When life gives you lemons, make life (Image: Stock Connection/REX)

We are a step closer to understanding how life began, and we can thank the humble lemon.

For the first time, genetic information has been copied inside a simple cell designed to mimic primordial life. Until now, such copying had the unfortunate side effect of destroying the cell, but researchers have found that the cell can be stabilised by adding a dash of citrate. The substance is synthesised from citric acid, a chemical found in lemons and oranges.

“We’ve found a solution to a long-standing problem in the origin of cellular life,” says Jack Szostak of the Massachusetts General Hospital in Boston.


The work is part of an ongoing project that aims to figure out how the first life on Earth formed from a collection of lifeless molecules. To reconstruct what happened, Szostak and his team have been experimenting with simple “protocells”, essentially bubbles of fatty acids. These protocells are crude versions of the cells that make up all modern organisms. Despite lacking any of the complex cellular machinery, they can reproduce by dividing to form daughter protocells. “What’s missing is a replicating genetic material,” Szostak says.

The first life on Earth probably used RNA instead of DNA to carry its genes. It is a simpler molecule and can perform a host of other functions that would have been helpful to the first organisms. Szostak has already persuaded his protocells to carry a cargo of RNA. The next step is to get that RNA to copy itself. That way, when the protocell divides, each daughter cell can be endowed with copies of all the genetic material.

Stop the destruction

RNA molecules make copies of themselves from a mix of smaller molecules called nucleotides, each of which is a “letter” in the genetic code. The nucleotides must come together on the existing RNA, and hook up.

In the lab, the assembly needs a helping hand from magnesium ions, or similar charged particles. But by itself that won’t work in Szostak’s protocells, because the magnesium ions react with the fatty acids, tearing the cell to pieces and dumping the newly minted RNA into the surrounding water where it would rapidly disperse.

With Katarzyna Adamala, Szostak has now found a way out. They tried adding lots of different chemicals to the magnesium and protocell cocktail, and eventually found one that stabilised the cells while still allowing the RNA to copy itself.

The wonder chemical is called citrate, and is easily produced from citric acid. In the protocells, each citrate molecule clamps on to a magnesium ion like a hand around a ball, preventing it from reacting with a fatty acid but still allowing it to interact with the RNA.

“It’s a very remarkable observation,” says Ramanarayanan Krishnamurthy of the Scripps Research Institute in La Jolla, California. “This citrate is able to stabilise RNA against degradation, and also stabilise the protocells against leakage.”

If citrate was an essential ingredient for the formation of the first life then it must have been abundant on Earth 4 billion years ago. Citrate is found in many modern organisms but it is unclear whether it could have existed that long ago. However, Krishnamurthy says that similar molecules certainly did form, and might work just as well. Szostak is also examining whether small peptides, which are known to bind magnesium ions, might do the trick. “We haven’t found a simple peptide that is as good as citrate yet, but we are looking,” he says.

Primordial Xerox

Szostak’s method is crude, and does not use any enzymes to help the copying along.

He says there is still some way to go before the system works well enough to sustain living organisms. For example, Szostak wants the copying to be faster and more accurate.

There is an alternative approach, promoted by Philipp Holliger of the MRC Laboratory of Molecular Biology in Cambridge, UK. RNA can act as an enzyme, so Holliger is trying to create an RNA enzyme that can self-replicate, by accelerating its own natural copying process. He recently built one that could copy strands of RNA longer than itself, a major step towards a self-copying enzyme.

However, Krishnamurthy says that such complex enzymes probably evolved at a later stage, once RNA-based life was established. “In the absence of the sophisticated enzymes, citrate could have played that role,” he says.

Journal reference: Science, DOI: 10.1126/science.1241888