The Importance of Tissue Banking and Tissue Research

The Importance of Tissue Banking and Tissue Research: Presentation on May 5, 2004 at “Conflicts of Interest, Privacy/Confidentiality, and Tissue Repositories: Protections, Policies, and Practical Strategies” Mark E. Sobel, M. D. , Ph. D. Executive Officer, American Society for Investigative Pathology mesobel@asip. org www. asip. org Copyright © 2004, American Society for Investigative Pathology

The Era of Molecular Medicine Molecular techniques, information generated from the Human Genome Project, and advances in information technology are transforming the: • public’s fears and expectations • practice of medicine Copyright © 2004, American Society for Investigative Pathology

“Eye on the Prize” Improve the public’s health • Conduct biomedical research to increase knowledge and understanding of biological processes. • Respect subjects’ rights and personal autonomy; minimize harm. Copyright © 2004, American Society for Investigative Pathology

Use of Human Biological Materials in Research Human subject protections are applicable not only to clinical trials but also to the use of human biological materials in research studies, including basic science projects. Copyright © 2004, American Society for Investigative Pathology

Human Biological Materials HBMs • Tissue samples • Blood, sputum, urine, bone marrow, etc.

Repositories • Tissue banks • Stored blood/urine samples • Freezers containing HBMs under individual control of principal investigators • Histologic slide files • Eiseman, E. and Haga, Susanne B. , “Handbook of Human Tissue Sources, ” Rand, 1999. Copyright © 2004, American Society for Investigative Pathology

Requirements of Repositories • • • Security of samples IRB oversight Record keeping for informed consent Confidentiality Anonymize samples Increased workload !! Copyright © 2004, American Society for Investigative Pathology

Challenges • Educating researchers • Use of previously archived HBMs that were obtained without consent • Re-use of HBMs • Utility of anonymized samples • Utility of autopsy specimens • Assessment of risk by IRBs: – What is genetic research? – Is “genetic” research necessarily high risk? • Demands on Tissue Repositories Copyright © 2004, American Society for Investigative Pathology

Educating Researchers • • Clinical research Translational research Basic science research What is a

Anonymized Samples • Value in basic science studies • Disadvantages for translational/clinical research – Studies not optimal – Inability to perform long-term follow-up or prognostic studies – Inability to request more of the sample or different samples that don’t duplicate the original – Clinically useful information cannot be conveyed (rare) Copyright © 2004, American Society for Investigative Pathology

Classifying HBMs: Assessment of Risk • Unidentifiable • Anonymous • Anonymized • Identifiable •

Use of HBMs in “Genetic” Research: Assessment of Risk • Germline – – Inheritability Implications for immediate and extended family Implications for ethnic group Use of “normal” tissues • Somatic cell- less risk – Acquired mutations – Use of diseased tissues – No implications for family Copyright © 2004, American Society for Investigative Pathology

Classifying HBMs: Assessment of Risk • Basic Science Studies • Source for substrates • Biochemical studies • Translational Research • Clinical Research Copyright © 2004, American Society for Investigative Pathology

HBMs in Research David Korn, “Contribution of the Human Tissue Archive to the Advancement of Medical Knowledge and the Public Health, ” in “National Bioethics Advisory Commission Report on Research Involving Human Biological Materials: Ethical Issues and Policy Guidance, ” Volume II, January 2000. Copyright © 2004, American Society for Investigative Pathology

HBMs in Research: Early History • Birth of the discipline of pathology: Autopsies performed by physicians on their deceased patients- Renaissance Italy • Origin of the science of pathology: systemic study of the causes, mechanisms and natural history of diseases- 19 th century Germany. Rudolph Virchow- the application of light microscopy to the study of diseased HBMs and the “cell theory of disease” Copyright © 2004, American Society for Investigative Pathology

HBMs in Research • Historical use of archived specimens • Re-use of specimens – Pathologists and the histological slide file • Increased demand for tissues – Tissue microarrays – Gene expression arrays Copyright © 2004, American Society for Investigative Pathology

Re-use of Archived Specimens • DES: – 1960 s: Robert Scully at MGH – Unusual tumor of the vagina- “clear cell adenocarcinoma of the vagina” – Mothers had been treated with the nonsteroidal estrogenic hormone diethylstilbestrol during their pregnancies – Establishment of a national registry – Early detection and cure rate of 90% Copyright © 2004, American Society for Investigative Pathology

Re-use of Archived Specimens • Hepatic Angiosarcoma – 1940 s-1950 s: recognition of carcinogenic potential of occupational and environmental agents from suspicions of a pathologist observing small clusters of unusual neoplasms and thinking about shared histories – Plastic starting materials: vinyl chloride and polyvinyl chloride – Thorotrast (contrast agent) Copyright © 2004, American Society for Investigative Pathology

Re-use of Archived Specimens • Bronchopulmonary Neoplasia – Oscar Auerbach, East Orange, NJ – Histopathological changes in the lungs of autopsied smokers compared to lung cancer – New York Times obituary: “pathologist who found the first evidence in human lung tissue of a link between cancer and smoking” Copyright © 2004, American Society for Investigative Pathology

Archived Specimens • Uranium Mining – Geno Saccomanno – Archive of pulmonary pathological and cytological specimens from underground uranium workers – Bronchogenic carcinoma – Apply direct, rapid modern detection technologies for candidate markers to existing specimens Copyright © 2004, American Society for Investigative Pathology

Autopsy Specimens: Brain • Prion Diseases • Cognitive Dementia – Altzheimer’s disease Copyright ©

Molecular Genetic Methods • Lymphomas: – Sklar and Cossman- 1970 s – Knowledge of normal genetic maturation of lymphocytes into immunocompetent cells – Proliferative lymphoid lesions bearing different histopathologic diagnoses – Fixed and frozen tissue collections Copyright © 2004, American Society for Investigative Pathology

Molecular Virology • Viral Neoplasias – Burkitt’s Lymphoma: childhood lymphoma prevalent in central Africa – 1970 s- Epstein and Barr show that Burkitt’s lymphoma cells harbor a virus – Infectious mononucleosis – Link between infectious mononucleosis and Hodgkin’s lymphoma Copyright © 2004, American Society for Investigative Pathology

Molecular Virology • Human Papilloma Virus (HPV) – Pap smears and collections of specimens – Sequential patterns of progression from normal to dysplastic to neoplastic changes in cervical epithelial cells – HPV difficult to culture – New diagnostic molecular tests for “aggressive” subtypes Copyright © 2004, American Society for Investigative Pathology

Molecular Virology • Influenza – AFIP in 1990 s – Samples of autopsied lung tissue from 198 soldiers who died of the “Spanish Flu” in 1918 – Understanding lethality – Similarity to modern strains Copyright © 2004, American Society for Investigative Pathology

Molecular Virology • Hanta. Virus – 1993 cluster of deaths in the American Southwest – Suspicious clinician, astute epidemiologist, observant Navajo elders, and specimen archives – CDC libraries of viruses, viral proteins and serum specimens – Pulmonary tissues from the autopsied victims Copyright © 2004, American Society for Investigative Pathology

Molecular Genetic Methods • APC gene: adenomatous polyposis coli – Frozen specimens of colorectal cancers – Banked DNA specimens from patients with familial adenomatous polyposis – Chromosome 5 q Copyright © 2004, American Society for Investigative Pathology

Molecular Genetic Methods: Cancer Genome Anatomy Project • 1997 - CGAP launched by NCI • Classify tumor genes by the type of cancer cell they come from and by degree of malignancy • Comprehensive molecular characterization of cancer and precancerous cells Copyright © 2004, American Society for Investigative Pathology

Conclusion (Korn Report): “Now more than ever before, the dramatic growth of the biomedical knowledge base and the applicability of powerful new technologies to tiny samples of diseased human tissues offer promise of major breakthroughs in understanding – and effectively managing- some of the most intractable diseases of humankind. (cont’d) Copyright © 2004, American Society for Investigative Pathology

Conclusion (Korn Report): To achieve that promise, public policy must continue to encourage the accumulation of the human tissue archive and facilitate its accessibility for medical research. ” Copyright © 2004, American Society for Investigative Pathology