For centuries, people have argued about what separates something that's alive from something that's simply chemistry.
Every living thing, from bacteria to blue whales is ultimately made from the same atoms as the rocks beneath our feet. The difference isn't the ingredients. It's how they're organised.
So how few ingredients can you assemble before chemistry starts behaving like life?
A team of synthetic biologists have taken a step towards answering that question by building what they call a synthetic cell entirely from carefully chosen chemical components. Published this week they assembled every component themselves, creating a tiny cell-like structure whose complete ingredient list is known.
The cell can't survive on its own, can't evolve naturally and still depends on scientists to feed it, but it can repeatedly feed, grow, copy its DNA and divide into daughter cells, performing several of the key behaviours we associate with life.
They carried out a series of experiments, each asking whether one more essential feature of life could be recreated from non-living ingredients.
Experiment 1 - Can you make an artificial cell grow?
The researchers began with tiny fat bubbles called liposomes as artificial cell membranes. Inside they placed a carefully designed 90,000-base-pair synthetic genome spread across seven plasmids, along with a purified protein-making system called PURE that could read DNA and build proteins.
Real cells grow by taking in nutrients, artificial cells can't, so the team invented tiny "feeder" liposomes loaded with fresh proteins, ribosomes, enzymes and membrane material.
The question was - can one artificial cell feed another?
To find out, they engineered the synthetic cells to manufacture a membrane protein called α-hemolysin carrying a short histidine tag. Feeder liposomes were coated with nickel-containing lipids that recognised this tag. When the two met, they fused together, delivering both nutrients and fresh membrane material.
The researchers watched the membranes merge, the contents mix and new proteins begin to appear inside the enlarged synthetic cells.
Remarkably, the ability to feed wasn't controlled externally, it was encoded by the synthetic cell's own DNA. Cells that produced more of the membrane protein fed more efficiently and grew larger.
Experiment 2 - Can it repeat the process?
Growing once isn't life, living cells must grow repeatedly.
Every 12 hours the synthetic cells were fed, their DNA copied and the population divided before beginning the cycle again.
The synthetic cells successfully completed five generations of feeding, genome replication and division.
Each generation produced new DNA, new RNA and new proteins while maintaining much of the original 90,000-base-pair genome. Around 30% of daughter cells still inherited the complete genome after five generations, an impressive result given that the system lacked many of the sophisticated mechanisms real cells use to organise DNA during division.
Experiment 3 - Can evolution begin?
This experiment asked whether the synthetic cells could experience something resembling natural selection.
The researchers deliberately introduced a tiny genetic change.
One version of the synthetic genome contained a stronger promoter controlling production of the feeding protein α-hemolysin. That meant these cells could produce more feeding proteins, fuse with more feeder liposomes and potentially grow faster.
They then mixed equal numbers of fast-growing and slow-growing synthetic cells together.
After just five generations, the faster-growing cells had become the majority.
When food became scarce, their advantage became even larger.
The synthetic cells weren't evolving in the full Darwinian sense because the beneficial mutation had been introduced by the researchers rather than arising spontaneously.
But they were undergoing selection.
The cells with the more advantageous genome produced more offspring, causing that genetic version to spread through the population, one of the defining processes that shapes life on Earth.
So... is it alive?
That depends on who you ask.
The synthetic cell doesn't yet tick every box that biologists would associate with life. It can't survive without scientists feeding it. It borrows ribosomes from bacteria rather than making its own. And while it can undergo selection, it doesn't yet evolve naturally because the beneficial mutations were introduced by the researchers rather than arising spontaneously.
The more interesting question isn't whether this tiny collection of chemicals has crossed some invisible line between chemistry and life. It's whether scientists are finally beginning to understand what that line actually is.
For the first time, researchers can begin asking not just what life is, but which parts of life are absolutely essential.
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