Possibly the most impactful scientific breakthrough in the 21st century with the potential to revolutionize genetics and medicine, but also to exponentially increase the destructive power of biological weapons.
By: Evan West
What Is CRISPR-Cas9?
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats and is the naturally occurring means by which bacteria cells defend themselves against attack from viruses. In bacteria, repeating sequences of DNA known as CRISPR arrays have spacers of DNA between the repetitions that are taken from bacteriophages that have attacked the bacterium before. Bacteria use RNA generated from the CRISPR arrays, known as guide RNA or gRNA, to recognize the bacteriophages and similar ones in the future. Then a nuclease known as Cas(CRISPR associated proteins) is used to cut apart the DNA of the virus thereby rendering it useless. The CRISPR-Cas9 system has been shown by researchers to have applications for manipulating gene expression and for gene editing in animals, plants, viruses, and more. In the system gRNA is used to identify to the system the target DNA sequence which the system cuts out and potentially replaces. Cas9, is the most commonly used protein in the CRISPR system cuts the DNA at the point specified by CRISPR. After the DNA is cut out, the cell will attempt to fix the missing link and, more likely than not, will repair it with mutations that can disable the gene. Disabled genes are good for research as they allow for the study of the effects of that specific gene, ie. what changed now that it’s gone. Alternatively, if a new DNA template is provided to the DNA repair components of the cell then the cell will use that template to fill in the missing information allowing for repairs or modifications to DNA.
CRISPR Versus Other Methods of Gene Modification
Meganucleases, ZFNs, and TALENs are all other means by which DNA cutting and varying levels of modification can be achieved. These other methods are effective, but CRISPR has some key advantages. First, CRISPR is the most efficient method as the structure of CRISPR already includes the means of cutting DNA strands, and therefore it doesn’t need to be used alongside another tool to cut the DNA. Next, CRISPR is more customizable than other options as it can be configured using the built in gRNA which can guide CRISPR to almost any DNA sequence. Finally, CRISPR can be used to cut and even modify multiple different DNA sequences at the same time allowing for researching and potentially changing complex characteristics that are reflected across multiple genes or even multiple chromosomes.
Timeline of CRISPR
In 2000, after almost a decade of work, Francisco Mojica recognized that what had been reported by scientists as unique repeat sequences in bacteria and archaea, actually shared a common set of features. Mojica coined the term CRISPR to describe these sequences and in 2005 he reported that these sequences that they had discovered in bacteria matched DNA from bacteriophages leading to the hypothesis that CRISPR is part of an adaptive immune system. Also in 2005, another scientist Alexander Bolotin discovered the nuclease Cas9 and he identified that the spacers all share a common sequence at one end, now known as the protospacer adjacent motif(PAM). PAM is required for target recognition. In 2007, scientists demonstrated that CRISPR indeed forms part of the immune system of bacteria and showed that Cas9 is likely the only protein required for interference. Then in 2008, CRISPR was shown by researchers to act on DNA targets which put to end the debate on whether CRISPR acted on DNA or RNA and showed that CRISPR had potential applications in non-bacterial systems. In 2010 CRISPR-Cas9 was first used to cleave DNA and in 2013 CRISPR-Cas9 was harnessed for animal genome editing by Feng Zhang. Currently, most CRISPR research is done on human cells and animal models to determine if the techniques are safe for use on people. A new technique known as CRISPR-Cpf1 was developed in 2015 by the scientists who developed Cas9. Cpf1 allows for simpler, more accurate, and more flexible uses than the Cas9 system.
Potential Medical Applications
Currently, most changes introduced with genome editing are limited to somatic cells. Changes to DNA in somatic cells can result in a multitude of changes in gene expression but these changes will not be passed on to future generations. Changing germline cells, however, can result in edits that are passed down. Which raises ethical questions regarding using this technology to enhance the characteristics of one’s descendants. Therefore, most medical applications will be limited to changes of somatic cells. Research is being done on using CRISPR as a cure for single-gene diseases such as cystic fibrosis, hemophilia, and sickle cell anemia. CRISPR is able to modify multiple genes at the same time and therefore could be a cure for more complex diseases. These could include cancer, heart disease, or HIV. In the pursuit of global research that benefits human health CRISPR had been shipped to 62 countries and shared with 2,339 institutions as of February 2018.
Potential Military or Terror Applications
Technology has no morality. This amoral nature can be demonstrated with a few simple examples. Nuclear technology can be used to provide large amounts of power, relatively cheaply and without contributing to global warming. Nuclear technology is also be used to create the most destructive bombs man has ever made. Computers allow billions of people around the world to connect, share ideas, and even sell or purchase products. Conversely, computers are also be used by black hat hackers to steal information or destroy property. The point here is that technology isn’t explicitly good or bad, but rather the morality of any technology depends on what it is used for. CRISPR is especially dangerous because researchers, inspired by the incredible potential of CRISPR to do good, are sharing their tools and findings with countries and institutions around the world. However, just like with other technologies there are people, organizations, and governments who will see CRISPR as a means to inflict terror, sickness, and destruction.
One such group is the Russian government and Russian researchers have been supplied with the tools to do their own CRISPR research. Russia is on the list of countries that have been supplied with CRISPR even though it’s common knowledge that Russia had a substantial Bioweapons program during the cold war and that they are currently developing the next generation of nuclear weapons with the goal of establishing regional dominance. It’s certainly imaginable that Russia would want to restart(if it ever actually ended) their bioweapons program and utilize CRISPR to further develop the destructive power of their weapons. Additionally, information about how to apply to get tools, basic information, and troubleshooting was easily findable after a quick google search. Coupled with the increasing simplicity, accuracy, and falling cost of CRISPR, this ease of access should raise concerns that radical groups could use this technology for their own purposes in the future. The potential of CRISPR to be used for destruction compelled Director of National Intelligence, James R. Clapper to include genome editing under the heading Weapons of Mass Destruction and Proliferation in February 2016’s Worldwide Threat Assessment of the US Intelligence Community. While the current state of the technology doesn’t allow for the complicated changes necessary to engineer effective weapons, CRISPR is developing rapidly across the globe. Additionally, because of advances in DNA synthesis, computational power, and information sharing it is not a question of if weapons could be developed using CRISPR, but when, who, and how destructive.
“According to biological warfare expert Dr. Steven Block, genetically engineered pathogens ‘could be made safer to handle, easier to distribute, capable of ethnic specificity, or be made to cause higher mortality rates.”
While the ability to control DNA seems like something out of a dystopian science fiction movie, CRISPR has cemented it as reality. Genetically modified super-soldiers, man-made epidemics, and changes to germline cells that negatively affect individuals and their future descendants are all potentially possible. Again, the technology as it stands now doesn’t allow for the complicated editing necessary to accomplish these modifications, but advancements in CRISPR’s abilities are occurring at a rapid pace moving these modifications closer to reality.
Conclusion
The potential of CRISPR as a tool to enhance weapons is terrifying. However, there is solace to be found in the knowledge that CRISPR is also a means by which countries can defend themselves against an attack by a mutated virus. CRISPR allows for the rapid genomic mapping of viral DNA which will give scientists an edge in creating a vaccine or identifying other effective treatments. Of course, it would be better to avoid an attack by a CRISPR modified agent in the first place so it is the opinion of this author that sharing of CRISPR technology and research should be restricted to friendly nations and groups. These restrictions wouldn’t completely stop bad actors from utilizing the technology, but they would certainly make it more difficult and easier for the international community to recognize and condemn those who do attempt to weaponize CRISPR. Unfortunately, it may already be to late for these restrictions to have maximum affect.
Glossary
DNA – deoxyribonucleic acid: the ‘source code’ of cells and life. Guides cell development and thereby the overall gene expression of the entire body.
RNA – ribonucleic acid: Generally used to carry messages from DNA to the proteins it binds with.
Nuclease – Protein that cuts Nucleotides in nucleic acids into smaller units. Typically used to cleave DNA or RNA.
Somatic cells – Cells that are not used for reproduction. In humans these are all cells except for sperm and eggs.
Germline cells – Cells that are used for reproduction.
References