It's crazy. I spent some time in a lab as an undergrad, they had a machine called a flow cytometer. It could identify phosphorescent markers and sort individual cells. It sorted cells individually, 10000 per second. That was just the start -- they had the yeast cells express a custom protein on their surface that was supposed to bind to an influenza spike protein. They attached the phosphorescent marker to the influenza spike protein. They were able to sort the cells, keep all of the ones that bound to the spike protein, and then run them through a second generation sequencer (one of Illumina's machines, I think). THAT gave them an accurate count of each genetic sequence that had bound to the influenza. Take the most successful genetic sequences, mutate them ten thousand different ways (using Rosetta protein folding models), order the new 10,000 DNA sequences on a chip, insert that DNA into plasmids, transform the plasmids into new yeast cells, and run the second generation of designs through the flow cytometer. Couple more generations, and they have designs that (when expressed on the surface of a yeast cell) bind to the influenza spike protein (though not necessarily in the desired location). Crazy stuff. New stuff. Unimaginable 25 years ago.
Cool, I worked on a genetic code expansion project in undergrad where we repurposed the UAG stop codon (also called the amber stop codon) to express proteins with non-canonical amino acids. The nice thing about using stop codons for repurposing is that it’s easy to know if you were successful because if it didn’t work, you just get a truncated short protein which is easy to identify. Also, the UAG stop codon is the least used in nature so it’s the low hanging fruit for repurposing. From what I understand the proposed uses are for making novel biological medicines, industrial purposes (things like fermentation or maybe nitrogen fixation), and to study enzyme structure/function in the lab. I’m no expert but it was a fun project.
Sweet! Has this been used to engineer proteins that carry toxic agents (such as radionuclides) to tumors or other diseases? Or to make enzymes that can repair damage?
You must be pretty lucky working on such a futuristic concept, that too in undergrad. All I did in biotechnology undergrad was preparing media, make some yoghurt, and make a ball-and-stick model for proteins. 😢
It's not really a good redundant setup though. More like someone set up a jump-table sprinkled with multiple jumps to the same target. Having just one valid encoding of each protein and point the extra ones to STOP would be a good start at improvement that kills of mutations and badly non-compatible viruses.
@@v4lgrind There are way too many things we still don't know about about genes. A few years ago we thought transposons don't do anything because they don't code for anything. Now we know that removing it, causes an organism's immunity to be compromised. Plus, the multiple jumps on the same target might not be such a bad thing. Different cellular conditions might need the genetic sequence to be transcribed at different instances. We should wait half a century before we reconsider this
@@v4lgrind Maybe. Specification and Precision are things to aim for in design. But the organism and target/item must be more compatible, no? Since the control it would give in biological entities may be ineffective due to the chaos of the world. As was said in the video, the bacteria were immune to certain viruses, but the virus proteins were just there. I would think the bacteria may have dissolved some of them, but a perfect entity in an imperfect world may be the problem.
@@rephaelreyes8552 Heh, half a century is probably accurate as far as approximate timelines go In the mean time, I'm all for experimenting on mice and e. coli
That’s actually really smart. With more redundancy I feel like cancer and cell death can be prevented. If anything, adding more redundancy can be good. If we were to do the whole gmo humans thing.
@@itsyurmumm8458 Prevented? No, not really. But I'd bet good money that the redundancy does provide some cancer resistance. If CAG and CAA are the same amino acid, then when a mutation occurs there's a 33% chance nothing changes. (....technically, my math is wrong there, but whatever, the point stands) But I don't think there's any way to build the system to prevent it altogether. Even if you could absorb a mutation in any spot, that mutation still happens, that spot is now vulnerable, and is passed on to the next generation.
We could actually create genetic error-correction theoretically, the same way that error correction is done on critical computers. All you need to do is make sure that any single base pair flip is closer to an existing codon. Then we could create cellular machinery that fixes the codon if a base pair changes. This would allow you to create genetic error correction. However, this would not be able to "cure cancer" in an already living person, as the person would need to be genetically engineered to have this genetic error correction.
@@Urammar Speaking of mRNA as it evolved as a system to decouple transcription and translation did you know that only Eukaryotes and Viruses use/have mRNA which is used as a pass code for RNA sequences to be allowed through the Nucleolus and Viral replication factory respectively. (One of the lines of evidence that led to the Viral Eukaryogenesis hypothesis So while adding an mRNA checksum would fix Eukaryotes and Viruses it would have absolutely no effect on Bacteria and Archaea which would be able to continue to evolve freely. As such the ultimate result would be a world where Bacteria and Archaea run unchecked as viruses couldn't stop them and Eukaryotes couldn't adapt either eventually leaving us all immunocompromised as pathogens continue to evolve while we don't. That is frankly terrifying....
Damn, if scientists can make ribosomes with CRC we can basically eradicate cancer and any other mutation related disease (but also evolution would slow down, but maybe we will be to control it this way)
@@Dragrath1 I'm not sure I understand? Or maybe you don't? One of us certainly doesn't. Bacterial infections would still be fought in the body as normal, but anything that makes use of DNA/RNA would break instantly. Thats virus replication, cancer, anything like that. Its 100% correct, human code, or it ain't replicating. This change wouldn't extend to nature at large, so it just means humans only have to fight bacteria, and only some at that, and everything else can bit my shiny science hiny. Virus matter would still exist in nature, and cancer, and a bunch of other stuff, it just wouldn't effect humans at all.
"Why does my experiment have 2 noses and 1 eye?" "You missed a 'stop' here" Yup, as someone who took many years of programming, I could see this happening =p
"Junk" DNA that doesn't code for anything might act as a "cancer buffer": since a lot of it can be disrupted without damaging active processes, it might be an "advantage" when it comes to resisting ionizing radiation or other DNA disruptors.
@@evanhughes9576 Redundant codons have been found to have uses. Strengthening the effects of a codon, or taking over if an identical codon is damaged, for example. This is amazing technology, but we need to be quite careful what we tinker with, and be able to undo edits we make, just in case, before we start using it actively. Of course, you would HOPE that scientific professionals would understand that. I'm all for editing out genetic diseases, and we know enough to at least start doing that now. Wish I was born about 500 years in the future, this "ageing" thing sucks, and by then we might be doing something about it...
@@mcchuggernaut9378 we already should be doing something about aging. Aging is like cancer, there is not a single cause, there are plenty of things going wrong, and some of them we might be able to fix with current technology
@Jotaro Kujo Somif I sent you a code written in Python, and you wrote a code that does the same things in Java or C+, is that version control? Or did I get something wrong?
O_O That would actually be a huge problem. If half of your genes had all their stop codons swapped out and the redundant tRNA reassigned, but the other half didn't.... Well, you'd die.
I mean, sure if we're talking about people. Do we really need redundancy for our protein producing bacteria though? It's not a huge deal if they die occasionally.
I learned that from watching videos about plan crashes. They often happen because multiple things failed because there's so much redundancy built into planes.
if we're just using it for bacteria, I don't see much harm. At worst, the bacteria will die, but scientists can always create more in the lab. Not a bad trade given increased versatility of its genetic code and bacterial immunity to bacteriophages.
@@HolyBlokes I kind of knew that but looked up both adjectives because of your response. Thanks! I hope you don't get too much flak for insisting on proper grammar because some of us do want to keep learning, improving.
"The Genetic Code Sucks. Let’s Do Better" That is one of the most ominous sounding lines ever if it were said in some kind of horror or sci-fi movie...
@@Redmilksteak Yeah, thank god we arent. Next time just say "i dont understand how genes or vaccines work". Less time for you to write, less time for us to read.
@@Redmilksteak Oh, damn, was that a virus thing? I'd been about to give you the benefit of the doubt, assume you were talking about the dangers of experimenting with technologies we barely understand. Thought maybe you were going to talk about the CRISPR gene drive we considered using in mosquitos or the human genome editing that happened in China. You know, valid concerns. But damn it all, if you don't understand that mRNA vaccines physically cannot change our DNA, then why are you here?
ah yes, I can't wait for the children of a hundred years from now to have comment-DNA with written apologies from the scientists explaining why they absolutely had to keep the appendix 2.0 because for some reason everything broke if they removed it
@@Ithirahad Heh, we might end up with comments that have some accidental function in the non-coding sections. Imagine that, code that breaks if you remove the comments
Some of those redundancies may affect how proteins are folded when being created from RNA. Since transcription is a physical process if AAA and AAU coded to the same amino acid, the A vs U at the end of a codon may correspond to a different electric/thermal/mechanical state in the amino acid causing it to turn or twist differently while the chain is being created and thus fold differently
@@user-dv7eu4wg6g the shape in witch is folded in changed, but this is a complicated topic, because DNA is connected to special protein that force it to fold in specific ways, so normal double strain DNA isn't folded by itself, but some portion that are single strain are doing exactly that and forms some kind of knobs called motif(this is a recent discovery that gets all the news) , also RNA that is normally single stain need to fold in a specific way to play a functional role in the ribosome and is coded directly by DNA .
@@user-dv7eu4wg6g The transcription process is ultimately a mechanical and a chemical (and electrical) process. Chemical bonds between atoms involve the movement of electrons which changes their electrical properties, which affects how they behave mechanically. Water, for example, has the electrons normally around the hydrogen atoms spending a great deal of their time with the oxygen atom instead, giving the hydrogen atoms a net positive charge due to their proton. This positive charge can attract or repel molecules with the opposite or same charge. tRNA is a gobetween for RNA and the amino acids, and a different codon for the same tRNA coding to an amino acid may attach the same amino acid but end with minor differences in temperature/momentum on the end product of the amino acid chain. I'm not saying that it definitely alters protein folding, only that it may be possible. Here's a video of the process. All of the molecules are "soft" and so small mechanical stresses transfer throughout pretty easily. ua-cam.com/video/gG7uCskUOrA/v-deo.html There's 1 inaccuracy in the video, at least some proteins will actually begin folding before the amino acid chain is complete, in this case it can be affected by actions in and around the ribosome
If I understand correctly, that's why the researchers select biased codons with low frequency, ones that the cells normally only use under high stress conditions when the normal tRNAs for that amino acid are depleted. It still has an effect, but it's minimized by recoding codons that the organism usually doesn't use, such as rare stop codons
In a way its kind of funny. Its like a robber going to lockpick a door. He sticks a pick in, and then a mousetrap goes off. Why the hell is the lock a mousetrap? How does the door even lock? What is he even supposed to do about it? Come back with a mouse?
Which might be bad too, as from what I'm understanding is viruses have been silent influencers of evolution form millions of years We only focus on sickness when it comes to viruses but don't see the scope how they essentially mix around code all throughout the ecosystem
As someone who spent a good chunk of their undergrad trying to get a bunch of cells to express our protein, this was a fantastic explanation for those who are not quite as well versed in biochemistry
Surely it’s tricky to rewrite genetic code to free up redundant codons, cos what if the cell in question has functional genes on both DNA strands such that two genes overlap, but run on opposite strands. The stop codon on one gene, when read in reverse might actually be useful for the other gene, and changing to a different stop codon might completely break it
YES! Exacly a problem that has to be dealt with by basically pulling the genes apart by slightly different methods and then recoding the offending codons, this usually works in the cases I have seen with little issue.
@@mattabesta would this be due to an issue during DNA replication, since both strands are being copied? Then the template strand would be replicated and the daughter cell would have the normal codons?
Well, it might be if you have quadruple redundancy. I mean, there are plenty more things we could do with a new assignment for a sequence. Personally, I'd like to be able to change my skin color at will. Wouldn't that be handy!
Certain types of redundancy are unnecessary specially when dealing with bounded finite automatas such as DNA which have markers in both ends of any word.
Exactly! I raised that point with my wife, but she didn't seem too happy with the whole polygamy thing. As a counter proposal, I said I was willing to try polyandry because I couldn't stand dealing with her full time... On an unrelated note, does anyone have a spare couch I can crash on?
The way this video relays quite complex findings and research to easily understandable explanations is awesome ! And the editing is so enjoyable and adds to it.
It's not even a joke. That's exactly why we want redundancy in our DNA. There are other organisms that are super hardy extremophiles and the main thing that makes them that way is the way they have redundant copies of DNA that act as self-repair mechanisms in case of accruing damage to other parts.
Removing redundancy seems dangerous, I mean its fine on bacteria and lab mice i guess since they are already genetic freaks but anything that has to live subjected to nature will need that redundancy...things like people, or food. I don't know how many stop codons are needed, but I know evolution has been working on it a lot longer than us.
I think you’re right that removing redundancy is probably a bad idea but also, mutations are completely random so the way that the genetic code is situated isn’t necessary the most effective way so it might be interesting to explore other versions but we should probably stick to e. Coli, at least for now lol
@@eoz27 we can always have obsessive version control (if for whatever reason any of the redundancies are false, then toss it and restore a previous version or majority version of the same thing) most likely case is it goes right (with enough redundancies) or goes really really wrong by accidentally making something that is extremely difficult to change (or even worse, completely nukes the body if enough change at once)
I think the point is that the results _won't_ be living in nature. As I understand it, the practical applications for this are for lab-grown organisms (like bacteria) that stay in specialized locations specifically created to facilitate their survival and function in order to serve whatever purpose they were designed for, like producing medical substances or some kind of industrial reactant or whatever. I think food would be left to unmodified DNA, even if growing it ends up being through cultures or 3D printing.
It was a pretty deep dive! Let's keep diving deep! I like it! The bite sized snippets you guys offer are great too, but sometimes some details go a long way.
There is another layer of imbedded information in terms of "codon pair bias" or codon context where combinations of adjacent codons don't follow expected frequencies.
Yea, and the researchers pick codons that have low expression frequency and target those for recoding. Super cool research but man, I wouldn't want to be the one changing the codons
@@Luminarada80 it can be done by hand but is usually done by computer (it can be done in R). What is more complex is keeping the codon frequency but changing how the codons are paired with each other.
There is either currently or in the near future a bacteria that can turn everything else on earth into non-specific organic soup just waiting for the wrong container to be dropped. It's not malice and weapons that will do us in it's lack of planning and clumsiness.
Am I only the one who heard "immune to viruses", immediately thought of viral antibacterial treatments and got terrified in light of all the issues we having with antibiotics?
@@TeddyLucia1006 Superbugs aka antibiotic resistant bacteria. If we were forced to resort to antibacterial viral medication, we wouldn't want bacteria to gain antiviral resistance either.
This is like self driven evolution, like not in the natural spontaneous mutation but rather we can choose the mutation for us and which direction we can drive ourselves into. This is amazing and has so many potential. I'm so hooked in this. Thanks for this episode guys.
@adamklam1 Just see what happens when the billionaires no longer need the working class. Farmers don't keep their animals around once they're no longer useful.
At first it'll be billionaires but as soon as it becomes possible at all, the costs would gradually reduce until all developed countries except America provides it as something basic. Also, things like Alzheimer's research isn't exactly for any particular person but simply benefits everyone, as it is science, which is normally done in the open.
@@cultofcaster9219 they don't directly control the government tho...? And since they are billionaires, they'd want to sell it to get even richer... overall it would probably be a good think
If someone were to write molecular biology fanfiction, I might not read it all the way through, but I would at least be curious enough to take a quick look at it.
It's saddening that the alarmist comments garner the most likes. Whether it be algorithm favorising negativity, society's recent (unjustified) disenchantment with science, or both. That's why I love seeing so many comments being simply thrilled by this knowledge. Even if they don't get much attention, they mean a lot
I'm pretty leery of any scientific notion of "redundancy" regarding genetics. It feels like a dangerous assumption to make in the face of something so complex. If we actually manage to create coherent organized life - from scratch - out of a primordial ooze, I'll feel less ambivalent.
I don't think it's an assumption when you know exactly what each codon does. However on a larger scale, such as redundancy of genes, yeah I don't want them assuming that has no purpose
In this case "reduntant" is merely a description of their ability to code for an amino acid, not a desctription of functional redundancy. Recoded organisms are generally less fit than their background, these effects are usually suprisingly small but plently large enough to explain the evolution of redundancy.
@@mattabesta Yes, exactly; I realized that after having already posted the comment halfway through the presentation, but decided to let it stay. In fact the chemistry/physics and maddening complexity of genetics totally defy my comprehension; it strikes me more like engineered high technology than something that just accidentally happened to emerge from the cauldron of Deep Time. Personally, I'm still unwilling to rule-out the (intellectually "un-cool") ET hypothesis; that this back-water planet from time to time has been used as a lab of sorts, perhaps for various Intelligences outside of humanity, messing around.
@@midplanewanderer9507 One shouldn't rule out hypotheses like that, since we have no way of proving or disproving them at this moment - we can only deduce the likelihood as we understand it. Of course, that would mean that the hypothetical other intelligent life forms would also have to have come from somewhere, so they either evolved out of random chemical jumbling or were also created from recursive cases of lifeforms doing experiments on planets while coming from similar experiments themselves. An interesting thought experiment.
Its already done prizer biotech labs Its mainstream rollout is the covid mRNA vaccine. Y do y think we r having the vaccine shoved down our throats? Its the same 50% of people r flat out refusing it
That's exactly what I was imagining the whole time. The cheery tone + potentially apocalyptic content fits neatly in the intro of a post-apocalypse comedy movie.
@@justinblake420 curious that everyone I know that works in biotech has taken it. If the people working in the field aren't concerned about it, why are you?
Thank you for this detailed review! It's amazing what we can achieve with modern genetic engineering techniques, so I hope we will continue to use these techniques respectfully. As a molecular biologist myself I would like to add that changing amino acids also helps in unraveling the functions of proteins in other ways. Many amino acids can be modified post-translationally, e.g. by phosphorylation of an amino acid. This can greatly impact overall protein function. So in research we often use special amino acids, which are e.g. constitutively phosphorylated, to investigate how phosphorylation in specific protein regions alters protein activity, substrate specificity etc. :)
Im impressed by how much information was shared in such a short of amount of time in this video. It was easy to understand and I learned new things as well as being reminded of things I haven't thought about since I was in school. This is why I love sci show
I must admit that most of that was over my head but I understood enough to know that the technology can be used in dangerous ways. Knowing how violent and destruction the human race can be, I find this to be scary.
This particular aspect of genetic engineering / molecular biology would be difficult to use destructively. It takes a lot of work, and a lot of precision, to engineer an organism to use a new amino acid in its proteins. It takes even more work beyond that to design a protein that uses the new amino acid to provide some useful function. And since you are sitting there, with your unmodified genetic sequence and cannon set of amino acids, none of that can affect you directly. Your body would not recognize or use a new amino acid. For now, it's a research curiosity. In a decade or two, we might engineer a bacteria with a new protein using a new amino acid that can easily break down plastics. But using this in humans? Oof, that would be difficult. You'd basically have to rebuild the entire genetic code from scratch. Because of that, we're still a very long way off. It's far more difficult than it would be in an E. coli On the other hand....what you could do is engineer a super bacteria. Course, it's not clear what advantage you'd get by introducing codons for new amino acids into its DNA---it'd probably be easier to keep its standard genetic code---but I'm sure we could figure something out. But on the flip side, we could also engineer bacteria (or fungus, or whatever) to produce brand new antibiotics that could kill the engineered super bacteria. Crazy stuff, but it probably evens out in the end.
That's EVERY technology, ever. Did you know that in 2021 the State of Texas publicly demonstrated the potential ability to kill a bunch of US citizens in their own homes by remotely turning off their AC units in the middle of a heat wave? Their intention was to protect the power grid, which is a pretty reasonable goal given the recent collapse it went through in the previous winter, but it produced such a big backlash that customers are fleeing away from green energy solutions like smart meters and thermostats.
The ideas behind eugenics have been around since plant and animal breeding was developed. Defining "superior" humans, though, has always, in the past, depended on personal prejudices, and religious and political opinions, and has mainly been promoted by people (it seems to me) with genocidal tendencies who are too prepared to treat other humans as domestic animals. But now, if you say "we can reprogram everyone's kids to have clearer eyesight, and see more wavelengths of light" - that seems to bypass the evils, and the assumptions, of eugenics and to be working towards actual improved humans. I can't think of any group who doesn't want better eyesight. Or better cell oxygenation. Or knee joints that are functional and pain free all of one's life. Or strong feet that stay healthy for a lifetime. Some religious folks will claim that genetic re-design is usurping their favorite deity's job, but they always have "revelations" eventually that let them change their theology to take advantage of scientific advances. Priests and popes and preachers originally claimed that lightning rods thwarted God's smiting of the wicked, and were blasphemous. And now, of course, churches and other religious buildings are routinely spiked with lightning rods - too many preachers and bell ringers got fried, and lightning rods obviously worked, so they quietly changed their theology.
Sure could -- it'd be a lot of work though. Each codon needs its own tRNA and amino acid, and if any two codons are too similar to each other, they might bind to the wrong tRNA
First he says there's a LOT of redundancy using 4 letter DNA (4^3=64) and THEN goes off on a tangent about 6 letter (6^3=216) and 8 letter (8^3=512) DNA, to make it even MORE redundant? WTF?
Yea that's the nice thing about adding nucleotides, but it's way harder right now. The cells REALLY don't like incorporating the synthetic nucleotides into their genome, and cut it out whenever possible. The researchers that got it to work had to constantly add the synthetic nucleotides, always have CRISPR present for the sequence to prevent the cells from cutting out the nucleotides when dividing, and add phosphate buffers because the phosphatases kept degrading the nucleotides (I'm a little hazy on the phosphatase part but I think that's what they were doing). And that was after adding the nucleotides to a single locus on the genome. Both methods require a ton of work, but adding nucleotides is orders of magnitude more difficult right now compared to using existing codons
this is helpful for people who have genetic disorders that prevents them from synthesizing certain amino acids. its good for curing diseases, it can also be used to develop immunity against certain toxins. looks promising , you could also modify it so that humans could survive better in harsh environments.
Hank, I'm so disappointed you didn't mention my favorite piece of microbiology jargon: CODON WOBBLE. Codon wobble is when the third nucleotide in a codon allows for so-called non-watson-crick base pairing. This is when A's bind with not T's and G's bind with not C's and vice versa. Codon wobble allows for mistakes to happen in mRNA synthesis and still result in a correct amino acid sequence in the resulting protein.
+SciShow The one thing that I am left wondering is; while I know that geneticists can “read the letters” just how well can geneticists “read the words that those letters spell” sort of speak…and if they do know what certain things in DNA actually do then what are a few examples of how they actually learned about those things and what they actually do?
The words those letters spell are genes which translate to proteins. Using the genetic code, geneticists can know exactly which sequence of amino acids compose the gene, but the current challenge is knowing how this sequence folds to make the end product. There's recent developments in this field with artificial intelligence, there's another video on that. It should be mentioned that this goes for coding dna, it was discovered that what we previously called "junk dna" is actually useful (I don't know more about this though)
3:14 . . . Spoiler Alert : *Real Life Forms* need redundant genetic coding to combat 2nd Law of Thermodynamics (at least locally) ! . . . e.g. corruption of vital information after copies are made.
Yea it makes nonsilent mutations way more likely. It's mainly a proof of concept right now, but will be used mainly for creating virus resistant bacteria that can produce new proteins for medical and industrial processes
Knowing viruses, its not an immunity. Its just a roadblock. Eventually you'll get a virus that will mutate just the right way to take advantage of the code again. But it would likely be 100% effective in the short term.
But for that whole your code must be rewritten. After that the only problems will be: bacteria, fungus, parasites and so on. Only being completely made of steel will eliminate most of that problems.
@@Sheen023 Short(ish) answer: quantum number eigenstates that make up (our knowledge about*) all matter Long answer: en.wikipedia.org/wiki/Field_(physics)#Quantum_fields en.wikipedia.org/wiki/Quantum_field_theory#Further_reading *Joke works cuz many people feel like regarding 'em as matter itself, which yours truly thinks is mystical mumbo-jumbo
This could be used to engineer dna in a way to eliminate over or under production of certain things that are common day problems like scurvy for lacking vitamin c, preventing certain disease from replicating and advancing and other things. Here's hoping it continues
Yeeesssss, but this is probably the least efficient way to go about those goals you described. We can solve those problems with regular old genetic editing and protein design. Molecular Biology is going to be able to cure every disease known to man within a century. Editing the genetic code to accept new codons is only useful if we want to build proteins containing new amino acids. We still have near infinite potential just working with the 20 cannon amino acids (after all, they are what built your entire body, every organ, every cellular pathway, every neuron, and every white blood cell) -- reengineering the entire genetic code is only worthwhile if there is very specific we were trying to accomplish. For now, the latest and greatest thing to get excited about is Google's AlphaFold 2 -- it's doing an incredible job tackling the protein folding prediction
@@tomc.5704 This kind of thinking accomplishes very little, breakthroughs happen because someone decides to go down the "least efficient" paths while the majority of us try to break our heads on a ceiling
@@Thros1 I'm....not sure that's even correct. I'd happily agree that many breakthroughs happen when someone tries something new, but I can't think of a single time off the top of my head when a breakthrough happened by someone going down the least efficient path. I'm sure it's happened, but I'd wager it accounts for at most 5% of breakthroughs. Heck, someone saying "I think there's an easier way" is probably responsible for more breakthroughs. And in this case, re-engineering the entire genome is more of a "next step" anyways. First we have to be able to edit the genome, then we have to be able to design custom proteins, then we need a complete understanding of our entire genetic and biological system, and _then_ we will have the tools to introduce proteins that utilize new amino acids. Not that it's stopped us from playing with the idea early; we've already made a few synthetic / custom engineered bacteria. We could probably use this to introduce a protein that could digest plastic ...... if we were able to design custom proteins to fulfil a function. See step 2 in the above paragraph.
Never underestimate your entertainment abilities, hank. I truly can’t grasp what you’re talking about at all, but I still watched and enjoyed the entire video :)
@@fennajarina Yeah they edited it diligently to be quite fast-paced. Anyway, think of the genetic code in transfer RNA as a to-do list, with mini instructions in groups of three. Each time a little manufacturer takes a trio of instructions, it brings the appropriate component to the assembly line (or terminates the current assembly if the three instructions correspond to a halt). We might be able to add alternate instructions at the beginning (beyond the usual four) or make a particular grouping of three of them ask the manufacturer to bring a different component to the assembly line, even a specially designed one.
My only concern is that there are some very large superstitious groups who will be strongly against this, having been convinced that we are "perfect" in all ways. Stem cell research is about 10 years behind because of those people, and I would hate to see that happen again.
@@sewpungyow5154 It would start w/ my Denial of the Presumption that "Science has all the Answers". The hubris wee humans continue to display w/ this admittedly powerful tool called "Science" only continues to show how very Ignorant wee all are of so very much. I'm not against Science--far from it. But Humans tinkering & continuing to FAIL on so many fronts w/ things like Organic, Chaotic Systems like Biomes & Forest Recovery, as stated above, makes me firmly believe we should slow down on all this "Progress."
Keep in mind that all of this is inside of living bacterial cells. There are also labs that work with a purified mix of all protein translation components in vitro and they can make ribosomes produce some very crazy stuff, so for a chemistry point of view this is just the beginning.
As an engineer...I don't know about this. Redundancies are there for a reason. Networks are redundant, roads are redundant, and water infrastructure is redundant. In the human body, we have redundant lungs and kidneys. Should we really mess with 4 billion years of evolution, especially without knowing completely how things work?
Genetic code has not been designed, so I am not sure your concern applies here. Life as we know it is patch over patch over patch, so, the closest thing an engineer could say about is: if it works, don't touch it. But that doesn't apply to a refactor, does it?
That's exactly how nature has done this during the last couple billion years.. throw it at the wall and see what sticks.. still does it like that. In that sense we're far more organized and goal oriented. But even then.. if you zoom out you could even add the scientific approach of 'understanding and testing molecular biology theory' to the 'throw it at the wall and see if it sticks' pile.. the timescales are huge and we make ourselves no picture of it. What are 10.000 or 100.000 years for nature? Nothing. And how important are humans in the big picture of things. Irrelevant.
That’s is so awesome buddy! When the body building community get hold of this , that’s big bucks generated ! For companies and R&D development of new products.
genetic code doesn't know anything since it's not sentient. The reason it works, some of the times, is due to survival biased selection among trillions and trillions of iterations.
@@vladimirseven777 Not really. 99.99% of the species are extinct. And even in your own species, it's full of errors (cancer, genetic diseases) and abortions (failed attempts to create life). Don't get started with prions (badly folded aminoacids) If you believe the current genetic code is that good, you are probably victim of the survivor bias.
@@BlueFrenzy that's a huge oversimplification of half dozen mass extinction events. And to say it's ineffective code because lifeforms eventually die and aren't immortal is also silly argument
This is one I'm going to have to watch a few times to follow all the twists and turns, but it is going to be fun like so many of your wonderful videos.
“ your scientists were so preoccupied with if they could, they never stopped to ask if they should!” Some guy in the year 2103 after the bio engineered mole people have enslaved humanity.
This is cool, i wonder how quantum computer will speed this stuff up, as simulating protien interactions could make it possible to quickly prototype this process.
As someone acquaintanced with haemophilia, I can tell how crucial redundancy is in certain cases. Women do not get haemophilia due to redundancy. Men don’t have that luck though
So basically, we know how to type out a genetic document, we just need to figure out how to make the genetic ink cartridges and genetic printer head so the genetic document prints correctly
"Damn, that's an interesting concept, I hope people with very little understanding of biology don't come to stupid conclusions" Sometimes I think comment sections are a mistake
Even when some people understand perfectly, they have a moral panic over dna engineering... We've modified species' dna for millenia through domestication. So we're not doing a different thing, we're doing the same thing differently. And no, we're not gonna apply it to us or our food before extensively researching the side effects
I'm impressed at how much precise, careful change we can exert on things that are microscopic.
What is even more amazing is how many parts of the process aren't fully understood yet, but still work.
Well said
Even crazier is quantum level computer design
It's crazy. I spent some time in a lab as an undergrad, they had a machine called a flow cytometer. It could identify phosphorescent markers and sort individual cells.
It sorted cells individually, 10000 per second.
That was just the start -- they had the yeast cells express a custom protein on their surface that was supposed to bind to an influenza spike protein. They attached the phosphorescent marker to the influenza spike protein. They were able to sort the cells, keep all of the ones that bound to the spike protein, and then run them through a second generation sequencer (one of Illumina's machines, I think). THAT gave them an accurate count of each genetic sequence that had bound to the influenza.
Take the most successful genetic sequences, mutate them ten thousand different ways (using Rosetta protein folding models), order the new 10,000 DNA sequences on a chip, insert that DNA into plasmids, transform the plasmids into new yeast cells, and run the second generation of designs through the flow cytometer.
Couple more generations, and they have designs that (when expressed on the surface of a yeast cell) bind to the influenza spike protein (though not necessarily in the desired location).
Crazy stuff. New stuff. Unimaginable 25 years ago.
@@tomc.5704 Wow. That is crazy!
I'm impressed that we still don't fully understand things like nutrition but we are already contemplating rewriting human genomes
Cool, I worked on a genetic code expansion project in undergrad where we repurposed the UAG stop codon (also called the amber stop codon) to express proteins with non-canonical amino acids. The nice thing about using stop codons for repurposing is that it’s easy to know if you were successful because if it didn’t work, you just get a truncated short protein which is easy to identify. Also, the UAG stop codon is the least used in nature so it’s the low hanging fruit for repurposing. From what I understand the proposed uses are for making novel biological medicines, industrial purposes (things like fermentation or maybe nitrogen fixation), and to study enzyme structure/function in the lab. I’m no expert but it was a fun project.
Sweet! Has this been used to engineer proteins that carry toxic agents (such as radionuclides) to tumors or other diseases? Or to make enzymes that can repair damage?
@@coopergates9680 not yet
Perfect description!
You must be pretty lucky working on such a futuristic concept, that too in undergrad.
All I did in biotechnology undergrad was preparing media, make some yoghurt, and make a ball-and-stick model for proteins. 😢
spits half of genetic theory and says i am no expert lmao
As a programmer my brain immediately lights up and goes "FOR GODSAKE NEVER EVER REMOVE REDUNDANCY".
It's not really a good redundant setup though. More like someone set up a jump-table sprinkled with multiple jumps to the same target. Having just one valid encoding of each protein and point the extra ones to STOP would be a good start at improvement that kills of mutations and badly non-compatible viruses.
@@v4lgrind There are way too many things we still don't know about about genes. A few years ago we thought transposons don't do anything because they don't code for anything. Now we know that removing it, causes an organism's immunity to be compromised. Plus, the multiple jumps on the same target might not be such a bad thing. Different cellular conditions might need the genetic sequence to be transcribed at different instances.
We should wait half a century before we reconsider this
Congratulations! You just found out where evolution comes from! I know, let's kill evolution and take over the process ourselves.
@@v4lgrind Maybe. Specification and Precision are things to aim for in design. But the organism and target/item must be more compatible, no? Since the control it would give in biological entities may be ineffective due to the chaos of the world.
As was said in the video, the bacteria were immune to certain viruses, but the virus proteins were just there. I would think the bacteria may have dissolved some of them, but a perfect entity in an imperfect world may be the problem.
@@rephaelreyes8552 Heh, half a century is probably accurate as far as approximate timelines go
In the mean time, I'm all for experimenting on mice and e. coli
Considering Veritasium's new video on ionizing radiation, I think I'm quite happy with my redundancy. No bit flips here, thank you.
That’s actually really smart. With more redundancy I feel like cancer and cell death can be prevented. If anything, adding more redundancy can be good. If we were to do the whole gmo humans thing.
Was thinking about that as well
@@itsyurmumm8458 Prevented? No, not really. But I'd bet good money that the redundancy does provide some cancer resistance. If CAG and CAA are the same amino acid, then when a mutation occurs there's a 33% chance nothing changes.
(....technically, my math is wrong there, but whatever, the point stands)
But I don't think there's any way to build the system to prevent it altogether. Even if you could absorb a mutation in any spot, that mutation still happens, that spot is now vulnerable, and is passed on to the next generation.
@@tomc.5704 Yeah definitely, I was just trying to elaborate in basic terms.
We could actually create genetic error-correction theoretically, the same way that error correction is done on critical computers. All you need to do is make sure that any single base pair flip is closer to an existing codon. Then we could create cellular machinery that fixes the codon if a base pair changes. This would allow you to create genetic error correction. However, this would not be able to "cure cancer" in an already living person, as the person would need to be genetically engineered to have this genetic error correction.
It's a shame that nature never figured out how to include a checksum on the mRNA.
Unironically tho. It would fix everything, ain't no virus in checksum land.
No evolution, either, though
@@Urammar Speaking of mRNA as it evolved as a system to decouple transcription and translation did you know that only Eukaryotes and Viruses use/have mRNA which is used as a pass code for RNA sequences to be allowed through the Nucleolus and Viral replication factory respectively. (One of the lines of evidence that led to the Viral Eukaryogenesis hypothesis So while adding an mRNA checksum would fix Eukaryotes and Viruses it would have absolutely no effect on Bacteria and Archaea which would be able to continue to evolve freely.
As such the ultimate result would be a world where Bacteria and Archaea run unchecked as viruses couldn't stop them and Eukaryotes couldn't adapt either eventually leaving us all immunocompromised as pathogens continue to evolve while we don't. That is frankly terrifying....
Damn, if scientists can make ribosomes with CRC we can basically eradicate cancer and any other mutation related disease (but also evolution would slow down, but maybe we will be to control it this way)
maybe scientists can one day fix that.
@@Dragrath1 I'm not sure I understand? Or maybe you don't? One of us certainly doesn't.
Bacterial infections would still be fought in the body as normal, but anything that makes use of DNA/RNA would break instantly.
Thats virus replication, cancer, anything like that. Its 100% correct, human code, or it ain't replicating.
This change wouldn't extend to nature at large, so it just means humans only have to fight bacteria, and only some at that, and everything else can bit my shiny science hiny.
Virus matter would still exist in nature, and cancer, and a bunch of other stuff, it just wouldn't effect humans at all.
Geneticist 1: I've successfully engineered this bacteria to read its DNA backwards!!!
Geneticist 2: AND?
geneticist 1: the bacteria's dead
Zlol.
Lol took me a second
"Inside-out Zergling. . . . not efficient"
That took me two takes. One take too long IMO.
"Why does my experiment have 2 noses and 1 eye?"
"You missed a 'stop' here"
Yup, as someone who took many years of programming, I could see this happening =p
you have an infinity loop here and you made a blob of ever growing mass
@@oldcowbb lol, "Akira!"
Indeed. Beware the missing semicolon.
@@oldcowbb Too late: immortal cancer cells already exist (HeLa).
As every programmer knows, "off by one" qualifies as "correct"
"Junk" DNA that doesn't code for anything might act as a "cancer buffer": since a lot of it can be disrupted without damaging active processes, it might be an "advantage" when it comes to resisting ionizing radiation or other DNA disruptors.
Sure, but in this video Hank is specifically describing genes that are expressed and repurposing redundant codons into new ones.
@@evanhughes9576 Redundant codons have been found to have uses. Strengthening the effects of a codon, or taking over if an identical codon is damaged, for example. This is amazing technology, but we need to be quite careful what we tinker with, and be able to undo edits we make, just in case, before we start using it actively. Of course, you would HOPE that scientific professionals would understand that. I'm all for editing out genetic diseases, and we know enough to at least start doing that now. Wish I was born about 500 years in the future, this "ageing" thing sucks, and by then we might be doing something about it...
but actually, less dna - less chance of disruption or mutation, so it is not as good for that purpose
@@mcchuggernaut9378 we already should be doing something about aging. Aging is like cancer, there is not a single cause, there are plenty of things going wrong, and some of them we might be able to fix with current technology
This video is not about junk DNA, it's about the specific parts that we already know code for proteins, codons.
Any competent engineer isn't going to remove redundancy, and competent software developer isn't going to mess with your version control.
What’s version control? I’m not a programmer
@Jotaro Kujo Somif I sent you a code written in Python, and you wrote a code that does the same things in Java or C+, is that version control? Or did I get something wrong?
@@__Brandon__ I see what you did there, *on steroids*
@@__Brandon__ thank you
Smart redundancy, not this disorderly style
Imagine trying to find a girlfriend if your genetic code is reprogrammed. "Sorry we can't have kids, I'm on DNA version 2.3, but I glow in the dark!"
Realistically you just send your genes in to be sequenced and translated to her version, then do the whole test-tube baby thing.
O_O
That would actually be a huge problem. If half of your genes had all their stop codons swapped out and the redundant tRNA reassigned, but the other half didn't....
Well, you'd die.
No need for that. All you'd need is some Green Florescent Protein gene CRISPR'd into your cells.
Technically we're all bioluminescent only we glow in infrared light.
Very useful for CIA and other alphabet bois
If Star Trek taught me anything (besides not wearing a Red shirt durring away missions) it's redundant systems are there for a reason!
@@sewpungyow5154 hahahaha
I was looking for a comment like this lol
I mean, sure if we're talking about people. Do we really need redundancy for our protein producing bacteria though? It's not a huge deal if they die occasionally.
I learned that from watching videos about plan crashes. They often happen because multiple things failed because there's so much redundancy built into planes.
if we're just using it for bacteria, I don't see much harm. At worst, the bacteria will die, but scientists can always create more in the lab. Not a bad trade given increased versatility of its genetic code and bacterial immunity to bacteriophages.
Our codons, straight from the Department of Redundancy Department.
I see what you did there 😂
;)
Let's not forget the Redundancy Department of Redundancy!
this is repetitive not redundant
@@HolyBlokes I kind of knew that but looked up both adjectives because of your response. Thanks! I hope you don't get too much flak for insisting on proper grammar because some of us do want to keep learning, improving.
"The Genetic Code Sucks. Let’s Do Better"
That is one of the most ominous sounding lines ever if it were said in some kind of horror or sci-fi movie...
Pretty sure we are living in some sort of sci-fi horror movie tbf
Eugenics! Jeeez, good thing we aren’t doing a reckless half cocked roll out of this technology on a global scale as we speak eh?
@@Redmilksteak yes, good thing that we aren't. Now go away and take your conspiracies with you.
@@Redmilksteak Yeah, thank god we arent. Next time just say "i dont understand how genes or vaccines work". Less time for you to write, less time for us to read.
@@Redmilksteak Oh, damn, was that a virus thing? I'd been about to give you the benefit of the doubt, assume you were talking about the dangers of experimenting with technologies we barely understand. Thought maybe you were going to talk about the CRISPR gene drive we considered using in mosquitos or the human genome editing that happened in China. You know, valid concerns.
But damn it all, if you don't understand that mRNA vaccines physically cannot change our DNA, then why are you here?
Hank: "What would you do with a rewritten genetic code?"
Me: "Unicorns and cat women, Hank. Unicorns and cat women."
😂
affirmative
Indeed.
As a programmer, if you leave humans to change your dna, YOU'RE GOING TO GET AN ERROR
that why i want an AI to change my dna not a human.
@@faliennata5350 Ai's make similar errors
Molecular biology fan fiction, huh? There's a sentence I never thought I'd hear.
Yes, isn't it cute -- he sees the word "canonical" and thinks we'd think of a TV series. Some of us know its wider application.
Scientists, pick your favourite ships now.
I always knew i was degenerate, but now i know that my DNA proves it
Same, bro. Same. 🙃
hear, hear!
When you start recoding DNA, you might want to reserve codons for marking comments, similar to "/*" and "*/" in C#.
ah yes, I can't wait for the children of a hundred years from now to have comment-DNA with written apologies from the scientists explaining why they absolutely had to keep the appendix 2.0 because for some reason everything broke if they removed it
You can just do 'comments' between stops and starts (AUG). They might have some subtle effects, but they won't be directly read.
@@Ithirahad Heh, we might end up with comments that have some accidental function in the non-coding sections. Imagine that, code that breaks if you remove the comments
Introns are comments
Some of those redundancies may affect how proteins are folded when being created from RNA. Since transcription is a physical process if AAA and AAU coded to the same amino acid, the A vs U at the end of a codon may correspond to a different electric/thermal/mechanical state in the amino acid causing it to turn or twist differently while the chain is being created and thus fold differently
That’s really interesting, how does a difference in the code affects the state of the amino acid?
@@user-dv7eu4wg6g the shape in witch is folded in changed, but this is a complicated topic, because DNA is connected to special protein that force it to fold in specific ways, so normal double strain DNA isn't folded by itself, but some portion that are single strain are doing exactly that and forms some kind of knobs called motif(this is a recent discovery that gets all the news) , also RNA that is normally single stain need to fold in a specific way to play a functional role in the ribosome and is coded directly by DNA .
@@user-dv7eu4wg6g The transcription process is ultimately a mechanical and a chemical (and electrical) process. Chemical bonds between atoms involve the movement of electrons which changes their electrical properties, which affects how they behave mechanically. Water, for example, has the electrons normally around the hydrogen atoms spending a great deal of their time with the oxygen atom instead, giving the hydrogen atoms a net positive charge due to their proton. This positive charge can attract or repel molecules with the opposite or same charge.
tRNA is a gobetween for RNA and the amino acids, and a different codon for the same tRNA coding to an amino acid may attach the same amino acid but end with minor differences in temperature/momentum on the end product of the amino acid chain. I'm not saying that it definitely alters protein folding, only that it may be possible.
Here's a video of the process. All of the molecules are "soft" and so small mechanical stresses transfer throughout pretty easily. ua-cam.com/video/gG7uCskUOrA/v-deo.html
There's 1 inaccuracy in the video, at least some proteins will actually begin folding before the amino acid chain is complete, in this case it can be affected by actions in and around the ribosome
If I understand correctly, that's why the researchers select biased codons with low frequency, ones that the cells normally only use under high stress conditions when the normal tRNAs for that amino acid are depleted. It still has an effect, but it's minimized by recoding codons that the organism usually doesn't use, such as rare stop codons
As a person who is now trying to enter synthetic biology, this is an amazing introductory video. I am mind blown.
I now need to find a way to put “molecular biology fan fiction” in my resume
Decades later, famous molecular biologists would be humiliated when the non-canonical proteins they created as grad students came to light.
This means I can Rewrite the genetic code of some ppl and turn tem back into Gorrilas
@@PhysicsOfParkour return to monke
As a scientist working in this field, I'm stealing this phrase, this was now my idea.
@@tom4ivo and that’s how I met you mother 🤣🤣🤣🤣
While it makes sense, it's still absolutely incredible that reprogramming the genetic code has the potential to completely incapacitate viruses
just wait until a virus figures out how to mutate and take advantage of it all over again. :P
@@halyoalex8942 Uh oh
@@halyoalex8942 Well HIV kinda did…..even before the Simpsons
In a way its kind of funny. Its like a robber going to lockpick a door. He sticks a pick in, and then a mousetrap goes off. Why the hell is the lock a mousetrap? How does the door even lock? What is he even supposed to do about it? Come back with a mouse?
Which might be bad too, as from what I'm understanding is viruses have been silent influencers of evolution form millions of years
We only focus on sickness when it comes to viruses but don't see the scope how they essentially mix around code all throughout the ecosystem
I'm sure this will end well.
I can 😸 taste the sarcasm
@@navjeetsingh8447 agreed it would end in disaster. As usual humans seem to think they are smarter than nature or God
Yeah, as gleeful as this video is, it's most likely the introduction to a horror story.
@@donnacsuti4980 God's not that smart if you look at the world.
As a molecular biologist, this was a very well done summary of synthetic biology. Great work!
As someone who spent a good chunk of their undergrad trying to get a bunch of cells to express our protein, this was a fantastic explanation for those who are not quite as well versed in biochemistry
Surely it’s tricky to rewrite genetic code to free up redundant codons, cos what if the cell in question has functional genes on both DNA strands such that two genes overlap, but run on opposite strands. The stop codon on one gene, when read in reverse might actually be useful for the other gene, and changing to a different stop codon might completely break it
YES! Exacly a problem that has to be dealt with by basically pulling the genes apart by slightly different methods and then recoding the offending codons, this usually works in the cases I have seen with little issue.
@@mattabesta would this be due to an issue during DNA replication, since both strands are being copied? Then the template strand would be replicated and the daughter cell would have the normal codons?
"degenerate" does sound inherently bad, but redundancy is never bad.
Well, it might be if you have quadruple redundancy.
I mean, there are plenty more things we could do with a new assignment for a sequence.
Personally, I'd like to be able to change my skin color at will.
Wouldn't that be handy!
Certain types of redundancy are unnecessary specially when dealing with bounded finite automatas such as DNA which have markers in both ends of any word.
Redundancy is the key to safety.
Exactly! I raised that point with my wife, but she didn't seem too happy with the whole polygamy thing. As a counter proposal, I said I was willing to try polyandry because I couldn't stand dealing with her full time...
On an unrelated note, does anyone have a spare couch I can crash on?
@@rajrigby8385 Easy there, Norm MacDonald.
The way this video relays quite complex findings and research to easily understandable explanations is awesome ! And the editing is so enjoyable and adds to it.
To me DNA "code" looks like a form of hex code, it's really cool and there's so much that could be done with it.
You count represent a DNA sequence using existing base-64 encodings because that's how many possible codons there are with 3 quaternary digits.
Tell me why I was thinking about this a few days ago!! But I agree there could be so much done with it! Very good observation
it Is quaternary with 3 number words.
As someone who works on IT I think redundancy is good, you don't want any data corruption there!
It's a bad joke I know.
It's not even a joke. That's exactly why we want redundancy in our DNA. There are other organisms that are super hardy extremophiles and the main thing that makes them that way is the way they have redundant copies of DNA that act as self-repair mechanisms in case of accruing damage to other parts.
Removing redundancy seems dangerous, I mean its fine on bacteria and lab mice i guess since they are already genetic freaks but anything that has to live subjected to nature will need that redundancy...things like people, or food.
I don't know how many stop codons are needed, but I know evolution has been working on it a lot longer than us.
I think you’re right that removing redundancy is probably a bad idea but also, mutations are completely random so the way that the genetic code is situated isn’t necessary the most effective way so it might be interesting to explore other versions but we should probably stick to e. Coli, at least for now lol
@@eoz27 we can always have obsessive version control (if for whatever reason any of the redundancies are false, then toss it and restore a previous version or majority version of the same thing)
most likely case is it goes right (with enough redundancies) or goes really really wrong by accidentally making something that is extremely difficult to change (or even worse, completely nukes the body if enough change at once)
I think the point is that the results _won't_ be living in nature. As I understand it, the practical applications for this are for lab-grown organisms (like bacteria) that stay in specialized locations specifically created to facilitate their survival and function in order to serve whatever purpose they were designed for, like producing medical substances or some kind of industrial reactant or whatever. I think food would be left to unmodified DNA, even if growing it ends up being through cultures or 3D printing.
It was a pretty deep dive! Let's keep diving deep! I like it! The bite sized snippets you guys offer are great too, but sometimes some details go a long way.
There is another layer of imbedded information in terms of "codon pair bias" or codon context where combinations of adjacent codons don't follow expected frequencies.
Also, switching between synonymous codons ("silent mutations") can be pathological if it messes up splice signals at the beginning/end of exons.
Yea, and the researchers pick codons that have low expression frequency and target those for recoding. Super cool research but man, I wouldn't want to be the one changing the codons
@@Luminarada80 it can be done by hand but is usually done by computer (it can be done in R). What is more complex is keeping the codon frequency but changing how the codons are paired with each other.
"It works fine right?" As someone with multiple, rare, genetics conditions I'd like to disagree.
And those redundancy are for safety measures.
You manage to get me hyped about stuff I didn't even know I was interested it. Cheers. Wish you made these while I was still in high-school.
This might be the most informative SciShow video I've seen. I actually learned a lot
This is either going to end in super humans or destruction of the human race…. My guess is the latter.
There is either currently or in the near future a bacteria that can turn everything else on earth into non-specific organic soup just waiting for the wrong container to be dropped. It's not malice and weapons that will do us in it's lack of planning and clumsiness.
win/win
Scientist: "Redundancy!"
Engineer: "Oh my sweet summer child"
Am I only the one who heard "immune to viruses", immediately thought of viral antibacterial treatments and got terrified in light of all the issues we having with antibiotics?
What issues did you have in mind?
@@TeddyLucia1006 Superbugs aka antibiotic resistant bacteria. If we were forced to resort to antibacterial viral medication, we wouldn't want bacteria to gain antiviral resistance either.
This is like self driven evolution, like not in the natural spontaneous mutation but rather we can choose the mutation for us and which direction we can drive ourselves into. This is amazing and has so many potential. I'm so hooked in this. Thanks for this episode guys.
10:14 Hey! My friend did a thesis on affecting proteins with light! At Gothenburg University ☺️
Ooh you got a link/DOI? I wanna read the thing 👀
@@jacquelinealbin7712 Not yet :)
Billionaires paying money to become immortal or gain hundreds of years of life seems inevitable.
It’s a possibility of that happening
Or ways to cure genetic diseases…
Anyway it’s a good thing
@adamklam1 Just see what happens when the billionaires no longer need the working class. Farmers don't keep their animals around once they're no longer useful.
At first it'll be billionaires but as soon as it becomes possible at all, the costs would gradually reduce until all developed countries except America provides it as something basic. Also, things like Alzheimer's research isn't exactly for any particular person but simply benefits everyone, as it is science, which is normally done in the open.
@@cultofcaster9219 they don't directly control the government tho...? And since they are billionaires, they'd want to sell it to get even richer... overall it would probably be a good think
If someone were to write molecular biology fanfiction, I might not read it all the way through, but I would at least be curious enough to take a quick look at it.
It's saddening that the alarmist comments garner the most likes. Whether it be algorithm favorising negativity, society's recent (unjustified) disenchantment with science, or both.
That's why I love seeing so many comments being simply thrilled by this knowledge. Even if they don't get much attention, they mean a lot
I'm pretty leery of any scientific notion of "redundancy" regarding genetics. It feels like a dangerous assumption to make in the face of something so complex. If we actually manage to create coherent organized life - from scratch - out of a primordial ooze, I'll feel less ambivalent.
I don't think it's an assumption when you know exactly what each codon does.
However on a larger scale, such as redundancy of genes, yeah I don't want them assuming that has no purpose
Like scientists saying lobotomy is healthy (literally stabbing someone in the brain until they become mute and deaf)
In this case "reduntant" is merely a description of their ability to code for an amino acid, not a desctription of functional redundancy. Recoded organisms are generally less fit than their background, these effects are usually suprisingly small but plently large enough to explain the evolution of redundancy.
@@mattabesta Yes, exactly; I realized that after having already posted the comment halfway through the presentation, but decided to let it stay. In fact the chemistry/physics and maddening complexity of genetics totally defy my comprehension; it strikes me more like engineered high technology than something that just accidentally happened to emerge from the cauldron of Deep Time. Personally, I'm still unwilling to rule-out the (intellectually "un-cool") ET hypothesis; that this back-water planet from time to time has been used as a lab of sorts, perhaps for various Intelligences outside of humanity, messing around.
@@midplanewanderer9507 One shouldn't rule out hypotheses like that, since we have no way of proving or disproving them at this moment - we can only deduce the likelihood as we understand it. Of course, that would mean that the hypothetical other intelligent life forms would also have to have come from somewhere, so they either evolved out of random chemical jumbling or were also created from recursive cases of lifeforms doing experiments on planets while coming from similar experiments themselves.
An interesting thought experiment.
Years from now, this vid will be seen as the day Hank created Zombieland.
Start workin' that cardio, peeps
Its already done prizer biotech labs
Its mainstream rollout is the covid mRNA vaccine.
Y do y think we r having the vaccine shoved down our throats?
Its the same 50% of people r flat out refusing it
That's exactly what I was imagining the whole time. The cheery tone + potentially apocalyptic content fits neatly in the intro of a post-apocalypse comedy movie.
@@justinblake420 curious that everyone I know that works in biotech has taken it. If the people working in the field aren't concerned about it, why are you?
There’s no way this could turn bad 😎
Sarcasm?
@@enelmartodoesfelicidad clearly :)
Thank you for this detailed review! It's amazing what we can achieve with modern genetic engineering techniques, so I hope we will continue to use these techniques respectfully.
As a molecular biologist myself I would like to add that changing amino acids also helps in unraveling the functions of proteins in other ways.
Many amino acids can be modified post-translationally, e.g. by phosphorylation of an amino acid. This can greatly impact overall protein function. So in research we often use special amino acids, which are e.g. constitutively phosphorylated, to investigate how phosphorylation in specific protein regions alters protein activity, substrate specificity etc. :)
Im impressed by how much information was shared in such a short of amount of time in this video. It was easy to understand and I learned new things as well as being reminded of things I haven't thought about since I was in school.
This is why I love sci show
Best Sci-Show Ep. yet. You guys gotta do more of these! Thanks Sci-Show Team!
I didn't understand everything, but this is pretty interesting.
My wife has a PhD in Molecular Biology. I smile and nod a lot.
@@makeracistsafraidagain that seems interesting to annoy 😉
lol i did get gud noob
That what I said about PBS Space Time!
I did and I still find it interesting.
I must admit that most of that was over my head but I understood enough to know that the technology can be used in dangerous ways. Knowing how violent and destruction the human race can be, I find this to be scary.
As we likely once feared the bluntness of hammers, and the sharpness of fishing spears, when they first came about.
it's a bit like fire, it sucks when cigarettes burn down a house, but central heating and cooked food are great!
This particular aspect of genetic engineering / molecular biology would be difficult to use destructively.
It takes a lot of work, and a lot of precision, to engineer an organism to use a new amino acid in its proteins. It takes even more work beyond that to design a protein that uses the new amino acid to provide some useful function.
And since you are sitting there, with your unmodified genetic sequence and cannon set of amino acids, none of that can affect you directly. Your body would not recognize or use a new amino acid.
For now, it's a research curiosity. In a decade or two, we might engineer a bacteria with a new protein using a new amino acid that can easily break down plastics.
But using this in humans? Oof, that would be difficult. You'd basically have to rebuild the entire genetic code from scratch. Because of that, we're still a very long way off. It's far more difficult than it would be in an E. coli
On the other hand....what you could do is engineer a super bacteria. Course, it's not clear what advantage you'd get by introducing codons for new amino acids into its DNA---it'd probably be easier to keep its standard genetic code---but I'm sure we could figure something out.
But on the flip side, we could also engineer bacteria (or fungus, or whatever) to produce brand new antibiotics that could kill the engineered super bacteria.
Crazy stuff, but it probably evens out in the end.
That's EVERY technology, ever. Did you know that in 2021 the State of Texas publicly demonstrated the potential ability to kill a bunch of US citizens in their own homes by remotely turning off their AC units in the middle of a heat wave? Their intention was to protect the power grid, which is a pretty reasonable goal given the recent collapse it went through in the previous winter, but it produced such a big backlash that customers are fleeing away from green energy solutions like smart meters and thermostats.
That was fascinating. Thank you Sci Show for the information!
This is the best SciShow I've seen in quite awhile. Congrats!
It's also very exciting :)
Wow! Love the deep dive. Thank you for making something complex accessible!
Love to see an episode on genetic engineering that completely avoids eugenics and designer babies, in favor of actual science.
The ideas behind eugenics have been around since plant and animal breeding was developed. Defining "superior" humans, though, has always, in the past, depended on personal prejudices, and religious and political opinions, and has mainly been promoted by people (it seems to me) with genocidal tendencies who are too prepared to treat other humans as domestic animals.
But now, if you say "we can reprogram everyone's kids to have clearer eyesight, and see more wavelengths of light" - that seems to bypass the evils, and the assumptions, of eugenics and to be working towards actual improved humans. I can't think of any group who doesn't want better eyesight. Or better cell oxygenation. Or knee joints that are functional and pain free all of one's life. Or strong feet that stay healthy for a lifetime.
Some religious folks will claim that genetic re-design is usurping their favorite deity's job, but they always have "revelations" eventually that let them change their theology to take advantage of scientific advances. Priests and popes and preachers originally claimed that lightning rods thwarted God's smiting of the wicked, and were blasphemous. And now, of course, churches and other religious buildings are routinely spiked with lightning rods - too many preachers and bell ringers got fried, and lightning rods obviously worked, so they quietly changed their theology.
We could use the 8 letter DNA to get lots more proteins, even with lots of redundancy.
Sure could -- it'd be a lot of work though. Each codon needs its own tRNA and amino acid, and if any two codons are too similar to each other, they might bind to the wrong tRNA
First he says there's a LOT of redundancy using 4 letter DNA (4^3=64) and THEN goes off on a tangent about 6 letter (6^3=216) and 8 letter (8^3=512) DNA, to make it even MORE redundant? WTF?
Yea that's the nice thing about adding nucleotides, but it's way harder right now. The cells REALLY don't like incorporating the synthetic nucleotides into their genome, and cut it out whenever possible. The researchers that got it to work had to constantly add the synthetic nucleotides, always have CRISPR present for the sequence to prevent the cells from cutting out the nucleotides when dividing, and add phosphate buffers because the phosphatases kept degrading the nucleotides (I'm a little hazy on the phosphatase part but I think that's what they were doing). And that was after adding the nucleotides to a single locus on the genome. Both methods require a ton of work, but adding nucleotides is orders of magnitude more difficult right now compared to using existing codons
"Your genetic code is neat, but could be better!
"
this is helpful for people who have genetic disorders that prevents them from synthesizing certain amino acids. its good for curing diseases, it can also be used to develop immunity against certain toxins. looks promising , you could also modify it so that humans could survive better in harsh environments.
I'm also happy with how this video turned out, Hank! Good job all.
"Non-canonical amino acids"
So... Amino acid fanfic? Amino acid fanfic.
Hey wanna see my amino acid ocs?
@@teathesilkwing7616 this is my OC, she is NOT a Mary Sue, DNT STEAL PLS
"It's not life as we know it Jim. It's something completely different."
- Doctor James McCoy
Gosh Hank, I love it when you talk genetics.
Hank, I'm so disappointed you didn't mention my favorite piece of microbiology jargon: CODON WOBBLE.
Codon wobble is when the third nucleotide in a codon allows for so-called non-watson-crick base pairing. This is when A's bind with not T's and G's bind with not C's and vice versa. Codon wobble allows for mistakes to happen in mRNA synthesis and still result in a correct amino acid sequence in the resulting protein.
This sounds a horrifically dangerous experiment.
+SciShow
The one thing that I am left wondering is; while I know that geneticists can “read the letters” just how well can geneticists “read the words that those letters spell” sort of speak…and if they do know what certain things in DNA actually do then what are a few examples of how they actually learned about those things and what they actually do?
The words those letters spell are genes which translate to proteins. Using the genetic code, geneticists can know exactly which sequence of amino acids compose the gene, but the current challenge is knowing how this sequence folds to make the end product. There's recent developments in this field with artificial intelligence, there's another video on that.
It should be mentioned that this goes for coding dna, it was discovered that what we previously called "junk dna" is actually useful (I don't know more about this though)
3:14 . . . Spoiler Alert : *Real Life Forms* need redundant genetic coding to combat 2nd Law of Thermodynamics (at least locally) ! . . . e.g. corruption of vital information after copies are made.
Yea it makes nonsilent mutations way more likely. It's mainly a proof of concept right now, but will be used mainly for creating virus resistant bacteria that can produce new proteins for medical and industrial processes
Making lifeforms immune to viruses? This might have some amazing applications. Hope we don't kill ourselves in the process.
Knowing viruses, its not an immunity. Its just a roadblock. Eventually you'll get a virus that will mutate just the right way to take advantage of the code again. But it would likely be 100% effective in the short term.
But for that whole your code must be rewritten. After that the only problems will be: bacteria, fungus, parasites and so on. Only being completely made of steel will eliminate most of that problems.
SciShow: "The Genetic Code Sucks. Let’s Do Better
"
God: "Get your own quantum fields"
Its not sci show it prizer doing it
@@justinblake420 sorry, what???
What's quantum fields?
Don't bring god into this discussion.
@@Sheen023 Short(ish) answer: quantum number eigenstates that make up (our knowledge about*) all matter
Long answer: en.wikipedia.org/wiki/Field_(physics)#Quantum_fields
en.wikipedia.org/wiki/Quantum_field_theory#Further_reading
*Joke works cuz many people feel like regarding 'em as matter itself, which yours truly thinks is mystical mumbo-jumbo
Playing god creates bigger problems than humanity can handle.
Exactly. The redundancy is there for a reason..
I agree 100%.
This could be used to engineer dna in a way to eliminate over or under production of certain things that are common day problems like scurvy for lacking vitamin c, preventing certain disease from replicating and advancing and other things. Here's hoping it continues
You know it won't happen because "god"
Extra hands to do more job or sleepless employees.
Yeeesssss, but this is probably the least efficient way to go about those goals you described. We can solve those problems with regular old genetic editing and protein design. Molecular Biology is going to be able to cure every disease known to man within a century.
Editing the genetic code to accept new codons is only useful if we want to build proteins containing new amino acids.
We still have near infinite potential just working with the 20 cannon amino acids (after all, they are what built your entire body, every organ, every cellular pathway, every neuron, and every white blood cell) -- reengineering the entire genetic code is only worthwhile if there is very specific we were trying to accomplish.
For now, the latest and greatest thing to get excited about is Google's AlphaFold 2 -- it's doing an incredible job tackling the protein folding prediction
@@tomc.5704 This kind of thinking accomplishes very little, breakthroughs happen because someone decides to go down the "least efficient" paths while the majority of us try to break our heads on a ceiling
@@Thros1 I'm....not sure that's even correct.
I'd happily agree that many breakthroughs happen when someone tries something new, but I can't think of a single time off the top of my head when a breakthrough happened by someone going down the least efficient path. I'm sure it's happened, but I'd wager it accounts for at most 5% of breakthroughs. Heck, someone saying "I think there's an easier way" is probably responsible for more breakthroughs.
And in this case, re-engineering the entire genome is more of a "next step" anyways. First we have to be able to edit the genome, then we have to be able to design custom proteins, then we need a complete understanding of our entire genetic and biological system, and _then_ we will have the tools to introduce proteins that utilize new amino acids.
Not that it's stopped us from playing with the idea early; we've already made a few synthetic / custom engineered bacteria. We could probably use this to introduce a protein that could digest plastic ...... if we were able to design custom proteins to fulfil a function. See step 2 in the above paragraph.
Never underestimate your entertainment abilities, hank. I truly can’t grasp what you’re talking about at all, but I still watched and enjoyed the entire video :)
So... you enjoy not getting it.... that's a healthy attitude.... i envy you.
@@MartinKuras ignorance is bliss so they say
@@fennajarina Yeah they edited it diligently to be quite fast-paced.
Anyway, think of the genetic code in transfer RNA as a to-do list, with mini instructions in groups of three. Each time a little manufacturer takes a trio of instructions, it brings the appropriate component to the assembly line (or terminates the current assembly if the three instructions correspond to a halt).
We might be able to add alternate instructions at the beginning (beyond the usual four) or make a particular grouping of three of them ask the manufacturer to bring a different component to the assembly line, even a specially designed one.
Him: The Genetic Code Sucks
Meanwhile Humans top of the chain.
It's a Joke
"I'm a genetic engineer, Ren!" -- Stimpson J. Cat
"YOU IIIIIDIOT!!!!" - Ren
Best sci-show episode yet!
This is a legit 💯
Has been a while since you guys have made a video this intresting
Please keep on making videos specifically like this
My only concern is that there are some very large superstitious groups who will be strongly against this, having been convinced that we are "perfect" in all ways.
Stem cell research is about 10 years behind because of those people, and I would hate to see that happen again.
This is how way too many movies begin...
yes fearmongering is a big problem.. like how Jaws decimated the shark population even though cows and toasters kill way more people..
@@sewpungyow5154 It would start w/ my Denial of the Presumption that "Science has all the Answers". The hubris wee humans continue to display w/ this admittedly powerful tool called "Science" only continues to show how very Ignorant wee all are of so very much. I'm not against Science--far from it. But Humans tinkering & continuing to FAIL on so many fronts w/ things like Organic, Chaotic Systems like Biomes & Forest Recovery, as stated above, makes me firmly believe we should slow down on all this "Progress."
I have been watching this stuff (rather distantly) for years now and I love it.
Keep in mind that all of this is inside of living bacterial cells. There are also labs that work with a purified mix of all protein translation components in vitro and they can make ribosomes produce some very crazy stuff, so for a chemistry point of view this is just the beginning.
*Me pretending to understand this*
"Ah, yes."
I didn't understand a single thing
I understood everything 😅
As an engineer...I don't know about this. Redundancies are there for a reason. Networks are redundant, roads are redundant, and water infrastructure is redundant. In the human body, we have redundant lungs and kidneys. Should we really mess with 4 billion years of evolution, especially without knowing completely how things work?
Genetic code has not been designed, so I am not sure your concern applies here. Life as we know it is patch over patch over patch, so, the closest thing an engineer could say about is: if it works, don't touch it. But that doesn't apply to a refactor, does it?
That's exactly how nature has done this during the last couple billion years.. throw it at the wall and see what sticks.. still does it like that.
In that sense we're far more organized and goal oriented.
But even then.. if you zoom out you could even add the scientific approach of 'understanding and testing molecular biology theory' to the 'throw it at the wall and see if it sticks' pile.. the timescales are huge and we make ourselves no picture of it. What are 10.000 or 100.000 years for nature? Nothing. And how important are humans in the big picture of things. Irrelevant.
Let's hope somebody doesn't engineer our DNA to make the Humans from "All Tomorrow's"
Great video! Made all the better by not being sponsored. I'm on my way to Patreon.
That’s is so awesome buddy! When the body building community get hold of this , that’s big bucks generated ! For companies and R&D development of new products.
as someone with multiple genetic disorders I am HYPED for genetic tomfoolery
As someone who has multiple genetic disorders, I am afraid of genetic tomfoolery.
@@itsyurmumm8458 fair enough lmao
Hank : Genetic code is "degenerate" .
Genetic code : Excuse me SIR ?
The genetic code doesn't suck...it knows exactly what it's doing
genetic code doesn't know anything since it's not sentient. The reason it works, some of the times, is due to survival biased selection among trillions and trillions of iterations.
@@BlueFrenzy it’s a personification
@@BlueFrenzy And it survived successfully so far for trillions of iterations and billion years.
@@vladimirseven777 Not really. 99.99% of the species are extinct. And even in your own species, it's full of errors (cancer, genetic diseases) and abortions (failed attempts to create life). Don't get started with prions (badly folded aminoacids) If you believe the current genetic code is that good, you are probably victim of the survivor bias.
@@BlueFrenzy that's a huge oversimplification of half dozen mass extinction events.
And to say it's ineffective code because lifeforms eventually die and aren't immortal is also silly argument
Loved this episode... this was genuinely stuff i didnt know and is so damn cool! Got that wide eyed wonder again! Thanks so much!
This is one I'm going to have to watch a few times to follow all the twists and turns, but it is going to be fun like so many of your wonderful videos.
“ your scientists were so preoccupied with if they could, they never stopped to ask if they should!”
Some guy in the year 2103 after the bio engineered mole people have enslaved humanity.
"Genetic power is the most awesome force the planet's ever seen, but you wield it like a kid that's found his dad's gun"
This is cool, i wonder how quantum computer will speed this stuff up, as simulating protien interactions could make it possible to quickly prototype this process.
Any deep dive that confuses viruses is darn well worth it 🤣👍⭐
As someone acquaintanced with haemophilia, I can tell how crucial redundancy is in certain cases. Women do not get haemophilia due to redundancy. Men don’t have that luck though
Hank thank you for teaching me more about how DNA works in the first 2 minutes of your video than my college professor has in the last week...
Preach, we just covered this topic in my grad course on genetic engineering last week and Hank explained the weeks material in 11 minutes
So basically, we know how to type out a genetic document, we just need to figure out how to make the genetic ink cartridges and genetic printer head so the genetic document prints correctly
"Damn, that's an interesting concept, I hope people with very little understanding of biology don't come to stupid conclusions"
Sometimes I think comment sections are a mistake
'Sort by newest first' is a blessing for comedy and a curse for sanity.
@@shleed I just sorted by newest. You are certainly right.
Even when some people understand perfectly, they have a moral panic over dna engineering...
We've modified species' dna for millenia through domestication. So we're not doing a different thing, we're doing the same thing differently.
And no, we're not gonna apply it to us or our food before extensively researching the side effects
You'd be a fool to remove redundancy
This was a GREAT episode. Pretty hard stuff... made it easier for me that I knew the basic facts, but it was very well explained. Thx!
"...or you have to keep providing it." and it's patented, so that amino acid's gunna cost you...