For decades, living cells have powered biomanufacturing. Pharmaceutical companies use microbes and cell cultures to produce insulin and other medications, while food innovators use engineered yeast to create animal-free versions of whey protein and other ingredients. In each case, the cells do the essential work. Now, a new wave of biomanufacturing takes the cells out of the equation. By isolating and reusing life’s essential molecular machinery — such as enzymes and ribosomes — scientists can produce valuable compounds with even greater precision and flexibility.
“Cell-free systems are a way to make proteins without the complicated living cell present,” explains Associate Professor Kate Adamala, a synthetic biologist in the College of Biological Sciences Department of Genetics, Cell Biology and Development, and a member of the BioTechnology Institute. “That gives you the flexibility of making proteins or protein-like products that have much more chemical diversity than natural proteins.”
That power underscores the potentially transformative nature of cell-free technologies, which have already entered the manufacturing pipeline for innovative pharmaceutical products. It’s also what motivates Adamala’s effort to ensure these systems are developed responsibly. Supported by a BioMADE grant funded through the U.S. Department of Defense, Adamala leads a collaboration with the Georgia Institute of Technology to study the security and safety implications of cell-free approaches. “People have a lot of ideas for what cool, useful things can be made with cell-free systems,” she says. “But no one has systematically looked at what needs to be done to deploy those products at scale — and to do it safely.”
The project will analyze potential environmental and biosecurity risks, identify gaps in existing regulations, and propose strategies to address them. One of the team’s key goals is to determine whether genetic material from a cell-free platform could be taken up by living cells through horizontal gene transfer, a process in which genes move between organisms rather than being inherited. For more conventional genetic engineering techniques, such as those used to develop high-yield or resilient crops, these questions have been thoroughly investigated. But when it comes to cell-free approaches, researchers are only beginning to understand what risks, if any, might exist.
A key component of the project is a public database that will document how cell-free systems behave under real-world environmental conditions. The resource will connect those findings to existing regulatory frameworks and serve as a shared reference for researchers and companies alike. At present, biosafety regulations don’t fully capture the nuances of cell-free technology, and many industry protocols have yet to catch up — another gap that Adamala’s project aims to fill. “We’re not promising a standard operating procedure for every company,” she says. “But we can provide the boundary conditions you need to develop safe operating protocols in your company.”
Adamala’s collaborator, Margaret Kosal, a professor in Georgia Tech’s Sam Nunn School of International Affairs, brings a policy and security perspective that complements Adamala’s technical expertise. A former science and technology advisor in the Office of the Secretary of Defense, Kosal has long worked to strengthen national and international safeguards against the misuse of emerging technologies. Together, their collaboration highlights that biosafety and biosecurity are shared responsibilities that extend across scientific research, industrial practice, and public policy.
Ultimately, Adamala views the BioMADE project as a capacity-building effort that provides a first step toward a comprehensive framework for evaluating next-generation biomanufacturing platforms. “It’s shaping the way we think about safeguarding these technologies,” she says. “It’s not just a single deliverable, like we’ve made a molecule and now we’re happy. We’re building the foundation for producing a huge variety of different products.” –Jonathan Damery