Paper 38th LAURISTON S. TAYLOR LECTURE: ON THE SHOULDERS OF GIANTS - RADIATION PROTECTION OVER 50 YEARS Fred A. Mettler, Jr.* Abstract—Most advances in science, technology, and radiation protection are not truly new ideas but rather build upon a foundation of prior work and achievements by earlier generations of scientists and researchers. This paper summarizes major achievements over the last 50–70 y in the various areas involved in radiation protection as well as giving information about some of those who were, and are, significant contributors. Health Phys. 108(2):102–110; 2015 Key words: National Council on Radiation Protection and Measurements; Health Physics Society; historical profiles; radiation protection
INTRODUCTION THIS IS the 38th Lauriston S. Taylor Lecture on the occasion of the 50th anniversary of the National Council on Radiation Protection and Measurements (NCRP). To begin, a few words about Laurie are necessary (Fig. 1). He was born in 1902 and began his incredible career in 1925 at Western Electric (which later became Bell Laboratories). At the very young age of 23 y, he was one of the founders of the International Commission on Radiation Units and Measurements (ICRU), and at age 26 y, he was a founder of the International Commission of Radiological Protection (ICRP). In 1927, he began work at the U.S. National Bureau of Standards and retired in 1965 after 37 y. He then worked for the National Academy of Sciences and in 1972 began work as President of NCRP until 1977. He was Honorary President of the NCRP until his death at age 102 y (Taylor et al. 2014). I first met Laurie at an NCRP meeting in the early 1980s when we were still considering and estimating effects from an all-out nuclear exchange. I asked him how common *University of New Mexico, Imaging Service, New Mexico VA Health Care System, 1501 San Pedro Boulevard, SE, Albuquerque, NM 87108. The author declares no conflicts of interest. For correspondence contact the author at the above address or email at [email protected]. Supplemental Digital Content is available in the HTML and PDF versions of this article on the journals Web site www.health-physics.com. (Manuscript accepted 7 October 2014) 0017-9078/15/0 Copyright © 2014 Health Physics Society DOI: 10.1097/HP.0000000000000234
people could have any idea what radiation doses were and how they could protect themselves. He smiled and told me a “secret,” which was “gin and tonic.” He assured me that the quinine sulfate in tonic water would scintillate at high dose levels, and if that happened, it was time to drink a lot of gin and become hypoxic (which would confer at least a minimal degree of radiation protection and a lot of comfort). The title of this lecture is derived from a quote commonly attributed to Sir Isaac Newton, which is, “If I have seen farther than others, it is because I was standing on the shoulders of giants.” In truth, a very similar quote is attributed to Bernard of Chartres in 1159. As the quote implies, most advances in science, technology, and radiation protection are not truly new ideas but rather build upon a foundation of prior work and achievements by earlier generations of scientists and researchers. A contrasting quote is attributed to Harold Abelson: “If I have not seen as far as others, it is because giants were standing on my shoulders.” This paper also summarizes major achievements over the last 50–70 y in the various areas involved in radiation protection as well as giving some information about those who were major contributors. I have been very fortunate in my education and early career to have been mentored by quite a number of these giants and will give a few examples. As a child, I was probably unknowingly influenced by my father’s colleagues, Harald Rossi (great microdosimetrist and luminary of ICRU) and Edith Quimby (a founder of nuclear medicine and Columbia Radiation Laboratory). The two of them would babysit my sister and me at scientific meetings. As an unknown high school student, I was looking for a biology science project and simply wrote to Dr. George Beadle and Edward Tatum (Nobel Prizes 1958) asking for ideas. They sent me enough material to outfit my entire basement into a microbiology laboratory to examine effects of radiation mutation on metabolism in molds. As a college student, I was accepted for a summer job by Dr. Boris Rajewsky at the Max Planck Institute of Biophysics, and he then referred me for a summer job with Alexander Hollaender at Oak Ridge National Laboratories. From there, I was referred to Louis Hempelmann at Rochester, Robert Brent at Thomas Jefferson, Robert www.health-physics.com
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Fig. 1. Lauriston S. Taylor.
Moseley at the University of Chicago, Edward Webster and Dade Moeller at Harvard, and Norman Rasmussen at the Massachusetts Institute of Technology. There was an intermediate stint as an intern for the U.S. Atomic Energy Commission at the Health and Safety Laboratory in New York with John Harley. From these very helpful and encouraging giants, I learned about radiation biology, effects on membranes and animals, epidemiology, medical physics, public health, nuclear engineering, radiology, and nuclear medicine. For the majority and remainder of this lecture, I would like to focus on the major achievements over the last 50–70 y in the various areas involved in radiation protection. In reviewing the history, it is clear that much of the progress we have made is the result of remarkable advances in technology, although some were due to new ideas and concepts. All, however, have been based on the foundational work of a great number of humble, sharing, and brilliant people. Since this is the Taylor Lecture of the NCRP, I have chosen to focus primarily (but not exclusively) on those from the United States. HEREDITARY EFFECTS AND PREGNANCY Hermann Muller is known for his work in 1927 when x-rays were used as the first intentional mutagen in fruit
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flies. He initially worked at Columbia University and then in Texas, Germany, and Russia, where he was head of the genetics laboratory in St. Petersberg. One interesting story is that due to the wars in Europe, he wanted to return to the United Kingdom and was forced to take a clipper boat airplane from Lisbon. After a delay of several days due to bad weather, the plane took off, and after an hour of flight, there was panic as 160 strains of very rare fruit flies in small jars were thought to have been left on the wharf. The pilot refused to turn around, but happily soon after the flies were discovered. Dr. Muller had put them in a breadbox, and the crew, believing it was actually bread, had stored the box in the plane’s kitchen. Interestingly, Dr. Muller was one of the first to warn of the potential harmful effects from radiology. As a result, he was criticized by many physicians for scaring patients away from radiology (a scenario that has been repeated over ensuing decades). Bill and Liane Russell (along with Paul Selby) were the scientists at Oak Ridge National Laboratory who conducted the genetic megamouse experiments and developed the specific-locus test (to detect recessive mutations in first generation offspring) and skeletal mutation changes. The mouse data were fundamental in estimating the genetic risk from radiation in humans. There are three population geneticists who stand out and worked with the atomic bomb survivors and their offspring. James Neel’s most interesting contribution was not actually observation of a hereditary radiation effect but rather the increased occurrence of neurofibromatosis and other abnormalities as a result of consanguineous marriages in Japan. He later went on to study Amazon tribes to determine whether there was a difference in population genetics for indigenous tribes versus urban populations. One of James Crow’s major roles was as one of the earliest proponents of the use of DNA in forensics. Seymour Abrahamson is best known for his study design of the F1 generation of the atomic bomb survivors. Over the last 50 y, there has been a lot of information gained on radiation effects during the in utero period and on the possible hereditary effects of radiation in humans (NCRP 2013). Dr. Robert Brent finished college when he was only 18 y old and went on to become the world’s greatest expert in teratology. He has compiled an amazing record of service to pregnant women, including over 25,000 consultations, most of which were with women considering an abortion because of minimal fetal radiation doses. Dr. Brent and his wife are also well known philanthropists to medical education. Jack Schull has contributed greatly with his study of mental retardation and microcephaly of children following high dose in utero exposure of atomic bomb survivors. Important negative findings regarding hereditary effects have been published regarding the offspring of
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atomic bomb survivors and childhood cancer survivors. Much of the latter work is from the Childhood Cancer Survivor Study published by Marilyn Stovall, John Boice, and others. RADIATION BIOLOGY There have been a number of consequential advances in radiation biology. Perhaps the first of these was the description of radiation track structure and the prediction of linear-quadratic dose response by Douglas Lea in his book Actions of Radiations on Living Cells (Lea 1946). Cloning of mammalian cells in tissue culture by Philip Marcus and Theodore Puck allowed investigation into cell survival curves after radiation exposure. Of interest is that while these researchers were able to grow cells together in a medium, they were unable to get single cells to grow and form colonies. The breakthrough came from the brilliant Hungarian atomic physicist Leo Szilard, who was having lunch one day with Dr. Marcus. He suggested simply fooling the single cells into believing that they were not alone by having a platform with single cells submerged in a container with a layer of feeder cells so that the single cells would recognize the diffusible substances from other cells (Puck and Marcus 1956). Hypoxia was known to confer radiation resistance as early as 1923; however, the notion that chronic hypoxia in tumors was a problem for radiation therapy was clearly defined by Thomlinson and Gray (1955) and triggered efforts to increase oxygen tension or use radiation other than photons. The future of radiation biology will almost certainly be combined with genetics, including DNA sequencing, genomics, gene expression, and epigenetics. Currently, we are fortunate to have a number of exceptional radiobiologists including Sally Amundson, Edward Azzam, Joel Bedford, David Brenner, Kathryn Held, Ann Kennedy, and Amy Kronenberg to provide the foundations for future work. RADIATION DOSES, LIMITS, AND DOSIMETRY Radiation doses and units became an issue soon after radiation was discovered and resulted in the formation of ICRU in 1925. Early units included the “roentgen” and the “rep.” By 1953, the rad and rem were in use. One of the luminaries of ICRP was Harold Wyckoff. There have been a number of changes over the last 50 y. The “genetically significant dose” has essentially disappeared as a result of the realization that hereditary effects in humans have not been as great as initially feared. Confusion continues with the terms rem and Sievert being used for both equivalent and effective dose. The first NCRP committee that I was on was tasked with recommending how to transition from older traditional units to the International System of Units (SI). I remember
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attending a meeting chaired by Randy Caswell when he announced that the transition should be completed in exactly 15 y. I inquired where the number 15 had magically come from, and I was greeted with laughter from the other committee members. I was told that they would all be retired within 15 y and would not need to be bothered, and they figured I was young enough to learn the SI units and conversions. There are a number of issues with dose limits. ICRP has reduced the recommended dose limits, and the United States has not kept pace with the changes. Most people do not realize that the ICRP reduction was not only based upon consideration of recent epidemiology but also upon the fact that historically the vast majority of recorded occupational doses were well below recommended limits, and there was no need to continue to allow a few employers to keep exposing employees near the former annual limits. A major continuing problem with dose limits is the public’s confusion regarding the ICRP 20 mSv annual dose limit for “existing situations” and reconciling this with the 1 mSv annual public dose limit. DOSIMETRY AND DOSE RECONSTRUCTION Dosimetry has been advanced by the remarkable increase in computer power, and this has led in turn to development of Monte Carlo modeling and voxel computed tomography (CT) scan-based male, female and child phantoms. There also has been significant development of dosimetry models of the respiratory and alimentary tracts. This work has been accomplished by many people, but notable standouts include Wesley Bolch, Keith Eckerman, and Rich Leggett. Major efforts in environmental dose reconstruction have resulted in a better understanding of the methodologies needed (NCRP 2009a). External dosimetry has seen progress in reassessment of the atomic bomb survivors. We have seen dose reconstruction of atomic veterans, releases from the Nevada test site, Hanford, Apollo, Rocketdyne, and Rocky Flats. There also have been significant efforts at dose reconstruction at foreign sites such as Chernobyl, Techa River, and Fukushima. People instrumental in these exceptional efforts include Lynn Anspaugh, John Auxier, Andre Bouville, Bruce Napier, Dan Strom, and John Till. ENVIRONMENTAL ISSUES Radiation studies of entire ecosystems were conducted in the 1950s at Brookhaven National Laboratories. The classic textbook on radioactivity in the environment was published by Merril Eisenbud (1973). Merril is a classic story of humility and how families often do not know that giants live in their own houses. One day after Fukushima,
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I received a telephone call from Jonathan LaPook, M.D., the medical correspondent for CBS news. He wanted to know what the effects of radioactivity in the environment might be. I mentioned that the classic book was published by Merril Eisenbud. He said “Merril? Why he is my uncle, and I never knew exactly what he did for a living.” I asked him if he had a copy of the book, and he indicated in the affirmative. I suggested that he take a few hours and actually look at his uncle’s book and then call me back (which he did). After the mid 1970s, funding for research into environmental issues declined markedly, and it was not until Chernobyl (and later Fukushima) that interest was rekindled and many studies were done, particularly regarding cesium. Interest continues with the extraordinary work of Ward Whicker and others. Ward has pointed out that most ecology populations appear unaffected if individual humans are protected. HEALTH PHYSICS The last 50 y has seen health physics grow and mature into a defined specialty (Roessler 2005). The Health Physics Society was founded in 1956 and the American Board of Health Physics in 1960. Herbert Parker (the first Taylor Lecturer) is generally credited with being the father of health physics. There were also remarkable women in the field, most notably Elda Anderson who worked both at Los Alamos and Oak Ridge on the Manhattan Project. J. Newell Stannard was a giant in many respects, but probably his most consequential achievement was the development of the Atomic Energy Commission educational program at the University of Rochester, which produced many giants in our field. While there are many who contributed to the health physics field, I would like to particularly single out John Cameron, John Frazier, and Ken Mossman. Before I did research for this lecture, I knew that John Cameron was instrumental in establishing a paramount radiological physics program at the University of Wisconsin and that he was in large part responsible for the change from film badges to TLDs. What I had not realized was that he essentially invented bone densitometry, which is widely used throughout the world today. RADON The link between mining and lung cancer has been known for over a century. The link with radon as the cause of lung cancer in miners became apparent in the 1950s as a result of John Harley’s work. In the last 50 y, there have been several important advances in understanding radon and its effects. Naomi Harley has contributed to a coherent
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approach between radon dosimetry and epidemiology. The interaction of smoking and radon has been elucidated by the exceptional work of Jay Lubin et al. (1994) with uranium miner studies. Most recently, North American and European meta-analyses have been able to provide data on the risks associated with residential radon (Krewski et al. 2006).
STATISTICS AND EPIDEMIOLOGY Statistics always has been one of my least favorite subjects, and I appreciate anybody who can simplify things. The statistician who has made statistics and epidemiology understandable for me is the quiet and thoughtful Charles Land. The most powerful, understandable and simple presentation of statistics is found in his four-line table showing how many people are needed to find a carcinogenic effect and different dose levels. Other statisticians who have made significant contributions are Dale Preston (formerly of the Radiation Effects Research Foundation) and Daniel Stram. The last half-century has seen major changes in radiation epidemiology. Enough time has passed that we have a fair appreciation of site-specific cancer estimates and their differences, although the small number of excess cancers often tempts people to treat all solid cancers as the same (which can sometimes lead to unfortunate and incorrect conclusions). Radiation epidemiology has discovered meta-analysis and used it as a means to generate more statistical power. While this can be helpful, the recent metaanalysis of nuclear worker studies has shown that one study with bias or errors can substantially influence the combined result (Wakeford 2005). It has also become abundantly clear that there is a practical lower limit to radiation epidemiology and that risks from doses in the range of 10–100 mGy require very large numbers. John Boice has engaged in this remarkable effort with a “million person study.”
RISK ASSESSMENT, LINEAR NON-THRESHOLD, AND PROBABILITY OF CAUSATION Probabilistic risk assessment methods became widely used after the publication of the WASH‐1400 report chaired by Norman Rasmussen in the 1970s. I was lucky enough to take his nuclear engineering course at the Massachusetts Institute of Technology, and it quickly became clear to all of us students that Norm was a devoted Red Sox fan. Every time the Red Sox were playing at Fenway, we had a teaching assistant for that class. Over the next three decades, both risk-informed and risk-managed decision making methods were employed. Current risk experts whose work stands out are David Hoel and Chris Whipple. Certainly adoption of the linear non-threshold (LNT)
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hypothesis for stochastic effects at low doses has been a major turning point in risk assessment. The LNT hypothesis has generated controversy for several decades, and it may or may not be true. Dr. Arthur Upton (former Director of the National Cancer Institute), who is known for his cautious judgment, chaired the committee that authored NCRP Report No. 136, and the committee concluded that there was “no conclusive evidence to reject the assumption” (NCRP 2001). The concept of LNT is not a comforting one for the public and has caused lots of angst and, some would argue, unnecessary expense. Interestingly, Laurie Taylor himself was not a fan of the LNT hypothesis. UNCERTAINTY At low doses, small numbers of excess radiationinduced cancers often lead people to say, “We don’t know what happens at low doses.” This is, of course, untrue, as we know that if effects were large, we would detect them. As a result of developments in the uncertainty field, we have had to add words such as “epistemic” and “aleatory” to our radiation vocabulary. One very useful advance has been a comprehensive evaluation of the uncertainties associated with risk estimation (NCRP 2012). These efforts have been led primarily by Owen Hoffman and his group. Small amounts of uncertainty do not bother me, but I discovered that Owen once wrote a paper on whether Crater Lake was really 592 or 594 m deep. His interest developed from his former career as a National Park Ranger. RISK COMMUNICATION AND PSYCHOLOGICAL ISSUES Risk communication and evaluation of psychological issues associated with radiation exposure are some of the most important issues but with the least progress (in terms of the public). Psychological issues have been acknowledged to be the most important health effect at Chernobyl and probably at Fukushima. Paul Slovic made noteworthy advances with his publications on risk perception, acceptability and issues such as amplification. Excellent work continues in this area by Steven Becker, Evelyn Bromet, Paul Locke, and Susan Wiltshire. This problem remains huge and transcends accidents, acceptance of nuclear power, and radiation uses in medicine. One of my favorite examples (pointed out to me by Abel Gonzalez) of how we have confused the public comes from the Fukushima experience. The limit for 137Cs in water is 10 Bq L−1, while for orange juice it is 100 times higher at 1,000 Bq L−1. For edible rice, the limit is 1,000 Bq kg−1, which is 10 times higher than for rice wrapping paper (100 Bq kg−1).
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NUCLEAR WEAPONS AND TERRORISM From the 1950s until the 1980s, we lived with the real threat of nuclear weapons during the Cold War, and then for about 25 y the threat subsided. With the rise of militant religious groups and more unstable governments having or developing nuclear weapons, the threat has reemerged. While there has been no intentional use of a nuclear weapon over the last 65 y, I predict that one will be used within the next 50 y. The additional threats of dirty bombs and improvised nuclear devices have many people and agencies worried. The foundational work of both Bryce Breitenstein and Pat Durbin on internally deposited radionuclides and decorporation is invaluable. Development of scenarios and models by Brooke Buddemeier, Cham Dallas, Charles Miller, and Robert Whitcomb has helped us to understand the nature and magnitude of the threats and prepare for them. Research on radioprotective methods by Judith Bader and Norman Coleman are essential, as are the long-standing efforts of William Blakely with regard to rapid personal dosimetry. NUCLEAR POWER AND NUCLEAR WASTE In the early and mid 1970s, nuclear power seemed to have a bright future. The accident at Three Mile Island in 1979 and Chernobyl in 1986 cast a pall over the landscape. The recent multi-reactor meltdown at Fukushima has been an additional problem. The expected renaissance never happened, nor is it likely to happen anytime soon. The Obama administration’s shutdown of Yucca Mountain has left us with a serious spent-fuel problem, and the “temporary” solution seems to be dry cask storage. If there is one bright light and giant in this field, it is the extraordinary work and effort of Richard Meserve (former NRC Commissioner and now President of the Carnegie Institution), who works tirelessly to try to make our politicians understand the issues. Legacy waste from nuclear weapons is a monumental problem that is going to be with us for a long time. At Hanford, there are 56 million gallons of waste in 177 tanks, 60 of which are leaking. Remediation began 20 y ago, and it is hoped that it may be finished in another 35 y at a currently estimated cost of $300 billion. NATURALLY OCCURRING RADIOACTIVE MATERIAL, RADIUM, PLUTONIUM AND URANIUM Since the mid‐1940s, we have learned a lot about the metabolism and dosimetry of radium, plutonium, and uranium. Radium received attention first with the pioneering work of Robley Evans and later Otto Raabe. Their foundational work has received an increase in attention as a result of the petroleum extraction industry and radium containing scale in oil pipes. The plaintiff’s attorneys have figured out
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that the oil companies have deep pockets and have filed many lawsuits due to exposure to scale. Whether hydraulic fracking will add to these naturally occurring radioactive material issues remains to be seen. Wright Langham at Los Alamos was known as the father of plutonium. The 50 y follow-up of the Los Alamos plutonium workers was conducted by George Voelz. George was another giant whose children were not exactly sure of what their father did. After George and I published an article on terrorism in the New England Journal of Medicine, I remember a remark by Valerie Voelz (who was then a medical student) that all her classmates were duly impressed, and she had no idea her father was so famous. Uranium and depleted uranium became an issue during the Gulf War and a public issue about uranium fabrication facilities. John Boice and his group have done many studies indicating that generally uranium does not cause a detectable increase in cancer (likely due to its slow decay rate and metabolic properties). DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY As documented in NCRP Report No. 160, there was doubling of the radiation exposure to the U.S. population between 1980 and 2006 largely as a result of medical diagnostic exposure, particularly CT scanning (NCRP 2009b). Most people do not realize that it was the success of the Beatles that resulted in development of the CT scanner. The unexpectedly large revenue that EMI Music received from the Beatles’ records allowed them to fund a pie-in-thesky research project by one of their engineers (Godfrey Houndsfield) and resulted in the invention of the CT scanner. CT scans, however, are associated with high doses compared to most other diagnostic examinations, and there have been instances of hair loss and skin erythema from improper use. In addition, the issue of potential increase in cancer rates in children was noted by David Brenner. This led a number of radiologists to champion a very successful effort to lower doses from CT scanning, particularly to children. Those radiologists include, among others, Kimberly Applegate, Donald Frush, and Julie Timins. We are also fortunate to have a number of medical physicists who have contributed to this issue, including Larry Dauer, Walter Huda, Cynthia McCollough, Mahesh Mahadevappa, and Terry Yoshizumi. The other major change in diagnostic radiology has been the complete switch in the last 15 y from film-based images to digital techniques. In 1994, the U.S. Food and Drug Administration (FDA) issued a warning about radiation injuries that were occurring as a result of high exposures during fluoroscopically guided interventional procedures. There has been a huge educational effort over the last decade by Steven Balter,
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Donald Miller, and Louis Wagner. In spite of this, we still see occasional skin ulcers from such procedures. These may decrease in the future with the FDA requirements for new machines to display dose indices in real time. Mammography has been a true success story. Over the last 40 y, we have gone from using high dose film to low dose film and now to digital techniques. FDA and the American College of Radiology instituted a required accreditation program that not only checks dose levels and image quality but also requires a certain level of annual experience and annual continuing education. All of this has resulted in lower dose but more importantly more accurate diagnoses. A lot of the credit for this goes to Stephen Feig, Lawrence Rothenberg, and Edward Sickles. NUCLEAR MEDICINE Progress in nuclear medicine has occurred in fits and starts and is a good example of how one invention often must wait for another to be successful. Prior to the 1960s, images were obtained with a rectilinear scanner using a variety of high energy radiopharmaceuticals. Hal Anger invented the gamma camera in 1956, but it was not widely used until the 1960s when 99mTc could be produced in hospitals from a generator. Gordon Brownell demonstrated the possibility of medical imaging with the positron-emission tomography scanner in the 1970s, but it was not until 30 y later that the technique became widely used after it was combined with a CT scanner and small cyclotrons for local isotope production became practical. James Adelstein has advanced radiation protection issues in nuclear medicine, and Mike Stabin has been instrumental in making dosimetry tools widely available. RADIATION ONCOLOGY Current radiation oncology practice relies on pivotal work of a number of giants. In the 1960s, George Casarett and Philip Rubin published an absolutely classic two volume book on clinical radiation pathology, which showed the underlying changes in tissues with various treatment protocols (Rubin and Casarett 1968). Rodney Withers was instrumental in elucidating the early and late response of tumor and normal tissues to various fractionation schemes (Withers 1969). The last several decades have seen profound changes in radiation oncology. Use of radium and 60Co are essentially nonexistent, and treatment now most commonly involves linear and particle accelerators. There has been rapid development of integrated computerized treatment planning as well as development of hybrid diagnostic and therapeutic equipment. The future is likely to be focused on patient- and tumor-specific biology. Extensive data on issues related to
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pediatric patients have been published by a number of authors but most notably by Louis “Sandy” Constine. Even though radiation oncology equipment has become much more technologically advanced, there continue to be occasional serious accidents. Since 1990, there have been large accidents in Costa Rica, France, Panama, and Spain all attributed to human error, and one might suppose that such accidents will continue in the future. ACCIDENTAL WHOLE AND PARTIAL BODY EXPOSURE Very high acute whole body exposures result in the acute radiation syndrome, which has a number of phases manifested by damage to various body systems. Historically, patients would die within a few weeks from a gastrointestinal syndrome or somewhat later from bone marrow failure. There have been advances in treatment, but this, in turn, has revealed other problems. The accident at Chernobyl involved 134 patients with acute radiation sickness. The world’s leading expert in this field is Angelina Guskova. With her team and advances in intensive care unit medicine, she was able to overcome these early problems with patients surviving doses as high as 8 Gy (Mettler et al. 2007). In a later accident in Belarus with a patient receiving ~12–15 Gy, the gastrointestinal and bone marrow phases were treated only to have the patient succumb at 90 d from death due to pulmonary failure. In the Tokaimura criticality accident in Japan, a remarkable physician, Dr. Kaz Maekawa, employed heroic and state-of-the-art medicine, but a patient who received 17 Gy expired at 82 d and a second who received about 10 Gy expired at 210 d (Maekawa 2000). It appears now that while short-term survival can be obtained with heroic measures, long-term survival after doses of 10–12 Gy and higher are unlikely until the late multi-organ system failure issues can be resolved. Accidents occurring as a result of stolen or lost high activity radioactive sources have continued to occur sporadically and result in serious injuries. NONIONIZING RADIATION Radiation protection to most of us in the field usually refers to ionizing radiation. NCRP has published a few reports on ultrasound and radiofrequency effects. These have been the result of notable work by experts such as Wesley Nyborg, Gary Zeman, and Marvin Ziskin.
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and Syria), and there are more than 119 person-y of experience in space. Ionizing radiation has always been an issue not only from the magnitude of exposure but the effects of particle and ion radiation. Francis Cuccinota has been the leader in this field, and his work will become even more important as Virgin Galactic is now selling space trips to the public, and plans are afoot to go to Mars. SPECIAL GIANTS While a discussion of giants and their work is interesting, I found in my research that there were three additional categories of giants that need to be mentioned separately. The first was the recognition that giants sometimes come in pairs and are married. Whether their efforts are additive or synergistic, I have not decided. The obvious pairs of giants are: Shirley and Michael Fry at Oak Ridge and their work in radiation medicine and biology, Naomi and John Harley and their work on radon, Genevieve and Charles Roessler and their work in health physics, and Liane and Bill Russell and their genetics research. There is one philanthropic giant, Yohei Sasakawa, who generously funds many foundations but also large radiation programs. His Nippon Foundation provided tens of millions of dollars for the major study of childhood thyroid effects after Chernobyl. He also has funded a number of programs related to the Fukushima Nuclear Accident. Of interest is that after the tsunami and earthquake, Sasakawa himself went to the accident areas and simply handed out cash to thousands of displaced persons so that they could buy food and water. There are giants who left us too quickly. These include Goeff Howe at Columbia and his work on lung and breast cancer epidemiology and Elaine Ron at the National Cancer Institute (NCI) and her outstanding work on the epidemiology of thyroid cancer. There is an interesting (and maybe even true) story about Geoff. He had become totally blind from diabetes and had a guide dog that he used occasionally. Most of us who saw Geoff give slide presentations at meetings would swear that he still could see. In any case, a visitor to see Geoff was having tea and cookies. When Geoff turned his head away from the cookies, the dog would snatch one. When Geoff turned his head toward the cookies, the dog would pretend he had done nothing. I guess even Geoff’s guide dog thought he could still see. PUBLISHED MATERIALS
SPACE Most people forget our early accomplishments in space and do not know that 12 people have walked on the moon, that there have been more than 535 astronauts in space from 37 countries (including Cuba, Malaysia, Mongolia,
Authors can be giants as a result of imparting information to many students. The classic textbook on radiobiology by Eric Hall is in its seventh edition and has been used by many generations of radiology and radiation oncology residents (Hall and Giaccia 2011). Jerrold Bushberg and his
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group also have produced a classic text on physics of medical imaging. The work of journal editors is huge and largely unappreciated; yet without their tireless efforts, dissemination of crucial material would not happen. Standout editors include Michael Fry, Gen Roessler, Mike Ryan, Richard Vetter, and Richard Wakeford. COLLECTIONS OF GIANTS In review of radiation protection over the last 50–70 y, there are some places where giants congregate, and giants seem to beget other giants. Specific universities always seem to crop up in the radiation literature. These include the Columbia University, University of California Berkeley, University of Chicago, University of Rochester, and University of Wisconsin. The Radiation Effects Research Foundation has provided the foundational epidemiological study of the atomic bomb survivors (Ozasa et al. 2012) with scientists such as Gil Beebe, Evan Douple, Seymour Jablon, David Hoel, Jim Neel, Dale Preston, William Schull, S. Shigematsu, Roy Shore, and now Bob Ullrich. The Lovelace Inhalation Toxicology Research Institute in Albuquerque has done remarkable work in inhalation and metabolism with scientists such as Bruce Boecker, Ray Guillmette, Fletcher Hahn, Joe Mauderly, Roger McClellan, and Bruce Muggenberg. Pacific Northwest National Laboratories has spawned giants such as Bill Bair (the first Ph.D. in radiation biology in the world), Les Braby, Tony Brooks, Ron Kathren, Bill Morgan, Bruce Napier, Kathryn Pryor, and Dan Strom. One cannot overlook Oak Ridge with such greats as Shirley and Michael Fry, Ron Goans, Clarence Lushbaugh, Bob Ricks, Dick Toohey, and Al Wiley. There are many unsung heroes in our federal and state government organizations. The most prominent is the NCI Radiation Epidemiology Branch with Gil Beebe, John Boice, Andre Bouville, Ruth Kleinerman, Martha Linet, Jay Lubin, Kiyohiko Mabuchi, Bob Miller, and Elaine Ron. Stars at FDA have included John McCrohan, Don Miller, Orhan Suleiman, and John Villlforth; at NRC, Don Cool and Vince Holahan; at EPA, Michael Boyd, Mary Clark, and Julian Preston; and at DOE, Stephen Musolino. There are a number of state regulators who deserve special mention, including Jill Lipoti and James Yusko. UNSCEAR AND ICRP As the U.S. Representative to the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) for 28 y, I have stood on the shoulders of many of my Alternate Representatives and Advisors. They have always been superb and a credit to our country. It is impossible to mention them all. They have included Charlie Meinhold and Warren
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Sinclair and for the last decade Lynn Anspaugh, John Boice, Naomi Harley, Vince Holahan, and Julian Preston. Since ICRP was formed in1928 by Laurie Taylor and others, it has been at the forefront of radiation protection. There have been many illustrious members, including Rolf Sievert. My interactions with the Main Commission included two who stand out in my mind and who taught me a lot: Daniel Beninson and Sir Edward Pochin. Both were integral in developing the concepts of weighting factors and effective dose. Once I found that Sir Edward Pochin was in Albuquerque visiting Sandia Laboratories, but nobody had invited him to dinner. I invited him to our house and told my two young boys that a “knight” was coming to dinner. They were very excited, no doubt expecting somebody on a horse and in a full suit of armor. When the doorbell rang and there was a white-haired man in a blue suit without even a sword, they were very disappointed. However, after dinner they asked him “Well if you really are a knight, how many dragons have you killed?” He smiled and put one of them on each of his knees and told them of many fights that he had with “anti-nuclear” dragons over the years. He did admit that he had not actually killed any of them, but my children went to bed happy anyway. ICRP continues to flourish, especially under the direction of Claire Cousins, the only woman to be chair of the Commission in almost a century. NCRP In preparing for this lecture, I reread many NCRP reports, and I wondered how many people had contributed to NCRP reports and who had done the most and was the true NCRP giant. As a result, I reviewed all reports from No. 1 through 174 and made a spreadsheet of all who were chairs or committee members. I did not include consultants and advisors. In total there were 1,354 persons. There were nine people who had been on six committees, four people who had been on seven committees, two people who had been on eight committees, and six people who had been on nine committees. However, the standouts were John Poston and Edith Quimby, who both had been on 12 committees! Giants could not do their work without the NCRP staff, and there are giants among them. These of course include the past presidents Laurie Taylor, Warren Sinclair, Charlie Meinhold, and Tom Tenforde; and Bill Beckner, Tom Fearon, Costa Maletskos, Will Ney, Marvin Rosenstein, Dave Schauer, Jim Spahn, and Ivan White. Very special recognition goes to Laura Atwell and Cindy O’Brien. CONCLUSION It has been an honor to give the 38th Taylor Lecture on the occasion of the 50th anniversary of NCRP and an
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interesting experience to reflect on the people and changes in radiation protection over more than the last half a century. All of us have stood on the shoulders of giants during our careers. While I have mentioned many giants, I am sorry that I could not mention them all. I am humbled at how many giants graciously advised and mentored me over the years. Radiation protection and medicine are timelimited careers, but family is forever. My personal giants include my wife, Gloria, and my sons, Erik and Larsen. A photograph of the night sky by my friend Ralph Johnson reminds me that while we have many giants in our field, there remains a vast universe out there about which we know very little. Note: A pdf file of the lecture slides can be found as Supplemental Digital Content, http://links.lww.com/HP/A39. REFERENCES Eisenbud M. Environmental radioactivity. New York: Academic Press; 1973. Hall E, Giaccia A. Radiobiology for the radiologist. Philadelphia, PA: Lippincott Williams and Wilkins; 2011. Krewski D, Lubin JH, Zielinski JM, Alavanja M, Catalan VS, Field RW, Klotz JB, Létourneau EG, Lynch CF, Lyon JL, Sandler DP, Schoenberg JB, Steck DJ, Stolwijk JA, Weinberg C, Wilcox HB. A combined analysis of North American casecontrol studies of residential radon and lung cancer. J Toxicol Environ Health 69:533–597; 2006. Lea DE. Actions of radiations on living cells. Cambridge UK: Cambridge University Press; 1946. Lubin J, Boice JD, Edling C. Radon and lung caner risk: a joint analysis of 11 underground miner studies, 1994. Washington, DC: U.S. Department of Health and Human Services; 1994. Maekawa K. An overview of medical care for highly exposed victims in the Tokaimura accident. In: Tsujii H, Akashi M, eds. Proceedings of international symposium on the criticality accident in Tokaimura: medical aspects of radiation emergency. Chiba, Japan: National Institute of Radiological Sciences; 2000. Mettler FA, Guskova AK, Gusev I. Heath effects in those with acute radiation sickness from the Chernobyl accident. Health Phys 93:462–469; 2007.
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National Council on Radiation Protection and Measurements. Evaluation of the linear-nonthreshold dose-response model for ionizing radiation. Bethesda, MD: NCRP; Report No. 136; 2001. National Council on Radiation Protection and Measurements. Radiation dose reconstruction: principles and practice. Bethesda, MD: NCRP; Report No. 163; 2009a. National Council on Radiation Protection and Measurements. Ionizing radiation exposure of the population of the United States. Bethesda, MD: NCRP; Report No. 160; 2009b. National Council on Radiation Protection and Measurements. Uncertainties in the estimation of radiation risks and probability of causation. Bethesda, MD: NCRP; Report No. 171; 2012. National Council on Radiation Protection and Measurements. Preconception and prenatal radiation exposure: health effects and protective guidance. Bethesda, MD: NCRP; Report No. 174; 2013. Ozasa K, Shimizu Y, Suyama A, Kasagi F, Soda M, Grant EJ, Sakata R, Sugiyama H, Kodama K. Studies of the mortality of atomic bomb survivors, report 14, 1950–2003: an overview of cancer and noncancer diseases. Radiat Res 177: 229–243; 2012. Puck TT, Marcus PI. Action of x-rays on mammalian cells. J Exp Med 103:653–666; 1956. Roessler G. The 50th anniversary of the Health Physics Society. Health Phys News XXXIII(5); May 2005. Rubin P, Casarett G. Clinical radiation pathology. Philadelphia, PA: WB Saunders; 1968. Taylor NW, Sinclair WK, Gorson RO. In memoriam, Lauriston S. Taylor: 1902–2004. 2014. Available at: http://hps.org/ aboutthesociety/people/inmemoriam/LauristonTaylor.html. Accessed 2 April 2014. Thomlinson RH, Gray LH. The histological structure of some human lung cancers and the possible implications for radiotherapy. Brit J Cancer 9:539–549, 1955. Wakeford R. Cancer risk among nuclear workers. J Radiol Prot 25:2; 2005. Withers HR. Capacity for repair in cells of normal and malignant tissues. In: Bond VP, ed. Proceedings of the Carmel conference on time and dose relationships in radiation biology as applied to radiotherapy. Upton NY: BNL Report 50203 (C‐57); 1969: 54–69.
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INTRODUCTION THIS IS the 38th Lauriston S. Taylor Lecture on the occasion of the 50th anniversary of the National Council on Radiation Protection and Measurements (NCRP). To begin, a few words about Laurie are necessary (Fig. 1). He was born in 1902 and began his incredible career in 1925 at Western Electric (which later became Bell Laboratories). At the very young age of 23 y, he was one of the founders of the International Commission on Radiation Units and Measurements (ICRU), and at age 26 y, he was a founder of the International Commission of Radiological Protection (ICRP). In 1927, he began work at the U.S. National Bureau of Standards and retired in 1965 after 37 y. He then worked for the National Academy of Sciences and in 1972 began work as President of NCRP until 1977. He was Honorary President of the NCRP until his death at age 102 y (Taylor et al. 2014). I first met Laurie at an NCRP meeting in the early 1980s when we were still considering and estimating effects from an all-out nuclear exchange. I asked him how common *University of New Mexico, Imaging Service, New Mexico VA Health Care System, 1501 San Pedro Boulevard, SE, Albuquerque, NM 87108. The author declares no conflicts of interest. For correspondence contact the author at the above address or email at [email protected]. Supplemental Digital Content is available in the HTML and PDF versions of this article on the journals Web site www.health-physics.com. (Manuscript accepted 7 October 2014) 0017-9078/15/0 Copyright © 2014 Health Physics Society DOI: 10.1097/HP.0000000000000234
people could have any idea what radiation doses were and how they could protect themselves. He smiled and told me a “secret,” which was “gin and tonic.” He assured me that the quinine sulfate in tonic water would scintillate at high dose levels, and if that happened, it was time to drink a lot of gin and become hypoxic (which would confer at least a minimal degree of radiation protection and a lot of comfort). The title of this lecture is derived from a quote commonly attributed to Sir Isaac Newton, which is, “If I have seen farther than others, it is because I was standing on the shoulders of giants.” In truth, a very similar quote is attributed to Bernard of Chartres in 1159. As the quote implies, most advances in science, technology, and radiation protection are not truly new ideas but rather build upon a foundation of prior work and achievements by earlier generations of scientists and researchers. A contrasting quote is attributed to Harold Abelson: “If I have not seen as far as others, it is because giants were standing on my shoulders.” This paper also summarizes major achievements over the last 50–70 y in the various areas involved in radiation protection as well as giving some information about those who were major contributors. I have been very fortunate in my education and early career to have been mentored by quite a number of these giants and will give a few examples. As a child, I was probably unknowingly influenced by my father’s colleagues, Harald Rossi (great microdosimetrist and luminary of ICRU) and Edith Quimby (a founder of nuclear medicine and Columbia Radiation Laboratory). The two of them would babysit my sister and me at scientific meetings. As an unknown high school student, I was looking for a biology science project and simply wrote to Dr. George Beadle and Edward Tatum (Nobel Prizes 1958) asking for ideas. They sent me enough material to outfit my entire basement into a microbiology laboratory to examine effects of radiation mutation on metabolism in molds. As a college student, I was accepted for a summer job by Dr. Boris Rajewsky at the Max Planck Institute of Biophysics, and he then referred me for a summer job with Alexander Hollaender at Oak Ridge National Laboratories. From there, I was referred to Louis Hempelmann at Rochester, Robert Brent at Thomas Jefferson, Robert www.health-physics.com
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Fig. 1. Lauriston S. Taylor.
Moseley at the University of Chicago, Edward Webster and Dade Moeller at Harvard, and Norman Rasmussen at the Massachusetts Institute of Technology. There was an intermediate stint as an intern for the U.S. Atomic Energy Commission at the Health and Safety Laboratory in New York with John Harley. From these very helpful and encouraging giants, I learned about radiation biology, effects on membranes and animals, epidemiology, medical physics, public health, nuclear engineering, radiology, and nuclear medicine. For the majority and remainder of this lecture, I would like to focus on the major achievements over the last 50–70 y in the various areas involved in radiation protection. In reviewing the history, it is clear that much of the progress we have made is the result of remarkable advances in technology, although some were due to new ideas and concepts. All, however, have been based on the foundational work of a great number of humble, sharing, and brilliant people. Since this is the Taylor Lecture of the NCRP, I have chosen to focus primarily (but not exclusively) on those from the United States. HEREDITARY EFFECTS AND PREGNANCY Hermann Muller is known for his work in 1927 when x-rays were used as the first intentional mutagen in fruit
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flies. He initially worked at Columbia University and then in Texas, Germany, and Russia, where he was head of the genetics laboratory in St. Petersberg. One interesting story is that due to the wars in Europe, he wanted to return to the United Kingdom and was forced to take a clipper boat airplane from Lisbon. After a delay of several days due to bad weather, the plane took off, and after an hour of flight, there was panic as 160 strains of very rare fruit flies in small jars were thought to have been left on the wharf. The pilot refused to turn around, but happily soon after the flies were discovered. Dr. Muller had put them in a breadbox, and the crew, believing it was actually bread, had stored the box in the plane’s kitchen. Interestingly, Dr. Muller was one of the first to warn of the potential harmful effects from radiology. As a result, he was criticized by many physicians for scaring patients away from radiology (a scenario that has been repeated over ensuing decades). Bill and Liane Russell (along with Paul Selby) were the scientists at Oak Ridge National Laboratory who conducted the genetic megamouse experiments and developed the specific-locus test (to detect recessive mutations in first generation offspring) and skeletal mutation changes. The mouse data were fundamental in estimating the genetic risk from radiation in humans. There are three population geneticists who stand out and worked with the atomic bomb survivors and their offspring. James Neel’s most interesting contribution was not actually observation of a hereditary radiation effect but rather the increased occurrence of neurofibromatosis and other abnormalities as a result of consanguineous marriages in Japan. He later went on to study Amazon tribes to determine whether there was a difference in population genetics for indigenous tribes versus urban populations. One of James Crow’s major roles was as one of the earliest proponents of the use of DNA in forensics. Seymour Abrahamson is best known for his study design of the F1 generation of the atomic bomb survivors. Over the last 50 y, there has been a lot of information gained on radiation effects during the in utero period and on the possible hereditary effects of radiation in humans (NCRP 2013). Dr. Robert Brent finished college when he was only 18 y old and went on to become the world’s greatest expert in teratology. He has compiled an amazing record of service to pregnant women, including over 25,000 consultations, most of which were with women considering an abortion because of minimal fetal radiation doses. Dr. Brent and his wife are also well known philanthropists to medical education. Jack Schull has contributed greatly with his study of mental retardation and microcephaly of children following high dose in utero exposure of atomic bomb survivors. Important negative findings regarding hereditary effects have been published regarding the offspring of
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atomic bomb survivors and childhood cancer survivors. Much of the latter work is from the Childhood Cancer Survivor Study published by Marilyn Stovall, John Boice, and others. RADIATION BIOLOGY There have been a number of consequential advances in radiation biology. Perhaps the first of these was the description of radiation track structure and the prediction of linear-quadratic dose response by Douglas Lea in his book Actions of Radiations on Living Cells (Lea 1946). Cloning of mammalian cells in tissue culture by Philip Marcus and Theodore Puck allowed investigation into cell survival curves after radiation exposure. Of interest is that while these researchers were able to grow cells together in a medium, they were unable to get single cells to grow and form colonies. The breakthrough came from the brilliant Hungarian atomic physicist Leo Szilard, who was having lunch one day with Dr. Marcus. He suggested simply fooling the single cells into believing that they were not alone by having a platform with single cells submerged in a container with a layer of feeder cells so that the single cells would recognize the diffusible substances from other cells (Puck and Marcus 1956). Hypoxia was known to confer radiation resistance as early as 1923; however, the notion that chronic hypoxia in tumors was a problem for radiation therapy was clearly defined by Thomlinson and Gray (1955) and triggered efforts to increase oxygen tension or use radiation other than photons. The future of radiation biology will almost certainly be combined with genetics, including DNA sequencing, genomics, gene expression, and epigenetics. Currently, we are fortunate to have a number of exceptional radiobiologists including Sally Amundson, Edward Azzam, Joel Bedford, David Brenner, Kathryn Held, Ann Kennedy, and Amy Kronenberg to provide the foundations for future work. RADIATION DOSES, LIMITS, AND DOSIMETRY Radiation doses and units became an issue soon after radiation was discovered and resulted in the formation of ICRU in 1925. Early units included the “roentgen” and the “rep.” By 1953, the rad and rem were in use. One of the luminaries of ICRP was Harold Wyckoff. There have been a number of changes over the last 50 y. The “genetically significant dose” has essentially disappeared as a result of the realization that hereditary effects in humans have not been as great as initially feared. Confusion continues with the terms rem and Sievert being used for both equivalent and effective dose. The first NCRP committee that I was on was tasked with recommending how to transition from older traditional units to the International System of Units (SI). I remember
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attending a meeting chaired by Randy Caswell when he announced that the transition should be completed in exactly 15 y. I inquired where the number 15 had magically come from, and I was greeted with laughter from the other committee members. I was told that they would all be retired within 15 y and would not need to be bothered, and they figured I was young enough to learn the SI units and conversions. There are a number of issues with dose limits. ICRP has reduced the recommended dose limits, and the United States has not kept pace with the changes. Most people do not realize that the ICRP reduction was not only based upon consideration of recent epidemiology but also upon the fact that historically the vast majority of recorded occupational doses were well below recommended limits, and there was no need to continue to allow a few employers to keep exposing employees near the former annual limits. A major continuing problem with dose limits is the public’s confusion regarding the ICRP 20 mSv annual dose limit for “existing situations” and reconciling this with the 1 mSv annual public dose limit. DOSIMETRY AND DOSE RECONSTRUCTION Dosimetry has been advanced by the remarkable increase in computer power, and this has led in turn to development of Monte Carlo modeling and voxel computed tomography (CT) scan-based male, female and child phantoms. There also has been significant development of dosimetry models of the respiratory and alimentary tracts. This work has been accomplished by many people, but notable standouts include Wesley Bolch, Keith Eckerman, and Rich Leggett. Major efforts in environmental dose reconstruction have resulted in a better understanding of the methodologies needed (NCRP 2009a). External dosimetry has seen progress in reassessment of the atomic bomb survivors. We have seen dose reconstruction of atomic veterans, releases from the Nevada test site, Hanford, Apollo, Rocketdyne, and Rocky Flats. There also have been significant efforts at dose reconstruction at foreign sites such as Chernobyl, Techa River, and Fukushima. People instrumental in these exceptional efforts include Lynn Anspaugh, John Auxier, Andre Bouville, Bruce Napier, Dan Strom, and John Till. ENVIRONMENTAL ISSUES Radiation studies of entire ecosystems were conducted in the 1950s at Brookhaven National Laboratories. The classic textbook on radioactivity in the environment was published by Merril Eisenbud (1973). Merril is a classic story of humility and how families often do not know that giants live in their own houses. One day after Fukushima,
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I received a telephone call from Jonathan LaPook, M.D., the medical correspondent for CBS news. He wanted to know what the effects of radioactivity in the environment might be. I mentioned that the classic book was published by Merril Eisenbud. He said “Merril? Why he is my uncle, and I never knew exactly what he did for a living.” I asked him if he had a copy of the book, and he indicated in the affirmative. I suggested that he take a few hours and actually look at his uncle’s book and then call me back (which he did). After the mid 1970s, funding for research into environmental issues declined markedly, and it was not until Chernobyl (and later Fukushima) that interest was rekindled and many studies were done, particularly regarding cesium. Interest continues with the extraordinary work of Ward Whicker and others. Ward has pointed out that most ecology populations appear unaffected if individual humans are protected. HEALTH PHYSICS The last 50 y has seen health physics grow and mature into a defined specialty (Roessler 2005). The Health Physics Society was founded in 1956 and the American Board of Health Physics in 1960. Herbert Parker (the first Taylor Lecturer) is generally credited with being the father of health physics. There were also remarkable women in the field, most notably Elda Anderson who worked both at Los Alamos and Oak Ridge on the Manhattan Project. J. Newell Stannard was a giant in many respects, but probably his most consequential achievement was the development of the Atomic Energy Commission educational program at the University of Rochester, which produced many giants in our field. While there are many who contributed to the health physics field, I would like to particularly single out John Cameron, John Frazier, and Ken Mossman. Before I did research for this lecture, I knew that John Cameron was instrumental in establishing a paramount radiological physics program at the University of Wisconsin and that he was in large part responsible for the change from film badges to TLDs. What I had not realized was that he essentially invented bone densitometry, which is widely used throughout the world today. RADON The link between mining and lung cancer has been known for over a century. The link with radon as the cause of lung cancer in miners became apparent in the 1950s as a result of John Harley’s work. In the last 50 y, there have been several important advances in understanding radon and its effects. Naomi Harley has contributed to a coherent
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approach between radon dosimetry and epidemiology. The interaction of smoking and radon has been elucidated by the exceptional work of Jay Lubin et al. (1994) with uranium miner studies. Most recently, North American and European meta-analyses have been able to provide data on the risks associated with residential radon (Krewski et al. 2006).
STATISTICS AND EPIDEMIOLOGY Statistics always has been one of my least favorite subjects, and I appreciate anybody who can simplify things. The statistician who has made statistics and epidemiology understandable for me is the quiet and thoughtful Charles Land. The most powerful, understandable and simple presentation of statistics is found in his four-line table showing how many people are needed to find a carcinogenic effect and different dose levels. Other statisticians who have made significant contributions are Dale Preston (formerly of the Radiation Effects Research Foundation) and Daniel Stram. The last half-century has seen major changes in radiation epidemiology. Enough time has passed that we have a fair appreciation of site-specific cancer estimates and their differences, although the small number of excess cancers often tempts people to treat all solid cancers as the same (which can sometimes lead to unfortunate and incorrect conclusions). Radiation epidemiology has discovered meta-analysis and used it as a means to generate more statistical power. While this can be helpful, the recent metaanalysis of nuclear worker studies has shown that one study with bias or errors can substantially influence the combined result (Wakeford 2005). It has also become abundantly clear that there is a practical lower limit to radiation epidemiology and that risks from doses in the range of 10–100 mGy require very large numbers. John Boice has engaged in this remarkable effort with a “million person study.”
RISK ASSESSMENT, LINEAR NON-THRESHOLD, AND PROBABILITY OF CAUSATION Probabilistic risk assessment methods became widely used after the publication of the WASH‐1400 report chaired by Norman Rasmussen in the 1970s. I was lucky enough to take his nuclear engineering course at the Massachusetts Institute of Technology, and it quickly became clear to all of us students that Norm was a devoted Red Sox fan. Every time the Red Sox were playing at Fenway, we had a teaching assistant for that class. Over the next three decades, both risk-informed and risk-managed decision making methods were employed. Current risk experts whose work stands out are David Hoel and Chris Whipple. Certainly adoption of the linear non-threshold (LNT)
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hypothesis for stochastic effects at low doses has been a major turning point in risk assessment. The LNT hypothesis has generated controversy for several decades, and it may or may not be true. Dr. Arthur Upton (former Director of the National Cancer Institute), who is known for his cautious judgment, chaired the committee that authored NCRP Report No. 136, and the committee concluded that there was “no conclusive evidence to reject the assumption” (NCRP 2001). The concept of LNT is not a comforting one for the public and has caused lots of angst and, some would argue, unnecessary expense. Interestingly, Laurie Taylor himself was not a fan of the LNT hypothesis. UNCERTAINTY At low doses, small numbers of excess radiationinduced cancers often lead people to say, “We don’t know what happens at low doses.” This is, of course, untrue, as we know that if effects were large, we would detect them. As a result of developments in the uncertainty field, we have had to add words such as “epistemic” and “aleatory” to our radiation vocabulary. One very useful advance has been a comprehensive evaluation of the uncertainties associated with risk estimation (NCRP 2012). These efforts have been led primarily by Owen Hoffman and his group. Small amounts of uncertainty do not bother me, but I discovered that Owen once wrote a paper on whether Crater Lake was really 592 or 594 m deep. His interest developed from his former career as a National Park Ranger. RISK COMMUNICATION AND PSYCHOLOGICAL ISSUES Risk communication and evaluation of psychological issues associated with radiation exposure are some of the most important issues but with the least progress (in terms of the public). Psychological issues have been acknowledged to be the most important health effect at Chernobyl and probably at Fukushima. Paul Slovic made noteworthy advances with his publications on risk perception, acceptability and issues such as amplification. Excellent work continues in this area by Steven Becker, Evelyn Bromet, Paul Locke, and Susan Wiltshire. This problem remains huge and transcends accidents, acceptance of nuclear power, and radiation uses in medicine. One of my favorite examples (pointed out to me by Abel Gonzalez) of how we have confused the public comes from the Fukushima experience. The limit for 137Cs in water is 10 Bq L−1, while for orange juice it is 100 times higher at 1,000 Bq L−1. For edible rice, the limit is 1,000 Bq kg−1, which is 10 times higher than for rice wrapping paper (100 Bq kg−1).
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NUCLEAR WEAPONS AND TERRORISM From the 1950s until the 1980s, we lived with the real threat of nuclear weapons during the Cold War, and then for about 25 y the threat subsided. With the rise of militant religious groups and more unstable governments having or developing nuclear weapons, the threat has reemerged. While there has been no intentional use of a nuclear weapon over the last 65 y, I predict that one will be used within the next 50 y. The additional threats of dirty bombs and improvised nuclear devices have many people and agencies worried. The foundational work of both Bryce Breitenstein and Pat Durbin on internally deposited radionuclides and decorporation is invaluable. Development of scenarios and models by Brooke Buddemeier, Cham Dallas, Charles Miller, and Robert Whitcomb has helped us to understand the nature and magnitude of the threats and prepare for them. Research on radioprotective methods by Judith Bader and Norman Coleman are essential, as are the long-standing efforts of William Blakely with regard to rapid personal dosimetry. NUCLEAR POWER AND NUCLEAR WASTE In the early and mid 1970s, nuclear power seemed to have a bright future. The accident at Three Mile Island in 1979 and Chernobyl in 1986 cast a pall over the landscape. The recent multi-reactor meltdown at Fukushima has been an additional problem. The expected renaissance never happened, nor is it likely to happen anytime soon. The Obama administration’s shutdown of Yucca Mountain has left us with a serious spent-fuel problem, and the “temporary” solution seems to be dry cask storage. If there is one bright light and giant in this field, it is the extraordinary work and effort of Richard Meserve (former NRC Commissioner and now President of the Carnegie Institution), who works tirelessly to try to make our politicians understand the issues. Legacy waste from nuclear weapons is a monumental problem that is going to be with us for a long time. At Hanford, there are 56 million gallons of waste in 177 tanks, 60 of which are leaking. Remediation began 20 y ago, and it is hoped that it may be finished in another 35 y at a currently estimated cost of $300 billion. NATURALLY OCCURRING RADIOACTIVE MATERIAL, RADIUM, PLUTONIUM AND URANIUM Since the mid‐1940s, we have learned a lot about the metabolism and dosimetry of radium, plutonium, and uranium. Radium received attention first with the pioneering work of Robley Evans and later Otto Raabe. Their foundational work has received an increase in attention as a result of the petroleum extraction industry and radium containing scale in oil pipes. The plaintiff’s attorneys have figured out
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that the oil companies have deep pockets and have filed many lawsuits due to exposure to scale. Whether hydraulic fracking will add to these naturally occurring radioactive material issues remains to be seen. Wright Langham at Los Alamos was known as the father of plutonium. The 50 y follow-up of the Los Alamos plutonium workers was conducted by George Voelz. George was another giant whose children were not exactly sure of what their father did. After George and I published an article on terrorism in the New England Journal of Medicine, I remember a remark by Valerie Voelz (who was then a medical student) that all her classmates were duly impressed, and she had no idea her father was so famous. Uranium and depleted uranium became an issue during the Gulf War and a public issue about uranium fabrication facilities. John Boice and his group have done many studies indicating that generally uranium does not cause a detectable increase in cancer (likely due to its slow decay rate and metabolic properties). DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY As documented in NCRP Report No. 160, there was doubling of the radiation exposure to the U.S. population between 1980 and 2006 largely as a result of medical diagnostic exposure, particularly CT scanning (NCRP 2009b). Most people do not realize that it was the success of the Beatles that resulted in development of the CT scanner. The unexpectedly large revenue that EMI Music received from the Beatles’ records allowed them to fund a pie-in-thesky research project by one of their engineers (Godfrey Houndsfield) and resulted in the invention of the CT scanner. CT scans, however, are associated with high doses compared to most other diagnostic examinations, and there have been instances of hair loss and skin erythema from improper use. In addition, the issue of potential increase in cancer rates in children was noted by David Brenner. This led a number of radiologists to champion a very successful effort to lower doses from CT scanning, particularly to children. Those radiologists include, among others, Kimberly Applegate, Donald Frush, and Julie Timins. We are also fortunate to have a number of medical physicists who have contributed to this issue, including Larry Dauer, Walter Huda, Cynthia McCollough, Mahesh Mahadevappa, and Terry Yoshizumi. The other major change in diagnostic radiology has been the complete switch in the last 15 y from film-based images to digital techniques. In 1994, the U.S. Food and Drug Administration (FDA) issued a warning about radiation injuries that were occurring as a result of high exposures during fluoroscopically guided interventional procedures. There has been a huge educational effort over the last decade by Steven Balter,
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Donald Miller, and Louis Wagner. In spite of this, we still see occasional skin ulcers from such procedures. These may decrease in the future with the FDA requirements for new machines to display dose indices in real time. Mammography has been a true success story. Over the last 40 y, we have gone from using high dose film to low dose film and now to digital techniques. FDA and the American College of Radiology instituted a required accreditation program that not only checks dose levels and image quality but also requires a certain level of annual experience and annual continuing education. All of this has resulted in lower dose but more importantly more accurate diagnoses. A lot of the credit for this goes to Stephen Feig, Lawrence Rothenberg, and Edward Sickles. NUCLEAR MEDICINE Progress in nuclear medicine has occurred in fits and starts and is a good example of how one invention often must wait for another to be successful. Prior to the 1960s, images were obtained with a rectilinear scanner using a variety of high energy radiopharmaceuticals. Hal Anger invented the gamma camera in 1956, but it was not widely used until the 1960s when 99mTc could be produced in hospitals from a generator. Gordon Brownell demonstrated the possibility of medical imaging with the positron-emission tomography scanner in the 1970s, but it was not until 30 y later that the technique became widely used after it was combined with a CT scanner and small cyclotrons for local isotope production became practical. James Adelstein has advanced radiation protection issues in nuclear medicine, and Mike Stabin has been instrumental in making dosimetry tools widely available. RADIATION ONCOLOGY Current radiation oncology practice relies on pivotal work of a number of giants. In the 1960s, George Casarett and Philip Rubin published an absolutely classic two volume book on clinical radiation pathology, which showed the underlying changes in tissues with various treatment protocols (Rubin and Casarett 1968). Rodney Withers was instrumental in elucidating the early and late response of tumor and normal tissues to various fractionation schemes (Withers 1969). The last several decades have seen profound changes in radiation oncology. Use of radium and 60Co are essentially nonexistent, and treatment now most commonly involves linear and particle accelerators. There has been rapid development of integrated computerized treatment planning as well as development of hybrid diagnostic and therapeutic equipment. The future is likely to be focused on patient- and tumor-specific biology. Extensive data on issues related to
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pediatric patients have been published by a number of authors but most notably by Louis “Sandy” Constine. Even though radiation oncology equipment has become much more technologically advanced, there continue to be occasional serious accidents. Since 1990, there have been large accidents in Costa Rica, France, Panama, and Spain all attributed to human error, and one might suppose that such accidents will continue in the future. ACCIDENTAL WHOLE AND PARTIAL BODY EXPOSURE Very high acute whole body exposures result in the acute radiation syndrome, which has a number of phases manifested by damage to various body systems. Historically, patients would die within a few weeks from a gastrointestinal syndrome or somewhat later from bone marrow failure. There have been advances in treatment, but this, in turn, has revealed other problems. The accident at Chernobyl involved 134 patients with acute radiation sickness. The world’s leading expert in this field is Angelina Guskova. With her team and advances in intensive care unit medicine, she was able to overcome these early problems with patients surviving doses as high as 8 Gy (Mettler et al. 2007). In a later accident in Belarus with a patient receiving ~12–15 Gy, the gastrointestinal and bone marrow phases were treated only to have the patient succumb at 90 d from death due to pulmonary failure. In the Tokaimura criticality accident in Japan, a remarkable physician, Dr. Kaz Maekawa, employed heroic and state-of-the-art medicine, but a patient who received 17 Gy expired at 82 d and a second who received about 10 Gy expired at 210 d (Maekawa 2000). It appears now that while short-term survival can be obtained with heroic measures, long-term survival after doses of 10–12 Gy and higher are unlikely until the late multi-organ system failure issues can be resolved. Accidents occurring as a result of stolen or lost high activity radioactive sources have continued to occur sporadically and result in serious injuries. NONIONIZING RADIATION Radiation protection to most of us in the field usually refers to ionizing radiation. NCRP has published a few reports on ultrasound and radiofrequency effects. These have been the result of notable work by experts such as Wesley Nyborg, Gary Zeman, and Marvin Ziskin.
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and Syria), and there are more than 119 person-y of experience in space. Ionizing radiation has always been an issue not only from the magnitude of exposure but the effects of particle and ion radiation. Francis Cuccinota has been the leader in this field, and his work will become even more important as Virgin Galactic is now selling space trips to the public, and plans are afoot to go to Mars. SPECIAL GIANTS While a discussion of giants and their work is interesting, I found in my research that there were three additional categories of giants that need to be mentioned separately. The first was the recognition that giants sometimes come in pairs and are married. Whether their efforts are additive or synergistic, I have not decided. The obvious pairs of giants are: Shirley and Michael Fry at Oak Ridge and their work in radiation medicine and biology, Naomi and John Harley and their work on radon, Genevieve and Charles Roessler and their work in health physics, and Liane and Bill Russell and their genetics research. There is one philanthropic giant, Yohei Sasakawa, who generously funds many foundations but also large radiation programs. His Nippon Foundation provided tens of millions of dollars for the major study of childhood thyroid effects after Chernobyl. He also has funded a number of programs related to the Fukushima Nuclear Accident. Of interest is that after the tsunami and earthquake, Sasakawa himself went to the accident areas and simply handed out cash to thousands of displaced persons so that they could buy food and water. There are giants who left us too quickly. These include Goeff Howe at Columbia and his work on lung and breast cancer epidemiology and Elaine Ron at the National Cancer Institute (NCI) and her outstanding work on the epidemiology of thyroid cancer. There is an interesting (and maybe even true) story about Geoff. He had become totally blind from diabetes and had a guide dog that he used occasionally. Most of us who saw Geoff give slide presentations at meetings would swear that he still could see. In any case, a visitor to see Geoff was having tea and cookies. When Geoff turned his head away from the cookies, the dog would snatch one. When Geoff turned his head toward the cookies, the dog would pretend he had done nothing. I guess even Geoff’s guide dog thought he could still see. PUBLISHED MATERIALS
SPACE Most people forget our early accomplishments in space and do not know that 12 people have walked on the moon, that there have been more than 535 astronauts in space from 37 countries (including Cuba, Malaysia, Mongolia,
Authors can be giants as a result of imparting information to many students. The classic textbook on radiobiology by Eric Hall is in its seventh edition and has been used by many generations of radiology and radiation oncology residents (Hall and Giaccia 2011). Jerrold Bushberg and his
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Lauriston S. Taylor Lecture c F. A. METTLER JR.
group also have produced a classic text on physics of medical imaging. The work of journal editors is huge and largely unappreciated; yet without their tireless efforts, dissemination of crucial material would not happen. Standout editors include Michael Fry, Gen Roessler, Mike Ryan, Richard Vetter, and Richard Wakeford. COLLECTIONS OF GIANTS In review of radiation protection over the last 50–70 y, there are some places where giants congregate, and giants seem to beget other giants. Specific universities always seem to crop up in the radiation literature. These include the Columbia University, University of California Berkeley, University of Chicago, University of Rochester, and University of Wisconsin. The Radiation Effects Research Foundation has provided the foundational epidemiological study of the atomic bomb survivors (Ozasa et al. 2012) with scientists such as Gil Beebe, Evan Douple, Seymour Jablon, David Hoel, Jim Neel, Dale Preston, William Schull, S. Shigematsu, Roy Shore, and now Bob Ullrich. The Lovelace Inhalation Toxicology Research Institute in Albuquerque has done remarkable work in inhalation and metabolism with scientists such as Bruce Boecker, Ray Guillmette, Fletcher Hahn, Joe Mauderly, Roger McClellan, and Bruce Muggenberg. Pacific Northwest National Laboratories has spawned giants such as Bill Bair (the first Ph.D. in radiation biology in the world), Les Braby, Tony Brooks, Ron Kathren, Bill Morgan, Bruce Napier, Kathryn Pryor, and Dan Strom. One cannot overlook Oak Ridge with such greats as Shirley and Michael Fry, Ron Goans, Clarence Lushbaugh, Bob Ricks, Dick Toohey, and Al Wiley. There are many unsung heroes in our federal and state government organizations. The most prominent is the NCI Radiation Epidemiology Branch with Gil Beebe, John Boice, Andre Bouville, Ruth Kleinerman, Martha Linet, Jay Lubin, Kiyohiko Mabuchi, Bob Miller, and Elaine Ron. Stars at FDA have included John McCrohan, Don Miller, Orhan Suleiman, and John Villlforth; at NRC, Don Cool and Vince Holahan; at EPA, Michael Boyd, Mary Clark, and Julian Preston; and at DOE, Stephen Musolino. There are a number of state regulators who deserve special mention, including Jill Lipoti and James Yusko. UNSCEAR AND ICRP As the U.S. Representative to the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) for 28 y, I have stood on the shoulders of many of my Alternate Representatives and Advisors. They have always been superb and a credit to our country. It is impossible to mention them all. They have included Charlie Meinhold and Warren
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Sinclair and for the last decade Lynn Anspaugh, John Boice, Naomi Harley, Vince Holahan, and Julian Preston. Since ICRP was formed in1928 by Laurie Taylor and others, it has been at the forefront of radiation protection. There have been many illustrious members, including Rolf Sievert. My interactions with the Main Commission included two who stand out in my mind and who taught me a lot: Daniel Beninson and Sir Edward Pochin. Both were integral in developing the concepts of weighting factors and effective dose. Once I found that Sir Edward Pochin was in Albuquerque visiting Sandia Laboratories, but nobody had invited him to dinner. I invited him to our house and told my two young boys that a “knight” was coming to dinner. They were very excited, no doubt expecting somebody on a horse and in a full suit of armor. When the doorbell rang and there was a white-haired man in a blue suit without even a sword, they were very disappointed. However, after dinner they asked him “Well if you really are a knight, how many dragons have you killed?” He smiled and put one of them on each of his knees and told them of many fights that he had with “anti-nuclear” dragons over the years. He did admit that he had not actually killed any of them, but my children went to bed happy anyway. ICRP continues to flourish, especially under the direction of Claire Cousins, the only woman to be chair of the Commission in almost a century. NCRP In preparing for this lecture, I reread many NCRP reports, and I wondered how many people had contributed to NCRP reports and who had done the most and was the true NCRP giant. As a result, I reviewed all reports from No. 1 through 174 and made a spreadsheet of all who were chairs or committee members. I did not include consultants and advisors. In total there were 1,354 persons. There were nine people who had been on six committees, four people who had been on seven committees, two people who had been on eight committees, and six people who had been on nine committees. However, the standouts were John Poston and Edith Quimby, who both had been on 12 committees! Giants could not do their work without the NCRP staff, and there are giants among them. These of course include the past presidents Laurie Taylor, Warren Sinclair, Charlie Meinhold, and Tom Tenforde; and Bill Beckner, Tom Fearon, Costa Maletskos, Will Ney, Marvin Rosenstein, Dave Schauer, Jim Spahn, and Ivan White. Very special recognition goes to Laura Atwell and Cindy O’Brien. CONCLUSION It has been an honor to give the 38th Taylor Lecture on the occasion of the 50th anniversary of NCRP and an
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interesting experience to reflect on the people and changes in radiation protection over more than the last half a century. All of us have stood on the shoulders of giants during our careers. While I have mentioned many giants, I am sorry that I could not mention them all. I am humbled at how many giants graciously advised and mentored me over the years. Radiation protection and medicine are timelimited careers, but family is forever. My personal giants include my wife, Gloria, and my sons, Erik and Larsen. A photograph of the night sky by my friend Ralph Johnson reminds me that while we have many giants in our field, there remains a vast universe out there about which we know very little. Note: A pdf file of the lecture slides can be found as Supplemental Digital Content, http://links.lww.com/HP/A39. REFERENCES Eisenbud M. Environmental radioactivity. New York: Academic Press; 1973. Hall E, Giaccia A. Radiobiology for the radiologist. Philadelphia, PA: Lippincott Williams and Wilkins; 2011. Krewski D, Lubin JH, Zielinski JM, Alavanja M, Catalan VS, Field RW, Klotz JB, Létourneau EG, Lynch CF, Lyon JL, Sandler DP, Schoenberg JB, Steck DJ, Stolwijk JA, Weinberg C, Wilcox HB. A combined analysis of North American casecontrol studies of residential radon and lung cancer. J Toxicol Environ Health 69:533–597; 2006. Lea DE. Actions of radiations on living cells. Cambridge UK: Cambridge University Press; 1946. Lubin J, Boice JD, Edling C. Radon and lung caner risk: a joint analysis of 11 underground miner studies, 1994. Washington, DC: U.S. Department of Health and Human Services; 1994. Maekawa K. An overview of medical care for highly exposed victims in the Tokaimura accident. In: Tsujii H, Akashi M, eds. Proceedings of international symposium on the criticality accident in Tokaimura: medical aspects of radiation emergency. Chiba, Japan: National Institute of Radiological Sciences; 2000. Mettler FA, Guskova AK, Gusev I. Heath effects in those with acute radiation sickness from the Chernobyl accident. Health Phys 93:462–469; 2007.
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National Council on Radiation Protection and Measurements. Evaluation of the linear-nonthreshold dose-response model for ionizing radiation. Bethesda, MD: NCRP; Report No. 136; 2001. National Council on Radiation Protection and Measurements. Radiation dose reconstruction: principles and practice. Bethesda, MD: NCRP; Report No. 163; 2009a. National Council on Radiation Protection and Measurements. Ionizing radiation exposure of the population of the United States. Bethesda, MD: NCRP; Report No. 160; 2009b. National Council on Radiation Protection and Measurements. Uncertainties in the estimation of radiation risks and probability of causation. Bethesda, MD: NCRP; Report No. 171; 2012. National Council on Radiation Protection and Measurements. Preconception and prenatal radiation exposure: health effects and protective guidance. Bethesda, MD: NCRP; Report No. 174; 2013. Ozasa K, Shimizu Y, Suyama A, Kasagi F, Soda M, Grant EJ, Sakata R, Sugiyama H, Kodama K. Studies of the mortality of atomic bomb survivors, report 14, 1950–2003: an overview of cancer and noncancer diseases. Radiat Res 177: 229–243; 2012. Puck TT, Marcus PI. Action of x-rays on mammalian cells. J Exp Med 103:653–666; 1956. Roessler G. The 50th anniversary of the Health Physics Society. Health Phys News XXXIII(5); May 2005. Rubin P, Casarett G. Clinical radiation pathology. Philadelphia, PA: WB Saunders; 1968. Taylor NW, Sinclair WK, Gorson RO. In memoriam, Lauriston S. Taylor: 1902–2004. 2014. Available at: http://hps.org/ aboutthesociety/people/inmemoriam/LauristonTaylor.html. Accessed 2 April 2014. Thomlinson RH, Gray LH. The histological structure of some human lung cancers and the possible implications for radiotherapy. Brit J Cancer 9:539–549, 1955. Wakeford R. Cancer risk among nuclear workers. J Radiol Prot 25:2; 2005. Withers HR. Capacity for repair in cells of normal and malignant tissues. In: Bond VP, ed. Proceedings of the Carmel conference on time and dose relationships in radiation biology as applied to radiotherapy. Upton NY: BNL Report 50203 (C‐57); 1969: 54–69.
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