Did you always want to be a scientist?
I thought everything was interesting when I was a kid, so I had a hard time when it came to picking a college major. I thought chemistry was a practical thing to do, so I majored there with the idea that I’d switch into whatever I was actually most passionate about. In the end, although I was fascinated by economics and psychology, I found a passion for chemistry.
I think that part of the reason is in physical science you are constrained by the truth – whatever can be supported with data and facts. There’s something comforting about that. That’s probably also why I was drawn to mass spectrometry too. We can measure mass with great precision and accuracy. If the mass isn’t right, your hypothesis is wrong.
But it wasn’t until I went to graduate school that I learned how much I loved research. I’ve been doing it ever since and feel like I’ve never really had a job – it’s just been fun.
How did you end up in the mass spectrometry field?
Early in my senior year at a small liberal arts college, one of my professors asked me where I was going to go to graduate school. That wasn’t on my radar at all – I thought I’d just get a job. He said, “Unless you want to wash test tubes for somebody else, you really want to have a PhD.” That January I took an industrial internship, and the only person who really seemed to be having fun was the PhD – he was deciding what people in the lab should do and was genuinely excited. That convinced me to go to graduate school.
From there I looked at different groups, and it just so happened that Graham Cooks became my advisor. I visited his lab at Purdue, where he was doing mass spectrometry research. I knew nothing about it – my undergrad institution didn’t even have a mass spectrometer – but everyone in his lab seemed really excited about their work. Even though I didn’t understand it at the time, I thought, “I want to be that excited.”
So I joined his lab. Over time I grew to appreciate what you can do with mass spectrometry and just how multi-dimensional the field is. And that’s where I’ve stayed ever since.
Of all the labs you could have stumbled upon, Graham Cooks’s seems like quite a good one to land in first. What were some of the biggest lessons you took from him?
Oh, absolutely. We can all look back at events in our lives that turned out to be pivotal. We come to forks in the road all the time, and there are a handful of people in all our lives who make a huge difference. Graham was certainly one of those for me.
I think people outside science don’t realize just how important creativity is – and how creative scientists must be to do original work. That really hit home for me being around Graham, joining conversations with senior grad students, and seeing how they thought.
But creativity is just one side of the coin; the other side is discipline. Graham is a very disciplined scientist – he’s the hardest-working person I’ve ever met and I could see how that paid off. He once told me, “If you and I both have 50 ideas a day, and I pursue 10 of them while you pursue one, I will win.” That stuck with me. There’s just no getting around hard work. And he’s still that way today. And as far as I can tell, he hasn’t slowed down at all.
How do you cultivate creativity?
We all know that word, serendipity. You can’t plan discoveries – but you can plan work that’s likely to lead to discoveries. If you’re doing things no one’s ever done before, you’re likely to see things no one’s ever seen before. The challenge is: are you a good enough scholar to figure out what’s going on?
In my lab, a certain fraction of what we do is just turning over stones – trying something out and seeing what happens. There’s usually some kind of hypothesis or goal, but around 25 percent of the time we’re just exploring. Another 25–30 percent is following up on something we’ve found and turning it into a project. The rest is developing an idea toward some useful end.
So, for example, I might discover a new reaction, then try to understand the underlying principles. Once we know what’s going on, we ask: how could this be useful? Could it solve a measurement problem? Those stages – discovery, understanding, and application – are always going on in parallel in my lab. It’s a process that’s kept me going for more than 40 years. I can’t tell you what I’ll be doing five years from now, but I know there will be plenty to do as long as we keep turning over stones.
Are we sometimes too focused on impact and utility in analytical science?
I think so. There’s risk to the “turning over stones” approach, for sure. But there’s always going to be things worth discovering. Let me give you an example: I once asked my son, when he was about eight years old, if he knew what the phrase “necessity is the mother of invention” meant. He sort of got it – he said, you’ve got a problem, so you find a way to solve it. And that’s right. But then I asked him, have you ever heard of “invention is the mother of necessity”? He hadn’t – but to me, that’s a big part of the contribution of science. Take my phone: I didn’t ask for it, but now I can’t live without it. So much of what we have today has come from invention.
I’ve always tried to be intentional about that activity – studying phenomena that haven’t been studied before and figuring out how it might be useful. For many people, those ideas seem to come out of left field. But that’s the point. Of course, there’s a risk of irrelevance, so you always need some grounding in reality and an awareness of genuine challenges. But then you can get creative about tackling those challenges from completely new angles.
To me, it takes all kinds of approaches. If you’re super focused on utility, you’re probably not going to find what lies off the beaten path.
Are you solely driven by curiosity and discovery – or does potential impact factor in?
I think impact follows from curiosity. But the extent of that impact is really hard to predict. One of the great things about the university model is that it allows single investigators to go off in left field and do work that nobody asked for – and it can turn out to be very important.
On a personal level, I once took a Myers–Briggs personality test when I was working at Oak Ridge National Lab, and it came back that I was a “thrill seeker.” I didn’t see that in myself at all, but my supervisor said, “Of course you are – look at the way you do research.” And he was right. I’m always looking for the next discovery, and when I find it, I feel like I’m not even touching the ground.
The truth is, most of the time experiments don’t work. You’re struggling, things don’t pan out. But then one day you come across a result or a phenomenon you don’t yet understand – and it’s exciting. That intermittent reinforcement makes it all worthwhile.
So yes, I’m much more driven by the thrill of discovery than by trying to solve a specific problem. That said, it takes all kinds. I have huge admiration for people who are laser-focused on solving a problem no matter what it takes. But I’ve learned that what really motivates me to get up and go to work is discovery.
What are you most excited about in your current research?
That’s a hard question because I’m interested in everything we’re doing, even if I don’t know where it will lead. But the area that has really become “me” is studying reactions of oppositely charged ions inside the mass spectrometer – ion-ion reactions.
These days we can make ions from almost any form of matter, so the chemistry is vast. We’re constantly discovering new reactions by trying new things. Right now, for example, one of our projects involves making very large salt clusters of different compositions and reacting them with oligonucleotides and proteins. We’re manipulating their charges by transferring sodiums to them or removing sodiums, which we think will have practical applications in mixture analysis.
At the moment, though, we’re focused on understanding the chemistry itself. Some of these clusters have “magic numbers” and behave differently, which makes it challenging and fun – like solving a puzzle. I can already see the path to publishing papers showing how this approach can be applied to real problems. That’s how it always works: discovery first, applications later.
The dimensionality of ion–ion chemistry is so large that I’ll never run out of questions to pursue. It keeps things exciting, and I know I’ll never get bored of it.
Looking back over your career, what would you say has been the biggest impact of your research?
It’s really hard to say. My colleagues and I were pretty much on the ground floor when ion traps came out, and we did a lot of novel things with them – and still do – that have made their way into commercial products. Ion-ion reactions, for instance, are now commercialized by several vendors, and I expect their applications will continue to expand.
I’ve always liked to go back to first principles to understand how things work, and some of those fundamental studies have had lasting impact. For example, everyone uses collision-induced dissociation, and I wrote some early reviews about how it works fundamentally that people still cite today.
There are lots of examples like that. Our group at Oak Ridge put electrospray on an ion trap in the mid-1990s, and my colleague Gary Glish and I were consultants with Finnigan at the time. I sent them the preprint of our paper just before submission, and that weekend they started their LCQ project – the commercial electrospray 3D ion trap. For about a decade, it was the workhorse for bottom-up proteomics until the LTQ came along.
We didn’t patent anything – we just published. But those kinds of contributions ended up shaping commercial instruments and methods used across the field.
But I’d have to say my most important product has been my students.
How do you approach mentoring your students?
Communication is extremely important. We have group meetings where everybody presents what they did that week. That way, younger students see what the older students can accomplish in a week, and that motivates them. They also see how I, as someone who has been doing this for a long time, reacts to data when I see it for the first time – the kinds of questions I ask, the critical thinking involved. The older students, in turn, become good mentors themselves.
My philosophy has been to try to get most of my work done with graduate students rather than postdocs, whom I can mould into independent scientists – which is my primary goal. I’ve found that if I can get a graduate student up the learning curve quickly, by the time they’re senior students, they’re essentially working at the level of postdocs.
The only time I bring in a postdoc is if I need to import knowledge we don’t already have – for example, when we got into ion spectroscopy, I brought in someone with a PhD in that area.
Do you still feel that sense of fun and excitement around discovery that you felt in Graham Cooks’s lab?
Oh, absolutely. I really feel super privileged to have been a scientist during the period of my career. I really got started in the late ’70s, and from then until now I’ve had way too much fun – more than I deserve, doing what I do. Discovering something, or realizing something new, is just a tremendous high. I feel it as much now as I ever did – maybe more.
In fact, the more you know and understand, the more you can know and understand. Experience allows you to see the significance of things more quickly. I notice details my students might not, such as a small unlabelled peak, and I can recognize its importance right away. I don’t miss as much as I used to. So in many ways, I’m having more fun now than I ever did.
Scott A. McLuckey is John A. Leighty Distinguished Professor of Chemistry, Purdue University, West Lafayette, USA
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