The mystery of life’s broken symmetry

How did life originate? University of Groningen chemistry professor Ben Feringa believes this is the most important question for science. It has been at the back of his mind since he started out in chemistry. Especially the question of why life appears to prefer just one of the two mirror-image versions that many organic molecules appear in. It’s an unsolved riddle.

Ben Feringa has had a busy few months, to put it mildly, after winning the 2016 Nobel Prize in Chemistry with his colleagues Sir James Fraser Stoddart and Jean-Pierre Sauvage. In several of the interviews he gave at the time, he was asked which research questions he would like to tackle. He mentioned the origin of life on several occasions.

Many molecules can exist in two versions, so like your two hands they are the same but each is the other’s mirror image. During the chemical synthesis of these molecules, a 50/50 mixture of both ‘hands’ will appear. Feringa has spent a good deal of his career devising ways to produce just one of them. He estimates the market for chiral drugs (just one of the two versions) to be worth around EUR 350 billion per year. ‘In many pharmaceuticals, one version is usually active. The other might even be dangerous.’ This is what caused the thalidomide drama in the 1960s. One ‘hand’ produced the sedative action, the other caused congenital malformations in pregnant women.

Figure head

Living organisms prefer amino acids in their L-form (left hand) and sugars in their D-form (right hand). Enzymes make the necessary version in all cells. ‘But why does life use just one configuration when two are available? This chirality is seen as characteristic of life’, says Feringa, who is the ‘figurehead’ for the new Origins Centre, which will try to find out just how life could have formed. ‘So how did this preference start?’ That is the question that Feringa would dearly love to answer. And he has spent most of his career working on it.

‘It goes back to my time in the lab of my PhD supervisor and mentor Hans Wijnberg ’, recalls Feringa. ‘We discussed this question of how life became chiral, and got a bit carried away. We experimented to find out how the symmetry of prebiotic molecules or early replicators, precursors to life, could have been broken.’ The results were unconvincing. Several theories have been put forward since. Most describe how a small surplus of one form can occur, through pure chance or the action of circular polarized light . Other theories propose that chiral minerals or the coriolis effect may have stimulated chirality.

Relevant

‘One time I found a 0.06 percent amplification of chirality using circular polarized light ’, he recalls. Such a small difference could be important if chiral forms would then catalyze their own formation. ‘This autocatalysis has been shown to happen – but usually not in systems that are relevant to biology.’ Feringa himself recently showed auto amplification in a system where molecules aggregated into a gel made of fibres. Many other routes have been proposed, but in the end, Feringa says, ‘we have no idea how relevant they are’.

Last November, his PhD student Anne Schoonen defended her thesis on the subject. ‘This was part of an astrobiology programme. She tested a number of mechanisms for achieving homochirality under prebiotic conditions. But the results were a bit disappointing.’ Schoonen did her experiments in water, a biologically relevant solvent. Others have found more promising results, but not in water – which makes their work much less relevant.

Time

Feringa’s lab is not doing any ‘origin of life’ work at the moment. ‘It is on and off, depending on the availability of money. I do have some ideas, but it is difficult to get funding for research that has no immediate practical application.’ In that respect, the National Science Agenda might offer an opportunity. It promises extra funding to tackle questions proposed by the Dutch public. The Origins Centre will tackle the questions relating to the origin of the Universe and life. ‘My questions about symmetry breaking would fit in nicely.’

In the interviews mentioned above, Feringa speculated that it might take another thirty years to find answers. ‘It won’t happen overnight, but bit by bit we may find an explanation. Even finding a plausible mechanism for symmetry breaking would be a major breakthrough!’

This is the fourth part of a series on University of Groningen research into the origin of life and the Universe.
Part 1: New research centre on the origins of life, the universe and everything
Part 2: Evolving molecules point to principles of life
Part 3: Synthetic biology: building life

Part 5: Life amongst the stars
Part 6: Origins on a computer