The “Science” of Making Mewtwo

Of the many adventures we encountered over our journeying, one of the most mysterious was stumbling across Mewtwo. In the Pokémon Mansion on Cinnibar Island we are able to find the abandoned journal of a scientist, who documented his horrific gene-splicing experiments in order to create a highly skilled Pokémon of Herculean strength. The tragedy of this story is that the experiments performed on the offspring of Mew lead to the cold-hearted and malicious Mewtwo, who then destroyed the mansion in order to escape the abuse.

Image result for mewtwoMewtwo

Technically, gene splicing is completely possible, although the case of Mewtwo would be too advanced (and unethical) for present day scientists. In theory it is quite simple to splice a gene into another species even though it is much harder in practice.  But first, let’s talk about what gene splicing is.

The type of gene splicing that Mewtwo experienced refers to cutting the DNA of an original genome and adding in new DNA. This new DNA can be a gene, or part of a gene, from the same species, a different species or even completely artificially created. In science, gene splicing is a common method of learning how genes function (although we don’t call it gene splicing – we call it transgenics or gene knock in). Sometimes, if an organism is lacking a particular trait, we can insert a gene into the organism to see if it regains that function. Other times we may move a gene from one species into another, in order to make the new transgenic species grow better or produce a hormone (such as insulin) that we can use in medicine. Most of the time this happens between species that are similar, or is used solely for research purposes (such as florescent genes in animals or plants to understand gene expression), and you have to get an awful lot of licences and training to be allowed to do it. Even then, breaching the laws or genetic engineering or the terms of your licence can end in hefty fines and extended jail time. Obviously, we don’t know the law in Kanto, but if Team Rocket was funding the experiment it’s safe to say that the scientist who experimented on Mewtwo was probably doing it illegally.

Image result for transgenic examples Transgenic glowing fish

Introducing a transgene requires a few steps. First, you need to know the sequence of the gene you want to add. For many organisms, the genome has already been sequenced and it is easy to find the gene sequence on an open source database. It is also useful to know the function of the gene. Many databases can tell you this, but often the purpose of the transgenics is to learn the function. Secondly, you need to have some idea about where the gene is expressed. That means where or when the gene is “turned on”. Some genes will be expressed all the time, and others will only be expressed during a particular developmental stage or in only one tissue. It takes a little consideration, because it will depend on which vector you use in the next steps.

One you have chosen the gene and found the sequence, you need to isolate that DNA. This is actually really simple! We have special machines that are able to make lots of replicates of a chosen section of DNA (called Polymerase Chain Reactions). You need to choose two small sequence (about 20 nucleotides) that exactly match the sequence, one that matches it forward, and one that matches it in reverse. These sequences will recognize the area of DNA you want to target, and help to replicate only the section. After a few hours, you will have lots of DNA of your gene! You can then clean that DNA and prepare for the next step.

After you have your DNA, you have to prepare it so that it will be expressed in your organism. There are lots of mechanisms that are outside of your gene that need to work in order for your gene to be expressed. You need to put the gene in a special vector that will help it be expressed and that will deliver it into your organism. Again, this is relatively simple in theory, but it’s the step that likes to go wrong (for me at least). The double helix of DNA contains two strands that are bonded strongly together. This is because nucleotides make base pairs, where two molecules have a very strong affinity towards each other. This is useful in putting our gene into the bacteria for delivery. We use some special enzymes to make a (usually) uneven cut in the DNA of the vector that will help our gene express, so that it has a little over hang of a couple of nucleotides. Because of our careful planning, this overhangs will match the sequence we have engineered for our gene. When we put the cut vector and our gene fragment in the same tube, we can add another enzyme that will join the two together, because the nucleotides want to bond together.

Image result for digestion ligation

To add a gene into an organism, you need to use a bacterial pathogen that can break into the DNA and add the gene. The most common thing with use is a pathogen called Agrobacterium tumefaciens, which is able to infect the cells with its own DNA in a similar manner to a virus. We use this to deliver our gene into the organism. It can be as easy as dipping the flowers of a plant into the solution, but the more complex the organism, the harder it is. Your gene will then be delivered into seeds or eggs of that organism, and you can select some of the offspring that have your gene. Your gene will be delivered, but the rest of the genome will remain unaffected. Now you can grow those offspring up, and you have your own genetically modified organism!

Image result for agrobacterium mediated transformation

It’s important to deliver the gene into the organism when it is only a single cell. This is because it is much, much easier to change the genome of one cell than multiple cells. If it is at the single cell stage (such as when it is seed or a zygote) all the cells that make the organism will have originated from this transgenic cell and will contain your transgene. Mew gave birth to Mewtwo, so Mewtwo would have needed to be changed well before it was born. Potentially, Mewtwo was made with a fusion of embryos, which would make it a genetic chimera.

Image result for genetic chimeraA genetic chimera peacock!

This is the inconsistency with Mewtwo. From the flashing scenes in Pokemon: The First Movie, it sounds like he did a lot of the genetic mutation AFTER Mewtwo was born. This would be exceedingly difficult, because fully grown, somatic cells (like skin or liver cells) are tough to change. Even if you were able to, you would have to change every single one of the billions of cells in the area you wanted to target. Maybe the scientist only want to change, say, one finger, in which case he could potentially (but with great difficulty) mutate Mewtwo after birth. That would mean Mewtwo was a Mosaic – an organism with cells of different phenotypes. Furthermore, it seems like Mewtwo has an awful lot of different genes changed in it. It’s very, very hard to add multiple genes at once, so usually we will add one gene, and then add the next gene in the offspring and the next gene in the offspring after that. That would mean there would have been lots of different Mews giving birth to mutant offspring until we finally had Mewtwo, but it seems there was only one.

 

Alternatively, the scientist completely, synthetically built the entirety of Mewtwos genome, and used that to clone into mews egg. The problem with this is that it would have cost billions of dollars, so that would be a significant red flag that he was up to no good!

Image result for mewtwo experiments

Of course, the Science in Kanto is far more advanced than our own science, so this scientist may have simply perfected a way of delivering multiple genes after birth. However he did it, I think we can agree that it isn’t something we recommend Pokémon scientists should do, because we have to care for Pokémon, not abuse them!

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