The Ramazzini Institute
for Occupational and Environmental Health Research   

Inside

Who Are We?

Arthur Frank^[1]
The Scientific Contributions
of Iving J. Selikoff, MD

     Dr. Irving J. Selikoff was a remarkable physician and scientist who contributed to knowledge in several areas of medicine, and who helped train a generation of occupational physicians who now work around the world. He spent most of his career at the Mount Sinai Hospital, and subsequently the Mount Sinai School of Medicine after it opened, and clearly left his mark at that institution, among many others.
     Irving Selikoff attended medical school during World War II in Edinburgh, Scotland, with his educational program there interrupted by war activities which required one of his years of training to occur in Australia. Upon completing his studies in Scotland, he returned to New York City where he began work at the Sea View Sanatorium on Staten Island. At that institution he became well versed in matters related to tuberculosis, and was instrumental in assisting in the development of isoniazide, for many years a standard treatment for tuberculosis, and for which he was honored with the Lasker Award in 1955.
     His early scientific papers had to do with a variety of topics, going beyond tuberculosis to the study of amylodosis. He also tested the efficacy and safety of isoniazide on pregnant women.
     With several colleagues he established an early group practice in Patterson, New Jersey and it was at the Patterson Clinic that he first began to see patients from the nearby Unarco plant, and made the diagnosis of asbestosis. From this initial involvement he developed an international study looking at 17,800 unionized asbestos workers in North America. Working together with Dr. E. Cuyler Hammond of the American Cancer Society, and others, Dr. Selikoff published widely on the subject of asbestos-related disease, especially the cancers associated with asbestos. He was the first to point out, in a landmark paper in the Journal of the American Medical Association, of the synergistic effect of carcinogens, namely asbestos and cigarettes. With the opening of the Mount Sinai School of Medicine in 1968 he became active in this institution.
     Dr. Selikoff began training both medical students and established an occupational medicine residency program for advanced training. It was through these activities that there is now a generation of occupational physicians trained by him that work widely throughout the United States, and in Europe and Israel as well. His vision was broad, and many of his activities took on an international flavor.
     Dr. Selikoff was active in the New York Academy of Sciences where he served as a Governor, and was later made a Life Governor, an honor awarded to few. He also received other numerous awards, honorary degrees, and honorary fellowships, and was often honored by his colleagues at Mount Sinai. He served the broader scientific community by consulting with many national and international agencies, and served with distinction on the National Cancer Advisory Board. Dr. Selikoff also recognized that there was power in unity, and started several important scientific organizations.
     The first major organization he founded, and served as president, was the Society for Occupational and Environmental Health. This brought together scientists, academics, corporate physicians, government officials, and others in a concerted effort to address important scientific problems. He also linked up with scientists around the world, notably Dr. Cesare Maltoni, of Italy, in looking at a variety of occupational cancer problems. Together with Maltoni, and others, Dr. Selikoff founded in the 1980s the Collegium Ramazzini, named after the father of occupational medicine. This organization, a body of some 180 physicians and scientists devoted to occupational and environmental health issues, became a leading international organization contemplating the problems of workplace and environmental exposures on a worldwide basis. Dr. Selikoff served for many years as its first president.
     In addition, Dr. Selikoff understood the developments in many fields of science, and recognized that through work in the area of human genetics that additional developments would occur in the diagnosis and treatment of human disease. His vision was to integrate genetic research with occupational and environmental exposures, and to deal with these issues in an ethical and forthright manner.
    Dr. Irving J. Selikoff is surely recognized as one of the leading pulmonary and occupational physicians of his time, and his ultimate contribution will be more fully clarified as he takes position among the physicians who have made a significant impact on the health of mankind.

[1] Arthur Frank, MD, PhD, is a graduate of Mt. Sinai School of Medicine and an early post-graduate student  of Dr. Selikoff. He served as Selikoff’s deputy in the Environmental Sciences Laboratory prior to leaving Sinai for research in Cell Biology at the National Institutes of  Health. Currently, he is Professor of Occupational and Environmental Health at Drexel University School,of Public Health, Philadelphia, and Adjunct  Professor at the University of Texas Health center at Tyler.  Dr. Frank is Treasurer of The Ramazzini Institute and Medical Director of  the Institute-assisted Amarillo Health Consortium.

William N. Rom

     William N. Rom, MD, MPH, pictured above at the National Press Club in 2000 receiving the Selikoff Award for Cancer Research, is President of The Ramazzini Institute and Director of the Pulmonary Division of New York University School of Medicine. He was a post-graduate student of Dr. Selikoff and a member of Selikoff’s Taskforce on Genetics in the Workplace.
     Dr. Rom has established an Institute-facilitated Lung Cancer Biomarker Center as part of the National Cancer Institute’s Early Detection Research Network. Co-Principal Investigator is Dr. Arthur Frank.
     The mission of the Center is to develop new and more effective methods of identifying pre-cancerous cell changes and lesions and to detect lung cancer at a very early stage. The Center is able to closely monitor those who show any signs of having pre-cancerous cells and refer workers to treatment programs earlier to increase their chance of survival.
     Now in its second year of operation, the Center is focused on those at highest risk of lung cancer, namely those with a history of smoking and workplace exposures to known causes of cancer, such as asbestos, solvents, and ionizing radiation.
     Patients currently are drawn from two populations, utility and construction workers in the New York Metropolitan area and active and former workers at the Department of Energy’s Pantex Nuclear Weapons Facility in Amarillo, Texas, recruited through the Amarillo Health Consortium organized by the Amarillo Metal Trades Council of the Metal Trades Department, AFL-CIO and The Ramazzini Institute.
     The total number of workers in the program will be limited to about 1000 individuals, who will have access to the earliest cancer detection tests and may have access to new ways to interrupt the chain of events that lead to cancer.

      During the past year at the NYU Center, 346 individuals have been evaluated with spiral chest CT scan, spirometry [a breathing test], sputum, blood and questionnaire for respiratory symptoms and occupational exposures. Nineteen patients have returned for recommended annual follow-up screening. In Texas, 219 current and retired Pantex Nuclear Weapons plant workers have been screened with chest radiographs, spirometry, sputum, and blood.
     The New York University Center is specially equipped to use advanced methods of bronchoscopy for diagnosis, including fluorescent bronchoscopy. Both populations are providing blood and sputum, which will be analyzed to see if changes in cell structures and chemical changes and mutations in the DNA can be detected of the p53, K-ras, and Rb genes, and associated enzymes, in the web of factors that promote or suppress cancer.
     From these studies, new tests are being devised to detect pre-cancerous conditions or to be used in treating cancer in the earliest and most treatable stages. Possible new treatments may be devised based on identifying cancer-suppressing genes whose function may have been silenced by cancer promoting chemical changes or by deletion. These tests will use DNA from blood, sputum or bronchial brushes. Center scientists are also looking at genes in actual lung cancer resections and evaluating gene expression in microdissected pre-cancerous lesions. Hopefully these tests will lead to novel approaches to identify lung cancer at its earliest stages, and provide a rationale for future chemoprevention studies in individuals at high risk.
     In addition to the multiple levels of protections for confidentiality and privacy afforded research subjects by National Institutes of Health regulations, including Institutional Review Boards at the University of Texas and New York University, recruitment, education, and follow-up procedures are monitored by the Institute to be sure that they are designed to protect the decision making rights of the participants in the program through their personal involvement and access to full information necessary in making a rational choice.

Antonio Giordano

     In the picture above, Antonio Giordano, M.D., Ph.D. (right), Professor of Biology and Medicine and director of the Sbarro Institute for Cancer Research and Molecular Medicine in the College of Science and Technology at Temple University, and post doctoral fellow Marcella Macaluso perform electrophoresis on DNA samples extracted from human tissue that have been placed in agarose gel. Agarose gel electrophoresis of DNA is the first step in doing Rb2/p130 diagnostic tests for breast, lung and other cancer. Giordano discovered Rb2/p130, a tumor suppressor gene, while a researcher at Temple's Fels Institute for Cancer Research and Molecular Biology in the early 1990s.
     Dr. Giordano, a recipient of The Selikoff Cancer Research Award and a director of The Ramazzini Institute, was a member of Dr. Selikoff’s taskforce on genetics in the workplace. His most recent work has demonstrated that the progressive lack of the tumor suppressor gene Rb2/p130 could be an early indicator of prostate cancer in males. He and his colleagues looked at the pattern of protein expression in a variety of molecular markers in prostate cancer, including Rb2, p107, p27, p53, Mdm-2, and Ki-67.
     "The results we obtained with Rb2, which is a tumor suppressor gene, indicate that this gene demonstrates a lower expression in the prostate as it progresses from normal to cancerous," says Antonio Giordano, Ph.D., M.D., head of the Sbarro Institute and one of the study's lead researchers. "The lack of this tumor suppressor gene can, in a certain sense be, an indicator of tumor progression in the prostate gland." Giordano says the results of the study show that in addition to PSA (prostate specific antigen), a protein whose level in the blood increases in some men who have prostate cancer, there are other factors that could serve as major indicators for individuals susceptible to developing prostate cancer, which is the leading cause of death by cancer of American men.
     The study is leading to an early diagnostic test for cancer. Giordano notes that while doctors can now test for the level of Rb2 expression in an individual by examining tissue samples taken from the prostate through a biopsy, his team of researchers aim to develop a quick and inexpensive blood test that will yield the same results.Giordano adds that his co-researchers are also aiming to develop a therapeutic model to re-introduce Rb2 back into the prostate. By doing so, they hope to determine if the gene is able to block the growth of cancer cells. The study is an international collaborative effort, and included the Sbarro Institute, Thomas Jefferson University, Drexel University, the University of Naples and the Cancer Institute of Naples in Italy. The National Institutes of Health and the Sbarro Health Research Organization funded the research.
     Giordano points out that the task now for researchers is to determine how genes communicate with one another in the development of cancer. "Clearly there is a 'communication' taking place," he adds. "Probably it will not only be our Rb2 gene involved, but it will be like an orchestra, in which all these genes have a specific role. How genes cooperate among themselves in the development of cancer will be "a fantastic tool," he says, “in the hands of an oncological clinician or surgeon because it will allow them to tailor more specific therapies based on the genetic damage in each one of the genes."

     The Ramazzini Institute is expanding its Board to aid a planned increase in its activity in the United States and Europe. William N. Rom, MD, MPH, has been elected President of The Ramazzini Institute. He becomes the third president of the Institute, replacing Arthur C. Upton, MD, who has been elected President Emeritus and Board Chair. Paul Brandt-Rauf, MD, PhD has been elected to the Board to replace Dr. Rom, who previously served in that position. The addition to its leadership of Dr. Brandt-Rauf, highly respected internationally by government, management, labor and public health groups, strengthens the Institute’s role in facilitating occupational and environmental health research consortia.
     Dr. Rom is Professor and Director, Division of Pulmonary Medicine at New York University School of Medicine. He was a post-graduate student at Mt. Sinai School of Medicine and close associate of Dr. Irving J. Selikoff, the founding president of the Institute, and a member of his Taskforce on Genetics and the Workplace from which The Ramazzini Institute evolved. With Institute Treasurer Arthur Frank, MD, PhD, newly-appointed Professor of Environmental and Occupational Health at Hahnemann School of Public Health, he is conducting cancer detection research through the Institute-facilitated Amarillo [Texas] Health Consortium.
     Dr. Upton, who was also a member of Selikoff’s Taskforce, is Clinical Professor of Occupational and Environmental Medicine at the University of Medicine and Dentistry of New Jersey. A former Director of the National Cancer Institute, he has chaired the committee of the National Academy of Science that sets the basis for the environmental regulation of ionizing radiation.
     Dr. Brandt-Rauf, incoming Chair of the Department of Environmental Health Sciences at Columbia University’s School of Public Health, has been serving as Editorial Advisor to the Institute’s web journal, Genes, Ethics & Environment! He participated in the 1990 meeting of scientists, labor leaders and government officials from the United States and other countries, in Airlie, VA, convened by Dr. Selikoff, Dr. James D. Watson, President of Cold Spring Harbor Laboratory, and Institute Vice President Sheldon W. Samuels. The meeting defined the primary agenda of the Institute: the ethical and controlled application of the new molecular biological technologies to risk assessment and management in the work and community environments.

The Ramazzini Institute for Occupational and Environmental Health Research, Solomons Island, Maryland, Is a 501[c]3 registered charity.

The Institute operates in the United States and Europe “without walls” through partner organizations, to facilitate collaborative projects and consortia for research and education.

     The Institute reserves to itself only those education, organization, research and program evaluation functions for which it has unique capacities. All activities are directed by volunteers who use the resources of partner organizations for activities funded by the Institute’s Selikoff Fund, grantors or contracting agencies. The Institute grew out of a taskforce* convened by the late Dr. Irving J. Selikoff to implement his agenda for the ethical application of the benefits of advances in molecular biology to diseases of the work and community environments.

· The Institute is now entering its third year as publisher of Genes, Ethics & Environment!, an internet public policy journal. No subscription is charged, and no advertising is accepted. Readers are primarily university faculty, state and national government officials, scientists, and members of labor, environmental and genetic disorder support groups. Government, university, and private institutions with websites have provided links to our site from their own. Among the most popular search machines in the internet, for key subjects within its special domain, GEE! essays more often than not are listed among the first ten.

· The partnership of the Institute, the University of Texas Health Center at Tyler, and the Amarillo Metal Trades Council has resulted in a community controlled Amarillo Health Consortium. Besides serving the needs of nuclear weapons and other workers in Amarillo, the Consortium serves as a model program. With seed funds from the Institute’s Selikoff Fund and program support through New York University Medical Center and the University of Texas of funds from the National Cancer Institute, the Consortium is providing research support, family and community education for an early cancer detection research program that includes genetic testing. AHC is preparing to facilitate long term medical surveillance of former nuclear workers funded by the Department of Energy and conducted for them by Institute scientists. The Institute, which facilitated the NCI and DOE proposals, but in keeping with its ‘no walls’ policy was not the applicant organization, will evaluate the screening program. In cooperation with the International Association of Machinists and Aerospace Workers, research is being completed to aid the design of a peer group and family-oriented counseling program to mediate the effects of environmental and socioeconomic stresses, and assist workers and families interpret the result and meaning in their lives of medical tests.

· The Institute continues to explore the ecology of human values that impinge genetic research in the workplace, underlie the need for protections of workers and families from genetic discrimination, and affect the fair distribution of the benefits of advances in genetic science. This work is reported in professional and lay conferences and through publication. Volume two of Genes, Cancer, and Ethics in the Work Environment, the Institute’s inaugural publication, is expected to be published by OEM Press in 2002. The book will include the Institute’s evaluation of the Department of Energy’s Beryllium Workers Medical Surveillance program, which has been published in the web journal, and its probe of DOE employee assistance programs.

· An historical and prospective comparative study is being conducted in mining communities of the interaction of moral and cultural values in the perceptions and causes of occupational disease and associated suicidal and parasuicidal behaviors. The research is taking place on the western slopes of the Rocky Mountains and in the Erz Gebirge of Central Europe. This work began with a special taskforce that entered East Germany and northern Czechoslovakia immediately after the fall of the “Berlin Wall”. Appointed by Dr. Selikoff, the investigative group was headed by Dr. Hans-Joachim Woitowitz of Justus-Liebig University of Giessen, and included the late Dr. Cesare Maltoni of the University of Bologna and Sheldon W. Samuels of The Ramazzini Institute. The investigators have accessed medical and environmental records, historical archives, and clinics. Mine authorities, community leaders and workers have been interviewed. Preliminary reports have been published in volume one of Genes, Cancer, and Ethics in the Work Environment and in lay and professional journals. The research is expected to be completed in 2003, and published in a definitive monograph in 2004. Interim results shaped the Institute’s work among nuclear weapons workers in DOE facilities and in the design of a model for the ethical application of genetic and other medical surveillance tools in the workplace.

President Emeritus and Board Chair: Arthur C. Upton, MD, Clinical Professor of Occupational and Environmental Medicine, University of Medicine and Dentistry of New Jersey*

President: William N. Rom, MD, MPH, Professor and Director, Division of Pulmonary Medicine, New York University School of Medicine*

Vice President: Sheldon W. Samuels, Director Emeritus of Health, Safety and Environment, Industrial Union Department, AFL-CIO*

Treasurer : Arthur Frank, MD,. PhD, Professor of Environmental and Occupational Health at Hahnemann School of Public Health [July 1, 2002] .

Director: Paul Brandt-Rauf, MD, PhD. Chair, Department of Chair of the Department of Environmental Health Sciences at Columbia University’s School of Public Health [July 1, 2002] .

Director: Patricia A. Buffler, PhD, MPH, Professor of Epidemiology and Dean Emerita of the School of Public Health, University of California at Berkeley.

Director: Michael Flynn, President, CREST: International Association of Machinists and Aerospace Workers

Director: Antonio Giordano, MD, PhD, President, Sbarro Institute and Professor of Biology and Medicine,
College of Science and Technology, Temple University*

Director: Ivan Gut, MD, PhD, DSc, Center of Hygiene and Occupational Diseases, Czech Institute of Public Health

Director: Philip J. Landrigan, MD, DIH, Professor and Chair, Community Medicine, Mt. Sinai School of Medicine*

Director: Tor Norseth, MD, PhD, Senior Toxicologist, Norwegian Occupational Health Institute

Director: Knut Ringen, DrPH, MHA, MPH, Occupational Health Consultant, Seattle, Washington

Director: Hans-Joachim Woitowitz, MD, PhD, Professor and Director, Institute for Occupational And Social Medicine, Justus Liebig University of Giessen, Germany

Director: Charles Xintaras, DSc, Environmental Health Scientist, Athens, Greece