Leading The Way Towards A New Paradigm Of Medicine

Despite having a well-established structure, the healthcare system is not working so much in favor of the patients. Harald HHW Schmidt dedicates his research to present a new paradigm of medicine that is more patient-friendly. In this episode, he talks about his book The End of Medicine as We Know It, inspired by the realization that getting grants and writing papers do not do enough for patients. He also makes an interesting analogy between getting your care serviced and seeing the doctor. Furthermore, Harald discusses the importance of thinking about the management aspects of being a researcher and clinician.

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Listen to the podcast here

Leading The Way Towards A New Paradigm Of Medicine

A Discussion With Harald HHW Schmidt

We have a very interesting guest, largely because he's trying to push a new idea or viewpoint of how we should think about disease. I'll be talking to Harald Schmidt, the Professor and Chair of Pharmacology at Maastricht University, who happens to be quite close to me here. I come across his profile on LinkedIn. We connected, and I saw this book where he talks about network medicine. We'll get into that in some detail and how that's a different way of viewing disease in patients. We also touched base upon the real challenge of what happens when you've worked hard on something like a grant and it gets rejected, also about what it is to be a manager in science and a researcher and a lot of other topics. I found this a very interesting and inspiring show. Sit back and enjoy.

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My name is Harald Schmidt. I'm a medical doctor and a Pharmacist. I'm a Professor of Pharmacology and Personalized Medicine at Maastricht University in the Netherlands

Thank you very much for coming to the show. We were chatting before we started. There are a lot of synergies and similar thinking between us and a lot of people I work with. I'm looking forward to the interview. I think it's going to be pretty obvious. What impact do you intend to make in your role?

I do medical research. In the beginning, as a young researcher, you have to make sure that you have a lot of papers. I impact journals and so forth. I get a couple of fellowships and grants. At this stage of my career in medicine, I measure myself for what I have impacted for patients. What has come out of years of research that patients benefit from? I'm not doing biology. I'm in medicine. That's what counts for me.

In that shift in mind, what made that happen that, “I'm focusing on papers? I'm focusing on making a difference.” Was it always there?

In the beginning, you get the carrots in front of you that your senior teachers present to you and what everyone else does. You think that's how it has to be. It is exciting to see your name for the first time on a paper. After a while, I felt that it makes no sense chasing the next possible hot paper, but we need to think about what are the biggest issues in medicine, knowledge gaps, and how can we solve it? I had a Eureka moment when shortly after I came to mastery, a colleague showed me a paper from László Barabási. He's a physicist and a network scientist. He has written the book Linked on the network of all human diseases.

The key message of this paper was the way we have divided up medicine is` basically organ by organ. For every organ, we have a clinic, discipline and research area. We have neurology, neurologists and neuroscience. We have cardiology, cardiologists and cardiovascular research. That absolutely does not make sense because, in these networks, you can link diseases by genes, drugs, symptoms, and co-morbidities.

However you do it, you see that diseases somehow belong together that we treat in different disciplines and doctors, but somehow, biology shows us they belong together. We keep them artificially apart. Let’s say I'm a cardiologist and the patient has a symptom in the heart. The patient also has a symptom in the lung and skin.

We say, “That's none of my business.” I refer him to a nephrologist and to a dermatologist. In research, we will never understand diseases. The reason is evidenced by the fact that we have many chronic diseases. Almost every disease is chronic. It’s like if you bring your car to a garage. The garage would tell you, “We fixed a little bit your car, but I'm afraid it's chronically broken. You have to come now every three months. We fixed it a little bit. We charge you a little bit. That's it. Your car is chronically defective.” You would say, “Thank you very much. I think I'll go to a different garage.” In medicine, we can't. That's the status of medicine. That is the knowledge gap that I felt that we have. This paper came and then my whole brain rearranged. I could not do what I had done before. We were completely different now.

Maybe you can go into what is different. What do you do differently think compared to what you did before?

The normal secret is you need to do some basic research, then test it in an animal model and then do a clinical trial. This system does not exist. It's not working like that. The basic scientists and preclinical researchers more or less work for papers in journals to get research funding. With it, they produce more papers. No one looks at what comes out of this for true patient benefit. With respect to clinical research, we have very little investigator-initiated clinical research where clinicians design the study, get the money, contact the study, ideally multicentric, analyze it and publish it.

Most of the clinical trials are industry-driven regulatory trials. We have the whole reproducibility issue that we have this positive publication bias. Accidentally, positive data are published, and journals like to publish, “Gene A is relevant for disease B rather than gene A has nothing to do with disease B.” Therefore, you get all these supposedly positive data in the literature.

We all know from five papers now that over 50% is not reproducible. We have a big issue. Everyone has settled nicely in the system, academic research industry, pharmaceutical industry, healthcare system, or the sick care system. We don't really have a healthcare system. Everything is working nicely, but not for the patient.

What you're saying is that what you do differently now is instead of looking to get the papers, you say, “What needs to happen next in this field for the benefit of the patients? That's what we need to research next.”

The change was if these networks show based on big data that the diseases are completely differently connected and what we nowadays call a disease, in which typical symptoms like hypertension or heart failure, are underlying molecular mechanisms. We have to get down to these molecular mechanisms. A good example is rare diseases.

“It makes no sense to chase the next research without solving the biggest knowledge gaps in medicine first.”

In rare diseases, we very often have one gene that's affected. Unfortunately, that gene is important because this already causes the disease. Those rare diseases very often have symptoms in 2, 3 or more organs even though they're caused only by one gene. Our current system of medicine would easily make out of that 3 or 4 entirely different diseases if we didn’t know that it is this one gene.

In all other chronic diseases, we also have symptoms in several organs. We declare them different diseases, and we don't know the underlying cause. This is what we have to overcome. Therefore, we completely shifted with a lot of bioinformatic collaborators and completely different approaches. Very little animal work to have this new approach to disease. What we also then found is that in order to prove this, we need to do clinical trials.

We have to provide clinical evidence here, “If you do it this way, if you define a disease differently, if you diagnose it by a molecular mechanism,” and treat that mechanism, you can cure a disease with high precision. I may still be totally wrong, but that's the risk. We have to prove this as soon as possible in the clinic. I've done my knock-in mouse, even enzymology experiments and now we're doing almost completely clinical trials.

In a way, rheumatology has done this to some degree because they shifted it to, “Let's see what we can do to modify the disease course.” What I understand from talking to rheumatologists is that it came about by the same thing of saying, “Let's not make a consensus about this. Let's just make a research roadmap.” Everybody started doing research, and then that influenced clinical practice eventually. What you're talking about is much more explicit in driving in that way.

Cancer, for instance. The oncologist field is also a driver. When I studied Medicine, basically, the neurologist was treating his brain tumors, the gastroenterologist, his colon carcinomas and the pulmonologist, his lung tumors. In every good hospital nowadays, there is a tumor board and no matter in which organ the tumor sits, the tumor is treated based on the genetic profile or the drug responsiveness. A tumor in the colon may have exactly the same mechanism as a lung tumor.

Two histologically identically looking lung tumors could have completely different mechanisms for why the tumor developed and then they would need different treatments. There, we are maybe a step further. Maybe we are not totally there yet. We know a lot of driver genes in oncology, about 380 or so, but our current drugs target only 80 of them. There's a lot of room for development.

It's foreseeable that we will treat cancer completely differently in a few years. What other diseases? As you said, rheumatoid arthritis and asthma are similar discussions. You see more and more that some doctors realize, “You can't go on like that anymore. We can't use this disease definition in the 21st century anymore.”

You described a lot of this in nice detail because I've read some of it in your book The End Of Medicine As We Know It. I encourage people to take a look at that because what I like about it is you provide some nice evidence behind some of this stuff. You go into some of the details of the literature behind it and the rationale, which you want that in a book, not just put the idea out there, but you want something to help you. I commend you on the book. I think it's fantastic. Maybe it's an assumption, but you're somewhat of at a high point in your career. What was the lowest point of your career?

I have a couple of them. One of the worst things is when you spend the whole summer, usually three months, writing on the grant. You think left and right. The grant submission dates are the 1st of September or something. The summer is gone. In December or so, you get a response like, “Interesting, but too ambitious. Too risky.” That's tough to then say, “No. I'll carry on. I will submit again next year.” I've had cases where the grant was rejected. When I got my first ERC, I submitted the same thing again and it got accepted, which means there is an arbitrary effect over all of that.

When you get such a rejection, that's tough. You need to go outside walk, breathe deeply, and carry on. When it comes to management, I have made every possible management mistake one could possibly do. I'm more or less immune against it, but in my case, it was learning by doing. It would have been nice if I had some training. Later, when I was more senior in Australia, for the first time, I got personal development training and self-management training. As a German professor, there is a little bit of attitude that all this knowledge comes upon you like the holy ghost. You automatically learn those things. In Australia and Netherlands, for the first time, I had this. I wish I had it earlier.

You'd probably recommend that whenever you get the opportunity to take that kind of training you should avail yourself.

I cleaned out my bookshelf here and threw away all the leadership books that I bought over the years. In the beginning, it was The One Minute Manager and stuff. The only two books that I kept were Getting Things Done and The 7 Habits of Highly Effective People. These are the two books I at least recommend to all my junior staff. With these two books, that's enough. Don't read anything else. Try to be a well-balanced person, not a workaholic.

It's one of my hypotheses about what makes a good leader in the field. It's people that not only just read articles but also read books. You are starting to support that hypothesis in that way because there are all these other aspects. If you're going to go beyond just writing papers, you need to understand all those other aspects because it's going to be frustrating, like the grants. That's something I also dealt with because, for fifteen years, I've helped people try to get grants. You see it all the time. You've already said what the future of medicine is.

The part that I mentioned that we should define diseases more precisely and treat them more precisely is certainly one aspect. The real potential in medicine is prevention. We spend only 1% of our healthcare budgets on true prevention. That even sometimes include early detection of cancer, for instance, prostate cancer, colon cancer, and so forth, which is not the prevention of cancer. It's early detection.

“It is tough to face rejections, but you need to go out and face them. Breathe deeply and just carry on.”

We know that about 80% of all chronic diseases would be preventable by preventing risky behaviors, like excessive alcohol, smoking, unhealthy eating, not good stress management, not good social contacts, and climate crisis. All these things add up, maybe not all of them for everyone, which is a problem because prevention means that all of these things are suggested to everyone.

To do that more precisely and in a clever way. I don't think medical doctors are trained for that. We will see other jobs coming up like preventogists, nutritional coaches, personal trainers or psychologists, and so forth that tell people to address their personal risk by prevention, which is much more effective than waiting 40 years until the first myocardial infarction comes up or the blood pressure has risen.

I’d love to get your perspective on this. What about preventative therapies? That's starting to come up and a question people have is, “That's great, but there's no regulatory framework for this.”

That's why I said we have a sick care system. We don't have a healthcare system. You only become a user of the healthcare system when you are sick, then you can go to a doctor, and then you'll get in touch with the system. That's what needs to change but in an evidence-based manner. What you said about therapy, diabetes is maybe a good example of where prevention kicks in and where still drug therapy kicks in.

In the ‘60s, we had a prevalence of 1% of diabetes in our population. At that time, we called it diabetes of the elderly. Those people were usually slim, not overweight, not obese. Hardly anyone was obese in the ‘60s. That was an almost preventable form of diabetes, Type 2. The increase in the population from 1% to 7% or 8% now of diabetes, this data is lifestyle. Those people should be exclusively targeted by lifestyle as soon as possible instead of drugs or moving them into diabetes disease management programs.

They need massive lifestyle intervention. Only those people who have this genetic risk to get even with the best lifestyle diabetes, they would probably need to have this mechanism, which we don't know, identified. Maybe from the age of 30 or so, treat them with some drugs so that their diabetes does not develop. The majority of this so-called diabetes pandemic needs lifestyle, but there is a small fraction that probably needs drugs.

You've thought a lot about these things and that you're a leader in not only research but innovation. What does being an innovation leader mean to you?

One thing is that these types of projects that I run, I could never do on my own. Almost nothing in medicine and research you can nowadays do on your own, but this work is particularly interdisciplinary and interdomain. I work with mathematicians, bioinformaticians, clinicians, and diagnostic experts. It’s extremely broad. You need to find the right collaboration partners. You need to entice them and lead everyone to stay on track.

I don't see myself as the leader. It’s basically like a pyramid. I'm in this team, the person with the biggest talent of making sure that the direction is correct. I would not necessarily say I'm on top of everyone. There are people that do methodologies or they have this precision that maybe sometimes I like because I do ten things at the same time.

You have to appreciate everyone in such a team and make sure that everyone benefits from being in this team, whether they are locally or whether they are collaborators somewhere else. That's a very important duty that you have. Otherwise, every team will fall apart. If someone has the feeling, “I'm not sure whether I can contribute or I'm appreciated or whether I get anything out of this. I'm valued,” then people will disappear.

What you described is collaborative leadership or leadership 2.0. Instead of being on top leaders doing what you're saying, making sure everybody's engaged and everybody has their role, everybody feels that they're part of the whole thing. This level of intense collaboration is what we need to keep the vision like you were saying, understanding mechanisms and getting rid of the disease definitions. That's important.

Also, communicate a lot because, in the end, it's a lot of change management. I talked to a lot of established people in different clinical fields, regulatory fields, health insurers or politicians to explain to them why this change is needed and how it's possibly going to look like so that they don't feel threatened. It is threatening if I tell a head of neurology who is 45 years old, “According to our systems medicine approach, you have to eventually give up your organ focus. You need to work more interdisciplinary, more systemic like in cancer.” You have to say it in a way that there is still a positive message in there.

Are there leaders that inspire you?

I've worked with great people. I worked in Chicago with Robert Furchgott, who got the Nobel Prize for a new signaling molecule that he identified. Later, I met interesting people. I took bits and pieces from different people that I liked and I thought they were good at. In the end, you have to be authentic. You have to do the stuff that fits you. There wasn't a single person that I almost imitated, but I always noticed very nice features that I tried to adopt from you.

“Make medical research fun so you can enjoy it all the time. You won’t even feel like you’re working.”

I've read things about this before, especially with regard to mentoring. You don't have one mentor. You may have several and you take different aspects. You may say, “What that mentor is saying isn't what it is exactly, but I'll take that from him.”

I still have one mentor who is ten years older than I am. I'm still in touch with him. Although, I'm over 60 now. He's over 70. I don't consult him that frequently, but I like to hear his view. I like it when he says, “That's great stuff. That's interesting.” Equally, I feel responsible for PhD students or postdocs that work with me that stay in touch. It's nice when they contact you over a couple of years here, “What do you think about that? What do you think about that career move? What do you think about that project?” It's give and take.

One thing I would like to ask you is what is something that you do when nobody else is watching it enhances your performance as a leader?

I can sometimes be pedantic. When I've finished tasks, particularly those that I have procrastinated for quite some time, it's a wonderful pleasure to tick it off physically on my to-do list or to delete the recurrent item in my agenda that I said, “I have to do this,” then I delete it. That's, for a short moment, a very nice feeling.

There's a third book that I liked. It's called Fierce Conversations. Sometimes you have very difficult meetings that I prepare for. They are potentially confrontational. I prepare very well for those meetings. That’s a nice book. It doesn't mean aggressive conversation, but to the point, a conversation that you prepare for a mutually agreeable solution, but you also make your point and show a way out of it. I do this on my own.

What advice would you give to a younger version of yourself?

What you hear a lot is work-life balance, also in research. I think research is one of the few jobs where you don't work a pile of paper in the morning, and by 5:00 PM, the pile is gone. You have ticked all the boxes and you can go home and then don't think about work. Sometimes I don't think about work during the day because I don't feel like that. I have no idea. I don't want to, and then I do it in the evening. All of a sudden, I enjoy doing that. It is one of the few jobs that can be extremely creative, but similar to a violinist that says, “No, I only play the violin from 9:00 to 5:00, then it's the end of work.”

Ideally, your job in research is fun. You enjoy it so that you don't even feel it's work. You need to be balanced. You need to have other activities, hobbies, activities with friends, family sports, all of that as well. I never felt that research was work. The exception maybe is when your grant gets rejected. Question yourself, “Is this what you want?” Don't do it because you say, “It would be nice to stay in academia, then you have a fixed position. It would be nice to be a professor. That's a nice position.”

Do it because you think research is what you want to do. I also think teaching needs to be research-driven. If you're not a top researcher, you teach basically from a textbook. If you teach from a textbook, you teach 5 or 10-year-old knowledge. You teach how your field was in the past. Our responsibility is to teach how the field will be when you have left university. Even in ten years, you are like, “I heard about this at university and now it's there.” That's my personal view.

When I was in medical school, there were teachers who were teaching their research. A neurophysiologist was teaching cardiology. Maybe he was thinking not that way, but maybe it was correct. That’s a great insight. What I want to point out is that it's often under-appreciated that research has a creative activity.

If you look at the literature on creativity and at one point, I learned a lot about creativity from John Cleese from Monty Python because he gives lectures on creativity and it is exactly like what you said. Going away is when you're out walking your dog or waking up in the morning is when the ideas that break through.

Also, in the middle of the night. I had to put a notepad next to my bed in case I had this brilliant idea. I don't want to forget it. One tip is to have a notepad next to your bed that you can write it down and literally take one in the middle of the night, “That was the idea,” then you can sleep.

This has been great and we could probably go on. Maybe down the road, we'll have a second episode. Is there anything else you want to comment on or make a point about?

No, I'm fine. I made my point. What we're doing is a beautiful theory, very logical and clean, but it may still be wrong. That happens. We will see once the clinical trial is done. I have to research this, and we celebrate.

Important Links

About Harald HHW Schmidt

Dr. med. Harald H.H.W. Schmidt is a medical doctor and pharmacist and Professor and Chair of Pharmacology & Personalised Medicine at Maastricht University’s Faculty of Health, Medicine and Life Sciences. He led a research program as European Research Council (ERC) Advanced Investigator, which translated into a current ERC Proof-of-Concept grant to develop a first-in-class neuroprotective therapy for ischemic stroke. He co-led a EUROSTAR programme which led to the development and commercialisation of a NOX4 inhibitor.

As a science leader, he founded/led two European Science Foundation COST actions, one on reactive oxygen (EUROS), one on Systems Medicine. He now co-coordinates the EU-funded Horizon 2020 programme REPO-TRIAL on Systems Medicine and is work package leader in the EU-funded Horizon 2020 programme FeatureCloud. Before Maastricht, prof. Schmidt had worked in Australia, Germany and USA in different academic and business leadership positions. These include chair of Monash University’s Centre for Vascular Health, Australia, Maastricht University Faculty of Medicine innovation platform, the Netherlands, different chairs in pharmacology and director of a drug discovery CRO at TransMIT, Giessen, Germany.

He also co-founded and for two years led as CEO Vasopharm GmbH, a drug discovery company now entering into phase III clinical development. His research focuses on cardiovascular and neurological disease mechanisms, target validation, drug and biomarker discovery, personalised and network medicine. Professor Schmidt has published over 200 peer-reviewed papers, reviews, books and patents (Hirsch-index of 95). He was member of the Executive Board of the European Association of Systems Medicine (EASyM), founded the International Society of Systems and Network Medicine (IASyM), co-founded and is co-editor-in-chief of the journal Network and Systems Medicine. He has been awarded the Roche Molecular Biochemicals Research Prize for Cell Biology, the Phoenix Research Prize in Pharmacy, and the Pro Scientia Prize. He is officially registered as policy advisor at the German Parliament (Deutscher Bundestag), co-founder of the patient network patientenwiewir.de, and advises the patient network dopanet.org.

Leading The Way Towards A New Paradigm Of Medicine

Listen to the podcast here

Leading The Way Towards A New Paradigm Of Medicine

A Discussion With Harald HHW Schmidt

Important Links

About Harald HHW Schmidt

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