How DOE Research in the Physical Sciences
Has
Contributed to Medicine
Compiled by Mary V. Schorn
Over the years, DOE and its predecessor agencies have conducted significant research that has contributed to medicine. Among these contributions are decoding the human genome and accelerating the decoding process; findings about protein structures and their ability to help fight disease, insights into Legionnaires' disease and a treatment for Parkinson's disease; boron neutron capture therapy; laser applications to medicine; and radioisotope discovery and production.
Devices and software that have had a positive impact on medicine include the Superconducting Quantum Interference Devise (SQUID); the positron emission tomography (PET) and single photon-emission computed tomography (SPECT) imaging systems; the computed axial tomography (CAT) and Magnetic Resonance Imaging (MRI) scanners, and the "Electron-Gamma-Shower" (EGS) software. These have been, and continue to be, used for mapping the human brain, determining the biochemistry of human addiction, diagnosing and/or treating cancer, heart disease, stroke, abdominal pain, stress fractures, epilepsy, Graves' disease, gastrointestinal (GI) bleeding, hidden abscesses, lung disease, and Alzheimer's disease.
Brief descriptions of these contributions are provided below. Additional information may be found at DOE's Decades of Discovery Web site, at the DOE R&D Accomplishments Web site, and in Converting Energy to Medical Progress.
1) Decoding the Human Genome. Scientists are close to completing the genetic blueprint for a human being, thanks in large part to DOE funding, which supported the completion of high-quality draft sequences of chromosomes 5, 16, and 19. Together these chromosomes contain some 12,000 genes, including those implicated in forms of kidney disease, prostate and colorectal cancer, leukemia, hypertension, diabetes, and atherosclerosis.
2) Engineered Enzyme Accelerates DNA Sequencing. The international effort to decode the human genome is ahead of schedule, thanks in part to new tools that have accelerated DNA sequencing and reduced its cost. (The DOE sequencing team can generate more data in 8 days now than it did in all of 1998, its first full year of operation.) One such tool developed by DOE researchers in the mid-1990s is an enzyme, a new type of DNA polymerase, which produces more usable data than was generated previously. The resulting commercial enzyme, ThermoSequenase, has improved the quality of sequencing data and reduced the costs.
3) Putting A Virus to Practical Use. A virus is usually viewed as a problem, but T7, a bacteriophage (bacteria-eating virus), turned out to be useful, even valuable. DOE scientists determined the DNA sequence of T7 and correlated the genetic map with T7's protein production, thereby acquiring a detailed understanding of how such viruses control their own replication. The T7 system is noted for its reliability and adaptability and has become one of the most commercially successful, biologically-based systems for producing large quantities of specific proteins. Recent work on a protein associated with Lyme disease, OspA, has led to the development of improved vaccines.
4) Studies of Protein Structure Help Fight Lyme Disease. The original Lyme disease vaccine often failed for reasons that were unclear until DOE scientists identified variations in the structure of a key surface protein, OspA, from the bacterium that causes Lyme disease. The OspA structure contains several regions that vary among different strains of the bacterium and other regions that are invariant. The original vaccine was developed against a variant region from only one strain, so it did not protect against other strains. This research on other Lyme disease proteins has led to the development of a rapid, highly accurate diagnostic test that was granted approval by the Food and Drug Administration.
5) Legionnaires' Disease: Causal Factors. DOE research has provided a plausible explanation of why Legionnaires' disease is associated with the dispersion of waste heat by means of building air conditioning systems and industrial cooling towers. Concentrations of disease producing organisms, including both amoebae and Legionella, may be amplified by heated waters. In addition, Legionella may be further and dramatically amplified by the presence of amoebae. Finally, the physical operation of cooling systems provides two aggravating conditions, the heated waters and the pathway into the lungs via airborne mist.
6) L-Dopa Treatment for Parkinson's Disease. DOE research resulted in the successful application (very gradual administration over long periods) of L-dopa to individuals with Parkinson's Disease. This approach extends life expectancy and delays disability.
7) Superconducting Quantum Interference Devices (SQUID). DOE researchers, studying the brain to determine the location of both the responses to external stimulation and the source of spontaneous signals, are using multiple SQUID to determine where the processing of visual and aural signals takes place. A very important aspect of SQUID is that they are entirely noninvasive and do no damage to tissue. By contrast, the alternative methods are invasive, requiring the placement of electrodes on the surface of the brain itself.
8) Improving Neutron Beams for Cancer Treatment. Adaptation of existing nuclear fission converter technology produced a novel type of neutron beam that was generated for use in a medical reactor. DOE supported the detailed scientific and engineering design needed to put the concept to practical medical use. In boron neutron capture therapy (BNCT), the patient consumes a drink containing boron, which is taken up by tumor cells. The tumor then is irradiated with a neutron beam, causing the boron to split into two highly energetic particles that destroy the tumor cells while largely sparing adjacent healthy cells. Preliminary trials of BNCT therapy, supported by DOE, have shown promise for the treatment of malignant melanomas.
9) Laser Application in Medicine. DOE has granted funding to five Centers of Excellence for Laser Applications in Medicine to support research that will advance the application of laser technology in the clinical practice of medicine.
10) A Better, Safer Artificial Heart. Using laser imaging and other advanced equipment originally developed to study the microscopic flow of coal liquids, DOE researchers were able to improve the design of the artificial heart pump, and later an artificial lung device, to minimize areas where blood stagnation could promote clotting.
11) Improved Artificial Hip. With ion implantation, particle beams are used to embed a thin layer of ions near the surface of a material to alter its chemical structure. Ion implantation has been successfully used to reduce the wear of artificial hip joints by 400 times, saving replacement operations.
Nuclear Medicine
12) Radioisotopes. DOE researchers created iodine-131, with a half-life of eight days, and played pivotal roles in the discovery and application of additional radio-pharmaceuticals, including tritium, carbon-14, fluorine-18, thallium-201, technetium-99m, and gallium-67. These radioisotopes have been used to diagnose and/or treat the polycythemia vera disease, leukemia, hyperthyroidism, heart disease, and Hodgkin's disease.
13) Radioisotope Production. DOE has provided a supply of research and clinical radioisotopes for use in nuclear medicine. The research program has supplied small quantities of radioisotopes to support nuclear medicine research.
14) Scanners. DOE researchers developed the Anger scintillation camera, which enables physicians to detect tumors and conduct other medical diagnoses by imaging gamma rays emitted by radioactive isotopes. Over time, it has evolved into modern imaging systems such as PET (positron emission tomography) and SPECT (single photon-emission computed tomography). Other contributions include the multi-crystal whole body scanner; the gated heart single gamma tomography; the computed axial tomography (CAT) scanner, and the Magnetic Resonance Imaging (MRI) scanner. CAT and MRI scanners have revolutionized diagnosis of disorders of soft tissues, especially disorders of the head and brain. Most shock-trama units or major neurological clinics have one of these machines on-site or at their immediate disposal. PET cameras are operating in hospitals and in medical and research facilities worldwide.
15) Mapping Human Brain Function. Many mysteries of the human brain have been unraveled by positron emission tomography (PET), an imaging tool used worldwide to diagnose cancer and heart disease and perform scientific studies. A radiotracer called 18-fluorodeoxyglucose (a combination of the short-lived radioactive element fluorine-18 and a sugar, glucose) was developed and used to generate the first functional map of the human brain at work. When a radiotracer is injected into the body, its signal is picked up by PET equipment. This development enabled scientists to see, for the first time, regions of the human brain "lit up" in response to stimuli such as looking, listening, and remembering. Scientific uses include studies of human metabolism, brain activation and function, addiction, and mental illness. This research laid the foundation for imaging procedures now used in hospitals worldwide to diagnose disease, saving thousands of lives each year. These developments opened new vistas for mapping of human brain function in schizophrenia, Alzheimer's disease, stroke, addiction, and other psychiatric and neurological disorders.
16) The Biochemistry of Human Addiction. Dopamine, a brain chemical linked to pleasure and elation, also has a dark side--a link to addiction. Research has shown that addicts have fewer than average dopamine receptors in their brains, so that weaker dopamine signals are sent between cells and life has less joy. Addicts thus seek to derive pleasure from dopamine-stimulant drugs, such as alcohol, cocaine, and nicotine. This cycle was first identified in 1990, when DOE scientists showed that cocaine addiction blunts the dopamine signaling system. Using positron emission tomography (PET), they determined the critical biochemical changes and where they occur in the brain in response to addictive drugs. These studies demonstrated that addictions are associated with high levels of dopamine in a pleasure center in the brain and have led the way in debunking the idea that sheer willpower is a cure for addictions. Understanding of the molecular mechanisms underlying drug addiction could lead to new approaches for interrupting addictive behavior and have lasting impacts on how society copes with this public health problem.
17) The Role of the Extracellular Matrix in Cancer. The extracellular matrix (ECM), the network of proteins surrounding cells in the body, long was believed to function mainly as inert scaffolding for tissue. DOE scientists conducted experiments which showed that in standard cultures, cancerous breast cells grew at the same rate and took on the same flat appearance as healthy breast cells. But when ECM was added to the culture, the healthy cells once again became plump and round and began secreting milk, whereas the cancerous cells grew wildly into a tumorous mass. This new understanding of the ECM provides information essential to the diagnosis and successful treatment of cancer. This work suggests that, even after cancer genes have been activated and lesions have formed, it may still be possible to reverse the process and restore the cells to normal appearance and function.
18) EGS Software. A medical physicist needs a computer program to calculate radiation effects in the body and plan treatments. The problem is how to give maximum radiation dose to the tumor with minimum damage to healthy tissue. The "Electron-Gamma-Shower" (EGS) software solves this medical problem. The EGS is now the most accurate method available to calculate radiation effects in body tissue and determine dosages. The EGS program is used as the "gold standard" to check whether simpler, faster, approximate calculation methods that are used by practitioners are doing the job accurately enough.
19) Tests and Scans. DOE-funded research makes it possible for today's doctors to rely on nuclear medicine tests and scans, which are performed at virtually all hospitals, as well as many clinics and private doctors' offices.
A) Cardiology: Patients with Heart Disease. Heart scans can show whether certain regions of the heart muscle lack an adequate supply of blood, which can help cardiologists decide whether a patient needs angioplasty, bypass surgery, or changes in lifestyle. Images that show metabolic activity can help predict the success of these revascularization procedures.
B) Oncology: Patients with Cancer. Scans can detect and stage many types of cancer. These scans can also show how well a patient responds to treatment, such as surgery, chemotherapy, or radiation therapy. In some cases, nuclear medicine can be used to treat selected cancers.
C) Neurology: Patients at Risk for, or Recovering from, Stroke. Brain imaging can show regions of the brain with inadequate blood flow or metabolism, which can help doctors choose therapy for preventing a stroke. Brain scans obtained after a stroke can help doctors monitor the patient's recovery.
D) Digestive Diseases: Patients with Abdominal Pain. Tests can show whether the gallbladder functions normally or whether a patient has gallbladder disease. These scans are also used after surgery to detect abnormal bile drainage from the liver.
E) Sports Medicine: Athletes at Risk for Stress Fractures. Bone scans play a major role in sports medicine since they can detect stress fractures before they show up on x-rays.
F) Surgery: For Children with Epilepsy. Brain scans can guide surgeons to operate on the region of the brain that causes a child's epilepsy when the seizures cannot be controlled with drugs.
G) Thyroid Disorders: Patients with Graves' Disease. Tests help evaluate many thyroid disorders. Moreover, therapy with radioactive iodine has become the treatment of choice for overactive thyroids (Graves' disease) and for most thyroid cancers following surgery.
H) Gastrointestinal Disease: Patients with GI Bleeding. Tests can determine whether a patient is actively bleeding into the bowel. Such gastrointestinal (GI) bleeds can be caused by polyps, ulcers, tumors, inflammation, diverticulitis, and other GI disorders. Frequently, the scan also discloses the location of the bleeding site so the problem can be treated more efficiently.
I) Infection: Patients with Hidden Abscess. Scans can identify a hidden abscess in a patient with an internal infection. Typically, these patients have fever of unknown origin, a sign of infection.
J) Pulmonology: Patients with Lung Disease. Lung tests are used to evaluate respiratory disorders, providing information about the extent and severity of such disorders as emphysema, cystic fibrosis, chronic obstructive pulmonary disease (COPD), and life-threatening blood clots in the lung.
K) Dementia: Patients with Alzheimer's Disease. Brain scans can help doctors diagnose Alzheimer's disease, and differentiate it from other types of dementia early in the course of disease when treatments are more effective.