Chemistry Nobel for “directed evolution” (2018)

  1. Very nice. Congratulations! But where is the “directed evolution” oxymoron in this story? The process used is simple organism breeding as done by mankind for thousands of years, in this case sped up by advanced technologies. “Random mutations” are not entirely random as the mutations desired had to converge towards a clear, specified target. Random generator devices also generate within specific ranges, say 0 to 9, rejecting outright any “randomness” outside that range (‘a’, ‘#’, ‘21’ will all be rejected). “Natural selection” is also missing as the selection has been clearly done by qualified researches pursuing a specific goal. At best this would be called “artificial selection”, but even that is misleading since organism breeding is a human activity that goes well beyond simple ‘selection’.
  2. The researchers induced mutations in proteins and selected those that best met the goals of the research. The winners were Frances Arnold of the California Institute of Technology, George Smith of the University of Missouri and Gregory Winter of the MRC molecular biology lab in Cambridge, England.
  3. Smith showed in 1985 that inserting DNA into these viruses would make them display proteins linked to that DNA on their surfaces. It was a way to find an unknown gene for a known protein. Winter adapted the approach to create useful antibodies, proteins that target and grab onto disease-related targets. Winter introduced mutations to make antibodies progressively better at binding to their targets. In 1994, for example, he developed antibodies that grab onto cancer cells.
  4. Arnold was seeking ways to make improved enzymes, which are proteins that encourage chemical reactions to occur. In 1993, she showed the power of “directed evolution” for doing that. First she created random mutations in DNA that lets cells produce an enzyme. Then she slipped these mutated genes into bacteria, which pumped out thousands of different variants of the enzyme. One variant did a particularly good job at a certain task, so she made a new round of mutations in this variant. That produced another variant that worked better. When she made mutant versions of that variant, she got an even better version. It contained a combination of 10 mutations that nobody could have predicted would work so well, the Swedish academy said.
  5. This process also resembles a mechanism of the immune system: though antibodies are very similar, a small region at the tip of the protein (hypervariable region) is extremely variable, allowing millions of antibodies with slightly different tip structures, or antigen-binding sites, to exist. The large and diverse population of antibody paratope (antigen-binding sites) is generated by random recombination events of a set of gene segments, followed by random mutations in this area of the antibody gene, which create further diversity (VDJ or VJ recombination). During antibody production, one allele of V, one of D, and one of J is chosen and joined together using random genetic recombination to produce the paratope.

29 Replies to “Chemistry Nobel for “directed evolution” (2018)”

  1. Mung Mung
    Ignored
    says:

    If Nonlin.org has some evidence that the mutations were not random in the sense of random employed by evolutionary biologists when speaking of the correlation between the mutation and the fitness I am hoping he will share that information.

  2. Entropy Entropy
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    says:

    Mung,

    You better have a seat Mung.

  3. Mung Mung
    Ignored
    says:

    It seems to me that if the mutations were non-random that the selection process would not be necessary. But sometimes I’m just dumb. Forget selection, use amplification!

  4. Rumraket Rumraket
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    says:

    I agree with Mung. I’d like to see what kind of evidence Nonlin has that the mutations aren’t random. I’m sure the selection process is nonrandom, and scientists are deliberately rejecting some mutants.

    But Nonlin seems to be operating under the misapprehension that random means something like “completely unconstrained”. So a mutation is not just changes in sequence of nucleotides, but apparently must involve something like spontaneous alteration of matter into anything concievable. ACTG must be able to “mutate” randomly into a nuclear submarine, or a tiger, or pocket lint.

    Is that what he’s saying?

  5. Entropy Entropy
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    says:

    Rumraket,

    Better for you to also have a seat. Only nonsense can be expected from Nonlin. So, if you two expect answers from her/him you’re better off seating.

  6. Mung Mung
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    says:

    I like to think of the possibilities offered by quantum tunneling.

    Why not a nuclear submarine?

  7. Rumraket Rumraket
    Ignored
    says:

    Mung:
    I like to think of the possibilities offered by quantum tunneling.

    Why not a nuclear submarine?

    Quantum tunneling is all well and good, but I don’t think those processes are normally considered as relevant contributions to evolutionary change, nor a kind of mutation. 🙂

  8. Mung Mung
    Ignored
    says:

    LoL.

    ok, I think I have it.The mutations are non-random not because they are biased towards the desired function but because they are biased away from the desired function.

  9. Entropy Entropy
    Ignored
    says:

    This seems to be the only part written by Nonlin, since it exhibits Nonlin’s “classic” incoherence.

    Very nice. Congratulations! But where is the “directed evolution” oxymoron in this story?

    Oxymoron is putting together contradictory terms. Evolution is a process whereby variation builds up, and some of such variation is filtered out by the circumstances under which the variation emerges (metaphorically called natural selection). Since the scientists awarded the Nobel use the same principles, only under the control of researchers, theres’ nothing contradictory in putting those terms together. It’s not as if evolution was necessarily “undirected,” and it’s not as if this was the first time humanity has used some principle learned from nature to their advantage,

    The process used is simple organism breeding as done by mankind for thousands of years, in this case sped up by advanced technologies.

    Nope. These were not organisms breeding. These were molecular manipulations.

    “Random mutations” are not entirely random as the mutations desired had to converge towards a clear, specified target.

    The mutations were random. Otherwise there would be no need for selection. Selection is what made those sequences “converge” towards the scientists’ goals. This is fucking simple, yet Nonlin manages to miss it. I suspect that Nonlin is desperately trying to dismiss the “inconvenient” fact that an evolutionary principle worked so well that the results made those scientists deserving of a Nobel prize.

    Random generator devices also generate within specific ranges, say 0 to 9, rejecting outright any “randomness” outside that range (‘a’, ‘#’, ‘21’ will all be rejected).

    There wasn’t a computer random generator, this was experimentally induced mutations.

    “Natural selection” is also missing as the selection has been clearly done by qualified researches pursuing a specific goal.

    Which is why this was called directed evolution, not what-you-see-in-nature evolution.

    At best this would be called “artificial selection”, but even that is misleading since organism breeding is a human activity that goes well beyond simple ‘selection’.

    Again, this wasn’t breeding Nonlin, did you actually read what “you” wrote later about proteins and DNA? Did you plagiarize that part without paying any attention to it? Do you know what proteins and DNA are?

    Of course there was artificial selection, but the name of the process wasn’t selection, it was directed evolution, which conveys the idea of a process that mimics evolutionary phenomena, not selection alone.

    Nonlin, your desperation to dismiss an evolutionary-inspired success is duly noted.

    Since I know that you don’t understand much, now I leave you to your nonsense. You’ll cry, you’ll yell, you’ll pretend to laugh, you’ll call everybody a moron, and still those evolutionary principles will have worked. It doesn’t matter how much nonsense you sprout, or how much you ridicule your own intelligence. So go for it Nonlin. Ridicule yourself some more.

  10. Richardthughes Richardthughes
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    says:

    Demise of TSZ, evidence 87642834

  11. Fair Witness Fair Witness
    Ignored
    says:

    Mung:
    LoL.

    ok, I think I have it.The mutations are non-random not because they are biased towards the desired function but because they are biased away from the desired function.

    You can’t go wrong with a good old-fashioned false dichotomy.

  12. Nonlin.org
    Ignored
    says:

    Mung: If Nonlin.org has some evidence that the mutations were not random in the sense of random employed by evolutionary biologists when speaking of the correlation between the mutation and the fitness I am hoping he will share that information.

    There’s a nuance there: “not entirely random” versus your demand for “not random”. See the difference, Mung?

    Why does it matter? Because as far as I can tell, there’s nothing “entirely random” out there. Take a 6 face die. Can you get 7, 8, 9? NO. Try for yourself: can you think of anything that is entirely random? NO.

    In this case, those mutations were constrained as much as possible to generate new versions of the desired features, not just random anything. So, once again, we have the Intelligent Agent hard at work limiting randomness.

  13. Nonlin.org
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    says:

    Entropy:
    Nonlin: Very nice. Congratulations! But where is the “directed evolution” oxymoron in this story?

    Oxymoron is putting together contradictory terms.

    Yep. Classic case!

    Unless you think “evolution” is directed which would make you an ID proponent. Probably not what you want to say.

  14. Rumraket Rumraket
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    says:

    Nonlin.org: Why does it matter? Because as far as I can tell, there’s nothing “entirely random” out there. Take a 6 face die. Can you get 7, 8, 9? NO. Try for yourself: can you think of anything that is entirely random? NO.

    So I was right. Nonlin thinks that random essentially means anything can happen.

    Mutations can’t be “random” if they’re constrained merely to changes in DNA sequences, they have to be able to turn into anything and everything. See that adenosine nucleoside? It doesn’t spontaneously turn into a late stage supergiant star, or a fungal spore, or 942 atoms of some obscure isotope of Tellurium, so it’s not really random.

    Is there no end to the absolute gibberish this individual spews?

  15. Mung Mung
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    says:

    Moved a comment to Guano.

  16. J-Mac
    Ignored
    says:

    Rumraket: Quantum tunneling is all well and good, but I don’t think those processes are normally considered as relevant contributions to evolutionary change, nor a kind of mutation.

    Of course quantum tunneling driven mutations are not normally considered by Darwinists because they imply non-randomness just like in case of adaptive mutations… When the results of the EXPERIMENTS were first published in Nature in 1988 it was considered as heresy by the “truth seeking scientists and worshipers of Darwin”… because their dogma and ideology is more important than experimental result that contradict their preconceived ideas…
    What else? Their commitment to materialism obscures experiential and true science…How did it happen? Who is behind this conspiracy? Who allowed this to happen? How???

    The origin of mutants.
    Cairns J 1, Overbaugh J, Miller S.

    Abstract
    “Nucleic acids are replicated with conspicuous fidelity. Infrequently, however, they undergo changes in sequence, and this process of change (mutation) generates the variability that allows evolution. As the result of studies of bacterial variation, it is now widely believed that mutations arise continuously and without any consideration for their utility. In this paper, we briefly review the source of this idea and then describe some experiments suggesting that cells may have mechanisms for choosing which mutations will occur.”

    Darwinism and its dictatorship bully the whole scientific community into what is presented as true and what is presented as false. Materialism and Darwinism first, right or wrong…

    Random mutations idea is not even wrong…

  17. DNA_Jock
    Ignored
    says:

    J-Mac: describe some experiments suggesting that cells may have mechanisms for choosing which mutations will occur.

    Turns out that isn’t what’s happening.
    Either way, it’s got nothing to do with quantum tunneling.

  18. Allan Miller
    Ignored
    says:

    J-Mac,

    Darwinism and its dictatorship bully the whole scientific community into what is presented as true and what is presented as false. Materialism and Darwinism first, right or wrong…

    You side very firmly with the proponents on this, and dismiss all objections. Why is that? You seem generally eager to seize on anything vaguely contrarian, for its own sake.

  19. Mung Mung
    Ignored
    says:

    Allan Miller: You seem generally eager to seize on anything vaguely contrarian, for its own sake.

    I’ve been meaning to have a talk to him about that. That spot is already taken.

  20. faded_Glory faded_Glory
    Ignored
    says:

    Nonlin.org: Yep. Classic case!

    Unless you think “evolution” is directed which would make you an ID proponent. Probably not what you want to say.

    Evolution is directed by the environment. Life in water will evolve in very different directions than life on land. Thinking this would only make me an ID proponent if the environment is intelligent.

  21. Entropy Entropy
    Ignored
    says:

    Mung:
    Moved a comment to Guano.

    I don’t understand why. 😁

  22. Mung Mung
    Ignored
    says:

    LoL.

    Questions about moderation belong in the moderation issues thread. 😀

  23. Nonlin.org
    Ignored
    says:

    Rumraket: So I was right. Nonlin thinks that random essentially means anything can happen.

    Mutations can’t be “random” if they’re constrained merely to changes in DNA sequences, they have to be able to turn into anything and everything. See that adenosine nucleoside? It doesn’t spontaneously turn into a late stage supergiant star, or a fungal spore, or 942 atoms of some obscure isotope of Tellurium, so it’s not really random.

    Ridiculous. You don’t seem to understand the basics of ‘randomness’, but you were “right” about someone else’s understanding?

    Can you grasp these basics?
    1. Randomness is a useful THEORETICAL concept like Circle, Line, or Point.
    2. We can NEVER be certain that a system is random or not based on its outcomes
    3. There are NO PURELY random systems out there

  24. Nonlin.org
    Ignored
    says:

    faded_Glory: Evolution is directed by the environment. Life in water will evolve in very different directions than life on land.

    Nonsense. How do you get humans to differentiate from apes (or any organism from any other) in the same environment while so many populations span multiple environmental zones? This was discussed extensively.

  25. J-Mac
    Ignored
    says:

    Nonlin.org: Can you grasp these basics?
    1. Randomness is a useful THEORETICAL concept like Circle, Line, or Point.
    2. We can NEVER be certain that a system is random or not based on its outcomes
    3. There are NO PURELY random systems out there

    Hi Nonlin,

    I think I agree with you but I wouldn’t mind to hear you elaborate more on the example of dice; 6 out of 6 constraint you used…

    I disagree with you on #3.

    In quantum mechanics, as far as it is known, there is an infinite number of probabilities of the “location” of a particle, which is viewed as totally random, until a measurement of that particle is carried out…

  26. dazz dazz
    Ignored
    says:

    J-Mac: In quantum mechanics, as far as it is known, there is an infinite number of probabilities of the “location” of a particle, which is viewed as totally random, until a measurement of that particle is carried out…

    That doesn’t mean the particle could be anywhere though, right? So, just like dice are restricted to 1 – 6, their possible positions are restricted too.

  27. Alan Fox Alan Fox
    Ignored
    says:

    Moved comments to guano.

  28. Nonlin.org
    Ignored
    says:

    J-Mac: I think I agree with you but I wouldn’t mind to hear you elaborate more on the example of dice; 6 out of 6 constraint you used…

    I disagree with you on #3.

    In quantum mechanics, as far as it is known, there is an infinite number of probabilities of the “location” of a particle, which is viewed as totally random, until a measurement of that particle is carried out…

    Quite simple. All so-called random events have a distribution function that limits randomness. Take the 6-face die. It’s like an infinite uniform distribution that someone (the Die Maker) re-shapes: can’t have 6 and can’t have non-integers.

    The quantum wave function has a well defined [nonrandom] shape. Same deal as above. Can you see the Wave Maker’s fingerprint?

  29. Mung Mung
    Ignored
    says:

    Moved a comment to Guano.

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