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CRISPR/Cas9: the double-edged sword of molecular biology

In recent months the media outlets lit up with the news that a team of scientists have successfully used CRISPR/Cas gene editing technique to repair a gene causing a common form of heart disease in human embryos. Following this recent breakthrough the public has been left divided both expressing excitement and concern over modern scientific capabilities.

The CRISPR/Cas technology used to modify embryos is a simplistic immune system of unicellular prokaryotic organisms - a collective term for bacteria and archaea. When a prokaryote encounters a novel pathogen such as a virus, it cuts its genetic information into snippets and retains them within its cell. This way, if a prokaryote encounters the same virus again it is able to rapidly recognise it and initiate its defence mechanisms. The gene modifying approach used by researchers acts similarly; it is composed of a Cas9 nuclease, a protein which can unwind and cut DNA, and a pre-designed sequence of guide RNA (gRNA), which is custom built to recognise a gene of interest. When a gRNA binds to its complementary genetic sequence it is cut by the nuclease and this in turn allows researchers to remove or add desired genes.

Graphic by Hugh Allison, GBR Community Coordinator

 

The simplicity and elegance of this technology means it has many potential applications in healthcare, agriculture and industrial biotechnology. We are now able to generate cell cultures to study pathology of human diseases, target genes encoding antimicrobial resistance, mosquitoes transmitting malaria or weeds plaguing food crops. It allows straightforward generation of disease model mice, the workhorses of biomedical research, which up until now required a lengthy and complicated derivation process. CRISPR/Cas has also reinvigorated efforts for improved human transplants and preliminary studies have eradicated traces of cancer causing EBV virus from donated organs as well as eliminated proteins causing transplant rejection. Finally, this technology has facilitated further research into using porcine organs for human transplants, which previously have been halted due to presence of retroviruses in pig genomes. Today, however, we have the ability to eliminate these viral traces and thus, abandon long organ waiting lists.

The major concern about application of CRISPR/Cas to human embryos comes from the fact that it implies modification of germline cells. Unlike somatic cells, gene editing in germline cells means the genetic modification can become heritable. In the 2016 Pew Research study on US public opinion on the future use of gene editing half respondents were for and the other half against germline editing of serious diseases showing the division in the societal views.

 

Where do we draw the line between a cure from a life-threatening condition and Huxley's dystopia?

How do we eliminate genetic conditions plaguing our society while preserving and celebrating diversity?

Will individuals who can’t afford or refuse to pursue enhancement be discriminated against?

Should we even take up the responsibility of tinkering with the human evolution?

Or would doing nothing constitute a decision in itself – a decision to bar humanity from using the tool, which has the potential to save millions of lives?

Jennifer Doudna, who is one of the pioneers of the technique, raised her concern that modification of human embryos has the potential to create the “gene gap”. CRISPR/Cas, at least initially, will be expensive and hence, likely to be only available to the wealthy members of our society. This in turn can create an even bigger division between classes as well as create a new level of genetic segregation.

Professor Jennifer Doudna, CRISPR pioneer. Image source: Drew Kelly for The Wall Street Journal

 

The first thing taught in university evolution classes is that diversity is a lot more advantageous to the species as a whole. While a certain set of traits may be deemed favourable in a specific environment or society, a rapid change in surroundings such as nutrient availability or disease can completely wipe out a population bearing little diversity. Populations with high diversity, on the other hand, are more likely to survive the “bottleneck” effect, where the set of traits, while not necessarily favourable in the previous environment, become beneficial. However, we must remember that evolution is not a directed force and it does not follow an intelligent design. Evolution in nature is flawed and occasionally this results in debilitating genetic conditions putting strain on affected individuals and their families. If we can eliminate inherited conditions such as BRCA caused cancers, Huntington’s disease or cystic fibrosis (with carrier frequency of 1/20 in the UK) – why wouldn’t we?

While CRISPR/Cas gene editing technology is one of the most important advancements of our generation, it is a long way from the clinic and the journey will be a winding one. The dialogue about safety regulations and ethical handling has already been initiated but it will take years of rigorous research to ensure patient well-being is not compromised. Furthermore, translation of CRISPR/Cas into the clinic would have to be a multinational effort and all nations must agree on a set of laws and guidelines applicable across the globe. What is certain, however, is that we are on a cusp of new era of medicine, biotechnology, ethics and law.

 

By Alisa Molotova

PhD Student, University of Cambridge
and GBR Alumni Manager

Categories: Blog

Tags: Future Health Gap, Science News, CRISPR

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