Donald E. Ingber

Donald E. Ingber, (born May 1, 1956, East Meadow, NY) is an American cell biologist and bioengineer, Founding Director of the Wyss Institute for Biologically Inspired Engineering at Harvard University, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences. He is a founder of the emerging fields of biologically inspired engineering.

Ingber's pioneering scientific work led to the discovery that a universal set of building rules based on tensegrity architecture guides the design of organic structures—from simple carbon compounds to complex cells and tissues—as described in his Scientific American article entitled "The Architecture of Life".^[1] Tensegrity was first described by Buckminster Fuller and the sculptor Kenneth Snelson; it describes structures that stabilize themselves mechanically by balancing local compression with continuous tension. In addition to his theoretical work, Ingber devised novel methods and carried out numerous experiments which showed that mechanical forces, such as tension and compression, play a fundamental role in control of tissue development and disease, and that the use of tensegrity by cells enables them to carry out mechanotransduction— the process by which cells sense mechanical forces applied to surface molecules, such as integrin receptors, and respond by altering their intracellular biochemistry and gene expression.^[2][3]

Ingber's insights have helped create the fields of mechanobiology, angiogenesis, tissue engineering, nanobiotechnology, and biomimetics. Through his interdisciplinary collaborations with experts in chemistry, physics, engineering, magnetics, and optics, Ingber also has helped develop multiple new experimental nano- and microtechnologies, as well as engineered tissues and angiogenesis inhibitor-based cancer therapeutics that have entered human clinical trials.

Academic career

Ingber received his B.A. in molecular biophysics and biochemistry from Yale College in 1977; his M.A. in molecular biophysics and biochemistry from Yale Graduate School in 1977; his M.Phil. in cell biology from Yale Graduate School in 1981; his M.D. from Yale University School of Medicine in 1984; and his Ph.D. in cell biology from Yale Graduate School in 1984. From 1984 to 1986 he completed his training as an Anna Fuller postdoctoral fellow under the mentorship of Dr. Judah Folkman in the Surgical Research Laboratory at Children's Hospital Boston and Harvard Medical School.

Ingber began his independent career in 1986 as a research instructor in pathology at Harvard Medical School and Brigham and Women's Hospital, and in surgery at Boston Children's Hospital. He progressively moved up the ranks at Harvard until he was promoted to professor of pathology at Harvard Medical School in 1999. In 2004, Ingber was named the first incumbent of the Judah Folkman Professorship of Vascular Biology at Harvard Medical School. In 2008, he was named a professor of bioengineering at the Harvard School of Engineering and Applied Sciences.

In 1984, Ingber became a research associate in surgery at Boston Children's and in pathology at Brigham and Women's Hospital and Harvard Medical School. In 1993, he also became a research associate in pathology at Children's Hospital, and in 2002, he became a senior associate in the Vascular Biology Program at Children's Hospital.

Current research

Ingber maintains active laboratories in the Vascular Biology Program at Boston Children's Hospital and at the Wyss Institute, both of which are in the Longwood Medical and Academic Area of Boston. The Ingber Laboratory at Children's Hospital addresses the fundamental problem of how mechanical forces influence how cells decide whether to move, grow, contract, differentiate, or die during tissue development. A major focus is on angiogenesis—the growth of blood capillaries—a process that is critical for the growth of cancer and many other debilitating diseases.

In addition to providing vision and leadership for the Wyss Institute, Ingber heads its biomimetic microsystems platform, in which microfabrication techniques from the computer industry are used to build functional circuits with living cells as components. His most recent innovation is a technology for building tiny, complex, three-dimensional models of living human organs. These "organs on chips," which mimic complicated human functions, are being designed to replace traditional animal-based methods for testing of drugs and toxins.

The first organ-on-a-chip was first reported in Science in 2010. It is a complex, three-dimensional model of a breathing lung on a microchip that incorporates living human lung cells within microfluidic systems. This device mimics the complicated mechanical and biochemical behaviors of the human lung to provide information on the effects of environmental toxins, absorption of aerosolized therapeutics, and the safety and efficacy of new drugs. As an alternative to animal studies, this "lung-on-a-chip^[4]" could accelerate the introduction of new drugs to market, while also significantly lowering research costs.

In 2012, Ingber and his team demonstrated in a landmark paper in Science Translational Medicine the ability to mimic a complex human disease on the “lung-on-a-chip”—specifically pulmonary edema, or “fluid on the lungs.”  They closely mimicked a drug toxicity that produces pulmonary edema in humans, identified potential new therapies to prevent this life-threatening condition, and revealed new insights about the disease—specifically demonstrating on the chip that the physiological breathing motion of the lungs exacerbates drug toxicity-induced edema. They also studied the disease process in real time, precisely tracking fluid flow and clot formation, which cannot easily be done using an animal model.

On the heels of this publication, in 2013, Ingber received the prestigious the NC3Rs 3Rs Prize for his lung-on-a-chip from the UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).  The award champions innovations that reduce (refine, and ultimately replace) the need for animal testing.

Ingber also has published work on development of other organ chips, including a human gut-on-a-chip that undergoes peristalsis and a human kidney proximal tubule on a chip that mimics drug toxicities observed in humans. Working with Wyss Core Faculty Member, Kevin Kit Parker, he is also developing a heart-lung-micromachine with funding from the National Institutes of Health and the U.S. Food and Drug Administration (FDA). The proposed device would combine two different organ systems—a beating heart and breathing lung—within a single microsystem for the first time.^[5] Ingber and Parker are also leading a major effort funded by the Defense Advanced Research Projects Agency (DARPA) in 2012 to develop an instrument that will support fluidic coupling of ten different human organ chips, and permit analysis of pharmacokinetics and pharmacodynamics (PK/PD) of drugs injected into this multi-organ physiological system in an attempt to replace animals for testing of drugs and toxins.

In separate work also supported by DARPA, Ingber is leading the development of a novel biospleen device that works as a dialysis-like device to clear the blood of a wide range of pathogens and toxins, much as a living human spleen does, without removing normal blood cells, proteins, fluids, or electrolytes.^[1]

Ingber’s range of interdisciplinary research is large, and other ongoing research efforts include development of:

• A biospleen device that works as a dialysis-like device to clear the blood of a wide range of pathogens and toxins, much as a living human spleen does, without removing normal blood cells, proteins, fluids, or electrolytes.^[1]
• A fluid shear stress-activated nanotherapeutic device that selective delivers clot-busting drugs to sites of vascular occlusion.^[6]
• Manufacturing of an artificial insect cuticle from chitosan isolated from shrimp shells and silk fibroin called ‘Shrilk’ that can be used for medical applications and as a commercial bioplastic.^[7]
• Demonstration that mechanical forces can control whole organ formation using embryonic tooth as a model system.^[8]
• Identification of embryonic materials that can induce breast cancers to stop growing and normalize.^[9]
• Windows for buildings that contain a microfluidic ‘circulatory system’ to increase energy efficiency.^[10]

Administrative leadership

Ingber helped to bridge Harvard University, its affiliated hospitals, and the Massachusetts Institute of Technology (MIT) through his involvement in the Center for Integration in Medicine and Innovative Technology, Harvard-MIT Division of Health Sciences and Technology, and Dana-Farber/Harvard Cancer Center. He also is a member of the Center for Nanoscale Systems and the Materials Research Science and Engineering Center at Harvard, as well as the MIT Center for Bioengineering.

In 2009, Ingber was named Founding Director of the Wyss Institute for Biologically Inspired Engineering at Harvard University, which was launched with a $125 million gift—the largest philanthropic gift in Harvard's history—from Hansjorg Wyss.^[11] It is dedicated to the emerging field of biologically inspired engineering in which insights into the design principles used by nature are applied to the development of bioinspired materials and devices for medicine, industry, and the environment. The Institute is a partnership among Harvard University, its major affiliated hospitals (Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, Dana-Farber Cancer Institute, Massachusetts General Hospital, Spaulding Rehabilitation Hospital), Boston University, and the University of Massachusetts Medical School as it is designed to harness the innovative power of the entire Boston/Cambridge region.

Policy and public service

Ingber was a member of the Space Studies Board of the U.S. National Research Council (NRC), which advises the National Academy of Sciences, National Academy of Engineering, and National Institute of Medicine, and he chaired its Committee on Space Biology and Medicine. He has also been an external reviewer of multiple NRC reports, including “Plan for the International Space Station,” “Future Biotechnology Research on the International Space Station,” “Assessment of Directions in Microgravity and Physical Sciences at NASA,” and “The Astrophysical Context of Life.” In 2010, Ingber was elected to the Board of Directors of the National Space Biomedical Research Institute.^[12] He has also served on the Innovation Review Panel of the Grand Challenges in Global Health grant program for the Bill & Melinda Gates Foundation, the Nanobiotechnology Committee of the National Institutes of Health and the National Science Foundation, and the Board of Directors for the Eunice Kennedy Center for Mental Retardation. In addition, Ingber has served as a consultant to various governmental agencies, public companies, and private corporations, including the U.S. Department of Defense, Office of the Director of National Intelligence, Merck & Co., Biogen Idec, Digene Corporation, Advanced Tissue Sciences, Chanel, BG Medicine, and WNYC New York Public Radio.

Because of his broad range of scientific interests and accomplishments, Ingber travels the globe sharing his work with artists, architects, and designers, as well as scientists, physicians, engineers, and the lay public. Examples of his involvement in the art/design community include his participation in the "Cellular Design" Exhibition at Le Laboratoire in Paris in 2010, the "On Growth and Form: Textiles and the Engineering of Nature" exhibition at the Textile Museum of Canada in Toronto in 2001, and in the "Image and Meaning" conferences at MIT in 2001 and at the Getty Center in Los Angeles in 2005. He also presented his work on tensegrity and nanobiotechnology at the Boston Museum of Science in 2002 and 2010. His scientific achievements have been highlighted in multiple episodes of Nova, CBS News Sunday Morning, National Public Radio, Studio 360, Cablevision, and Netherlands Public Broadcasting, among others.

Awards and achievements

Ingber has authored 375 publications in scientific journals, and is an inventor on more than 85 patents in fields ranging from anti-cancer therapeutics, tissue engineering, medical devices, drug delivery systems, biomimetic materials, and nanotechnologies to bioinformatics software. Among his many important clinically relevant innovations is the discovery of the first angiogenesis inhibitor compound (TNP-470) to enter clinical trials for cancer and development of a nanomagnetic blood cleaning device that could reduce deaths from sepsis in hospital patients[4] . He serves on the editorial advisory boards of numerous scientific journals, and he has cofounded two biotechnology start-ups.

Ingber's many scientific accomplishments have been recognized with numerous awards and distinctions.

In 2013, Ingber received an award from the UK’s National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) for his innovative lung-on-a-chip microdevice.  He was also honored with the Society of Toxicology’s Leading Edge in Basic Science Award for his Organs-on-Chips research. In 2012, Ingber was elected to the Institute of Medicine (IOM) of the National Academies, which is one of the highest honors in the field of medicine in the United States.  He also won the World Technology Award in the biotechnology category in 2012. These awards honor the world's most significant innovators in science and technology who are "creating the 21st century.”  In 2011, he was inducted into the American Institute for Medical and Biological Engineering's College of Fellows on the basis of his contributions to cell and tissue engineering, angiogenesis and cancer research, systems biology, and nanobiotechnology.^[13] That same year, he received the Holst Medal in recognition of his work exploring the cellular mechanisms that contribute to mechanical control of tissue and organ development and his development of bioinspired technologies.^[14] In 2010, he received the Lifetime Achievement Award from the Society for In Vitro Biology^[15] and the Rous-Whipple Award from the American Society for Investigative Pathology.^[16] In 2009, he received the Pritzker Award from the Biomedical Engineering Society.[9] In 2008, he received a Breast Cancer Innovator Award[8] from the Department of Defense. In 2002, he was named to Esquire's list of the world's "Best and Brightest." In 2000, he received the John F. and Virginia B. Taplin Award from Harvard-MIT Division of Health Sciences and Technology.

Ingber has also been named to multiple Who's Who lists including: Business Leaders and Professionals—Honors Edition (2007), Medicine and Healthcare (1999), the World (1997), America (1994), and Science and Engineering (1991). From 1991 to 1996, he was the recipient of an American Cancer Society Faculty Research Award.

Personal life

Ingber lives with his wife, son, and cat in Boston and in Chilmark, Massachusetts. His interests and activities outside of science include art and architecture, as well as writing scripts for stage and television, drawing cartoons for postcards, and writing for the lay public.

References

External links

• Donald Ingber’s webpage at the Wyss Institute website
• Donald Ingber’s lab at Children’s Hospital Boston
• Donald Ingber’s webpage at Children’s Hospital Boston
• Donald Ingber’s faculty webpage at Harvard Medical School
• Donald Ingber’s faculty webpage at the Harvard School of Engineering and Applied Sciences
• "Tensegrity" Scholarpedia article, written by Donald Ingber
• Public radio interview