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of the patient’s personal wishes as an "improperly biasedprocedural obstacle" that was really designed to frustrate the"fundamental right to be free of unwanted artificialnutrition and hydration".Nancy Cruzan’s parents, defeated in their struggle to

speak for their daughter, went back to court in Missouri withnew evidence. Additional friends testified and her attendingphysician, who had originally opposed ending her

treatment, now supported allowing her to die. The State ofMissouri also withdrew its opposition. This time the trialcourt again ruling that treatment could be stopped,described the evidence of her wishes as "clear and

convincing".The importance of the case is twofold. First, the US

Supreme Court for the first time articulated the existence ofa constitutionally protected liberty interest that

encompasses a right to refuse life-sustaining treatment,including tube feeding. States may now regulate the exerciseof the right to ensure that individual wishes are beinghonoured, but they may not deny it to their citizens. All earlyindications are that states are more likely to act to expandtheir law to allow families to speak for incompetent patients,rather than limiting the exercise to those who have clearlyspoken for themselves. Second, and just as important, theCruzan family, by publicly persevering on behalf of whatthey know their daughter would have wanted, heightenedthe whole country’s awareness of the issues that face manypatients and families. Nancy Cruzan, like others before her,became a symbol of medicine’s ability to sustain life formuch longer than the patient herself would have wanted.Death for 70% of Americans is now an orchestrated event;someone-patient, family, or physician-makes a decisionto stop or not give some form of treatment that could haveprolonged life. The Cruzan case drew public attention tothis and motivated hundreds of thousands of people to maketheir personal wishes known.

260 W 57th St,New York, NY 10107, USA

Fenella Rouse,Executive director,Concern for Dying Societyfor the Right to Die

Noticeboard

Cancer families and tumour suppressionAs genetic causes of cancer, oncogenes have held the limelight.

But another group of genes can also be involved in initiation ofcancer. These are the tumour suppressor genes, whose usualfunction seems to be to control cell proliferation. Tumorigenesisresults when this function is altered by mutation. There is goodevidence that retinoblastoma, Wilms’ tumour, and one form ofcolon cancer, for example, arise in this way. Two groups of USworkers, both based at the National Cancer Institute, Bethesda,have now identified two different mutations within a single gene infamilies with Li-Fraumeni syndrome.12 Members of families withthis rare genetic syndrome, which is inherited as an autosomaldominant trait, are highly susceptible to a variety of malignancies,especially of the breast. Li, Fraumeni, and colleagues’ andSrivastava et alz have traced the genetic origin of the syndrome togermline mutations in a tumour suppressor gene, p53, onchromosome 17.The rarity of cancer families, the high mortality rate among

affected family members, and the lack of an unambiguous definitionof the syndrome meant that linkage studies would not be helpful inthe search for the miscreant gene. The alternative was to look for acandidate gene, and the most likely one was p53, since mutations inthis gene had already been found in a large proportion ofnon-familial human tumours (though not in the patients’ normal

cells). In one Li-Fraumeni family Li et al identified a pointmutation in codon 245 (a C-G substitution, leading to the

production of aspartic acid instead of glycine) in non-cancerous skinfibroblasts from four members (the proband and his brother, father,and paternal aunt), all of whom had cancer; all the cells studied alsohad one normal allele. The mutant gene was not found in cells fromthe proband’s mother and paternal grandfather, both of whom hadmarried into the cancer-susceptible lineage. Srivastava et al found aC-T substitution (which changed an arginine to tryptophan) incodon 248 in skin fibroblasts or lymphocytes in two of five familieswith the syndrome.Two puzzling features of these germline p53 mutations are that

the associated tumours may take around 30 years to develop and thatonly one or two tumours usually develop in an individual, despitethe presence of the mutation in all body cells. Probably the inheritedmutation is only the initiating event in carcinogenesis in Li-Fraumeni families, the onset of malignancy depending on anaccumulation of mutations, not just the loss of the wild-type p53allele.An international working group recently set up to investigate

Li-Fraumeni syndrome has so far enrolled nearly a hundredfamilies. One of its tasks will be to examine members for p53germline mutations. The ability to detect germline p53 mutationscreates another, more onerous, one, as Li and colleagues pointout-that is, to develop strategies for the care of carriers of themutation, who are at exceptionally high risk of cancer.

1. Malkin D, Li FP, Strong LC, et al Germ line p53 mutations m a familial syndrome ofbreast cancer, sarcomas, and other neoplasms. Science 1990, 250: 1233-38

2. Srivastava S, Zou Z, Pirollo K, Blattner W, Chang EH. Germ-line transmission of amutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome Nature1990; 348: 747-49

Disinfectants

Every year in the USA$1 billion are spent on disinfectants for usein hospitals, schools, restaurants, and homes, but up to 20% of the4000 disinfectants on the market may be ineffective, according to areport from the US General Accounting Office (GAO).’ Users ofdisinfectants, the report points out, may be placing themselvesand others at risk of infection, as well as spending moneyunnecessarily. The GAO review was prepared in response to

mounting public concern in the US about the efficacy ofdisinfectants and was the subject of a major Congressional hearing.Under the Federal Insecticide, Fungicide, and Rodenticide Act,

all disinfectants have to be licensed with the EnvironmentalProtection Agency (EPA) before they can be marketed. The EPAmay register a disinfectant only if it judges that the product iseffective, when used as proposed, without causing an unreasonablerisk to health or the environment. However, the EPA does not itselftest for efficacy but relies on data provided by the manufacturers.

Until 1982 the EPA carried out limited testing, both before andafter registration, but abandoned this practice because of budgetconstraints. Moreover, the EPA has no enforcement strategy toensure that disinfectants, once registered, work as claimed. As aresult, manufacturers can, intentionally or inadvertently, sellineffective batches of disinfectants after registration.Almost all the disinfectant efficacy test methods and performance

standards accepted by the EPA have, says the report, been"embroiled in scientific controversy" for over a decade. Lack ofagreement between the results of different tests has discouragedsome states from attempting to enforce their own efficacy standards,and the GAO review criticises the EPA for accepting the testswithout evaluating their validity. The EPA is urged to establishspecific criteria for evaluating tests and for determining whenindependent laboratory data are needed.The EPA is also recommended to set up an enforcement strategy,

in conjunction with states, user groups, and industry, and toconsider charging fees for registraton to finance laboratory facilitiesthat would enable the EPA to resume testing and research.

1. Disinfectants: EPA lacks assurance they work. United States General AccountingOffice report to Congressional requesters (GAO/RCED-90-139). 1990. Up to 5free copies may be obtained from the US General Accounting Office, PO Box 6015,Gaithersburg, MD 20877, USA (tel 202-275-6241).