The Orbitrap Man!
Sitting Down With… Alexander Makarov, Director Global Research LSMS, Thermo Fisher Scientific, Bremen, Germany; Professor of High-Resolution Mass Spectrometry, Utrecht University, The Netherlands; and Fellow, Royal Society, UK
Margot Lespade | | 5 min read | Interview
Thinking back to your childhood, did you always want to be an inventor?
Strangely enough, yes! I know it sounds odd but, even at the age of seven or eight, I tried to invent a device to collect wheat. As a city dweller in Siberia, I had not really seen much wheat nor many collection devices – but that happened to be my first idea. I also attempted to invent different kitchen utensils for my mother. Unfortunately, she was not too pleased with my proposals, because my ideas were not very practical and did not really address the need for safety or cleanliness.
However, one great thing I had in my childhood was a special journal for budding engineers. In this journal, there was a section, called something like “the patent office of young engineers,” where they invited children to submit invention ideas. I wrote to this journal several times and, interestingly enough, I always received an answer. It could take up to three months – but they would usually send me a long response, with both positives and constructive criticism. And, of course, in the majority of cases, these ideas were already long-invented by proper adult engineers – but I kept doing this until I grew up myself.
How did you become interested in mass spectrometry?
Even as an adolescent, I had this idea in my mind that I didn’t want to explore nature – but instead create a “second nature.” In a sense, this is what I'm doing now – though, at the time, I wasn't thinking in those terms. Initially, I actually wanted to create what is now known as a 3D printer – a concept that didn’t exist at the time. So, I started to look for an institute where this might be a possibility.
When I arrived at the Moscow Physics Engineering Institute, I asked if they had this type of instrument – that could build objects atom by atom, molecule by molecule. They said no, but that they had the opposite: technology that takes objects and breaks them down to a molecular level and analyzes them. So I decided that if I could not do assembly, I would do disassembly! And that is how I ended up in mass spectrometry – it seemed to be the closest to my idea at the time.
There were various groups dealing with molecular analysis and I really wanted to be involved. Eventually, a professor of mass spectrometry gave me a chance – despite my limited knowledge – as well as some literature on analyzers and ion sources, and a laboratory position as a technician. My first assignment was to repair a leak in a vacuum pump, which is how I started working with older students – one of whom co-invented mass cytometry (now at Standard BioTools) – who showed me what high voltages were, how mass spectrometers worked, and so on.
I was then diverted in a different direction by another PhD student working on a spark ion source – his analyzer was delivering too low performance, so he asked me to look for alternatives, and that’s when I started to learn about all different mass analyzers. Eventually I found an analyzer with hyper-logarithmic potential from Lidia Gall’s group and attempted to realize it with a spark ion source. And so, when the need arose for Orbitrap technology, I was already well equipped for taking the next step.
How does it feel to be a superstar in the world of mass spec technology?
In principle, it sounds great doesn’t it? When you step into an elevator and people start whispering or simply being recognized as the “Orbitrap man.” But on the other hand, I realized I shouldn’t get carried away; these things are just superficial. More importantly, people really take your word for truth. You have to be careful with what you say – and what you promise – because expectations are high.
When I found myself in this position for the first time, I naturally suffered from imposter syndrome, especially because so many colleagues contributed to the Orbitrap success. For the new generation of scientists, the Orbitrap is something that has always existed.
And although mass spec is a relatively narrow field, when I am at ASMS – or any other big mass spec conference – it is nice to feel at home. I like being able to help people and give people advice. It’s an aspect I really enjoy.
Do you have further ambitions for the Orbitrap analyzer?
First of all, I want to bring the Orbitrap story to completion. Essentially, I want to make it an analytical technique for every laboratory – something that could be considered a commodity. And we are getting there already! There is currently a five-digit number of Orbitrap instruments working 24/7 around the globe; in most big and medium cities, there will be one or more somewhere – in labs or in a university. Although these instruments still provide industry-leading performance even after 17 years of development under competitive conditions, it would be great to see Orbitrap technology go from a high-end technique to a routine method, especially in clinics and biopharmaceutical industry.
Therefore, my major goal is to make this technology as stable and robust as possible, so that, whatever comes next, Orbitrap instrumentation has a niche where it is doing its job best.
If you weren't a scientist and inventor, what would you be doing instead?
I am really interested in all types of unusual theories, particularly theories relating to history – where you can examine the question “what if?” – leading us to imagine what could have happened if certain events had happened differently. A book that specifically impressed me was Jared Diamond’s “Guns, Germs, and Steel”, where he explores why history went the way it did, and why Eurasian and North African civilizations have survived and conquered others and not vice-versa. So if I wasn’t a scientist, maybe I would be studying history – or maybe even working as a tour guide!
As someone with a significant innovation under your belt, what are your views on innovators?
I would say that not many people are capable of true innovation. And a large number of simple “doers” – who just do what they are told – cannot replace a single person who is able to innovate, although they are really needed when innovation gets scaled up. So, if you find one of these innovators, you really need to protect them and fight for them; they are very difficult to replace!