The human body as the most complex machine

Lude Franke is an Oncode Investigator and professor of Functional Genomics at the University Medical Center Groningen. His work focuses on the elucidation of genetic diseases using bioinformatics. He tries to make his work as meaningful as possible while maintaining a healthy work environment.

Foto: Marloes Verweij, Laloes Fotografie

Did you always dream of a career in medical science?

When I was young, I loved to draw, but also wanted to understand how machines work. In secondary school, I got a computer and taught myself how to program it. That struck a chord. When I had to decide what I was going to study, I had to pick one of these two talents. I chose medical biology because of my love for the human body as the most complex machine. At the same time, I started designing book covers and company brandings. During my time at university, I discovered I was clumsy in wet lab work. Luckily, I was able to circumvent that with an internship at the genetics department. That turned out to be the best step in my life – it allowed me to use my programming skills too. Eventually, I obtained my Ph.D. in statistical genetic research. Graphic design still has a place in my work: it taught me how to present data in a visually attractive way and to explain difficult concepts to others.

Is that combination what makes your work interesting?

I think so. For me, my work is where ambition and passion meet. There is never a dull moment in genetics. From the moment the first GWAS (genome-wide association study, red.) was finished in 2007, the big question was ‘what can we do with all that data?’. Even now, we’re still learning what most genetic associations mean. At the same time, functional genomics allows us to study these genetic variants at an exceeding level of detail. It is possible to unveil novel biologic pathways and pave the way for the wet lab follow-up of the genes we find. It’s complementary science – we deliver the leads, others do the follow-up.

“The human body is the most complex machine”

Where do you see the field of genetics in ten years?

It has always been hard to conduct functional research on human diseases caused by single mutations. We used to invoke inactivating mutations in cell lines or model animals and just watched what happened. With the advent of base-editing, organs-on-a-chip, organoids and single-cell technologies that method has changed completely. Those new technologies allow us to invoke a single mutation in a miniature organ, and subsequently perturb it. That gives us a more complete image of what is going on in the human body and how to interact with it. It’s not yet in vivo, but it’s close. Yet, the work is mainly done by hand. I predict an upscaling step – not one single organ-on-a-chip, but a hundred, side by side.

How can bioinformatics contribute to the genetic body of knowledge in terms of cancer?

In archeology, the knowledge of history is being refined with every new excavation. Roughly the same goes for biology: we adjust the image of our human body constantly by generating and (re)analyzing genomic data. I think it’s cool being able to contribute to society with our combination of experimental techniques and machine learning. That methodology now allows us to sometimes predict which mutation in a single patient causes a rare disease in hindsight. Although we’re not able to cure them, we can give them a diagnosis that explains their symptoms. By contributing to the clinical process, we can offer people comfort, knowledge, and insight. That makes my work meaningful.

Is it an incentive for you to do meaningful work?

I am a genuinely inquisitive person, so for me, it comes naturally to conduct research. At the same time, we are using taxpayers’ and charity money for our work. I strongly feel that if you fund your research with public funding, you should feel obliged to make that research as meaningful as possible. It’s important to note, though, that research does not always have to be useful. Just like an artist, it can inspire others. My work often is socially relevant, like the Lifelines Corona Research project that I lead, in which we have longitudinally followed 100,000 people during the COVID19 pandemic. I felt obliged to contribute to the coronavirus pandemic from my specialism. Within a few months after the start of the project, we were able to contribute to the identification of the first set of genetic risk factors for getting a severe COVID-19 infection. 

“I strongly feel that if you fund your research with public funding, you should feel obliged to make that research as meaningful as possible.”

How do cooperation and atmosphere play a role within your research group?

My group does fundamental research, which is not only stimulated by Oncode, but also by myself and my enthusiasm. To promote that, all of us work together on a variety of projects in teams of three or four people. I don’t like people to be on their own little island, supervised by a postdoc. To be able to work as a team, I think atmosphere is important and people must be able to trust each other. For that, I’m using my intuition in trying to be as accessible and kind as possible. Time has helped me with that: it shifted me from being a sometimes bluntly critical person to someone gentler. I learned to have more patience too – it always pays off and it evokes trust. Especially in fundamental research, it’s okay if a project takes a little longer to come together.  

How do you keep your patience in an often competitive scientific world?

This summer, I read a column in a magazine, comparing scientific research to the Olympic games. The author stated that science was similar to performance sport. Aside from the fact that most performance sporters already retire at 35, I disagree. The image of research as performance sport is an image that most people cannot live up to. Funding is always limited, causing a lot of stress. If we all keep believing hard work is supposed to be part of the job, there won’t be any obstacle for the low remuneration from funds. Young talented people are leaving research because they just cannot keep up. In terms of recognition and appreciation, we’ve come a long way. However, we still have a long way to go. In my view, the only solution is fewer grants and more structural funding, like Oncode Institute provides.

What would you like people to say about you at your retiring party?

For me, the most fulfilling thing would be that my co-workers have had the feeling they could prosper by working on meaningful research subjects in a safe environment without too much stress. I do understand there is a kick and the satisfaction after a day’s hard work, but that can become problematic when it’s not in moderation anymore. That’s why I try to refrain from work in the evenings and weekends. I hope I’ve set an example to conduct healthy science.

Dit artikel verscheen in de Oncode Quarterly Update van oktober 2021.