All of us come into the world designed by evolution to survive. Failing some rare mishap, we arrive equipped with immune systems ready to do battle with unfriendly biologic mischief makers. The wizards within us that enable this microscopic life-preserving enterprise reside in the nuclei of our 75-100 trillion cells.
Just as millions of ‘0s’ and ‘1s’ arrayed in lines of computer code serve as the language of a computer’s operations, a sequence of roughly 100 millions of four different kinds of organic molecules, or nucleotides, arranged in pairs between two identical DNA strands, provide the instructional language for our cells’ functions. These lengthy strands (estimates range from about 3 to 5 feet) are wound in a double helix and folded over themselves repeatedly in order to fit within the chromosomes of cell nuclei, thanks to some very clever engineering work by proteins, our bodies’ ‘hard hats.’
DNA molecules govern our cells’ functions, their development and their reproduction. After a limited number of generations, they ensure cell death to make way for new cell growth.[1] Cell reproduction requires that the two DNA strands separate and unwind (more work for proteins), each strand then directing the synthesis of a new, identical partner. The new, double stranded DNA in the new “daughter” cell must be an exact replica of its parent. To make sure that that happens, DNA is capable of detecting and repairing any damage that might have occurred in a microscopic process of remarkable complexity, mastered by living organisms eons ago.
These complex molecular structures are composed of intricate flotillas of atoms, atoms that have combined—by exchanging or sharing electrons—to form them. Imagine, then, the consequences for living cells if their smallest subunits—atoms—lose their electronic stability (their balance of positive and negative electric charges). They become ionized, or electrically charged ions; we know them as chemically unruly ‘free radicals.’ This can occur in a variety of ways, one of which is bombardment with very high frequency electromagnetic radiation (e.g., x-rays and gamma rays), which can break lose one or more electrons.[2]
The effects of ‘ionizing radiation’ can include the destruction of the molecules that form our DNA. Certain proteins in our cells will enable those molecules to continue growing—but without the regulatory guidance of their finely constructed DNA. This unregulated cell growth is what we call ‘cancer,’ named for the crab which it often resembles.
Radiation surrounds us and is as common to our lives as the night follows the day. The sun’s radiance provides energy that turns into matter by powering natural and vital rearrangements of atoms’ electrons into different molecular combinations. Among plants, for example, photosynthesis uses light energy from the sun to convert carbon dioxide and water into food, which is then consumed by animals—and ourselves.
Thus a certain amount of background or natural radiation is essential to life, and part of the DNA code that guides our cellular functions includes instructions for the repair of molecules damaged by ionizing radiation. But at some point for each living organism the radiation it receives may exceed the native cellular repair capacity of its organs. Just what that point is varies from individual to individual. Beyond a certain dose and duration of exposure, ionizing radiation is certain to overwhelm the orderly cell repair capacity of most people.
Medical x-rays represent a significant net increase to our cumulative radiation exposure over any given period of time. In the 1970s, when annual mammography screening of asymptomatic women at low or normal risk for breast cancer began, medical x-ray exposure already “accounted for approximately 90 percent of . . . total radiation other than natural background [radiation].”[3]
X-rays effect different organs and tissues in different ways. Variations in “probability and severity of harm” to living things from radiation are described by the International Atomic Energy Agency as “detriment,” which the IAEA calibrates by using a “tissue weighting factor” to determine the actual effective radiation dose for particular organs and tissues. These tissue weighting factors (WT) range from 0.01 for skin and bone surface tissue, to 0.12 (or a multiple of 12) for bone marrow, breast, colon, lung and stomach tissue.[4] Thus comparing x-radiation damage to breast tissue to general background radiation risk may understate the risk by as much as a factor of twelve.
Information about medical x-ray dosing in the case of mammography typically relies on ratings given by manufacturers of specific equipment used. Such ratings assume a standard thickness of the compressed breast, a standard combination of glandular and adipose tissue (breast density), and standard x-ray beam characteristics. In real life, however, the absorbed glandular dose (measured in Grays[5]) received during a mammogram can vary by nearly 50%, depending upon breast thickness and density.[6] The newer three dimensional mammogram, or ‘breast tomosynthesis,’ which is similar to a CAT scan of the breast, involves yet more radiation.
Numbers are useful for calibrating machines, but when we discuss medical x-ray risk in terms of numers we imply that there is a number that represents relative safety, and that we know what that number is. The numbers that represent radiation doses from mammography machines have little to do with our as yet imperfect understanding of the biology of cancer, which cannot be calibrated. By relying such numbers—whatever the quantity of millisieverts we might agree upon—we are dissembling, pretending that we can adequately predict what will happen to an individual’s organs when struck by ionizing radiation, what results will follow, and most importantly, how and for how long those results will make a difference to the normal functioning of that person’s body. But we cannot.
Long before the Health Insurance Plan (HIP) of Greater New York began its mammography trial in 1963, scientists had demonstrated that carcinogenic capacity of ionizing radiation delivered as x-rays. A major contribution to that research came from the German cytologist Theodor Heinrich Boveri’s studies of the chromosome in cell division and heredity.
In 1902 Boveri concluded from his work that there was a strong link between cancer and chromosomal abnormalities within the cell:
“The tumour problem is a cell problem . . . The cells of even the most malignant tumours can be formed from normal tissue cells. . . . the differences between the cells of different tissues are ultimately determined by differences in the state of the chromosomes. . . . . The primordial tumorigenic cell . . . is a cell that harbours a specific faulty assembly of chromosomes as a consequence of an abnormal event. This is the main cause of the propensity for unrestrained proliferation that the primordial cell passes to its progeny . . . .”[7]
Boveri’s findings were first published in 1914 in his native German. By 1929 his booklet was available in six English language editions both in the United States and Great Britain. A half-century after the first appearance of Boveri’s essay on the chromosome and tumorigenesis, Science magazine in 1964 published an appreciation written by his fellow biologist and biographer, Fritz Baltzer.[8]
Meanwhile, the power of x-rays to infiltrate our bodies’ invisible depths has been known to us since Wilhelm Conrad Röntgen, experimenting with cathode ray (vacuum) tubes in 1895, discovered that electric current passing through a cathode ray tube could penetrate various materials and leave marks on photosensitive plates or film. When such rays fail to penetrate, or are absorbed by, an intervening material such as the calcium in bone, they leave a white shadow on the dark background of a photosensitive surface.
Five years later, in 1901, Röntgen would receive the Nobel Prize in physics for a discovery which, by then, had—in today’s parlance—gone “viral.” As medical imaging’s historian Bettyann Holzman Kevles describes it,
“Within weeks . . . X-ray Boy’s Clubs sprouted in the United States, and X-ray slot machines were installed in Chicago and Lawrence, Kansas, where, for a coin, you could examine the bones in your own hand. . . . Anybody could cobble together an X-ray machine, and just about anyone did. . . . There was no hint of danger.”[9] It did not take long for the possible medical and industrial applications of X-ray machines to become apparent. But danger, there was.
Initially, in the early 20th century, medical and dental exposures lasted for hours at a time, as patients, dentists, physicians, and x-ray tube makers all endured burns and deeper tissue damage, not to mention fatal metastatic carcinomas. Thomas Edison famously abandoned work on x-ray tubes after his glassblower, Clarence Madison Dally, died in 1904, having suffered from what would later be called radiation sickness, and then finally losing both arms to cancer.[10]
Soon on the heels of Röntgen’s discovery, English physicist Joseph John Thomson, further investigating the properties of electricity as it passed through vacuum tubes, detected individual particles which were a thousand times smaller than atoms. These he identified as subparticles of atoms, which he named electrons, produced when x-rays struck atoms with sufficient force to disperse one or more of their electrons, leaving behind unstable ions.
By the end of the 1920s biological investigations of genetic mutations had converged with research into the long-term damage from ionizing radiation. Geneticist Hermann Joseph Muller, experimenting with varying doses of X-rays, discovered a directly proportional connection between radiation exposure and lethal genetic mutations in fruit flies. His work, reported in 1926 at a scientific conference in Berlin, earned him the 1946 Nobel Prize in Physiology or Medicine.
Thus by World War II scientists had not only connected abnormal disruptions to the molecular structure of the chromosome and aberrant cell growth, but recognized that x-rays could produce those disruptions. What had been previously only observed—a link between cumulative or prolonged x-ray exposures and cancer—was now understood. All that remained was to determine the minimum extent of x-ray exposure that might produce oncogenes—or whether there was such a thing as a safe minimum exposure at all.
Within a few months after the U.S. atomic bombings of Hiroshima (August 6, 1945) and Nagasaki (August 9, 1945), Japanese and American scientists collaborated on the Atomic Bomb Casualty Commission to assess the radiation consequences of the bombings. (Their work was continued, after 1975, by the Radiation Effects Research Foundation.) Their efforts were handicapped by the difficulty of establishing the precise nature of the radiation emitted in any given location and relating those findings to other than broad-scale epidemiological data. Added to that was the difficulty of determining the long-term effects of low-level ionizing radiation, because carcinomas can have long latency periods. For decades after 1945 attributions of cancer cases to radiation from the bombings relied on estimates, and were regularly disputed.[11]
The National Academy of Sciences created in 1955 a committee on the biological effects of atomic radiation, with six subcommittees which investigated radiation’s effects on genetics, pathology, meteorology, oceanography and fisheries, agriculture and food supplies, and the disposal and dispersal of radioactive wastes. The committee issued an initial assessment in 1956, which was updated for its 1960 report.[12]
The group examining genetic effects confirmed that irradiation of female mice produced genetic damage. It also confirmed genetic consequences for the “children of survivors of the atomic bombings at Hiroshima and Nagasaki,” as well as “children elsewhere whose parents received radiation for medical or other reasons.”[13]
However, cautioned the report, “. . . most of the man-made radiation to which the population of the United States is exposed involves dose rates not yet adequately investigated experimentally. For example, we do not know whether the effects of low doses given at high dose rates, as in medical exposures, will be more like the response from acute irradiation or more like that from chronic irradiation.” Pathologies such as skin cancer and leukemia may result from “relatively low level” exposure “from time to time over a period of years. . . .” and it is “characteristic” of radiation that its “effects may manifest themselves not only immediately, but perhaps only after a long period of intermittent . . .exposure.
“Delayed manifestation of biological effects results from the fact that “all types of induced and spontaneous tumors appear not to arise at once . . . . There is much evidence indicating that malignant change ordinarily develops only after a series of ‘precancerous’ changes or a state of tissue disorder has taken place.”[14]
Given what the subcommittee on pathological effects had learned, and the questions remaining, it recommended against predicting “human tumor incidences from small radiation doses based on extrapolation from the observed incidences following high dosage,” such as those recorded after the atomic bombings of Japan. Furthermore, prediction ” . . . requires evaluation of the possibility that there is a threshold dose below which there is no probability of inducing leukemia, a concept which implies a factor of safety that would be most reassuring to those who are exposed to radiation in excess of the natural background . . . . However, no member of the Subcommittee feels that he can estimate the size of the threshold or, for that matter, even prove its existence. Accordingly, the Subcommittee believes it is prudent to assume that there is no threshold.” [15]
Subsequent reports from the National Academy of Sciences’ Committee to Assess Health Risks from Exposure to Low Level Ionizing Radiation have affirmed this conclusion. For example, “. . . at the level of cancer-associated gene or chromosomal mutation, the presence of a true dose threshold demands totally error-free DNA damage response and repair. The detailed information available . . . argues strongly against a DNA repair-mediated low-dose threshold for cancer initiation. [16] James V. Neel, who served on the Academy’s subcommittee on genetic effects of atomic radiation, ensured that the entire medical profession could readily learn of its findings with his article in the February 22, 1958 issue of the Journal of the American Medical Association, titled “The Delayed Effects of Ionizing Radiation.”[17]
And so, by 1960 the medical as well as scientific communities should have been fully aware that directing x-rays at any portion of the female body could violate the physician’s ethical duty to “do no harm.” And yet women are still advised by generally trusted sources that screening mammography “is safe; there is only a very tiny amount of radiation exposure,” and “strict guidelines ensure that mammography equipment is safe and uses the lowest dose of radiation possible.” [18]
The National Cancer Institute has always been was somewhat less breezy on the subject, cautioning women to “always let their health care provider and the x-ray technician know if there is any possibility that they are pregnant, because radiation can harm a growing fetus.”[19] Embedded in this caution is the recognition that it is not only the breast, but a woman’s entire torso, which is exposed (through x-ray scatter) to ionizing radiation.
Advances in all technological fields that contributed to allied victory in World War II included improvements in x-ray technology, first widely used in military hospitals during the previous world war. By the 1960s breast compression, improvements in film, and the use of high milliamperage-low voltage x-ray technique had led to successful efforts at M.D. Anderson Cancer Hospital in Houston, TX to find possibly cancerous anomalies in the breasts of 1,000 women with no palpable symptoms. Nearly all of the 245 ultimately confirmed breast cancers found during the experiment —including one that was as small as eight millimeter in diameter–had been detected by newly specialized mammography x-ray equipment.[20]
The availability of x-ray machines designed for breast imaging, along with the successful experiments at M.D. Anderson, inspired the hope that breast cancer deaths generally could be reduced as a result of x-ray screening for such small (“early”) cancers.[21] Given the interventionist imperative of modern medicine, reinforced by a capitalist economy in which the conquest of disease is marketable, few questioned the necessity for further diagnostic mammography and biopsies for barely visible white (radiopaque) spots in the breast representing calcification–a sign of possible cell death. Fewer still doubted the need to treat all detected “early” cancers. Few women were likely to appreciate that such irregularities do not in themselves represent cancerous growths. Cancers are actually identified through diagnostic mammography and biopsies, which require additional and significantly more radiation exposure.
Only later would physicians begin to question the wisdom of attacking cancers that might otherwise never have caused symptoms or death in a woman’s lifetime, while subjecting women to surgical deformities, toxic radiation and chemotherapy. Then there were the longer term risks— radiation induced lymphedema, new cancers, breast cancer metastasis, recurring breast cancers, and cardiac toxicity.[22]
All that was necessary at the end of the 1960s for the triumph of the new breast x-ray technology, not to mention its remunerative industrial and institutional infrastructure, was universal adoption of the policy, “early detection saved lives.” That declaration came, without rigorous theoretical and experimental proof, from the Health Insurance Plan of Greater New York.
Meanwhile, the American Cancer Society in 1972, during the nation’s Cold War against the spread of communism, began its own national campaign to promote routine x-ray screening for breast cancer for all women, benefiting from the Nixon administration’s newly launched national “war on cancer.” The ACS was ready to begin field testing its own version of a costly new weapon. Thousands upon thousands of trusting and unsuspecting women provided the proving grounds.
(Published June 9, 2015. Following posts will examine the risks to which women have been subjected as a result of the screening mammography experiment, and the unraveling of “mammography saves lives” as a medical protocol.)
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[1] RNA or ribonucleic acid, also resident in the human chromosome, has more varied structures thanks to its principal roles, which are to convey DNA instructions to proteins and to assist in the transfer of DNA during cell division.
[2] Higher frequency ultraviolet radiation begins to have enough energy to break chemical bonds. X-ray and gamma ray radiation, which are at the upper end of magnetic radiation, have very high frequency in the range of 100 billion Hertz and very short wavelengths 1 millionth of a meter. Radiation in this range has extremely high energy, enough to strip off electrons or to break up the nucleus of atoms. See: “Ionizing & Non-Ionizing Radiation,” Environmental Protection Agency, http://www.epa.gov/radiation/understand/ionize_nonionize.html. Downloaded November 13, 2014.
[3] J. Samuel Walker, Permissible Dose: A History of Radiation Protection in the Twentieth Century (University of California Press, 2000), p. 80.
[4] International Atomic Energy Agency, Training Material on Radiation Protection in Diagnostic and Interventional Radiology, “Radiation Units and Dose Quantities.” https://rpop.iaea.org./ Downloaded March 3, 2014. [Slide 26].
[5] A gray is a measure of the radiation energy absorbed per a unit of mass. One ‘gray’ = one joule of radiation energy by one kilogram of matter.
[6] V. Patel et al, “Patient Specific Average Glandular Dose in Mammography,” Paper presented at the 55th Annual Meeting of the American Association of Physicists in Medicine, August 4-8, 2013, Indianapolis, Indiana.
[7] Theodor Boveri, “Concerning the Origin of Malignant Tumours,” Translated and annotated by Henry Harris, Journal of Cell Science (January 1, 2008). Originally published as Zur Frage der Entstehung maligner Tumoren (Jena, 1914), trans. by Marcella Boveri as The Origin of Malignant Tumors (Baltimore, 1929).
[8] OCLC WorldCat. “All Editions for ‘The Origin of Malignant Tumors.” Fritz Baltzer, “Theodor Boveri,” Science, Vol. 144 (15 May 1964), pp. 809-815. See also Samantha Hansford and David G Huntsman, “Boveri at 100: Theodor Boveri and Genetic Predisposition to Cancer,” The Journal of Pathology, Vol. 234 (October 2014), pp. 142-145.
[9] Bettyann Holtzmann Kevles, Naked to The Bone: Medical Imaging in The Twentieth Century (Rutgers University Press, 1997). Kindle edition, location 390.
[10] Bettyann Holtzmann Kevles, Naked to The Bone: Medical Imaging in The Twentieth Century (Rutgers University Press, 1997), Chapter 2. See also K. Sansare, V. Khanna, and F. Karjodkar, “Early Victims of X-rays: A Tribute and Current Perception,” DMFR: Journal of Head & Neck Imaging (February, 2011), pp. 123-125, and Percy Brown, M.D., American Martyrs to Science through the Roentgen Rays (Springfield, Ill.: Charles C. Thomas, 1936).
[11] For an account of these post-Hiroshima investigations and the resulting disputes see J. Samuel Walker, Permissible Dose: A History of Radiation Protection in the Twentieth Century (University of California Press, 2000), especially Chapter 5. Also: M. Susan Lindee, Suffering Made Real: American Science and the Survivors at Hiroshima (University of Chicago Press, 1994), William J. Schull, Effects of Atomic Radiation: A Half-Century of Studies from Hiroshima and Nagasaki (New York: Wiley-Liss, 1005), and U.S. General Accounting Office, Problems in Assessing the Cancer Risks of Low-Level Ionizing Radiation Exposure (EMD-81-1) January 2, 198l.
[12] National Academy of Sciences-National Research Council, The Biological Effects of Radiation: Summary Reports (Washington, DC: 1960).
[13] National Academy of Sciences-National Research Council, The Biological Effects of Radiation: Summary Reports (Washington, DC: 1960), p. 3.
[14] National Academy of Sciences-National Research Council, The Biological Effects of Radiation: Summary Reports (Washington, DC: 1960), pp. 27-29.
[15] National Academy of Sciences-National Research Council, The Biological Effects of Radiation: Summary Reports (Washington, DC: 1960), pp. 32-35.
[16] National Academy of Sciences, Biological Effects of Ionizing Radiation, V (National Research Council, 1990), National Academy of Sciences, Biological Effects of Ionizing Radiation, VII, Phase 2 (National Research Council, 2006), p.245.
[17] James V. Neel, M.D., Ph.D., “The Delayed Effects of Ionizing Radiation,” Journal of the American Medical Association, Vol. 166 (February 22, 1958), p. 908.
[18] “Mammography: Benefits, Risks, What You Need to Know,” www.breastcancer.org, downloaded March 20, 2014;
[19] “Mammograms Fact Sheet,” National Cancer Institute, http://www.cancer.gov, downloaded February 19, 2015.
[20] Barron H. Lerner, “’To See Today with the Eyes of Tomorrow’: A History of Screening Mammography,” Canadian Bulletin of Medical History, Vol. 20:2 (2003), pp. 300-302. Radiographic image quality is a function of kilovoltage, amperage, and time of exposure.
[21] For a more recent critique of the limits of ever advancing breast imaging technology, see C.W. Stevens and E. Glatstein, “Beware the Medical-Industrial Comples,” Oncologist Vol. 1 (1996). http://www.nvbi.nlm.nih.gov/pubmed/10388005. Downloaded January 5, 2015.
[22]National Cancer Institute, “Brest Cancer Institute: Harms of Screening Mammography,” updated February 6, 2015. http://www.cancer.gov/cancertopics/pdq/screening/breast/healthprofessional/page8. Downloaded February 21, 2015).
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