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Education and the human genome: Reflections on the 107th Association of American Medical Colleges Meeting
Education and the Human Genome: Reflections on the 107th Association of American Medical Colleges Meeting 1 Wilbur L. Smith, MD
Meeting Overview The American Association of Medical Colleges (AAMC) includes as sponsoring organization the Council of Academic Societies (CAS), of which the Association of University Radiologists (AUR) is a member society. CAS represents the faculty of academic medical centers and defines an agenda for input and implementation by the AAMC. CAS concerns typically deal with teaching and scholarship, including the effect of privacy, ethics, and funding mechanisms on research. Practice issues, while a concern, are usually considered as they affect teaching and scholarship. The AUR has been ably represented in the past by Paul Friedman, MD, and Everitt James, MD; Wilbur Smith, MD, is the current AUR representative. He would be happy to discuss and receive input from AUR members on issues of importance to radiology that might be appropriate for CAS action. The targeted concerns of CAS for 1998 are (a) a new definition of scholarship that follows the paradigm of meaningful objectives, evaluation, and outcome measurement and (b) examination of the effect of managed care on the ability of faculty in academic medical centers to practice scholarship and teaching. Both of these issues will have a marked effect on radiologic practice; however, the second is something we cannot control, while the first has potential for a profound change in faculty evaluation and performance documentation. It appears that this is an area in which CAS may have a profound effect. The new scholarship model era-
Acad Radio11998; 5:312-314 1From the Department of Radiology, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242-1077. Received and acc e p t e d November 24, 1997, Address reprint requests to the author. © 1998, AUR
312
phasizes measurable ends and the value of these deliverables to the institution as the criteria for successful performance by a faculty member. This is a measurable, outcome-driven process that may be very different from more traditional scholarship in which knowledge was sought for its own sake and passed on to students without measurement of outcome. The new model requires thoughtful input in advance of implementation. The plenary portions of the AAMC assembly dealt with issues of leadership, including several addresses with common themes. These themes were best summed up by Judith Rodin, PhD, president of the University of Pennsylvania. Dr Rodin noted that leadership requires five characteristics: courage to support and profess your convictions, strength of your beliefs, wisdom, passion, and vision manifest as a fervent belief in the creation of new knowledge. There is no doubt that we are on the cusp of major changes in the academic medical center. The strategies discussed at the AAMC meeting may help us thrive.
Human Genome Project The human genome project has profoundly changed our understanding of disease and will certainly change the practice of radiology in the near future. A major symposium on the genome project was presented by CAS. Douglas L. Brutlag, PhD, professor of biochemistry and medicine at Stanford, opened the symposium by offering definitions of two key terms in medical genetics: genomics and bioinformatics. Genomics is the study of the gene itself, that is, defining precisely the DNA sequences. Bioinformatics (to a geneticist) is the flow of information from the genes, that is, RNA encoding and protein synthesis. The two concepts are heavily interrelated but also differ in how they are studied and manifest themselves both in health and disease.
Vol 5, No 4, April 1998
Genomics typically involves the mendelian concepts that have traditionally formed the basis of molecular diagnostics and epidemiology. Diagnostic tests for classic mendelian disorders use a "chip" impregnated with RNA bound to a fluorescent substance. This chip is incubated with a DNA sample from the patient. Comparison of the product-imprinted RNA with "normal" standards can demonstrate marked variations from the normal or standard DNA activity pattern for any given chromosome. The key term here is marked variation, as minor variations occur about once per 1,500 base pairs. The genomes of two different normal individuals have about 3 million variances in base pairs! These genetic chips, which give information about both the presence and activity of the genes, are available to screen for over a third of the known mendelian inherited disorders. The bioinformatics portion of the genome project focuses on protein synthesis. This portion will have more profound effects on medicine and imaging as we practice it than. the genomics portion. The proteins generated by RNA contain marked variations both in amino acid sequence and in configuration. These variations represent the interface between genetics and environment, as either can alter protein structure and activity. Currently, the major thrust of the project is in looking for "target" areas in active proteins that can be used either for drug development or for molecular epidemiology. It is not a major step from locating drug activity sites to protein tagging for creation of disease-specific imaging markers that measure when gene synthesis of proteins (eg, the colon cancer gene) become active. The possibilities for diagnosis, monitoring, and targeted treatment with radiopharmaceuticals is enormous. Dr Brutlag emphasized that currently we can diagnose many more diseases than we can treat; however, the distance between basic research and clinical application has never been shorter. Huntington Willard, PhD, from Case Western Reserve, noted several myths and the corresponding facts associated with the human genome project. Myths include the following: (a) we will know the causes of all diseases; (b) there will be easy presymptomatic diagnosis for a variety of disorders; (c) effective gene therapy will soon be available. The facts are (a) we will know all the genes; (b) in selected disorders it will be possible to predict the likelihood of presymptomatic disease; (c) no disease has yet been cured with gene therapy. In the genetics of disease there are currently two forms of genetic variation. Mendelian variation is present in conditions in which a clearly defined chromosomal muta-
EDUCATION A N D THE H U M A N G E N O M E
tion defines the disease (eg, cystic fibrosis). Complex variation is present in patients in whom common variations in the genome do not necessarily directly cause the disease, but they do interact with other factors, including the environment, to cause disease (eg, alcoholism). Diseases that result from complex variation tend to affect older individuals and may occur as a result of gene activation or the deactivation of a protective genome. In the immediate future the genome project will provide a "genomic triage" for these conditions, defining populations that need intensive screening. Cancer genetics in particular is likely to "explode" within the next 5-10 years. The implications for imaging are huge. High-risk populations that require intensive imaging screening and diagnostic services will be defined; however, for some diseases where mass screening is now used without genetic triage, the population needing screening will dwindle. Balancing these competing needs for imaging diagnosis and screening will change the role of the radiologist within a decade. Translational research in imaging, as related to the genome project, offers immense opportunities for radiology in the next 2 decades. Nancy Wexler, PhD, from Columbia University, chairs the Ethical, Legal, and Social Advisory Committee of the National Institutes of Health Human Genome Project. She emphasized the human implications of the project by demonstrating the effects of genetic information on the lives of patients. In her own work with Huntington chorea she noted a substantial psychiatric event (either suicide attempt or profound depression) in nearly 1% of individuals who received information on their own genetic proclivity to disease. It appears that humans have limited capacities for tolerating the implications of learning their future. We in imaging who will be called on to do genetic-directed screening need an acute sensitivity to this fact.
The other major theme of the AAMC meeting was a change in the paradigm of education. Jordan Cohen, MD, president of the AAMC, delivered an eloquent address reminding all that dissemination of knowledge is the prime function of a university. He noted that, at present, universities have a near monopoly on education, but, as with other monopolies, the educational monopoly can be rapidly eroded if the educational needs of students are not met in an efficient and effective manner. From this realization the Medical School Objectives Project (MSOP)
313
was founded and charged with developing objectives for medical school training that accurately reflect both the needs of medicine and those of society. The primary questions being asked are, What knowledge, attitudes, and skills does a physician need for the year 2000? How do we best select individuals who possess desirable precepts of our profession, including altruism, respect, compassion, honesty, and integrity? Dr Cohen suggested that while testing and grades represent and remain a threshold measure for predicting knowledge acquisition, we must develop other measures to select students who are likely to manifest the precepts and behaviors we desire. While emphasizing the paradigm of accountability, we must also learn to measure the achievement of these goals. The MSOP is, therefore, a long-range, ongoing program to improve the educational process through educational research which yields measurable results. An accompanying program on MSOP was cosponsored by the CAS. Kenneth Ludmerer, MD, from Washington University, emphasized the historical changes in educa-
314
tional needs of medical learning, including a shift from " acute to chronic disease management, a new era of information management, and an emphasis on resource restraint. He noted that without careful attention, many educational experiences could become more vocational than educational, particularly in the ambulatory setting. Rita Charon, MD, from Columbia University and president of CAS, discussed the need of educational programs to relate to the real concerns of students and the society in which they hope to practice. She identified faculty education as a major goal of the MSOP, observing that it is hard to ask students to conform to a higher standard of behavior than their mentors. The emphasis of the MSOP on objectives, assessment, and measurement closely parallels the educational program of the "new scholarship" that will be a major project of CAS in 1998. The initial MSOP efforts emphasize undergraduate medical education; however, lest any of us become smug or doubt its relevance, graduate medical education (residency training, fellowships) and continuing medical education are defined as the future targets of the MSOP process.
Meeting Overview The American Association of Medical Colleges (AAMC) includes as sponsoring organization the Council of Academic Societies (CAS), of which the Association of University Radiologists (AUR) is a member society. CAS represents the faculty of academic medical centers and defines an agenda for input and implementation by the AAMC. CAS concerns typically deal with teaching and scholarship, including the effect of privacy, ethics, and funding mechanisms on research. Practice issues, while a concern, are usually considered as they affect teaching and scholarship. The AUR has been ably represented in the past by Paul Friedman, MD, and Everitt James, MD; Wilbur Smith, MD, is the current AUR representative. He would be happy to discuss and receive input from AUR members on issues of importance to radiology that might be appropriate for CAS action. The targeted concerns of CAS for 1998 are (a) a new definition of scholarship that follows the paradigm of meaningful objectives, evaluation, and outcome measurement and (b) examination of the effect of managed care on the ability of faculty in academic medical centers to practice scholarship and teaching. Both of these issues will have a marked effect on radiologic practice; however, the second is something we cannot control, while the first has potential for a profound change in faculty evaluation and performance documentation. It appears that this is an area in which CAS may have a profound effect. The new scholarship model era-
Acad Radio11998; 5:312-314 1From the Department of Radiology, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242-1077. Received and acc e p t e d November 24, 1997, Address reprint requests to the author. © 1998, AUR
312
phasizes measurable ends and the value of these deliverables to the institution as the criteria for successful performance by a faculty member. This is a measurable, outcome-driven process that may be very different from more traditional scholarship in which knowledge was sought for its own sake and passed on to students without measurement of outcome. The new model requires thoughtful input in advance of implementation. The plenary portions of the AAMC assembly dealt with issues of leadership, including several addresses with common themes. These themes were best summed up by Judith Rodin, PhD, president of the University of Pennsylvania. Dr Rodin noted that leadership requires five characteristics: courage to support and profess your convictions, strength of your beliefs, wisdom, passion, and vision manifest as a fervent belief in the creation of new knowledge. There is no doubt that we are on the cusp of major changes in the academic medical center. The strategies discussed at the AAMC meeting may help us thrive.
Human Genome Project The human genome project has profoundly changed our understanding of disease and will certainly change the practice of radiology in the near future. A major symposium on the genome project was presented by CAS. Douglas L. Brutlag, PhD, professor of biochemistry and medicine at Stanford, opened the symposium by offering definitions of two key terms in medical genetics: genomics and bioinformatics. Genomics is the study of the gene itself, that is, defining precisely the DNA sequences. Bioinformatics (to a geneticist) is the flow of information from the genes, that is, RNA encoding and protein synthesis. The two concepts are heavily interrelated but also differ in how they are studied and manifest themselves both in health and disease.
Vol 5, No 4, April 1998
Genomics typically involves the mendelian concepts that have traditionally formed the basis of molecular diagnostics and epidemiology. Diagnostic tests for classic mendelian disorders use a "chip" impregnated with RNA bound to a fluorescent substance. This chip is incubated with a DNA sample from the patient. Comparison of the product-imprinted RNA with "normal" standards can demonstrate marked variations from the normal or standard DNA activity pattern for any given chromosome. The key term here is marked variation, as minor variations occur about once per 1,500 base pairs. The genomes of two different normal individuals have about 3 million variances in base pairs! These genetic chips, which give information about both the presence and activity of the genes, are available to screen for over a third of the known mendelian inherited disorders. The bioinformatics portion of the genome project focuses on protein synthesis. This portion will have more profound effects on medicine and imaging as we practice it than. the genomics portion. The proteins generated by RNA contain marked variations both in amino acid sequence and in configuration. These variations represent the interface between genetics and environment, as either can alter protein structure and activity. Currently, the major thrust of the project is in looking for "target" areas in active proteins that can be used either for drug development or for molecular epidemiology. It is not a major step from locating drug activity sites to protein tagging for creation of disease-specific imaging markers that measure when gene synthesis of proteins (eg, the colon cancer gene) become active. The possibilities for diagnosis, monitoring, and targeted treatment with radiopharmaceuticals is enormous. Dr Brutlag emphasized that currently we can diagnose many more diseases than we can treat; however, the distance between basic research and clinical application has never been shorter. Huntington Willard, PhD, from Case Western Reserve, noted several myths and the corresponding facts associated with the human genome project. Myths include the following: (a) we will know the causes of all diseases; (b) there will be easy presymptomatic diagnosis for a variety of disorders; (c) effective gene therapy will soon be available. The facts are (a) we will know all the genes; (b) in selected disorders it will be possible to predict the likelihood of presymptomatic disease; (c) no disease has yet been cured with gene therapy. In the genetics of disease there are currently two forms of genetic variation. Mendelian variation is present in conditions in which a clearly defined chromosomal muta-
EDUCATION A N D THE H U M A N G E N O M E
tion defines the disease (eg, cystic fibrosis). Complex variation is present in patients in whom common variations in the genome do not necessarily directly cause the disease, but they do interact with other factors, including the environment, to cause disease (eg, alcoholism). Diseases that result from complex variation tend to affect older individuals and may occur as a result of gene activation or the deactivation of a protective genome. In the immediate future the genome project will provide a "genomic triage" for these conditions, defining populations that need intensive screening. Cancer genetics in particular is likely to "explode" within the next 5-10 years. The implications for imaging are huge. High-risk populations that require intensive imaging screening and diagnostic services will be defined; however, for some diseases where mass screening is now used without genetic triage, the population needing screening will dwindle. Balancing these competing needs for imaging diagnosis and screening will change the role of the radiologist within a decade. Translational research in imaging, as related to the genome project, offers immense opportunities for radiology in the next 2 decades. Nancy Wexler, PhD, from Columbia University, chairs the Ethical, Legal, and Social Advisory Committee of the National Institutes of Health Human Genome Project. She emphasized the human implications of the project by demonstrating the effects of genetic information on the lives of patients. In her own work with Huntington chorea she noted a substantial psychiatric event (either suicide attempt or profound depression) in nearly 1% of individuals who received information on their own genetic proclivity to disease. It appears that humans have limited capacities for tolerating the implications of learning their future. We in imaging who will be called on to do genetic-directed screening need an acute sensitivity to this fact.
The other major theme of the AAMC meeting was a change in the paradigm of education. Jordan Cohen, MD, president of the AAMC, delivered an eloquent address reminding all that dissemination of knowledge is the prime function of a university. He noted that, at present, universities have a near monopoly on education, but, as with other monopolies, the educational monopoly can be rapidly eroded if the educational needs of students are not met in an efficient and effective manner. From this realization the Medical School Objectives Project (MSOP)
313
was founded and charged with developing objectives for medical school training that accurately reflect both the needs of medicine and those of society. The primary questions being asked are, What knowledge, attitudes, and skills does a physician need for the year 2000? How do we best select individuals who possess desirable precepts of our profession, including altruism, respect, compassion, honesty, and integrity? Dr Cohen suggested that while testing and grades represent and remain a threshold measure for predicting knowledge acquisition, we must develop other measures to select students who are likely to manifest the precepts and behaviors we desire. While emphasizing the paradigm of accountability, we must also learn to measure the achievement of these goals. The MSOP is, therefore, a long-range, ongoing program to improve the educational process through educational research which yields measurable results. An accompanying program on MSOP was cosponsored by the CAS. Kenneth Ludmerer, MD, from Washington University, emphasized the historical changes in educa-
314
tional needs of medical learning, including a shift from " acute to chronic disease management, a new era of information management, and an emphasis on resource restraint. He noted that without careful attention, many educational experiences could become more vocational than educational, particularly in the ambulatory setting. Rita Charon, MD, from Columbia University and president of CAS, discussed the need of educational programs to relate to the real concerns of students and the society in which they hope to practice. She identified faculty education as a major goal of the MSOP, observing that it is hard to ask students to conform to a higher standard of behavior than their mentors. The emphasis of the MSOP on objectives, assessment, and measurement closely parallels the educational program of the "new scholarship" that will be a major project of CAS in 1998. The initial MSOP efforts emphasize undergraduate medical education; however, lest any of us become smug or doubt its relevance, graduate medical education (residency training, fellowships) and continuing medical education are defined as the future targets of the MSOP process.