Friday, January 11, 2019

Jurassic Park and Jurassic World: Why can't we clone dinosaurs yet?


Related imageI’ll preface this blog by stating that I have a Ph.D. in biology with post-doc experience too. I’m not an expert in the field of cloning, however, so there may be people who disagree with the arguments I’m stating. To those people, I say…put it in the comments, I’d love to hear from you! If you’d also like more info about some of the details because you don’t own a science background, you can also post it in the comments and I’ll respond promptly. Also, I know they're movies and that they're not meant to be realistic, but that definitely isn't going to stop me from making you think about how silly the idea of cloning dinosaurs is. 
Now then, nearly everyone who enjoys movies has seen both Jurassic Park and Jurassic World (hereto referred as JP and JW), including me. JP is a series built on the premise that humans could effectively clone dinosaurs from bits of DNA hidden in the preserved blood of mosquitos. They were both pretty great movies (although the most recent sequel, Jurassic World: Fallen Kingdom, wasn’t great), with THE most memorable animals ever developed for film. The dinos from JP had so much personality and were so realistic that I remember people debating how feasible it was to create them way back in the 1990s. Still, some have been talking about bringing old creatures back to life, like the wooly mammoth, which lived thousands—not millions—of years ago. Dinosaurs, however, are an altogether different thing.
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Look how tiny that velociraptor is!
I’d like to assume that people reading this blog know what dinosaurs are, but I won’t assume that they know everything about dinosaurs, so I’ll take the educational road and give the details I’ve learned after reading books to my dino-obsessed 4-year-old son. Dinosaurs lived around 250 to 65 million years ago in the Mesozoic era, which is divided into three different periods: Triassic, Jurassic, and Cretaceous. Jurassic Park doesn’t actually mean anything, since most of the dinosaurs it focuses on lived in the Cretaceous period, especially Tyrannosaurus Rex, which lived at the end of the Cretaceous. They were basically reptiles with specific types of hip bones that walked on land, some had feathers, and eventually evolved into birds (fun fact: animals like the pterodactyl and mosasaurus aren’t actually dinosaurs!). Dinosaurs and a whole swath of other creatures ultimately went extinct, though no one is sure exactly why (probably a giant meteor combined with a rise in volcanic activity and the fact that it took dinosaurs an exceptionally long time to gestate). Also, the velociraptors in the films aren’t really velociraptors, but probably a mix between the pack-hunting deinonychus and a utahraptor.
The science behind JP and JW involves taking mosquitos fossilized in amber, harvesting the blood they sucked from dinosaurs, purifying the DNA from the blood, and cloning dinosaurs in what can effectively be called top-down synthetic biology (basically, using a shell, like a bacterial cell without DNA for instance, to insert genetic material you know works and creating a new lifeform from it). From a scientific perspective, there is so much wrong with all this wtf. First of all, how does anyone know that the DNA they’re looking at comes from a dinosaur? No one knows the first thing about dinosaur DNA, yet they somehow identify it as belonging to X dinosaur species. How do they even know how many chromosomes it has? I can maybe see how they might differentiate dinosaur DNA from any sort of unicellular bacteria that might also be in the sample, but still. There would only be one way to verify the sample and that’s trying to clone the DNA into a nucleus-free cell and seeing what sort of animal you’d get. Now, say you wanted to try this approach and clone the animal, which basically means taking the DNA from somatic cells (like muscle cells or anything that’s not a gamete, like sperm or eggs), and replacing the DNA from a fertilized egg with the somatic DNA, then letting it grow inside the uterus of the animal. You need a fertilized egg from the same species of animal and you need to let it grow inside the uterus of the same species. You might try to remove the DNA from a fertilized egg from another kind of reptile, then let it grow inside the egg until it hatches. But how big should the egg be so that the embryo develops normally? Will it get the proper nutrients inside a lizard egg? Maybe you can make synthetic eggs and artificially supply nutrients, but you still don’t know the size or nutritional requirements for the animal to grow. It might work, but it’s unlikely you’d find just the perfect situation for this DNA to produce a living, breathing animal without complications.
Image result for mtor signaling pathway growth complex
An example of how complicated regulating gene
expression can be.
This brings us to our most bizarre plot twist: they say that to make a new dinosaur, they need to “fill in the holes” with the DNA of other animals. With regards to genetic engineering, that they need to fill in the holes of the genetic code with DNA from frogs and other animals is puzzling. How do they know that the genetic code needs filling in, since they’ve obviously never seen dino DNA before? What parts need filling in? And how are they filling it in? I suppose the how is actually the easiest part of the whole bonanza. Assuming they needed a few genes to insert into the genome, they could pretty efficiently modify the genome using CRISPR, a gene editing technique that’s become famous for producing the first ever genetically modified babies. First, they’d need to sequence the entire genome of the dinosaur, find the appropriate area to insert a gene, and devise constructs that they could insert. You wouldn’t insert them directly into any “holes” per se, but into continuous lengths of DNA that make up chromosomes. So, if you want spikes (I'm looking at you, triceratops hybrid from my son's JW book), you could theoretically insert the gene for spikes into the dino genome when it was only a fertilized embryo, before implantation into an artificial egg. HOWEVER, this is extremely short-sighted as there are probably numerous genes that coordinate to produce spikes, so you’d need to know how the entire system worked, then insert it ALL into the right spot in the genome to have an organism that produces spikes in the right place at the right time. Gene circuits can be extremely complicated, with multiple proteins and other DNA sites (promoters and enhancers) regulating the expression of a gene and its levels, as well as microRNAs that regulate the stability of the transcript you’re producing, and post-translational modifications to the protein of interest. The chance you’d magically find a gene that does what you want it to in an organism that you’ve never worked with before is just…stupid. You’d also have to do it without affecting the rest of the genome and producing any undesirable off-target mutations, which could have pretty unpredictable effects on your dino, like making it more prone to developing tumors (dino cancer, a novel concept!).You'd also have to find the appropriate gene (remember, you've never seen dino DNA before), and you COULD overexpress it during the right period of development, but that would still take a whole lot of time to get right (if it ever worked). And don't get me started on merging two dinosaurs together, like the Indominus, which would produce zero fertilizable embryos. What parts of which genomes did they even decide to incorporate?! My brain is slowly melting...
The likelihood that dinosaurs will be revived within our lifetime is highly improbable, but you never know. People get creative and come up with all sorts of weird things, like robots that feed people tomatoesArtificial intelligence and 3D bioprinting (which can be used to print living 3D models of tissues) are also avenues that could be used one day to create a reasonable facsimile of a dinosaur, though both technologies are still in their relative infancy, with a long way to go before we can use them to even make functional organs, let alone full dinosaurs. So, the best thing to do in the meantime is to simply wait, get comfortable on your couch, and go re-watch your favorite movies…like JP and JW.




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