講題一（對學生）從病毒性肝炎看醫學研究
人類的健康維護源自以往許多醫學研究，什麼是醫學研究呢？本次演講將以肝炎研究為例來闡釋醫學研究，由如何確認問題開始，怎樣找到病因，再由病因被找到後的一連串發展來探討醫學研究的意義。
自古以來，人類就被「黃疸病」所困擾，然而原因一直不清楚，直到 1883 年德國醫生 L u rman 對 Bremen 港 1289 名接種過天花疫苗後發生黃疸的 190 名（ 15% ）工人作了詳細的記載，才逐漸有了些概念。其後由於醫療的進展，須要以注射的方法給藥，給藥後也有一些人發生黃疸，導致 1943 年 MacCallum 指出可能因注射針／筒消毒不全有病原體存在而產生黃疸的觀念。 1943 年 Beeson 也指出輸血可能引起黃疸。其間有許多學者以各種動物接種想要找出病原體，但全都失敗，然而在人體試驗方面，則有可觀的成果，證實了病原體比細菌還小 ─── 也就是濾過性病毒，而且也知道可以引起黃疸的病毒可能有兩種，其一是經口而入，潛伏期較短；另一種則是經注射或輸血引起，潛伏期較長，後來前者被命名為 A 型肝炎而後者則命名為 B 型肝炎。可惜一直沒有辦法找到病原體，直到 1960 年中期， Blumberg 發現了澳洲抗原，後來證實澳洲抗原其實是 B 型肝炎病毒外套上的成份，這個發現影響深遠，除了讓我們暸解 B 型肝炎，還讓我們知道如何來加以防治，其後更帶動了 A 型肝炎、 D 型肝炎、 C 型肝炎以及 E 型肝炎病毒的發現，貢獻實在很大，因此 Blumberg 獲頒 1976 年的諾貝爾醫學獎。
此次演講，也將介紹 B 型肝炎對台灣人的危害，以及科學家如何對抗 B 型肝炎，並藉以闡明醫學研究如何幫忙解決我們自己的健康問題，以及我們所獲得的成果。希望能幫助同學們暸解醫學研究如何創造新知、解決問題，為人們謀更大的福祉。
建議讀物：
1. Hepatitis B: The Hunt for a Killer Virus. Baruch S. Blumberg. Princeton University Press. Princeton , 2002.
中譯本： B 型肝炎：發現 B 型肝炎病毒與疫苗的諾貝爾獎之路。巴魯克．布倫伯格著 陳彥甫譯 商周出版 台北， 2004 年。
2. 肝炎聖戰：台灣公共衛生史上的大勝利。楊玉齡 羅時成著 天下遠見出版 台北， 1999 年。
Medical research: Explored from studies on viral hepatitis
Health of mankind is maintained and promoted by the achievements from medical research. What is medical research? I will explore this question by using the example of man's fight against viral hepatitis.
From ancient time, people suffered from an illness called “icterus” (Greek), “jaundice” (English) or “Huang-Dang-Bin” ( 黃疸病 ， Chinese) and the cause was unknown. The earliest scientific description was in 1883 when L u rman in Bremen (Germany) documented the occurrence of icterus in 1289 workers of the seaport. The 1289 workers had received small pox vaccination and 190 (15%) developed icterus (or jaundice). By contrast, none of those who received a different batch of vaccine developed jaundice. Human serum was added as stabilizer of the vaccine at that time. In later years, because of the progress in medicine, several drugs had to be given by injection and some patients developed jaundice subsequently. These observations led MacCallum to suggest needles and syringes in transmitting the agent that causes jaundice in 1943. In the same year, Beeson reported that blood transfusion could cause jaundice. Studies also revealed that jaundice was the result of injury to liver cells i.e., hepatitis. At that time, many investigators tried to identify the causal agent by animal experiments, but all in vain. On the other hand, human experiments yielded invaluable results, proving that the etiologic agent was smaller than bacteria, i.e., what we call virus nowadays. There was also evidence that there were two types of hepatitis, one with a shorter incubation period and the virus was transmitted orally, and another was with a longer incubation period and the virus was transmitted through injection or blood transfusion. Later, the former was designated hepatitis A and the latter hepatitis B.
The causal agent, however, remained unidentified until mid-1960s when Blumberg discovered Australia antigen that was later found to be the component of the coat of hepatitis B virus (hepatitis B surface antigen or HBsAg). This was the first time a specific marker was identified for one of the hepatitis viruses. The influence of this discovery is enormous. It played a key role for us to understand hepatitis B and to prevent the related diseases, and subsequently led to the identification of hepatitis A, D, C and E. For these reasons, Blumberg won the Nobel Prize in Medicine or Physiology in 1976.
In this lecture, I will also discuss hepatitis B in Taiwan , how Taiwan 's scientists fighted against the disease. From these examples, one will learn how medical research can solve our own health problem and what achievements we have got. After this lecture, I hope that all of you can understand how medical research can create new knowledge, solve problems and pursue betterment of humankind.
講題二（對高中教師）談科技進展對醫學進步的影響
基礎科學和技術影響的層面很廣，自然而然對醫學的影響也不例外。反之，醫療的需求，也刺激著科技的發展，兩者互為因果，交相作用，過去幾世紀中一直力爭上游，進步神速。
自從 Vesalius 在 16 世紀 (1543) 奠定了人體解剖學的基礎而 Harvey 在 17 世紀中葉 (1616) 宣佈血液大體循環的發現之後，由於顯微鏡的發明，使得 Malpighi 能在 17 世紀中葉 (1616) 發現了微血管，將大體循環的動脈與靜脈兩系統聯結起來，同時也對肺、脾、腎、肝、及皮膚的顯微構造開始有了概念，這可以說是科技對醫學進步影響最早的範例。 Boyle 證明了空氣是生命及燃燒所需，而 Lavoisier(1743-1794) 對氧氣的發現更進一步闡明了呼吸是一種燃燒的概念，而 Galvani(1737-1798) 及 Volta(1745-1827) 顯示了肌肉與神經的電氣生理現象，開啟了電氣生理學的大門。 Magendie(1783-1855) 及 Bernard(1813-1878) 利用動物實驗研究種種生理及藥理現象，建立了「實驗醫學」 (Laboratory medicine) 的基石。
Jenner 對牛痘的觀察與實驗 (1796.5.14) 也開始了預防接種的新頁。 Wohler 由無機物在實驗室中產生了尿素 (1828) 。打破了以往認為有機物只能來自於有機體的錯誤觀念。 Pasteur(1822-1895) 對發酵的研究進而引伸出微生物的角色，也證實了 Bassi 前所提出疾病的感染與微生物有關的理論 (1846) 。這些基本的概念大大帶動了醫學的進步，而引起 19 世紀快速的發展，其中以各種細菌的分離及傳染病的預防最為明顯，在 1898 年 Loffler 及 Frosch 也發現有比細菌還小的致病體 ── 即病毒的存在。此期間組織學、病理學、生理學及藥理學的快速進步及改變使得 19 世紀末葉的醫學轉型而成與以前完全不同。化學冶療則在 Ehrlich(1854-1915) 的開創之下漸具雛型，於 Domagk 合成磺胺劑 (1935) 及 Fleming(1929) 發現青黴素後不可一世。物理學方面則由 Rontgen 在 1895 年 11 月 8 日 發現 X 光及 Curie 發現鐳 (1898) 之後，使醫學進入全新的另一個領域。
Busch 發明電子顯微鏡 (1926) 把人類的視線又向前推進，解決了一些前所未見的問題， Harrison 發現動物組織可於適當的體外環境中存活 (1907) ，是組織培養的濫觴。最值得一提的是 Watson 及 Crick 發現 DNA 雙螺旋構築 (1953) ，使得遺傳信號的結構被根本的了解，開啟了分子生物學的大門，這一發展不僅可以對基本的生命現象有所闡釋，對疾病原因的探討、遺傳子的組成、病原體的確認等，也都有了根本的了解，這些科技，也使人類能從事基因的重組及改造，進而對疾病的診治有劃時代的貢獻，預期二十一世紀會有不少疾病將只有應用細胞治療、基因治療或其他相關的科技才能加以控制。
Influence of science and technology on the advancement of medicine
The influence of basic science and technology is immense, and its influence on medicine is no exception. The need in medicine, on the other hand, sometimes also stimulated the development in science and technology. These interactions were most evident in the last two centuries.
The ground of anatomy was laid by Vesalius in the 16th century (1543). Subsequently, Harvey discovered blood circulation in 1616. The invention of microscope enabled people to extend the observation further. Malpighi discovered capillaries (1616), bridging the gap between artery and vein. Meantime, the microscopic structures of lungs, spleen, kidneys, liver, skin and many other organs were revealed gradually. This is an excellent example how a technical breakthrough (microscopy) can contribute to the advancement of biomedical science. Boyle then proved that air is essential for life and combustion, and Lavoisier's (1743-1794) discovery of oxygen led to the concept that respiration is a kind of combustion. Galvani (1737-1798) and Volta 's (1745-1827) experiments demonstrated the phenomenon of electrophysiologic functions in muscles and nerves. Their discoveries laid the foundation of electrophysiology. Magendie (1783-1855) and Bernard (1813-1878) then applied animal experiments to conduct physiologic and pharmacologic studies, thus establishing the discipline of laboratory medicine.
Jenner's observations on cow pox culminated in vaccination against small pox (1796). Pasteur's (1822-1895) studies on fermentation and others indicated the role of microbes and proved the concept that diseases may be related to infections of microbes, that had been proposed by Bassi earlier in 1846. These concepts and investigations promoted the progress of medical science. This is especially evident in 19th century when various pathogenic bacteria were cultured and isolated. Bacteriology and immunology were rapidly expanded during 19th and 20th century. Meanwhile, in 1898 Loffler and Frosch discovered pathogens that were smaller than bacteria — i.e., what we call viruses today. Ehlich (1854-1915) started treating diseases by chemicals. He synthesized Salvalsan for the treatment of syphilis. Domagk synthesized sulfadrugs (1935) and Fleming (1929) discovered penicillin, aiming at treatment of bacterial infections. The discovery of X-ray by Rontgen (1895) and radium by Curie (1898) not only contributed greatly in physics and chemistry, but also opened a new era in medicine.
The invention of electron microscope by Busch (1926) enabled us to explore the structures that are invisible by light microscopy. Harrison (1907) found that animal tissues could stay viable in vitro, this was the very beginning of modern tissue/cell culture. The most striking event in 20th century was Watson and Crick's discovery of double helix structure of DNA in 1953. The discovery elucidated the chemical/structural basis of genetic information, and thus is the fundamental of molecular biology. It explains the basic life phenomenon on a scientific ground, contributes to the search of etiology of diseases and to the understandings of disease mechanisms. In addition, the information yielded by the discovery also helped form today's biotechnology. And thus, the contributions are tremendous. In 21th century, many diseases will be able to be treated by applying cell therapy, gene therapy or other new methods developed from the cutting-edge knowledge of modern science and technology.
It is evident that most of the advancements in medicine are the results of progress in basic science and technology. Research on basic science is thus important and fundamental to the advancement of biomedical science. |
