Duke University

Duke Medical Discoveries

Irwin Fridovich (Department of Biochemistry) – His laboratory discovered the way living things protect themselves from oxygen toxicity by rapidly degrading superoxide ions that are generated normally by numerous biochemical processes from man to bacteria. He discovered and characterized extensively a key protective enzyme that he named superoxide dismutase. These studies opened up a whole new field in biological science and several scientific journals are now devoted entirely to research reports in this field. Superoxide and other “reactive oxygen species” have now been associated with a large number of natural and pathological conditions, including aging, Alzheimer’s disease, and numerous cancers, among others.

Robert Lefkowitz (Departments of Medicine and Biochemistry) – His laboratory is associated with the seminal research carried out on “G-coupled protein receptors,” a group of proteins that constitute the largest and most ubiquitous family of biological receptors in nature. These receptors — protein switches that are buried in the cell membrane — include the beta-adrenergic receptors that mediate the body’s fight-or-flight response, as well as virtually all sensory receptors.

Fritz London (Departments of Physics and Chemistry) – Following his arrival at Duke he continued his work on the theory of superconductivity and superfluids and specifically applied this theory on liquid helium. This discovery-characterization had major applications in low temperature physics, theoretical chemistry and materials, and served as the underlying basis for studies of low-temperature physics that later led to several Nobel prizes, including that received by Duke alumna Bob Richardson.

Margaret Pericak-Vance and Allen Roses (Department of Medicine) – They found that people who inherit a version of the gene called apolipoprotein-E (ApoE) are at significantly increased risk for developing Alzheimer’s disease. The ApoE protein helps deliver cholesterol to construct the membranes of newly forming cells. It comes in three versions, and people who inherit one version, called E4, are at increased risk to develop Alzheimer’s later in life.

Jane and David Richardson (Department of Biochemistry) – They analyzed the ways proteins are folded to form the three-dimensional structures required for their biological activity and were able to show that despite gross differences in biological activity many proteins share very similar folds in parts of their structures. They pioneered the development of graphical ways to depict protein folds and thereby enhanced considerably our understanding of protein structure, a cornerstone upon which contemporary Structural Biology is laid.

Knut Schmidt-Nielsen (Department of Zoology) – Among his many seminal contributions to the study of animal functional morphology, he discovered the nose gland of birds and reptiles, a completely new and unsuspected excretory organ capable of manufacturing urine more concentrated than sea water. This enables turtles, gulls and penguins to live where there is only sea water to drink. Another of the many important discoveries made during his long career at Duke was demonstrating how camels and kangaroo rats can survive so long without drinking water.

Fritz Thurstone, Olaf von Ramm and Gregg Trahey (Biomedical Engineering) – Thurstone, along with a bright graduate student, Olaf Von Ramm, demonstrated the first clinically successful ultrasound machine, known as the cardiac ultrasound phased-array imaging system, which images fast moving biological tissue in real time. For example, it permits measurement of the volume of the heart’s chambers continuously while the heart is beating. Subsequently, Duke faculty member Von Ramm and his student Stephen Smith invented the 3D ultrasound scanner which forms the basis for all ultrasound imaging systems. Over the course of many years, the research of these two Duke scientists (along with Greg Trahey) has been instrumental in the development of the ultrasound technology, which is routinely used now as a medical diagnostic.

(Additional Major Duke Discoveries)

Arts and Sciences:

Andrea Bertozzi (Department of Mathematics) – She discovered the equations that govern the motion of contact lines of thin liquid films flowing on hard surfaces. Many important applications ranging from the spin-coating of microchips to the de-icing of airplane wings depend on understanding and controlling the motion of the interface at the film, air, solid boundary.

William Fairbank (Department of Physics) – Before he moved to Stanford, he made several seminal discoveries in the field of low temperature physics: 1) the detection of the beginning of Fermi degeneracy in liquid helium 3 based on predictions by Fritz London, 2) the phase separation of liquid helium 3 and helium 4 below 0.90 K, which was later known as the “tricritical point,” and 3) the logarithmic divergence of the specific heat of helium 4 at the superfluid transition.

Albert Goshaw (Department of Physics) – He and the Duke high energy physics group played a major role in the discovery of the top quark at Fermilab. The top quark is the heaviest elementary particle known and, with the exception of the Higgs boson, completes the collection of components of the standard model of particle physics.

Norman Guttman (Department of Psychology) – He was the first to measure “stimulus generalization,” the hypothesized but not before clearly demonstrated fact that conditioning an organism to one simple stimulus (e.g., a wavelength, a tone) also causes it to learn to respond to similar stimuli according to a measurable gradient.

David Morrison (Department of Mathematics) – He (along with Brian Greene of Cornell University and Andrew Strominger of the University of California at Santa Barbara) showed that in superstring theory, there is a process which can convert microscopic black holes into superstrings, and vice versa. As a consequence, many solutions of the “superstring equations” that had previously appeared to be distinct were shown to coincide, dramatically reducing the number of solutions to these equations.

Horst Meyer (Department of Physics) – His systematic studies of solid helium-3 at low temperature led to a good estimate of the temperature for the nuclear ordering transition – a new phenomenon at that time. Bob Richardson, with his Duke PhD in hand, continued the search for this transition at Cornell but stumbled instead on the superfluid transition of helium 3 – for which he was the co-recipient of the 1996 Nobel Prize along with his collaborators Osheroff and Lee.

Henry Newson and Edward Bilpuch (Department of Physics) – They spearheaded an important achievement at the Triangle Universities Nuclear Laboratory when they measured the nuclear level spacing statistics, which provided definitive experimental proof that the atomic nucleus is a chaotic quantum system. This is still the textbook example for quantum chaos, which forms the basis for our modern understanding of nanoscale systems.

Bruce Nicklas (Department of Zoology) – He discovered that tension is a major regulator of the metaphase checkpoint during cell division in both mitosis and meiosis. Because of that discovery it was possible to focus on how tension works to force all chromosomes to align at the metaphase plate during cell division before allowing anaphase to begin.

Henry J. Oosting (Department of Botany) – He and his student Catherine Keever established that plant succession in any given ecosystem is triggered and controlled by the life cycles of particular species in a regular and predictable pattern. This understanding has had a fundamental effect on agriculture and forestry in North America from California to the Maritimes.

Michael Reed (Department of Mathematics) – He (together with Jeffrey Rauch of the University of Michigan) discovered that singularities traveling on characteristics in semilinear hyperbolic partial differential equations create new singularities when they cross. The analysis of these singularities and the patterns they generate stimulated research in a new field of mathematics, nonlinear harmonic analysis.

Leslie Saper and Mark Stern (Department of Mathematics) – They solved the long-standing “Zucker conjecture,” which relates the L2 co-homology of an arithmetic variety to the intersection co-homology. This work relates several different parts of pure mathematics — topology, number theory, and representations of groups — and creates powerful new connections among them.

Weitao Yang (Department of Chemistry) – His application of density functional theory to large biomolecules using his “divide and conquer” approach is a development that enables chemical theorists to investigate complex molecules at a high level of theory.

Duke Medical Center:

Dani Bolognesi (Department of Surgery) – His discovery of the drug now commercially known as Fuzeon opened a new era in drug development for treating HIV by uncovering a new class of drugs, the “fusion inhibitors.”

Y. T. Chen and Priya Kishnani (Department of Medicine) – They developed an enzyme replacement treatment for Pompe’s disease and other glycogen storage diseases which heretofore were fatal in children.

Robert DeLong (Department of Medicine) – He demonstrated in China that iodinating irrigation water can eliminate Iodine Deficiency Disease (cretinism), a finding that has been of immediate and direct benefit to some millions of people in China.

Andy Wallace and Will Sealey (Department of Medicine) – They developed a cure for Wolff-Parkinson-White Syndrome. This is a conduction abnormality with an aberrant conduction pathway. They figured out how to cut the pathway and cure the disease.

Merel H. Harmel (Department of Anesthesiology) – He pioneered the development of monitoring systems and was one of the first to provide anesthesia to “blue babies.” He also pioneered the invention of the first world-wide computerized vital signs monitoring system, called the Duke Automatic Monitoring Equipment (DAME). Duke subsequently became internationally recognized as a center of monitoring and informatics.

Joanne Kurtzberg (Department of Medicine) – She has pioneered the use of umbilical cord and blood bone marrow transplantation for treatment of several malignant and non-malignant diseases.
Louise Markert and Bart Haynes (Departments of Immunology and Medicine) – They pioneered the development of Thymus Transplantation that cures DiGeorge Syndrome (children born without a thymus, the organ that makes T cells). Infants born without a thymus die by two years of age from immune deficiency. Working in mice and in tissue culture, they figured out how to transplant thymus into immunodeficient infants. Markert subsequently carried this technique into the clinic where most infants who are transplanted are now considered cured of their immunodeficiency.

Paul Modrich (Department of Biochemistry) – He discovered the biochemical mechanisms involved in repair of DNA synthesized with the wrong nucleotide sequence as the result of mismatched base pairing in DNA. His studies on “mismatch repair” from bacteria to humans explain how DNA is replicated with high fidelity from generation to generation and prevents the accumulation of mutations leading to defective proteins and ultimately cell death. These studies have led to a rational understanding at the molecular level of how cancerous cells are generated, at least in part, from normal cells and, as such, they represented a major step in cancer research.

John Moore (Department of Physiology) – He discovered that a poison found in the ovaries of the female puffer fish will specifically block voltage-gated sodium channels. This poison is known as tetrodotoxin and was the first pharmacological tool used to understand the basis of nerve conduction. It is also the basis of a category of local anesthetic. While the initial finding of the tetrodotoxin took place in Japan, Duke researchers were the first to use it in voltage clamp experiments, which proved its mechanism of action, and they also used it to calculate the number of Na channels involved.

Montrose Moses (Department of Microbiology) – He discovered the synaptenemal complex that holds chromosomes together during meiosis. That complex allows for crossing over and, as such, is a cell microstructure that is necessary for genetics and genetic variation in all eukaryotes.

Dr. Joseph Nevins (Department of Genetics) – He discovered the E2F transcription factor and demonstrated that E2F was a target and co-factor for the growth regulatory action of the retinoblastoma tumor suppressor protein. The significance of these discoveries lies in the central importance of the E2F/Rb pathway in the control of cell proliferation; a pathway that is disrupted in virtually all human cancers

Laura Niklason (Department of Anesthesiology) – She has been a pioneer in cardiovascular-engineered artificial vessels. She was the first to develop a novel bioreactor system that mimics the fetal environment in order to use cells taken from swine arteries to grow blood vessels that look and act like the real thing. This cardiovascular tissue engineering approach could eventually serve to treat heart disease patients.

Ned Patz (Department of Radiology) – He carried out pioneering work in the use of PET imaging in the diagnosis and staging of lung cancer, which essentially revolutionized the field.

Eugene Stead (Department of Medicine) – While not discoveries per se, he established the first comprehensive cardiovascular database as well as the first Physician’s Assistant training program, both of which are now mainstays of modern medicine.

Cathy Wilfert (Department of Medicine and Microbiology) – She originally proposed that Zidovudine (AZT) should be studied to see whether it could prevent mother-to-child transmission of HIV. When the hypothesis was tested at Duke, the rate of transmission decreased from 26% in the placebo group to 8% in the treatment group.

Duke Medical Center Firsts (not attributed to any one individual)

Duke was the first to use insulin pumps in children under age three.

Duke was a leader in the development of expertise to detect child abuse on physical examination.

Duke was one of the first hospitals in the country to perform newborn screening for sickle cell anemia.

Duke was the first center to use ethyl nitrite to treat pulmonary hypertension in newborns.

Duke surgeons were the first to successfully reattach a severed thumb more than eight hours after it was traumatically amputated.

Duke was the first to use UV light in the operating room to reduce the risk of operative wound infection.
The cochlear implant program at Duke has produced a number of breakthroughs in the design and performance of implant systems. The single most-notable achievement was the development of the continuous interleaved sampling (CIS) processing strategy for cochlear implants. This strategy has produced large improvements in speech reception abilities for implant patients.

Nicholas School of the Environment and Earth Sciences:

Richard Barber (Duke Marine Laboratory) – He discovered that El Nino warms the ocean temperature in a wave that travels across the Pacific from West to East and, as a consequence, has effects on weather patterns in North America.

Bruce Rosendahl (Department of Geology) – He discovered the thick sedimentary sequences in the African rift lakes through project PROBE (Proto Rift Ocean Basin Evolution), which was a major contribution to our understanding of plate tectonics and the relationship of such deposits to oil accumulations in lacustrine sediments.

Pratt School of Engineering:

Kenneth Hall (and a host of others – Jeff Thomas, Laurens Howle, Lawrie Virgin, Robert Clark, Robert Kielb and Earl Dowell – Department of Mechanical Engineering) – They have done pioneering experimental and theoretical work on nonlinear aeroelasticity, including the oscillations that occur in modern aerospacecraft which can be fatal to the vehicle and pilot. They have created definitive experimental databases and also developed novel and highly effective computational models for predicting and avoiding these potentially fatal oscillations.

Ray Ideker with Pat Wolf and Bill Smith (Department of Biomedical Engineering) – They optimized biphasic stimulation of the heart, which improved clinical defibrillators and makes implantable defibrillators possible.

Jim McElhaney (Department of Biomedical Engineering) – He developed a general theory of spinal cord injury mechanisms that describes how the spinal cord is injured in various traumatic situations. This theory has been applied in the design of football and motorcycle helmets, auto airbags, and occupant restraint systems. He and Richard Stack also developed a mechanical device for removal of plaque from arteries.

Robert Plonsey (Department of Biomedical Engineering) – He developed a mathematical theory for electrical activity of the heart that predicts heart fibrillation.

Madison Spach (Department of Biomedical Engineering) who worked originally with Tom Gallie (Departments of Mathematics and Computer Science) and Theo Pilkington (Biomedical Engineering) – They initiated systematic measurements of the sequence of electrical events within the normal heart at the size level of cells, structures (atria and ventricles) and on the body surface, together with the development of the mathematical and numerical models describing how one size scale evolves into the next.

More Recent Discoveries (still in gestation):

Robert Cabeza (Department of Psychological and Brain Sciences) – His recent research has shown that older adults recruit both brain hemispheres to perform tasks that require basically one hemisphere in young adults. Available evidence suggests that this change plays a compensatory role in the aging brain.

Warren Meck and Christina Williams (Department of Psychological and Brain Sciences) – Their studies of the benefits of prenatal choline supplementation on learning and memory has been instrumental in the Institute of Medicine’s decision to elevate choline to the status of an essential nutrient for humans — particularly pregnant and nursing women.

Miquel Nicolelis (Department of Neurobiology) – He and his team of collaborators have taught rhesus monkeys to consciously control the movement of a robot arm in real time, using only signals from their brains and visual feedback on a video screen (brain-machine interface). The animals appeared to operate the robot arm as if it were their own limb. This research represents a very important step toward technology that could enable paralyzed individuals to control “neuroprosthetic” limbs, and even free-roaming “neurorobots” using signals from their brains.

Jonathan Stamler (Department of Medicine) – He has pioneered studies of the role of nitric oxide-dependent signaling pathways in mammalian systems subject to redox control and was the first to demonstrate that nitric oxide reacts with the blood protein hemoglobin in a reaction termed S-nitrosylation. Nitric oxide has been implicated in a wide range of biological functions, including vasodilation, airway relaxation, long-term potentiation, immunity and erectile function. His studies of S-nitrosylation reactions have provided insight into the mode of transport and targeting of NO in biological systems, the means by which its potential toxicity is mitigated, and its mechanism of regulation of a diverse array of cellular functions.

John Thomas (Department of Physics) – He recently developed the first stable optical trap for neutral atoms and used this trap to create and explore a new state of matter: an ultracold, strongly interacting Fermi gas of atoms. This gas is universal — it tests theories of strong interactions in many fields: high temperature superconductors, neutron stars, and even a quark-gluon plasma. John’s group was also the first to observe the anisotropic expansion of the gas and recently obtained the first evidence of superfluid hydrodynamics in this system.

Miscellaneous:

Jim Ellis and Tom Truscott (both Duke undergraduates) – They conceived of the idea of having two computers at different sites use telephone lines to communicate news and correspondence between the two machines. They discussed the idea with Steve Bellovin, a student at UNC, and together they developed a Unix-based program that implemented the idea. (Other students who joined the effort were Steve Daniel and Dennis Rockwell.) They gave their system the name USENET and began sharing their code and thus the communication capabilities with other institutions. The system spread quickly across the world and was said to serve over 1200 news groups by 1993. By 1999, the number of news groups had grown to over 37,000. These developers, in 1993, were given the Electronic Frontier Foundation Pioneer Award for their contribution.

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