Science - March 15, 2018

Making things come alive: Lee Cronin wants to recreate the transition from dead to living matter

Albert Sikkema

On 9 March Lee Cronin gave the keynote speech at Wageningen University’s 100th Foundation Day. The unconventional British chemist links an age-old question – how did life come about? – with ultramodern chemistry. ‘In this I am God the creator. Not in order to play God but in order to understand how life came about.’

Text Albert Sikkema photo Guy Ackermans

Lee Cronin poses one of the most fundamental and crucial scientific questions: how did life on earth come about? If we turn back the evolutionary clock, we end up about four billion years ago with the bacterial cell, the oldest and smallest living creature to be subject to evolution. But how did that first bacterium emerge from the dead material – atoms and molecules – on Earth, wonders the British professor.
We have an established image of the process as a turbulent ocean, a kind of primal soup of chemical elements with thunder and lightning on the horizon. The storm creates electricity and life emerges from the convergence of electricity and matter. Cronin is familiar with this time-honoured story but says, ‘To be honest, we have no idea whether it’s right.’

Cronin, who works at the University of Glasgow, also assumes that life on earth emerged from dead matter. ‘The main evidence for this is the fact that there is life on earth. It is an open and very exciting question. Many researchers focus on the question of what chemistry was needed for life, but nobody works on the functional systems that make life possible. Our group thinks this is the only way to answer this question.’
So Cronin is trying to recreate the transition from dead to living material in the lab. And he thinks evolutionary theory applies to this process as well. ‘The fact that evolution takes place in the biological systems we know gives us starting points for the idea that evolution might also have played a role in the formation of the first living cell. We are now researching in laboratory experiments how the first cells might have come into being. This seems to us to be the only way biology can have started on Earth.’
Cronin is not afraid of being provocative. During the Masterclass for Wageningen researchers, he gives reasons why creationism cannot be right. Creationists think life on Earth came about through a unique act of creation, and life only exists on Earth. The chances of that are as big as the chances that a monkey you sit down at your computer will happen to write a novel, argues Cronin.  

Not in order to play God but in order to understand how life came about.

Evolution machines
The chemist wants to build an ‘evolution machine’. ‘In this I am God the creator,’ he says. ‘Not in order to play God but in order to understand how life came about.’
In his lab he seeks to bring together the fundamental building blocks for life. This means atoms and molecules that react to each other and form new structures, fed by a source of energy. In these ‘fitness landscapes’ there are no proteins and no DNA, elements of biological life as we know it. Using software programmes, he tests countless random combinations of atoms and molecules, hoping thus to find ‘evolutionary algorithms’ that convert dead matter into living matter.
‘The question how life on Earth came about is actually a historical question. The only thing I can do as a chemist is conduct experiments in the laboratory and see whether my experiments lead to living systems.’

Printing drugs
As well as this quest for the origin of life, Cronin also works on practical matters such as how to print medical drugs. Medicines are complex molecules, and are currently made by pharmaceutical companies. The chemist wants to make them using a 3D printer, so that one day everyone will be able to print their own drugs. To achieve this, Cronin needs a toolkit of basic molecules. All medicines are made up out of carbon, hydrogen and oxygen molecules. As well as these chemical building blocks, he needs a recipe: the right combination of basic molecules for the drug. ‘We need to divide the manufacturing process into different steps with precisely defined building blocks,’ he explains. If you combine those building blocks with the right reagents, you get a kind of ‘ink pattern’, as it were, with which the 3D printer can construct complex chemical structures. Cronin’s group has successfully produced the painkiller ibuprofen this way.
Cronin foresees a future in which people keep the basic ingredients for medical drugs at home, in the same way as they have the ingredients for a meal in the fridge. If they need a medical drug, they get a recipe from the pharmaceutical company to print it at home. ‘The value is in the recipe, which has been validated by research, and not in following the recipe. The drug is an app, essentially.’
Cronin’s chemical computer, or ‘chemputer’, opens up the possibility that medical drugs can be made anywhere in the world, but also that drugs can be developed for small or poor groups of people. It also makes it possible to test new molecules on human cells quickly, speeding up the development of new drugs considerably.

Wild ideas
Cronin expects chemistry to change a lot in the coming years. ‘The chemists of the future will also have to be able to program computers, build databases and design semiautomatic systems for integrating their chemical knowledge so as to create new applications.’ 
Throughout the masterclass, Cronin throws out challenges to the physicists and biologists in the room. He thinks these disciplines can learn a lot from each other, under the influence of computer science and bio-informatics. ‘The biggest problem is that physicists, chemists and biologists speak different languages and don’t understand each other.’ He thinks the young computer-savvy generation is going to change things. ‘If I am allowed to allocate research funding, I don’t give any money to old researchers with brilliant track records. Because they will just do more of the same research. I put my money on young researchers with wild ideas, without track records.’

Before the formalities of Foundation Day, Lee Cronin (in lilac trousers) poses with the cortege of professors.
Before the formalities of Foundation Day, Lee Cronin (in lilac trousers) poses with the cortege of professors.

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