According to the researchers, the breakthrough could open the way to a new era of synthetic biology, in which scientists design custom-made organisms that function like "living machines". For now, however, SpudCell—the name given to the laboratory-created structure—is only a prototype and cannot be considered a living organism.

The synthetic cell may nevertheless help scientists better understand the origins of life on Earth and provide new tools for solving important biological problems.

Drew Endy, a synthetic biology expert from Stanford University who was not involved in Adamala's research, told CNN that the synthetic cell equivalents created by scientists cannot yet be fully considered a form of life, although they resemble living cells.

Kate Adamala, a biochemist at the University of Minnesota, studies artificial life, synthetic biology and astrobiology. The structure created by her team is a microscopic droplet of water surrounded by a lipid membrane and filled with chemicals and DNA fragments containing instructions for just 36 genes. In many ways, it resembles a simple bacterial cell.

The structure, named SpudCell, can grow by combining with other similar membrane-bound structures, duplicate its genome and divide. However, it remains far from a living cell because it can only divide for a limited number of generations—around five—and cannot evolve.

Scientists have been trying to create artificial cells in the laboratory for decades. The goal has been both to understand the fundamental principles of life and to develop cells that could be more easily modified to produce specific chemicals.

Most researchers, however, have previously focused on recreating individual cellular functions, such as nutrient uptake or growth. Combining multiple essential functions into a single artificial system has proved to be a much greater challenge.

"Being able to incorporate all of these modules together in a synthetic cell is the feat that the field has been waiting for," says Job Boekhoven, a systems chemist at the Technical University of Munich, although he stresses that the claims made in the new paper still need to be peer reviewed.

Scientists attempting to create synthetic cells from scratch have generally followed one of two approaches: using existing biological molecules, such as DNA and fatty acids, or developing completely synthetic building blocks. Adamala's team chose the first approach, relying on the PURE system, a technology developed decades ago.

The PURE system acts as a basic toolkit of biomolecules—including proteins and ribosomes—that are needed to transcribe DNA into messenger RNA and translate RNA into proteins.

Previous researchers have placed these components inside liposomes—tiny vesicles surrounded by a layer of lipids that resemble a cell membrane and contain an aqueous environment similar to a cell's cytoplasm.

However, those systems were never able to feed themselves and divide according to instructions encoded in their own genome.

"But [the droplets] were never able to feed and divide based on their genome," Adamala explains, quoted by Science.

To overcome this problem, her team engineered SpudCell's small genome, which is around 50 times smaller than that of a typical bacterium, with genes that allow it to produce special molecular tags. These tags are displayed on the surface of the lipid membrane and act as anchor points for feeder vesicles, enzymes and other molecules needed for growth and replication of the synthetic cell's genetic material.

SpudCell does not contain a cytoskeleton, a structure that plays an important role in the division of living cells. To solve this problem, the researchers introduced an alternative division mechanism into the synthetic cell's genome.

The mechanism relies on another type of surface tag called FLAG, which can bind to a large molecule called streptavidin. When enough streptavidin is added to the surrounding environment, the interaction creates repulsive forces between molecules on the cell surface, which can cause the synthetic cell to split into two.

The division process, however, remains highly inefficient. To achieve multiple rounds of division, researchers had to mechanically split SpudCells by forcing them through a membrane containing tiny holes.

Repeating this process revealed another problem. Because the duplicated genomes do not separate neatly during division, only about 30% of SpudCells still contained a complete genome after five division cycles.

The synthetic cell also faces another limitation: its protein-making machinery, based on ribosomes derived from E. coli bacteria, gradually breaks down over time. The system is unable to produce new ribosomes or remove old ones, meaning it cannot maintain itself indefinitely.

Despite these limitations, Drew Endy described SpudCell as "a catalyzing moment" for the field.

"It proves that by putting four or five different things together from disparate academic accomplishments, you can just barely get this thing growing and dividing," he says.

Science reports that Adamala's colleagues initially wanted to name the laboratory creation after her.

"Call it something that's not my name, call it a potato for all I care," she told them.

The team ultimately named the synthetic cell SpudCell.

According to Adamala, the fact that SpudCell's components are well understood means researchers should be able to improve it step by step.

"It's inefficient, but you know exactly how it's built," she says.

Although SpudCells do not yet possess one of the defining characteristics of life—the ability to evolve—Adamala's team carried out experiments showing that the system can undergo a primitive form of selection.

Researchers introduced a genetic mutation into some SpudCells that caused them to produce more surface tags for feeder vesicles. This allowed the modified cells to take in more "food" and grow faster than non-mutated versions.

After five rounds of growth and division, around 60% of the genomes carried the mutation. However, the researchers stress that this was not natural Darwinian evolution because the mutation was introduced by scientists and the cells still had to be mechanically divided.

"It’s a very cool paper. But I don’t think it means we’re close to creating a fully synthetic cell," says Seraphine Wegner, a researcher at the University of Münster.

Despite these limitations, many scientists, including Drew Endy, consider SpudCell a major advance. When Endy first saw the results more than a year ago, he began approaching government and philanthropic funders to support an ambitious effort to accelerate the development of fully synthetic cells.

Together with Adamala and two other researchers, Endy later founded a public-benefit research organisation called Biotic, which aims to coordinate research groups and speed up progress in the field. According to Endy, the organisation has secured seed funding of around $10 million and plans to distribute most of that money as research grants.

The project has also attracted criticism. Before releasing the work publicly, Adamala's manuscript was rejected by the journal Cell after one reviewer argued that SpudCells were not "real biology".

Adamala then sent the 190-page manuscript to journalists under confidentiality agreements before uploading it to the preprint server bioRxiv, where other scientists could examine and assess the research. She said her team plans to submit the work to another journal.

"It's an unusual way of doing things," comments Kerstin Göpfrich, a synthetic biologist at Heidelberg University, as quoted by Science.

Adamala defended the decision, arguing that releasing the research quickly—even before peer review—was important to encourage collaboration and accelerate progress towards synthetic cells.

She has also emphasised that the core SpudCell technology should remain open to researchers. Academic institutions and non-profit organisations would be able to use it free of charge, while commercial users would be subject to licensing fees.

"Right now, SpudCell cannot make anything useful, it’s not efficient enough. What I’m excited about is we’re gathering the international community to actually speedrun the development for it to become useful," Adamala told CNN.

According to Endy, SpudCell poses no current biosafety risk and could not, for example, be used to produce a biological weapon.

"It can only divide if you feed everything, including ribosomes. It has zero capacity to reproduce itself outside that context," he says.

Katarzyna Adamala studied chemistry at the University of Warsaw before earning a doctorate in biochemistry from Roma Tre University and Harvard University. She later completed a postdoctoral fellowship at the Massachusetts Institute of Technology (MIT).

A paper on SpudCell is available here. (PAP)

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