World-renowned genetics researcher Eric Boerwinkle, Ph.D., the new dean of Uthealth School Of Public Health, sat down with William F. Mckeon, executive vice president and chief strategy and operating officer of the Texas Medical Center, to discuss the exciting field of genomics and how collaboration through the TMC Genomics Institute will play a key role in developing future clinical applications.
Q | Tell us about your formative years.
A | I was born in North Central Ohio to a family that valued hard work. It was a rural part of Ohio, and my childhood was dominated by farm life and playing in nature. It was a working farm, although my father had a full-time job. With the encroachments of suburban Cleveland, the land was sold and there are now people who literally live on the farm land and commute to Cleveland every day. When I was a child, we went to Cleveland once a year at Christmastime wearing white shirts and ties to look at the window displays. My brother now farms in Central Ohio, and my mother’s side of the family farms in Indiana—some of the best agricultural land in the world. I feel very fortunate to have grown up with a farm background.
Because I was very busy with everyday life on a working farm, I was not the best student in the world. I recall spending about 15 minutes selecting a college, which is a huge contrast with my own children who toiled for years, accompanied by professional counselors, guidebooks and visitation weekends. I didn’t want to go to Ohio State because it was too big. It was, unfortunately, right after the Kent State event, so that was out of the question.
I picked the University of Cincinnati, which was a great choice because it was my first experience living in a city and it is a great school.
Q | What led you to select biology?
A | When one grows up in a rural setting, you are surrounded by life and nature, and I was just fascinated by it all. I was one of those kids who picked up rocks and looked at the critters underneath. I was very interested in fishing, because of the peace and relaxation that it offered me after working hard, and every trip seemed to offer something new about the natural world we live in. It was an obvious choice.
Q | Our paths are often determined by a series of pleasant accidents along the way. Tell us about how that may have influenced your path.
A | Absolutely. I am a big fan of serendipity. It plays a huge role in all of our lives, and my case in particular. Growing up on a farm, I was exposed to genetics from an early age. You could say we cloned things the old fashioned way, and the seeds we planted were the results of genetic research. A lot of people don’t know it, but there is a very tight historic relationship between the development of genetics and the development of statistics. Many early geneticists were statisticians, and many early statistical tools were developed because of genetic problems. The triumvirate between genetics, agriculture and statistics is very strong.
I, however, was interested in humans. For a while, I toyed with the idea of going to medical school, but I discovered human genetics—in fact, human statistical genetics—at a very young age. I had a professor in Cincinnati, his name was Alex Fraser, and he was involved in genetic analyses, so I had a little glimpse of the field. When I was approaching graduation in Cincinnati and was looking at graduate schools, it was really pretty straightforward. There weren’t many undergraduates who were interested in statistical genetics. I ended up at the University of Michigan in Ann Arbor, which was another very good choice. It was a nice city, a big university, great medical school, and really one of the first and best human genetics departments in the country.
The human genetics department in Ann Arbor was very much involved in the aftermath of the bombing of Hiroshima and Nagasaki. When the atomic bombs were dropped, it was the first world catastrophe associated with radiation, so there was a lot of interest in the effect of radiation on the mutation rate in humans.
As a graduate student, we were looking at proteins in an exposed mom and dad and their unexposed child. We were looking for mutations in the child as a result of the parents being exposed to radiation from the atomic bomb. I was looking for ways to automate this very laborious and tedious process. The Cold War was still going on, and at the same time the U.S. government was taking pictures of Cuba and looking for trucks or buildings that were moving around. Again, there was a need to automate this process. I became involved in the statistics of analyzing those pictures, but applying the methods to those pictures of the proteins from mom, dad and their child. We were looking for a protein spot that was in the kid but it wasn’t in mom and dad, which was a great candidate to be a new mutation.
One of the problems with analyzing the process of finding new mutations was genetic variation. Recall that we have two sets of chromosomes—one from mom and one from dad. A new mutation would look like an AA mom, AA dad, and an Aa child. An Aa parent would complicate this algorithm. I almost randomly picked a few proteins that had naturally occurring genetic variation so I could train the algorithm in more detail. I picked three, and it turned out that two of the three were proteins that are involved in heart disease. One of them was APOE that is involved in heart disease and Alzheimer’s disease, and the other was APOA4 that is involved in triglyceride metabolism. This simple chance event forever captured me into a career on the genetics of heart disease and its risk factors and the genetics of Alzheimer’s disease.
While I was a Ph.D. student in human genetics, I spent most of my time getting a master’s degree in statistics. My adviser and mentor, Charlie Sing, demanded that I was trained in statistical theory. I guess he figured that I was getting plenty of practical training in applied statistics with him inhumangenetics.Igotmymaster’s in statistical theory, which is probably one of the smartest things that I did, because later, I was unusual in that I could speak the language of biology and the language of statistics and data analysis. It set me apart then and it still does so today.
There was, and still is today, a tight relationship between human genetics at the University of Michigan and UTHealth. In 1972, Jack Schull moved from Ann Arbor to Houston to found something called the Center for Demographic and Population Genetics. Much later (1986), Jack recruited me to Houston, and I moved down here at a young age. Someone once told me I was the youngest tenure track faculty member in the UT system at the time—I was 26 years old. I have been here ever since, so about 30 years. I have worked hard and enjoyed every day. I have particularly benefited from the many colleagues that I have worked with at UTHealth and Baylor College of Medicine through the years.
Q | Can you share your perspective on the advances we have made since sequencing the first human DNA?
A | It’s unbelievable, and it is even unbelievable to me who spends every day immersed in it. To think that sequencing of the first individual genome occurred only about eight years ago. And in the eight years since, we go from sequencing the first individual genome to today where we are sequencing and analyzing tens of thousands of genomes. It is just mind-boggling.
To make this a reality, we need to think about the parallel development of two technologies: DNA sequencing and accessible computing. There is a strong partnership between the Human Genetics Center at UTHealth, which is very strong in statistical genetics, and the Human Genome Sequencing Center at Baylor College of Medicine. I am a big fan of collaboration in modern biomedical research. Since my early years in Houston, I have always had a strong collaboration with colleagues at Baylor, especially in genetics and in medicine. Richard Gibbs at Baylor and I had a series of meetings together and we made a conscious decision not only to join forces, but to join forces and focus our attention on human disease and precision medicine. We are both adamant and passionate about using genomic and analytic technologies to understand human disease, to use this improved understanding to prevent human disease and prevent bad outcomes for those diagnosed with disease.
This shared vision is embedded in the heart of the Texas Medical Center. I encourage people who are visiting the Texas Medical Center to pause and just look around. There is nothing like it in the world. It is an incredible resource.
But unlike the serendipity of my early career—and I would guess most peoples’ early careers—I would say our recent advances in human genomics and precision medicine are really the result of a lot of hard work. I like to have a big, bold vision and then to define a logical and systematic path to achieve that vision. I am fortunate to love to work with people, and bringing together these people with the latest sequencing and analysis technologies, along with the patient populations at such profound institutions as MD Anderson Cancer Center and Memorial Hermann. That is the path forward to success. We have the infrastructure to be the very best in the world. That is why I am so enthusiastic about the developments in TMC3, which is bringing these institutions together to realize this dream. With the great leadership at all of our institutions, I think it is within our grasp.
Also, let’s not forget the people of Houston and the people of Texas—the people and the populations we proudly serve. First, they are as generous as can be, and we should all thank the philanthropic community. Second, we should cherish and encourage diversity in our community. We have enormous ethnic diversity in Texas, but Houston in particular. In some ways, it is a window to what the United States is going to look like in 2050. We are really laying the foundation for medicine of the future by understanding the role of genetic diversity and the impact of disease in different populations. There is no better living laboratory, if you will, than Houston, Texas, for genomics and precision medicine. These are the tools of the future to reduce health disparities.
Q | What excites you most about the future standard of care, as genomics plays a greater role in medicine?
A | Having the sequence of every patient that comes to the Texas Medical Center—making it so routine that frankly we take it for granted that we have this information as a foundation of the electronic health record. We sequence these individuals at a young age and integrate that information into the electronic health record, which will then follow them through life. The information may be used in infants to understand congenital heart defects, in toddlers to understand allergies, in teenagers to understand propensity to high-risk behaviors, in young adults to understand the risk of developing diabetes in heart disease, and in the elderly to prevent the occurrence of Alzheimer’s disease and dementia. It sounds like science fiction, but I can assure you it is not science fiction. We are rapidly getting to that point, and this is the right place to do it.
Again, collaboration is key. Heart disease patients get cancer, and cancer patients get heart disease. We are living with these diseases now as chronic conditions. That DNA sequence, which is now a part of the person’s electronic health record, will follow the patient between hospitals. Interoperability of the electronic health record in the Texas Medical Center is one key to our future success. I would like to pause here and make one other point. We need to make sure that the benefits of genomics is not just for the rich and the rarefied. We need to make sure we get it to all of the people. Partnerships with Harris Health and the VA system will be critical.
Q | We are in the process of developing the TMC Genomics Institute. Why is this important?
A | I love building bridges among these institutions and I have seen the good that comes from it. It has been said that these institutions have grown and achieved prominence based on competition; we are going to continue to grow and achieve greatness based on cooperation. I think that’s an important point for all of us to remember. My competition is not with Baylor and MD Anderson; it is with Boston and San Francisco. And I really believe that cooperation is the way we are going to continue to grow and place the third coast, the Gulf Coast, on the map of enviable biomedical research and translation hubs. Going back to the philanthropic community of Houston, they are going to appreciate and reward such cooperation.
Q | How important is it to have co-location of all of these great minds?
A | It is incredibly important. It is important to have people in a more casual setting, in a routine setting to share ideas and to plan next steps. Building a large program is an interesting combination of having individuals that have a real vision, but also have the ability to translate that vision into a series of very concrete steps to accomplish it.
You get to the level that we work in, and there are a lot of really good ideas. There are very few people that have the sort of engineering approach to take those visions and set down a series of very concrete steps to accomplish that vision. It is a lot of hard work. And fortunately, in the genetics initiative, we have brought together a group of people who not only can work together and articulate a vision, but also have the experience of really doing the systems engineering—what Andy Futreal at MD Anderson calls the ‘plumbing’—to pull this together and accomplish the vision. And having individuals together in close proximity, we can really refine that vision and do the plumbing and the hard work.
And that takes me back to the beginning. One of the things about growing up in a rural setting is you respect people; you respect people no matter who they are, and also you aren’t afraid of hard work. And a lot can be said there.
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