Chemistry is a hands-on profession. For centuries, chemists have spent time in the lab weighing solids and measuring liquids to make molecules and discover new reactions that could change the way a product is made. “Chemistry is still a highly experimentally demanding discipline – you need to work in the lab to get results” says Cristina Nevado, an organic chemist at the University of Zurich, Switzerland.

But automation is changing the game. Using robotics, an automated flow reactor is capable of optimising a reaction that might take a human chemist weeks or even months, in only one day, whilst the drug discovery robot Eve, combines lab skills and artificial intelligence (AI) to test and modify a hypothesis at a rate that a human chemist could never achieve. In addition, automation has also played an important part in making chemistry and synthetic synthesis more efficient. For example, Unimate, the first industrial robotic arm patented in 1961, has been continually modified and is now able transfer vials and tubes into analytical machines or dispense amounts of liquid too small for human hands to handle. Automation also removes errors and inconsistencies present when humans measure the substances. Whilst many of these machines are still expensive for individual labs to bring in, chemical synthesis made simple by a machine could transform science. When Har Gobind Khorana synthesised the first gene in the 1960s, few could have predicted how rapidly automation would contribute to DNA sequencing and synthesis technology. Today, however, ‘Oligonucleotide synthesis’ has gone from being a lengthy process for even a large team of skilled chemists, to a straightforward process that is entirely automated, enabling wider DNA nanotechnology such as genetic circuits. 

 

Indeed, learning from this success, scientists are considering constructing whole genomes from scratch – something unthinkable a couple of decades ago. Martin Burke from the University of Illinois at Urbana-Champaign, is a pioneer in the field of modifying chemistry who is actively pursuing the evolution of automated chemistry. He built a small molecule synthesiser to prove technology could not only free chemists from the more tedious parts of their work, whilst completely changing the way molecules are made. He explains: “Most automation efforts have been predicated upon the assumption that each molecule requires a customised synthesis route. So, we have been developing machines that can do many different reactions. Our pitch is the opposite; let’s instead try to figure out how to make everything with one reaction.” Burke’s team applied this idea in a small compound synthesiser and managed to prepare 14 different classes of small molecules, including fatty acids, polyketides, oligophenylenes and steroids from the one robot. Burke estimates that given a larger number of building blocks – around 5,000 – the machine could make up to three-quarters of all 260,000 small natural products known to date. However, as Ross King from the University of Manchester, UK, who led the work on robo-chemist Eve says: “automation brings technical and sociological challenges.” 

 

These arise as most chemists are not trained in computer science, but to do lab work manually. Therefore, a wealth of reskilling and retraining needs to be done in order to realise the potential of fourth industrial revolution-led technology in chemistry. Automation in applied chemistry is only the beginning. Combining robots that are becoming increasingly useful in the lab and the emergence of ‘Big Data’ could change the field of chemistry completely. For instance, Peter Seeberger, of the Max Planck Institute of Colloids and Interfaces believes that in the future, chemists will share data and use pooled facilities. “In the next two to three years, chemists will run their practical experiments remotely at synthesiser farms – the only people that work there will be there to make sure there’s always enough reagents and the machines run properly.” Does this mean that in the not-too-distant future chemists will be obsolete? Quite the opposite, Seeberger says. “We train people to think about chemistry, not to do manual labour, and to think and be creative, those are skills that are never going to be replaced by machines.”