by David Salazar Marcano
CRISPR: if you haven’t heard about it already, you probably won’t escape from its influence for much longer. Although CRISPR may sound like just a fancy new name for a brand of crispy snacks, it is actually a very useful biological tool which in just a few years has completely transformed the landscape of Genetic Engineering and will potentially have monumental impacts on society. The discovery of CRISPR’s application in the editing of genes has made scientists and non-scientists alike re-consider questions previously confined exclusively to science fiction in novels such as Aldous Huxley’s Brave New World, as well as films, like Gattaca.
What if when having a baby you could decide what eye or hair colour you wanted your baby to have, while it was still in the womb? What if you could tweak every physiological feature of the unborn baby to your satisfaction, for example, to eliminate the chance of any genetic disorders and even reduce the propensity to other diseases such as cancer?
Indeed, these questions are no longer a matter for just far-fetched science fiction but rather our very possible near-future scientific reality. In fact, babies have already been born in China whose genes were genetically modified using CRISPR. In November of 2018, Chinese biophysicist He Jiankui shocked the scientific community by announcing that he had genetically edited the embryos of two twin girls, known as Nana and Lulu, which were born earlier that year. The announcement was met with widespread condemnation and resulted in He losing his job as associate professor at SUSTech. He is now under surveillance by the Chinese government and could face criminal charges.
He used CRISPR to target only one specific gene of Nana and Lulu. The gene that was edited by He corresponds to a protein which HIV uses to enter cells, since it had been reported that individuals with a naturally occurring mutation in the gene for this particular protein were innately resistant to HIV. As a result, He claimed that the aim of the experiment was to edit the gene and produce babies which are naturally immune to HIV infections. However, as noble as this may seem, members of the scientific community have pointed out multiple issues with the experiment, questioned whether it was even completely successful as well as claimed that the edits could give the babies another disease instead while providing no protection from HIV. In addition, the experiments were performed in secret without a proper ethical review and potentially without accurately informing the couples that participated.
However, CRISPR’s breakthrough is not in enabling us to modify genes, as this was already possible before by different methods. The real ground-breaking aspect of CRISPR is how easy, quick and cheap it is to do. This has made genetical engineering much more accessible to most labs. It is also believed to be significantly more accurate than previous techniques although there are still concerns about its accuracy, particularly when it comes to editing human DNA for gene therapy. Moreover, CRISPR is not limited to editing the human genome but is actually applicable throughout most organisms. Hence, this opens the door to a wide range of possibilities.
What is CRISPR and how does it work?
First of all, CRISPR stands for “Clustered Regularly Interspaced Short Palindromic Repeats” which really says it all doesn’t it? Ok, maybe not. At least, you probably wouldn’t guess from the name that CRISPR is actually a part of the genetic code of bacteria (i.e. a type of bacterial DNA) which is used by bacteria’s immune system.
Yes, bacteria have immune systems too. Although this may seem odd as our own immune system often focuses on getting rid of harmful bacteria, we do share a common enemy with them: viruses. Hence, bacteria can also be attacked by viruses but the consequences for them are much more dire than a runny nose, coughing or a sore throat courtesy of the common cold virus.
Bacteriophage or “bacteria-devouring” virus (left) & bacterium (right)
When a virus attacks a bacterium, it injects its genetic code into the bacterium in order to essentially turn it into a factory of more viruses, which eventually ends up killing the bacterium in the process as the new viruses are released. However, if the bacterium survives the infection relatively unscathed, it copies the genetic code of the virus and inserts it into its own genetic code so that it can recognise and destroy viral DNA if the same virus attacks again in the future. This sequence of genetic code is what is known as CRISPR. The CRISPR sequence can then be used by Cas proteins which look for pieces of DNA which match almost exactly with those in the CRISPR sequence. If the protein finds a match, it cuts the viral DNA to inactivate it.
Although the presence of CRISPR in the genetic code of E. Coli was known since 1987 it wasn’t until almost 20 years later, between 2003 and 2007, that its function was elucidated. Almost surprisingly now, at first, the publication of this discovery was initially rejected by many important publications failing to recognise its significance. Fortunately, the findings were indeed finally published and only a few years later, in 2012, Emmanuelle Charpentier and Jennifer Doudna’s research groups demonstrated that this CRISPR/Cas bacterial immune system could be used to specifically target and cleave DNA of choice in vitro. Then, in 2013 Feng Zhang’s and George M. Church’s research groups showed that the CRISPR/Cas system could also be used in mammalian cells. Since then, the field of CRISPR-based genetic engineering has exploded with thousands of papers published on this topic.
The CRISPR/Cas system as a gene editing technique has many consequences across biology. It can accelerate medical research by helping us understand the effect of genetic mutations, facilitate the drug discovery process, and bring us a step closer to eradicating diseases such as malaria, to name just a few applications. However, as always, with great power comes great responsibility since the potential for its misuse is just as great. Hence, most importantly, the advent of such a powerful force for change also forces us to confront serious ethical questions.