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Gene Genie: what actually *is* CRISPR and why are people so excited about it? 18.08.17

Last week, a team from the University of Washington, comprising of both biologists and cyber security experts, managed to encode a gene with a computer virus. The code, while not malicious, entered the computer that was reading it and began executing commands, demonstrating a cyber threat that caused our Head of Ops to consider “taking the family and going to live in the woods with a wind-up radio and guns. Lots of guns.” Indeed, a collective “wtf?” resounded through the office as the news broke.

This isn’t the first story involving the editing of a fundamental biological molecule to elicit this reaction. In July, researchers at Harvard encoded a GIF of what may be the first ever moving image (nice touch) into a bacteria’s genome. They then retrieved it by getting a machine to read back and copy the genome (this is gene sequencing, by the way). They quite literally turned a bacterium into a hard drive. I had a brief chat with a friend who sent me the news.

“Dunno man. Mental.” I think that’s a pretty fair summary of how the majority of people see CRISPR, the technique that’s making these feats possible. It has the potential to change many areas of everyday life forever, and could shift our view of biology and humanity to one that more resembles the 1s and 0s of digital technology.

For the uninitiated, CRISPR is hard to get your head around. Luckily our jobs at AprilSix Proof require us to become knowledgable on a subject in super-quick time, so I turned to my trusted companion in such situations: good ol’ Google. I came across a guide from the Harvard University Graduate School of Arts and Sciences that is one of the most succinct summaries of the technology I’ve yet read.  It still has a lot of genetics jargon in though, so here’s my attempt at distilling it:

– A CRISPR is a sequence of DNA found in a bacteria cell that forms part of its immune system. There are many CRISPR sequences found in a bacteria’s DNA.

– When a virus enters a bacterium, the CRISPR sequence helps defend it. It does this by creating and guiding a molecule – RNA – that chops up the virus’ genome, preventing it from working.

– RNA is a temporary copy of part of a DNA strand created in reaction to something; in this example it is a copy of the CRISPR sequence, created in reaction to the virus entering the cell.

How does CRISPR guide the RNA molecule, you may ask?

– Once the virus genome is chopped up (killing the virus), remaining bits of genome are inserted into the bacteria’s DNA, in between CRISPR sequences.

– When attacked again, these bits of now-bacterial DNA are copied, creating an RNA molecule.

– This RNA has part of the virus genome within it, helping it identify what needs to be killed.

And how does this allow us to edit DNA sequences?

– All cells create RNA; it plays an important role in copying our DNA when cells multiply.

– If we know what is in a DNA sequence, we can make RNA that exactly matches this sequence. After all, RNA is simply a copy of it.

– This RNA, much like in bacteria where it chops up the virus genome, allows us to remove the section of DNA it matches.

– This then leaves a gap in the DNA which we can then fill in with, for example, a new gene.

The discovery and subsequent development of this process has already begun to change how we use biological material in our lives. Through our work with IBioIC, we speak with those regularly using the CRISPR technique to create new materials; indeed, the sheen of the new technology has already worn off as it has become crucial to every day operations.

Because of this, while the public is still catching up on what CRISPR means for them, the gene editing industry has moved on rapidly. If I wanted to, I could design a strand of DNA and get it sent to me, courtesy of the Edinburgh Genome Foundry which, with the right tools and knowledge, I could manipulate. I could invest in gene editing companies that are using CRISPR to create gene therapy treatments for a wide range of health problems, from cancers to blood diseases. Or, I could receive a donor organ from a pig that is far more likely to be accepted by my body thanks to alterations to the pig’s genes.

These biological and medical advancements are huge when compared to previous methods we used to treat ourselves, such as invasive pacemakers or implants that deliver drugs. It has the potential to create a wave of personalised medicine as our genes are mapped and that information then used to create and deliver treatments tailored to us. But there are major concerns.

One centres around the germline, the DNA within sperm and eggs that are the origin of all DNA in our bodies, and all generations that follow us. It is one thing to alter the DNA in, say, a specialised muscle cell of an adult, but quite another to forever alter the DNA that forms a part of our, and our descendants, being. Astoundingly, we have this capability, and more. In 2015 it was reported that we can create a germ cell from any other type of cell in our body. Using the CRISPR technique, we can then edit its genes ahead of using the cell in the reproductive process. No wonder some are worried that we’ll begin to meddle with the fundamentals of our biological make up.

Another concern looks at how CRISPR techniques allow us to alter the genetic make-up of animals in the wild. A report in Nature cites our ability to alter the genes of mosquitos to not only lower the numbers of offspring, but to also ensure that the edit sweeps through the population, eventually wiping it out. But, our understandings of ecosystems are limited at best and past meddling in animal populations don’t reflect well on us; one needs only to look at the North Sea and 20th century fishing to see how we can alter an entire ecosystem.

The same report in Nature also highlights how CRISPR editing is not 100 per cent foolproof. “These enzymes will cut in places other than the places you have designed them to cut, and that has lots of implications,” says a molecular biologist from Brandeis University in Massachusetts. At the moment we don’t have a technique that effectively finds all of the cuts made by the CRISPR process, so using these techniques is not as accurate or as well understood as the ‘genetic scissors’ comparison suggests. When changes and alterations in DNA are the drivers behind cancer, it makes sense to know exactly the edits being made before using these techniques on people.

But while there are major biological questions still to be answered, there are an equal amount of philosophical ones. Our ability to change the germ line of our species is a serious ethical dilemma. Yes, we could remove genes that are linked to, say autism, but at what cost? An article in Time cites numerous examples of good and bad genes that are connected and can’t (yet) be cut individually. These genes offer trade-offs; for example one might protect you from heart disease, but could shorten your attention span. Another could increase the risk of autism, but improve immune responses. Which is best? Who decides? There are multiple layers of morality here, but the overarching one being that, ultimately, someone, somewhere is deciding what makes us human. Who has that right? Do we want to “industrialise the genome” and, by extension, ourselves, or do we want to encourage “neurodiversity” in all its forms?

It’s a debate that will no doubt take up many more column inches before it’s over, but what is not up for debate is that CRISPR will have profound implications on healthcare and what we as a species view as acceptable when we have the ability to alter the very make-up of ourselves.