How to detect a human-made biological threat

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A new, very transmissible strain of influenza emerges. A pesticide-resistant insect is decimating huge areas of crops. A patient ends up in the emergency room with a bacterial strain that does not respond to any available antibiotics. Any of these scenarios could occur due to natural evolutionary changes among pathogens or pests. But as genetic engineering becomes cheaper and easier, it becomes increasingly plausible that they could one day be the product of deliberate manipulation.

To guard against these potential threats, the US government is funding the development of tests to detect dangerous bioengineered organisms before they have a chance to cause significant harm. The effort was announced in 2017 by the Intelligence Advanced Research Projects Activity, or Iarpa, within 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% accurate in identifying the presence of bioengineering. “We just never know what sample is going to walk through the door of a government lab, and we have to be prepared for anything,” Markowitz said at the press conference.

One of the platforms, created by the Cambridge, Mass.-based nonprofit Draper, is a rapid, portable testing device that uses a thumbnail-sized chip to detect genetic material. amended. The other is software developed by Boston biotech company Ginkgo Bioworks that uses machine learning to identify engineering in genomic data generated from organism samples. (The companies have yet to publish their results in a peer-reviewed journal and their platforms are still in development.)

Crops and animal feeds are already extensively screened for the presence of genetic traits that cannot be found in nature or created through conventional breeding. Scientists use a test called PCR, or polymerase chain reaction, to determine if bio-modified DNA is present and in what quantity. When it comes to food labeling, scientists usually know what genetic change they are looking for. But no general-purpose tools exist to detect altered genetic material in bacteria, viruses, or other organisms that could appear in any setting.

Until now, detecting the presence of bioengineering has relied on laborious and slow manual analysis. Through a process called sequencing, researchers can generate a readout of 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 determine whether an organism’s genetic code has been altered, scientists need to know what its genome and those of its close relatives normally look like. Then they can look for areas that are out of the ordinary.

DNA can be manipulated by at least half a dozen processes. A conventional method is to add a gene from one species to another, usually for bioengineered crops. Pieces of DNA can also be moved from one part of an organism’s genome to another part, a type of change called translocation. Crispr gene editing, which is being explored as a way to treat disease in humans and improve plants and animals bred for human consumption, can remove 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 behind bioengineering signatures. For example, scientists can tell if a gene has been added or moved by comparing that organism’s genome to a reference sample. When using Crispr, deletions sometimes appear in other parts of the genome that look like the targeted section, but are not. Talens and zinc finger nucleases also tend to produce these “off-target” effects. Deliberate use of radiation can also produce traceable DNA mutations.

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