<<<<Professor Lee Cronin is a likably impatient presence, a one-man catalyst. “I just want to get stuff done fast,” he says. And: “I am a control freak in rehab.” Cronin, 39, is the leader of a world-class team of 45 researchers at Glasgow University, primarily making complex molecules. But that is not the extent of his ambition. A couple of years ago, at a TED conference, he described one goal as the creation of “inorganic life”, and went on to detail his efforts to generate “evolutionary algorithms” in inert matter. He still hopes to “create life” in the next year or two.
At the same time, one branch of that thinking has itself evolved into a new project: the notion of creating downloadable chemistry, with the ultimate aim of allowing people to “print” their own pharmaceuticals at home. Cronin’s latest TED talk asked the question: “Could we make a really cool universal chemistry set? Can we ‘app’ chemistry?” “Basically,” he tells me, in his office at the university, with half a grin, “what Apple did for music, I’d like to do for the discovery and distribution of prescription drugs.”
The idea is very much at the conception stage, but as he walks me around his labs Cronin begins to outline how that “paradigm-changing” project might progress. He has been in Scotland for 10 years and in that time he has worked hard, as any chemist worth his salt should, to get the right mix of people to produce the results he wants. Cronin’s interest has always been in complex chemicals and the origins of life. “We are pretty good at making molecules. We do a lot of self-assembly at a molecular level,” he says. “We are able to make really large molecules and I was able to get a lot of money in grants and so on for doing that.” But after a while, Cronin suggests, making complex molecules for their own sake can seem a bit limiting. He wanted to find some more life-changing applications for his team’s expertise.
A couple of years ago, Cronin was invited to an architectural seminar to discuss his work on inorganic structures. He had been looking at the way crystals grew “inorganic gardens” of tube-like structures between themselves. Among the other speakers at that conference was a man explaining the possibilities of 3D printing for conventional architectural forms. Cronin wondered if you could apply this 3D principle to structures at a molecular level. “I didn’t want to print an aeroplane, or a jaw bone,” he says. “I wanted to do chemistry.”
Cronin prides himself on his lateral thinking; his gift for chemistry came fairly late – he stumbled through comprehensive school in Ipswich and initially university – before realising a vocation for molecular chemistry that has seen him make a series of prize-winning, and fund-generating, advances in the field. He often puts his faith in counterintuition. “Confusions of ideas produce discovery,” he says. “People, researchers, always come to me and say they are pretty good at thinking outside the box and I usually think ‘yes, but it is a pretty small box’.” In analysing how to apply 3D printing to chemistry, Cronin wondered in the first instance if the essentially passive idea of a highly sophisticated form of copying from a software blueprint could be made more dynamic. In his lab, they put together a rudimentary prototype of a chemical 3D printer, which could be programmed to make basic chemical reactions to produce different molecules.
He shows me the printer, a nondescript version of the £1,200 3D printer used in the Fab@Home project, which aims to bring self-fabrication to the masses. After a bit of trial and error, Cronin’s team discovered that it could use a bathroom sealant as a material to print reaction chambers of precisely specified dimensions, connected with tubes of different lengths and diameters. After the bespoke miniature lab had set hard, the printer could then inject the system reactants, or “chemical inks”, to create sequenced reactions.
The “inks” would be simple reagents, from which more complex molecules are formed. “If I was being facetious I would say that to find your inks you would go to the periodic table: carbon, hydrogen, oxygen, and so on,” Cronin says, “but obviously you can’t handle all those substances very well, so it would have to be a bit more complex than that. If you were looking to make a sugar, for example, you would start with your set of base sugars and mix them together. When we make complex molecules in the traditional way with test tubes and flasks, we start with a smaller number of simpler molecules.” As he points out, nearly all drugs are made of carbon, hydrogen and oxygen, as well as readily available agents such as vegetable oils and paraffin. “With a printer it should be possible that with a relatively small number of inks you can make any organic molecule,” he says.
The real beauty of Cronin’s prototype system, however, is that it allows the printer not only to control the sequences and exact calibration of inks, but also to shape, from a tested blueprint, the environment in which those reactions take place. The scale and architecture of the miniature printed “lab” could be pre-programmed into software and downloaded for use with a standard set of inks. In this way, not only the combinations of reactants but also the ratios and speed at which they combine could be ingrained into the system, simply by changing the size of reaction chambers and their relation with one another; Cronin calls this “reactionware” or, because it depends on a conceptualised sequence of flow and reorientation in a 3D space, “Rubik’s Cube chemistry”.
“What we are trying to do is to combine the notion of a reaction with a reactor,” he says. “Conventionally the reactor is just the passive space or the environment in which a reaction takes place. It could be something as simple as a test tube. The printer allows it to be a far more active context.”
So far Cronin’s lab has been creating quite straightforward reaction chambers, and simple three-step sequences of reactions to “print” inorganic molecules. The next stage, also successfully demonstrated, and where things start to get interesting, is the ability to “print” catalysts into the walls of the reactionware. Much further down the line – Cronin has a gift for extrapolation – he envisages far more complex reactor environments, which would enable chemistry to be done “in the presence of a liver cell that has cancer, or a newly identified superbug”, with all the implications that might have for drug research.
In the shorter term, his team is looking at ways in which relatively simple drugs – ibuprofen is the example they are using – might be successfully produced in their 3D printer or portable “chemputer”. If that principle can be established, then the possibilities suddenly seem endless. “Imagine your printer like a refrigerator that is full of all the ingredients you might require to make any dish in Jamie Oliver’s new book,” Cronin says. “Jamie has made all those recipes in his own kitchen and validated them. If you apply that idea to making drugs, you have all your ingredients and you follow a recipe that a drug company gives you. They will have validated that recipe in their lab. And when you have downloaded it and enabled the printer to read the software it will work. The value is in the recipe, not in the manufacture. It is an app, essentially.”
What would this mean? Well for a start it would potentially democratise complex chemistry, and allow drugs not only to be distributed anywhere in the world but created at the point of need. It could reverse the trend, Cronin suggests, for ineffective counterfeit drugs (often anti-malarials or anti-retrovirals) that have flooded some markets in the developing world, by offering a cheap medicine-making platform that could validate a drug made according to the pharmaceutical company’s “software”. Crucially, it would potentially enable a greater range of drugs to be produced. “There are loads of drugs out there that aren’t available,” Cronin says, “because the population that needs them is not big enough, or not rich enough. This model changes that economy of scale; it could makes any drug cost effective.”
Not surprisingly Cronin is excited by these prospects, though he continually adds the caveat that they are still essentially at the “science fiction” stage of this process. Aside from the “personal chemputer” aspect of the idea, he is perhaps most enthused about the way the reactionware model could transform the process of drug discovery and testing. “Over time it may redefine how we make molecules,” he believes. “In particular we can think about doing complex reactions in the presence of complex chemical baggage like a cell, and at a fraction of the current cost.” Printed reactionware could vastly speed up the discovery of new proteins and even antibiotics. In contrast to existing technologies the chemical “search engine” could be combined with biological structures such as blood vessels, or pathogens, offering a way to quickly screen the effects of new molecular combinations.
After publishing some of this thinking and research in recent papers, Cronin has of course been talking to various interested parties – from pharmaceutical companies intrigued by its implications for their business models, to Nato generals responding to the idea of the ultimate portable medicine cabinet on the battlefield.
He hopes that large-scale humanitarian organisations – the Bill and Melinda Gates Foundation and the rest – might take a hard look at the public health and cost benefits of introducing such a possibly revolutionary technology to the developing world. As a scientist, Cronin tends to play down the potential legal and practical obstacles that will no doubt challenge the idea – “I don’t imagine gangsters printing their own drugs, no” he says to one question – and sees only benefits.
“As yet,” he says, “we don’t even know what the device would look like.” But he believes that now the idea is established “there is no reason at all – beyond a certain level of funding – why it all couldn’t happen very soon.” Cronin is impatient to get on with it as quickly as possible. “As well as transforming the industry and making money,” he says, “we could be saving lives. Why wait?”>>>>
