Friday, November 26, 2010

Life Lines 52


I studied radiation genetics with H. J. Muller, the geneticist who founded the field of radiation genetics. I learned how to induce gene mutations and chromosome breakage by exposing fruit flies to x-rays and used this technique to induce a number of mutations in a given gene to study its structure. In the 1950s when I was Muller’s student, the world was steeped in debates about the effects of radiation from nuclear bomb testing and the world was fearful of an atomic war between the two sides of the on-going Cold War. Muller discovered the induction of gene mutations by x-rays in 1927. As he analyzed and tried to map these mutations he noted that a significant portion of these must be associated with something that prevented their being mapped. By 1929 he and his colleagues showed that these events were caused by chromosome breakage that rotated parts of chromosomes, deleted portions of others, or switched pieces among the chromosomes. This left behind a puzzle. At the high doses he used, about 90 percent of the eggs laid did not hatch. He called these dominant lethals. It was not until 1940 that he designed experiments with his student G. Pontecorvo, and showed that these were caused by breakage leading to what Barbara MacClintock called “the breakage-fusion bridge cycle.” In Muller and Pontecorvo’s analysis, they proved that the death of these embryos was caused by the abnormal joining of chromosome fragments that tied up cell division and killed the cell.

The recognition of the breakage-fusion-bridge cycle allowed Muller to interpret radiation sickness in Hiroshima and Nagasaki, where the cells of dividing tissues (such as our skin, guts, blood vessel linings, and blood-forming tissues) die and produce the symptoms of that disease. It also made Muller an advocate of radiation protection, because he and his colleagues had demonstrated that the induction of gene mutations or chromosome breaks was proportional to the dose received. He even showed that diagnostic doses of x-rays induce gene mutations and cautioned medical personnel to shield their patients and themselves from these minor doses, which are cumulative. It took a long time to educate the public about radiation protection. In the 1920s x-rays were used to measure foot size in shoe-stores, to straighten out bowlegs in children, to induce ovulation in infertile women, and to check the position of a fetus in the last trimester of pregnancy. None of these practices are done today.

What we need to know is how to balance medical need and our own risks. We need to know that at diagnostic doses (chest x-rays, dental x-rays) that risk is very low (but not non-existent). We also need to know that shielding protects our reproductive cells and thus diagnostic radiation cannot induce mutations to be passed on to future generations. We also need to know that in a choice between living now or dying much later from a possible tumor cell induced for treatment of another immediate disease, it makes sense to be treated with chemotherapy or radiation treatment. Because I am science literate I requested shielding for my family and myself at a time when it wasn’t standard practice to do so by physicians and dentists. Weighing risk and benefit should be our choice as much as possible.

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