Episode 5: Working Together
Working collaboratively has been one of the hallmarks of Prof Daniel Lowenstein’s career. His passion for an inclusive approach has enabled him to bring together teams and achieve research results that would not have been possible without collaboration. In his clinical practice Prof Lowenstein is committed to providing well-explained, holistic, state-of-the-art care to all patients.
Hosted by Kris Pierce and David Cunnington, parents of Will, who has SCN2A.
Prof Daniel H. Lowenstein is the Robert B. and Ellinor Aird Professor of Neurology and Executive Vice Chancellor and Provost at the University of California, San Francisco (UCSF), Director of the UCSF Epilepsy Center, and Director of Physician-Scientist and Education Training Programs for the UCSF School of Medicine. He is known internationally for his contributions in the field of epilepsy including laboratory-based and clinical research, the clinical care of patients with epilepsy, and advocacy for the needs of patients and family members living with epilepsy.
Prof Lowenstein’s profile page from University of California, San Francisco
Ms Kris Pierce RN MHSc MWellness, is a rare disease advocate and mother to Will who has SCN2A. Kris has held a range of board, project management, advocate and consumer representative roles and has been instrumental in working with local, state and federal governments to secure funding for multi-million dollar projects. Kris is highly skilled in building teams to work together collaboratively and is a co-founder of Genetic Epilepsy Team Australia (GETA) and SCN2A Australia, and a RARE Global Advocacy Leadership Council member.
Intro: Welcome to SCN2A Insights bringing you the latest research and clinical updates on SCN2A and genetic epilepsy from around the world.
Kris Pierce: Hi, I’m Kris Pierce.
David Cunnington: And I’m David Cunnington.
Kris Pierce: Welcome to this episode of SCN2A Insights.
David Cunnington: In this episode, we interview Professor Dan Lowenstein who is the Executive Vice Chancellor and Provost at the University of California, San Francisco. And as you will hear as we interview Dan, he has had a very long career in both epilepsies and genetic epilepsies, pulling together collaborations and hopefully, you will hear that through the interview, the power of working together and what it can achieve in research.
Kris Pierce: Hi, Dan. Thank you for helping us out today. I have not long returned from my trip to Washington which was fantastic and I attended the Epilepsy Precision Medicine Conference, which was inspiring as a patient advocate. What was your impetus for convening the Epilepsy Precision Medicine meeting?
Dan Lowenstein: Kris, thanks for your participation in the meeting. It’s meant a lot to have representatives of a patient and family groups from all around the world. The meeting really had as its origins the commitment that a large number of us working in the field of epilepsy genetics and epilepsy in general more than 6 or 7 years ago now when we thought it would be appropriate to bring together the stakeholders from all around the world, to focus in on the prospects for precision medicine in epilepsy. That is the direction that we are all dreaming of in which we are able to provide very, very precise diagnoses for every person who has developed a severe disorder and more importantly, then be able to deliver extremely effective treatments if not cures on an individual basis.
So we actually held that meeting in 2014 in Half Moon Bay here in California. And after the passage of about five years or so, we decided the time was right to bring together again an international group and focus in on that same topic of where are we now and what is the future holds for precision medicine in epilepsy.
David Cunnington: And so Dan, what was the motivation for trying to bring together all the stakeholders?
Dan Lowenstein: It has become very clear to me over the course of my career that we are able to accomplish more by ensuring that we have as full a spectrum of perspective and experience around the table in order to analyze the problems that we are tackling and to try to come up with creative solutions. And as we think about the problem of seizure disorders and epilepsy, there’s a clinical aspect of physicians and other healthcare providers being able to assist people who have developed seizure disorders. There is the research component, those individuals who are thinking about how do we understand the underlying basis for the existence of epilepsy and what do we need to understand to identify effective diagnostic techniques and cures.
And at least equally important, we need to have the perspective of people living with epilepsy and families who are living with epilepsy so that we can really have a full understanding of what the nature of epilepsy is, how it affects an individual, what are the ramifications of various approaches to diagnosis and therapeutics.
So, I’m just a firm believer in having as broad a spectrum of experience as possible to solve big problems.
David Cunnington: And other examples where you found you haven’t been able to pull those groups together and how has then impact on moving the field forward?
Dan Lowenstein: I’ve been really fortunate to have been engaged in a number of very large collaborative efforts over the last two decades. My own experience started when we decided to try to tackle an obvious problem which was with the ability to sequence the full human genome which really came about in the latter part of the 1990s and was effectively announced in 2000s.
It became very apparent to those of us in the world of medicine and specifically those of us working in the field of epilepsy that the time was going to come when the folks who are doing the sequencing given the advancement and the technology that they would be able to provide a sequence data. But we were going to have to be in a place where we could provide them the blood samples for many, many, many people with epilepsy so that we would have the datasets that they would need in order to do the sequencing. I hope that made sense.
So in other words, the problem that we were facing was we need to bring together a large number of people living with epilepsy and enroll them into a study which would allow us to get careful information about the nature of their epilepsy and then also get blood samples so that we could have DNA to actually sequence.
It was really clear right at the outset here again in the early 2000s that the only way that we could possibly do that would be to make large scale collaborations of investigators all across the world because no individual scientist would be able to collect the numbers of patients that were needed in order to do that level of research. This is one of now many, many, many examples across the whole spectrum of medicine and science at large which is what we call team science, the science that has done beyond the individual investigate on laboratory.
Kris Pierce: We certainly saw that coming together in Washington where groups were getting together and talking about their work and how they can support each other and also enhance what each other are doing for the betterment of that and treatment goal. It was fantastic to see it in real life.
Have you seen across your time, Dan, some barriers that come up with this working together across all those different stakeholders and what can we do I guess as a patient advocacy group, what can we be doing to support that collaboration to make it work better for the researchers?
Dan Lowenstein: Yeah, that’s such a great question. So yes, I have definitely seen things evolve over the course of the last two decades. Going back again to the early 2000s, the project that we eventually put together was called the Epilepsy Phenome/Genome Project. As we set up the ground rules if you will for the project, we needed to make it very clear that the only way that this was going to work would be if people were, as one might say, willing to play together in the sandbox. We had to think through what would it mean to be an effective team member in such sort of a larger scale research project. We came up with a number of policies if you will that people needed to actually sign on to in order to be part of the project.
Two examples, one had to do with authorship. As you know, those of us who do research, the only way a research is of any value is if it’s seen by the rest of the world in the form of a publication. But one of the hang-ups about publications is that they sort of convey the work that you’ve been doing. It’s a way of being given credit for the research that you are doing. The challenge that we face is, how do you make sure that everyone gets credit?
With the Epilepsy Phenome/Genome Project, all the investigators who signed on agreed that every single main paper that came out of the project would have as its authors the EPGP collaborative and no individual member would be named as the first or the senior author. That was a little bit challenging for some people to accept. Those who couldn’t accept it weren’t part of the project.
What happened over the last 15 to 20 years is more and more researchers are recognizing that in order to do this kind of team science, you have to let go of this need to want to get as much credit as you possibly can as an individual. Fortunately, there are more and more people who are willing to not be the main focus under the light of recognition. That requires also giving up a little bit of your own ego, if you will. That has been the main challenge. But again, I’ve been very heartened by just how many researchers are out there who are willing to see that we can accomplish so much more if we sort of let go of the need for getting credit.
A couple of other ideas about how we can advance this, no question that funding is critical. The way the systems are currently designed for funding for research, they tend to favor individual efforts. The more that we can do to press our governmental agencies to provide funding for large collaborative efforts, the better.
The same I think was true for foundations, patient family groups who are raising money for research in their area. The more that you can use that money as leverage to essentially encourage if not force investigators to work together as a team I think the better.
Then the last thing is I think there is – I can’t overstate the importance of folks like you who are really, really making us see that at the center of all of this work is the patient and the lives that they are leading that have been so impacted by epilepsy and how desperate we all are for finding effective treatments and cures.
The other thing, and Kris alluded to this, there are definitely some groups of investigators and members of patient family groups as well as clinicians who were definitely beginning to think about some new research studies that could be carried out based on the interactions they had at the meeting.
David Cunnington: It does show you the power of getting interested parties together in a room to just talk through things. And thank you for organizing that.
Dan Lowenstein: Oh, you bet!
David Cunnington: The field of genetic epilepsy is really evolving rapidly. What do you see as the major things to come in the next few years?
Dan Lowenstein: In the area specifically of understanding the genetic basis of epilepsy which we think is a major contributor to these various forms of epilepsy out there, with the increased size of cohorts of patients with epilepsy, we are going to be able to extract a lot more meaningful data out of a larger and larger datasets of sequences. And that’s going to allow us to tackle the much more complex genetic basis of the more common epilepsies out there.
As you know, we’ve had the most success with some of the more severe forms of a genetic epilepsy that typically arise early in infancy and childhood, and those epilepsies have a simpler sort of underlying genetic mechanism. But the more common or the vast majority of genetically-based epilepsies clearly have a much, much more complicated structure if you will, and that’s going to take sequencing, lots and lots of patients.
We are now up to well over 25,000 patients in a big team science project called Epi25 which is being carried out the Broad Institute in Boston. And the results of the initial phase of that study of a portion of those patients was just published just a couple of months ago and we have another again, 8,000 to 10,000 patients that will be added on to that. I expect to see some advances there.
Another area that I think will evolve quite rapidly over the coming 5 years is going to be what we call epigenetic or other aspects of the cascade of molecular events that occur in a cell that are over and beyond just the genetic code itself. We are focusing in on genes because they are relatively easy to study compared to the RNA that’s made by those genes and then – which is the messenger that then is able to encode the proteins that ultimately are the determinants of the function of a cell. I expect that over the next number of years, we are going to begin to see more and more advances at these deeper and deeper levels of the molecular structure of a cell. With that, I hope, we will be able to better identify the targets that could have an impact with sort of precision targeted therapy.
David Cunnington: Great. Thanks a lot for those insights, Dan.
Dan Lowenstein: Of course.
Kris Pierce: What a great interview with Dan. He highlighted across the interview the importance of collaboration and showing some real-life examples of who he has done that throughout his career, a great example to us all.
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Outro: This podcast is not intended as a substitute for your own independent health professional’s advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider within your country or place of residency with any questions you may have regarding a medical condition.