For the very first time, biologists packed nonliving components into a cell-like membrane, piece by piece, and watched the bag of molecules start behaving like life.

Kate Adamala, a synthetic biologist at the University of Minnesota, led the team that built SpudCell — a fully synthetic cell constructed entirely from individually purified, non-living components. It contains 36 enzymes, a 90,000-base-pair genome split across nine DNA molecules, and a simple lipid membrane. And it just completed a full cell cycle: growing, replicating its DNA, and dividing into daughter cells.

"It's an impressive step," said Jack Szostak, who studies the origins of life at the University of Chicago and was not involved in the research. "I don't know of any other effort to put together an artificial cell from biological components that has progressed so far."

The cell is not alive by any definition. It cannot survive without constant deliveries of food and ribosomes. It has no defenses, no metabolism, no waste-removal system. But it is the strongest demonstration yet that life-like behavior can emerge from dead molecules — a goal synthetic biologists have chased for decades.

How It Works

Unlike earlier minimal-cell projects that carved genes out of living bacteria, SpudCell was built bottom-up. Its genome does not encode metabolic genes, so the cell must be fed through "feeder liposomes" — tiny lipid bubbles packed with sugar, enzymes, and ribosomes that fuse with the cell membrane. A protein the cell makes from its own DNA controls whether it can feed, how fast it grows, and how large it becomes.

For division, Adamala's team sidestepped one of the field's biggest bottlenecks. Natural cells divide using a cytoskeleton — an internal protein scaffold that requires dozens of coordinated proteins. Building one from scratch has proven nearly impossible. Instead, SpudCell uses a trick borrowed from the lab of Reinhard Lipowsky: proteins crowd together on the membrane surface until mechanical stress forces the cell to split. Cells that make more of this surface protein divide more efficiently, directly coupling the genome to reproductive success.

"It's a big step forward to this holy grail of making a living thing out of dead components," said Sijbren Otto, a systems chemist at the Stratingh Institute for Chemistry in the Netherlands.

Selection and Competition

The team didn't stop at division. When researchers introduced a genetic change that increased production of the fusion protein, cells carrying that change grew faster and produced more offspring. After five generations, the faster-growing variant had outcompeted the original — selection and competition operating in a fully synthetic chemical system.

"Combining all of these things is a staggering technical accomplishment," said John Glass of the J. Craig Venter Institute. "I think it will prove to be a watershed event for the synthetic-cell field and biology in general."

Not Without Controversy

The work has not yet been peer-reviewed. Adamala sent the 190-page manuscript to journalists under embargo before uploading it to a preprint server — an unusual move that drew criticism from some colleagues. The paper was rejected by the journal Cell after one reviewer said SpudCells were "not real biology." Adamala says her group will submit to another journal soon.

Alongside the results, Adamala and collaborators announced the formation of Biotic, a nonprofit that will make their synthetic biology tools freely available to researchers worldwide.

"The modern cell is like a Dreamliner," Adamala said, referring to the Boeing 787. "We built a Wright flyer... the first bike frame with wings that flies 100 feet."

Sources: Quanta Magazine, Biotic/SpudCell, Science