Perhaps the most noteworthy element of Osmosis from Elsevier’s Year of the Zebra educational initiative is the new, open-access, peer-reviewed journal Rare. Open Research in Rare Diseases.It joins Elsevier's leading collection of 2,500 publications in science and medicine. Rare is an open journal in multiple senses because, in an unusual step, contributions are being welcomed from patients as well as scientists. “We need the patient's voice to find out what their needs and challenges are every day,” says editor-in-chief, Dr. Wendy van Zelst-Stams. “We really want to have both a clinical impact on rare disease patients and an impact on their well-being in daily life.” Dr. van Zelst-Stams is taking on this new role in addition to her work leading the Clinical Genetics Section in the Department of Human Genetics of the Radboud University Medical Center and the Dutch Society of Clinical Genetics. In this enlightening conversation with host Shiv Gaglani, you’ll learn about Europe’s efforts to improve care for rare disease patients, the “DNA-first” approach her program takes to reduce the diagnostic odyssey, and the types of content that will be featured in this multidisciplinary scientific journal.
Mentioned in this episode: https://www.sciencedirect.com/journal/rare
Shiv Gaglani: Hi, I'm Shiv Gaglani. One of the most exciting elements of our Year of the Zebra campaign is the launch of a brand-new journal devoted to rare diseases from Elsevier. It's called Rare. Open Research in Rare Diseases, and it will give researchers, healthcare professionals, policy makers and the rare disease community open access to a scientific publication that covers all aspects of living with these disorders.
I'm delighted to welcome the editor-in-chief of Rare, Dr. Wendy van Zelst, to Raise the Line. She is head of the clinical genetics section at the Department of Human Genetics of the Radboud University Medical Center in Nijmegen, the Netherlands, and president of the Dutch Society of Clinical Genetics. Dr. van Zelst focuses on implementing new genetic diagnostic tools in daily clinical practice, especially in the field of rare and undiagnosed diseases. She's also the national coordinator for the designation of centers of expertise for rare diseases, and one of the two Dutch representatives on the board of member states of the European Reference Networks for Rare Diseases at the European Commission.
In addition to learning all about the new journal, we'll be asking her about what is happening in Europe to improve the quality of care for patients with rare diseases. Before we get started, I'd like to thank my Elsevier colleagues, Max Dumoulin, who first recommended Wendy, and Judith Escales, who's the publisher working with Wendy on the journal Rare.
Thanks so much, Wendy, for taking the time to be with us today.
Dr. Wendy van Zelst: Well, thank you for having me.
Shiv: I'd like to start by learning more about your background. What got you interested in a career in medicine, and then particularly genetics?
Dr. van Zelst: Well, actually, I've always wanted to become a medical doctor since I was a young kid, so I don't know anything else, and I wanted to work in a hospital. Fortunately, I was lucky enough to become a medical doctor. When I first was a medical doctor, I started to work as a pediatric resident in a small regional hospital, which was located near the Bible Belt area so there were a lot of consanguineous couples over there. I saw relatively many children with autosomal recessive diseases and that's what really got me intrigued and motivated, actually, to become a clinical geneticist.
Shiv Gaglani: Wow. Yeah, it's fascinating and interesting. So, there's a Bible Belt region in the Netherlands?
Dr. van Zelst: Definitely.
Shiv Gaglani: Really? I've learned something new right now, because obviously we know that term in the US, but I did not know that about that in the Netherlands. So, tell us a bit more about how your career has evolved from then. You're working at Radboud University Medical Center. What have you been focused on over the course of your work there?
Dr. van Zelst: Well, before I got to the Radboud University Medical Center, I did my PhD in Rotterdam, at the University Medical Center over there, which was a combination of pediatrics, oncology and genetics. Then I got my training to become a clinical geneticist in Maastricht, in the southern part of the Netherlands, and after that, I started working at the Radboud University Medical Center which is actually located in the eastern part of the Netherlands.
We have, I think, the largest genetics department in the Netherlands, and I think also in Europe. We are very specialized in rare and complex diseases and combine academic medical care with education and research and collaborate with other experts in this field on several levels: regional, national and international. We closely work together with our genetic colleagues in Maastricht in the southern part of the Netherlands as the Academic Alliance in Genetics.
We are actually quite known for our good quality of care in clinical genetic diagnostics and counseling, as well as personalized medicine and reproductive medicine. Our department consists of three sections, as we call it: genome medicine, genome diagnostics and genome research. As you said already, I'm head of the genome medicine section and focus on early diagnostics in rare disease patients, and we do that by DNA-first programs, as we call them. That means that we aim to have a diagnostic-first strategy after referral to our university medical center to actually decrease the diagnostic odyssey that patients with rare diseases experience. We perform this strategy for multiple indications like developmental disorders, oncogenetics or newborns admitted to the Neonatal Intensive Care Units. My own clinical experience is oncogenetics, so I mostly see patients with cancer that want to know if they have a tumor predisposition syndrome or, of course, healthy individuals that are aware of hereditary cancer in their family or have questions about the prevalence of cancer in their family and if it could be hereditary.
Shiv Gaglani: Wow, that's fascinating and it’s a very exciting time, I think, to be in genetics. A lot of our audience members are current or future healthcare professionals, and genetics touches all aspects. Even if somebody doesn't become a clinical geneticist like yourself, genetics will touch their practice of medicine and their research, especially now with the accessibility to whole genome sequencing. I think Illumina earlier this year announced a $200 whole genome sequence. I'm just curious, before we get into rare diseases, what do you think about this moment in clinical genetics and what gets you most excited as far as the future for genetics?
Dr. van Zelst: Well, I think, luckily, we have we have had huge technical technology developments. I think now we have the possibility with whole genome sequencing to diagnose a lot more patients at a much more early stage, if the costs go down, of course. Two thousand dollars is still a lot of money if you want to have it broadly available in healthcare. In the Netherlands, we're quite lucky, actually. Our healthcare system is built on a solidarity principle, which means that basic healthcare is reimbursed totally, and genetics is included. So, we can offer whole genome sequencing to our patients if they are referred to us.
Shiv Gaglani: That's awesome. That's great to hear and, obviously, the cost curve will keep going down, so hopefully that'll become more accessible not just in Europe and in the US, but all over the world. So, let's switch gears to the journal. It’s very exciting that you are editor-in-chief of Rare, the open access journal for rare disorders. First of all, tell us about your journey to becoming editor-in-chief and then maybe what you're hoping to achieve with the journal.
Dr. van Zelst: Well, it's a quite short journey, actually, because Max and Judith, who you mentioned already, reached out to me I think just before Christmas last year and asked me if I would be interested to become editor-in-chief of this new journal. We were discussing why a new journal would be necessary and if it would be necessary and what chances we would have to promote this new journal in a broad scientific field already. There are already a lot of genetic journals and also some rare disease journals with high impact. But they're mainly focused on patients that are diagnosed already, and so there's not much room anymore for case reports or specific attention for patients without a diagnosis. I think especially these patients would benefit by case reports with deep phenotyping to recognize patterns
So, I think there is room for a new journal, especially if we would align with a worldwide consortium like the Undiagnosed Diseases Network International. We really want to have not only a medical impact on rare diseases but also an impact on the well-being of these patients in daily life. I think a lot will be necessary to get there. We need the patient's voice, the patient journeys, to find out what their needs are and what their challenges are that they face every day.
Shiv Gaglani: Yeah, absolutely. I think that's actually what inspired not only the journal, but the Year of the Zebra concept in the first place. There's a lawyer in Switzerland named Philippe Pakter, who you may know of or seen. We had him on the podcast last year. He has a daughter, Lysiane, who's five and who was born with Pierre Robin sequence in a French hospital, though the Pierre Robin Center of Excellence actually is in Germany. So, he's dealing with all these cross-border rare disease treatment issues that he's still moving forward with.
He submitted a paper from a parent's perspective about Pierre Robin sequence to Seminars in Fetal and Neonatal Medicine, which is one of the journals Elsevier publishes that is not open access, and he wasn't able to get open access for his paper initially. So, we emailed our CEO, Kumsal Bayazit, asking for the open access to be granted and the fee to be waived, which Kumsal more than happily did for him and other patients who want to submit to those kind of journals.
Then one of your country colleagues, Lydia Tacx on the Elsevier team -- I don't know if you've run into her -- but she was responsible for a lot of our open access work at Elsevier, including helping get this journal off the ground. Her daughter, by the way, is a medical student at Leiden University. I don't know where you went to med school in the Netherlands, but she's going to be a physician in the Netherlands as well.
Dr. van Zelst: So, I went to Rotterdam. That's really nearby, actually.
Shiv Gaglani: Yeah, great. And so anyways, I’m personally, very interested in this, I know she is. So, it's been a whole journey and the Year of the Zebra concept started in large part because a parent of a child with a rare disease wanted to publish exactly the type of article that you're describing you want to get in the journal Rare. So, how are you going about getting in front of people? I know we're obviously sending it out in our weekly newsletter to patient groups that we work with. But what are some of the ways you want to get more submissions to Rare? And what are the things our audience should know about submitting to Rarebecause many of the people who listen to this are researchers and clinicians who could be authors in the new journal.
Dr. van Zelst: A lot of attention, of course, needs to be raised about this new journal and what possibilities it gives the patients or the parents of patients to present their journey and to describe the needs they have. We’re putting together a very broad and diverse editorial board -- not only diverse by background -- but we also have patient advocates in our board, and scientists from different backgrounds. We've invited an EMA regulator to join the board, but we also want to be diverse by location. So, we not only have, as usual, US or European or Australian professionals, but we have invited a lot of professionals from Asia as well as Africa. We are searching for a representative from South America to have as well. Hopefully, that will help in distributing the journal and raise attention and awareness of the journal. And your weekly videos by Osmosis really are helpful, I think, to raise awareness and attention in the field of rare diseases, and very useful.
Shiv Gaglani: Thank you. I was actually just yesterday looking at the statistics for the year. We're recording this just at the end of March in 2023, and so far this year alone, less than three months in, the videos we've made on rare conditions have been seen 1.2 million times. That's not just by medical students and practicing professionals, but also patients and their family members which you can see in the comments. My hope is anybody listening to this or watching those videos will not just consume content but consider being the creator of content and submitting to Rare as well.
I'm glad to hear about also the diversity and inclusion that you're doing, because that's the other piece about rare conditions. In the US, we have 330 million people, so a one in a million disease would impact 330 people. But if you expand that globally to eight billion people, that would be eight thousand. So, in order to advocate for policy changes or to do clinical trials with a high enough sample size, you need to start being able to reach more of these people across borders, which actually is a good transition to a question I had for you about your work in Europe. You've been involved with the European Commission. Do you want to talk to us a bit about that work as well? What the EU is doing or EC is doing to improve quality of care for rare patients?
Dr. van Zelst: Yes, sure. In 2009, the European Union came with a recommendation to improve the quality of care with patients with rare diseases. That was actually because of a request and a study Eurordispresented -- The Voice of 12,000 Patients study -- to the European Union to show that on average, patients with rare diseases need to visit over five medical specialists before they get a diagnosis. It takes them five to seven years before they are diagnosed, etc.
So, this really came to attention then and they really stated that each European member state should make a national plan on rare diseases by 2014 and designate centers of expertise based on a set of European criteria which were determined by a European expert group on rare diseases. This group was represented by a variety of stakeholders from policymakers to patient advocates, regulators, pharmaceutical companies, but also medical specialists, of course. That was actually the start of policymaking in the field of rare diseases in Europe.
In 2019 and 2020, there were some new discussions with a 200 or more-member multidisciplinary panel of experts, which was assembled for the Rare 2023 Projects, as it was called, and led to a set of new recommendations as a key policy priority at European and national levels. Lots of topics were addressed actually, and recommendations were made to be achieved by 2030, like data collection and utilization; accessibility and availability of orphan medical products and medical devices; basic clinical, translational and social research; diagnostics; integrated social and holistic care; patient partnership, and access to healthcare.
With the designation of the centers of expertise, these European reference networks were started. These are virtual networks that involve centers of expertise across Europe, and they review, for instance, patient diagnosis and treatment and have virtual advisory boards of medical specialists across different disciplines. In this way, the medical expertise and knowledge travels rather than the patient. so you skip the cross-border issues in this case. Twenty-four thematic European reference networks started and comprised over a thousand centers of expertise located in over 300 hospitals in all twenty-seven member states.
They made a five-year plan with aims and goals to achieve. For instance, create more clinical guidelines, invest in research and innovation, generate and share evidence and data, and engage in knowledge sharing by trainings and e-learnings. We're in the midst of an evaluation of these European reference networks to determine if they indeed achieved their goals and aims and how to move forward.
Shiv Gaglani: That’s incredible. It'll be interesting to see how that evolves. I've learned so much over the past year, not only from what you just shared there but Philippe as well, talking about how the EU is different and certainly it could be a model for collaboration if it works out well. It’s definitely more challenging than what we experienced here in the United States, where - while the borders are strong and there's a big difference between New York and Texas, as examples -- everyone speaks the same language and there's a bit more ease, I think, of collaboration, especially with one federal government being able to set that criteria.
I know we're coming up on time, so one question I have is, you know, Osmosis is a teaching company. That's how we grew up. We teach complex medical subjects, not only to medical students and now practicing professionals, but also patients and family members. If you could snap your fingers and have Osmosis produce one or more videos or a course on some topic to some group of people, what would it be and why? What type of knowledge gap would you want us to fill?
Dr. van Zelst: Well, I can think of a few, actually. I think there's a lot unknown about clinical trials in rare diseases. So, what type of trials should you design to move this forward? We need to get more insight in when to use what kind of design. So, that would be an interesting topic.
The other thing is, last week I attended an international conference on rare diseases and I heard a lot of patients and parents’ stories. I think that was really motivating, actually, to get more insight into what patients really need in their daily life and how to move science or research in that way...to get more ideas and inventions. For instance, a father there talked about his son who had absence seizures and therefore had poor school performance because of the fact he missed a lot of information during his classes. So, he ordered a wearable EEG and could see the readouts on his phone and send it to the neurologist and asked the neurologist if he could make any sense out of this readout.
The neurologist said, “Yes, of course, I see absences over there,” and then he actually put this together with some real time AI technology. Now, his son wears a headband which records his EEG, has his iPhone on his desk and if he has an absence, then the iPhone will shine a light so that the teacher knows that his son has an absence and he doesn't get the information. That way the teacher knows to repeat it again when he's present. I think these kinds of things are really helpful in creating ideas from a different aspect and point of view for us.
Shiv Gaglani: That's awesome. That's a really great example and kind of emblematic of what I've heard talking to rare disease parents and patients. They become so engaged and innovative and creative when they channel their energy for turning this tragic thing, this tragic diagnosis into something helpful, not only to them and their families, but anyone facing those conditions and, frankly, other people, because I'm sure this type of technology could be used for not just this condition that this child has, but for other people. That's wonderful. That's a really good example.
Two last questions. You have this great background as a researcher and clinician and policy advocate and now editor-in-chief of this journal. What is some advice you would give to our audience about approaching their careers?
Dr. van Zelst: Well, that's always difficult to say, but I think what's really helpful is that you look for a topic or focus that gives you energy. If you're really engaged, if your heart is in it and you get a lot of energy, then you know it's your topic and your focus and you should move forward in that direction. Of course, I think we have similar challenges -- limited finances, increasing demands on healthcare and also on healthcare professionals -- but as long as you get enough energy from your work, I think that's really helpful. I also think you should take opportunities if they are presented to you. Just try, and if you don't succeed, well, OK, don't be too hard on yourself. At least you tried and you learned.
Shiv Gaglani: That's wonderful advice. Both of those things. We talk about work-life balance a lot, and I agree that's important, but sometimes it doesn't feel like work, right? There are all these people who say that if something's giving you energy, if you're excited, if you're passionate about something, you can be working fifteen hours a day and it doesn't feel like work because you're so excited and you're grateful. You wake up excited about what you're going to be doing that day because you care about the patients or, you know, you're making an impact scientifically or whatever happens. So, that's great advice.
Is there anything else that we haven't covered that you want to get across to our audience about Rare, about you, about clinical genetics or the EU?
Dr. van Zelst: I just want to invite everybody to have a look into Rare, what our aims and goals are and what we try to achieve. If you have a voice and you want the audience to hear your voice, please submit a paper.
Shiv Gaglani: Awesome. We will definitely be linking out, and we feature the journal every week on the Year of the Zebra newsletter. I know there are a lot of people in our audience who are already excited about submitting. So, thank you, Wendy, so much for not only taking the time to be with us on this podcast, but more importantly, for your career helping people in the rare disease community.
Dr. van Zelst: Thank you very much, Shiv, and thanks for having me.
Shiv Gaglani: And with that, I'm Shiv Gaglani. Thank you to our audience for checking out today's show and remember to do your part to raise the line and strengthen our healthcare system. We're all in this together. Take care.