If you’re not familiar with the terms “synthetic biology” or “biohybrid systems,” you may want to add them to your vocabulary. If the US Army Research Laboratory (ARL) and other research institutions can carry out their plans, the technology will be mainstream in a decade.
ARL is betting that engineered living organisms — called synthetic biology — can be integrated into living and non-living (abiotic) systems to perform material synthesis, enhance human performance, provide environmental sensing, and control autonomous biohybrid devices.
“As synthetic biology has realized new possibilities, we’ve really started to look at how we can manipulate organisms to control devices,” confirms Bryn Adams. Dr. Adams is a biotechnology researcher at ARL’s Adelphi, Maryland facility. She recently published a feature article in the Synthetic Biology edition of the Journal of the American Chemical Society in which she predicted a future where scientists will place engineered DNA into systems, including engineered versions of the genes for photosynthetic proteins, that can be introduced into bacteria that are integrated into electronic devices to power them.
“I certainly hope to see that reflected in my career. We are certainly moving towards seeing synthetic [organisms] first integrated into systems as sensors or actuators, which perform a secondary function in a device,” said Dr. Adams. “I definitely see science moving that will allow us to create autonomous bio-hybrid devices where biology controls the device , makes the decisions, gives feedback, heals damage.”
Bacteria can be genetically engineered to both taste and smell biologically and interact with electronics to form a sophisticated biosensor. Scientists may one day even reach a point where they can engineer microorganisms into functional groups (consortia) that work as symbiotic systems, with different types of bacteria performing complementary functions. The goal would be to develop their coordination and hardness to the point where we can essentially 3D print biological structural materials like wood.
The field of synthetic biology gained momentum in the mid-2000s when scientists gained the ability to sequence and synthesize DNA quickly and cheaply, explains Dr. Adams out. Researchers began to understand how to design organisms from the bottom up. “When we were able to make our own DNA, control it, sequence the genomes and determine their function…that’s when doors really opened.”
ARL has been integrating natural organisms into developed systems for more than a decade, in systems such as the production of waste into energy (biofuels). “Now we’re moving from some of these natural organisms that work for us in the real world to engineering them [for other tasks].”
But placing synthetically engineered cells in living and abiotic systems is an order of magnitude more difficult. Organisms, even photosynthetic ones, need a constant supply of nutrients. Without them, they stop growing and divide, go dormant or form spores and stop functioning. To understand how cells respond to an environment – what they tell us – we need to use ‘readouts’ that require DNA sequencing or fluorescence microscopy. Finally, engineered genetic circuits in cells require a robust host, a carrier cell or “chassis” as ARL calls it, that can withstand the real world. All these complications make for challenging work.
Until now, synthetic biology has generally used E. coli as a host for engineered genetic circuits. Dr. Adams wrote a paper about an experiment she led to develop E.coli to integrate with abiotic surfaces (minerals, soil, water), including specific metals. But the lab strains of E.coli cells simply aren’t strong enough to survive outside a lab environment. (In fact, lab strains are specially designed to fail in the real world.) Researchers will have to find another chassis to make the science work.
“I see that as the biggest challenge. We can do really complex things in E.coli, but it will never be able to survive things like 3D printing or withstand the natural environment,” said Dr. Adams to Ars. She added that host bacteria need to thrive, not just survive as dormant entities. “We want organisms that do transcription, that reproduce, produce proteins in response to environmental signals.”
Can scientists really identify robust hosts and provide them with nutrients? Bryn Adams says they are taking the first steps. ARL is collaborating with several research institutions, including MIT, where Professor Chris Voigt developed a new broad-spectrum DNA transfer system that ARL is now using. The Voigt Lab at MIT has also developed a way for the cells to report on what they are doing.
A synthetic biology programming language called Cello automates the design of genetic circuits and allows the bacteria to record environmental conditions in DNA, which can then be read out by sequencing. “That makes it possible for us to build in all sorts of things, so we are not just dependent on a GFP [green fluorescent protein] marker,” says Dr. Adams. “Bacteria will never become computers. They will never do the complicated data processing that a computer does, but in E.coli we can already do simple computational tasks in the cell in terms of capturing information and giving information about things that the cell has been through, now it’s just taking that knowledge base and extending it to other organisms so we can do the same.
With that expansion comes the ability to integrate engineered cells into living systems, probably within the next five years. The military would use such designer microbes to improve human performance, among other things, potentially making soldiers stronger, faster, immune to certain infections and even self-healing to a greater extent.
Within the next 10 years, we could see microbes act as simple sensors or actuators in non-biological devices. Adams thinks autonomous biohybrid devices in which microbes regulate or heal the device will happen within her lifetime. The US has some of the brightest minds in synthetic biology, she says, but it’s certainly not the only leader in science. Other nation-states will accelerate its application.
“These aren’t lab demonstrators,” says Adams. “These are things that will be used in the field by militaries, governments and for commercial use.”
Eric Tegler is a freelance author and broadcaster from Maryland. His work appears in a variety of international publications on topics ranging from political and government affairs to the military, auto racing, business, aviation and car reviews, and lifestyle.