How atomic bomb survivors have transformed our understanding of radiation’s impacts, Science. By Dennis Normile, Jul. 23, 2020 , HIROSHIMA—Kunihiko Iida wants the world to know that the atomic bombs the United States dropped on Hiroshima and Nagasaki 75 years ago next month are still claiming lives and causing suffering.Iida was 3 years old in August 1945. His father had died in battle; he was living with his mother and her parents in a house 900 meters from Hiroshima’s hypocenter, the spot right beneath the detonation. The blast crumpled the house. The family fled the city, but Iida’s mother and older sister soon died from their injuries, a fact the little boy didn’t grasp. “Until I entered elementary school, I thought they were living and that we would meet someday,” he says.
His injuries left him bedridden for years, and he has suffered debilitating illnesses ever since. Childhood anemia caused him to collapse at school. He’s had ulcers and asthma, underwent two surgeries to remove brain tumors, and now has thyroid growths. “There has never been a break in these illnesses,” he says.
Yet Iida has survived. Thousands of others died prematurely over the years because of radiation-induced cancer, a tally that is still growing. Collectively, they have left an important legacy. Most of what is known today about the long-term health effects of radiation has come out of research with those survivors. The work, now run by the Radiation Effects Research Foundation (RERF), is making “major contributions to our understanding of radiation effects,” even today, says Richard Wakeford, a radiation epidemiologist at the University of Manchester. RERF studies also underpin the limits that countries have set for occupational and medical exposure to radiation.
Iida has participated in the studies since the late 1950s, because, he says, “They are trying to accurately grasp the misery of the atomic bomb,” something he hopes will promote peace. People don’t understand the unique impacts of nuclear weapons, Iida says. He and other participants “have helped the entire world,” says Ohtsura Niwa, chairman of RERF.
The survivors’ ranks are now rapidly thinning. About 70% of the original 120,000 participants enrolled in RERF’s Life Span Study (LSS) have died; most of those remaining are in their 80s and 90s. “We have an ethical obligation” to follow the cohort through the last surviving member, Niwa says—but at the same time, “We have to expand our mission.”
RERF researchers believe they can continue to gather epidemiological findings from existing life and health histories of the LSS participants, but they are also starting entirely new studies, for example of the molecular mechanisms by which radiation exposure leads to cancer. And biological samples from 30,000 study participants collected over 7 decades await genomic analysis………
One of Atomic Bomb Casualty Commission (ABCC) ‘s most immediate concerns was the possible impact of radiation on survivors’ children. It was clear that the bombings affected children already conceived in August 1945, resulting in an increased number of babies born with a small head size. And fruit fly studies showing that irradiation of adults causes heritable genetic changes and birth defects in offspring suggested there might be longer term effects………..
“Leukemia is a very rare disease, but clinicians became aware that it was appearing a lot among the survivors,” says Kotaro Ozasa, an RERF epidemiologist. ABCC showed the disease was especially prevalent among those closest to the hypocenter. Previous studies among people exposed to radiation in a medical context had hinted at the link, Wakeford says, but “the findings from Japan provided convincing evidence.”……..
How radiation exposure affected health
Studies in Hiroshima [shown on map below on original ] and Nagasaki conducted over the past 75 years have yielded important insights into the health effects of radiation. Researchers went to great lengths to determine survivors’ exposure, which depended partly on their distance from the hypocenter of the bombings………..
Year after year, the researchers have tracked the incidence of more than a dozen different types of cancers in the survivors, along with mortality. “Radiation risk is very complex,” says RERF epidemiologist Alina Brenner. It depends on sex and age at exposure and can be influenced by genetic susceptibility and lifestyle factors such as smoking. And risks “change over time as a population ages,” she says. But the sheer size and duration of the LSS, along with its detailed data on exposure, age, and sex, allowed researchers to draw many conclusions as the decades passed.
Dose was clearly very important. Among those who were within about 900 meters of the hypocenter and received more than 2 grays of radiation, 124 have died of cancer. (That dose is about 1000 times the average annual radiation dose from natural, medical, and occupational sources combined.) In its
latest LSS update, RERF scientists conclude—based on comparisons of cancer deaths between the exposed group and unexposed controls—that radiation was responsible for 70 of those deaths (see graphic, above). Scientists call this number, 56.5%, the attributable fraction. The numbers of deaths are low because few who were close to ground zero survived the blast, explains Dale Preston, a biostatistician at Hirosoft International who previously worked at RERF. But among these people, “Most of the cancers are due to the radiation,” Preston says
At 1 gray of exposure, the dose roughly 1100 meters from the hypocenter, the attributable fraction is 34.8%, and it decreases linearly for lower doses. Women suffered more radiation-associated cancers than men, largely because of cases of breast cancer. Both men and women exposed at a younger age were more at risk as they aged: “It’s thought that actively dividing cells are more susceptible to radiation effects, so younger people are more sensitive,” Ozasa says. Radiation most increased the risk of leukemia among survivors, followed by cancer of the stomach, lung, liver, and breast. There was little impact on cancers of the rectum, prostate, and kidney. Exposure also heightened the risk of heart failure and stroke, asthma, bronchitis, and gastrointestinal conditions, but less so; for those with a 2-gray exposure, 16% of noncancer deaths were deemed attributable to radiation………..
New data are still coming in. In papers published in 2018 and 2019, for example, RERF scientists reported that women exposed to bomb radiation at the age of menarche, the first occurrence of menstruation, were at a higher risk of developing
breast or
uterine cancer later in life than those exposed before or after puberty. The proliferation of breast and uterine tissue during puberty provides “a lot of potential for DNA damage induced by radiation,” Brenner says.
The breast cancer study also gives a glimpse of RERF’s future agenda. The first analysis did not try to distinguish among the several major breast cancer subtypes, which vary in their biological mechanisms and prognoses, Brenner says. RERF is now analyzing cancerous tissue collected from patients to determine whether any of those subtypes occur more frequently in radiation victims. If so, that could provide hints about just how radiation damages tissue and raises cancer risk.
SAMPLES ARE ONE RESOURCE RERF has in abundance. During detailed biennial health examinations of more than 23,000 of the survivors (including some exposed in utero), researchers have collected and preserved blood and urine samples, some dating back to the late 1950s. RERF has also amassed frozen cell lines from parents and children in 500 families in which at least one parent was exposed to radiation, plus an equal number of control families.
DNA in those samples—which so far has not been sequenced—could provide a check on the early data about the health of survivors’ offspring. Despite the reassuring findings about birth defects, some researchers worry radiation may have caused mutations in testes and ovaries that children born years later might have inherited. Researchers plan to compare the number and types of mutations found in the families to see whether any are more common in children of radiation-exposed parents, Ullrich says.
https://www.sciencemag.org/news/2020/07/how-atomic-bomb-survivors-have-transformed-our-understanding-radiation-s-impacts
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