Deniz Kirik

Credit: L. Dareberg

A doctor's dilemma

Soon after he first entered medical school, Deniz Kirik realized he was in the wrong place. He had been drawn to medicine by his desire to better understand the human brain, but he found that doctors in his native Turkey have little opportunity for research. Kirik, who nonetheless earned his medical degree, fought hard to make his way into translational research, eventually turning what first felt like a failure to pick the right career track into an advantage.

Today Kirik, a neuroscience professor at Lund University in Sweden and co-founder of a spinoff company, uses his medical background to develop novel gene-based therapies for Parkinson’s disease and bring them to the clinic. In October, Kirik secured a partnership with his regional government in southern Sweden to build a gene therapy center to push his and others’ results into clinical trials and train clinical staff to deliver gene therapies. As director of the center, Kirik has also been charged with the task of building a specialized hospital with full-scale clinical trial and treatment capabilities.

I haven’t left the medical profession; I am just contributing to it from a different perspective.

—Deniz Kirik

This interview was edited for brevity and clarity.

Q: How did you get into science?

A: I was interested in science as a high school student, and in fact, my favorite subjects were physics and mathematics. I wanted to pursue engineering, but my family and friends encouraged me to consider being a doctor, and so I went to medical school. My thinking at the time was that the challenge of searching for answers would be much greater if the unknown I wanted to explore was how our brain functions rather than why a mobile phone fails. But my frustration at realizing that my purpose for entering medical school clashed with what was expected of me as a medical doctor in Turkey led me to start looking for opportunities to try my hand at doing research. I used after-class hours and nearly all my summer vacations to learn anything I could about science. Several people on campus opened their laboratories to me, allowing me, for example, to learn how to isolate DNA and conduct animal experiments on the perception of auditory stimuli. They understood that I was looking for an exit door and prompted one of their colleagues at Lund University to invite me to come and work in his laboratory for a short period of time. This was in 1995, and I had just completed my fifth year of medical school, but I still needed to do my final-year clinical residency to graduate. So I decided to take a break from medical school and, once in Sweden, to stay on for a Ph.D.

Q: Was it hard to change course?

A: My decisions were neither well understood nor well received back home, where medicine is one of the most highly valued careers. I remember my relatives calling my parents, lamenting that I had lost purpose in life and pretty much giving their condolences. Even my professional colleagues seemed to think that research was the wrong path to follow.

It is not common in my country for medical students to take time off to do research, and I was entitled to one legitimate leave of absence. Once it was over, the faculty board asked me to return, threatening to dismiss me from medical school if I didn’t. They thought, or so it seemed, that I was the black sheep of the school, the one that failed. After a 4-year-long uphill battle and a lot of back-and-forth between the two countries, I eventually managed to finish my medical studies. I earned my medical degree out of principle, because it was important for me to state that what I was trying to do wasn’t any less good; it was a different path, but it was to be considered as equally prestigious as medical practice. By the time I graduated, I had advanced my doctoral studies in Sweden to a point where I knew I could do well in research. I finished my Ph.D. 2 years later.

Q: Is your medical background helpful today?

A: Even though venturing through medical school initially felt like a failed attempt at fulfilling my career ambition, that decision eventually brought me to where I am today: doing science in a basic and translational research environment, still within a medical faculty. Had I studied medicine in another country, I probably would have found a way of pursuing a career combining research and medical practice. But if I’m successful in what I do, the research in my lab will become the basis for clinical trials and, eventually, new therapeutic interventions for patients. So I haven’t left the medical profession; I am just contributing to it from a different perspective.

Today, my medical background is also an advantage in some direct ways. I’ve had to convince hospital directors of the need to invest space, time, and competent people into a translational project like this. Had I had no engagement with the clinical world as a trainee years ago, I would also probably have had a less clear view on what I needed to accomplish to get clinicians’ attention and commitment. In turn, our ability to understand clinical challenges is improved when some of us on the research team have a medical background in that area.

Q: What is your research about today?

A: During my Ph.D., I investigated treatment strategies for Parkinson’s disease, and I have since remained within the field of neurodegenerative diseases. In the second half of the 1990s, a major hurdle in gene therapy was overcome through the implementation of new viral vectors, which prompted the neuroscience community, and me as a Ph.D. student, to begin using viral vectors to deliver genes to the brain. I continue to work with these valuable tools today.

In particular, I am now looking into the possibility of controlling the activity of the proteins encoded by therapeutic genes. So far, the only mode of treatment allowed by gene therapy in clinical trials has been the application of a continuous, constant dose of therapy, but we work with progressive diseases, and so the needs of the patient will change over time. Regulating the activity of therapeutic proteins, for example by controlling their folding, would allow us to provide personalized treatments.

This is an extended version of this week's Working Life story.

This is an extended version of this week's Working Life story.

Credit: Robert Neubecker

Q: What bottlenecks have you encountered on your way toward translation?

A: Translating basic research into a clinical reality is not an easy road. First, although it is much talked about, translational research is not particularly encouraged by funding bodies. One exception is the European Research Council (ERC), which gave me a Starting Grant to prove, using animal models, that the concept of tunable gene expression could work in the brain and, thus, pave the way for translational studies.

Translational research must also take place in an environment that involves industry, otherwise the bridge between the lab and the clinic is very vulnerable. A Proof of Concept grant that I later obtained from the ERC enabled me to start carrying out a market evaluation and writing a business plan for a promising therapy that emerged from the research. The momentum I was able to generate around this grant and the fact that we were now going to launch a spinoff allowed me to start approaching industry for funding.

Then, clinical translation is much more complex and unlikely to be successful in an area like gene therapy than it is in traditional drug development. This is because, rather than working with small-molecule drugs, we are performing biologics-type of research, where we deal with live viruses and cells and genetic modifications of the target organisms and, consequently, with a lot of unknowns and risks. So far, there is also a lack of facilities to conduct large-scale clinical trials for nontraditional drugs, even in the university hospital next to my research building. To address that challenge for when my project scales up, over the last few years I have engaged in discussions with the university hospital’s top management and local politicians so that they would give us a possibility to build a specialized hospital dedicated to gene therapy. The regional government is now partnering with our spinoff to build such a clinical trials and implementation facility at the heart of the university hospital.

Q: What new skills did you have to learn as you ventured into business?

A: I had interacted with companies as an academic expert before, but that is very different from asking venture capital firms, private equity investors, or industry to invest in a project at an early development stage. Over time, I came to realize that the humble and grounded manner in which we scientists present our findings doesn’t come across as exciting to investors. Industry executives want to see groundbreaking products, disruptive technologies, cutting-edge this and that, and to secure industry funding, it’s representing our facts in their style that counts.

The content of an industry presentation is also different. Traditional academic presentations include proper checks and controls, documentation of the facts, and details of how you reached the conclusions. Industry is looking for a business opportunity, so your research finding constitutes only the beginning of the story. Then you have to describe the entire path of how this business will develop and eventually return money to investors.

Q: How do you juggle your work activities and personal life?

A: As scientists, we are immersed into the questions we work on, and so they just become part of our personal identity. But that presents a challenge, in that I am married with two small kids. My wife is as prominent as I am in her research career, and she is also an active clinician. We have established a routine whereby we prioritize and share taking care of the children after daycare. I wouldn’t say it’s been easy, but because we work in the same environment, we understand the challenges we both face in our professions. And so we buffer each other’s difficult times by slowing down when the other has to really push the limits at work and trying to keep everything in balance.

Q: What’s your advice for young scientists?

A: Defining the purpose of their life and their ambitions is very important. Then they need to determine what path will lead them to their goals, which is something they need to revise and iterate continuously. To get through that path, they will often need a lot of strength and persistence.

Also, it’s ironic, but the things that taught me the most are the things that I failed at. I’ve always investigated the reasons for my failures much more intensely than my successes, and failing always drives me to try harder next time. More than 5 years ago, I filed my first patent and co-founded a spinoff company. But I decided to quit soon after, realizing after about 1 year of working on the project that the business plan didn’t meet the criteria I wanted to see. Failing—and accepting the fact that I failed—allowed me to identify and put my energy into this new gene-therapy venture that I believe is now much stronger than it would have been had I been successful the first time.

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