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Medicine Science

Scientists Create World's First Living Organism With Fully Redesigned DNA 158

Posted by BeauHD from the first-of-its-kind dept.
An anonymous reader quotes a report from The Guardian: Scientists have created the world's first living organism that has a fully synthetic and radically altered DNA code. In a two-year effort, researchers at the laboratory of molecular biology, at Cambridge University, read and redesigned the DNA of the bacterium Escherichia coli (E coli), before creating cells with a synthetic version of the altered genome. The artificial genome holds 4m base pairs, the units of the genetic code spelled out by the letters G, A, T and C. Printed in full on A4 sheets, it runs to 970 pages, making the genome the largest by far that scientists have ever built. The DNA coiled up inside a cell holds the instructions it needs to function. When the cell needs more protein to grow, for example, it reads the DNA that encodes the right protein. The DNA letters are read in trios called codons, such as TCG and TCA.

The Cambridge team set out to redesign the E coli genome by removing some of its superfluous codons. Working on a computer, the scientists went through the bug's DNA. Whenever they came across TCG, a codon that makes an amino acid called serine, they rewrote it as AGC, which does the same job. They replaced two more codons in a similar way. More than 18,000 edits later, the scientists had removed every occurrence of the three codons from the bug's genome. The redesigned genetic code was then chemically synthesized and, piece by piece, added to E coli where it replaced the organism's natural genome. The result, reported in Nature, is a microbe with a completely synthetic and radically altered DNA code. Known as Syn61, the bug is a little longer than normal, and grows more slowly, but survives nonetheless.
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Scientists Create World's First Living Organism With Fully Redesigned DNA More

Scientists Create World's First Living Organism With Fully Redesigned DNA

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  • Ok then (Score:1)

    by Anonymous Coward

    Sounds pretty fucked up

    • This is great news! (Score:2, Funny)

      by Anonymous Coward

      This is fantastic news! Now we can have E.coli tainted lettuce that has been genetically engineered to take up less paper when printed out. Think of all the trees that will save! More wood for PG&E power poles! What will those kooky scientists come up with next?

      • Re: (Score:1)

        by beavhd ( 5702430 )
        Wake me up when they can make something 50% man, 50% bear, and 50% pig.

        -beav

      • This is fantastic news! Now we can have E.coli tainted lettuce that has been genetically engineered to take up less paper when printed out. Think of all the trees that will save! More wood for PG&E power poles! What will those kooky scientists come up with next?

        A process to make you understandable?

      • I am a bit worried what happens when this escapes from the lab and and breeds with natural E.Coli and creates a superbug that would not occur in nature that then kills us all. Nice job lads!

  • Drop that shit. It's embarrassing. Pathetic beaten to death senseless meaningless journalist trash analogy.

    • Re: (Score:1)

      by necro81 ( 917438 )

      Drop that shit. It's embarrassing. Pathetic beaten to death senseless meaningless journalist trash analogy.

      would you prefer if they had printed it on Letter-sized pages, instead?

  • refactor (Score:5, Funny)

    by phantomfive ( 622387 ) on Wednesday May 15, 2019 @10:56PM (#58600484) Journal

    . More than 18,000 edits later, the scientists had removed every occurrence of the three codons from the bug's genome.

    Sounds like the most miserable refactor ever. Sometimes it's better to write that shit from scratch.

  • I hope some safety tests are done (Score:3)

    by ITRambo ( 1467509 ) on Wednesday May 15, 2019 @11:06PM (#58600518)
    Is this bug resistant to antibiotics and other treatments? What happens when it infects the gut, skin, or blood of mammals? Just doing something mindlessly, even when it's a lot of work, isn't enough. We need to know the answers to the "what if" questions.

    • Is this bug resistant to antibiotics and other treatments?

      No, it's not.

      • Re: (Score:2)

        by kbg ( 241421 )

        Well how do you know? Did they specially test all known antibiotics? I seriously doubt so. All changes in DNA can have unforeseen consequences not known at the time.

        • Re: (Score:2)

          by cusco ( 717999 )

          Why would you test "all known antibiotics"? There are a lot of antibiotics that normally don't kill e. coli, some antibiotics only work on gram positive bacteria, others only on gram negative, etc. Unless your purpose is to deliberately waste the researchers time and money.

          Ah, you're opposed to genetic research of all kinds, aren't you?

          • Re: (Score:2)

            by kbg ( 241421 )

            Why would you test "all known antibiotics"? There are a lot of antibiotics that normally don't kill e. coli, some antibiotics only work on gram positive bacteria, others only on gram negative, etc.

            Of course I am reffering to all known antibiotics that work on Ecoli.

            Ah, you're opposed to genetic research of all kinds, aren't you?

            Of course not. I am an avid supporter of science. But any GMO that is able to multiply itself has some dangers associated with it if it gets out of control. Also any GMO that you inject into your body like food for example can possibly be dangerous. This is just something that has to be acknowledged.

            • Re: (Score:2)

              by Shaitan ( 22585 )

              Simply being bacteria and able to replicate doesn't make it harmful to humans in the first place. Everything carries some kind of theoretical danger but one must consider the level of danger in order to give context.

              For instance, marijuana has harmful effects and risks but relative to other common and generally considered harmless substances like Aspirin it could never be considered dangerous. Focusing on the gotcha of there being some kind of harm or risk and leaving out any sort of relative comparison of

              • Simply being bacteria and able to replicate doesn't make it harmful to humans in the first place. Everything carries some kind of theoretical danger but one must consider the level of danger in order to give context.

                You miss the point of the parent. How could you give a (clear) level of danger when you don't clearly know what you are dealing with in the first place per your post? Instead of attempting to give any level of danger, cautiousness should be given, and that's what the parent post is saying. "What if" is something to beware for any danger from the unknown. Cautiousness is not the same as rejection. Your attitude is too optimistic and don't expect for the worse; thus, no preparation for any down side of the si

                • Re: (Score:2)

                  by Shaitan ( 22585 )

                  "How could you give a (clear) level of danger when you don't clearly know what you are dealing with in the first place per your post?"

                  You aren't talking about a specific change or how damaging that specific change is here. You are talking about an unknown, so you look to the probability. A change specifically introduced to be safe with controls has a lower probability of being negative of any danger level than one introduced at random. These changes happen at random in nature without any guiding intention o

        • It produces all the same proteins--organisms are basically constructed by proteins shaped such that they physically move small molecules around to cause chemical reactions--and antibiotics react to specific proteins by denaturing them or react to specific cellular structural components or other things produced by those proteins. Some bacteria build cell walls (gram+ and gram- are types of cell walls) and are targeted by antibiotics that interfere with the chemical reaction which produces those cell walls,

          • Re: (Score:2)

            by kbg ( 241421 )

            Some bacteria build cell walls (gram+ and gram- are types of cell walls) and are targeted by antibiotics that interfere with the chemical reaction which produces those cell walls, for example.

            It's basically the same machine with some of the timing tweaked, and sticking a wrench in the same spot will break it all the same.

            So how do you then explain Ecoli antibiotic resistence? Obviously it will not break all the same, if the machine has been changed in some way. You may think you are just changing the timing but you are possibly changing other things at well.

            • Random transcription errors when copying the bacteria can create a broken genome (proteins don't form anymore, the cell dies), a semi-broken genome (there were multiple genes coding the same protein; a few don't work, it's less-efficient), a genome that codes the same proteins differently (some of those genes are different, but they make the same protein), a genome that codes a similar protein that serves the same function (different molecule, same purpose, possibly more- or less-active at different tempera

              • Re: (Score:2)

                by kbg ( 241421 )

                I know how evolution works. But that is exactly my point. It all comes down at the end to arrangement of the DNA. DNA arrangement dictates how the organism survives, including resistance to antibiotics.

                • DNA arrangement dictates the components of the machine. This DNA produces the same components, so it's resistant to the same drugs and vulnerable to the same drugs.

                  Like, this DNA may build a phosphated cell wall slightly more-rapidly or more-slowly than the original, due to using a different base pair set to make the same amino acid. That may happen at a different speed, so the components may be available more-rapidly or more-slowly. Think bricks and mortar being manufactured and trucked in a bit more

    • Antibiotics don't depend in any way on the genetic code of the bacterium, so it should make no difference initially to antibiotic resistance. However because its code is incompatible with other bacteria, it can't gain or pass on antibiotic resistance to others. So the antibiotic situation is better than nature. If you wanted to use bacteriophages (viruses which infect bacteria) to control them, an approach which is currently rare but might become common, you'd need a virus engineered for this bacterium, you

      • Antibiotics don't depend in any way on the genetic code of the bacterium, so it should make no difference initially to antibiotic resistance.
        Obviously they do ... or which magic makes a bacterium resistant if it is not its genes?

        • The specific sequence of the DNA doesn't make a difference, the resulting proteins are the target of the anitbiotics. What they've done is swap in different codons that code for the same amino acids. So... if a manual is written in English or Chinese, you still build the same engine from it and it still breaks if you pour sugar into the gas tank.

          • What they've done is swap in different codons that code for the same amino acids.

            Except that the resulting bacterium grew slower, and was a little longer, so it was not completely identical.

            • It could code for the same amino acid but through a slower process. It's possible if they swapped the other direction it might have grown faster.

            • Yes, remember that biology is applied chemistry. While the coded amino acid is the same, the reaction you're coding from has changed subtly. It may have a slightly different activation energy, temperature sensitivity, etc. Bacteria like these undergo binary fission, so longer and slower growth go hand in hand. The amino acids balance they've been optimized to keep around for DNA synthesis just changed, after all. You can code on a mechanical keyboard or an onscreen keyboard and the input and output are

          • A good question would be -- why wouldn't there exist in nature in the first place if the sequence of the DNA doesn't make any differences? There must be a reason for it. If we don't know the reason but attempt to make guesses, then your "the end justifies the mean" is still not acceptable. We still need to be cautious and not whole heatedly accept it. Besides, your analogy is too oversimplified. Mechanical shouldn't be used to explain biological matter.

            • If you look at the code, two of the bases in the codon are very important, and the third only matters sometimes. The reason is that biology is messy: remember this is all randomness and natural selection, no one came up with the genetic code on a napkin. There needn't be a reason it works the way it does other than that the life that works this way ate the ones that worked another way and then eventually begat us. The genetic code gets people thinking of it like computer code, whereas the mechanical anal

      • The genetic code here would be compatible. It needs Serine, it gets Serine; it may produce Serine a little more-slowly, more-quickly, or more- or less-frequently. The crossbreed won't produce hybrid vigor, either, because the proteins are the same, rather than different outputs which may exhibit different characteristics (e.g. active temperature range, sensitivity to pH) while performing the same function.

    • The genetic code is a degenerate code: multiple codons code for identical amino acids. In the example above, either TCG or ACG give you serine. So this is more like replacing deprecated Excel commands in an old spreadsheet than it is writing from scratch. Nothing changed about how the organism works, apart from presumably some minor metabolic changes from the tweak to the amino acid balance needed to reproduce.

      • Let's hope god doesn't work for MS or we'll see some funky results somewhere down the line because of undocumented side effects.

      • Re:I hope some safety tests are done (Score:4, Insightful)

        by Mab_Mass ( 903149 ) on Thursday May 16, 2019 @11:35AM (#58603068) Journal

        In theory, nothing should have changed, since these were synonymous changes. In practice, though, it has. From TFA:

        Known as Syn61, the bug is a little longer than normal, and grows more slowly, but survives nonetheless.

        In other words, simply changing *how* various proteins are encoded has had a measurable phenotypic difference. To me, this is the undersold part of the story - illustrating how complex life actually is, and that synonymous changes can actually have visible consequences.

    • There are millions of different e-coli bactgeria and only a handful of them are harmful for us. Right now you have tons of various e-coli in your guts.
  • They should really watch it.

  • Fully redesigned? (Score:5, Informative)

    by Guillermito ( 187510 ) on Wednesday May 15, 2019 @11:15PM (#58600554) Homepage

    Whenever they came across TCG, a codon that makes an amino acid called serine, they rewrote it as AGC, which does the same job

    So they basically performed the equivalent of searching for tabs and replacing with spaces in source code. I'm pretty sure this is a great feat, but I wouldn't call that a "Fully Redesigned" organism.

    • Re: (Score:1)

      by Anonymous Coward

      It IS a great feat! It's supershit!

    • Re: Fully redesigned? (Score:4, Funny)

      by ljw1004 ( 764174 ) on Thursday May 16, 2019 @12:07AM (#58600718)

      *narrows eyes* can't tell if you're a tab-lover or a TCG-lover...

    • That's why the new bugs are bit longer, because the tabs are a bit longer than the spaces.
      It all makes sense now.

    • Re: (Score:2)

      by rtb61 ( 674572 )

      Well at least it is on the path to fully genetically redesigned algae as super customisable foods. Although with the wide diversity of algae it will be more cut and paste from one type to another. To create the, nutrition type, the right trace element balance, virtual elimination of allergy inducing molecule, and every imaginable taste and texture.

    • Re: (Score:3, Funny)

      by Anonymous Coward

      So they basically performed the equivalent of searching for tabs and replacing with spaces in source code. I'm pretty sure this is a great feat, but I wouldn't call that a "Fully Redesigned" organism.

      I'm really impressed by the work, but that's because I've got a biology degree, not autism.

    • Whenever they came across TCG, a codon that makes an amino acid called serine, they rewrote it as AGC, which does the same job

      So they basically performed the equivalent of searching for tabs and replacing with spaces in source code. I'm pretty sure this is a great feat, but I wouldn't call that a "Fully Redesigned" organism.

      It explains why they could get a bacterium to work, but not a Python ...

      Ba-dum ching!

  • Comment removed based on user account deletion

  • God will charge royalties.

  • So if they created the DNA (presumably actually RNA) strand, protein by protein, then did they add any epigenetic molecules to it? If not, that might explain why it's bigger and reproduces slower.
    I'd be somewhat worried about a more-efficient version of E. Coli infecting people's microbiota, as that could lead to worse problems with eutrophy.

    • Until I read this, it had not occurred to me to wonder whether epigenetics happens in bacteria, or just in eukaryotes.Wikipedia [wikipedia.org] to the rescue:

      "While epigenetics is of fundamental importance in eukaryotes, especially metazoans, it plays a different role in bacteria. Most importantly, eukaryotes use epigenetic mechanisms primarily to regulate gene expression which bacteria rarely do. However, bacteria make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions

    • most e. coli strains are harmless. you have them in your intestines if you're healthy.

  • Process (Score:2, Insightful)

    by freedom4us ( 1828474 )
    The process seems the highlight here, not the actual code. They edited the DNA, so they altered some other creators code -which the crispr method is famously known for-, not built something from scratch (they did synthesize the DNA but did not create the code and it is a huge huge difference). Creating a new living organism seem still light years away from human understanding. Anyhow, it deserves congratulations.

  • Serine is one of the simplest amino acids in chemical terms, therefore is argued to have entered biology early in the formation of the (nucleic acid amino acid) relationship which is so fundamental, and so sophisticated, today. The alternative codon AGC which they picked is argued to be the original dominant encoding for biophysical reasons: codons ending in C are energetically less expensive to separate from the nucleic acid stack for reading or copying https://www.cambridge.org/core/journals/quarterly-r

  • Do you want zombies? Because I'm pretty sure this is how you get zombies. :)

  • I mean, why not some other bacteria that doesn't already cause worldwide illness?

    • Most of the 700+ strains of e. coli are harmless. you have them in your intestines.

      they're common and very well studied, and perfect for these kinds of experiments.

  • ..zombie apocalypse.

    Also,
    4 million base pairs
    ..for a simple bacteria?

    Wow, I thought some programming languages had bloated runtime libraries. If you're going to redesign it, write it in assembly language or something, and learn to use loops, kthxbye.
  • They made 18,000 edits that do the same thing as before? Did I read that correctly?
  • over another? i am sure e.coli wasnt picked at random-or pretty sure and some thought went into a working hypothesis at one point or another. very interesting whatever way it is done-all of it

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