Drugs on demand with 3D-printed reactors

It may soon be possible for anybody to synthesise pharmaceuticals at home, with little or no expertise in organic chemistry required. But is this a good idea?
Drugs on demand with 3D-printed reactors

Synthetic organic chemistry is a highly specialised subject requiring years of training to acquire expert knowledge and skills. Much like a professional chef, the organic chemist must develop an intimate and encyclopedic knowledge of chemical reactivity and synthetic recipes, as well as a deft and expert hand at benchtop techniques, in order to craft complex molecules from simple ingredients. Unlike cooking, however, very few of us possess even rudimentary skills at organic synthesis. What if we could take all this expert knowledge, digitise it, and put the power of organic chemistry into the hands of the general public instead?

This is the goal of Prof. Lee Cronin and his group in their recent article "Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals", published in Science. Building on his previous work in Nature Chemistry, where he first introduced and demonstrated the concept of using 3D printers to make bespoke reactionware for chemical synthesis and analysis, here Prof. Cronin goes a step further by 3D-printing a modular reactor capable of performing multi-step organic synthesis, illustrated for the case of baclofen, a muscle-relaxant.

The entire synthetic process, including the design of the reactor, is coded so that anyone could in principle make the reactor and duplicate the synthesis at home. Since the synthesis is broken down into simple modular steps, only the correct starting materials, reaction volumes and temperatures are required to be used, in the correct order and for the right amount of time. Ultimately, the long-term aim is to develop a “universal chemical Turing machine”, i.e. a device that can create any molecule on demand, with the minimum amount of human input required.

Why would we want to digitise chemistry in this way? The motivation is 3-fold: (i) Digitising synthetic procedures into computer code will enhance transparency and reproducibility; (ii) It will allow non-experts to use the tools of organic chemistry to create complex molecules on demand, potentially saving lives as well as increasing the democratization of knowledge; (iii) Automating synthesis will free up time for organic chemists to focus on other things, such as downstream assessment, rather than toiling away over a hot round-bottomed flask.

Prof. Cronin is not the only one trying to simplify and streamline organic synthesis. Prof. David Leigh's work on programmable molecular machines has demonstrated the possibility of creating complex molecules using nano-sized "molecular assemblers", whereby the desired products may be obtained through very simple parameter adjustments. The two approaches might be complementary; in the future one could imagine Leigh's molecular assemblers being supplied along with other starting materials to facilitate chemical synthesis in Cronin's 3D-printed modular reactors.

The idea of cheap, small-scale reactors for the manufacture of fine chemicals and pharmaceuticals at their point-of-use certainly sounds attractive, and could potentially carry multiple benefits to the user in terms of efficiency-of-delivery and robustness-of-supply. The possibility to create life-saving drugs at home is undoubtedly an exciting prospect. But how will governments and law makers ensure this technology is not used illegally, such as for the local production of recreational drugs or explosives? Similar concerns have already been raised in relation to 3D-printed weapons, the blueprints for which are readily available on the dark web, causing a major headache for law-enforcement agencies. Clearly, as highlighted in Cronin's paper, a new and robust regulatory framework will need to be developed around the use of such technology. Even so, difficult ethical and legal questions lie ahead if the digitisation of chemical synthesis is going to find its way into our homes.

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