|NLMFF interviewed Susan Birren, Ph.D., Associate Professor of Biology at Brandeis University about the autism work that she undertook during her NLMFF-funded sabbatical year, her current research, and her NLMFF-supported course at Brandeis entitled, “Autism and Human Developmental Disorders.”
NLMFF: Could you tell us a bit about your academic and professional background, and the circumstances which led to your interest in autism and developmental disorders?
Dr. Birren: I received my Ph.D. in Biological Chemistry from UCLA studying how genes are regulated and how changes in gene expression affect the functions of cells. I was interested in applying these molecular and cellular approaches to problems that could provide insight into human health and disease and I became very interested in studying the development of the mammalian nervous system. I did a postdoctoral fellowship at the California Institute of Technology where I studied the proteins, genes and signaling pathways that regulate the development of neurons in the mammalian peripheral nervous system. The process by which undifferentiated cells become functional neurons and contribute to neuronal circuits is absolutely fascinating and the fact that these circuits organize themselves in the brain in ways that permit human learning, memory and cognition is nothing short of astonishing. From this realization it was a short step to wonder how mishaps in the organization of these circuits lead to disorders of development. It was after I started my own laboratory at Brandeis University that it became clear that the mechanisms of development that we were uncovering in the peripheral and central nervous systems, including the role of neurotrophic factors in the developmental regulation of excitation and inhibitory properties of neurons, were the same processes that were disrupted in developmental disorders.
NLMFF: Could you tell us about the autism-related activities that you undertook during your NLMFF-funded sabbatical year?
Dr. Birren: I developed and taught a new course at Brandeis on Autism and Human Developmental Disorders. Along with Art Wingfield I organized and participated in a Brandeis University and NLMFF- supported symposium on Autism. The Symposium brought together an international group of distinguished scientists as well as Boston area researchers and lay people to hear about current approaches in autism research. With funding from the NLMFF, I organized a University seminar series that brought autism researchers to Brandeis to give lectures on cutting edge research in a variety of autism-related fields. This series was coordinated with the undergraduate Autism class that I taught, so the scientists came to Brandeis, lectured in the course, gave a seminar for Brandeis faculty, graduate students and postdocs, and spent an additional day meeting with members of the Brandeis community. I also attended meetings focused on autism research, including meetings of the Boston Club and a meeting organized by NAAR to bring together basic and clinical researchers interested in autism. Overall, these efforts significantly expanded the awareness of Brandeis researchers to the critical current issues in autism research.
NLMFF: Could you describe the nature and progress of your research supported by the National Alliance for Autism Research?
Dr. Birren: Several studies over the past few years have demonstrated that the brain's cholinergic systems are disrupted in autism and related disorders. I found these studies extremely interesting because, in animal models, cholinergic inputs to the cortex are critical for the development of normal behaviors. My laboratory has a long-standing interest in the role of neurotrophic factors in the development of excitatory and inhibitory synapses, and emerging evidence has suggested that there may be altered expression of neurotrophic factors in autism and related disorders. Putting this all together, I started a research project to investigate how cholinergic projections from the mammalian basal forebrain influence the development of cortical synaptic connections and the role of neurotrophic factors in setting the level of excitatory and inhibitory transmission in this system. We have demonstrated a novel, neurotrophin-dependent mechanism for the development of excitatory cholinergic and inhibitory GABAergic neurons in the basal forebrain that we believe plays a developmental role in setting the level of cholinergic transmission between the basal forebrain and the cortex. We believe that disruptions in this system in autism and related disorders could alter the development of cortical circuitry and contribute to behavioral changes. In the future we plan test this hypothesis using a variety of animal models that can be used to recapitulate some aspects of autism-like disorders.
NLMFF: In Fall 2004, you taught a NLMFF-supported course at Brandeis University entitled, "Autism and Human Developmental Disorders." Could you tell us a bit about the goals and scope of this course?
Dr. Birren: The course was called "Autism and Human Developmental Disorders". It was taught as a Biology and Neuroscience elective and was taken by Juniors, Seniors and first year graduate students here at Brandeis. The goal of the course was to cover a number of different fields broadly to integrate the current state of knowledge about the epidemiology, biology, pathology, genetics, psychology, and social issues associated with autism spectrum disorders. The course was structured to include lectures, discussions and student presentations, and to give students the opportunity to hear from distinguished guest speakers who are leaders in the field of autism research.
NLMFF: There is considerable disagreement over the exact nature of autism. How have you introduced and defined "autism" to your students?
Dr. Birren: It is true that there is a great deal that we don't understand about autism, and I think that the disagreements emerge out of those gaps in our knowledge. But there is also a great deal that we do know, and that is a good place to start when introducing the subject to students. We know that autism is a devastating disorder that affects the developing brain and that has profound and life-long effects on behavior. We know that it is a disorder that is based in genetics and is likely to involve a number of different genes and interactions. Those are all great jumping off points to start discussing the complexities of the disorder, the impacts on families and the interactions with the broader community. Starting from there we can explore the controversies that have been associated with how people think about autism and explore the bases of the disagreements.
NLMFF: "Autism and Developmental Disorders" includes a broad range of issues and topics. Could you describe some of the major topic area s that this course focused on?
Dr. Birren: We covered a very wide range of topics in the course. We started with an overview of developmental disorders, defining what is meant by the term and discussing them from a historical perspective. We talked about the medical aspects, diagnosis, treatment, and epidemiology, and looked at the primary data behind the idea that the incidence of autism has been increasing. We spent time talking about the structure and function of the brain, examining evidence that autism is, in fact, a disorder of development, and discussed the implications of these developmental disruptions on behavior. We then moved on to the genetics of autism and discussed twin studies and other data suggesting a genetic component to the disorder. We talked about prospects for uncovering genes that might be involved in autism. In the last third of the course we covered cognitive, social and societal issues associated with autism spectrum disorders, examining cognitive models and issues of language and communication. We thought about how autistic people and their families navigate in society and discussed current and potential future approaches for treatment. In a series of student presentations we addressed old and new controversies surrounding the autism field including the evidence for vaccines as a contributing cause of autism.
NLMFF: Were your students generally knowledgeable about autism prior to enrolling in the course? What types of majors did your students come from? Are there other opportunities to learn about autism at Brandeis outside of your course?
Dr. Birren: There was quite a range of students in the course. Some came in knowing very little about autism but with a great deal of interest. Other students had worked with autistic children in various ways including as counselors at camps. Still others had a family member with an autism spectrum disorder. None of them knew a lot about brain development and genetics in autistic children, and all of them were very motivated to learn.
NLMFF: In your opinion, how successful was this course overall? Did the course attract many students? Did students express interest in a follow-up course? Will the course be offered on a consistent basis in the future?
Dr. Birren: I thought that the course met all of its goals and was a success. More students wanted to take the class than we could accommodate and the final enrollment was about 45 students. This is quite a large class by Brandeis standards. Since the course was offered I have had a number of students who did not take the course express interest in having it offered again. I will offer the course again next semester (Fall 2006) and I expect that it will generally be offered every other year.
NLMFF: Is there a course website where interested individuals could learn more about the details of the course?
Dr. Birren: There was a course website available for students in the course, but I don't know if it is now accessible. Over the next couple of months I will be starting to work on a new site for the course to be offered next fall.
NLMFF: What guidance could you offer to other professors interested in beginning a new neurobiology course on autism at their respective universities similar to yours at Brandeis?
Dr. Birren: I think that there are many possible ways to teach this course, so it is important to decide what the goals are. I taught a course aimed at upper division undergraduates and graduate students with some background in biology and I chose to teach the course as a broad overview of many different disciplines. But a course aimed as a survey for non-science majors or a more in depth examination of the biology and genetic of developmental disorders could also be done. Teaching an integrative course took me beyond my fields of expertise, so it was incredibly useful to talk to people interested in autism using many different approaches. For me that meant gaining perspectives from people involved in functional imaging, language processing and treatment programs. Everyone I talk to was incredibly helpful and contributed to making the class a success.
NLMFF: What advice would you have for undergraduate and graduate students who are interested in pursuing a career in autism research? What types of degrees and training would be necessary to develop a career in the different areas of autism research?
Dr. Birren: Here is what I learned from teaching the class: There are so many overlapping areas in which it is possible to make an impact on our understanding of this disorder. We can tackle it from the clinical side, from the perspective of basic developmental biology and genetics, from work in education and social policy. Students who are interested in pursuing autism research can really be guided by the aspects that they find most exciting. One student in the course had been working in a basic molecular biology lab but became fascinated by problems of language in autism. She switched her undergraduate research project to a Brandeis psychology and neuroscience laboratory to study human language processing. So graduate work in a number of fields including medicine, psychology, genetics and education are all going to provide a great background for working in the field. I think that one of the greatest potential impacts of an undergraduate course such as the one that I taught is to start students thinking about what aspects of research they are interested in and, more importantly, to give them awareness of the interconnecting aspects of the different approaches to autism research.
NLMFF: What surprised you most about the field of autism research as you prepared to teach this course? What lies ahead? Do you see major gaps in the present approaches being taken?
Dr. Birren: I think I was most surprised by the many, many sources of information and the differences in interpretation. Ultimately, everyone wants the same thing- to understand the causes of autism and to have better treatment options. Yet there are conflicting opinions about many aspects of autism, from the meaning of increasing diagnosis rates to the best approach to treatment. There is nothing simple about understanding this disorder and there is much work to do on many fronts. In the future I think that communication between people with different research approaches will be critical to putting all of the pieces together and shaping the direction of future research. In particular I am interested in the links between human behavior, the genetics of autism and the still early field of animal model development. We really need to know more about the basic biology and neurobiology of how the brain develops and the processes that are disrupted in autism. This means that information has to flow in both directions to provide the framework for advances in the laboratory and the clinic.
NLMFF: How did teaching this course influence your own choice of research directions?
Dr. Birren: It actually made me more interested in pursuing reasonable animal models for autism spectrum disorders. It seems to me that bridging the gap between basic research on neural development and an understanding of how those developmental processes are disordered in autism would be greatly facilitated by mouse models that provide convincing linkage between molecular and cellular changes and behavior. While a truly "autistic mouse" is unlikely, it may be possible to examine aspects of behaviors in genetically manipulated or lesioned mice in the context of developmental changes in brain connectivity. To this end, I have recently proposed to work with several different mouse models, each of which recapitulates some aspects of autism.
NLMFF: Thank you for your thoughts and insights.