A Joint Program from the Very Beginning
In the 1960s, there was no widely accepted definition of biomedical engineering. One way of looking at the past 50 years is through the work done by UVA and biomedical engineering departments in general to determine the themes and boundaries the field.
A History of BME at UVA
Adapted from a talk given by Fred Epstein at the BME 50th Anniversary Celebration in November 2017
Our first students were recruited in 1962, and the Board of Visitors approved the new biomedical engineering initiative in 1963. In 1967, the initiative officially became an academic department—a joint program from the beginning spanning two schools, both Engineering and Medicine—with Ernst O. Attinger recruited from the University of Pennsylvania as the department’s first chair. In 1967, the department graduated its first student. In 1968, Françoise Attinger was appointed assistant professor of pediatrics, and she began teaching physiology to BME grad students.
During the next three years the department grew slowly but steadily, often as current faculty members like Donald Wright and David Lewis received a change of title. Antharvedi Anné (also from U. Penn) joined in September 1968, Thomas Kenner in July 1969, Michael Wilkins, Michael McCartney and Jen-Shih Lee in September 1969, and James Allison and George Theodoridis (who had had a post-doc with Lawrence Stark at Berkeley) a year later. Yong Kim arrived in the 1970s. Milton Adams joined the faculty in the late 1970s, already sporting his signature bowties.
In the 1970s and 1980s, these faculty members laid foundations in cardiovascular research, imaging, computation and modeling, and cell biology—research themes that shape the department to this day.
The First Thread: Vascular/Cardiovascular Research
A powerful early influence on the development of the program was the University’s longstanding expertise in cardiovascular research, beginning with Eugene Landis’ pioneering microcirculation work in the late 1920s. Bob Berne was another pioneer. In 1968, Berne joined the faculty as chair of the Physiology Department, where he continued his groundbreaking work on adenosine.
Thus, the department’s enduring emphasis on the cardiovascular system has its origins in this longstanding focus of the School of Medicine. Early hires reflected a desire to strengthen this thrust. For instance, Attinger had done his doctoral work on biomechanics and frequency analysis of the cardiovascular system. When he arrived here, he brought with him a systems-level view.
The strength in cardiovascular research was reinforced in 1992, when Dean Bob Carey founded the Cardiovascular Research Center, which was endowed by Berne’s patents. Brian Duling, the first director of the center, had a joint appointment in BME. Klaus Ley arrived two years later to conduct research on the role of leukocyte rolling in atherosclerosis and inflammation. Although Klaus came here as an experimentalist, he wanted to work with people who could model the vasculature. This emphasis on combined experimental research and modeling of a system has become a distinctive characteristic of the department’s approach to biomedical engineering.
The Second Thread: Medical Imaging
During the 1980s, the School of Medicine recognized the potential growth and important future of medical imaging. Imaging in general—and cardiovascular imaging specifically—emerged as a strong research theme. In 1984, the radiology department installed an MRI scanner, the first in Virginia, which led to a surge in research collaborations involving faculty like John Mugler (at that time a BME graduate student), Mike Merickel, and Jim Brookeman. Our expertise in ultrasound research came through collaborations with the cardiology department. Sanjiv Kaul, who had a joint appointment in BME, worked with Tom Skalak and Rich Price, and this collaboration led, among other things, to Rich’s present work on focused ultrasound-mediated drug delivery. BME Professor Kathy Ferrara was another leader in ultrasound research here in the 1990s.
The world-class research being done by UVA cardiologist George Beller led to collaborations involving nuclear imaging. Collaborations between BME and cardiology are very strong to this day, involving work with Chris Kramer, Mike Salerno, Ken Bilchick, Brian Annex and others. With Craig Meyer, John Hossack, Kim Kelly, Song Hu, Brent French, Rich Price, John Mugler, Fred Epstein and others, biomedical imaging is presently one of the main research strengths of the department. We have expanded beyond cardiovascular imaging to imaging in cancer, neurological diseases, and other conditions.
The Third Thread: Using Quantitative Methods to Study Biology
Another emphasis of the department is on quantitative biology, which currently manifests as Systems Biology, Computational Modeling, and Biomedical Data Sciences This emphasis was initially developed in the context of our concentration on the cardiovascular system, and it has become more and more computational over the years. Indeed, computing is part of the DNA of the department. The first members of the department brought with them an emphasis on computers in medicine. Attinger and Anné worked with a LINC (laboratory instrument computer) at U. Penn, and they brought laboratory computers to UVA. Specifically we had a Digital Equipment Corporation PDP 11/20 in 1972, and subsequently a much faster EDP 11/70 for database applications.
In the 2000s, under Tom Skalak’s leadership, the Systems Biology thrust gained prominence. Starting in 2004, the department hired a young crew of systems biologists: Jason Papin, Jeff Saucerman, Shayn Pierce-Cottler, and Kevin Janes. More recently we continued hiring in this area with faculty such as Eli Zunder, Matt Lazarra, and Mete Civelek. With the hiring of these faculty members, the department extended its research foci to infectious diseases, cancer, and other areas.
Highly detailed models help us to make sense of the vast complexity of biological systems. Today, our faculty use a broad range of models that include finite element models, mass action kinetics models, and agent-based models, among others, crossing scales from molecular and cellular modeling to modeling tissues and organs, as done by Professors Silvia Blemker and Jeff Holmes.
In this regard, hiring of Phil Bourne is the latest reaffirmation of our strength in systems biology and deepens our expertise in big data. A key to future breakthroughs will be the ability to deploy big data in non-reductionist ways—tackling, at least to some degree, the great complexity of biological systems and mechanisms of disease.
A distinctive feature of our approach to systems engineering and modeling is that our faculty in these areas all do experimental work. If you are going to model how cells and systems behave, you also have to be doing experiments to validate your model. You don’t often find modelers who themselves bridge modeling and experimentation, but this is the UVA way.
The Fourth Thread: Tissue Engineering and Regenerative Medicine
The interest of our modelers to engage in experimentation is one reason that we have been able to grow our tissue engineering and regenerative medicine thread. Former faculty members Cato Laurencin and Ed Botchwey led the department’s initial efforts in this area. More recently people like George Christ, Tom Barker, Don Griffin, Steven Caliari, and Chris Highley came here because they value our emphasis on systems biology and modeling and our quantitative approach to imaging and biomechanics. This thread in tissue engineering, regeneration, and advanced biomanufacturing reaches back to work done by Klaus Ley on inflammation and Tom Skalak on wound healing. You can’t regenerate a tissue unless you understand inflammation and how blood vessels grow, as Shayn Peirce-Cottler will tell you.
Collaboration in BME at UVA
The department is characterized by a tight, interrelated group of strengths in cardiovascular research, imaging, systems biology and big data, tissue engineering and regenerative medicine, and biomechanics. Our ability to tie our themes together is not simply the product of circumstance, but of culture. Instead of faculty members going their own way, there is a sense of collegiality here that has been cultivated deliberately. Faculty members are hired because they possess an affinity for collegiality, as well as for their expertise. They are appreciative of the work of their counterparts and, when they see opportunities, they are eager to collaborate.
This collaborative environment is also due to our institutional structure, bridging as we do the Schools of Medicine and Engineering. The collaborative culture is reinforced by our co-location with the School of Medicine, making it easier to develop relationships with physicians and basic scientists and to partner with them to address unmet clinical needs and engage in discovery science. The collaborative, collegial environment has the added, critically-important advantage of leaving its mark on our students. No matter where their careers take them, our students understand the importance of being a collegial team player.
Seizing Opportunities - The Whitaker and Coulter Awards
There have also been a number of moments in the department’s history where there have been critical opportunities in the field of BME to compete for major funding to grow and enhance the department—namely for Whitaker and Coulter awards.
The decision of the Whitaker Foundation to divest itself of its assets transformed the field of BME, as Whitaker eventually contributed more than $700 million to universities to develop their biomedical engineering programs. Its support was critical to the growth of BME at UVA. During the mid-1990s, Tom Skalak, Jen-Shih Lee, and Brian Duling wrote a series of proposals for Whitaker, ultimately securing a $10.5 million grant, which was the largest foundation award in the sciences or engineering that the University had ever received at the time.
The award changed the department in fundamental ways. It deepened our expertise in cardiovascular research and imaging. It enabled us to build and move to MR5 (some $7.5 million of the grant went to the building) and facilitated our expansion into systems bioengineering.
Not too long after the Whitaker award, another transformative opportunity arose in the form of the Coulter Foundation and their emphasis on translational research in BME. People were keenly aware here, thanks in part to Adenocard and to MRI technology licensed to Siemens, of the value of commercializing intellectual property. Through strong vision and a lot of work, Tom Skalak led the successful effort to win the $25 Million Coulter endowment.
As a result of the Coulter award, we went from being largely a basic science department to one that also emphasizes applying the insights of basic science to addressing unmet clinical needs. This was a big cultural shift for the department. The benefits for society and for the department as a result of this shift in culture have increased over time. It has led to a series of companies commercializing our technology, and it’s made the department an example that the University can point to as they demonstrate the contributions we are making to society.
Introduction of the Undergraduate Program
Another major shift was the introduction of the undergraduate program. During its first 33 years, the department offered only graduate degrees. In 2000, the Engineering School introduced a minor in biomedical engineering, followed in 2004 with a Bachelor of Science degree. The undergraduate program was first accredited by ABET in 2007.
The undergraduate program has been hugely popular at UVA, growing from a few dozen students per class in the early years to 120 students per class now, and our undergraduates are among the best students at UVA. They are high achievers academically and in research, and after UVA they go on to be leaders in industry or to graduate school, medical school, law school, and many other careers.
Futher Defining Features: Emphasis on Biology & Research that Spans Scales
There are two other defining characteristics of BME at UVA. The first is our emphasis on biology. We have always placed biology at the core of our curriculum. We don’t outsource the teaching of biology to other departments. We teach it ourselves because we think it is important to view biology through the lens of an engineer. This makes us unique. Our emphasis on biology obviously affects our teaching, but it also affects our research. We always consider the biological basis of a problem before developing technology to address the biological problem.
The second additional characteristic is that our research spans spatial scales. We have strength at the cell and molecular level, at the tissue level, and at the organ level. This broad approach has served us well as the department has expanded and entered new fields. We also have the modeling and imaging capabilities to work at different scales and the expertise to combine scales. This broad perspective is increasingly critical as the field moves into an era of intervening in fundamental ways to alter the course of disease.
Reflecting & Taking Stock
Recently, we’ve undergone major evolution and growth, building on our historical strengths and focusing on systems biology, computational modeling and now big data, biomedical imaging with many different modalities, tissue engineering and regeneration and now biomanufacturing, and biomechanics. These technologies are now applied to the cardiovascular system, cancer biology, the musculoskeletal system, infectious diseases, neurological diseases, and other conditions that require research and progress.
Our educational programs are also evolving with the removal of the enrollment cap to make the BME B.S. degree accessible to all interested engineering undergraduates and enhancing the diversity of our student body. BME Going Pro is providing unique professional development opportunities for our graduate students. Our reach is now extending to more of UVA, with Jeff Holmes leading the $10M Center for Engineering in Medicine, which is facilitating the engagement of all engineering disciplines to help tackle unmet clinical needs. We’ve also seen new funding, equipment, and faculty recruitments in biomanufacturing and big data.
The vision, hard work, and good faith of several generations of faculty members, students, and staff have created a department with unique strengths, and one that is well-positioned to do exciting and important work in the future. It is a department with a tradition of acting boldly and a culture of collaboration that should serve us well as we navigate the next 50 years.