© Martin Lugger

“When It Comes to Research, You Need to Stay Focused”


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His time in the civilian service kindled his interest in the medical profession before a shrewd scientist awakened his passion for research. Today, Jan Schwab is among the top researchers in the field of spinal cord injuries. His speciality: the paralysis of the immune system.

Tübingen, Tel Aviv, New York, Paris, Boston, Salzburg, Berlin, and – now – Columbus… What sounds like an exciting world trip is a summary of Professor Jan Schwab’s career. The 46-year-old German is a neurologist and scientist. His area of expertise is the field of spinal cord injuries. Since 2004, he has been in charge of scientific matters at Wings for Life. He currently lectures, conducts research, and treats patients at the Ohio State University in the US. It’s high time for an in-depth interview. Professor Schwab, you are one of the most renowned specialists in the field of neurological regeneration.

Was that the plan all along?
Actually, I was born into a family of architects. At first, the most obvious choice was to follow in those footsteps. When I was almost 20 years old, I had to do my compulsory civilian service and decided to join the emergency services. I thought it would be exciting and formative, nothing more. In retrospect, that decision was groundbreaking. Early on, I was confronted with chronic patients and individuals with severe neurological issues. It was quite clear that merely applying a cast would not be enough in these cases. It was apparent that the damage was more extensive and that the patients – and their respective families – would face great difficulties. That’s when the field of medicine became tangible for me – and it impressed me.

What happened next?
After studying medicine, I started developing an interest in neurosurgery. This field requires an understanding of pathology. In the process, I took an in-depth look at injuries to the central nervous system. At the time, I managed to establish that the inflammatory reaction after an acute injury to the human brain persists much longer than previously thought.

Was that the beginning of your career as a scientist?
That and my life-changing meeting with Friedrich Bonhoeffer, who was then a director at the Max Planck Institute in Tübingen. He was an ingenious, shrewd, and fabled pioneer in the field of neurobiology. He was attempting to find out how nerve fibres find their way through the body during the human developmental phase. Why do certain nerves exit where they exit? And why does that – ultimately – enable a person to move a hand? There has to be a blueprint of some sort, but what does it look like? How do nerve fibres know in which direction they need to grow? For me, personally, those are the most impressive and fundamental questions one can ask. Bonhoeffer was looking for answers and was able to prove that guidance molecules pass on instructions to the axon. His tendency to think big is what really inspired me.

This is what whetted your appetite for knowledge, right?
For me, it was clear that there are two basic approaches to medicine. One option is to utilise what we know today to treat a patient. It’s already a huge challenge in itself to do that proficiently. The second approach is to look at incurable diseases with a view to making them curable or – at least – enabling them to be treated more efficiently. I have devoted myself to the latter. I want to take responsibility for the future.

Your area of expertise lies in the understanding of the connections between the immune system and the processes involved in the escalating damage following a spinal cord injury.
Yes, exactly. If you injure your skin, it triggers an increase in blood circulation. The skin reddens briefly before the inflammation disappears and the wound heals. The whole process takes no longer than 24 hours. Injuries to the spinal cord are different in this respect. Once an inflammation has occurred, it only subsides very slowly. It persists locally for a year or even longer.

Why is that the case?
The central nervous system is immuneprivileged. As a highly protected organ, it is ill-equipped for handling a severe inflammatory reaction. This is why it is protected from inflammation cells from the blood by a blood-spinal cord barrier. It is like a firewall that prevents inflammation, because an inflammation in this area would be much too dangerous. In the event of an injury, there are – in comparison to our skin – hardly any effective mechanisms for reducing the inflammation. Thus, even fairly simple inflammatory reactions result in the destruction of nerve cells. 

What exactly does that mean?
A spinal cord injury damages the connection between the central nervous system and the immune system. This, in turn, also damages the control of the central nervous system via the immune system. After sustaining a spinal cord injury, one does not “only” experience an obvious paralysis of the motor system, but also an immune paralysis. Spinal cord injury patients are immunocompromised after the injury, not unlike patients who have undergone chemotherapy. They find it difficult to shake off threatening infections and suffer inflammations in the bladder and lungs. Up until now, it has been overlooked that the immune system is one of the essential factors.

Why is that so detrimental?
Whether a patient develops an infection – an inflammation of the lungs, for example – determines how many neurological functions he or she can recover. In this case, we are talking about up to two affected spinal cord segments, which can make a huge difference for patients with a high neck injury. This affects the ability to move arms and hands, which – in consequence – determines the ability to do up a shirt button, manage the transfer from a bed into a wheelchair, and guide a spoon towards the mouth. In addition, an infection can develop into a sepsis, which could be fatal for the spinal cord injury patient. For a long time, we didn’t understand this phenomenon and simply took it for granted. In 2003, I was the first to prove an immune paralysis in a human being.

What can one do?
Well, the inflammation is already there. This means it can only be inadequately treated with anti-inflammatory medication. Instead, it is paramount to improve the removal of inflammatory cells from the inflammatory site. One could compare it to a blocked drain. In 2006, we managed to find one of the first molecules (resolvines) that can actively combat inflammation.

What can you do with this knowledge?
The aim is to develop a therapeutic approach. One can search for patterns that allow you to treat the injury earlier, in a more precise manner, and more aggressively. We are currently testing several approaches – including a pharmacological angle – that could enable us to prevent inflammation. 

You moved to Columbus almost two years ago. What does your daily routine at the clinic involve?
I treat inpatients and outpatients at the Spinal Cord Injury Clinic of the Dodd Hospital and at the newly established Brainn& Spine Hospital. At the same time, I have set up a laboratory to examine unexplained clinical symptoms on a molecular level and – in the process – to develop new therapeutic approaches. Successful approaches then serve as a basis for clinical studies. This allows us to implement translational research in a qualitative and effective manner. I am also a member of a team headed by Phil Popovich. We have been working on neuroimmunology following spinal cord injuries for a total of 15 years now.

Research requires a lot of patience…
In terms of research, it is crucial to remain focused. And you need to be highly critical. A good scientist always tries to disprove himself; that can take ages in many cases. Turning an idea into a finding and – ultimately – proving a hypothesis can easily take decades. One needs a high level of tolerance for frustration. As a scientist, you have to understand that you may only be able to work on a single pioneering and clinically relevant approach in your lifetime. Nevertheless, a new discovery feels a little like being the first human to scale a certain mountain peak. To extract one of nature’s many secrets that allows you to treat a patient more effectively is invaluable.

You were involved in the founding of Wings for Life. How did that come about?
I myself used to ride motocross and Enduro bikes, so I knew Heinz Kinigadner as a legend of the sport. During a KTM training session, I met Alfie Cox, a friend of Kinigadner and a motocross icon in his own right. When Heinz’s son, Hannes, had his accident in 2003, Alfie remembered me and invited me to give my opinion as an expert. There were no tried and tested therapy options for spinal cord injuries at the time. The only way to change this was to set up a foundation that promotes top research in this field. Wings for Life was born. Together with Dr Vieri Failli, we started with 20 research applications per year in 2004. Everything was very transparent right from the start and we soon welcomed international top researchers to our scientific advisory board. It always has been – and still is – important to us to listen, to never discount anything, and to continue developing. Today, we handle more than 250 research applications per year.

Im Gespräch mit Wings for Life Stiftungs-Mitbegründer Heinz Kinigadner.
Im Gespräch mit Wings for Life Stiftungs-Mitbegründer Heinz Kinigadner. 
 

Do you base your own lifestyle on a certain maxim?
Jonas Salk, a doctor and immunologist, inspires me. He focused on what was really possible, how one can push those boundaries, and how the reality of the future could look. He was prepared to leave his comfort zone. 

How are you as a family man?
Today, I have a different sense of responsibility and I don’t ride motocross bikes anymore. I follow the development of my two children with joy. I hope that they remain curious and find out where their respective talents lie. I’d love to see them blossom into brave and self-determined individuals.

Professor Dr. med. Dr. rer. nat.Jan Schwab is the scientific director of Wings for Life and the head of spinal cord injury unit at the Wexner Medical Centre on the campus of Ohio State University in the US. He has published more than 80 papers and has received several awards for his pioneering achievements.

 

GLOSSARY
Axon: A long, fibrous extension of a nerve cell which carries electrical impulses from the cell body and establishes contact with other nerve, muscle, or gland cells.

Immune-privileged organs: In these organs, the activation levels of the immune system are strictly regulated. In the brain and spinal cord, the reaction of the immune system is reduced in order to protect tissue that struggles to regenerate.

Translational: Rapid implementation of pre-clinical research into clinical development.


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