The word transmutation originates from the never-realized goal of ancient alchemists to transform, or transmute, the base metals into gold. Today scientists seek ways to transmute radioactive waste into nonradioactive elements, thereby eliminating the radiological hazards and waste disposal problems.

An example of two radioactive isotopes that can be transmuted into less hazardous forms are technetium-99 and iodine-129. Both of these isotopes are very long-lived and require disposal strategies that will isolate them from the environment for long periods of time. Both iodine and technetium are considered difficult to isolate because they dissolve readily in groundwater and move easily throughout the ecosystem. Irradiation of the long-lived technetium-99 isotope by neutrons will cause it to absorb a neutron and become technetium-100, which undergoes complete radioactive decay into stable ruthenium within minutes. Similarly, the iodine-129 isotope can be transformed by neutron absorption into stable xenon isotopes.

Another class of radioactive wastes that can be transmuted into less hazardous forms are the actinide elements, particularly the isotopes of plutonium, neptunium, americium, and curium. When irradiated with neutrons in a nuclear reactor, these isotopes can be made to undergo nuclear fission, destroying the original actinide isotope and producing a spectrum of radioactive and nonradioactive fission products. Isotopes of plutonium and other actinides tend to be long-lived with half-lives of many thousands of years, whereas radioactive fission products tend to be shorter-lived (most with half-lives of 30 years or less). From a waste management viewpoint, transmutation of actinides eliminates a long-term radioactive hazard while producing a shorter-term radioactive hazard instead.

A challenging aspect of this waste management strategy is the required waste partitioning. Just as household wastes must be partitioned into categories, such as paper, glass, and aluminum, before they are recycled, radioactive waste must also be sorted before being recycled back into nuclear reactors.

One particularly challenging partitioning task involves the actinide and lanthanide (rare earth) elements. Actinide and lanthanide elements are chemically similar and, thus, very difficult to separate efficiently. Most lanthanide isotopes are nonradioactive, and the few radioactive lanthanide isotopes are long-lived, so there is little incentive to invest neutrons in transforming them into stable elements. However, lanthanide elements tend to absorb neutrons efficiently (they are so-called neutron poisons) and will prevent the efficient transmutation of americium and curium if they are intermixed. Improved methods of separating lanthanides from actinides are needed to reach the goal of actinide transmutation.

The largest program at ORNL focusing on partitioning and transmutation is investigating methods for accelerator transmutation of wastes (ATW). Conceived by scientists at Los Alamos National Laboratory, ATW uses a linear accelerator system to produce neutrons for transmutation of excess weapons plutonium and other radioactive DOE wastes, such as technetium-99 and iodine-129. Activity at ORNL is centered on developing chemical separations technology, including processes for performing actinide-lanthanide separations, and on studying, designing, and ultimately testing the reactorlike flow loops in which the transmutation occurs.

A second program is developing technology for using a nuclear reactor to transmute the actinides in spent nuclear fuel from light-water reactors (LWRs). This program offers an alternative to direct disposal of LWR fuel in geological repositories. ORNL researchers are developing techniques for the front-end processing of LWR fuel to prepare it for introduction into the chemical partitioning system and are examining wasteform technologies for immobilizing some of the unique waste streams produced during the partitioning process. Additionally, we have performed several studies to characterize the benefits and disadvantages of recycling spent nuclear fuel.

Recently, interest at ORNL has turned inward to see whether partition-ing and transmutation offer any near-term advantages for management of some of our own radioactive wastes. Transmutation of highly radioactive europium isotope wastes (currently stored at ORNL solid waste area groups) into nonradioactive gadolinium isotopes appears to be practical and is being studied further. These europium wastes pose the dominant health risk to the public in certain environmental scenarios, and their elimination might be beneficial to the Laboratory. As proposed, the transmutation device would be the High Flux Isotope Reactor or the proposed Advanced Neutron Source. The physical and chemical partitioning of the radioactive europium from nonradioactive europium and gadolinium represents a key technology that must be developed for this task.

Ultimately, the potential of partitioning and transmutation to waste management is this: If a radioactive waste stream no longer exists, then it poses no radiological hazard. More than anything else, this simple fact has spurred the recent resurgence of interest in partitioning-transmutation technology.--Gordon E. Michaels, Chemical Technology Division


Probing the Mouse Genome

Rick Woychik of the Biology Division can tell you almost anything you want to know about mouse genes. So, what does this have to do with sequencing the human genome? Well, as it turns out, there are a number of similarities (perhaps more than we'd like to admit) between mouse genes and human genes. And, as a practical matter, it's a lot easier to conduct a controlled study of a mouse in a lab than a man on the street.

Woychik looks at efforts to sequence the human genome as the first step in understanding how the genetic code actually works. "Once we've sequenced and analyzed all the DNA bases of the human genome," he says, "we will know where all the genes are, but we won't know what they do." Studying the mouse genome could provide some of the missing pieces of the genomic puzzle.

"If we determine the function of a particular mouse gene whose location we know," Woychik says, "we can often look at the corresponding area on a human chromosome and locate the functionally equivalent human gene."

One of the techniques Woychik uses to probe the mouse genome is known as insertional mutagenesis. In this technique, hundreds of identical pieces of DNA are injected into mouse zygotes (fertilized eggs) in the hope of creating mutations in the resulting offspring. The DNA fragments, or "transgenes," are then incorporated, seemingly at random, into the zygote's genetic code. More often than not, this process results in normal laboratory mice, but every so often an unusual variation in the appearance or physical structure of one of the offspring, such as malformed limbs or internal organs, suggests that a mutation has occurred. "When we see an abnormality in the appearance of the offspring," Woychik says, "we test to determine whether the gene that was interrupted by a transgene is responsible for the change in appearance."

Another technique used to investigate the function of various mouse genes is known as targeted mutagenesis. In contrast to the random mutations introduced by insertional mutagenesis, targeted mutagenesis allows researchers to determine the effect of introducing a mutation at a specific site on a selected gene.

This degree of accuracy is achieved by introducing changes in the chromosomal DNA of cultured embryonic cells using a process called homologous recombination. In this approach, altered genetic material is inserted back into the context of a living mouse by microinjecting the manipulated cells into a host blastocyst (a 4-day-old mouse embryo).

Uncovering all the functional parallels between the genes of mice and humans could easily occupy several research lifetimes, but Woychik and his group have a more modest goal. Says Woychik: "We hope we can begin to establish molecular connections between individual genes on the genome and specific developmental processes in both mice and men.


The Russells: A Family Affair

William Lawson (Bill) Russell and Liane Brauch (Lee) Russell, the eminent husband-and-wife team who have studied mammalian genetics for 45 years at ORNL's Biology Division, have much in common. Both received the International Roentgen Medal, both earned Ph.D. degrees in zoology and genetics from the University of Chicago, and both worked at the Jackson Memorial Laboratory in Bar Harbor, Maine, before coming to the Laboratory, where they have headed genetics research in the Biology Division. Also, both were elected to the National Academy of Sciences, one of only 11 couples so honored.

Bill Russell, the former scientific director of the Mammalian Genetics Section in the Biology Division and now an ORNL consultant, is a native of Newhaven, England, with a B.A. degree in zoology from Oxford University. Lee, head of the Mammalian and Genetics Development Section of the Biology Division since 1975, is a native of Vienna, Austria, with a B.A. degree in chemistry from Hunter College in New York City.

In 1947, Bill wanted to leave Jackson Memorial Laboratory but would only accept a new position if Lee were offered one, too. Alexander Hollaender, director of the new Biology Division at Clinton Laboratories, came through with such an offer, and Bill and Lee came to Oak Ridge in November 1947 shortly after Jackson Memorial Laboratory burned to the ground.

Bill's first achievement in Oak Ridge was to develop efficient and reliable genetic methods to determine the rate at which mouse genes are mutated by different types and levels of radiation. But, to do this, he had to set up the Mouse House, a national resource that contains more than a quarter million mice, for which he designed cages, food containers, racks, and machines for washing bottles and cages. Soon after experiments got under way, he found that the mutation rate in the mouse was 15 times that in the fruit fly. As a result, the National Council on Radiation Protection and Measurements reduced the permissible levels for occupational exposure to radiation.

In 1952, as a result of Lee's studies of the vulnerability of early embryos of irradiated mice, the Russells recommended that physicians use diagnostic X rays on the pelvic regions of childbearing women only during that part of the menstrual cycle when pregnancy cannot occur.

In 1958, the Russells and Elizabeth Kelly discovered that the mutation rate in mice exposed to chronic radiation (spread over time) was between one-third and one-fourth the mutation rate in mice exposed to acute radiation (delivered in a matter of minutes). It was a significant finding because no dose-rate effect had been found in fruit-fly studies and because it suggested that a genetic repair mechanism corrects minor damage caused by low doses of radiation. By the mid-1960s the Russells had proved that sensitivity to radiation differs not only between mice and fruit flies but also between male and female mice. They then started a new area of investigation: determining the genetic effects on mice of chemicals from drugs, fuels, and wastes. In 1971, Bill and his associates published a paper recommending that, based on mouse studies, the drug hycanthone should continue to be used as a therapeutic drug for schistosomiasis, a debilitating parasitic disease common in the Third World. In 1975, Lee developed a fur-spot test for identifying chemicals likely to be mutagenic in reproductive cells. In 1979, Bill found that the laboratory chemical ethylnitrosourea (ENU) is the most potent mutagen ever tested in mice, making it a prime tool for studying mechanisms of mutagenesis.

In the 1980s, while continuing her research on the effects of chemicals on mice, Lee enlarged her genetic studies on the nature of mutational lesions caused by different treatments. Under her leadership, her section has increased in scientific staff and moved into areas of modern molecular genetics, including insertional mutagenesis and targeted mutagenesis--techniques that alter random or selected mouse genes. The research may unlock the secrets of human DNA by locating specific genes responsible for specific functions or malfunctions, such as diseased kidneys. DOE has recently recognized the section's unique capability for adding to the genome research effort.

In 1991, the international journal Mutation Research dedicated a special issue to Bill on his 80th birthday. In their introduction, the journal's editors stated, "No single person has contributed more to the field of mammalian mutagenesis, and thus to genetic risk assessment in man, than Dr. W. L. Russell." They might have added that his accomplishments likely would have been half as impressive without the scientific research conducted by his wife. Together, the Russells have formed one of the most fruitful collaborations in the annals of American science.


The Biology Division looks forward to moving into a 250,000-square-foot building that will have modern laboratories specifically designed for biological research. It will accommodate working arrangements for the single researcher or for large groups. The center will house the very extensive mouse colony, and, in separate, isolated quarters, a facility for sensitive transgenic or immune-deficient mice. X-ray crystallography, flow cytometry, electron microscopy, computer workstations, and other facilities will be accommodated with easy access to the laboratories. The biology library and conference rooms will be in the same building, as will the offices and classrooms of the ORNL-University of Tennessee Graduate School of Biomedical Sciences.

In the immediate neighborhood of the building will be the current Environmental Sciences Division buildings, and, not far away, the anticipated Advanced Neutron Source, with facilities specifically dedicated to analyzing biological materials. Within easy walking distance will be other basic science divisions like Health Sciences Research (including Nuclear Medicine), Chemical and Analytical Sciences, Physics, Solid State Physics, Engineering Physics and Mathematics, Instrumentation and Controls, and the new Center for Computational Sciences.

The Center for Biological Sciences will be readily accessible to visitors and guest users--and ready to move into the 21st century.


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