Friday, July 27, 2012

The 'Chemputer' That Could Print Out Any Drug


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 TEDconference, 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 prescriptiondrugs."

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."

by Tim Adams, The Guardian |  Read more:
Photograph: Murdo Macleod