Is ‘Frankenbacteria’ our best hope to defeat future bioterrorism?

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Bioterrorism is terror by science, the intentional release of toxins, bacteria or toxins to cause illness, death and panic. When situations like the Ebola crisis happen, biological weapons of mass destruction using disease become a major concern for the public.

Unstable situations around the world make the threat palpable. Terrorist organizations in both Pakistan and India are focusing on both biotechnology and nuclear weapons, with the possibility of using them against civilians and security forces. Recent border skirmishes between Pakistan and India, the cloud of civil war in Afghanistan and the emergence of the Islamic State of Iraq and Syria (ISIS) in the Persian Gulf and the Arab world further underscores the possibilities of the complex threat of chemical and biological terrorism. 

Yet even when biological WMDs are not getting publicity, the United States Department of Defense has a whole division devoted to that field, called the Defense Threat Reduction Agency (DTRA), and they spend almost $4 billion each year to protect our public health infrastructure – ‘gloves and drugs’, as they call it. What are they working on? The actual list of biological threat agents is classified but when Ebola became a source of public outcry, DTRA disclosed that it had quietly been funding a drug called ZMapp and it was rushed into use.

Gloves and drugs are certainly needed now but the future of threat protection belongs to programmable agents that can react to whatever threats happen, as they happen. DTRA recently revealed that scientists working for them have created a hybrid bacteria – a cyborg mix of computer chip and genetically modified organism – that can not only detect infectious diseases but automatically mobilize to defeat them.

To accomplish it, the researchers have created DNA microarrays with a twist. DNA microarrays are a common tool for biological research – for example, a tiny device gets embedded with a protein to find out what is happening.

The biohybrid device receives both chemical (enzyme reaction precursor) and electronic inputs, and through biochemical intermediates, translates them to both electrochemical signals and biological cell responses. A representation of the components of the multi-domain fusion protein (HLPT) is shown . By varying the electronic inputs through the electrodes on which HLPT is attached, they can vary the attenuation of HLPT activity and thus affect the electrochemical and biological responses in proportion to the input. Credit: Created for the Department of Defense by Dr. William E. Bentley, University of Maryland 

The new research takes that to the next level. Rather than using DNA microarrays
to simply investigate what is happening, they have actually controlled cell metabolism – all on a chip. That’s a real breakthrough, it could lead to genetically engineering ‘smart’ bacteria to defeat infectious diseases that could be utilized by 21st century bioterrorists.

The proof of concept was a reduction-oxidation (redox) molecule called autoinducer-2, which they used to tune what is called a multi-domain fusion protein – HLPT, which gets its name from the purification domain (His6),the catalytic domain (LuxS and Pfs) and the assembly domain (Tyr5). Since they were able to control the output based on the electrical input, it means they can change its biological behavior.

In the graphic above, you can see that their bio-hybrid device has both enzyme reaction precursor and electronic inputs, which get translated to both electrochemical and biological responses in the cell.

When the signal was introduced, the researchers got the cells to ‘act together’ and create a blue fluorescent proteinThe application was touted as being valuable for drug discovery and it certainly will make drug discovery far less expensive, but population-wide biological behavior that can be modulated electrically, allowing researchers to alter the enzymatic generation of a signal molecule, has a lot of potential for next-generation defense, exactly the reason that the Defense Threat Reduction Agency supported the project.

Such ‘smart’ bacteria could be programmed in the field, using a laptop or even a tablet, to automatically guide their actions based on chemical cues which reveal what bioterrorists might be throwing at soldiers.

Hank Campbell is founder of Science 2.0 and an award-winning science writer who has appeared in numerous publications, from Wired to the Wall Street Journal. In 2012 he was co-author of the bestselling book Science Left Behind. Follow him on Twitter @HankCampbell.

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