On-demand chemistry raises as many questions as it answers
I am dictating this using the voice recognition software on my mobile phone. It’s a device with hardware more powerful than the best mainframe computers in the 1960s. Yet no technical knowledge is required to operate it. Work that was once restricted to a few experts is now, literally, in everybody’s hands.
It took less than 40 years to elapse from the time when IBM estimated there were only 10 powerful computers needed globally to the advent of desktop computers in almost every home and office. Efforts to automate some parts of chemistry have, similarly, come a long way. So why can’t synthetic chemistry, today practiced by highly trained chemists, eventually follow the same pattern? Could we be about to enter the age of ‘personal chemistry’, where devices in our homes make our medications and materials on demand, with no need for scientific knowledge or skill?
The role of chemists
Reading this, many synthetic chemists may be concerned their discipline will be rendered obsolete by automated instruments. Worry not; I am not suggesting this will happen any time soon, and definitively not in the next 10 years. On the contrary, the ingenuity of synthetic chemists is why lay people will be able to make ever more complex molecules.
This ingenuity and increasing complexity has been on display throughout the history of synthesis. Unsurprisingly, biopolymers that are comprised of a limited number of building blocks and are connected via one type of chemical linkage were first tractable by automated assembly. Robert Bruce Merrifield’s automated solid-phase peptide synthesis in the 1960s was followed by DNA (1980s), RNA (1997) and finally oligosaccharides (2001). Today, the radioactive diagnostic agent 2-fluorodeoxyglucose (FDG) is automatically synthesised and purified every morning in medical centres around the world for immediate use. Entire genes can be ordered by hobby enthusiasts and are delivered within days; in the early 1970s the same process required tens of man-years to complete. Amateurs are now using oligonucleotides as ‘bio-bricks’ and entire genes to participate in synthetic biology experiments.
The structural universe of natural products is much more complex, however. Myriad different connections are possible, and synthesis requires many more reliable chemical transformations. Very recently, an instrument to automatically and repeatedly construct carbon–carbon bonds via boronate coupling reactions was introduced and applied to the automated assembly of several complex natural products. ‘Modular assembly systems’ are an alternative approach, which are based on flow chemistry modules that are each responsible for a particular chemical transformation. The utility of such as system was illustrated by the synthesis of five blockbuster drugs by just changing the input, order and connectivity of five modules.
Key to any automation process are high yielding, efficient and robust reactions that can tolerate many solvents and the presence of functional groups. It will be synthetic chemists who find increasingly powerful and, in many cases, catalytic reactions to conduct the desired transformations. In doing so, a set of reliable and robust transformations will emerge that can be executed by automated instruments to create ever more complex molecules on demand using a set of basic chemicals.
Threats and opportunities
But although chemists remain essential, synthesis will increasingly become part of daily life. Amateur enthusiasts can already purchase or build chemical assembly machines that are capable of carrying out a range of key chemical transformations. Coming years will see an expansion of this concept.
The advantages of this ‘on demand’ personal chemistry are clear. If you live in a remote location and your child urgently needs a lifesaving medication, you could just start the machine and make it. Yet at the same time, anybody who might desire a chemical warfare agent, strong poison or illegal drug could do the same. The implications of personal chemistry can be as scary as they are desirable. And, unlike the digital revolution, chemistry creates not just information but chemical matter, with all its upsides and its risks. Access to chemicals used as starting materials is controlled for a good reason, and will need to be controlled in the future.
In the next 10 years, I foresee the use of modular chemical processes not by amateurs and hobby enthusiasts, but rather by a decentralised network of trained professionals. Automated or semi-automated modular devices will enable the on-demand synthesis of ever more complex molecules for a host of applications, ranging from pharmaceuticals to materials. These systems will allow developing countries to produce their own lifesaving drugs with less technical skill needed and with remote online monitoring by regulatory authorities.
The societal upside is immense! But, as with all new technologies, greater responsibilities will come along with our improved capabilities. It is the dawn of the personal chemistry age – and chemists must act as guides in this new world.
Peter Seeberger is director at the Max Planck Institute of Colloids and Interfaces in Potsdam, Germany
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