Meet the CSO: Mark Mackey

Dr Mark Mackey founded Cresset with Andy Vinter almost 10 years ago and has been involved in every product Cresset has released since.  Before Cresset, Mark earned a PhD in Chemistry from Cambridge, and developed his molecular modelling and software development skills at Napp Pharmaceuticals and Merck.

Mark is the bright, focussed man behind the software and Cresset has grown to its current state in large part because of his good work.  Meet our CSO, Mark Mackey:

1. What was your first job?

My first real job (apart from paper rounds and the like) was working for a department store in Hobart on Friday nights and Saturdays, to earn some money while I was a student. Despite having no knowledge whatsoever about gardening, I was put in charge of the garden department after the previous incumbent got sacked. He’d been told to water the plants, took the instruction to heart, and drowned several thousand dollars of cacti. I managed to avoid that pitfall, at least, but I can’t claim that the plants thrived under my care!

My first proper science-related job was in the six months gap between finishing my undergrad degree and starting my PhD. I worked in the oceanography division of CSIRO (the Australian government research agency), developing a mathematical model to predict the abundance of different types of phytoplankton from HPLC measurements of phytoplankton pigments in seawater. The paper from that work has more citations than everything else I’ve published since put together, which in a way is rather depressing.

2. What would you say is your career highlight thus far?

Helping found Cresset! I’d worked with Andy previously, at a small pharma company called Napp, and as a result was one of the few people who knew Andy’s code. When he was putting Cresset together, he asked me to come on board. It took a lot of soul searching to leave a comfortable, secure job for life with a big Pharma company to join a tiny start-up with limited funding. However, I’m glad I did, as getting Cresset to where it is today has been great fun. Also, Merck closed the site that I’d been at less than two years after I left, so the “job for life” wouldn’t have worked out anyway…

3. Are there any exciting new changes or developments in the pipeline at Cresset?

I’m really excited about the new QSAR and molecule design product that we’re putting together at the moment. I think it will be an incredibly useful tool for the hard-worked drug designers out there.

4. Who has been your biggest influence professionally

It would have to be Andy [Cresset founder, Vinter]. I’d originally wanted to do my PhD with Andy, but that didn’t happen for funding and departmental reasons. However, I worked alongside Andy’s postdocs while doing my PhD, and jumped at the chance of an industrial postdoc with him through Napp. We’ve had great fun over the years drilling down to the physics of intermolecular interactions to try and really understand what’s going on.

5. What do you think about the future of Drug Discovery technology?

In my gloomier moments I sometimes wonder if there is one – many big pharma companies seem to be imploding under the weight of short-termism and management fads. However, there are still many unmet clinical needs, so we need more, better drugs. They’re getting harder and harder to find, at least in part because all of the easy targets have been done so that we’re now into the realm of Things That the Biologists Don’t Really Know Enough About (e.g. the controversy about the secretases and Alzheimer’s). I don’t have a simple answer for this, although I reckon that there’s definitely an argument for more phenotypic assays – it’s a rare protein where we know for certain what the biological effect of occupying an active site is going to be.

The one thing that the last decade or two has taught us, I think, is that more data isn’t necessarily better. Building libraries of 10¹⁵ molecules and running assays against the whole proteome doesn’t get you useful small molecule drugs any faster. These technologies are useful, no doubt about it, but they aren’t magic bullets. Pharma company management loves magic bullets, though, so the one prediction that I can confidently make is that in ten years’ time everyone is going to have spent bucketloads of money on Index Phased Array Flow Chemistry or whatever the next fad is. I can also confidently predict that it will turn out to be moderately useful but nowhere near as useful as its proponents originally made out.

In essence, to do small molecule drug discovery well, you need some really good chemists to work on a series of molecules until they understand in their guts what’s going on in the SAR. Computational chemistry, if done well, can really assist with this, but it’s a brave modeller who’ll try and outguess the educated mark I eyeball.

6. What do you love most about your job?

I love programming, and I love chemistry. I’m lucky to have the chance to do both together! I get the most satisfaction, I suppose, from seeing a scientific technique that I worked on get turned into software that people actually use. Writing papers is important, but let’s be honest: most published work gets read a few times, cited a few times and then largely forgotten. However, if you turn your great idea into a piece of code that’s released and used worldwide, you know that your ideas have made a real difference.

7. Which kind of developments are you most excited to work on?

Methods development! I enjoy the applications side of modelling, and I enjoy programming, but most of all I love trying to find new computational techniques to do nifty stuff with molecules.

8. What would you eat for your last meal on earth?

I’m allergic to dairy products, and have been largely milk-free since I was a teenager. Given the lack of time for the effects to come and bite me, I’d go overboard on chocolate éclairs, camembert, and ice cream!

9. What are you reading right now?

I’m alternating reading “Altered Carbon”, by Richard Morgan (Jet-black noir SF), with Paladin of Souls by Lois McMaster Bujold (theologically-inclined fantasy). In between there’s a stack of papers in the “to be read” pile!

10. You’re forced to go on holiday tomorrow.  Where would you go?

The Moon. It’s 2012, dammit, there ought to be daily scheduled services by now. Given that there aren’t any, I’d go to somewhere on the Great Barrier Reef and learn to scuba dive.

Want to speak with Mark about Cresset’s innovative science or just chat about space travel?  Contact him at mark@cressetgroup.com and he’ll be please to speak with you.