Tritium: Tracking the Molecules of Life

Heart disease, cancer, and stroke, continue to be the top three causes of death in the United States; pneumonia/influenza, and diabetes take the sixth and seventh slots, and HIV/AIDS is a fast-rising number eight. For women in their 40s, the leading cause of death is breast cancer. What these deadly diseases have in common is that all are being studied by medical researchers with the help of trace amounts of a radioactive form of hydrogen called tritium.

Hydrogen is the simplest, most common of all the elements. More than 60-percent of the atoms in a human body, for example, are hydrogen, consisting of a nucleus with a solitary proton. Tritium is an isotope of hydrogen, meaning its chemical properties are identical but its nucleus is different -- in addition to a proton it also contains two neutrons. This neutron-rich nucleus of tritium is unstable; it "radiates" energy as it "decays" into a harmless helium nucleus. Though the radiation emitted by tritium is weak, it is immensely valuable as a means of observing chemical processes that would otherwise be invisible.

Researchers use tritium as a sort of homing device, attaching it to a protein or other type of molecule in order to trace the molecule's progress through the steps of a chemical reaction. One or more of the normal hydrogen atoms in the molecule is replaced with tritium to create a new molecule that gives off a detectable signal. This signal stems from tritium's emission of a beta particle when one of its neutrons becomes a proton. Tritium's beta radiation is so weak it cannot penetrate human skin. However, it is readily detected even through a dense crowd of atoms and molecules.

The process of replacing tritium for hydrogen in a chemical compound is called "labeling." Some tritium-labeled compounds can be obtained from commercial sources or are manufactured by pharmaceutical companies for their own use. However, many of the highly specialized tritium-labeled compounds used in biomedical studies are available from only one source in this country: the National Tritium Labeling Facility at the Lawrence Berkeley National Laboratory.

Established in 1982, the NTLF at Berkeley Lab has been a place to which biomedical researchers can come and be assisted in the creation of new tritium-labeled compounds, often using brand new labeling techniques. This collaboration has led to the development of a number of radiotracers (compounds tagged with radioactive atoms) that are now staple tools of medical science. From norepinephrine, a hormone used in the treatment of stroke victims, to cyclosporine, an immunosuppressant used in tissue and organ transplants, to interleukin, a protein used to help protect the immune systems of AIDs patients, compounds tagged with tritium at the NTLF have dramatically expanded the scope of medical research at the cellular and molecular levels.

"Through a combination of radiation detection and nuclear magnetic resonance spectroscopy techniques, we can identify the precise location of tritium atoms in labeled compounds, and track their location and metabolism in living systems (cells in culture, insects and mice)," says Phil Williams, a chemist who manages the NTLF and is one of its principal investigators. Tritium labeling makes compounds a thousand times more sensitive to detecion than radiocarbon which means it can be used to follow biological activities that involve tiny quantities of substances.

Collaborators and users who have availed themselves of the scientific expertise and unique instrumentation at the NTLF hail from all around the U.S.A. Mostly, they come from academia: from the nation's top research schools, such as the Universities of California, Michigan, and Pennsylvania, the State University of New York, Rutgers, MIT, and Yale; and from smaller programs at schools such as the University of the Pacific, Emporia State University in Kansas, and the Universidad Central del Caribe in Puerto Rico.

"Academic researchers are more willing than scientists in private industry to take on difficult and speculative studies," explains Williams. "Also, academic researchers tend to be more interested in studying mechanisms rather than medicines which means they go after the roots of problems."

Federally funded by the Department of Energy and the National Institutes Of Health, the NTLF is open to all qualified researchers. Collaborators and users have also come from pharmaceutical companies such as Bristol Myers Squibb, the Pharmacia & Upjohn Company, and Genentech; and from non-profit organizations such as the American Health Foundation.

Weak though it may be, tritium's beta-emissions can be harmful if inhaled or ingested into the human body. In a given year, the NTLF uses approximately 10,000 curies of tritium gas which is almost enough to fill a one gallon container. Of this amount, about two-percent actually goes into a labeled compound, 80-percent is recycled, and 17-percent is disposed of as radioactive waste. Less than one-percent escapes into the environment, equivalent, in liquid form, to less than a drop of water.

"Working with tritium is like working with any other hazardous material, you have to understand the hazards and be careful," says Williams. Handling and monitoring procedures at the NTLF are strict and even though the facility has operated well within regulatory limits, improved control systems and additional protective features are continually being installed.

What are the health risks posed by the NTLF? The exposure to local residents, including UC Berkeley campus students and visitors to the Lawrence Hall of Science, is too low to be measured and must be calculated from computer models. The model used in a "risk assessment" study found that local residents incur virtually no increased risk as a result of operations at the NTLF.

Further information on the NTLF health risk assessment can be found at the University of California Main Library second floor main documents room, south end. For more information about the NTLF write to the National Tritium Labeling Facility, MS 75-123, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720.

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