Center for Radiological Research

The Columbia University Center for Radiological Research (CRR) was founded more than 75 years ago to better understand the human health risks associated with exposure to ionizing radiation exposure. It is the oldest and largest such research center in the world.^[1] The Center's efforts are focused on unraveling the biological and molecular mechanisms underlying radiation effects in cells, tissues, organ systems and living organisms and how radiation exposure affects human health. Its primary mission is to provide an unbiased, comprehensive and independent source of scientific information about radiation risks to governmental agencies, elected officials, non-profit institutions and private entities to enable them to make sound, evidence based policy decisions. The CRR also provides basic science training to the next generation of radiobiologists, medical and health physicists and clinical radiologists. The Center's multidisciplinary staff encompasses professionals from diverse fields including molecular biology, cell biology, radiation physics, computational physics, engineering, radiation oncology and public health.

History

Harald Rossi

Harald Rossi was born in Vienna, Austria in 1917 and, due to the impending conflict in Europe, emigrated to the United States where he obtained a Ph.D. in physics from Johns Hopkins University in 1942. He served in the US Army during WWII where he met Gioacchino Failla who asked him to join him at Columbia University to work on the Manhattan Project in the Radiological Research Laboratory. During that time, he developed improved methods of radiation dosimetry and was involved in measurements of the early nuclear tests. After the war, Dr. Failla appointed him to the Columbia University staff where he remained for the rest of his career, eventually succeeding Failla as Professor of Radiology and Director of the Radiation Research Laboratory. Dr. Rossi loved instrument design and was instrumental in the evolution of the new field of microdosimetry which has now become essential in radiation protection and delivery of radiotherapy.^[2]

In the 1960s, Dr. Rossi fostered a collaborative effort with Brookhaven National Laboratory, resulting in, among other findings, the identification of high values for neutron RBE at low doses. Further investigations of the relationship between RBE and dose was a continuing interest with important implications for risk assessment, understanding specific action mechanisms of ionizing radiation and explaining the biological effectiveness of different radiations.

His seminal work on neutron RBE was critical to understanding and resolving issues in radiation epidemiology arising from problems with dosimetry in A-bomb survivors at Hiroshima because of the larger neutron component as compared to Nagasaki. During a long and distinguished career, he served on a numerous national and international scientific and review bodies, committees and panels. He was a member of the National Council on Radiation Protection and Measurements from its inception in 1964 and delivered the prestigious NCRP Lauriston S. Taylor Lecture in 1984.^[3] He provided invaluable assistance and counsel to the International Atomic Energy Agency and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Dr. Rossi was President or the Radiation Research Society from 1974 to 1975 and received the Distinguished Scientific Achievement Award of the Health Physics Society in 1987. Harald died in 2000, at 82 years old, after a long battle with heart disease.

Eric J. Hall

Eric J. Hall was born in Wales, received his undergraduate degree from University College, London in 1953 and his doctorate from Oriel College, Oxford University. He is a Fellow of the American College of Radiology and the Royal College of Radiologists. He is currently the Higgins Professor emeritus of Radiation Biophysics at the College of Physicians & Surgeons of Columbia University where he retired as Professor of Radiation Oncology and Radiology in 2007. During his career, he received numerous awards and honors including the Gold Medal of the Radiological Society of North America, the Gold Medal of the American Society of Therapeutic Radiology & Oncology, the Failla Award of the Radiation Research Society, and the Janeway Medal^[4] of the American Radium Society. Still active in research, his interests are varied and broad, including study of the mechanisms underlying radiation induced mutagenesis and carcinogenesis, the health effects of environmental radon exposure, estimation of human health risks from space radiation including the radiobiological effects of neutrons, alpha particles and HZE particles, development of new techniques and approaches for the use of radiotheraphy in cancer treatment, in particular low dose-rate and pulsed brachytherapy and better understanding of the genetic determinants underlying radiosensitivity.

He is the author of over 350 peer reviewed articles and book chapters as well as five books and is the author of Radiobiology for the Radiologist, now in its 7th edition, a widely utilized text for residency training worldwide. He lectures frequently and instructs residents in Radiology and Radiation Oncology during the course of their training.

David J. Brenner

David J. Brenner is the 4th and current Director of the Center for Radiological Research and the Higgins Professor of Radiation Biophysics at the College of Physicians & Surgeons of Columbia University. He has a joint appointment in the Mailman School of Public Health in the Department of Environmental Health Sciences. He has published more than 250 papers in the peer-reviewed scientific literature and is the author of two books on radiation for the lay person: Making the Radiation Therapy Decision and Radon, Risk and Remedy. Dr. Brenner was the recipient of the 1991 Radiation Research Society Annual Research Award, and the 1992 National Council on Radiation Protection and Measurements Award for Radiation Protection in Medicine. In 2011, he received the Failla Award from the Radiation Research Society at the 14th International Congress of Radiation Research in Warsaw, Poland.

Dr. Brenner received a BA and MA in Physics from Oxford University and a MSc in radiation physics from St Bartholomew's Hospital University of London. He received a PhD in Physics from the University of Surrey in 1980. Dr. Brenner’s research focuses on developing mechanistic models for the effects of ionizing radiation on living systems, both in cells and in living organisms. His interests include the effects of high doses of ionizing radiation such as that used in radiotherapy and the effects of low doses of radiation arising from diagnostic, environmental and occupational exposures.

To better apprise the public of relative health risks from radiation exposure, Dr. Brenner has been a frequent media guest expert on the potential health effects of radiation. He has appeared on National Public Radio (NPR), Nightline, and MSNBC among others and has been extensively quoted in the New York Times and the Wall Street Journal. He serves as a scientific advisor to various non-profit cultural institutions concerned about health issues related to radiation exposure including the Metropolitan Opera and America Ballet Theatre.

Teaching

For more than 75 years, the Center has trained undergraduates, medical and graduate students in radiobiology, health physics and medical physics. The faculty instructs medical residents in Radiology and Radiation Oncology in the Columbia University School of Physicians & Surgeons and offers a citywide course for Radiology medical residents as part of their post-graduate training.

International collaboration

The CRR faculty have multiple collaborations with a wide range of international and national educational institutions, research laboratories, academic leaders in radiological sciences, non-profit organizations, advisory groups and governmental agencies and have served as consultants and advisors for the International Commission on Radiological Protection (ICRP), the National Council on Radiation Protection and Measurements (NCRP), Nuclear Regulatory Commission (NRC) and the International Atomic Energy Agency (IAEA). The Center is a member of the International Consortium for Medical Care of Hibakusha (A-bomb survivors) and Radiation Life Science organized by the Graduate School of Biomedical Sciences of Nagasaki University, Japan to promote international collaboration in radiation research and graduate education.

National Security/Radiological Terrorism

The National Institutes of Health (NIH) funded Center for High Throughput Minimally-Invasive Radiation Biodosimetry and the Biomedical Advanced Research and Development Authority (BARDA), funded research efforts at the Center have led to development of novel assays and rapid screening techniques to enable accurate determination of individual radiation exposures in large numbers of potentially exposed persons. The CRR is especially interested in the evaluation of individual risk from radiation exposure and provides advice and guidance to regulatory and governmental officials worldwide.

Expertise

Radiation accidents

The recent Fukushima Daiichi nuclear disaster, as well as previous nuclear accidents in Chernobyl, Three Mile Island and elsewhere have heightened concerns about the human health risks from accidental exposure to radiation. Despite intensive research efforts, considerable uncertainty surrounds the long-term human health risks from prolonged and/or chronic low-level radiation exposure following such incidents.

Department of Energy and NIH funded CRR scientists are working to better understand the human health consequences of low-level radiation exposure using a combination of approaches including laboratory investigations into cellular, molecular and biochemical mechanisms, genetically defined animal models and analysis of human epidemiological data.

Diagnostic and therapeutic uses of radiation

For half a century, the CRR has focused on efforts to refine the use of ionizing radiation in diagnosis and lower the potential risk(s) of x-ray exposure. Several treatment modalities including the now widespread use of high dose-rate fractionated brachytherapy in prostate cancer treatment) were developed by scientists at the CRR.^[5]

CRR investigators have sought to understand the individual health risks from repeated diagnostic CT exposure, the age-related risk of cancer arising from prior radiation exposure and the genetic determinants underlying individual sensitivity to ionizing radiation exposure. A better understanding of the individual genetic determinants of radiosensitivity is fundamental to advances in personalized medicine and individualized application of radiation in diagnosis and treatment.

CRR scientists also focus on evaluation of potential human health risks arising from accidental overexposure during medical diagnosis and treatment.

Radiological terrorism and national security

Worldwide concerns about the potential for nuclear attack or radiological terrorism (e.g., a "dirty bomb”) have escalated in our increasingly uncertain geopolitical environment. Individual health risks following exposure, as well as follow-up medical care and treatment, are directly related to radiation dose. One of the critical and, to date, unmet needs of emergency and medical care workers following such an event is accurately assessing the radiation dose individuals were exposed to.

Scientists at the NIH funded CRR Center for High Throughput Minimally-Invasive Radiation Biodosimetry as well as CRR investigators funded by BARDA, The Biomedical Advanced Research and Development Authority (BARDA), within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services, are developing novel assays and rapid screening techniques to enable accurate determination of individual radiation exposures in large numbers of potentially exposed persons.

At the same time, the potential population-wide health risks from exposure to screening devices employing low-dose radiation exposures (e.g., airport use of backscatter X-ray machines) has become an area of increasing concern. The CRR has led efforts to evaluate individual risk and provide advice and guidance to regulatory and governmental officials.

Space radiation

Compared to ionizing radiation exposures on Earth, astronauts are exposed to potentially higher levels of radiation (mainly protons, HZE particles and neutrons) from galactic cosmic sources, periodic solar flares and trapped radiation belts surrounding our planet. NASA is concerned about the acute and long-term health effects of such exposures to crews during long-term manned space flight. Because of the unique nature of space radiation, it is relatively difficult to reduce exposure by shielding and impossible to eliminate entirely. Efforts to assess radiation risks in space have been further complicated by considerable unknowns regarding the combined biological effects of these radiations and the difficulty in reproducing them in a controlled environment on Earth.

NASA funded investigators at the CRR are examining the effects of space radiation on blood vessel formation and function, cataract formation, and the genetic influence(s) underlying the body’s response to DNA damaging events arising from exposure.

Instrument design and development

The CRR has a long history of innovation and creativity in instrument design for both basic science research and clinical use in radiotherapy and diagnosis, including the development of the Microbeam to deliver radiation into single cells. A fully equipped and well staffed machine shop designs and builds unique, technologically advanced apparatus for both research and experimental clinical use.

Radiobiology

A major focus of the Center for Radiological Research (CRR) is unraveling the biological and molecular mechanisms underlying radiation effects in cells, tissues, organ systems and living organisms. A basic understanding of the process(es) whereby ionizing radiation results in cellular damage and the mechanism(s) whereby cells respond to and repair injury is fundamental to evaluating the human health risks of exposure as well as for optimizing the responsible use of ionizing radiation to diagnose and treat human disease, including cancer. In addition to basic research, translational research being performed at the CRR, in collaboration with other clinical departments at the Medical Center and at other institutions, helps bring research findings from the lab bench to the bedside.

NIH, NASA, Department of Energy and other federally funded CRR research addresses a broad range of questions including molecular details of radiation induced DNA damage and the repair, activation and regulation of specific genes following ionizing radiation exposure, the role of microRNA’s (miRNA) in regulating the damage/repair response, and the chemistry and pathological role of reactive oxygen intermediates and free radicals following radiation exposures.

A large program project grant addresses multiple cellular signaling questions surrounding the Radiation Bystander Response; how cells not directly damaged by ionizing radiation exposure nevertheless are affected by irradiation of nearby cells. Future translation of these findings into clinical practice has direct implications regarding the potential effects of cancer radiotherapy on neighboring healthy tissue.

Radiological Research Accelerator Facility

The Radiological Research Accelerator Facility (RARAF) is a National Resource Center supported by the National Institutes of Health. It is based on a Van de Graaff accelerator and provides well characterized radiations for experiments in radiobiology and radiological physics. Experiments are conducted by members of the CRR, visiting scientists and outside users. A new facility to provide neutrons with energies in the range of 10 to 100 keV is being developed. Available beams include: Single particle microbeam to irradiate individual cell nuclei with single ions; monoenergetic neutrons with mean energies from 0.2 to 15 MeV; charged particles (protons, deuterons, helium-3 and helium-4 ions) with defined LET in the track-segment mode; molecular ions providing pairs of particles of known average separation; 50 to 250 kVp X-rays from standard x-ray machines; and monoenergetic X-rays with energies between 0.3 and 3.0 keV produced by proton-induced x-ray emission (PIXE).

Other environmental exposures and human health risks

In addition to its basic and translational research efforts and experience in understanding the human health effects of ionizing radiation exposure, the CRR is also involved in understanding the health risks arising from exposure to other environmental hazards, most notably naturally occurring Arsenic contamination of groundwater and environmental asbestos exposure. For example, investigators at the CRR were the first to describe the oxidative mechanisms underlying arsenic toxicity.

Advisory Council

The Center has recently created an Advisory Council to provide lay advice, guidance and strategic planning on how best the CRR might serve the public interest and provide timely, accurate, scientific advice and council to local, state and national agencies and organizations. Members include nationally recognized leaders in government, industry, law, public policy, public health and non-profit management.

References

1. NY Times March 26, 2011 Denise Grady; "Countering Radiation Fear with Just the Facts". Scientist at Work
2. Kellerer, AM (1982). "Microdosimetry: reflections on Harald Rossi". Radiat. Prot. Dosim. 99: 1–4.
3. Rossi, Harold (1985). "Lauriston S. Taylor lecture, limitation and assessment in radiation protection". Am. J. Roentgenol. 144: 1–8. doi:10.2214/ajr.144.1.1.
4. DelRegato, JA (1970). "The Janeway Medal and its allegory". Am. J. Roentgenol. Radium Ther. Nucl. Med. 108: 429–430.
5. Brenner, D.J.; Hall, E.J. (1999). "Fractionation and protraction for radiotherapy of prostate carcinoma". Int. J. Radiat. Oncol. Biol. Phys. 43: 1095–1101. doi:10.1016/s0360-3016(98)00438-6.