Have you heard the story about some scientists trying to turn purple petunias more purple, and instead the petunias threw a tantrum and turned white?
The theory I heard was that because the method to insert new genes into an organism usually involves using a modified virus, when the plant was “infected” with the extra purple, it’s “immune system” treated the gene like an attack and as a result just it shut down all together – and thus, white flowers.
IT TURNS OUT THOUGH, it’s a bit more complex than even that – and eventually, this little failed experiment led to the discovery of a major gene editing tool.
So back in the 90’s, the scientist who tried to purple-fy the petunias (Richard Jorgensen) actually added the gene through transfection instead of transduction – essentially meaning they got the gene into the cell by non-viral means.
HOWEVER, despite not actually being exposed to a virus, those petunias did respond like they were being attacked. This is because inserting foreign genetic material is exactly how viruses work, and in response, most organisms’ from plants to worms to humans, have developed protections against it.
And this is especially true for RNA, since that’s what most viruses are made of – and what most cells need to defend against.
A quick overview of RNA, for the unfamiliar. It’s a nucleic acid like DNA (“ribonucleic acid”), and it’s essentially DNA’s little brother. If DNA holds the blueprints for all the different proteins and things a cell needs to make, RNA is the way those instructions are translated and then messaged to the rest of the cell – AKA mRNA. This comes into play with viruses, because they function essentially like spam mail – they attack cells and add their own RNA instructions, which tricks and hijacks the host cell into making whatever the virus wants (usually more of itself). So cells have a defense to combat this.
For one, mRNA on the job only has one strand (instead of 2 like DNA), so that it’s instructions can be read easily. However, nucleic acids come in pairs, so if another strand of RNA happens to come along that has the right matching pair, the two strands can get stuck together like legos – blocking the instructions and stopping the expression of that gene/protein. This is what researchers figured happened with the petunias, and several similar experiments with worms. However, another surprise occurred when researchers Andrew Fire and Craig Mello tried to do a control experiment where they inserted cells with a strand of mRNA that was supposed to have no effect – they still saw gene silencing!
Looking deeper into it, they found that the cause was actually double strands of RNA that accidentally formed before injection. Apparently these pre-paired RNA strands were even better at stopping gene expression than a single strand – which raised more questions as to why.
And here’s where viral defense come in. Double strands of RNA (dsRNA) don’t really occur normally in cells, but they ARE common in certain viruses. So what these researchers discovered (and won a Nobel Prize for), was that plant and animal cells have a naturally occurring enzyme call Dicer that (as you might guess) finds and dices these dsRNA into little parts; and then it goes even further and takes those un-paired parts and uses them to hunt down and deactivate their partners – effectively erasing whatever virus, protein, or gene that was encoded in the targeted RNA. This is called the RNA interference pathway, or RNAi.
Now it was known at this point that, at least in mammals, introducing long strands of dsRNA for potential gene therapies/medicines wasn’t really possible, since they often triggered a larger immune response. However, learning about this silencing method inside cells allowed scientists to determine that very small strands of dsRNA could be used to reduce and effectively erase a gene or protein. And these small interfering RNA (siRNA) have become key to creating groundbreaking new gene therapies, like treatments for debilitating genetic diseases, HIV, and potentially even cancer.
Quite a lot, to come from a seemingly failed flower experiment!