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Icosagen's Grand Old Lady, Urve Toots, has decided to retire. Below, you'll find an interview recounting her career and a life full of constant improvement. Urve Toots led the proteomics department that handles production of challenging recombinant proteins. She was also part of the management board.
On the one hand, my departure may seem unexpected, but the idea has been quietly lingering in the back of my mind for a while. My feelings are mixed. I’ve been working with CEO Mart Ustav in the same lab since 1976 and more closely since 1992. Just think—I was at the university and Fit Biotech even before Icosagen was established. I joined Icosagen way back when it was still called Quattromed. So, in that sense, I can’t quite imagine what’s going to happen next. Right now it doesn’t feel real. I don’t yet know what it will be like when Mart doesn’t come in the morning with a new development idea and then, by the next day, ask “Urve, is that thing we talked about yesterday ready?” He’s always been the kind of person who goes from idea to action in no time. I really can’t picture it yet.
Emotional celebration on Urve’s last official workday, where the Icosagen family gathered in the foyer to thank her and wish her all the best.
I’m not worried about leaving my department because, fundamentally, I believe in people taking responsibility for their own work. It’s just not possible for them to stand around waiting for me to show up and say what needs to be done today. In our production area, each specialist has their own domain under their full control. I’ve sent the message that it’s their work and their responsibility. Fortunately, I’ve never had someone in my team who doesn’t do their work wholeheartedly. I’ve been incredibly lucky in that regard.
My approach is to provide input as well as trust. At first, people may lack confidence and hesitate, but we look at things together initially. A sense of responsibility is very important—it increases both efficiency and commitment when someone isn’t just following orders but is in charge of their own piece of work. To be honest, I can’t work strictly under orders myself, and Mart has always understood that. For example, I could not work in our newly built GMP production facility, where every step is highly regulated.
About a year and a half ago, a new person joined the team. During the first month, she would come in every morning asking “What should I do today?” as she was used to receiving daily assignments. I was anxious, wondering if she would still be asking after a month. But instead of giving her tasks, I asked, “Where did you leave off yesterday? What’s unfinished? How far did you get, and what’s next?” Of course, I had to teach and remind her, but after that initial period, she never again asked, “What should I do today?”—she knew exactly which tasks were hers. We both understood the timelines. In my view, a person’s whole demeanor at work changes the moment they truly take ownership.
I actually will remain at Icosagen for a while longer as a consultant on a part-time basis, so I can smoothly hand over my protein production department to Kaja. We’ve poured day-and-night effort into this initiative, so it’s crucial that the work doesn’t end up in limbo. In fact, we created an entirely new department specially for producing challenging recombinant proteins, running up to 40 productions each week. This department has successfully produced more than 4,000 functional recombinant proteins—a monumental task!
We start with only a UniProt number or a gene name, and we have to figure out everything else ourselves—testing, analyzing, and optimizing production processes. It’s a huge workload, requiring constant changes and process optimization. You need to be open to innovations and ready to adapt existing methods. You have to look for new solutions on the market, test them, and then put them into practice. I just came from a meeting with Kaja, where we’re doing the first projects together, and later I’ll still be available if any questions arise.
Throughout the years and different roles, Urve has always kept her connection to the lab.
It’s a very intense department, but I love working on projects that have a high impact. When a recombinant protein fails to express, I can’t rest until I find a solution. I naturally start testing and developing improvements. By applying some successful developments, we’ve managed to produce more than 50% of previously failed recombinant proteins. It feels fantastic if we manage to produce 100% of the proteins planned for a period. If we manage “only” 98%, I still want to see if we can push it to 100%. (Urve laughs.)
My mother thought I should become a doctor, but the idea that one mistake could put a patient’s life at risk scared me. When I enrolled at university, I chose biology and somehow ended up in plant physiology, which was challenging as I struggled with memorizing Latin plant names and not creating an understanding or a logical system. Today, you can find everything you need online, but back then it was much harder to access information. Professor Miidla gave me a stack of old literature for my research project, but I wanted to read the latest scientific articles. That caused some friction—he considered the older texts to be “classics.”
Around the same time, I ran into Ain Laving, who told me about the labs run by Artur Lind and Mart Saarma, where they were doing new and exciting work in a completely new scientific branch—molecular biology. That truly resonated with me because I was fascinated by what happens at the cellular level. I started purifying plasmids, growing bacteria, and conducting molecular biology experiments. I was even the first person in Estonia to isolate restriction enzymes. People came to learn from us how to create and purify plasmids or to use restriction enzymes.
We definitely didn’t have the modern conveniences we do now. For instance, we used to prepare meat peptone broth by literally grinding up real meat in a meat grinder and autoclaving it—all to cultivate bacteria. It sounds unbelievable today, but that’s how it was. It was all new and exciting, a bit like the initial stages of building a house—once you’ve stuck the spade in the ground, you don’t want to leave until the walls and roof are up.
I worked in Saarma’s lab for about a year, researching factors that induced neurite outgrowth in cells. After having children, I joined Fit Biotech, where we focused on developing an HIV DNA vaccine. Not only we, but also many other companies at that time struggled to make any breakthroughs in this area. I was the internal lab manager. Together with Andres Männik, I produced plasmids that were intended to serve as the basis for the DNA vaccine.
The hope in DNA vaccines was huge back then, particularly for poorer countries where many children were born with HIV. Transporting and storing a protein-based vaccine can be very costly in such environments, whereas a DNA molecule is far more stable. Unfortunately, none of these attempts proved successful. After ten or eleven years at Fit Biotech, when the development department was eventually shut down, Mart invited us to join Icosagen (back then still Quattromed). I still keep an eye on DNA vaccine research and occasionally read new articles, looking to see if there’s been a breakthrough. So far, though, no true HIV vaccine has been fully developed.
The biggest and most significant work period for me has been the development and launch of stable episomal production technology—QMCF—at Icosagen. When Quattromed sold off its diagnostics division, only the cell factory segment remained. At that point, we had some inefficient production vectors that did not meet our expectations. I still recall how, in the early days, we once planned a project for producing an antibody with a timeline like a pregnancy—nine months—for just 100 milligrams of antibody. Compared to what we do now, that’s extraordinary: today, we measure production times in days, not weeks or months.
We needed to create a brand-new system for service offerings. We started by redesigning the vectors, adding essential elements like robust promoters and introns to ensure production stability and effectiveness. By incorporating viral elements into CHO cells and plasmids, we achieved a balance where the plasmid not only replicated well but also produced protein efficiently. We tested all sorts of promoters to achieve sufficient expression without overburdening the cells.
We produced and tested many different vectors, and after multiple adaptations, we found the best combination for industrial production. That cell line became our main “workhorse,” and with some modifications, is still in use today. Overall, launching the protein production service was a lengthy and challenging process. We were a team of scientists and didn’t have many experienced salespeople back then. Since we were a completely unknown company, earning trust took time.
"During technology development, there was no time to lose. We shared results on the fly," Urve recalls.
Mainly, I’ve focused on advancing protein production technology, including developing and refining methods for producing and purifying VLPs (virus-like particles) used in the production of transmembrane proteins.
I’ve only dabbled in other developments here and there. At one point, we needed to develop technology for antibody discovery, but I realized there were many components that still didn’t function adequately for a service offering. I tried helping for a while, but because I was already leading all the clients’ production projects at the time and my days were very long, I decided I couldn’t manage it all. Mart Ustav found a way, and thankfully Gaily Kivi took on the HybriFree development and completed it successfully.
I have also been involved in various international scientific projects in collaboration with universities and research institutes. Our academic partners appreciate us because it’s usually difficult to find a company that meets all the necessary requirements—not just for invoicing and simple reports, but actual production of proteins and antibodies, along with R&D. Icosagen, with its dedication, can offer all of this, and we consistently receive positive feedback.
Icosagen has been a place where I could fully utilize my energy and knowledge. One of the company’s biggest pluses is its people: they’re open-minded, always looking for new solutions, and ready to take responsibility. We started with only a few dozen employees, and now we can’t even fit everyone into the foyer at once.
Mart Ustav has been a key driver of this development, guiding the company to where it is today. I can honestly say I’ve been very satisfied at Icosagen—I’ve had the opportunity to shape my own story here to a large extent. For anyone new joining Icosagen, you need to be dedicated, willing to learn, and have a strong work ethic and perseverance. A sense of responsibility is critical—you can’t dodge difficult tasks, hoping someone else will do them. Several major projects are so large that one person alone can’t handle them all, so close cooperation with other teams is vital.
Initially, I plan to just rest and do nothing—though Mart Ustav thinks I can keep up that inactivity for only three days. I haven’t really had many hobbies. I don’t knit or sew, but now I’m looking forward to having time to read more books. I love visiting museums and going to concerts, and my friends, my sister, and I are already planning small trips to Copenhagen, London, or Amsterdam—short getaways every couple of months.
I’ve also been slightly involved in evaluating EIS' (Estonian Business and Innovation Agency) projects, where I look at applicants’ plans, scientific articles, and achievements—it keeps me connected to my field. I’m not looking to become a homebody in slippers, so from here on, I’ll focus more on myself and hope new and interesting ventures will emerge.
Icosagen must keep its eyes open to notice when something isn’t working and not be afraid to fix it. It requires deliberate and determined effort, but in the end, we can grow and develop even more. A company is just a name if it doesn’t have good, motivated people. Leaders need to clearly communicate goals and expectations to your team without harming their dignity or motivation. All in all, I hope that Icosagen will keep its reason and consistency, and treasure its great people.
Interviewed and written by Karl Mumm
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