I once saw a picture online of the Dragon Lady. It was really quite extraordinary: although born a human being, she now lives as a reptile. Her skin is tattooed all over with green scales, her tongue’s split in two, and she’s had her nose and ears surgically removed. There aren’t many humans who can claim metamorphosis, but this lady has made a remarkable attempt. It might be an extreme example, but most people would like to change something about their physical appearance – and some will resort to surgical procedures to achieve the desired change. But what if we could change our appearance without resorting to surgery? Could the latest genetic technologies allow us to become a dragon?
In the last few years, molecular research has been revolutionised by the introduction of a technique called “gene editing”. A gene is the set of instructions for making a protein – the coded information is written in DNA, which makes up the chromosomes in every cell of the body. This new technology allows precise changes to be made to DNA sequence – in theory, allowing alterations to human genes. By using an enzyme naturally produced by some bacteria (called “CRISPR”), scientists have been able to edit the DNA sequence in human cells. Many researchers believe this technology has the potential to fix errors in a person’s DNA, curing them of devastating genetic disorders, such as sickle cell disease and cystic fibrosis. For example, in sickle cell disease – a painful and debilitating blood disorder common to people of African and Caribbean descent – one of the red blood cell genes has a single letter error in the DNA. In most people, the gene code reads “GAG”, but in those with sickle cell disease it reads “GTG”. This results in an abnormal red blood cell that cannot function efficiently. Gene editing with CRISPR could reverse this genetic mutation: changing “GTG” back to the usual “GAG” code, and curing the person of disease.
But, in theory, gene editing could be used to introduce any change into the human genetic code. So could it be used to turn a human into a dragon?
I don’t know which particular dragon the Dragon Lady had in mind, but to me, the central bearded dragon seems like a fine fellow (Figure 1). Unfortunately for anyone with dreams of transformation, he only has 6 full size chromosomes and 10 miniature chromosomes (in comparison with the human’s 23 pairs). The architecture and DNA sequence of the chromosomes is so different between reptiles and humans that it would be impossible to introduce even 1% of the total changes. However, we might be able to produce some reptilian features. One particularly striking feature of the Dragon Lady was her emerald green eyes, produced by injection of dye. Perhaps gene editing would allow us to recreate this trait?
Eye colour is reasonably well understood at a genetic level. We all have two genes that control the basics of eye colour – let’s call them the Brown gene and the Green gene. When looking at the Brown gene, there are two naturally occurring versions – big “B” and little “b”. If you have a big B on either (or both) of your chromosomes, you will have brown eyes (humans have two of every chromosome, so two of every gene). You will only have lighter coloured eyes if you have little b on both chromosomes (bb). Our dragon eyes come from the Green gene. Here, again, there are two versions of the gene: big “G” and little “g”. Having one big G will give you light green eyes, having two big G genes will give you bright-green eyes – but only if you have no big B genes! In other words, our emerald-eyed dragon would need to be bbGG (Figure 2). So, to create emerald eyes in a blue-eyed person, we would have to use gene editing to alter bbgg to bbGG. Simple!
It is not as easy as it sounds, though. If it were a case of one letter change in each gene — like in sickle cell disease – then it would be possible. However, the B and b variants don’t differ at a single letter of DNA, but at many – and the same goes for G and g. This means that multiple sequential gene edits would have to be made to alter g to G. At present, this is tricky – if not impossible. Not many human traits are controlled in a simple way by one genetic change in one gene. The colour of our eyes, the shape of our nose and the length of our fingers are controlled by an incredibly complex interaction between multiple variations in multiple genes, and scientists are only beginning to understand the basics. We’re a very long way from fully appreciating the subtleties of the genetic code.
So for now, metamorphosis will remain in the realm of science fiction and fairy tales. It is certain, though, that gene editing technologies have revolutionised molecular research and are likely to bring benefits to people suffering with serious genetic disorders in the not too distant future – but dragons will have to wait.
By Dr. Anna Rose
Academic Clinical Fellow in Paediatrics; Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford