I was excited to prepare for a seminar at the Biological Engineering Department at the University of Minnesota. It has been 30 years since I began my journey in the field of biomedical engineering when I enrolled in Shanghai Jiaotong University in 1987.
At that time, I did not know any other biomedical engineer in my life. I was attracted by the description of “biomedical engineering”. Solving medical problems with the knowledge of biology and tools of engineering appealed to me as a promising field. Biomedical Engineering was a newly created department at Chinese Universities. We went to many other departments on-campus or off-campus for classes. We rubbed shoulders with other students in electrical engineering and mechanical engineering classes. We rode bikes to anatomy and physiology classes at a nearby medical college. Our own professors taught us computer programming, ultrasound and medical instrumentation.
By the end of the four-year college in 1991, most of us got jobs in the instrumentation department at a hospital or at a few medical companies in China which manufactured x-rays and other medical equipment. Many graduates of my college had left China to study abroad. The opportunities for admission to a US university and obtaining a student visa were rare in the early 90s in China. For many, it was a path to a bright future.
I was admitted to the University of California, San Diego. The Bioengineering program at UCSD was founded by Professor YC Fung, and chaired by Shu Chien at the time. Professor Fung initiated the field of research on biomechanics, which studies tissue properties of muscles and circulation. In an outing with new students, Professor Fung recalled how he got his start in biomedical engineering. He had been an aeronautics professor at Caltech. When he found that his mother was developing an acute glaucoma, he began to immerse himself in the medical literature to learn about it, and sent his notes to his mom’s physician in China. The intense learning led him to a close collaboration with a medical doctor, and later, with many other physicians in areas of heart and lung mechanics. Professor Fung no longer taught classes in the department, but told me the first real-life story of a biomedical engineer.
Dr. Chien took me into his laboratory research in cell mechanics. I studied the aggregation of red blood cells, a phenomenon that occurs in life but with little understanding of why and how. I spent countless hours in a dark room with a powerful electron microscope, but was unable to find what bound these cells together. To this day, I still remember what Dr. Chien said, “You are going to be a scientist. You want to learn everything there is to learn on your project.”
My learning continued at the University of Utah, where I decided to pursue a PhD in its Bioengineering Department. My growing interests in the electrical system of the heart found a home with two mentors at the Cardiovascular Research and Training Institute. Bruno Taccardi was studying how heart muscles affected electrical wave propagation in each heartbeat. He devised systems with hundreds of electrodes that placed directly in a beating heart to measure electrical field during propagation. Rob MacLeod, my PhD advisor, had developed computer programs for visualization and simulation of these complex systems based on some of Bruno’s measurements.
Bruno was in his late 60s at the time. He “retired” from his institute in Parma Italy, where he was the director, and came to Utah to continue his research. Bruno wanted to know everything about electrical propagation in the heart. He only wrote a few papers in his career, but one of them was read by nearly every researcher in the field. Rob MacLeod was a young faculty member and I was lucky to be his first student. I could not have asked for a better mentor. Rob recognized my challenges with scientific writing. He gave me a list of classic papers on cardiac electrophysiology, and critiqued my review summary of each paper. The exercise went on for a few years, and ended with our first paper together on interpolation of electrical potentials in the heart. After six years, I finished my PhD in biomedical engineering. I was ready and anxious to solve problems in the real-world.
It was an exciting time in implanted device industry with recent introduction of cardiac resynchronization therapy, a new therapy for patients with heart failure due to an electrical conduction problem in the heart. I was impressed by the enthusiasm of scientists I met during the interview with Guidant Corporation, one of the three companies that manufactured cardiac pacemakers and defibrillators. I decided to join them after the interview and hoped one day to work on a new therapy myself.
I was open to work on any problems. The first problem I worked on was a condition called chronotropic incompetence. With aging, many of us lose the ability to regulate heart rate with increasing metabolic demand, for example, during exercise. In traditional cardiac pacemakers, an algorithm increased heart rate based on body motion detected by an accelerometer sensor. This had limitations, for example, an accelerometer would not determine the different metabolic demand between climb upstairs versus downstairs. I started with a project to measure respiration using an implanted respiration sensor in a cardiac pacemaker. This was a new feature in the pacemaker to provide heart rate support during patients’ exercise. The pacemaker can sense the increase of respiration with an impedance sensor and changes of motion with an accelerometer. The combined information would improve the algorithm to regulate heart rate with the metabolic demand during the exercise.
The ability to monitor respiration in an implanted device soon led me to a discovery that many cardiac pacemaker patients stopped breathing frequently during sleep, a disorder called obstructive sleep apnea. In a collaborative study with a cardiac electrophysiologist doctor and a pulmonary doctor in Pittsburgh, we found nearly half of his VA pacemaker patients had undiagnosed sleep apnea. We formed a new team in 2001, the apnea team, which included original team members of Kent Lee, Jess Hartley and Jeff Stahmann. Our goal was to detect and monitor sleep apnea with a cardiac pacemaker and explore new treatment options. Boston Scientific, which bought Guidant, now produces pacemakers that can monitor sleep apnea status every night for this chronic condition based on our original work.
Once diagnosed, sleep apnea treatment is another major clinical challenge. The standard of care is positive airway pressure delivered by a mask placed over the nose and mouth during sleep. I made a good effort trying the treatment myself for two weeks and I had a very hard time to get to sleep. So it was not a surprise that nearly half of the patients with sleep apnea do not use any treatment.
My opportunity to work on a solution for sleep apnea treatment came in 2008. Tim Herbert, Mark Christopherson and others had worked on an implanted neuromodulation approach for treating sleep apnea while at Medtronic in the 1990’s. The idea was based on the finding that tongue relaxation during sleep was causing airway obstruction, and the tongue could be controlled via the hypoglossal nerve. The Medtronic team developed an implanted device to stimulate this nerve, and demonstrated in a small study that hypoglossal nerve stimulation would stiffen and move the tongue forward and could resolve upper airway obstruction. Medtronic did not continue this project, as it was not in their core therapy areas. In 2007, as a true entrepreneur, Tim quit his job in Medtronic, licensed the technology from them, and recruited Mark to join him to start Inspire Medical Systems, whose singular goal would be to develop and commercialize a neurostimulation therapy for obstructive sleep apnea. During one of our conversations before joining them, I asked Tim what made him believe they could accomplish what Medtronic could not in developing this new therapy. Tim put a children’s book in front of me, and asked if I remembered reading A Little Engine that Could. I told Tim that I grew up in China and had not heard of the book. After finding the book at a bookstore, I liked the attitude of “I think I can”.
In April 2008, I left my job at Boston Scientific and joined the Inspire team and began the next chapter of my journey as a biomedical engineer in finding a solution to help people sleep better.
