BIOENGINEERING: Building the Future of Biology and Medicine
Bioengineering advances the nation’s health by applying engineering principles and techniques to biological problems. The rewards most obvious to the public are novel devices and drugs, but bioengineering also offers further insight into biological processes, new methods for using data from genetics, and increased ability to visualize the brain and other organs.
History tells us that most of the revolutionary changes that have occurred in biology and medicine have depended on new methods that are themselves often the result of fundamental discoveries in many different fields. Thus biological problems are too
complex to be solved by biologists alone; we need partners in many disciplines, including
physics, mathematics, chemistry, computer sciences, and engineering.
Summary
The National Institutes of Health (NIH) convened the NIH Bioengineering Symposium to investigate research opportunities and develop recommendations that will serve as underpinnings for future medical and biological advances. The Symposium's structure ensured that recommendations would address priorities across a wide range of
bioengineering sciences, which would involve multiple Institutes and Centers at the NIH
and Agencies of the Federal Government. Implementation of the recommendations will
realize the goal of exploiting bioengineering’s capacity to bring innovative concepts and
approaches to research in biomedicine and health.
Bioengineering improves quality of life through its contribution to advances in science
and technology related to human health. It is unique in its ability to integrate principles
from a diversity of fields. It crosses the boundaries of academia, science, medicine, and
industry. As such, it is uniquely positioned to impact the health of the nation. The
enthusiasm and excitement generated by the symposium are important indicators of the
vitality of the profession.
The Future of Computation
The complexity and amount of biological information are increasing dramatically. New approaches will be needed to analyze and integrate this information.
The Vision
Bioinformatic databases must be transformed into functional models of cell and tissue processes. Accomplishing this requires harnessing the knowledge of all relevant disciplines, including computer science, mathematics, bioengineering, and biological sciences. The models will range from empirical correlations of databases to mechanistic and systemic descriptions of complex biological processes. Comprehensive informaticbased descriptions of model organisms and organs need to be developed and tested in
concert with basic biological research to uncover the rules of nonlinear cellular and
systemic regulation. Algorithms and other computational tools for predicting and
exploring intrinsic and emergent properties of these modeled processes will be needed.
Goals for the Next 5–10 Years
· Support cross-disciplinary collaborations that hold promise for (1) developing better
understanding of complex biological regulation, (2) modeling complex systems
coupled with experimental validation, and (3) developing mathematics and software
tools for discovering emergent properties of biological systems.
· Develop database and software infrastructure standards.
· Seek improved definition, interpretation, and analysis of sequence data, including
development of automated annotation methods and better algorithms.
· Develop methods for visualizing and interpreting large and possibly heterogeneous
data sets and the results of multivariate, time-dependent simulations of biological and
biomolecular systems.
· Move beyond sequence data to incorporate metabolic pathways, genetic circuits, and
cell, tissue, and organ function into models.
· Translate empirical data into concepts that can be applied to the development of
therapeutic, metabolic, tissue, organ, and prosthetic device engineering and design.
· Develop new tools that are predictive of complex biological properties, i.e.,
redundancy characteristics, emergent properties, and evolutionary dynamics.
· Design experiments to build mesoscopic databases, including those describing the
physico-chemical properties of gene products and databases on physiological
function.
· Develop genome-based organism-scale models for the analysis, interpretation, and
prediction of the genotype-phenotype relationship.
· Establish bioengineering as the home for interdisciplinary educational programs and
courses (bioinformatics, biomedical modeling, and computing).
· Develop a funding infrastructure that allows science and technology to be developed
simultaneously and allows for methods- and development-driven research.
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Education and Training
To effectively explore the potential for bioengineering approaches to advance biomedical research, scientific leaders must anticipate the necessary skills investigators will need in order to address future research challenges.
The Vision
In recent years, understanding of the fundamental mechanisms of disease has
improved enormously, with commensurate changes in the practice of medicine. These
changes have driven an exponential growth in the potential for engineering to contribute
to medicine through increased biomedical understanding, innovative diagnostics and
therapeutics, and improved health care delivery. For this potential to be realized,
however, there is a need to focus on the educational infrastructure expected to produce
the biomedical engineering leaders of the next century.
In considering the educational infrastructure, interdisciplinary and integrated are key
words that emerge from any perspective. From the perspective of career paths,
biomedical engineering education must provide a foundation for industry, academic
science, and medicine. Each path provides enormous opportunities to improve the social,
economic, and health status of the United States. A cadre of bioengineers is necessary to
translate the country’s lead in biomedical science into industrial opportunities and
economic development, to increase the scope and speed of scientific advances in
biomedical science, and to bring an increased analytical perspective to the practice of
medicine.
From the disciplinary perspective, many problems in medical science respond only to
the combined contributions of engineering, science, and medicine. Thus, the educational
infrastructure must provide a mechanism for students to integrate across multiple
disciplines.
From a more general perspective, biomedical engineers must be able to adapt to a
changing science base and to the internationalization of the work place and must be able
to appreciate the ethical and political implications of research.
As the number of educational programs begins to grow in response to these
opportunities, bioengineers have focused intensely on – and led the way in – establishing
innovative organizational structures and teaching paradigms for integrated,
interdisciplinary education.
Goals for the Next 5–10 Years
· Identify a core curriculum for bioengineering.
· Develop training strategies appropriate to the differing career paths of bioengineering
graduates in industry, academic science, and medicine.
· Find the best academic structures and teaching paradigms to generate bioengineers
who can adapt to changing science bases and internationalization of the workplace
and can appreciate the ethical and political implications of research.
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Biomechanical Solutions
Biomechanics is a branch of engineering science dealing with the roles of force, deformation, and motion in living organisms. The field has made important contributions over the years to understanding human physiology and pathology and to the development of advanced medical diagnostic and treatment procedures, processes and products. The
continued application of biomechanics combined with other bioscience disciplines will
lead to further innovation and advances in stategies for improving health. Future
directions include the biomechanics of biomolecules, DNA, genes, genetic circuits, cells,
extracellular matrix and tissues, and the integration of molecular biomechanics with the
physiology of organs and the whole individual.
The Vision
Biomechanics is a branch of engineering science dealing with force, deformation, and motion in biology, from molecules to whole individuals. Biomechanics impacts every area of medical disease. No disease will ever be fully understood unless it undergoes a complete stress analysis. All cells in the body – stem cells, endothelial cells, embryonic
cells, etc. – are strongly affected by the geometry and stress factors in their environment,
factors that influence key functions such as gene expression, growth, and development.
Biomechanics has contributed to understanding physiology and pathology,
development of medical diagnostic and treatment procedures, design and manufacture of
prostheses, improvement of human performance in workplace and sports and automobile
safety, injury prevention, and protection of the aged, handicapped, sick and injured.
Biomechanics has addressed problems of blood circulation, musculoskeletal systems,
ultrasound imaging, tissue remodeling, mass transport in kidney dialysis and in cancer
drug delivery, development of artificial internal organs and joints, automated gait
analysis, human tolerance, and tissue engineering. It is relevant to treatment strategies for
many diseases, from gene therapy to surgery.
In vigorous development for the future are the biomechanics of biomolecules, DNA,
genes, genetic circuits, cells, extracellular matrix and tissues, and the integration of
molecular biomechanics with the physiology of the organs and the whole individual. As
an engineering discipline, biomechanics is uniquely qualified to address these broad
issues. Biomechanics must be an integral part of a solution to the grand challenge of
integrating bioengineering with biological research of the next 1-2 decades.
Goals for the Next 5–10 Years
1. Adaptation to stress, including repair, fatigue and failure.
All cells and tissues
experience stress in vivo, and respond to their mechanical environment by adaptation,
remodeling, and a host of subcellular and molecular events, whose normal course is
essential to function and whose abnormal course can lead to failure or disease. Thus, it
is important to understand the mechanics of these processes and the mechanical
aspects of the entire stimulus-response cascade that translates mechanical force to
molecular processes from the molecular level, through increasing sizes of scale, to
observable change.
2. In Vivo biomechanics.
There is a need to emphasize the use of biomechanics to solve
problems in vivo. Data on forces (stresses) and motion (strains) in vivo at the
subcellular, organ, and whole-body levels are required to provide the basis (i.e.,
boundary conditions) for analysis of function.
3. Molecular biomechanics.
There is a need to develop molecular mechanics to
understand the mechanical behavior of biomolecules, the dynamics of the interaction
of molecules in cells, the pathway of force transmission from extracellular matrix
through the cells, how force and deformation of the cell membrane induce forces in the
nucleus to cause gene expression and production of proteins, how cells interact with
each other through mechanical contacts, and how tissue formation, growth, and
remodeling are influenced by molecular mechanics.
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Combinatorial Approaches to Biology
Combinatorial chemistry and combinatorial biology-based approaches for the development of novel pharmacological agents and biomaterials have emerged as powerful long-term solutions for discovery of novel pharmaceuticals.
The Vision
The panel envisions the development of generally valid paradigms and techniques
based on combinatorial approaches for the design, synthesis, characterization, assay, and
end-use evaluation of complex, novel molecular entities and interactions. It is expected
that within 5-to-10 years, combinatorial paradigms will become an engine of innovation
in a variety of fields with particular emphasis on pharmaceutical sciences and drug
delivery, medical device development, and materials design and engineering.
Goals for the Next 5–10 Years
Significant opportunities and challenges for combinatorial technologies lie ahead.
Significant synergies exist between combinatorial biology and chemistry and allied fields
of bioengineering, genomics, and bioinformatics. The pharmaceutical industry has
already adopted combinatorial methodologies as a key technology for its drug discovery
effort. Indeed, several compounds discovered from combinatorial chemistry libraries
have advanced to clinical trials.
Success has already been evident in the combinatorial
biology arena, with directed manipulation of a natural product biosynthetic pathway
leading to the commercial development of an antiparasitic agent. Although these
successes are evident, advancing fundamental aspects of combinatorial approaches will
undoubtedly lead to more rapid discovery and efficient development of new
pharmaceutical agents and advanced biomaterials for improved health of the nation.
Implementation Strategies
To address these priorities, the NIH should foster development of cross-disciplinary
research and education initiatives and of funding mechanisms for centers focused on
high-impact combinatorial research.
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