How to detect an artificial bio-threat

A new one, high transmissible influenza strain arises. A pesticide-resistant insect decimates huge crops. A patient ends up in the emergency room with a strain of bacteria that is unresponsive to available antibiotics. Any of these scenarios could occur due to natural evolutionary changes in pathogens or pests. However, as genetic engineering becomes cheaper and easier, it is becoming increasingly plausible that it may one day be the product of deliberate manipulation.

To protect against these potential threats, the US government is funding the development of tests to detect dangerous bioengineered organisms before they have a chance to do significant damage. The effort was announced in 2017 by the Intelligence Advanced Research Projects Activity, or Iarpa, in the Office of the Director of National Intelligence. In a livestreamed update in October, Iarpa program manager David Markowitz announced that two platforms developed under the program were both 70 percent accurate in identifying the presence of bioengineering. “We just never know what sample is going to walk through the door in a government lab, and we have to be prepared for anything,” Markowitz said during the press conference.

One of the platforms being developed by non-profit organization Draper, based in Cambridge, Massachusetts, is a portable rapid testing device that uses a thumbnail-sized chip to detect genetically engineered material. The other is software developed by Boston-based biotech Ginkgo Bioworks that uses machine learning to identify engineering in genomic data generated from sample organisms. (The companies have yet to publish their findings in a peer-reviewed journal, and their platforms are still evolving.)

Crops and animal feed are already being extensively studied for the presence of genetic traits that are not found in nature or can be produced through conventional breeding. Scientists use a test called PCR, or polymerase chain reaction, to determine whether and how much bioengineered DNA is present. When it comes to food labeling, scientists usually know what genetic modification they are looking for. However, there is no one-size-fits-all tool for detecting genetically engineered material in bacteria, viruses, or any other organism that might appear in any context.

Until now, proof of bioengineering has relied on manual analysis, which is labor intensive and slow. Through a process called sequencing, researchers can read off an organism’s entire genetic code: a series of As, Cs, Gs, and Ts, or bases, that make up the building blocks of life. Every microbe, plant, animal and human has a unique configuration of these letters.

To tell if an organism’s genetic code has been tampered with, scientists need to know what its genome – and that of its close relatives – normally looks like. Then they can look for areas that look unusual.

DNA can be manipulated by at least half a dozen processes. A traditional method involves adding a gene from one species to another—usually for genetically engineered crops. Pieces of DNA can also be moved from one part of an organism’s genome to another part, a type of change called a translocation. Crispr gene editing, which is being researched to treat diseases in humans and improve plants and animals raised for human consumption, can delete bits of DNA. Older editing techniques such as zinc finger nucleases and talens have also been used for these purposes, but have not been as successful as Crispr.

Each of these processes can leave traces of biotechnology. For example, scientists can determine if a gene has been added or moved by comparing the genome of that organism to a reference sample. Sometimes when using Crispr, deletions appear in other parts of the genome that look like the target region but aren’t. Talenes and zinc finger nucleases also tend to produce these off-target effects. The intentional use of radiation can also lead to traceable DNA mutations.