Bioengineering December 1, 1997 Volume 27 Issue 4 Fall Issue of The Bridge on Bioengineering. The Emergence of Bioengineering Monday, December 1, 1997 Author: Robert Nerem The melding of engineering and the biological sciences will require bold and creative changes in the engineering profession. During the latter half of this century, there has been a revolution in the biological sciences. Biology has truly come of age, achieving an importance equal to that of physics and chemistry. The March 10, 1997, issue of Business Week highlighted this fact by declaring the arrival of "The Biotech Century." The magazine was bold enough to state that "biology will define scientific progress in the 21st century." Although some date the ascendancy of the biological sciences to the work of Watson and Crick (1953), which revealed the double-helix structure of DNA, there was a significant advance earlier in the century that laid the foundation for the exciting developments that we have witnessed in recent years. This advance was, in a very literal sense, a "cultural revolution," one that made it possible to grow living, biological cells in the research laboratory. I refer, of course, to the advent of cell culture (Leff, 1983). This "out-of-body" technology has made possible much of what we have learned about cell and molecular biology over the past 50 years. This is not to in any way underrate the achievement of Watson and Crick, for their work led us to our knowledge of a cell's genetic program and the development of recombinant DNA technology. The first products resulting from this technology began to appear more than a decade ago. We are now in the midst of the human genome project, whose goal it is to map and sequence the entire human genetic structure. While this is a laudable aim, biological information, or bioinformatics, requires more than knowing the genetic make-up of a biological system. The greater challenge is to relate cell, tissue, and organ function to a cell's genetic program. This has enormous implications for industry, with applications ranging from drug design to next-generation medical implants. As we enter the 21st century, we should expect a surge in the development of new biology-based industries. In a sense, biology has become too important to be left to the biologists. This should be taken by the biologists as the compliment it is intended to be, for their achievements have opened up a whole new world for others. Thus, a key challenge facing the engineering profession today is how to respond to the biological revolution, how to make the engineering contributions necessary for the Biotech Century to achieve the potential that exists. To start with, we need to make biology a part of the science foundation required of any person with a university education. This includes, of course, engineering students. There already are a few schools that have implemented this approach in their curricula. The same should be done by every university, certainly by all engineering schools. It also is an opportunity to define engineering in the context of biology, much as engineering disciplines in the past were defined within the contexts of physics and chemistry. Solving Problems in Unique Ways While there are some individuals from traditional engineering majors who have acquired a background in the biological sciences, there is an urgent need for engineers who have the ability to think in a way that integrates biology and engineering. These biology-based engineers, or bioengineers, should be able to solve problems in unique ways. Because of their knowledge of biology, they will be able to identify new opportunities for the application of engineering and for commercial development. Because of their knowledge of engineering, they will bring innovative approaches to solving problems in biology and medicine. Bioengineering is a very broad discipline. In thinking about the field, one could imagine a matrix that along one side has all the areas of biology and along the other all the fields of engineering. The applications that arise out of this matrix are virtually limitless. Bioengineering, however, is more than this matrix, for as we move into the next century, there clearly is a need for a true integration of biology and engineering, just as we previously have integrated physics and chemistry into the practice of engineering. Bioengineering has historical roots that extend back to the 17th century. Robert Hooke, Leonhard Euler, Thomas Young, Jean Poiseuille, Hermann von Helmholtz, and Horace Lamb are among some of the better-known contributors to the development of engineering as an applied science. All of these individuals worked on biological problems, and since the modern-day inception of bioengineering a half-century ago, there have been many more pioneers, a number of whom are members of the National Academy of Engineering. Bioengineering today is moving from being an inter- and multidisciplinary activity to a discipline in its own right. It is the application of engineering principles and methods to problems in biology and medicine. Bioengineering combines biology, the other sciences, mathematics, and various engineering areas into a synthetic whole. Biology is the science that is most central to bioengineering, yet bioengineers must also be able to use advanced engineering tools and methods. Quantitative approaches - measurements modeling, and the ability to integrate knowledge - are vital in bioengineering, as they are in all of engineering. In many areas of bioengineering, we will more and more see the application of mathematical approaches, and computational biology will be applied to a wide spectrum of problems ranging from the single molecule to the integrated system. A major area of application in bioengineering today is biomedical engineering. Biomedical engineers work to solve medical and biological problems and design new health care technologies, including medical devices and implants, diagnostic procedures, and therapeutic approaches. The pharmaceutical, medical device and implant, biotechnology, and tissue engineering industries are all served by bioengineering. The spectrum of technological applications ranges from artificial organs and imaging to the design and delivery of drugs and the development of biological substitutes (Bronzino, 1995). Artificial organs and imaging are areas that have received extensive attention over the past 25 years. They are now entering a new stage. From all the hoopla of the total artificial heart, this technology has now moved to the clinical use of the left ventricular assist device. Imaging is shifting from an anatomical focus to the measurement of function (i.e., functional imaging). Drug design will be done concurrently with the design of delivery systems. And tissue engineering, representing the interface of biotechnology with the traditional medical implant industry, is developing tissue and organ substitutes that incorporate living cells and natural biological materials into synthetic biomaterial scaffolds and substrates. The first such living products have received Food and Drug Administration approval and are now reaching the marketplace. The further development of products will require the talents of a variety of disciplines, including biochemists, cell biologists, engineers, immunologists, materials scientists, and surgeons. Bioengineering departments were first formed in the early 1970s, an outgrowth of academic initiatives started a decade before. These were strictly biomedical engineering departments, and the leading ones in general were institutions where there was a high-caliber medical school and where the engineering school could leverage that excellence in medicine. These engineering schools were frequently small or medium sized. More recently, there have been a number of new initiatives aimed at building academic bioengineering. Of particular note is the transformation of agricultural engineering departments into biological engineering departments at a number of institutions. Equally noteworthy is that some of the larger U.S. engineering schools have begun to build academic bioengineering units. This trend is indicative of the emerging importance of biology-based engineering. Among these new initiatives at major engineering schools are those based at: Georgia Tech (a joint biomedical engineering department with Emory University School of Medicine), University of Michigan (a new graduate-level biomedical engineering department), University of Minnesota (a biomedical engineering research institute with tenure-track faculty positions), Massachusetts Institute of Technology (a new Division of Bioengineering and Environmental Health), and University of California at Berkeley (a new department with the University of California at San Francisco). The Whitaker Foundation In the case of Georgia Tech and Emory, the biomedical engineering department represents a very unique unit. It is not only a joint department between an engineering college and a medical school, but also a partnership between a public institution and a private one. However, Georgia Tech's bio-initiative is broader than just biomedical engineering. The Institute for Bioengineering and Bioscience will expand into other areas of biology-based applications. There also will be a parallel thrust into environmental science and technology. In combining these efforts, Georgia Tech's bio-initiative recognizes the centrality of biology to both biomedical and environmental research and the aim of both fields to improve human health. Why are these new initiatives appearing? Some say a major factor is the Whitaker Foundation, located in Arlington, Virginia, and dedicated to the support of biomedical engineering. However, what these institutions are doing is responding to student interest, to the emergence of new industries, and to the exciting new engineering problems posed by developments in biology. The support of the Whitaker Foundation has been and will continue to be important; however, these institutions are investing resources of their own, which in many cases are far in excess of the support they are receiving from external sources. Molecular Biology as a "Tool" Although molecular biology is a science, and genetic engineering is part of that science, molecular biology also represents a set of tools. These are tools that biology-based engineers will need to use. Take, for example, the engineering of cell function. Cell function can be engineered by manipulating either the extracellular environment or the genetic program of a cell. Some may say that genetic engineering is not really engineering. However, if by design one engineers a cell's genetic program to produce a certain type of cell behavior or function, this is as much engineering as any of the more traditional activities we readily accept as engineering. Furthermore, if this is engineering, then we should accept the responsibility of training these people in our engineering schools. We also need to recognize that the next stage of genetic engineering will be much more quantitative. For example, there are researchers working to create a bioartificial pancreas, in which cells are genetically engineered to be insulin secreting and glucose responsive. These cells then are encapsulated so they are immunoprotected when implanted. However, it is not enough that these cells be insulin secreting and glucose responsive; they must secrete insulin at a specific rate corresponding to the glucose concentration present in the blood. It is this quantitative genetic engineering for which we will need engineers educated to use the tools of molecular biology and who can think and work quantitatively. Genetic engineering will become an important part of biomedical engineering. In the future, however, the application of genetic engineering will be far broader. It thus will have an impact not only in the biomedical area, but increasingly in many other areas of application within the emerging discipline of bioengineering. In a few years on New Year's Eve, the citizens of spaceship Earth will take a small chronological step from one century into the next. With this small step, the engineering profession will need to take a leap into the world of biology. This process has already begun, for the Biotech Century is upon us. Yet, we have seen only the tip of the iceberg so far. As we move into the 21st century, biomedical engineering, though continuing to be an extremely important area of application, will cease to be the dominant field within bioengineering. As changes in science and industry accelerate, the engineering profession will need to respond. Biology will need to become an important element both in engineering education and engineering research. There will need to be an expansion in biorelated research in all areas of engineering. At the same time, the number of bioengineering departments will need to continue to expand. It is these departments that are giving birth to bioengineering. It is these departments that will educate individuals who can truly integrate biology and engineering. There will be a further and very significant growth in biorelated industries, resulting from the commercialization of ideas based on the biological and medical sciences. Earlier this year, I predicted that by the year 2020 at least 20 percent of U.S. industry would be medically or biology based, including such areas as agricultural and environmental technology. I was chided for being too conservative in my estimate. Perhaps a more realistic estimate is in the range of 30 to 35 percent. Whatever the exact number, biology-based industries will be a very significant economic force in the 21st century. The growing relevance of bioengineering - to technological progress and the U.S. economy - will need to be reflected in our engineering schools and in the curricula we offer our students. It already is reflected in the interests of our students, with the best and the brightest of them being attracted to bioengineering at both the undergraduate and graduate levels. Furthermore, bioengineering is drawing women and underrepresented minorities and so will be an important factor in the diversification of the engineering profession. Finally, bioengineering will need to be reflected increasingly in the research done by engineering faculty. Just as the emergence of chemical engineering early in this century impacted the engineering profession, so too will the emergence of a biology-based engineering. As we learn how the human body and other biological systems are engineered, we will be able to apply this knowledge to engineer man-made systems. Thus, if we look at where we are today, it seems clear that the upcoming step across the century line will require bold and creative changes in the engineering profession. We are facing nothing less than a cultural revolution, one as important as that which led to the advent of cell culture at the beginning of this century. This journey into the Biotech Century will take us into new and exciting territory, in many ways unknown but offering enormous challenges and opportunities. It is there for our taking. Acknowledgments Credit for many of the ideas reflected in this presentation must go to the membership of two different groups chaired by the author and with whom he has had ongoing, stimulating discussions. The first of these is the Editorial Board for the Teaching Materials Program of the Whitaker Foundation. This board is composed of the following individuals: Joseph Andrade, James Bassingthwaighte, Carl Jaffe, Douglas Lauffenburger, John Linehan, Murray Sachs, and Peter Katona, with others from the Whitaker Foundation regularly participating in the discussions. The second group is the organizing committee for the 1997 NAE Annual Meeting Symposium, which is composed of Thomas Budinger, George Bugliarello, Stephen Drew, and Bill Greatbatch. To all these individuals the author offers his thanks. References Bronzino, J. D. 1995. The Biomedical Engineering Handbook. Boca Raton, Fla.: CRC Press. Leff, D. 1983. New biological assembly line. Pp. 20?27 in The Cell: Inter- and Intra-Relationships. An NSF Mosaic Reader. Wayne, N.J.: Avery Publishing Group. Panitz, B. 1996. Bioengineering: A growing new discipline. ASEE PRISM (November):22?28. Watson, J. D., and F. H. Crick. 1953. General implications of the structure of deoxyribonucleic acid. Nature 171:964-967. About the Author:Robert Nerem, a member of the National Academy of Engineering and the Institute of Medicine, is professor and director, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology. This paper is based on remarks he made at the 1997 NAE Annual Meeting Technical Symposium, held 8 October.