I wrote here about the Cronin lab at Glasgow and their work on using 3-D printing technology to make small chemical reactors. Now there's an article on this research in the Observer that's getting some press attention (several people have e-mailed it to me). Unfortunately, the headline gets across the tone of the whole piece: "The 'Chemputer' That Could Print Out Any Drug".
To be fair, this was a team effort. As the reporter notes, Prof. Cronin "has a gift for extrapolation", and that seems to be a fair statement. I think that such gifts have to be watched carefully in the presence of journalists, though. The whole story is a mixture of wonderful-things-coming-soon! and still-early-days-lots-of-work-to-be-done, and these two ingredients keep trying to separate and form different layers:
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. . .
Unfortunately, "science fiction" isn't necessarily a "stage" in some implied process. Sometimes things just stay fictional. Cronin's ideas are not crazy, but there are a lot of details between here and there, and if you don't know much organic chemistry (as many of the readers of the original article won't), then you probably won't realize how much work remains to be done. Here's just a bit; many readers of this blog will have thought of these and more:
First, you have to get a process worked out for each of these compounds, which will require quite a bit of experimentation. Not all reagents and solvents are compatible with the silicone material that these microreactors are being fabricated from. Then you have to ask yourself, where do the reagents and raw materials come in? Printer cartridges full of acetic anhydride and the like? Is it better to have these shipped around and stored than it is to have the end product? In what form is the final drug produced? Does it drip out the end of the microreactor (and in what solvent?), or is a a smear on some solid matrix? Is it suitable for dosing? How do you know how much you've produced? How do you check purity from batch to batch - in other words, is there any way of knowing if something has gone wrong? What about medicines that need to be micronized, coated, or treated in the many other ways that pills are prepared for human use?
And those are just the practical considerations - some of them. Backing up to some of Prof. Cronin's earlier statements, what exactly are those "loads of drugs out there that aren't available because the population that needs them is not big enough, or not rich enough"? Those would be ones that haven't been discovered yet, because it's not like we in the industry have the shelves lined with compounds that work that we aren't doing anything with for some reason. (Lots of people seem to think that, though). Even if these microreactors turn out to be a good way to make compounds, though, making compounds has not been the rate-limiting step in discovering new drugs. I'd say that biological understanding is a bigger one, or (short of that), just having truly useful assays to find the compounds you really want.
Cronin has some speculations on that, too - he wonders about the possibility of having these microreactors in some sort of cellular or tissue environment, thus speeding up the whole synthesis/assay loop. That would be a good thing, but the number of steps that have to be filled in to get that to work is even larger than for the drug-manufacture-on-site idea. I think it's well worth working on - but I also think it's well worth keeping out of the newspapers just yet, too, until there's something more to report.