(Inside Science) -- On August 6, 1945, American pilots dropped the Little Boy bomb, obliterating Hiroshima, Japan. The bomb exploded around 600 meters above a hospital with a force of around 12,500 tons of TNT. Three days later, the Americans dropped a second, more powerful bomb, Fat Man, on the port city of Nagasaki.
More than 100,000 people died from the sheer force of the explosions and the searing temperatures, which reached nearly 4,000 degrees Celsius, hot enough to boil tiles and vaporize people unlucky enough to be in the immediate vicinity. Then there was the radiation: intense bursts of high-energy gamma rays that swept outward spherically from the exploding bombs ahead of the physical force. Those near the hypocenters -- the points on Earth above which the bombs exploded -- absorbed some of the highest doses of radiation ever delivered to humans before or since. The radiation burned images of people’s clothing into their skin, and thousands more died of acute radiation poisoning in the months after the explosions.
But many who survived the blasts also recovered from the immediate effects of the radiation. They were left facing an uncertain future: What long-term impacts would they -- and their future children -- endure from the hits radiation had dealt to their cells and the DNA within? Radiation biology was still in its infancy, and no one had ever studied the effects of an exposure even remotely on the scale of that delivered by atomic weapons.
As a result, survivors of the bomb have become one of the largest and longest-studied medical cohorts ever. “It’s a large population exposed at a wide range of ages, male and female, and at a wide range of doses,” said Kiyohiko Mabuchi, an epidemiologist at the National Cancer Institute in Rockville, Maryland. “So it can be extrapolated to many other populations.”
Indeed, the findings from a decades-long study of the survivors have been used to set radiation exposure standards around the world. But increasingly, such standards are looking antiquated. In today’s world of far more frequent medical scans and air travel, and widespread deployment of nuclear power, people are far more likely to receive low doses of radiation spread out over years or decades, rather than concentrated doses. Many radiation biologists say that lab and animal studies suggest such low doses are unlikely to be harmful and could in some cases even improve health, but regulators worry that such studies cannot be easily applied to humans. The only thing scientists seem to agree on is that more sophisticated standards are needed. But what those standards will end up being is anyone’s guess.
A long-term research collaboration
Studies of radiation’s effects on atomic bomb survivors began in 1946 with the American-led Atomic Bomb Casualty Commission, which later became an American-Japanese partnership known as the Radiation Effects Research Foundation, or RERF, now based in Hiroshima. RERF’s Life Span Study came to encompass around 94,000 survivors who were within a few kilometers from one of the bomb hypocenters, and a 26,000-person control group of people who were farther away and received no significant radiation from the bombs.
Japan has rigorously tracked tumors in its citizens since the 1950s, which has provided RERF scientists with much of the data they need. Additionally, a fraction of the study population comes in once every two years for medical exams.
“There’s no other study [of radiation effects] that can match it in terms of the statistical power and the precision of the estimates,” said epidemiologist Roy Shore, who recently retired from RERF.
RERF scientists have meticulously reconstructed the radiation doses to which each survivor was exposed, based on the distance that person reported he or she was from the hypocenter and what buildings and other materials were around to provide shielding against the bombs’ radiation. Scientists working for the Department of Energy (DOE) at Los Alamos National Lab in New Mexico even recreated the Little Boy bomb to ensure they understood how the bomb, which had a now seemingly primitive design compared to bombs built later, spread its radiation throughout Hiroshima.
Scientists knew even before 1945 that radiation can mutate genes and cause cancer, so it came as no surprise that cancers that showed up at higher than usual rates among bomb survivors. The first impact was a rash of leukemia, or blood cancer, which peaked in the early 1950s. By the year 2000, 310 members of the study population had died from leukemia, and RERF estimates that 103 of those deaths can be attributed to radiation released by the bombs.
After the discovery in the early 1950s that genes are encoded in DNA, scientists began to unravel the process by which radiation turns cells cancerous. Leukemia appeared first, theorizes Mabuchi, because DNA-damaged blood cells become cancerous more easily than do other cells. He added that scientists do not yet fully understand how the changes that radiation induces in cells lead to cancer in people.
Meanwhile, cases of cancers with solid tumors attributed to the radiation have slowly accumulated over the course of the study. Compared to the control group, bomb survivors have developed 853 “excess” cancerous tumors, according to the latest data released by RERF. By comparison, researchers estimated the study group developed 16,595 tumors from other causes, such as smoking, diet, and other genetic and environmental factors. The researchers also found among survivors a smaller excess of cardiovascular disease and a few other, more minor conditions such as cataracts. They have found no genetic effects or cancers in the children of survivors, although children born in the months following the explosions later developed neurological problems at higher than normal rates.
In study after study, RERF scientists have found that the higher the dose a bomb survivor received, the higher the chance that person would at some future time get cancer. This relationship has turned out to be almost perfectly linear, meaning that doubling the radiation dose doubles the excess cancer risk. The link has held regardless of sex, age at exposure, and cancer type, with one exception, leukemia, for which risk increases faster; at higher doses, a doubling of the dose roughly quadrupled leukemia risk.
Studies of other groups that have been exposed to radiation, including nuclear accident cleanup crews and workers in nuclear plants and hospitals who receive small radiation doses regularly, have confirmed the linear relationship found by RERF. Taken together, these findings have led to a so-called “linear no-threshold” assumption -- that no matter how low a radiation dose someone is exposed to, that person’s cancer risk increases. In other words, regulators setting radiation exposure standard generally err on the side of caution, assuming that even the tiniest possible dose of radiation presents some risk.
How big is low-dose danger?
But many scientists question this assumption. In both the RERF and other epidemiological studies, excess cancers in subjects who received doses below around 100 millisieverts (a commonly used unit for measuring radiation dose) are so rare that they become statistically insignificant. One hundred millisieverts is a large dose by the standards of normal life; by comparison, a head CT scan delivers about 2 millisieverts, and someone flying across the U.S. receives around one-fiftieth of that amount, 40 microsieverts.
Moreover, epidemiologists cannot control the doses or dose rates that their study subjects receive, potentially limiting the application of their findings. “The atomic bomb happened in one crack, people were exposed, and then that was it,” said Gayle Woloschak, a biologist at Northwestern University's Feinberg School of Medicine, in Chicago, Illinois. “What would happen if you’re living close to a dump site, or something like that? You’re talking about a chronic everyday low-dose-rate exposure.”
And even with utmost care, added Nori Nakamura, biologist and former chief scientist at RERF, doses remain to some extent uncertain. Atomic bomb survivors have long faced discrimination due to poorly founded fears about the long-term effects of radiation, so they have a strong incentive to overestimate how far they were from the hypocenter. Additionally, noted Nakamura, a ghastly “black rain” reportedly fell on Hiroshima in the hours after the bombing. How much radiation did that rain send out? No one will ever know. Nakamura is trying to settle the matter by analyzing bomb survivors’ tooth enamel, which unambiguously records radiation exposure. But getting intact teeth is much harder than, say, drawing blood. “It took 10 years for me to collect 300 teeth,” he said, and many of those teeth proved useless for his study, because they were decayed or covered in metal. The study is still ongoing.
To get a fuller picture of radiation’s effects, biologists such as Woloschak and Nakamura turn to studies in animals and cells. In these experiments they can control the exact dose of radiation delivered, as well as whether it’s delivered all in one go or spread out over time. And they can experiment on as many animals as their funding allows. Hundreds of thousands of mice and tens of thousands of dogs have been sacrificed to the cause.
The data from biological studies have led to several “paradigm shifts,” said Antone Brooks, a radiation biologist and former chief scientist of the DOE's Low Dose Energy Research Program. Biologists now understand that radiation does not just damage DNA directly; it can also affect the cellular machinery that controls which genes are “on” or “off” in a cell, which in turn determines which proteins the cell produces. Similarly, cells next to the one that take a direct hit from radiation can also respond, perhaps by killing the damaged cell to protect the organism.
Many experts say that biological studies are providing mounting evidence that low doses of radiation are unlikely to be harmful, and could in some cases provide protection against higher doses received later, by triggering a cell to activate genes involved in radiation defense. Biologists call this an adaptive response. Studies also suggest that low doses accumulated over time do less damage than the same total dose delivered in one shot, as in the 1945 bombings. The bottom line, said Brooks, is that compared to factors such as diet, smoking and genetics, “radiation is not a big hitter.”
But scientists say that as much as they’ve learned, there’s even more they need to learn—specifically, about how different doses and dose rates actually affect the rates at which people get sick. Yet the DOE, the major funder of such studies in the U.S., has all but ended its low-dose radiation research program. And Woloschak had to personally rescue the department’s unique archive of irradiated mouse and dog tissue after the department threatened to trash it due to space concerns; it is now housed at Northwestern, where researchers can study the samples using techniques that are more advanced than when the original experiments were done. “Nobody’s going to do a 49,000-mouse experiment again,” Woloschak said.
The future of low-dose research
Recent results from biology and epidemiology seem to be diverging. The latest major epidemiological study, which appeared in June in Lancet Haematology, pooled more than 300,000 nuclear workers in the U.S., the U.K. and France and found a small excess risk of certain types of leukemia even at lifetime exposures below 100 millisieverts. But skeptics have questioned some of the study’s statistical methods, and argued that inter-country differences and outside-of-work exposures, such as during medical tests, were not fully considered.
To try to increase epidemiology’s statistical power, John Boice, president of the National Council on Radiation Protection and Measurements in Bethesda, Maryland, and others have launched a “Million Worker Study,” pooling populations of U.S. soldiers, sailors, nuclear workers and medical workers who have received long-term, low-dose exposures. Meanwhile, Europe is ramping up its radiation biology program, and some in the U.S., such as House Science Committee Chairman Lamar Smith, are calling for renewed investment in radiation research. But in the immediate future, experts agree, the impasse is unlikely to be broken.
Since August 9, 1945, few people have been exposed to a nuclear weapon at close range. But much smaller radiation exposures have become part of daily life. Despite scant evidence that low radiation doses cause cancer in adults (some evidence suggests children’s developing bodies may be more vulnerable), many people still avoid medical and airport scans, and fear nuclear power. The atomic bomb is the most powerful physical weapon ever unleashed on a population, and it may be the most powerful psychological weapon as well. When it comes to radiation, even though it is 70 years later and a vastly different world, Little Boy and Fat Man still set the standard.