CRISPR Dual-Use and Security Implications

Alonzo Jackson

CRISPR-Cas9 Mechanism

Today, scientists have discovered a new gene editing process that helps scientists modify DNA more efficiently than ever, called CRISPR-Cas9. CRISPR-Cas9 is a powerful tool for editing genomes as it allows scientists to change DNA sequences to modify gene function. Gene editing is a group of technologies that would enable scientists to change an organism's DNA. Scientists can edit DNA by adding, removing, and altering specific parts of a genome. In the last 15 years, CRISPR has created a lot of excitement in the science community because it allows scientists to edit genes faster, cheaper, and more accurately than other methods. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and Cas-9 stands for CRISPR-associated protein. CRISPR was adapted from a naturally occurring genome editing system discovered in a bacteria's immune system. The CRISPR-Cas9 system consists of two molecules that introduce a change in the DNA. Cas9 is an enzyme that acts as a molecular scissor that can cut two strands of DNA in a specific location so that DNA can be added or removed. The second molecule is a guide RNA that consists of a small piece of pre-designed RNA sequences about 20 base pairs long that bind to the DNA, and the predesigned sequence guides the CAS9 to the correct part of the DNA. This allows the Cas9 enzyme to be cut at the right point in the genome.

Maturation of CRISPR-Cas9

CRISPR was discovered out of scientific curiosity in the 1980s by scientists working on basic bacterial viruses. CRISPR was first found in 1987 in the bacterium Escherichia or E.coli. At the time, CRISPRs researchers thought it was just an oddity of nature until researchers detected CRISPRs in many other species throughout the early 2000s. Before naming this odd phenomenon "CRISPR," scientists would use various confusing acronyms before a Dutch researcher eventually classified it as CRISPR in 2002. As time went on in the early 2000s, more researchers discovered that CRISPRs were abundant in nature and could be found in a third of almost all bacteria and archaea. Archaea are a type of single-celled microorganisms usually found in extreme environments. But before CRISPR's discovery, the biological nature of bacteria had been almost a complete mystery. In 2005, Francisco Mojica published an article in the Journal of Molecular Biology that explained how, using bioinformatics, he was able to find viral DNA sequences in the repeating sections of DNA, discovering that the bacteria had stored the viral genetic code in their memory. Out of this came an abundant amount of research on the bacterium.

One of the first significant experiments started in 2007 when scientists attempted to generate virus-resistant strains of the bacterium Streptococcus thermophilous, which is used to ferment milk into yogurt and other dairy products. By intentionally infecting their strains with different viruses and analyzing the bacteria's DNA, they discovered that those bacteria gained what they classified as adaptive immunity. Once found, the belief that bacteria only had one defense against viral pathogens was overturned, and researchers worldwide began to discover a new understanding of bacteria. 2012 was the start of a scientific breakthrough called the "CRISPR Craze." It began when scientists Jennifer Doudna and Emmanuelle Charpentier published the first article, A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity, to describe the essential components of CRISPR cas9 and how it can be utilized for gene editing. After this article was published began to figure out how effective CRISPR gene editing is in mice and human cells. This period was the start of an explosion of research and experiments.

Current Applications of CRISPR

Today scientists can use CRISPR to engineer the genome in ways that may seem unimaginable. Scientists have discovered ways to remove pathogenic DNA sequences, repair genetic mutations, turn genes on and off, and so much more. For example, scientists have found ways to clone a deceased dog, grow super strains of tomatoes that stay ripe for long periods, and create mushrooms that don't brown after storage. Using CRISPR, scientists have discovered how to clone a deceased dog using genetically edited skin cells. CRISPR applications are diverse and continue to grow as scientists have a more effortless ability to target specific genes of interest in various organisms. Plant breeders are excited about CRISPR allowing them to engineer new traits into major cash crops genetically. Using CRISPR to modify crops genetically may be less invasive than the ones we traditionally use to create GMOs. Traditional GMOs are a product of gene splicing where foreign DNA sequences are forced into the genetic material of an organism being modified. Unlike traditional GMOS', genetically edited organisms would not carry foreign DNA in their genome. CRISPR allows scientists to change an organism's genetic code and has already been proven effective in combating and treating various illnesses. For example, CRISPR research has resulted in a breakthrough in treating multiple cancers and sickle cell anemia. In 2021, scientists used CRISPR gene therapy to treat a patient with sickle cell anemia. After successfully treating the first patient, doctors used the same CRISPR treatment for 45 patients suffering from the same genetic disease.

CRISPR Dual-Use and Security Implications

Malaria is one of the deadliest diseases humans are infected with every year, as it has claimed the lives of millions of people around the globe. In 2020, the World Health Organization reported there were 240 million people infected with Malaria around the globe and it killed 627,000 people. In recent years scientists and researchers have sought to use CRISPR and mosquitos to fight Malaria. In addition, scientists have developed a strategy to use 'gene drives to fight this disease. Gene drives would also allow scientists to selectively engineer malaria-infecting mosquitoes to intentionally spread specific traits through their population designed to block the transmission of malaria parasites. Scientists at the University of California successfully inserted DNA sequences into the gene-drive-engineered mosquitos that were intended to block the transmission of malaria parasites. Once the gene-drive mosquitos mated with normal mosquitos, they passed the malaria-blocking trait to 99.5 percent of their offspring. As a result of this research done by the University of California, the National Institute of Health, DARPA, and the Bill and Melinda Foundation asked the National Academy of Science to create an Ad-hoc committee of experts to examine this field to ensure the responsible conduct of gene drive research.?

CRISPR should raise concern for its potential dual-use security implications as it lowers the barrier for developing biological weapons. Compared to the previous method of genetic engineering at a low cost, any nefarious actor could misuse this technology. CRISPR could be used to create a variety of bioweapons ranging from increased virulence pathogens to neurotoxins and de novo viruses. In 2018, the Department of Defense requested a study examining the potential risks of using CRISPR, as their most profound concern was the re-creation of known pathogens like smallpox. CRISPR could allow a nefarious scientist to increase the virulence of a pathogen that, for example, wouldn't be able to transmit as fast. The study would assess the present and future risk of the recreation of pathogens, smallpox being their biggest concern. Malicious usage of CRISPR could potentially become a biosecurity threat. On a global scale, the World Health Organization (WHO) has made great strides in monitoring efforts in genome editing. They are explicitly monitoring gene drive usage to determine if gene editing will require policymakers to regulate this activity. The US Department of Health and Human Services has also outlined a safety framework for companies' gene editing companies on how they should monitor customers for potential malicious activity. Another concern CRISPR raised was the possible unethical engineering of human embryos. In 2018 a Chinese scientist, He Jianku, raised ethical concerns after he implanted genetically edited embryos into two women. He was found guilty of conducting illegal medical practice and sentenced to 3 years in prison. Some of the other dual-use security concerns involve agricultural pathogens, where nefarious actors could purposely enhance the virulence of pathogens toward specific crops, and the potential for amateur scientists and regular citizens to use CRISPR in harmful ways.

CRISPR is a groundbreaking tool for technological advancement in its dual use, allowing many breakthroughs for biological advancement. Since its creation, CRISPR, has helped the innovation of many scientific and medical discoveries that will help improve human life. At this moment, no one solution will dissolve the potential risks that can arise from the misuse of biotechnology, but some tools can be implemented to help prevent bad behavior. As biotechnology continues to evolve, it will be crucial for scientists and policymakers to revisit the mechanisms put in place to ensure the safety of not just the United States but humanity. It will take an international effort to proactively discover and identify emerging threats to biosecurity that arise in the years to come, as failing to do so is not an option.

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