JOVANA
Library Glossary Getting Started Three Levels Fields How it works Mission
Join the mission
Back to the library
醫學 1922

胰腺的內分泌

弗雷德里克·班廷 與 查爾斯·貝斯特

一份胰腺提取物,把瀕死糖尿病狗的血糖拉了回來——也給了世界胰島素。

Choose your version
In depth · the introduction

一個世紀以前,被診斷出糖尿病,幾乎等於一紙死刑——直到兩個年輕的加拿大人,從狗的胰腺裡做出一份提取物,把一隻瀕死動物的血糖,從懸崖邊拉了回來。

核心想法

你的胰腺,同時在做兩件事。它的大部分,在製造消化液;而散落其間的一小簇簇細胞——朗格漢斯島——則在製造一種激素:胰島素,它讓你的身體能把糖當作燃料來用。在糖尿病裡,那些胰島細胞失靈了,糖便危險地在血裡堆積起來;而在 1922 年以前,對此束手無策。

班廷與貝斯特推斷:要想救出胰島的那種激素,你得先把腺體裡負責消化的那部分除掉——他們懷疑,正是它,在人們每次試圖提取激素時,把激素「嚼碎」了。於是,他們把那些排出消化液的導管結紮起來。「斷了糧」的消化組織,在數週內枯萎凋零,把珍貴的胰島留了下來。他們從那萎縮的腺體裡擠出一份提取物——注入一隻糖尿病狗體內時,牠那高得嚇人的血糖,一次又一次地降了下來;而且劑量越大,效果越顯。

它是如何誕生的

弗雷德里克·班廷是一位年輕的外科醫生,幾乎沒什麼研究經驗,只有一個執拗的念頭——1920 年的某個夜裡,他把它草草記在了筆記本上。他把這念頭帶去找了 J·J·R·麥克勞德,多倫多大學一位受人敬重的生理學家;麥克勞德將信將疑,卻還是在 1921 年的那個夏天,把實驗室的一角、十條狗,以及一名學生助手——查爾斯·貝斯特——交給了班廷,由貝斯特來做血糖測定。

那個夏天極其殘酷:狗接連死去,提取物屢屢失敗,經費也見了底。可到了秋天,他們已經有一條靠著提取物活下來的狗了。麥克勞德把整個實驗室都投了進來,又請來生物化學家詹姆斯·科利普,由他把提取物純化到足以在人身上一試的程度。1922 年 1 月,一個名叫倫納德·湯普森的垂死少年(14 歲)接受了注射;他的血糖下降,漸漸康復。從一個念頭到一種藥物,這場賽跑,前後不過十八個月。

它為何重要

胰島素並沒有治癒糖尿病——至今仍未——但它把一場迅速而確定的死亡,變成了一種人們可以與之共處數十年的狀況。不出兩年,它便以噸計地被製造出來、運往世界各地。很少有哪項發現,如此直接而迅速地,挽救了如此多的生命。

它還承載著一樁靜默的良心之舉:班廷、貝斯特與科利普,把那項專利以「每人一美元」的價格賣給了多倫多大學,他們相信,一項如此重要的發現,應當屬於每一個人,而不該讓他們暴富——這份立場,在今天關於胰島素價格的爭論裡,仍有回響。

一個可以想像的畫面

想像一座果園,緊挨著它蓋了一間罐頭廠。這罐頭廠(胰腺裡負責消化的那部分)離得太近,以至於你每次想去採摘果子(胰島產出的那種激素),機器都會把它絞爛。班廷與貝斯特的妙招,是先把罐頭廠關停——切斷它的供應線,任它鏽壞——好讓果子終於能被整顆摘下。把負責消化的組織斷掉,激素便能存活得夠久,等你來收集。

一張糖尿病狗血糖的可互動曲線圖:拖動劑量滑桿,看曲線如何變化。不注射時,血糖危險地居於約 300 的高位;中等劑量把它帶回健康區間;劑量過大則把它壓得過低,隨後胰島素失效、血糖再度爬升。

它的位置

胰島素,是內分泌學——研究身體裡那些化學信使的學問——的第一項偉大成就。在它之前,人們剛剛意識到:腺體可以通過血流,從遠處掌控身體;而在它之後,是會把胰島素的結構一個字母一個字母讀出來、甚至讓細菌來培育它的現代分子生物學。這個故事,也與本館中另一個故事押著韻:亞歷山大·弗萊明的青黴素——同樣是一份來自卑微來源的提取物,同樣改變了醫學的能力邊界——只不過,胰島素從實驗台走到病床,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