problem, as Raffle notes, is that the number of women with CIN far exceeds the number who would develop cervical cancer in the absence of treatment. I too am concerned about the anxiety and costs generated by a “positive” result leading to “ten being treated for every one that would develop cancer”. However, I am perplexed by the statement that “an abundance of lesions that are classified as cancer . . . represent a reversible symptomless phenomenon in most cases”. Does this mean that invasive lesions are reversible? How are we to fill the void if we cease to “seek out and destroy ‘precursor lesions’”? Cervical screening and the treatment of detected high-grade lesions is not perfect but it does prevent many cancers that would have developed in the absence of screening. J Thomas Cox Student Health Service, University of California, Santa Barbara, CA 93106-7002, USA 1
Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1998. CA Cancer J Clin 1998; 48: 6–29 [published erratum appears in CA Cancer J Clin 1998; 48: 192]. Hakama M. Screening for cervical cancer: experience in Nordic countries. In: Franco E, Monsonego J, eds. New developments in cervical cancer screening and prevention. Oxford: Blackwell Science, 1997: 190–99. Raffle AE, Alden B, MacKenzie EFD. Detection rates for abnormal cervical smears: what are we screening for? Lancet 1995; 345: 1469–73. Quinn M, Babb P, Jones J, Allen E, UK Association of Cancer Registries. Effect of screening on incidence and mortality from cancer of the cervix in England: evaluation based on routinely collected statistics. BMJ 1999; 318: 904–08. Sasieni P, Cuzick J, Farmery E. Accelerated decline in cervical cancer mortality in England and Wales. Lancet 1995; 346: 1566–67.
Modern epidemiology: forward to the 18th century! Sir—The historical father of epidemiology is claimed to be John Snow. This view should be reconsidered after a careful reading of another work by the philosopher Jean le Rond D’Alembert (1717–83), published in 1760 by the Académie Royale des Sciences de Paris. D’Alembert addressed the safety of inoculation against smallpox, a major controversy in Europe in the mid-18th century. In 48 pages, d’Alembert developed a visionary analysis of risks for decision-making.1 I would like to set
out extracts from this pioneering work, translated from old French: “From the age of four until the average age of death, smallpox kills between 1/8 and 1/7 of French residents. On the other hand, inoculation is said to be associated with a risk of death in the order of 1/300, ie, as it is said by inoculation supporters, 40 times lower that the risk induced by the disease itself. Can we accept this kind of comparison? Obviously not! The risk of death induced by inoculation concerns the two following weeks, with a maximum of one month, while the risk of dying from natural smallpox is spread over all the life which means that the probability of contracting smallpox during the rest of life decreases with age. Conversely, it would be inappropriate, as proposed by the opponents of inoculation, to compare the risk of death caused by natural smallpox and by inoculation during the month following the latter. Indeed, during this time interval, the risk induced by inoculation is much greater, whatever the age of the subject, than the risk of being infected. However, after this one-month delay, the probability of contracting smallpox is assumed to be null for inoculated subjects, while for the others the cumulative risk increases month after month and becomes much greater than 1/300, at least if the subject is young enough”.
It is fascinating to see such basic evidence of risk assessment, which at times is forgotten today, so clearly expressed 240 years ago by a man whose name is omitted by most medical dictionaries and textbooks of epidemiology. I thank Jean René Brunetière (Executive Director of the French Medicines Agency) for providing me with d’Alembert’s manuscript and to Nicholas Moore (Université Victor Segalen, Bordeaux) for his valuable comments.
Bernard Bégaud Unité de Pharmaco-épidémiologie, Université Victor Segalen Bordeaux 2, 33076 Bordeaux, France 1
Jean Le Rond d’Alembert. Réflexions sur l’inoculation. Paris: Académie Royale des Sciences de Paris, 1760.
DEPARTMENT OF ERROR Tacrolimus in refractory polymyositis with interstitial lung disease—In this research letter by Chester V Oddis and colleagues (May 22, p 1762) the wrong figure was published. The correct figure is shown below.
D’Alembert developed the principles for considering the time variable when assessing and comparing risks: “From the preceding data, one may estimate that the risk of dying from smallpox is, on average, 1/3000 per month for a subject previously not infected and living in Paris. This crude estimate is not satisfactory because it does not consider the age of the subjects. It is obvious that the cumulative risk of contracting the disease varies according to age and decreases when approaching the expected term of life.”
Some pages earlier, D’Alembert refuted step by step the risk modelling made by his colleague Daniel Bernoulli assuming a constant hazard rate over life: “Calculations made by Bernoulli conclude that the life-expectancy of a smallpox-free 30 years old man which is 24 years and 3 months, would be increased to 27 years by inoculation. If one wants to evaluate the benefits of inoculation, it is simplistic to compare, as Bernoulli did, the immediate risk of fatality induced by inoculation (ie, 1/300 over one month) to the average gain in life expectancy. Doing that, this man would accept a probability of dying of 1/300 at the age of 30, in the prime of life, for an average gain of 2 years and 8 months after the age of 54, a period where abilities and quality of life are, by essence, decreased”.
Plasma homocysteine and all-cause mortality in diabetes—In this research letter by J D Kark and colleagues (June 5, p 1936), the second sentence of the second paragraph should have read: “Of the 239 participants reporting a physician’s diagnosis at the study interview in 1985 to 1987 . . .” In the second sentence of the third paragraph “albumin” should have been “protein”. In the fifth paragraph, the first sentence should have read: “. . . Jerusalem population (not described in all studies2) . . .” The Nobel Chronicles (1958)—In the figure of this Nobel Chronicle (June 12, p 2082), George Beadle is situated on the left, Joshua Lederberg in the middle, and Edward Tatum on the right. The Nobel Chronicles (1959)—In this Nobel Chronicle (June 19, p 2166), the correct spelling of one of the Nobel Laureates is Severo Ochoa. There is also an error of fact concerning Arthur Kornberg (the other Laureate): he moved in 1953 from the NIH to Washington University School of Medicine, St Louis, Missouri, until 1959, and then to Stanford University School of Medicine, California, where he has since remained.
THE LANCET • Vol 354 • July 31, 1999