Looking at CRISPR

We are truly living in a magical age. Never has there been a time when technological advancement has been so rapid and more importantly, poised to be so profound. Every day scores of articles are published about a breakthrough in a field of research or about some radical new startup landing funding. Consider this piece on flying cars published in TC today, for example. It seems like we’re closer than ever to realizing many things that we once thought would always remain as science fiction. The crown jewel of this is AI with many of the world’s technological leaders warning us of its potential harm to humanity as we march towards singularity. But while AI, as evidenced by our current efforts in deep learning, has the potential to profoundly change the way we interact with the world around us, CRISPR has the potential to completely change how we exist as a species.

What’s CRISPR?

tl;dr CRISPR is an emerging technology that’s allowing us to cheaply and efficiently perform genome engineering with unprecedented precision.

Its name, Clustered Regularly Interspersed Short Palindromic Repeats, is a mouthful but significant. Basically, scientists found that in the genome of bacteria and other microorganisms, there exist these repeating DNA sequences that are regularly interspersed. In between these repeating sequences are unique sequences that match the DNA of viruses that attack these bacteria. What this means is that CRISPR contains the code of malicious viruses that the microorganism has encountered in the past. And this is only half the story. There also are genes that exist very close to CRISPR sequences that encode what are called “Cas” (CRISPR associated proteins). Cas has the ability to slice DNA. The most well known is Cas9 that comes from the bacteria responsible for strep. Together, the two form a powerful defense mechanism for these microorganisms.

Source: http://sitn.hms.harvard.edu/flash/2014/crispr-a-game-changing-genetic-engineering-technique/

This is how it works:

1. A malicious virus invades a bacterial cell
2. The host cell somehow gets a hold of some of the virus’ genetic material and inserts it between two CRISPRs. Remember those unique sequences I was talking about? They’re formally called “spacers”
3. The host cell makes a molecule of RNA that contains a sequence that matches that of the offending virus. This is called the “guide RNA”.
4. Together, this guide RNA forms a complex with Cas9. The guide RNA moves fast to find its target — the matching sequence within the viral genome. When it does, it latches on tightly to the target DNA, sort of like strangling the enemy. Cas9 proceeds to “cut” the target DNA preventing the virus from replicating.

Why does this matter?

These microbes were able to essentially build a guided missile that attacks a specific sequence within viral DNA. Scientists soon realized that this mechanism could be engineered to target not just viral DNA, but any DNA sequence at a specific location (*That’s…huge!*). DNA consists of four bases: A,C,T and G. Cas9 can apparently recognize sequences that have upto 20 bases, which means that it can be tailored to specific genes. As this article says:

All you have to do is design a target sequence using an online tool and order the guide RNA to match. It takes no longer than few days for the guide sequence to arrive by mail. You can even repair a faulty gene by cutting out it with CRISPR/Cas9 and injecting a normal copy of it into a cell. Occasionally, though, the enzyme still cuts in the wrong place, which is one of the stumbling blocks for wider use, especially in the clinic.

Let’s say we eliminate the hurdle posed above and the various other hurdles that stand in the way of CRISPR becoming a medical reality. Then, as the same article points out:

With CRISPR/Cas9, it’s theoretically possible to modify the genomes of any animal under the sun. That includes humans. CRISPR could one day hold the cure to any number of genetic diseases.

In short, by allowing us to tweak our own “source code”, CRISPR lets us play God. But with great power comes great responsibility. And while the thought of designer babies and potentially curing cancer is enticing, there are still some downsides that cannot be ignored.

Questioning CRISPR

1. An interesting point that this piece makes is related to the unintended consequences of CRISPR. It does so through the example of CRISPR potentially eradicating malaria spreading mosquitos. CRISP-Cas9 makes it, for the first time, possible to insert “gene drives” into organisms. Gene drives means populating an entire species within a given area with a “selfish gene”, one that has a certain trait that we might want that species to have. In this scenario, CRISP-Cas9 would make it possible for the rapid spreading of genetically modified mosquitos that are less fertile and that do not carry malaria. This would spell the end of regular mosquitos. Actually, it could even spell the end of mosquitos as a whole. As the above author aptly asks, what happens then to the bats that feed on mosquitos? You can see where this questioning leads. Nature’s natural hierarchy, established for years, could come crashing down before we know it. Are we truly aware of the extent of influence that CRISPR based techniques exert on the world around us?
2. Another question that came about during a conversation with a friend was “what is bad code?” It seems that while CRISPR might produce short term gains, its long term benefits are unclear. This is especially true if genetic diversity is necessary for the survival of a species. Imagine a situation where every child that was found to have Aspergers in the womb had his/her “bad code” removed. If you believe that some great scientific discoveries have originated from people with Aspergers, then you could argue that we’d have fewer of these great scientific discoveries in the long run. Similarly, lets say we determined that a child born with [X] genetic defect, while hindered in some obvious way, was found to be immune to some [Y] environmental effect that “normal” people were not and thus likely to live longer or with some other benefit that normal people did not have access to. This rationale can be generalized to a multitude of situations but more importantly, it points us to the question of whether CRISPR runs the risk of making us genetically homogenous and thus, less likely to survive an unexpected adverse environmental event. It also segues into my final set of questions:

Who really should be allowed to make the decisions for some of the situations in (2)? Should parents, who fear that their kids might not fit in, be denied the right to remove what they think is bad code from their children? If CRISPR ever becomes a viable genetic defect treatment, should it be in the hands of governments or privatized? Should there be a central board that governs the ethics of CRISPR?

Thanks for reading! Feel free to share this post and share your thoughts. I’m anaganath on Twitter if you would like to discuss further!