now, Unknown?

    4. Well geez SRM, if they did not do that then just what did they do??

      F%$k, the cell has DNA error detection and repair capabilities but it doesn't (or couldn't) have HGT analysis and sorting capabilities?

      Talk about cognitive dissonance.

      SRM, hope you don't work in a lab...especially on people's tax dime.

      SRM bleeped: "Sigh. Are recipient cells reading the DNA and discerning its function before making decisions about what genetic material to uptake from the environment and incorporate into the genome? "

    5. I don't know if Mikkel is being dense as some sorta deep rhetorical device or whatnot.

      But humor us. What is the point of HGT to organism if not for some adaptive benefit?

      Is this one of those evo-devo "the cell just happened to pick up this hitchhiker gene on route to it's next nutrient uptake station and decided the extra mouth to feed could do some work around the house so it let the stranger hang around and lol it was so good at cleaning out the gutters...well the cell said its a keeper" explanations we are accustomed to hearing from in-the-know evolutionary biologists????

    6. But humor us. What is the point of HGT to organism if not for some adaptive benefit?

      Yes, and people have sex in order to pick out a particular advantageous set of genes for the offspring.

      What, they don't?

      Ah, Steve shows microbes are more intelligent than humans - or rather he shows they would have to be, in order for his "understanding" of HGT to be correct.

      So they not only have opinions, they do advanced genetic engineering as they procreate.

      Good luck getting your theory scientifically accepted, Steve. Let me know when your IQ test results on bacteria are ready.

    7. Steve: "What is the point of HGT to organism if not for some adaptive benefit."

      Why does it have to have a point? You are confusing function and purpose.

    8. Steve,

      "F%$k, the cell has DNA error detection and repair capabilities but it doesn't (or couldn't) have HGT analysis and sorting capabilities? "

      Because a cell has DNA error detection and repair capabilities doesn't say anything about whether or not it has HGT analysis and sorting capabilities. That's like saying dolphins have echolocation and adaptations to hear underwater, why can't they have the ability to breathe water?

      No one said there couldn't be HGT analysis and sorting capabilities. There just isn't any evidence for it. Unlike DNA error detection and repair, for which a great deal is known about mechanisms, enzymes involved, etc.
      No cognitive dissonance there.

      "What is the point of HGT to organism if not for some adaptive benefit."
      Why do men have nipples?

    9. Steve said: SRM, hope you don't work in a lab...especially on people's tax dime.

      Not only do I work in a lab (when I have the time), but I also run one.

      But from your non-existent grasp of basic molecular biological concepts, I am certain that you don't.

    10. @SRM - But sir, if you run a lab that has anything to do with bacteria, surely ye've heard tha wee beasties chattering 'mongst themselves, sharing opinions, as 'twere? Else I put it to you sir, what is the adaptive benefit of runnin' a lab now, eh?

    11. What SRM is saying is he knows diddly squat about the mechanisms organisms have to handle HGT but he sure does know it has absolutely nadda to do with intelligence.

      See, to SRM el all organisms are just a bunch of chemical reactions that just happen but f#$k if he knows how they are able to be integrated, corrdinated, controlled without intelligence.

      But it doesn't matter. He doesn't need intelligence to explain it. Just explain each process individually, add water and voila, its all explained.

      Put THAT in your TEDX talk and smoke it!

    12. ....and judmarc chimes in yet again with his tidbit anti-intelligence soundbites.

      it goes like this...Nope, nope, no intelligence in a bacterium. Its so damn small. How in the hell could it have any intelligence. Think about it?!

      judmarc slamdunks the notion that intelligence can be had without a brainstem.

      But, but, google go has no brainstem, said Lee Sedol...and it beat me 8 times outta 9.

      Stay tuned!

    13. Steve, you're getting increasingly incoherent.

      Some day you might try looking in the mirror and asking yourself whether it's the best use of your time to be trying to tell people who are professional biochemists that electrons need guiding intelligence to form chemical bonds. Since the quantum physics math works perfectly well to explain that, what you're doing in effect is telling people 2+2 needs God to equal 4.

    14. @judmarc - silly analogy! Without guiding intelligence a 2 might accidently hook up with a 3. What then would become of its quest to be a 4?

    15. There's really no effective response to that!

    16. Steve: "See, to SRM el all organisms are just a bunch of chemical reactions that just happen but f#$k if he knows how they are able to be integrated, corrdinated, controlled without intelligence."

      Still question begging, Steve? Why is coordination and control of biochemical systems beyond that capabilities of chemistry? (Pro tip: much of these 'coordination and control systems' as you like to call them are pretty well characterized, and they are based on - you guessed it - chemistry) Does "intelligence" not rely on the same chemistry? If not, what is the stuff of "intelligence"?

    17. Steve,

      What evidence do you have that natural chemical reactions are integrated, coordinated and controlled with intelligence?

    18. So Brian, Chris B, judmarc, SRM are not intelligent entities. They don't control what they do.

      Chemistry makes them do whatever they do. Oh, and they don't drive cars. See the gas being exploded in the piston chamber is responsible for driving the car. So dont blame them if their car stall, crashes, run over an old lady

      Chemistry is responsible for all of it.

      "nuff said.

    19. judmarc,

      The incoherence is in you et all denying intelligence.

      It is a self-defeating, irrational position to take.

    20. ChrisB,

      Next time someone asks you how the F-35 raptor was made, don't tell them a team of thousands of engineers did the work.

      That would be a lie.

      The truth is thousands upon thousands of of individual, complex, unrelated chemical reactions did all the work.

      Absolutely no intelligence was involved. None whatsoever.

    21. So Brian, because you can't wrap your brain around a vexing problem, you just declare it doesn't exist and walk away?

      Brilliant solution!

      A TEDX recruiter is knocking on your door as we speak.

    22. Ah yes, the F35, the pinnacle of human engineering. With major design flaws, huge software issues and massive cost overruns. Yeah, clearly superior intellect is at work on the F35.

    23. irrational position

      ...says the person whose argument requires bacteria to have opinions and do advanced genetic engineering while procreating (which involves splitting in half - Steve, what sort of advanced engineering would you be doing while procreating and splitting in half at the same time?), and thinks God is required to instruct electrons on how to form chemical bonds.

    24. Next time someone asks you how the F-35 raptor was made, don't tell them a team of thousands of engineers did the work.

      We can recognize the difference between a team of thousands of engineers being able to design an airplane, and the bacteria in their guts being able to do more advanced genetic engineering than any human.

      So who was smarter, Steve, Jesus or his intestinal bacteria?

    25. Steve, please answer my previous question regarding what it is you think "intelligence" is made of.

    26. Steve,

      "The truth is thousands upon thousands of of individual, complex, unrelated chemical reactions did all the work."

      Is that really the way you think of evolutionary processes Steve? Individual, complex, unrelated chemical reactions? Do you really think that we think of evolution, life itself, and natural phenomena that way?

      If you do you're incredibly stupid.

    27. If you do you're incredibly stupid.

      I have a feeling confirmation would not involve a paradigm shift.

    28. Steve,

      "Next time someone asks you how the F-35 raptor was made, don't tell them a team of thousands of engineers did the work."

      Straw man argument. I said nothing of the sort.

      You have yet to provide a single shred of evidence to support your claim that a conscious intelligence is required for biochemical reactions to proceed.

      What evidence do you have that natural chemical reactions are integrated, coordinated and controlled with intelligence?

    29. Steve, I'm with Brian... any ideas regarding the nature and mechanism of this intelligence you speak of?

    30. "evidence to support your claim that a conscious intelligence is required for biochemical reactions to proceed"

      The evidence is that they don't just proceed. They start and stop on cue.

  5. I agree there is abuse of the "paradigm shift" claim. in fact the whole concept to me is just a admittance to error in conclusions by "science' that said the conclusions were proven by science.
    Thats why its a useful term for creationists but in reality is a fable.
    its just people being wrong in a subject where they won't admit they cAN be wrong. SCIENCE. its like Fonzie, remember him, who couldn't articulate the word WRONG.

    I agree one can't say there is a paradigm shift until it has occurred. Those smelling it coming are as likely to be wrong as right. So it means nothing to say it.
    I do see a PS coming in most of origin biology, led by ID and YEC, .
    I do see evolutionism on its last legs.
    Yet not yet. 15 years or so will do it probably.

    So PS is useful in SCIENCE because by definition science is about proven conclusions. Yet in reality its just people being wrong about complicated, in origin matters invisible, things.
    There is no PS but human error and human pride.

  6. I think Kuhn's thesis is accurate. The problem is that a paradigm shift only becomes visible after it occurs.

  7. Larry,
    If its not too much trouble could you give a reference or 2 for those hybridization studies in the 70s that showed pervasive transcription. It would be nice to have something specific to offer in a debate on the topic.
    I'll do a pubmed search but I have a feeling the search terms that would find the paper are not the ones we're interested in here.

    1. The best source of information is Benjamin Lewin, the editor and founder of the journal Cell and the author of the Genes books. The first two editions of the textbook cover the experiments in excruciating detail.

      The results of RNA hybridization experiments show, in general, that for any one cell type in humans there appear to be about 35,000 mRNAs. This is near the upper end for the total number of genes and that's just one tissue. The evidence suggested that other parts of the genome were being transcribed into mRNA-like molecules.

      The total amount of RNA in the nucleus covered somewhere between 20-30% of the entire genome in any one cell type and those RNAs did not overlap completely. This suggests that as much as 50% of the genome is transcribed. This includes much of the repetitive sequences.

      Lewin favored the idea that large heterogeneous RNA in the nucleus (hnRNA) was a precursor of mature mRNA but at the time (~1975) this was not the majority opinion. He thought that each gene was surrounded by repetitive DNA sequences and the precursor transcripts (hnRNA) needed these repetitive sequences for control of gene expression.

      It was known that some of the transcripts were present at very low levels and this could represent "leaky" expression.

      I have copies of the three volumes of the 1974 edition of Genes—then called Gene Expression. I suspect most of you didn't keep your old textbooks. Or maybe you weren't born yet. :-)

      Here's a couple of reviews that give you a flavor of the times.

      Lewin, B. (1975) Units of transcription and translation: the relationship between heterogeneous nuclear RNA and messenger RNA. Cell, 4:11-20. [doi: 10.1016/0092-8674(75)90128-2]

      Lewin, B. (1975) Units of transcription and translation: sequence components of heterogeneous nuclear RNA and messenger RNA. Cell, 4:77-93. [doi: 10.1016/0092-8674(75)90113-0]

      And here's a discussion about the number of genes in the human genome.

      Lewin, B. (1974) Sequence Organization of Eukaryotic DNA: Defining the Unit of Gene Expression. Cell 1:107-111. [doi: 10.1016/0092-8674(74)90125-1]

  8. Not paradigm-mongering again! About 1980 there was a generation of new graduate students and postdocs who had heard of Thomas Kuhn's work and concluded that only dummies did "normal science", that smart people like themselves had to originate new paradigms. So almost daily new paradigms were announced in evolutionary biology. Us older folks had to clean up the mess.

    I used to say that I would become famous by being the only scientist of my generation to do "normal science".

    Let's hope that this paper is not the first in a wave of new paradigms. Actually the "Third Way" people have already introduced at least 40 new paradigms, because they disagree wildly with each other, and there is no one Way that they all support. It reminds me to Stephen Leacock's famous declaration that "Lord Ronald said nothing; he flung himself from the room, flung himself upon his horse and rode madly off in all directions."

    1. Instead of calling themselves "the third way", perhaps for clarity they should each take a number. Dibs on 7.

    2. Well, there are N of them. When I first counted, N = 43. Now about 50. So when I talked about them at Panda's Thumb last year, I said they were the 3rd through 45th Ways of Evolution.

      But then I noticed that the first way of evolution was the currently accepted way. And, according to the Third Way, the 2nd Way was creationism.

      But creationism is not a "Way of Evolution". It is a No-Way. So the numbers they should have taken were 2 through 44. Nowadays more.

    3. So you don't count statistical phylogenetics as creating a new paradigm? Wouldn't doing "normal science" be just sticking to pop-gen like you learned in grad school?

      It reminds a bit of Hull -- he made the interesting observation that claiming a new paradigm or claiming that one is simply adding a brick or two to the edifice of science is a conscious choice that works both ways: not only do some people hype up pedestrian results as revolutionary, others hide revolutionary results as pedestrian in order to sneak them into the mainstream.

    4. Jonathan: Since statistical phylogenetics is a collection of methods for inferring genealogical relationships in evolution, I don't count it as a new paradigm for what happens. Like a new Modern Synthesis, for example.

  9. Typo alert-
    5th paragraph 2nd sentence after the last box-
    “However,… If many of the real EXPECTS…’ (should be experts)

    I agree ‘paradigm shift’ is over used. People like ‘breakthroughs’ and ’new discoveries’ and communications that include those will engender interest and excitement. After a while the ‘real experts’ who knew it all along start to sound like the ‘true scotsmen’ of fame.

    The real history can be just as interesting as the phony one and we really don't need a new paradigm every week or so.

    Good luck Dr. Moran.

  10. The way I look at it "evolution by natural selection" theory will still be based upon a model with natural selection based variables. Having to start there limits the amount of change that can be made to it. It's expected that in time it will self-correct a given way, according to wherever the evidence leads its future development. The theory can be tweaked, but it's still developing the same model.

  11. The worst thing about legacy is the attitude of non-scientists who think that they are better equipped than to detect paradigms that will shifted soon or rather need to and have to be shifted on their demand. Obviously, Suzan Mazur has an agenda she is pushing by monkeying Cato's Carthago delenda est. Just google her name and "evolution paradigm". As Jeff Shallit rightly put it: Suzan Mazur - Perpetually Clueless

    1. I spotted Susan Mazur long ago as a dyed in the wool opportunist, someone with no interest in facts, just finding something she might turn into profit.

    2. Susan Mazur is wrong to define a paradigm shift as occurring/occurred.
      YET she is sharp because she rightly sees it coming.
      Time will prove if she was ahead of the curve.
      The recent dissent against evolution by the third way folks is disaster for evolutionary biology.
      No other 'science idea" ever has this or could and still expect to survive.
      YEC/ID/THIRD WAY /independent thinkers aplenty all point to a curve on the graph that evo bio is unlikely to survive.
      Its critics are defining it today and not its defenders.
      Evo bio NEVER had bio evidence behind it and thats why so much error got under the radar. It was based on a desire/need for explanation for important ideas on bio origins. Then unrelated subjects were used to back it up. YET NOT BIO EVIDENCE.
      This has been smoked out , even by Mazur journalists, and so new explanations are needed to replace the old one.
      Mazur is not YEC or even ID. Just on the trail of a paradigm shift.
      Just premature in the catch .

  12. I think that there was one scientific paper published in the 20th century that was unequivocally a paradigm shift, namely Einstein's 1905 papers on the special theory of relativity. The notion that that the speed of light was independent of the velocity of the observer and that it was the upper limit of velocity that could be achieved were both paradigm shifts of major proportions.

    1. Single papers do not shift paradigms. From 1905 to 1915, the physics community gradually adopted the new perspective as it became clear that Einstein was right. When the paper first came out I imagine that most scientists were skeptical, as they should be.

    2. Actually, Einstein wrote 2 papers on Special Relativity in 1905. At least, one could argue that a paradigm shift began in 1905, even if it took some time to be accepted.

      Another example was yet another paper by Einstein on the photoelectric effect (for which he was awarded the Nobel Prize in Physics) which introduced the concept that light was both a wave and a particle. The notion that light consisted of particles had been proposed by Isaac Newton back in the 17th Century but had been all but abandoned due to the success of Huygens' principle in explaining diffraction (although this is not generally known, Newton actually considered the notion after receiving a copy of Huygens paper on the subject. He soon discarded it as the mathematics that would lay a foundation for the theory of quantum mechanics (Hilbert spaces) did not exist at the time.)