Synthetic Cells: Building Life from Scratch with Kate Adamala and Drew Endy

In this Shortwave episode, Kate Adamala and Drew Endy discuss the quest to build a cell from scratch. They compare bottom-up synthetic biology with minimal-genome approaches, and describe how a programmable, cell-like system could advance cancer therapy, medicine production, and green energy. The conversation uses vivid analogies—such as a building-sized cell and a bookstore inventory—to explain how scientists might design, test, and understand living systems. They also address the shift from biology as a mystery to an engineering discipline, the timelines involved, and why achieving synthetic cells could transform both science and industry.

Introduction: The Physics of a Cell and the Drive to Build

The episode opens with a provocative question: can we construct a living cell from non-living parts, and what would that enable? Kate Adamala, a biological engineer at the University of Minnesota, and Drew Endy, an engineer at Stanford, describe a field moving from empirical tinkering toward programmable design. They frame synthetic cells as not just a medical or energy solution, but a way to reveal how life works by allowing researchers to observe and predict cellular behavior in a controlled construct.

Two core themes emerge early: first, the field is advancing from working with existing cells to assembling a cell from fundamental parts; second, this shift is not purely academic. If scientists can master synthetic cells, they anticipate new cancer therapies, cheaper drug production, and engineered systems for artificial photosynthesis. Yet they acknowledge that life’s full complexity remains, and that even with synthetic tooling, biology will retain mysteries that engineering cannot fully erase.

Three Pathways in Synthetic Biology

Drew Endy outlines three historical streams converging on the same target: understanding and constructing cellular life. The origins-of-life researchers have long pursued creating cells; another stream has minimized natural cells to essential components, producing minimal synthetic cells. The third stream, which has accelerated in the last decade, brings engineering to the fore, expanding genetic programming from single genes to complex pathways inside living cells. The conversation emphasizes that Build-a-Cell represents a bottom-up approach, where researchers select and assemble DNA blocks to boot a functional system from scratch, rather than transplanting a genome into a natural recipient cell.

The Bottom-Up Vision: A programmable cellular “inventory”

Adamala describes a synthetic cell as a bookstore you fill shelf by shelf, but with complete knowledge of what each component is supposed to do and where it should go. The goal is not merely to recreate life, but to understand and predict how each part contributes to overall behavior. This requires moving beyond observing a complex natural cell to constructing a controllable, testable proxy that behaves like a cell while staying within engineered bounds. The dream is a fully open system, unbounded by the constraints of existing lineages, enabling designers to explore alternative biological architectures and functions.

Historical Context: From Genome Transplantation to Full Boot-Up

The conversation traces a shift from early genome-synthesis efforts, where synthetic genomes were used to control existing cells, to the more ambitious aim of booting an entire system from scratch. This progression changes the problem from modifying a living cell to building a living, operating system from the ground up. The panelists highlight that the recent advances empower engineers to specify every DNA block and its role, potentially enabling predictable means to harness biology for medicine and energy while pushing the boundaries of what constitutes a living system.

Why Build Synthetic Cells Now: Economic and Scientific Drivers

The speakers connect synthetic-cell research to broader societal needs: a green economy, reduction of petrochemical dependence, and equitable technological progress. They argue that true understanding of molecular biology requires the ability to construct, test, and iterate at the most fundamental level. By building a cell from the ground up, researchers hope to unlock new therapies, scalable production of pharmaceuticals, and engineered systems for sustainable energy, aligning with broader scientific and economic goals rather than relying solely on natural cellular platforms.

Implications and Reflections: Limits, Promises, and the Next Steps

Both participants acknowledge that while progress is real and accelerating, defining life remains philosophically and scientifically challenging. The field is moving toward “cell-like” entities that perform core life functions, yet full complexity remains a distant horizon. The discussion emphasizes that synthetic-cell research is not merely about replication or novelty; it is about building a robust engineering framework that can illuminate biology, drive practical applications, and shape future policy and ethics around engineered living systems.

Quotes

"The synthetic cell would be like a bookstore that you're filling one shelf at a time," says Kate Adamala, describing a controlled, knowledge-driven build.

"Booting up the whole thing from scratch gives us this full operational control over every element of it," Adamala adds, underscoring engineering aims.

"If scientists can create cells, they can be programmed to do all sorts of things," notes Drew Endy, highlighting the transformative potential of programmable biology.

Adamala continues, explaining that this approach is essential to realize bioengineering’s promises and address global challenges.

Endy emphasizes that the field seeks to invent capabilities biology never bothered doing, expanding the scope of what engineered life can achieve.