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ORNL Review in the Summer of 1992

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ORNL Review in the Summer of 1992 ON THE COVER In this silicon nitride material made by microwave processing at ORNL, the interlocking network cif hexagonal fibers (as shown in this electron micrograph by Dorothy Coffey) strengthens the ceramic. ORNL has made important contributions to the processing of silicon nitride for use in high-temperature, energy-efficient engines, as described in the first two items in ''Technical Highlights" on p. 56. The Oak Ridge National Laboratory Review is published quarterly and distributed to employees and others associated with ORNL. The address of the editorial office is Building 4500-South, M.S. 6144, Oak Ridge, TN 37831-6144. Telephone: internal, 4-7183 or 4-6974; commercial, (615) 574-7183 or (615) 574-6974; FfS, 624-7183 or 624-6974; FAX, (615) 574-1001 If you have changed your address and want to remain on the mailing list, please notify the editorial office. ORNL is managed by Martin Marietta Energy Systems, Inc. for the Department of Energy under contract DE-AC05-840R21400 Printed in the United States of America. Available from National Technical Information Service, U.S. Department of Commerce, 5285 Port Royal Road, Springfield, VA 22161 . ISSN 0048-1262 Editor Carolyn Krause Associate Editor Jim Pearce Consulting Editor Bill Appleton Designer Vickie Conner Technical Editing Mike Aaron Electronic Publishing Bob Eldridge Larry Davis Photography, Graphic Arts, and Printing and Duplicating departments Volume 26 Number One, 1993 FEATURES 2 Scurfy Mice: A Model for Autoimmune Disease Virginia Godfrey ORNL has demonstrated the role of the thymus in educating part of the body to attack itself. 8 The Fate of Nutrients in Streams Patrick Mullholland ORNL studies of streams may influence their management to preserve or enhance their value to people. 16 New Uses for ORNL's Ultrasensitive Mass Spectrometer Marilyn Morgan Analytical chemists can monitor uranium in workers and toxins in trees and detect counterfeit bolts. 22 Regulation of Carcinogens: The Problem and a Solution David Kocher and Owen Hoffman Two ORNL scientists propose a scheme for making health risk regulation consistent and sensible. 30 Intelligent Robots! Do We Need Them and Can They Be Built? Reinhold Mann Intelligent robots are needed to work where humans dare not go. ORNL has built three such machines. DEPARTMENTS 39 Awards and Appointments 43 Pick a Number-Modeling subsurface processes 44 User Facilities--100,000 hours of Oak Ridge Electron Linear Accelerator operation 48 Educational Activities-ORNL researchers meet youngsters at the Environmental Fair 50 R&D Updates--Metal-ceramic composite ideal for cutting tools; coal converted to liquid fuel by enzymes; funding for genome research at ORNL extended; trace gases and global warming 56 Technical Highlights--Decision to market silicon nitride ceramic influenced by ORNL studies; microwave-processed silicon nitride; Inchworm robot for inspecting pipe leaks; frozen fruit flies hatched; removing nitrate from radioactive waste; ORNL monitoring system for NASA launch control; variable tree response to atmosphere enriched in carbon dioxide; effect on tree pollen of increased ultraviolet-B radiation; computer model for spaceship design; computerized training program for repairing manufacturing systems 72 Technology Transfer-CRADAs for Intel parallel supercomputer, Optics MODIL work for SDI, ceramic composites, furnace assemblies, fuel studies, and removal of uranium from contaminated German mine water using microbes; awards for chlorine removal process Oak Riilge National Laboratory is a multiprogram, multipurpose laboratory that conducts research in the physical, chemical, material and life sciences; infusion, fission, and fossil energy; and in energy conservation and other energy-related technologies. toimmune disease-the Lymphocytes are divided into two major condition in which the body categories based on their development pathways attacks its own tissue-has been an and functions. B lymphocytes recognize a foreign objectA of public concern recently. Former antigen by their cell surface antibody receptors. President George Bush and his wife Barbara both When stimulated by the appropriate foreign are afflicted with Graves' disease in which the antigen, B lymphocytes can be transformed into body's own immune system attacks the thyroid antibody-producing factory cells called plasma gland. The safety of breast implants was called cells that secrete antibodies specific for that into question because of evidence that some antigen. Like a protective cover for an electrical "Scurfy" recipients had developed autoimmune disorders outlet, an antibody attaches to the foreign antigen. mice are such as rheumatoid arthritis, systemic lupus This antigen-antibody complex then attracts erythematosus, and scleroderma. Women, the scavenger-type white blood cells called helping us media pointed out, have a higher-than-average macrophages that ingest and destroy the offending better incidence of many autoimmune disorders. These microorganisms. understand events suggest the need to know more about what T lymphocytes are so named because they the role of makes the immune system work so well and what develop and mature within the thymus, a hi-lobed makes it go awry. gland next to the heart. They recognize an antigen the thymus At ORNL's Biology Division, we have made by their cell surface protein called the T cell gland in progress in understanding the underlying causes receptor. T lymphocytes develop into two types of autoimmune of immune disease by studying mice having a cells having different functions: killer cells and disease that causes them to be underdeveloped; to helper cells. Killer T cells carry the CDS cell disease. have scaly skin, small ears, and large spleens; to surface protein associated with their T cell open their eyes late; and to die early. These receptors and act to destroy virus-infected cells or "scurfy" mice are helping us better understand the cells with foreign tissue antigens (as in graft role of the thymus gland in autoimmune disease. rejection). Helper T cells are the master coordinators of the immune system. Carrying the B and T Lymphocytes CD4 cell surface protein next to their T cell receptors, helper T cells respond to foreign Our immune system protects us from diseases antigens by releasing a host of chemical signals by its unique ability to distinguish our own "self' called interleukins. These interleukin molecules molecules from those of invading call lymphocytes and other white blood cells to microorganisms. To make this distinction, the the site of the immune response, enable other immune system must first learn to recognize and lymphocytes to proliferate, and help B tolerate self molecules during growth and lymphocytes transform into antibody-producing development. This critical function is performed plasma cells. The CDS and CD4 cell surface by lymphocytes-<:irculating white blood cells proteins are often referred to as "markers" for the that search for foreign cells or microorganisms Tc and Th subclasses ofT cells because and directly or indirectly cause chemical attacks monoclonal antibodies to these proteins can be on these invaders to inactivate them. Each invader used to count these cells using fluorescent carries antigens-proteins or carbohydrates that, staining. when introduced into the body, stimulate the Obviously, anything that goes wrong within production of a specific immune response. this complex, interlocking system can have Foreign antigens are recognized by lymphocytes. profound effects on the individual. For example, Virginia Godfrey holds a female mouse (weighing 18 grams) and her smaller male sibling of the same age (weighing about 6 grams). The male mouse has scurfy disease. Number One, 1993 3 SCURFY MICE: A MODEL FOR AUTOIMMUNE DISEASE the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) attacks and destroys CD4 helper T cells. As a result, the immune system is devastated and the AIDS patient is left vulnerable to a host of life-threatening infectious diseases. Persons or animals born without a thymus (such as the nude mouse) lack T lymphocytes entirely and are, therefore, severely immune deficient. Other inherited immunodeficiencies cause the inability to make some or all types of antibodies. On the other hand, excessive or incorrect functions of the immune system can have equally harmful effects. These may range from the discomfort of allergies (overreaction to pollens, animal dander, etc.) to life-threatening autoimmune diseases such as juvenile diabetes, systemic lupus erythematosus, or scleroderma. The immune system's mistaken attacks on the body's own normal tissues may be limited to very specific tissues, such as the pancreatic islet cells in juvenile diabetes, or they may involve entire organs or organ systems. Currently, the causes of autoimmune disease are unknown. Treatments consist of powerful immuno-suppressive drugs such as those given to recipients of organ transplants. These drugs have severe side effects and only inhibit the symptoms of autoimmune disease, not the root causes. Mutant Mice In 1987, I joined Richard Griesemer's laboratory in ORNL's Biology Division to investigate several mutant mouse stocks as potential animal models of human disease. We quickly settled upon an animal of historic importance in the genetics community-the scurfy mouse. Close-ups of healthy and scurfy (mutant) mice. At top are two dark mice siblings (the one on the left has scurfy disease), a light-colored normal mouse (middle), and a hairless scurfy-sparse fur mouse (right). Sparse fur is a second mutation that is closely linked to scurfy on the X chromosome. The lack of hair caused by the sparse fur mutation is used as an indicator of the linked gene, scurfy, in mice less than 12 days of age (when lesions of scurfy itself first become visible). In the middle is a hairless, scurfy-sparse fur mouse (right) and its normal male sibling (left). At bottom are the healthy female mouse with her male sibling, which is smaller because of scurfy disease. 4 Oak Ridge National Laboratory REVIEW The scurfy mutant mouse was discovered by was reacting uncontrollably, possibly against its William L. Russell in 1949. Russell, who was own tissues.
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