DOE Openness: Human Radiation Experiments: Roadmap to the Project
How Does Radiation Affect Humans?
How Does Radiation Affect Humans?Radiation may come from either an external source, such as an x-ray machine, or an internal source, such as an injected radioisotope. The impact of radiation on living tissue is complicated by the type of radiation and the variety of tissues. In addition, the effects of radiation are not always easy to separate from other factors, making it a challenge at times for scientists to isolate them. An overview may help explain not only the effects of radiation but also the motivation for studying them, which led to much of the research examined by the Advisory Committee.
What effect can ionizing radiation have on chemical bonds?The functions of living tissue are carried out by molecules, that is, combinations of different types of atoms united by chemical bonds. Some of these molecules can be quite large. The proper functioning of these molecules depends upon their composition and also their structure (shape). Altering chemical bonds may change composition or structure. Ionizing radiation is powerful enough to do this. For example, a typical ionization releases six to seven times the energy needed to break the chemical bond between two carbon atoms. This ability to disrupt chemical bonds means that ionizing radiation focuses its impact in a very small but crucial area, a bit like a karate master focusing energy to break a brick. The same amount of raw energy, distributed more broadly in nonionizing form, would have much less effect. For example, the amount of energy in a lethal dose of ionizing radiation is roughly equal to the amount of thermal energy in a single sip of hot coffee. The crucial difference is that the coffee's energy is broadly distributed in the form of nonionizing heat, while the radiation's energy is concentrated in a form that can ionize.
What is DNA?Of all the molecules in the body, the most crucial is DNA (deoxyribose nucleic acid), the fundamental blueprint for all of the body's structures. The DNA blueprint is encoded in each cell as a long sequence of small molecules, linked together into a chain, much like the letters in a telegram. DNA molecules are enormously long chains of atoms wound around proteins and packed into structures called chromosomes within the cell nucleus. When unwound, the DNA in a single human cell would be more than 2 meters long. It normally exists as twenty-three pairs of chromosomes packed within the cell nucleus, which itself has a diameter of only 10 micrometers (0.00001 meter). Only a small part of this DNA needs to be read at any one time to build a specific molecule. Each cell is continually reading various parts of its own DNA as it constructs fresh molecules to perform a variety of tasks. It is worth remembering that the structure of DNA was not solved until 1953, nine years after the beginning of the period studied by the Advisory Committee. We now have a much clearer picture of what happens within a cell than did the scientists of 1944.
What effect can ionizing radiation have on DNA?Ionizing radiation, by definition, "ionizes," that is, it pushes an electron out of its orbit around an atomic nucleus, causing the formation of electrical charges on atoms or molecules. If this electron comes from the DNA itself or from a neighboring molecule and directly strikes and disrupts the DNA molecule, the effect is called direct action. This initial ionization takes place very quickly, in about 0.000000000000001 of a second. However, today it is estimated that about two-thirds of the damage caused by x rays is due to indirect action. This occurs when the liberated electron does not directly strike the DNA, but instead strikes an ordinary water molecule. This ionizes the water molecule, eventually producing what is known as a free radical. A free radical reacts very strongly with other molecules as it seeks to restore a stable configuration of electrons. A free radical may drift about up to 10,000,000,000 times longer than the time needed for the initial ionization (this is still a very short time, about 0.00001 of a second), increasing the chance of it disrupting the crucial DNA molecule. This also increases the possibility that other substances could be introduced that would neutralize free radicals before they do damage.
Neutrons act quite differently. A fast neutron will bypass orbiting electrons and occasionally crash directly into an atomic nucleus, knocking out large particles such as alpha particles, protons, or larger fragments of the nucleus. The most common collisions are with carbon or oxygen nuclei. The particles created will themselves then set about ionizing nearby electrons. A slow neutron will not have the energy to knock out large particles when it strikes a nucleus. Instead, the neutron and the nucleus will bounce off each other, like billiard balls. In so doing, the neutron will slow down, and the nucleus will gain speed. The most common collision is with a hydrogen nucleus, a proton that can excite or ionize electrons in nearby atoms.
What immediate effects can ionizing radiation have on living cells?All of these collisions and ionizations take place very quickly, in less than a second. It takes much longer for the biological effects to become apparent. If the damage is sufficient to kill the cell, the effect may become noticeable in hours or days. Cell "death" can be of two types. First, the cell may no longer perform its function due to internal ionization; this requires a dose to the cell of about 100 gray (10,000 rad). (For a definition of gray and rad, see the section below titled "How Do We Measure the Biological Effects of Radiation?") Second, "reproductive death" (mitotic inhibition) may occur when a cell can no longer reproduce, but still performs its other functions. This requires a dose of 2 gray (200 rad), which will cause reproductive death in half the cells irradiated (hence such a quantity is called a "mean lethal dose.") Today we still lack enough information to choose among the various models proposed to explain cell death in terms of what happens at the level of atoms and molecules inside a cell. If enough crucial cells within the body totally cease to function, the effect is fatal. Death may also result if cell reproduction ceases in parts of the body where cells are continuously being replaced at a high rate (such as the blood cell-forming tissues and the lining of the intestinal tract). A very high dose of 100 gray (10,000 rad) to the entire body causes death within twenty-four to forty-eight hours; a whole-body dose of 2.5 to 5 gray (250 to 500 rad) may produce death within several weeks. At lower or more localized doses, the effect will not be death, but specific symptoms due to the loss of a large number of cells. These effects were once called nonstochastic; they are now called deterministic. A beta burn is an example of a deterministic effect.
What long-term effects can radiation have?The effect of the radiation may not be to kill the cell, but to alter its DNA code in a way that leaves the cell alive but with an error in the DNA blueprint. The effect of this mutation will depend on the nature of the error and when it is read. Since this is a random process, such effects are now called stochastic. Two important stochastic effects of radiation are cancer, which results from mutations in nongerm cells (termed somatic cells), and heritable changes, which result from mutations in germ cells (eggs and sperm).
How can ionizing radiation cause cancer?Cancer is produced if radiation does not kill the cell but creates an error in the DNA blueprint that contributes to eventual loss of control of cell division, and the cell begins dividing uncontrollably. This effect might not appear for many years. Cancers induced by radiation do not differ from cancers due to other causes, so there is no simple way to measure the rate of cancer due to radiation. During the period studied by the Advisory Committee, great effort was devoted to studies of irradiated animals and exposed groups of people to develop better estimates of the risk of cancer due to radiation. This type of research is complicated by the variety of cancers, which vary in radiosensitivity. For example, bone marrow is more sensitive than skin cells to radiation-induced cancer.
Large doses of radiation to large numbers of people are needed in order to cause measurable increases in the number of cancers and thus determine the differences in the sensitivity of different organs to radiation. Because the cancers can occur anytime in the exposed person's lifetime, these studies can take seventy years or more to complete. For example, the largest and scientifically most valuable epidemiologic study of radiation effects has been the ongoing study of the Japanese atomic bomb survivors. Other important studies include studies of large groups exposed to radiation as a consequence of their occupation (such as uranium miners) or as a consequence of medical treatment. These types of studies are discussed in greater detail in the section titled "How Do Scientists Determine the Long-Term Risks from Radiation?"
How can ionizing radiation produce genetic mutations?Radiation may alter the DNA within any cell. Cell damage and death that result from mutations in somatic cells occur only in the organism in which the mutation occurred and are therefore termed somatic or nonheritable effects. Cancer is the most notable long-term somatic effect. In contrast, mutations that occur in germ cells (sperm and ova) can be transmitted to future generations and are therefore called genetic or heritable effects. Genetic effects may not appear until many generations later. The genetic effects of radiation were first demonstrated in fruit flies in the 1920s. Genetic mutation due to radiation does not produce the visible monstrosities of science fiction; it simply produces a greater frequency of the same mutations that occur continuously and spontaneously in nature.
Like cancers, the genetic effects of radiation are impossible to distinguish from mutations due to other causes. Today at least 1,300 diseases are known to be caused by a mutation. Some mutations may be beneficial; random mutation is the driving force in evolution. During the period studied by the Advisory Committee, there was considerable debate among the scientific community over both the extent and the consequences of radiation-induced mutations. In contrast to estimates of cancer risk, which are based in part on studies of human populations, estimates of heritable risk are based for the most part upon animal studies plus studies of Japanese survivors of the atomic bombs.
The risk of genetic mutation is expressed in terms of the doubling dose: the amount of radiation that would cause additional mutations equal in number to those that already occur naturally from all causes, thereby doubling the naturally occurring rate of mutation.
It is generally believed that mutation rates depend linearly on dose and that there is no threshold below which mutation rates would not be increased. Spontaneous mutation (unrelated to radiation) occurs naturally at a rate of approximately 1/10,000 to 1/1,000,000 cell divisions per gene, with wide variation from one gene to another.
Attempts have been made to estimate the contribution of ionizing radiation to human mutation rates by studying offspring of both exposed and nonexposed Japanese atomic bomb survivors. These estimates are based on comparisons of the rate of various congenital defects and cancer between exposed and nonexposed survivors, as well as on direct counting of mutations at a small number of genes. For all these endpoints, no excess has been observed among descendants of the exposed survivors.
Given this lack of direct evidence of any increase in human heritable (genetic) effects resulting from radiation exposure, the estimates of genetic risks in humans have been compared with experimental data obtained with laboratory animals. However, estimates of human genetic risks vary greatly from animal data. For example, fruit flies have very large chromosomes that appear to be uniquely susceptible to radiation. Humans may be less vulnerable than previously thought. Statistical lower limits on the doubling dose have been calculated that are compatible with the observed human data. Based on our inability to demonstrate an effect in humans, the lower limit for the genetic doubling dose is thought to be less than 100 rem.