1651 inmates than do the UK, France, Spain, Sweden, and Finland combined.13 Rates are expected to soar under new "three strikes you’re out" legislation (ratified in the November, 1994, California election), which locks inmates away for life for third felony arrests. By the year 2000, California will probably house over 230000 inmates, that number requiring an additional twenty-four prisons (data from California Department of Corrections, Office of Communication, Sacramento). We are confronting the AIDS epidemic. Are we ready to confront the new epidemic of prison growth? Jan Diamond Merrithew Memorial Hospital, Martinez, California, USA 1 Global Programme on AIDS. WHO guidelines on HIV infection and AIDS in prisons. Geneva: World Health Organization, 1993. 2 Hammett TR, Harold L, Gross M, Epstein J. 1992 update: HIV/AIDS in correctional facilities. Washington, DC: US Department of Justice, National Institute of Justice, 1994. 3 Centers for Disease Control and Prevention. Risk behaviors for HIV transmission among intravenous drug users not in drug-treatment— United States, 1987-1989. MMWR 1990; 39: 273-76. 4 Castro K, Shansky R, Scardino V, Narkunas J, Coe J, Hammett T. HIV transmission in correctional facilities. VII International Conference on AIDS, Florence, 1991 (abstr MC 3067). 5 Horsburgh CR, Jones JQ, McArthur T, Ignacio T, Stock P. Seroconversion to HIV in prison inmates. Am J Public Health 1990; 80: 209-10. 6 Centers for Disease Control and Prevention. HIV/AIDS surveillance report; 6(1): 15; October, 1994. 7 Albert P, Eisenberg R, Hansell D, Marcus JK. National Lawyers Guild, AIDS practice manual: a legal guide. 3rd ed, 1992: 14·15-14·23. 8 Greenberg R. Voluntary HIV testing in the San Francisco county jails, an ethical dilemma. In: X International Conference on AIDS, Yokohama, 1994: PD0525 (abstr). 9 Behrendt C, Kendig N, Dambita C, Horman J, Lawlor J, Vlahov D. Voluntary testing for HIV in a prison population with a high prevalence of HIV. Am J Epidemiol 1994; 139: 918-26. 10 Andrus JK, Fleming DW, Knox C, et al. HIV testing in prisoners: is mandatory testing mandatory? Am J Public Health 1989; 79: 840-42. 11 Hoxie NG, Vergeront JM, Frisby HR, Pfiser JR, Golubjatnikov R, Davis JP. HIV seroprevalence and the acceptance of voluntary testing among newly incarcerated male prison inmates in Wisconsin. Am J Public Health 1990; 80: 1129-31. 12 Harding TW, Schaller G. WHO Global Programme on AIDS, HIV/AIDS and prisons: updating and policy review, a survey covering 56 prison systems in 31 countries. Geneva: WHO, 1992: 15-17. 13 Mauer M. Americans behind bars: the international use of incarceration 1992-1993. Washington, DC: Sentencing Project, 1994. 14 Bureau of Justice Statistics. Midyear prisoner statistics. Washington, DC: Bureau of Justice, 1994. Superoxide dismutase and ALS An association between mutations in the gene for copper/zinc superoxide dismutase (SOD-1), and familial amyotrophic lateral sclerosis (FALS, motoneuron disease) was reported last year.’ A meeting in September organised by researchers from the University of Chicago, who were involved in the initial discovery, offered the opportunity to assess subsequent developments. The aims were to assess progress in ascertainment of SOD-1 mutations in FALS families, to determine the relation between SOD-1 mutations and the mechanism of neuronal death in FALS, to discuss the role of free radical toxicity in ALS, and to look forward to the potential treatment approaches raised by these findings. The initial report of SOD-1 mutations was based on large ALS families who were participating in genetic linkage studies. Smaller families were then investigated, and 23 different mutations, in 17 codons of the SOD-1 gene, have now been reported.2-8 Mutations have also been found in apparently sporadic cases of ALS, but further investigation usually revealed a previously unknown family history. Consequently the prevalence of SOD-1 mutations in sporadic ALS is thought to be very small. As more families have been studied, the frequency of mutations of SOD-1 in FALS has declined from about 50%, to around 15-20%.9 FALS accounts for about 5-10% of all ALS, so these mutations are found in less than 2% of all patients with ALS. We do not know whether these patients with FALS have the same disease mechanism as those with the non- familial disorders but individuals with SOD-1 mutations cannot be distinguished clinically from those without mutations. An autosomal recessive juvenile onset type of FALS has been linked to a region on chromosome 2,’ and the genetic causes in the remaining 80% of FALS have yet to be elucidated." 11 Discovery of SOD-1 mutations has led to a flurry of research into the potential involvement of free radicals in the pathogenesis of ALS. Results accumulated over 20 years have implicated free radicals in many diseases, including other neurodegenerative conditions such as Parkinson’s disease.’2 Copper/zinc SOD is an intracellular enzyme that is present throughout the body but with a differential tissue expression. SOD activity has been studied in erythrocytes and cerebral cortex in ALS," and a reduction of around 50% has been reported in affected members of some families. 14 One suggestion was that replacement of SOD might be curative. However, those with longstanding experience in SOD biochemistry have reservations about some of the techniques and conclusions-for example, the assay might merely be measuring protein instability, which is not important in vivo. Transgenic mice expressing human SOD with the mutations found in FALS have now been produced in several laboratories.9 Some of these mice develop a progressive disease with features of both flaccidity and spasticity. Pathologically there is clear lower motor neuron degeneration, but whether the mouse disorder is a true model of human ALS remains to be determined. Some mice that have developed the disease have normal SOD activity but a striking increase in mutant SOD protein. So, is FALS due to reduced SOD activity, with consequent free-radical-mediated damage to neurons, or to an altered or toxic function of the mutated SOD protein? Some human FALS SOD-1 mutations also seem to have normal SOD activity. 15 Since there is a subtle interrelation between the various enzymes involved in free radical biochemistry-including manganese SOD (SOD-2, mitochondrial SOD), extracellular SOD (SOD-3), glutathione peroxidase, and catalase-correction of a presumed SOD deficiency may not achieve the expected biochemical effect. Moreover, if there is no physiological deficiency of SOD activity, supplementation of SOD may exacerbate the disease through free-radical mechanisms. There are difficulties with the administration of the currently available bovine SOD, and pharmaceutical companies are developing other agents with similar function. Treatment of the specific group of FALS patients with the SOD-1 mutation is complex. Therapy should probably begin before the onset of disease, but within a family the onset may vary widely-eg, from age 20 years to 80 years. Some affected individuals may have a normal life without ever manifesting the disease. Animal models pave the way for