Show notes
Our guest today is Dr. Euan Ashley, a pioneer in the use of genomic sequencing to solve some of our most puzzling medical mysteries. Medical genomics, and the precision medicine it will enable, has the potential to predict, prevent, and diagnose many common (and uncommon) diseases.In today’s interview, we discuss:— Euan’s work with a colleague who was just the fifth person in the world to have his genome sequenced.— Precision medicine and how Euan has helped establish medical genomics.— Technological advances that made sequencing cost-effective for individuals.— How pathogenic labels will transform healthcare.— The Undiagnosed Disease Network, which includes physicians from across the country who work with patients and families to solve medical mysteries.— Research from his lab that shows how all forms of exercise, particularly endurance exercise, confer benefits across all domains of health and function.Euan is a Scottish-born professor of medicine and genetics at Stanford University. He’s also the author of The Genome Odyssey: Medical Mysteries and the Incredible Quest to Solve Them.Show notes:[[[[[[[[[[[[[[[00:27:19] Dawn mentions that in 2010 Euan wrote a paper about Steve, his aforementioned friend who had his genome sequenced. The paper described how Euan put together a team to undertake an integrated analysis of a complete human genome in a clinical context. Dawn explains that this was a groundbreaking paper because it asked the question of how one brings together the entirety of the genetic literature and everything that is known about associations between genes and disease and variants of diseases. Dawn goes on to say that Euan built all these questions into an algorithm that could be deployed in the context of a single patient in a primary-care practice.[[[[[00:43:36] Ken shifts the conversation to Euan’s recent research. Ken mentions that Euan had a study last year that looked at the impact of genetic sequencing in critical-care settings. Because a genetic diagnosis can improve the prognosis of critically ill patients and therefore guide the clinical management of their care, a lot of effort has gone into developing methods that result in rapid, reliable results. In critical-care situations, decisions need to be made in hours, but traditional testing requires weeks and even rapid testing requires days. Ken goes on to explain that Euan’s paper reported on a new method he and his colleagues developed for rapid sequencing of the whole human genome in patients in as little as five hours. This new ultra-rapid genome sequencing has the potential to lead to significantly faster diagnostics. Ken mentions that this study used a technology called nanopore sequencing and asks Euan to explain what this is and how it works.[[[00:54:05] Dawn mentions that Euan recently published a paper in Nature that introduced COSMOS (Computational Sorting and Mapping of Single Cells), a cloud-enabled platform that performs real-time cell imaging and analysis. Dawn goes on to explain that COSMOS uses AI and microfluidics to achieve high-throughput imaging that can sort cells using deep morphological assessment. Cell morphology has been used by pathologists and clinicians for years as the gold standard for disease diagnosis and prognosis. Dawn mentions that although there have been technological advances in making single-cell characterization at the genomic, transcriptomic, and proteomic levels, tools for assessing high-dimension cell morphology have not kept pace. Dawn asks Euan to talk about the challenges he and others have faced in performing real-time deep-learning assessment and sorting of cells and how COSMOS helps address these challenges.[[[01:01:02] Dawn pivots back to the work Euan did with Steve and his genome. Dawn mentions that Steve pointed out to Euan in that encounter a variant in one of his genes associated with heart disease, a variant that could be life-threatening. Dawn goes on to explain that accurate assessment of cardiac function is crucial for diagnosing cardiovascular disease. In one of Euan’s papers, he addressed the limitations of human assessment of cardiac function. In order to overcome this challenge, Euan and his colleagues developed a video-based deep learning algorithm, EchoNet-Dynamic, which surpasses human observation in several critical tasks related to the assessment of cardiac health. Dawn asks what went into the development of EchoNet-Dynamic and what makes it standout as an assessment of cardiac function.[01:05:13] Ken explains that IHMC has three primary overlapping research focus areas: artificial intelligence; robotics and exoskeletons; and human healthspan, resilience and performance. He also mentions that IHMC is building a new research complex dedicated to healthspan, resilience and performance research. Dr. Marcas Bamman will be the director of the new complex and will help lead clinical and translational research to advance knowledge on optimizing the performance and resilience of elite performers. Because of this research, Ken was particularly interested in Euan’s paper in Nature last year titled “The Genetics of Human Performance.” The article points out that while we have substantial epidemiological evidence supporting the beneficial effects of exercise, we really don’t know a lot about the molecular mechanisms through which these effects operate. But we do know that exercise extends healthspan. Ken explains that the article reviewed the current understanding of the genetics of human performance, and it begins by pointing out that compared to our recent hominid ancestors, humans seem to have evolved for endurance physical activity. Ken asks Euan to talk about this and why it matters in terms of modern humans.[[[[[01:19:11] Dawn asks Euan about his book “The Genome Odyssey,” which was described by the Wall Street Journal as an impassioned, firsthand account of the effort to bring genomic data into clinical practice. Dawn asks what Euan was hoping to accomplish with the book.[[[Links:Euan Ashley bioLearn more about IHMCSTEM-Talk homepageKen Ford bioKen Ford Wikipedia pageDawn Kernagis bio