British-born cardiologist Dr Euan Angus Ashley, 49, is one of the pioneers in the application of gene sequencing in medicine and part of an international network of specialists working tirelessly to make the long-held dream of genetic-based medicines an everyday reality.
Based in California, where he serves as Professor of Medicine and Genetics at Stanford University as well as the Head of Stanford Center for Undiagnosed Diseases, and the founding director of the Center for Inherited Cardiovascular Disease as well as Stanford’s Clinical Genomics Program, Dr Ashley has just published new popular science book The Genome Odyssey, which reveals how our understanding of the human genome is now revolutionizing medicine, unlocking the secrets of mystery diseases and leading to powerful new treatments for our most intractable illnesses.
In this exclusive interview, Dr Ashley discusses his fascinating new book, explains why we are currently in a golden age of genomic medicine, and reveals just how fundamentally the rise of genetic healthcare will transform society for the better.
Q. How can our genetics cause illnesses? To what extent would you say that diseases and morbidity ultimately have bad genes to blame?
A. Essentially, all diseases have a genetic component. For some diseases they can be almost entirely explained by one letter change in the genome, for others it’s half nature and half nurture, and for some others still, a pathogen (like a virus) or the immune system is more to blame than the human genome, which plays a smaller role. Even for those diseases, though, genetic sequencing can help us understand the pathogen or the changes in our immune cells.
Q. As you make clear in your new book, The Genome Odyssey, we are on the cusp of a new era of genetic-based medicine. Why should we be excited about this?
A. We are finally understanding diseases that have remained mysterious for hundreds of years. And that understanding now allows us to develop medicines that can very precisely target those diseases. We sometimes call this “precision medicine”. Devastating illnesses that affect millions of people around the world like sickle cell disease or haemophilia could in the near future be, essentially, cured. This is not business as usual. This is a revolution.
Q. You say that we will all benefit from genetic medicine in the future. Does this mean that the costs of genetic sequencing and treatments have come down significantly in recent years?
A. It’s hard to think of an example where a technology has become as accessible so quickly as is the case with genome sequencing. People often talk about how fast computers advance in their computing power but genome sequencing has advanced much faster. It’s like being able to buy a Ferrari for a penny!
Q. What has been your role in the development of genetic-based medicine?
A. Back in 2009 I walked into a colleague’s office and he showed me his genome. He was the fifth person in the world to have his genome sequenced. After he started showing me his genome I recognized a few of the genes in which he had variations, and which were known to be associated with hypertrophic cardiomyopathy, an inherited cause of sudden death. I started asking him about his family medical history to see if there were cases of sudden, unexplained deaths. It turned out his family had quite a lot of these incidents, including his cousin’s son who had died suddenly aged 19 years. Long story short, shortly after, he became the first patient in the world to walk into a doctor’s office with his genome. And rather terrifyingly at the time, that doctor was me!
Q. The Genome Odyssey provides a fascinating survey of genetic medicine. What motivated you to write it?
A. I love stories. I live in awe of my patients and what they go through living from one day to the next with these challenging diseases. I wanted to tell the stories of these brave individuals in the hope that it would give others strength and inspiration. I am also fascinated by stories of scientists and innovators who break boundaries to push technologies to the limits. I love the fact I get to live among these amazing scientists here in Silicon Valley. I try to emulate them and make discoveries to help humanity. I hoped in the book to weave the very human stories of the patients and families affected by disease together with the stories of the scientists who make those breakthroughs possible. I explain some science along the way but always try to keep it light and anchor each chapter with a remarkable story from a patient so we can understand how those scientific breakthroughs come to affect real people.
Q. In your book you compare doctors involved with genomic medicine as akin to fictional detective Sherlock Holmes. Can you explain the similarity?
A. Solving medical mysteries is exactly like solving crimes. In fact, not many people realize that Sherlock Holmes’ creator, Arthur Conan Doyle, was himself a physician (an ophthalmologist) and that he based the character of Holmes on a Scottish surgeon with an uncanny eye for detail. In medical or criminal mysteries, you have to survey the scene, interrogate the witnesses, come up with hypotheses, and then test them. What TV shows like House, M.D. and CSI: Crime Scene Investigation have illustrated is that the application of technology to these mysteries raises the odds of solving the case. The genome is a big part of that.
Q. Towards the close of your book you project forward to future applications of genetic medicine. One of these involves identifying and harnessing the genetic powers of ‘superhumans’. What do you mean by the term ‘superhuman’, and how do you think learning about their genetic codes will help make us all healthier?
A. It turns out that if you study large populations of humans (who are willing to share their health and genetic data) you find out a lot about disease. One of the unusual things you can detect is that some people are remarkably resilient to disease. I discuss a few examples in the book, such as an Olympic athlete, a woman with extremely low cholesterol, and a young boy who didn’t feel pain. These genetic superheroes can, in effect, teach us how to make everyone else just a bit more “super”. And it’s now a big focus for pharmaceutical companies. More than that, it appears to be paying off. New drugs developed following on from this genomic revolution are coming to market and showing major benefits. In fact, it would be reasonable to say that no drug will likely be developed in the future without someone asking if there is human genetic evidence that it will work. This is a big change from how we used to develop drugs, where we would often test a number of theories in small animals like mice before we ever got near humans.
Q. You mention in your book that the UK is leading the way in the field of genomic medical research. Can you explain more?
A. The UK is, indeed, at the forefront of genomic research globally. In fact, the genetic technology that has been responsible for the genome revolution came together in Cambridge! And a new disruptive sequencing technology is being developed in Oxford. But the UK is also at the forefront of population genetic studies. Without doubt the most influential genetic population study in the world today is the UK Biobank. Literally thousands of papers have been written as a result of the 500,000 UK citizens being willing to share their health and genetic data. I discuss a few examples in the book of insights that have come from the UK biobank research. But those insights are just the beginning. Also in the application of genome sequencing to medical care, Genomics England is one of the world’s most successful endeavours—having sequenced more than 100,000 individuals with rare disease to try to find answers. Finally, the UK is not resting on its laurels, launching soon a new program called “Our Future Health” which aims to recruit five million Britons into the largest study of preventive genomics anywhere in the world. Our Future Health is focused on incorporating knowledge of your genome to help you better direct lifestyle and preventive efforts to avoid disease.
Q. You also discuss the development of gene therapy in providing new treatments for such conditions as haemophilia. What are the current challenges in changing genes or gene expression itself within the human body and how will these be overcome?
A. The history of genetic therapy has been long and winding, and many lessons have been learned along the path to the current golden age of genetic therapy—with many successes building on the lessons of the last 30 years. The challenges that remain now are to broaden the impact of therapies beyond the organs and organ systems that are easiest to deliver therapies to (the liver, the eye, and cells outside of the body like from our bone marrow). Getting gene therapies to the heart or the brain is much harder than to the liver or eye so we have to work towards new delivery systems using fat particles or inactivated viruses that can help us approach those conditions.
Q. Just how far do you think genetic-based testing and treatment will change the face of medicine in the coming decades?
A. I think genetic testing and treatment will touch every aspect of health and medicine. There isn’t a disease without a genetic component. And as we understand that better we will be able to integrate that with knowledge of our environment (it is often said that your postcode might be more important than your genetic code in predicting your future health, but in reality they are inseparable and each provides insight into how best to avoid or treat disease).
Q. The Genome Odyssey is packed with fascinating stories and information on the cutting edge of medical science, but what for you is the most interesting element of the book?
A. Well, the obvious answer is the stunning advances in genome sequencing, the computing that makes analysis of this data possible, and the patients it impacts. But the less obvious answer is that, at various times during writing, I became obsessed with other smaller things, many of which made it into the book in some form like Sherlock Holmes (I read all the books) or Homer’s Odyssey (that is a looong book) but many of which did not (or if they did, they live in the endnotes). For example, I got deeply obsessed with sentences that only contain the word “Buffalo” (little known fact: the word can be a verb, noun, and adjective). Related, the origin of Buffalo chicken wings was fascinating to me. Also, the origin of the Human Genome Project and things like the fact that two of the people drawing blood for the original volunteers were identical twins. I love these kinds of trivial and sometimes tangential observations.
Q. What first led you into becoming a doctor, and why did you choose to specialise in both cardiology and rare diseases?
A. For as long as I can remember I have always wanted to be a doctor. My dad was a GP in Glasgow and my mum a midwife, and they used to take me on their house calls when I was little. I was also always fascinated by the heart. I just loved the fact that it moved with rhythm and its movement made sounds like music. Genetics was somehow also in my destiny after my biology teacher gave me a copy of The Selfish Gene by Richard Dawkins when I was in secondary school (he also told my parents I was a “buffoon” who would never amount to much…challenge accepted). But it was my nerdy nature and the fact I loved to program computers that really sealed my fate. As genetics became a specialty where you needed large computers to understand the big data, I was drawn to that like a magnet. And Silicon Valley was the place it all seemed to be coming together. So today, I am lucky enough to get to do all this with amazing colleagues in a beautiful and sunny part of the world.
Q. What is the most satisfying part of your vocation?
A. My patients. I live for my patients. And I live in awe of my patients and what they go through. We get to stand next to them for a while as they go through life’s ups and downs but we should never forget that as we move on the next patient they are still there living through the challenges of their disease. So for me everything starts and ends with the patients. But I also love the scientific process. I love the excitement of a new idea. The frisson of the unknown. The anticipation of what might be. I also love the energy of teams. I feed off that energy and try to reflect it back.
Q. Being a doctor must take up most of your time but, in those rare moments that it doesn’t, how do you like to unwind?
A. Well, for many years I spent as much time playing saxophone in various jazz bands as I did learning medicine. I still love jazz and play now with my kids (my daughter plays saxophone and my youngest son just started drums). I also love sport and am on a quest to finally understand American sports (whereas football and rugby are engraved in my soul). I’m also known for my love of single malt and I enjoy imparting a little piece of Scotland to my California friends who are always eager to learn.
Q. What has been your proudest medical achievement to date, and what are you and your team currently working on?
A. I think seeing what our community around the world has been able to do with genome sequencing technology is very fulfilling. I am proud to have been a small part of that. We are currently working on how to make genome sequencing faster, cheaper, more accurate and, most importantly, more available to everyone who could benefit. But we also want to cure the diseases that cause heart failure and sudden death. Too many people still die unnecessarily, devastating the families left behind. We understand those diseases better now thanks to genome sequencing but the journey towards curing those diseases is just beginning.
The Genome Odyssey: Medical Mysteries and the Incredible Quest to Solve Them (St. Martin’s Press) by Dr Euan Angus Ashley is out now on Amazon in hardcover, eBook, and audiobook formats, priced £22.99, £9.49, and £20.47 respectively. For more information visit www.genomebook.info.