Darwin in a drop of water

Groningen molecules mimic life and evolution

Replication and speciation: until now, that's only been observed in living organisms. But in Groningen molecules appear to be doing it in test tubes. How does that work?

Text: Jean-Paul Keulen

Sometimes the best gift is something you didn’t ask for. That happened to Sijbren Otto, professor of organic chemistry at the University of Groningen. He and his team tried to make molecules that are folded just like proteins.

(photo credits: Kees van de Veen/HH)Everything starts with a drop of water in a test tube (photo credits: Kees van de Veen/HH).

Instead, something entirely different was created in the test tube with half a millimetre of water: a molecule that could replicate itself.

Building blocks, rings and stacks

Admittedly, Otto wasn’t the one to find the very first molecule that managed to pull off this stunt. ‘But previous molecules could only make a single copy of themselves and the two molecules would then remain stuck to each other. After that, the molecule and its copy didn’t do anything anymore,’ the chemistry professor explains. His molecule, on the other hand, kept copying itself. How does that work? You start with a drop of water in which the building blocks for the copying molecules are swimming around. Together they create different-sized rings. Rings consisting of three, four, five, six or more building blocks are all possibilities, for example. ‘Once they’ve been created, they constantly interchange building blocks. A ring with six of these blocks, a 6-ring, loses a building block, for example, and thus becomes a 5-ring. And if the lost building block ends up in a 3-ring, then that becomes a 4-ring.’

This continues until multiple rings of the same size stick to each other and create a stack. At that point, they stop relinquishing their building blocks. Rings of equal size are fished out of the surrounding water and added to a stack. The stacks thus continue to grow until the water essentially contains nothing else. These stacks consist of the so-called replicators that are the key to this entire process: the molecules that are able to replicate themselves.

(photo credits: ICMS Animation Studio)The stacks of replicators. These ring-shaped molecules are, as the name suggests, capable of replicating themselves. (photo credits: ICMS Animation Studio)

New ‘species’

Otto wondered what would happen if you put two different building blocks in the water. Let’s call them A and B. Do you then get one type of replicator that uses both building blocks? Or do two kinds of replicators emerge: one from building block A and one from building block B? ‘You could compare it to nature, where sometimes there are two available sources of food,’ Otto says. ‘Then you have one species that uses both sources of food, or two species that each use one source.’

What emerged initially during this experiment were replicators with a preference for building block A. But eventually replicators also emerged, that were the offspring of A, but that had a preference for building block B. ‘That’s comparable to how speciation happens in biology,’ Otto says. ‘There you also deal with mutations that eventually lead to the emergence of a new species.’

Molecule as predator

Earlier this year, Otto and his colleagues conducted an experiment that revealed less pleasant behaviour. This time the researchers began with two test tubes: one with building block C, the other with building block D. Replicators emerged immediately in the first test tube, whereas they replicated sluggishly in the second test tube.

Otto then added some replicators from the first test tube to the second. The result: suddenly replicators from building block D did grow, on top of the replicators from building block C. Thanks to the C replicators, the D replicators were able to reproduce.

Then the brand-new D replicators did something that could be considered ‘ungrateful’. ‘They tore the replicators made from building C to pieces,’ Otto says. ‘They used the building blocks that were freed as a result to multiply even more. I would call that parasitical behaviour, or even predatory behaviour.’

Feathers and stacks

It’s great, of course, that molecules display speciation when you give them different kinds of ‘food’, or that one disassembles the other. But Otto wants to take it one step further. ‘We want open-ended evolution. In other words, we don’t want replicators to only do things that we devise; we want them to discover new things themselves.’

That sounds like something from the distant future, but it has in fact already happened. It seems replicators can ensure that the building blocks in the surrounding water form rings more quickly than in water without replicators. And that favours the replicators. After all, they consists of a stack of rings. These stacks can’t do much with individual building blocks, they need rings to grow. Here too, Otto draws a comparison with evolution. ‘Sometimes something with a certain evolutionary goal is hijacked to achieve a completely different goal. Take feathers. Initially their function was to keep an animal warm. But then it turned out that you can use them to fly as well. Similarly, the first stacks of rings here emerge as a way for molecules to copy themselves. Subsequently it turns out that these stacks are also capable of accelerating chemical reactions in their environment that benefit replication.’

What is life?

If Otto’s stacks do all kinds of things that living beings also do, would it be accurate to call them a form of life? ‘Well, that begs the question: what is life? We don’t have a real answer to that yet. But you can make a list of conditions that life has to meet. One of these is that life has to be able to reproduce. Our molecules are doing that. Moreover, living systems are capable of metabolism. The ability to accelerate the conversion of building blocks into  rings that the replicators can use can be viewed as a first step in that direction. And finally, you want a life form to be an enclosed entity, just as a membrane compartmentalises a cell. Well, that can’t be said of our example. In our case it concerns strings floating around unprotected in a fluid.’

So we can’t call Otto’s replicator a life form yet. But it’s not far off. Not bad for a molecule that was a surprise gift for the scientist from Groningen.

How did life originate?

Can the replicators in chemist Sijbren Otto’s lab tell us more about how life on Earth could have originated from lifeless molecules? ‘The molecules that we work with are probably not the same as the ones with which life began on Earth 3.8 billion years ago. Which ones those were is a question occupying many scientists all over the world. But less research is being conducted on how these molecules replicated at the time. Perhaps they used the same trick as Otto’s molecules: replicate by assembling into larger structures, where the assembly process drives the formation of the very molecules that assemble. Otto would like to combine his search for which molecule was the catalyst for human life with his own research. ‘Who knows, we may be able to construct a plausible scenario of how life originated.’