| |
Radiation
Biology and the Radiation Research Program
The Department
of Energy (DOE) and its predecessor organizations, Energy Research
and Development Agency (ERDA) and Atomic Energy Commission (AEC),
always have been concerned about the health effects of ionizing
radiation. Extensive research has been conducted under their
sponsorship at all levels of biological organization from molecules
to man. Over the past 60 years, studies using every type of
radiation source have included exposure to both external radiation
sources and to internally deposited radioactive materials. These
exposures used different dose patterns and distributions delivered
over a wide range of experimental times. This extensive research
provided the basis for the new Low Dose Radiation Research Program,
linking the program directly to both the study of radiation's
health effects and recent developments in life sciences and
technology.
This brief
history will begin with the development of atomic energy and
proceed to a review of research programs designed to understand
the health effects of radiation in animals and man. Finally,
the impact of past research into radiation's effects at the
cellular and molecular level will be considered as a prelude
to the Low Dose Radiation Research Program.
Atomic
Energy
Parallel
development of the atomic bomb and the use of nuclear energy
for electricity production resulted in a difficult dilemma for
the public. Nuclear energy can be a source of massive death
and destruction but also has immense potential for useful applications.
Because of negative associations and connotations regarding
the A-bomb, concern about adverse health effects plays a major
role in the public's acceptance or rejection of nuclear power.
The history
of atomic energy has been reviewed extensively by the U.S. DOE
(see http://www.em.doe.gov/timeline/index.html).
Similar histories are available on the health effects of ionizing
radiation, including a very good one on research associated
with health effects induced by internally deposited radioactive
materials (J. N. Stannard, "Toxicology of Radionuclides," Ann.
Rev. Pharmacol. 13: 325–57, 1973) and the use of
this information to help establish appropriate standards. DOE
used these and other historic resources to help develop the
research setting that initiated the new Low Dose Radiation Research
Program. These historical summaries will not be reviewed in
detail here but will be covered briefly to provide some background
material.
The written
history of radiation began with three nearly simultaneous events
around the end of the 19th century. The nuclear era opened with
Roentgen's discovery of X rays in 1895, Antoine-Henri Becquerel's
observation in 1896 that uranium salts emit an invisible penetrating
radiation, and the Curies' isolation of radium in 1898. Soon
after the discovery of radiation, scientists became aware that
it could cause biological damage and therefore the amount of
exposure needed to be quantified, evaluated, and controlled.
Evidence of such damage was established when Becquerel developed
skin lesions from radium carried in his pocket. Injury to the
reproductive organs was observed in 1903, followed closely by
impairments in tissues that produce blood cells. In 1927 an
early geneticist, H. J. Muller, found that X rays induced mutations
in fruit flies. Bone cancer was observed in 1929 in workers
who painted radium dials on clocks. These health problems triggered
many animal studies to understand the dramatic biological effects
induced by high doses of radiation and stimulated a rapid increase
in radiation research. Over the next several decades, many advances
occurred in understanding radiation's potential for inducing
genetic effects and cancer.
Stimulated
by World War II, research in physics also increased rapidly,
culminating in 1945 with the explosion of the first atomic bomb
in Alamogordo, New Mexico. The devastating use of atomic bombs
in Japan to end World War II and the tragic acute effects of
intense radiation exposure resulted in unprecedented public
interest and concern over such adverse health consequences.
In 1946
Congress created the AEC, an independent civilian agency that
took over the research programs associated with radiation exposure.
A large research and educational effort begun at that time has
continued under ERDA and DOE. The national laboratories, which
were established to develop the atomic bomb, played a major
role in defining the biological effects of ionizing radiation.
Related research also has been conducted in major universities
throughout the world.
More than
100,000 people were killed in 1945 by the A-bombs and the resulting
radiation in Hiroshima and Nagasaki. Many years later, survivors
continue to provide the major source of data used to estimate
the risk for radiation-induced health effects following a single
high-level exposure. Initiated within 5 years after the bombs
were dropped, follow-up studies of the health status of survivors
have continued to the present. During the first decade after
exposure, the survivor population experienced a higher incidence
of leukemia, followed by a significant increase in the frequency
of solid tumors. In this population, there were over 450 cancer
cases or about 5% more than would have developed without the
radiation exposure.
Animal
and Human Studies
Experimental
animals have been used to estimate both the genetic and cancer
risks associated with radiation exposure. Begun in 1947 by Liane
and William Russell, the "megamouse" study at the Clinton Laboratories
(later Oak Ridge National Laboratory) exposed hundreds of thousands
of mice to radiation and measured the induction of mutations
in their offspring. A cornerstone of mammalian radiation genetics,
this work has helped place the risk of genetic disease in proper
perspective. Radiation-induced genetic risk was found to be
small relative to the cancer risk.
Life-span
studies in rodents and dogs determined the risk from both external
radiation exposure and the deposition of radioactive material
into the body. Internally deposited radioactive materials became
a major health concern because of fear about fallout from nuclear
testing. This fear also was associated with the potential release
of radioactive materials from nuclear reactors used to generate
electricity.
In the
1950s, the beagle was selected for study in a large coordinated
research effort among national and specialty laboratories and
university scientists. Research was conducted at the University
of California at Davis to estimate the health risk of ingested
radioactive materials such as 224Ra and 90Sr.
Strontium-90 is a radioisotope of great concern for nuclear
power and fallout. To estimate the risk to humans exposed to
these materials, the studies combined bone-cancer data from
radium-dial painters with cancer data from dogs. University
of Utah scientists, seeking to establish comparative toxicity
ratios, injected dogs and rodents with nuclear fuel cycle isotopes
such as 239Pu, 241Am, and 224,226Ra.
Information from these human and animal studies provided a basis
for predicting risk for humans exposed to 239Pu and
241Am.
During
the late 1950s and 1960s, researchers at Argonne National Laboratory
conducted studies on dogs and rodents to define the influence
of 90Sr and chronic gamma-ray exposure on cancer
induction, especially leukemia. Using a range of exposure protocols
and dose levels, scientists at Pacific Northwest Laboratory
and Lovelace Inhalation Toxicology Research Institute studied
the health effects of inhaled radioactive materials. These extensive
large-animal studies addressed such important problems as the
"hot-particle" hypothesis. This hypothesis, which suggested
that a single radioactive particle of 239Pu or 241Am
had a very high probability of causing cancer, was disproved.
These long-term studies, conducted over a span of more than
30 years, provided valuable input into the setting of radiation
standards for internally deposited radioactive materials. They
were especially instructive for isotopes, for which there were
limited or no human data.
The study
of radon in homes also was conducted under DOE funding. Radon,
a high-LET alpha emitter, represents the major environmental
radiation exposure. The mechanistic understanding of the radiation
dose delivered by radon, the importance of radon in the induction
of lung cancer, and the risk for lung cancer following exposure
to low levels of radon were studied and characterized. These
data were linked to those on the induction of lung cancer in
uranium miners, who had elevated occurrences of lung cancer
relative to the general population. As long-term animal studies
reached their goals and established the risk for radiation-induced
cancer from internally deposited radioactive material, they
were phased out. Funding for these large-animal studies, as
well as many other areas in radiation biology, decreased dramatically
between 1970 and 1999.
Cellular
and Molecular Studies
Following
the development of new methods for growing cells in tissue culture,
animal and human studies emphasized the effects of radiation
on cellular systems. During the period when radiation research
was at a low ebb, many of the studies that were conducted focused
on events at the cellular level to define the toxic effects
of radiation and the genetic and cytogenetic basis for radiation-induced
disease. This research greatly enhanced the understanding of
radiation's interaction with cells and tissues to produce changes
involved in late-occurring diseases such as cancer.
Rather
than using whole animals to determine the number of cancers
produced, more mechanistic research was applied to learning
how cancer develops. Such studies laid the scientific foundation
for interest in the genetic basis of human disease, and tools
developed in this research helped justify DOE's launching and
funding in 1986 of the Human Genome Initiative, later called
the Human Genome Program (HGP). Research conducted in the HGP
was essential for the development of the Low Dose Radiation
Research Program. [A brief history of DOE's role in developing
the HGP is on the DOE Web site at http://www.er.doe.gov/production/ober/hug_top.html]
Low
Dose Program
The studies
outlined above show that radiation biology has a rich history
of research. In recent years, major scientific advances have
been made in both cellular and molecular biology, particularly
in the genome programs. Recognizing the importance of applying
these new tools and techniques to address the health effects
of low levels of ionizing radiation, in 1998 Congress requested
that DOE initiate a research program to establish risk-assessment
standards and guidelines. These standards would be based on
a strong scientific and mechanistic foundation rather than on
the extrapolation of responses seen at high doses. Funding for
the Low Dose Radiation Research Program was included in the
Energy and Water Development Appropriations Act in 1998.
On June
1–2, 1998, a subcommittee drafted a research plan that was presented
to the Biological and Environmental Research Advisory Committee
(BERAC) and rewritten by a smaller committee to incorporate
BERAC's suggestions. This plan was used by the DOE Office of
Biological and Environmental Research (OBER) to draft a call
for proposals that was issued in the Federal Register with an
application deadline of April 13, 1999. From this call over
100 projects were peer reviewed, and 43 were selected for funding
at national and international laboratories and universities.
The program's
first contractors' meeting was held November 10–12, 1999, to
evaluate the current program, plan its future directions, and
focus the research toward standard setting. The meeting, which
was structured to optimize interaction and input from all attendees,
included members of the scientific community, regulatory agencies,
national and international review committees, general public,
and special interest groups. At the end of the contractors'
meeting, a program advisory group convened for the first time.
Members of this group were selected from a wide range of backgrounds,
including the public sector and different fields of science,
to provide guidance and direction to DOE OBER. The first committee
chairman is Dr. Sharon Friedman, Iacocca Professor and Director
of Science and Environmental Writing Program at Lehigh University.
The Low
Dose Radiation Research Program had its second and third contractors
meetings in 2001 and 2002 and continue to fund research. The
research areas of the dynamic program have changed from single
cell studies to those of more complex tissue and systems. These
studies can better evaluate the role of signally pathways, cell/cell
communication and cell/matrix interactions on the risk of cancer
following low-doses of radiation.
Efforts
are being made to study the shape of the dose-response relationship
and to evaluate the usefulness of the mechanistic studies on
risk assessment.
Return
to the top
|
|
Selected
Dates
1895
Roentgen discovers X-rays
1901
X-rays shown to be lethal
1902
X-rays shown to be harmful to the mammalian fetus
1913
Geiger unveils radiation detector
1938
Hahn first to split uranium atom
1942
Manhattan project formed to build atomic bomb
1943
Southam and Erlich introduce the term "Hormesis"
1945
Atomic bombs dropped on Japanese cities
1951
First atomic test in Nevada; fallout reaches New England in
two days
1952
First breeder reactor built
Great Britain
explodes first atomic bomb
1954
Public Law 83-703 authorizes AEC to conduct research on the
biological effects of ionizing radiation
1956
National Academy of Sciences issues report asserting no safe
threshold for radiation exposure
1969
Bloom paper concludes all exposure to high-energy ionizing radiation
produces damage
1972
BEIR I report recommends linear model for estimating radiation
risks
UNSCEAR
VI report questions validity of linear model for estimating
radiation risks
1979
Nuclear power plant at Three Mile Island, PA experiences meltdown
1981
Luckey revives issue of hormesis as it relates to radiation
1986
Nuclear power plant at Chernobyl, Ukraine experiences meltdown
1996
President's Advisory Committee publishes report "The Human Radiation
Experiments"
1998
Congress directs DOE to initiate Low Dose Radiation Research
Program (LDRRP)
|
