Pamela Sklar (1959–2017)

Pamela Sklar (photo courtesy Andy Chess, MD)View Large Image | View Hi-Res Image | Download PowerPoint SlideHow many of us get to transform a field? Yet, that is exactly what Pamela Sklar accomplished in her all-too-short career. Through her unusually keen intellect and considerable force of personality, she helped move the field of psychiatric genetics into the modern era and thereby forced the larger field of psychiatry to come to terms with the shattering implications of the genetic complexity of mental illness.Pamela got to this role through a traditional route. After completing a classical education at St. John’s College in Annapolis, Maryland, she pursued her MD and PhD degrees at Johns Hopkins, where she did her dissertation research with Sol Snyder. She then obtained residency training in psychiatry at Columbia, during which time she worked in Richard Axel’s laboratory. Upon completing training, Pamela was drawn to Boston to work in psychiatric genetics at the Massachusetts General Hospital and, a few years later, joined Eric Lander in the formative stages of the Broad Institute of MIT and Harvard to form the first psychiatric genetics group there. When the Stanley Center for Psychiatric Research at Broad was founded in 2007, Pamela built and led the genetics program until January, 2011, when she moved to Mount Sinai.Pamela had the creativity and drive to employ the latest advances in genetics and bioinformatics to study the large number of patients required—tens of thousands of individuals with psychotic illnesses and controls—to identify bona fide genetic variants that confer risk for these disorders. This required the creation of large international collaborations, including the International Schizophrenia Consortium and the Psychiatric Genetics Consortium, which she helped found and directed. With these numerous collaborators, Pamela led foundational work in psychiatric genetics, which included, for example, landmark studies in 2008, which first identified CACNA1C (encoding a voltage-dependent calcium channel subunit) as a risk factor for bipolar disorder; in 2009, which proved the long-standing hypothesis of the polygenic nature of psychotic illnesses; and in 2014, which demonstrated the predominance of rare variants in these illnesses. Because of these revolutionary advances, we now know that genetic risk for schizophrenia and bipolar disorder involves many hundreds of genes, each with small effect and most shared between the two disorders, thus challenging the field to approach the biology and treatment of these conditions in completely new ways.This was not an easy path for Pamela. She received little support or encouragement from the field of psychiatry, which remained addicted to studying the contribution of individual candidate genes to psychosis, a literature that has since been almost completely debunked. She received little support or encouragement from the field of genetics, which considered mental illness too complicated for rigorous analysis. And Pamela discussed with me on numerous occasions the additional challenges she faced as a woman scientist: not being taken seriously, not being given the same level of resources as some of her male colleagues, and being ignored, criticized, and invisible. If any of this fazed her, it was not apparent. She forged ahead and changed a field. And in the last few years, she began to receive the recognition she long deserved: she was elected to the National Academy of Medicine in 2013, and she received the Colvin Prize from the Brain and Behavior Research Foundation in 2016 and the Lifetime Achievement Award from the International Society of Psychiatric Genetics in 2017.I’ve had the privilege of knowing Pamela for over 20 years. In fact, I first tried to recruit her to Yale in the mid-1990s, when she was clearly staking out new ground in psychiatric genetics; I failed. I tried again to recruit Pamela in the mid-2000s, this time to Dallas; she quickly made it clear that this wouldn’t work. I finally succeeded a few years later in bringing her to Mount Sinai because of the unique opportunities offered but also because of her love for New York.We were so fortunate to have Pamela’s last seven years at Mount Sinai. She established a Division of Psychiatric Genomics—now one of the best in the country—through the recruitment of outstanding faculty, postdocs, students, and staff. She was unusually generous with her time and resources in promoting the careers of an entire generation of scientists to follow in her footsteps while also earning their fierce loyalty. Based on these achievements, Mount Sinai has named the division that Pamela founded the Pamela Sklar Division of Psychiatric Genomics and will be holding an annual lecture for the field in Pamela’s memory. We will have the first Sklar Lecture this spring as part of a larger symposium on psychiatric genomics to celebrate Pamela’s extraordinary contributions.A word that comes to mind when I think of Pamela is “tough”. Tough as I’ve already described in her career path. Intellectually tough, as well, holding the highest expectations for herself and for those around her. I could always count on Pamela to tell me like it was: she never candy-coated her feedback; she openly pointed out how we could do things better, such that when she gave her thumbs up, I knew she meant it. And, of course, tough in the way she faced her horrible illness for close to a decade: the strongest, most courageous colleague I’ve ever had.I relished the time I spent with Pamela, always enjoying a good laugh—and what a great mischievous laugh she had—about the ridiculous political intrigue of navigating a career in academic medicine or commiserating on the frustrating state of psychiatry and the still very long way we have to go to conquer mental illness. It was thrilling to work with Pamela to recruit the up-and-coming stars she brought to Mount Sinai and to see her magic in mentoring them.I am so deeply saddened by Pamela’s passing because all of us at Mount Sinai and our larger field were robbed of several decades more of her leadership, not only of the Division of Psychiatric Genomics, but also as Chair of the Department of Genetics and Genomic Sciences, a position she took just this past June. Pamela was robbed of those decades of life to see her contributions to science multiply and to see her children grow into adulthood. And her wonderful supporting husband, our Mount Sinai colleague Andy Chess, and her two incredible children, Michael Sklar Chess and Isabel Sklar Chess, are robbed of decades more of life with Pamela.But I also know that, if Pamela is reading this piece, at about this point, she’d be saying: thank you very much, but get back to work. Let’s all finish the work that Pamela started to better understand severe mental illness so that we can at long last bring better treatments and cures to the people who suffer from these devastating conditions. We owe it to Pamela. This will be her legacy.