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医学 1922

胰腺的内分泌

弗雷德里克·班廷 与 查尔斯·贝斯特

一份胰腺提取物,把濒死糖尿病狗的血糖拉了回来——也给了世界胰岛素。

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In depth · the introduction

一个世纪以前,被诊断出糖尿病,几乎等于一纸死刑——直到两个年轻的加拿大人,从狗的胰腺里做出一份提取物,把一只濒死动物的血糖,从悬崖边拉了回来。

核心想法

你的胰腺,同时在做两件事。它的大部分,在制造消化液;而散落其间的一小簇簇细胞——朗格汉斯岛——则在制造一种激素:胰岛素,它让你的身体能把糖当作燃料来用。在糖尿病里,那些胰岛细胞失灵了,糖便危险地在血里堆积起来;而在 1922 年以前,对此束手无策。

班廷与贝斯特推断:要想救出胰岛的那种激素,你得先把腺体里负责消化的那部分除掉——他们怀疑,正是它,在人们每次试图提取激素时,把激素「嚼碎」了。于是,他们把那些排出消化液的导管结扎起来。「断了粮」的消化组织,在数周内枯萎凋零,把珍贵的胰岛留了下来。他们从那萎缩的腺体里挤出一份提取物——注入一只糖尿病狗体内时,它那高得吓人的血糖,一次又一次地降了下来;而且剂量越大,效果越显。

它是如何诞生的

弗雷德里克·班廷是一位年轻的外科医生,几乎没什么研究经验,只有一个执拗的念头——1920 年的某个夜里,他把它草草记在了笔记本上。他把这念头带去找了 J·J·R·麦克劳德,多伦多大学一位受人敬重的生理学家;麦克劳德将信将疑,却还是在 1921 年的那个夏天,把实验室的一角、十条狗,以及一名学生助手——查尔斯·贝斯特——交给了班廷,由贝斯特来做血糖测定。

那个夏天极其残酷:狗接连死去,提取物屡屡失败,经费也见了底。可到了秋天,他们已经有一条靠着提取物活下来的狗了。麦克劳德把整个实验室都投了进来,又请来生物化学家詹姆斯·科利普,由他把提取物纯化到足以在人身上一试的程度。1922 年 1 月,一个名叫伦纳德·汤普森的垂死少年(14 岁)接受了注射;他的血糖下降,渐渐康复。从一个念头到一种药物,这场赛跑,前后不过十八个月。

它为何重要

胰岛素并没有治愈糖尿病——至今仍未——但它把一场迅速而确定的死亡,变成了一种人们可以与之共处数十年的状况。不出两年,它便以吨计地被制造出来、运往世界各地。很少有哪项发现,如此直接而迅速地,挽救了如此多的生命。

它还承载着一桩静默的良心之举:班廷、贝斯特与科利普,把那项专利以「每人一美元」的价格卖给了多伦多大学,他们相信,一项如此重要的发现,应当属于每一个人,而不该让他们暴富——这份立场,在今天关于胰岛素价格的争论里,仍有回响。

一个可以想象的画面

想象一座果园,紧挨着它盖了一间罐头厂。这罐头厂(胰腺里负责消化的那部分)离得太近,以至于你每次想去采摘果子(胰岛产出的那种激素),机器都会把它绞烂。班廷与贝斯特的妙招,是先把罐头厂关停——切断它的供应线,任它锈坏——好让果子终于能被整颗摘下。把负责消化的组织断掉,激素便能存活得够久,等你来收集。

一张糖尿病狗血糖的可交互曲线图:拖动剂量滑块,看曲线如何变化。不注射时,血糖危险地居于约 300 的高位;中等剂量把它带回健康区间;剂量过大则把它压得过低,随后胰岛素失效、血糖再度爬升。

它的位置

胰岛素,是内分泌学——研究身体里那些化学信使的学问——的第一项伟大成就。在它之前,人们刚刚意识到:腺体可以通过血流,从远处掌控身体;而在它之后,是会把胰岛素的结构一个字母一个字母读出来、甚至让细菌来培育它的现代分子生物学。这个故事,也与本馆中另一个故事押着韵:亚历山大·弗莱明的青霉素——同样是一份来自卑微来源的提取物,同样改变了医学的能力边界——只不过,胰岛素从实验台走到病床,要快得多。

The original document
Original source text
F. G. Banting & C. H. Best · J. Lab. Clin. Med. 7 (Feb. 1922): 251–266
The hypothesis underlying this series of experiments was first formulated by one of us in November, 1920, while reading an article dealing with the relation of the isles of Langerhans to diabetes. From the passage we drew the conclusion that, since the acinous but not the island tissue of the gland degenerates after ligation of the ducts, advantage might be taken of this fact to prepare an active extract of the islet tissue.
The subsidiary hypothesis was that trypsinogen or its derivatives was antagonistic to the internal secretion of the gland; and that, in former attempts to prepare an extract by ordinary methods, the active principle had been destroyed by the proteolytic ferment of the gland.
[ … ]
The ducts of the pancreas were ligated in a number of dogs. After an interval of from seven to ten weeks the degenerated gland was removed, cut into small pieces, ground with sand in a chilled mortar, and extracted with chilled physiological saline. The filtered extract was injected intravenously into dogs rendered diabetic by complete removal of the pancreas.
Intravenous injections of extract from dog's pancreas, removed from seven to ten weeks after ligation of the ducts, invariably exercises a reducing influence upon the percentage sugar of the blood and the amount of sugar excreted in the urine.
The extent and duration of the reduction varies directly with the amount of extract injected. The blood sugar of a diabetic dog may be reduced to a normal or subnormal level by the injection, and the excretion of sugar in the urine may be abolished. The respiratory quotient is raised, indicating that the animal is again able to burn carbohydrate.
Pancreatic juice destroys the active principle of the extract, a fact which lends support to the view that the failure of earlier workers was due to the destruction of the internal secretion by the external secretion of the gland during the process of extraction.
[ … ]
F. G. Banting & C. H. Best · Department of Physiology, University of Toronto · February 1922