The CRISPR “Sword and Shield”: DARPA’s Dual-Use Gene Technology

DARPA-funded researchers develop anti-CRISPR technology to control gene drives, raising ethical concerns about potential misuse and global implications for biological warfare.

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Girish Linganna
Girish Linganna
Girish Linganna is a Defence & Aerospace analyst and is the Director of ADD Engineering Components (India) Pvt Ltd, a subsidiary of ADD Engineering GmbH, Germany with manufacturing units in Russia. He is Consulting Editor Industry and Defense at Frontier India.

The world’s leading scientific journal published a patent on September 5 under the title “Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioral conditions in large cages.” This patent, developed by researchers from Imperial College London (UK) and an Italian biotechnology company, funded by DARPA, describes so-called anti-CRISPR technologies designed to control CRISPR gene drives, which are used to alter insect populations, such as malaria-carrying mosquitoes.

The ability to modify DNA segments has long been considered the Holy Grail of biotechnology, including for military purposes. CRISPR technology enables unprecedented speed and efficiency in this process. In fact, this method won the 2020 Nobel Prize in Chemistry for its discovery.

The acronym CRISPR first appeared in the late 1980s during research on salt marshes near Alicante, Spain. Graduate student Francisco Mojica studied archaebacteria living in saltwater and discovered strange palindromic sequences in their genomes.

Unique DNA segments of a similar length separated these DNA fragments, which were about 30 nucleotides long.

They were originally known as SRSR (Short Regularly Spaced Repeats) but later changed to CRISPR (Clustered Regularly Interspaced Palindromic Repeats).

Continuing his work, Mojica found similar repeats in many other bacteria, drawing significant attention. Bacteriophages, or viruses that infect and destroy bacteria, contain CRISPR fragments in their DNA. Essentially, bacteria store DNA fragments of their worst enemies within themselves.

It soon became clear that CRISPR is a bacteria’s immune memory, storing information about viruses they survived. A bacterial cell that survives a bacteriophage infection chops up the phage’s genome into small pieces, integrates them into CRISPR arrays, and passes this information to its descendants, making them resistant to the bacteriophage.

These CRISPR arrays serve as the bacteria’s immune system. Bacteria convert the stored DNA fragments into RNA. In the same region of the genome, bacteria code for something called tracrRNA. Together, they form guideRNA, which combines with a protein called Cas9.

Cas9 is a nuclease, an enzyme that cuts DNA. Using the guideRNA, Cas9 targets a segment in the bacteria’s DNA, attaches to it, and cuts it, preventing the virus from replicating.

Emmanuelle Charpentier (France) and Jennifer Doudna (USA) proposed a CRISPR-based technique for genome editing in a 2012 Science publication. In 2020, they received the Nobel Prize in Chemistry for their work.

Cutting DNA is the key step in genome editing, and CRISPR acts as genetic scissors or a gene drive.

Genome editing technologies existed before CRISPR but required laborious work over months. Each new edited genome costs several thousand euros. CRISPR reagents, however, cost only 10–20 euros, making large-scale DNA editing experiments feasible and much faster.

It’s worth noting that CRISPR allows mutations without leaving traces, as the RNA and protein introduced into the cell degrade, leaving only the mutation.

The recently published anti-CRISPR patent hints at deeper implications that DARPA is not openly discussing. Anti-CRISPR may become a key tool for global control over biological and genetic experiments. CRISPR gene drives can spread quickly and alter entire ecosystems. When misused, these technologies have the potential to launch targeted attacks on agricultural or natural systems, potentially leading to catastrophic outcomes.

In 2018, The Independent published an article by Steve Connor titled “Gene drive: Scientists sound alarm over supercharged GM organisms that could spread in the wild and cause environmental disasters.”

The article discusses how gene drive technology is revolutionizing medicine and agriculture, potentially stopping mosquito-borne diseases like malaria and yellow fever, as well as eradicating pests and invasive species. However, scientists working on these technologies warn that gene drives could pose a serious threat to the environment and human health if accidentally or intentionally released without proper safeguards. Some individuals fear the potential use of gene drives as bioterrorist weapons against humans or livestock.

The CRISPR/Cas9 method for targeted DNA editing allows for simple changes to any organism’s DNA, potentially replacing natural DNA with modified DNA in an entire population within a few generations. For insects and bacteria, this could lead to the rapid replacement of a natural population with a modified one. The method is cost-effective and highly efficient, making once-fantastical ideas, like those seen in comic books, seem possible.

DARPA’s anti-CRISPR technology could offer a strategic response to these threats. While the Pentagon creates biological weapons using gene drive technology, it also develops defenses against them.

By creating both a biological “sword and shield,” DARPA aims to establish global control over genetic engineering with the ability to counteract any CRISPR-induced changes. This could give the U.S. protection against potential biological threats and influence how other countries use these technologies. The Pentagon is already preparing for the possibility of using gene drives as biological weapons, and they could employ anti-CRISPR not only to prevent accidental errors but also to neutralize hostile actions.  

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