1979 March Faculty Journal

FACULTY JOURNAL UNIVERSITY OF UTAH COLLEGE OF MEDICINE Vol.2 No.1 March 1979Dr. Edmundson and Ms. Ely adjust a piece of an amino acid side chain of the Bence- Jones molecule model. Model represents the highly specific binding sites of an antibody. X- ray crystallography models provide clues to immunity Researchers in the Department of Biochemistry are leading an international effort to define the molecular basis of immunity. Led by Allen B. Edmundson, Ph. D., professor of bio-chemistry and biology, the team is using x- ray crystallogra-phy to study how antigens on large protein molecules stimu-late the production of antibodies. " The study of precise structural models by x- ray diffraction suggests how the geometry of the antibody com-bining site, and hence its specificity for an antigen, might be modified by making changes in the amino acid sequence," says Dr. Edmundson. Antibodies combine with corresponding antigens like pieces of a jigsaw puzzle to modify the outer structure of invading microorganisms to allow ingestion by white blood cells. The antibodies must be highly sensitive to minor struc-tural differences in the sequence of amino acid units so as not to cause problems of autoimmunity. The researchers are investigating the three- dimensional structure of antibodies by the x- ray diffraction of crystals from Bence- Jones ( B- J) protein, a molecule excreted in the urine of patients with multiple myeloma. B- J protein is thought to consist of a portion of an antibody molecule. " These proteins are the principal product of a tumor so they can be used as immunologic tools to study normal antibody- producing cells," says Dr. Edmundson. " Eventually, we hope to learn enough to be able to synthesize antigens which will stimulate production of antibodies against specific diseases." Dr. Edmundson cautions, however, that such a break-through may be several decades away. " You can't always see immediate applications of basic research," says the world- renowned biochemist. " In this case, it will take three to five years to make models after we produce crystals." The first crystals of the B- J protein, which are isolated from urine and are only one- third the size of an antibody, were grown in 1969. Since moving to Utah from the Argonne National Laboratories two years ago, the research team has reached the significant stage of crystallizing whole antibody-like molecules. The team includes Kathryn Ely, research instructor in biochemistry who does the primary crystallization; Enrique Abola, computer expert from the Phillipines; and S. S. Rajan, a post doctoral fellow in crystallography from the University of Madras in India. The team works closely with the Department of Medi-cine and the Division of Hematology/ Oncology. Bruce Cheson, M. D., assistant professor of hematology, coordinates the clinical research. " X- ray crystallography employs an automated diffrac-tometer so a computer can make an electron density map which corresponds to the shape and structure of the mole-cule," Dr. Edmundson explains. " We need to learn the specific sites where the antigens and antibodies bind together because the immunologic process is so delicate." The team uses a three- dimensional framework so medical personnel can better understand the binding process. Clinicians suggest which proteins are interesting and medi-cally significant. " The dramatic advances in immunochemistry in recent years have drawn a much clearer picture of how an antibody molecule fits itself to an antigen and have provided much information on the evolution of antibody structure," Dr. Edmundson concludes. " A rational molecular explanation for the capacity of the body's immune system to respond to apparently infinite varieties of antigens now seems to be at hand." A computer graphics system is used to determine the electron densities corresponding to the structure of an antibody. This is a low- resolution reproduction of the Bence- Jones protein. British cancer expert urges preventive approach " It's very fashionable but obviously complete non-sense to believe we can lay the blame for our cancer troubles on industry," asserts Dr. John Cairns, Imperial Cancer Research Fund, Millhill, London. " And this attitude diverts people's minds from the general question of lifestyle, which we're going to have to think about changing." Dr. Cairns, whose recent Med Center lecture on " Var-ious Strategies for Dealing with the Cancer Problem" was sponsored by the Howard Hughes Medical Institute and U of U Medical Center Cancer Planning and Coordinating Com-mittee, discussed existing and new methods of treatment of the disease, and cancer prevention. " Existing methods don't seem to be working any better now than they used to- I don't see why we should expect to get very far trying to improve those methods," says Dr. Cairns. He believes the fact that cancer incidence or mortality varies from one part of the world to another adds fuel to the " many very strong arguments that cancer is a preventable disease." In Israel, for instance, the cancer rate is lower than in the U. S. or Europe ( in both Jews and non- Jews). " And look at America's Seventh- day Adventists. They don't smoke, don't drink, don't eat meat. And their middle- age cancer rate is about half that of the U. S. generally, says Dr. Cairns. " It is Dr. Wrenn possible to hypothesize that the nation's cancer rate could be cut in half by adopting the habits of Seventh- day Adventists. And it may be possible to do even better than that with some knowledge of carcinogenic stimuli." Wrenn to head Radiobiology Lab The University of Utah's internationally recognized Radiobiology Laboratory has new leadership and an expanded scope. Dr. McDonald E. " Ed" Wrenn, an expert in the toxi-cology of energy- related materials, has been named director of the lab effective February 1, when it becomes a division of the Department of Pharmacology. The Radiobiology Laboratory will expand into environ-mental toxicology, according to Dr. Dixon M. Woodbury, chairperson of the Department of Pharmacology. " For more than 20 years, our researchers have been investigating the radiobiology of internal radia-tion," says Dr. Woodbury. " It is now important to study the impact on the environment of new energy sources such as coal, coal gasifica-tion, oil shale and solar energy." Dr. Wrenn notes that the U. S. Department of Energy has respon-sibility in areas much broader than the old Atomic Energy Commission and the Energy Research and Development Administration, which have been funding the laboratory. " We will be studying the chronic toxicology of energy-related materials," he says. The laboratory will quantify the uptake of substances from the environment to man." Dr. Wrenn has studied the metabolism of radionuclides and trace elements in primates at New York University Medical Center, where he is now assistant director of the Laboratory for Environmental Studies in the Department of Environmental Medicine. A Ph. D. in nuclear engineering and environmental health, Dr. Wrenn has studied the accumulation of thorium in the residents of Grand Junction, Colo., and has been a consultant to several large utilities and the Federal government. " I hope to develop a method to measure dosages of radiation to which people were exposed years ago," says Dr. Wrenn. " This would be very important in investigating any possible link between low- level radiation and the inci-dence of cancer in Utah, if the University is involved in such a project." According to Dr. Woodbury, the new director of the Radiobiology Laboratory will further enhance the inter-national stature of the lab. " Dr. Wrenn will be able to attract new Federal research grants and additional top researchers," Dr. Woodbury pre-dicts. " He is very eminent in his field." Med school applicant pool: Smaller but still mighty Utah, as are other U. S. medical schools, is experiencing a significant reduction in the number of student applications. But that doesn't mean that the quality of students admitted to the College of Medicine will decline, according to Fred L. Anderson, M. D., assistant dean for admissions. " We're still attracting an abundance of applicants with excellent credentials/' says Dr. Anderson. " Utah will remain competitive." The average number of applications has dropped from 350 to 250 a year in the last three years. Dr. Anderson thinks the chance of a Utahn being accepted might improve from one in three and a half to four, to one in two. Currently, the U guarantees 75 slots for state residents. According to a recent special issue of /. AM. A on medical education in the U. S., the pool of applicants has been dropping steadily since reaching a record high of 42,624 in 1974. The decrease is expected to total 2,000 between 1977 and 1978. There has been a close corre-lation between the declining num-ber of medical school applicants and the dwindling size of the 22- year- old population in the United States. " More people are selecting alternative careers because it's been tough to get in medical school," Dr. Anderson says. " But there Dr. Anderson could be another influx of applica-tions as students realize their chances of being accepted are improving." The assistant dean also cites the changing image of the medical profession and increased Federal involvement in medicine as possible reasons for the decline in applications. " Physicians are under much closer scrutiny by their patients and the public. There is more litigation and problems with malpractice insurance." What kind of student will the faculty see in coming years? " No one really knows, but there is no reason for alarm at this point," Dr. Anderson responds. " But as the number of applicants decreases and the class size is increased with the Medical Center expansion, it may be more difficult to find qualified students. We might have to recruit to maintain class sizes." The Admissions Committee still will look for persons with a record of personal and academic excellence, Dr. Anderson stresses. "This school will not modify its standards to fill a class from a shrinking applicant pool. In addition to academic achievement, it is important for a student to be active in the world around him. Outside interests and some experience in the health care field are desirable." Dr. Anderson predicts that the overall quality of stu-dents at Utah will remain high. He also expects graduates to continue to fare well in competition for post- graduate training and jobs. Rapid resolution needed in tenure disputes The machinery for dismissing tenured faculty who have been deemed incompetent is so cumbersome that it becomes easier simply to tolerate mediocrity than to under-take the " grueling task" of termination. That's the opinion of Dr. Marcus Jacobson, professor and chairperson of the Department of Anatomy, who calls for a new approach to retention and tenure questions which would ensure more rapid resolution of such matters. " I'm advocating some very con-servative revisions of a largely acceptable institution," stresses Dr. Jacobson. " Many opponents of tenure recommend radical surgery when cosmetic measures will do." The U anatomist believes that tenure disputes can be resolved within weeks without violating due democratic process. " One of the philosophies be-hind dragging out tenure actions is that it may give the faculty mem-ber a chance to rehabilitate himself, but this rarely occurs," explains Dr. Jacobson. " Instead, the person is so preoccupied with his case that his work slips even further, and bitterness frequently is generated on all sides." The existing, excruciating slow tenure machinery causes " featherbedding," and over the years makes institu-tions lower their sights to the level of the lowest common denominator, at which everyone can perform without any strain, according to the U department chairperson. " This negates the very idea of a university as a place in which to attain excellence," he says. Dr. Jacobson suggests reviewing faculty performance every three years. If the reviews are favorable, tenure would be granted- subject to future review- as an acknowledge-ment of a person's professional competence. And if performance is questioned, an arbitration com-mittee consisting of faculty, students and administrators would conduct reviews at the department, college and ( as a last resort, in a very small percentage of cases) at the univer-sity- wide level. Ideally, according to Dr. Jacobson, the entire question of tenure can be resolved on campus within a short time and, if incompetence is found, the person would be asked to leave within a year. Dr. Jacobson emphasizes that it's absolutely essential to protect faculty against things that are irrelevant to their professional competence, such as fiscal exigency and matters of personal belief, and to safeguard the faculty's right to engage in free debate. " I'm not against tenure and I would accept it, ask for it, if it is the generally agreed upon protection against arbitrary action- but not if it functions as a shield for the incompetent." Radiology's three- second scanner: Faster, clearer computer diagnoses A sophisticated whole- body computer tomography scanner has provided the radiology department with a level of diagnostic imaging performance far superior to that of conventional radiologic techniques in the diagnosis of tumors, head trauma, internal lesions and other problems. The scanner, which completes a scan in three seconds and reconstructs an image about 30 seconds later, was pur-chased by University Hospital last year and now is used on an average of five to eight patients per day in the special procedures division. Computer tomography ( CT) is a technique in which finely collimated x- ray beams are passed through the body to sensitive collectors which record x- ray absorption values for the tissues in each cross- section taken. The x- ray beams Dr. Jacobson and the collectors rotate as a unit during a full 360- degree scan. A computer calculates hundreds of thousands of these values and reconstructs an image which resembles an ana-tomic cross- section of the body. CT scanner completes a scan in three seconds and reconstructs a computer image about 30 seconds later. At $ 600,000 to $ 700,000, the three- second scanner is the most expensive piece of equipment in the department and possibly in the hospital, according to Ruben Koehler, M. D., head of the diagnostic radiology division. While many institutions have an 18- second CT scanner and a five- second scanner is located at McKay- Dee Hospital in Ogden, Dr. Koehler notes that the nearest three- second scanner is at a Las Vegas hospital. The major advantages of the instrument are its short scan time and large aperture. The 90- cm. diameter opening allows positioning of the patient to obtain scans from different angles. Because of the short exposure time, the effect of patient movement is minimized, allowing clearer images to be taken. " It's a great improvement over the more common 18- second scan, in which there is movement caused by breathing or intestinal motility," says Dr. Koehler. " The short expo-sure time eliminates the need for medication to control the bowels during an exam." The radiology department's head- scan instrument has a four- minute exposure time. Dr. Koehler says that by using the three- second whole- body scanner to do head scans on children and uncooperative patients, the need for anesthesia to control movement is almost completely eliminated. Dr. Koehler says the patient's cost for the scan is rela-tively high ($ 350), but it in many cases eliminates the need for other tests and longer hospitalization. The radiation dosage is about equal to that of a series of x- rays, he says. " There's a great deal of potential for further develop-ment of the CT scanner," Dr. Koehler says. " I expect the detectors to become more sophisticated, making it possible to differentiate between types of masses." Improved diagnos-tic techniques are expected to minimize exploratory surgery. Lazarus named Faculty Fellow Harrison M. Lazarus, M. D., associate professor of sur-gery and director of the Emergency Room, has received a David P. Gardner Faculty Fellow Award for the 1979- 80 academic year. He will be released from for-mal teaching duties during Summer Quarter, 1979 to pursue research on the effects of organ storage and hemorrhagic shock on chromatin and chromatin template activity. Dr. Lazarus will work in the University of Paris laboratory of L. Robert, M. D., Ph. D., director of the university's Institute of Re- , search on Vascular Diseases. Faculty fellow awards recently were made to 17 U of U professors on the basis of proposals submitted by the indi-vidual faculty members. The academic departments involved will receive $ 2,750 for each released professor for use in departmental programs. ACADEMIC HONORS Carlos E. Eyzaguirre, M. D., professor and chairperson, Department of Physiology, has been named a member of the Physiology Test Committee, National Board of Medical Examiners, 1978- 1981. Huntington Mavor, M. D., associate professor of neurology, is the newly elected president of the Western Electroencephalography Society. He also serves on the governing board of the American EEG Society and is chair-person of the Professional Advisory Board, Epilepsy Founda-tion of America/ Utah Chapter. John L. Swanson, M. D., professor of cellular, viral and molecular biology and pathology, has been named to NIH's Bacteriology and Mycology ( AHR) study section. Dr. Swan-son also has been appointed to the editorial board of the Journal of Bacteriology and reappointed to the editorial board of Infection and Immunity. Dr. Lazarus OFFICE OF THE DEAN Dean Lee There likely will be an early effort in this Congress to extend the implementation date of Sec. 227, Public Law 92- 603, a portion of the 1973 Medicare amendments impos-ing special regulations on physicians in teaching settings. The primary purpose of these regulations was to prevent double billing when hospital patients are treated by both residents and staff physicians. Sec. 227 has not been implemented because the regula-tions never have been finalized. The law had called for pub-lication of the regulations in the Federal Register by Oct. 1, 1978. However, the draft regula-tions circulated last summer were found to be so objectionable to colleges of medicine that a massive campaign was mounted to repeal the law. This effort failed in the hectic last stages of the 1978 Con-gress, but the need for a new look at the regulations was acknowl-edged by Sec. Califano. It is hoped that satisfactory revisions will emerge from negotia-tions currently underway between the Association of American Medi-cal Colleges and the Health Care Financing Administration. If not, there may be additional efforts to repeal the law, or attack it in the courts. As near as we can tell, the regulations as currently constituted would not be damaging to our own institution, but they would have a detrimental effect on medical educa-tion in many other prominent teaching hospitals, especially those that care for a large number of indigent patients. The draft regulations required that teaching physicians be compensated on a fee- for- service basis only if certain " tests" were passed: - Private patient test: No patient in a hospital can be considered a private patient for purposes of billing unless 85 percent of the institution's patients are considered private. Institutions with indigent " service" patients cared for by residents would be discriminated against by this provision. Hospitals might need to turn away indigents in order to qualify under the test. - Fiscal test: The majority ( 50 percent or more) of non-medicare patients in any institution must pay 80 percent or more of their bills. Again, patients presenting high finan-cial risks might be turned away in order to meet this test. - Payment to medical schools by hospitals for super-vision of residents is not allowed under the draft regulations ( currently, the U of U College of Medicine does not bill University Hospital for such services, but many Eastern schools do bill their affiliated hospitals). - If the private patient test and the fiscal test are not met, then physicians cannot bill but will be compensated on a cost basis through Part A of Medicare. The stickler here is that the cost formula allows only a part of the actual costs to be taken into account- only the doctor's base salary, rather than total salary, is an allowable cost. Medicare has vastly changed not only the way physi-cians are paid, but the way we train residents. Even though these regulations do not appear to threaten us now, the ideas on which they are based have made a " private" institution of us. All patients at University Hospital must be " private" patients. They must have a personal and identifiable physi-cian who cannot be a resident. Physician services must be personally provided or supervised before a bill can be rendered. Most of us would agree with the philosophy that all our patients should experience one class of medical care. Our challenge is to find ways of training residents effectively when the regulations make it difficult to delegate respon-sibility to them. 1£ F ORUM Editor's Note: Dr. Nabors serves as vice chairperson, Western Regional Minority Affairs Section, Association of American Medical Colleges and is the former head of the State Advisory Committee to the U. S. Commission on Civil Rights. He was named acting assistant dean for minority affairs in the College of Medicine in 1976 and became assistant dean for minority affairs in 1977. Since 1970, the U has graduated 32 Black, Hispanic and Native American physicians. Twenty-six minority students currently ar