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医学 1950

吸烟与肺癌

理查德·多尔 与 奥斯汀·布拉德福德·希尔

患肺癌的男性几乎全是吸烟者——从结局反推,照出了病因。

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In depth · the introduction

肺癌死亡,在一代人的时间里涨了十五倍——于是两位研究者问了一个简单的问题:在死于此病的男性里,有多少从未吸过烟?答案是:几乎没有。

核心想法

你不可能出于伦理去让人患上癌症,再来检验是什么导致了它。于是多尔与希尔把实验「倒着」做。他们找来一大批已经患上肺癌的病人(「病例」),又为每一位配上一名没有患病的相似病人(「对照」)——同性别、同年龄、同医院。然后,只是简单地问每个人:你吸不吸烟?

差距大得惊人。在患肺癌的男性中,几乎每一个都是吸烟者——649 人里只有 2 人从未吸过烟。而在匹配的健康男性里,不吸烟的要多得多。把这些数字摞起来,吸烟者落在癌症组里的可能性,约高出十四倍。这种「病例对比对照」的比较,后来成了医学中最有力的工具之一。

它是如何诞生的

第二次世界大战之后,英国的医生们大为警觉:死于肺癌的人数在一刻不停地攀升。两个嫌疑领跑——现代城市的煤烟与尾气,以及变得极为流行的香烟。年轻的医师理查德·多尔,与刚刚开创了随机临床试验的统计学家奥斯汀·布拉德福德·希尔联手,要弄清究竟是哪一个。

在 1948 到 1949 这两年里,他们派出受过训练的访谈者,走进二十家伦敦医院,询问了一千多名癌症患者,以及同样多的匹配对照。研究开始时,多尔自己也吸烟;结果如此清晰,以至于他在研究进行到一半时就把烟戒了。他们于 1950 年把论文发表在《英国医学杂志》上——恰恰与一支美国团队报告同一发现的那一周。

它为何重要

那时香烟无处不在——由医生代言、发给士兵、织进日常生活。要宣称它正在害死人,需要异常有力的证据,而单凭一项研究是会被驳回的。但这一项,先有一项平行的美国研究印证,又有多尔与希尔自己对四万名医生的长期随访佐证,慢慢扭转了大势。它支撑起其后的警示标签、广告禁令与公共卫生宣传——也教会了医学:当你无法做实验时,该如何去追猎疾病的病因。

一个可以想象的画面

想象某个街区接二连三地起火。你不能为了验证假设而去放火,于是你改为:走访每一户被烧过的房子,再走访它隔壁同样普通、却没被烧的房子,问问各家厨房里都有些什么。如果几乎每户失火的人家都有一台故障的取暖器,而没失火的大多没有,那么嫌疑就锁定了——你压根不必划一根火柴。这种「烧过对比没烧过」的倒推比较,正是病例对照研究所做的:癌症患者对比健康人,问谁吸烟。

一个可交互面板,两排各一百个圆点——患肺癌的男性与健康男性。两个滑块设定每排中有多少人吸烟;圆点随之换色,并算出一个比值比,显示吸烟在癌症患者中究竟常见多少。

它的位置

这是现代流行病学的一块奠基石。希尔早已给了医学随机试验(它检验疗法的方式);在这里,他与多尔又给了它病例对照研究(它寻找病因的方式)。这项工作,与本馆其他几个医学转折点并肩而立;而它的方法——把病人与健康人相比对、权衡其中的几率——如今潜藏在几乎每一条「什么对你有益、什么对你有害」的新闻背后。

The original document
Original source text
Richard Doll & A. Bradford Hill · British Medical Journal 2(4682): 739–748 · September 30, 1950
The increase in lung cancer
The number of deaths attributed to cancer of the lung provides one of the most striking changes in the pattern of mortality recorded by the Registrar-General. For example, in the quarter of a century between 1922 and 1947 the annual number of deaths recorded increased from 612 to 9,287, or roughly fifteenfold. This remarkable increase is, of course, out of all proportion to the increase of population — both in total and, particularly, in its older age groups.
The method of the investigation
Twenty London hospitals were asked to co-operate by notifying all patients admitted to them with carcinoma of the lung, stomach, colon, or rectum. … On receipt of the notification an almoner, engaged wholly on research, visited the hospital to interview the patient, using a set questionary.
As well, however, as interviewing the notified patients with cancer of one of the four specified sites, the almoners were required to make similar inquiries of a group of “non-cancer control” patients. … for each lung-carcinoma patient visited at a hospital the almoners were instructed to interview a patient of the same sex, within the same five-year age group, and in the same hospital at or about the same time.
The result
It will be seen that the vast majority of men have been smokers at some period of their lives, but also that the very small proportion of those with carcinoma of the lung who have been non-smokers (0.3%) is most significantly less than the corresponding proportion in the control group of other patients (4.2%).
[ … ]
This is not necessarily to say that smoking causes carcinoma of the lung. The association would occur if carcinoma of the lung caused people to smoke or if both attributes were end-effects of a common cause. The habit of smoking was, however, invariably formed before the onset of the disease … so that the disease cannot be held to have caused the habit ; nor can we ourselves envisage any common cause likely to lead both to the development of the habit and to the development of the disease 20 to 50 years later.
We therefore conclude that smoking is a factor, and an important factor, in the production of carcinoma of the lung.
Richard Doll · A. Bradford Hill · Statistical Research Unit of the Medical Research Council, London · 1950