Until recently, genetics has been like a read only document. We could see and map DNA, but we couldn’t change it in any significant way. That was, until CRISPR but where did it start? Today we’ll be talking about some very basic genetics and how bacteria have led to a massive change in how we interact with it.
Let’s start with some basic information on what genetics is. In genetics, scientists study DNA from multiple different living creatures. This ranges from bacteria to animals or plants, anything alive that has DNA is looked at and mapped. Until recently, genomic mapping was the main thing we were doing with DNA and looking at exactly what series of nucleotides (the building blocks of DNA) made what protein and where they were found on each different living thing’s genome.
Due to how volatile DNA is, until 1987 we struggled to interact with DNA or change it in any significant way. We could break it down and make a whole new copy, but we couldn’t edit the source material, you could only make an exact copy or denature the entire strand.
How CRISPR Was Discovered
In 1987 a Japanese scientist called Atsuo Nakata performed an experiment where he was analysing the genetic structure of the IAP gene in E. coli. This didn’t work however as he was looking in the wrong place on the DNA. Instead, he found something very interesting.
He found a code of nucleotides that was repeated around a section of DNA, it was similar to a DNA sandwich where there was a small code of DNA, then a random set of nucleotides and then the small code was repeated on the end. He didn’t think much of it, DNA does this a lot of the time but what piqued his interest was when he looked at the random nucleotides called a ‘spacer’ in between the repeating codes. He found that this spacer was DNA that could be found in viruses or DNA that would otherwise harm the bacteria.
Immunology in Microbiology
To understand why bacteria have this gene, we next need to look into immunology. Most people are familiar with some basics of immunology, it is the system in our body that gets rid of illnesses by cells identifying what isn’t us and destroying it. In animals, this is done by multiple different types of cells all working together. Some making antibodies to clump and stick the invasive illness together, some eating and digesting foreign bodies in the system and some killing off your own infected cells that are too far gone.
Animals are typically susceptible to illness caused by bacteria, fungi, viruses, or parasites, but what about bacterial cells? Being single-celled, they lack the ability to produce other cells to defend against potential harm. Thus, viruses and other bacteria pose a threat to them, necessitating the development of strategies to fend off these attacks. To combat this challenge, they evolved to modify DNA.
When a bacterial cell is exposed to viral DNA or DNA from another bacterial cell that is releasing harmful ‘plasmids’ (rings of DNA that other bacteria can absorb that code for different things) it takes small sections of this DNA and puts it into a spacer, surrounded by that sequence of repeating genes we talked about earlier. It takes a small section the harmful DNA and puts it in its own genome.
It then starts to transcribe this gene to turn it into proteins. The proteins produced by this specific gene are called CAS proteins which then get dispersed through the bacterial cell.
This is why the Spacer made up of harmful DNA is so important because that now acts as a sort of target and makes each CAS protein hyper specific. The CAS protein will look at all the DNA it can find around the bacterial cell and if it finds a matching code to the section of harmful DNA it has stored, it attaches to it. It then acts as a pair of molecular scissors and cuts the DNA into pieces, cutting the spacer out of the rest of the DNA from the full harmful DNA that is inside the bacteria. This means that the once harmful DNA is now harmless and the cell has that harmful piece of DNA stored so if it’s ever attacked by the same thing it can get rid of it by just remaking the specific CAS protein that corresponds to the threat.
Why This Was Revolutionary
Now we’re finally going back to genetics, with the discovery of CRISPR we found out something really important. We found a way to edit the original genome, at the start we talked about how a genome could only be read or destroyed, we couldn’t change the structure of the DNA or it’s sequence. With CRISPR it was found we could remove sections of DNA and replace them with something else. This has led this to be a massive breakthrough in genetic disease research as well as genetic engineering where people could now alter DNA to do many incredible things. One of its most current and well-known uses is it being used to mass produce insulin by splicing the insulin gene into a bacterial cell so they constantly make insulin that can then be refined and given to diabetic patients.
However, this technology still has its limits. Currently it is like we unlocked the copy and paste function; we cannot write our own genetic codes to place into these spacers. The spacer needs to be a small section of naturally occurring DNA because we do not yet have the technology to build DNA from scratch. This is also only useful in single cells; we cannot change all 30 trillion cells found in an adult human body. This means it is currently limited to altering single celled organisms.