當年開刀有他 老師輕聲說謝謝

2006/08/15

【記者許峻彬、施靜茹】

師生情誼逾半世紀的院士宋瑞樓（右）和陳定信，一笑就瞇了眼的宋瑞樓已不復當年嚴格形象；陳定信仍是一貫的談笑風生，逗得老師哈哈笑。記者邱勝旺／攝影

 

「我從來沒有謝謝過他，今天我要在這裡謝謝他！」培育出三位院士學生的醫界耆宿宋瑞樓在訪談最後，對繼承衣缽的陳定信輕聲說：「謝謝你。」那年，宋瑞樓盲腸炎開刀，當名醫成了病人，在家屬勿入的恢復室睜開眼，看到的是學生陳定信陪在病人老師身邊。

宋瑞樓與陳定信率領的台大醫學院肝炎研究團隊，揭開慢性肝炎、肝硬化演變到肝癌的致病機轉，並用這些科學證據說服政府進行新生兒Ｂ型肝炎疫苗預防接種計畫，也完成了疫苗防癌的全球創舉。

師生關係橫跨半世紀的這對師徒，除了理性科學研究精神的傳承外，也有醫者父母心的感性共通點。宋瑞樓語重心長地說：「沒有愛心的人不要來做醫師！」

宋瑞樓和陳定信這對醫界師徒，在台灣早已成為橫跨臨床、研究、政策與醫學教育的指標人物和典範，望重杏林。七月初的院士會議中，近九十歲的宋瑞樓直言批 評，如今醫師門診看一個病人只用五、六分鐘，「根本不算醫療行為」；住院醫師報告病例時也不報告病人病史。同為院士的陳定信則把老師意見寫成提案，獲得中 研院院長李遠哲高度重視。

一支肝炎研究團隊，出了四位院士，秘訣何在？陳定信說：「要感謝掌門人。」是宋瑞樓當年的洞見，立志解決台灣人深受其害的肝炎。一向謙遜的宋瑞樓說，是自己運氣好，有這麼多頭腦好又有愛心的年輕人願意跟著他。

宋瑞樓出身醫師世家，父親宋燕貽是竹東小鎮醫師，宋瑞樓原本該接續父親診所的，但陳定信透露：「老師回去做了五天小鎮醫師就跑回來了。」宋瑞樓笑說，他不能忘情研究，於是關了父親的診所，母親能諒解，卻是叔叔和街坊鄰居上門罵他不孝，「我只好趕快跑」。

醉心研究的歲月，也有不為人知的缺憾。有三名女兒的宋瑞樓說，他的獨子五歲時，在台大徐州路宿舍附近獨自玩耍，意外摔入池塘，送到台大醫院急救。他接獲通知時，獨子已回天乏術。

宋瑞樓如今語氣平和，但難以諒解當時驗屍的檢察官，竟然問他：「你對小孩子怎麼想？」言下之意，想確定是不是父親討厭孩子。宋瑞樓說，檢察官這樣的問法太令人傷心。

陳定信的父親在他大四那年罹患肝癌，四個月後辭世，這一直是陳定信心中的痛。為了在台灣陪媽媽、放棄出國深造的陳定信，從在走廊攔下宋瑞樓，要求：「我能 不能跟您一起做肝炎研究？」如今，陳定信不靠博士學位加持，以對肝炎研究與防治的斐然成就，獲選美國國家科學院院士，還成為世界肝臟醫學會理事長，他早已 用實力證明他自己。

【2006-08-15/聯合報】

Profile of Ding-Shinn Chen

Ding-Shinn Chen has used every strategy at his disposal to battle the worldwide devastation caused by hepatitis B. From public health strategies that lower the rate of hepatitis B infection to basic molecular research that solves the mysteries of how the virus causes disease, Chen, who was elected to the National Academy of Sciences as a foreign associate in 2005, has spent a career studying a virus that causes one of the world's most common disorders.

Worldwide, 350 million people are infected with the hepatitis B virus, one of five viruses that cause hepatitis that, in turn, increase the risk of chronic liver disease and liver cancer. Hepatitis B infection is especially prevalent in Southeast Asia and sub-Saharan Africa. Indeed, some of Chen's earliest work showed that hepatitis B infection in his homeland of Taiwan was far higher than in the West. Based on those findings, Chen worked to create a public health program in Taiwan that, for the past 23 years, has vaccinated nearly all of the newborns there against hepatitis B. The program already has reduced some forms of liver disease and, over the next several decades, should reduce it further or even eliminate it. Chen and his colleagues also have studied the molecular nuts and bolts of how hepatitis causes liver diseases. In his Inaugural Article (1), they report on a mechanism that may explain why hepatitis B causes liver cancer in males more than five times as often as females.

Chen is Dean of the National Taiwan University College of Medicine and Director of the National Taiwan University Center for Genomic Medicine. He is married, with a son, who works in the finance field, and a daughter, who is a protein biochemist at Taiwan's Academia Sinica.
     
Chen was born in Ying-Ge, Taiwan, south of the country's capital, Taipei. His interest in medicine began in high school, when his mother became ill and required surgery. His subsequent encounters with physicians and other health care workers convinced him to enter a seven-year medical program directly after high school at National Taiwan University College of Medicine. In his third year, while studying physiology, microbiology, and other building blocks of medicine, Chen began to realize the important contribution research makes to medical knowledge and treatment.

"My classmates and I thought we should also contribute to the knowledge of the future," he says. "I started to seek laboratories in my medical school which would allow a student to conduct some simple experiments."
He found such a laboratory in his fourth year, working on a simple animal experiment to determine whether there was a difference in immunological behavior between C57 black and AKR white mice.

"We used, at that time, a sophisticated way to determine the antibody-forming cells in the spleen (now called B cells)," says Chen. "We injected sheep red blood cells into the mice and analyzed the number of antibody-forming cells. Then we treated the mice with the immune suppressant methotrexate, an anti-cancer drug, and repeated the experiment to see if there was a difference between the black and white mice."

The study took Chen and a classmate two years to complete during summer vacations. "At that time, there was no computer system and you had to go to the library and look at the many, many volumes of Index Medicus to see the current state of knowledge on the topic and then design the experiment," says Chen. "I thought it was a very good experience for a young student like me"
 
After graduating from medical school and a year of compulsory military service, Chen began his residency in internal medicine in 1969. That was when his interest in hepatitis began. "At that time, internal medicine residency needed four years, and I started to think about which discipline I should choose after my training finished," he says. "Although we already knew we had very prevalent liver disease in Taiwan, we didn't know almost 80–90% of it was caused by chronic hepatitis B infection. If you look at the world, many people have liver disease. In Taiwan, many had chronic liver disease and many had a big liver with advanced primary cancer in it. So I chose gastroenterology as my subspecialty, which, in Taiwan, includes hepatology and liver disease."

After the discovery of the hepatitis B marker, now called hepatitis B surface antigen (HBsAg), by Baruch Blumberg in 1965, there was finally a way to identify and differentiate the etiology of liver diseases.

Chen and his mentor, J. L. Sung, found that across Taiwan, 15–18% of the population carried the antigen, much higher than the 0.1% carrier rate in Western countries. Even more interesting was that 90% of people with liver cancer had HBsAg in their blood, and 80% of people with liver cirrhosis had the antigen (3, 4). "That's a very important finding because it indicates that these two diseases are associated or closely related to chronic infection with the hepatitis B virus," Chen says. "Then we started to look at how these people got infected."

They concluded that many of the infections resulted from mother-to-infant transmission. The virus is very contagious and infective, so if the mother has it, the newborn with its undeveloped immune system will be exposed to it in the birth canal. "The infection occurs so early that the immune system does not recognize it as a bad one," says Chen. "This is why people had so high hepatitis B carriage. Of the 15–18% with it, some will develop chronic liver disease and/or liver cancer. During the 1970s and '80s, we made clear the natural history and role of early infection in chronic hepatitis B carriers" (5–7).

After identifying the transmission routes of hepatitis B, Chen and his colleagues began looking for ways to prevent it. "Before the virus was discovered there was no treatment and no effective way of prevention," explains Chen. "After Blumberg identified a specific marker, a lot of research went into the significance of the viral marker and the antibody to this antigen" (7, 8).

      Professor Chen and his research group.
Once a vaccine was developed and ready for public use in the early 1980s, Chen and Sung wanted to use it to decrease chronic carriage of hepatitis B in Taiwan. "We persuaded the government to launch a program to control hepatitis B in our people," recalls Chen. "We started to get in touch with the government around 1980, when the vaccine was just available. Finally, the government was convinced that the disease was very serious and prevention was worthwhile. So we got the budget and the system working and started the vaccinations. We were the first country in the world to initiate universal vaccination against hepatitis B in newborn babies. I still remember the first day of July 1984 when vaccinations began" (9).
Now, across the country, clinics vaccinate newborns as soon as possible. Doctors screen mothers to see whether they are carriers and measure how infectious they are before they give birth. "The exposure starts right during delivery, so we have to give the immunization as soon as possible," Chen says. "It's usually given within one week after delivery. It's quite complicated, because there are two types of carrier mothers."

One type is extremely infectious. Babies of these highly infectious mothers will make hepatitis B antibodies for themselves once given the vaccine, but because the virus already has infected them, doctors need to add protective antibodies produced by others to beat the virus, says Chen.

When the program started, it vaccinated approximately 400,000 babies per year. Taiwan's birth rate has since fallen, and it now vaccinates 210,000 per year. "This is something we promote a lot in Taiwan," says Chen. "The coverage is very good, about 98% in cities and 96% over all of Taiwan." The chronic carrier infection rate in people born since 1984 has dropped to 0.6% in Taipei City and to approximately 1% nationwide.

The hepatitis B vaccine was the world's first to fight cancer. Because liver cancer usually does not develop until an infected person's sixth decade, it will be awhile before Taiwan feels the full effects of the vaccination program. However, as an early proxy, Chen and other researchers have found that liver cancer already is appearing much less frequently in children (10). In addition, as they continue to track the vaccine's effects, they have found a drop in rates of liver disease in children born after the vaccination program's inception (11).
 
While Chen was battling hepatitis B on the public health front in Taiwan, he conducted basic research to better understand, on a molecular level, the virus that causes the disease. The hepatitis B virus is a small, 3,200 bp, partially double-stranded DNA virus. It makes four proteins: three are structural, and one, called HBx, trans-activates genes in the host cell. Unusually for DNA viruses, it must undergo reverse transcription and may integrate into the host's genome. Chen discovered this integration while visiting Robert Purcell's laboratory in Bethesda, MD, in 1979 (12).

Chen once again has added to our understanding of hepatitis B with his Inaugural Article, which may have found the answer to a long-standing mystery: why hepatitis B causes liver cancer in males much more often than females, by a ratio of between 5 to 1 and 10 to 1. He and his colleagues find that it has to do with an interaction between one of the proteins that make up the hepatitis B virus and male hormones.

"We found that HBx protein will work with androgen receptor (AR) in the presence of the male hormone testosterone and increase liver cancer," says Chen. "This HBx protein, the only nonstructural one of the virus, works in concert with androgen receptor and testosterone to promote carcinogenesis."

Chen says the interaction between HBx and AR also explains why hepatitis B is so much more prevalent in men (1). "We have other studies showing that the genetic alterations of AR are very important in liver cancer in males," says Chen. "But we did not know how this was related to hepatitis B. Now with the hepatitis B viral protein X working on AR, we have the connection."

Specifically, Chen and his colleagues propose that the HBx protein works through a signaling pathway called c-Src. They suggest that HBx and c-Src interact with the AR and then enter the cell nucleus to activate some of the effectors that promote liver cancer. The pathway they have identified also may be involved in other diseases, says Chen. "In many diseases, especially infectious disease, males are usually more susceptible, or the disease will be severer than in females," he says. "We think that perhaps this pathway will possibly explain the differences in other diseases as well."

Chen also has studied hepatitis viruses C and D and the severe acute respiratory syndrome virus. In the early 1990s, he and his colleagues (13) developed a treatment for chronic hepatitis C that combines interferon- and ribavirin, and this has become the standard treatment. He has also studied the replication cycle of hepatitis D, a shadow virus that depends on viral coat proteins from hepatitis B, and its role in liver disease (14–16).

Because hepatitis D is so small, some researchers do not believe it fulfills the criteria to be a virus, says Chen. "It cannot live by itself, and it always needs the hepatitis B virus surface antigen to form a viral particle. The virus is hiding with hepatitis B, so if there's no B, there will be no D. Although this phenomenon occurs in the plant kingdom, in the animal kingdom, this is the first one."

However, the majority of his work has been, and will be, focused on treating and eliminating hepatitis B. "Right now, hepatitis B is still the most important viral infection for human beings," says Chen. "In Western countries, the vaccines are very effective and you can control it more easily. But in the rest of the world, 500,000 to 1 million people are still dying of hepatitis B-related liver diseases every year, particularly in Asia and Africa. Regretfully, the countries with the highest scientific standards have shifted their interest to HIV, HCV, and other diseases, so hepatitis B is given less consideration. I think from a human point of view, we need to study more of hepatitis B."

There is still a long way to go before hepatitis B-related diseases can be significantly minimized or eliminated (17). "If we keep using the vaccination, the diseases will be controlled, but that will be 30 or 40 years away," says Chen. "People keep dying from this disease, and we can use this sad opportunity to study how this virus is causing disease. We still have a lot of uncertainties. This is my number one project."

One technique he has planned to solve these questions is genomic medicine. "If you look at some families, many are hepatitis B carriers, and almost all the carriers died of liver cancer, yet other families do not show the same phenomenon, even though the family members are also hepatitis B carriers," he says. "There must be some host factors or genomic differences that dispose them to this cancer or disease."

As if those goals were not enough, he adds, "I will also keep an eye on hepatitis C. It's still important in Taiwan and worldwide."

Footnotes
 
This is a Profile of a recently elected member of the National Academy of Sciences to accompany the member's Inaugural Article on page 2571 in issue 8 of volume 104.

© 2007 by The National Academy of Sciences of the USA

Ming T. Tsuang, M. D., Ph.D., D.Sc.

University Professor, University of California;

Distinguished Professor of Psychiatry,

Director, Center for Behavioral Genomics,

Department of Psychiatry, University of California, San Diego;

Director, Harvard Institute of Psychiatric Epidemiology & Genetics

 

Dr. Tsuang is Behavioral Genomics Endowed Chair and University Professor, University of California and Distinguished Professor of Psychiatry and Director, Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego. He also directs the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, MA. He was Stanley Cobb Professor of Psychiatry and Chairman, Department of Psychiatry, Harvard Medical School at Massachusetts Mental Health Center, where he served as Superintendent and President of Massachusetts Mental Health Institute of Psychiatry.   He received his M.D. degree from National Taiwan University and his Ph.D. in Psychiatric Genetics and D.Sc. (Doctor of Science) in Genetics Epidemiology from University of London.  He has been recognized worldwide for his research in schizophrenia, manic-depressive illness, and substance abuse. 

One of his areas of interest is in the interactions between genetic and environmental risk factors for severe mental disorders.  His current effort is to study prevention of psychiatric disorders before their onset, particularly in blood relatives of people suffering from schizophrenia, to identify traits that predispose a person to developing schizophrenia from both genetic and environmental perspectives.   

He is a member of the Institute of Medicine, National Academy of Sciences, and served on the National Advisory Mental Health Council, U.S. Department of Health and Human Services. He has been elected Fellow of the American Psychiatric Association, the American College of Psychiatrists, the British Royal Society of Psychiatrists, and Fellow and former President of the American Psychopathological Association.  He is a Council Member of the Taiwan National Health Research Institute (NHRI), and is an Academician, Academia Sinica of Taiwan (the highest academic institution in Taiwan). He served as the President of the International Society of Psychiatric Genetics (ISPG) from 2005 to 2010.    

Dr. Tsuang is the recipient of a myriad of awards for his work, among them: the Rema Lapouse Award for Mental Health Epidemiology, the American Public Health Association; the Stanley Dean Award for Research in Schizophrenia, the American College of Psychiatrists; the National Institute of Mental Health Merit Award; the Noyes Award for Research in Schizophrenia; the National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award; and the Paul H. Hoch Award, the American Psychopathological Association.  Dr. Tsuang also received the Lifetime Achievement Award from the International Society of Psychiatric Genetics, the Taiwanese-American Award for Achievement in Science and Engineering, the Gold Medal Award from the Society of Biological Psychiatry for pioneering contributions in the field of biological psychiatry, the Award for Research in Psychiatry, the American Psychiatric Association and The National Alliance for Research on Schizophrenia and Depression (NARSAD) Lieber Prize for Schizophrenia Research.

He has authored or co-authored over 650 publications in the areas of psychiatric epidemiology and genetics, major psychoses and substance abuse, and spiritual health.  Publications have appeared in peer review journal papers, book chapters and books (both general and textbooks).  In addition to serving on the editorial boards of many scientific journals, he is currently the Senior Editor for Neuropsychiatric Genetics, a section of the American Journal of Medical Genetics.

莊明哲獲NARSAD傑出成就獎

 

2010/10/30  7:00 AM  < 北美 >

圖左1是聖地牙哥中華科工聯誼會現任會長、僑務委員黃莉莉，左3是莊明哲教授。 駐外人員

 國際知名遺傳精神病學專家、美國加州大學（UC）總校教授莊明哲被美國「全國精神分裂與憂鬱症研究聯盟」（National Alliance for Research on Schizophrenia/Depression，簡稱NARSAD）授予傑出成就獎。

莊明哲畢業於台大醫學院，之後赴英國深造獲倫敦大學博士學位；赴美後又被布朗大學與哈佛大學頒授榮譽碩士學位，先後執教於愛荷華大學、布朗大學與哈佛大學，他加盟聖地牙哥加大後，未幾即被任命為「加大總校教授」，憑此榮銜可在加大系統任何分校從事教學或研究。
莊明哲早年所提出的精神分裂症遺傳理論，將遺傳因素確定為某些精神病的重要起因，他認為精神分裂症不但可被治癒，而且可有效預防，他已被選為美國國家醫學科學院院士與台灣中央研究院院士

【大紀元10月15日訊】（大紀元記者董婉如美國聖地亞哥編譯報導）加州大學總校教授莊明哲(Ming T. Tsuang, MD, PhD, DSc)今年被NARSAD授予「利伯」傑出成就獎。「利伯」獎每年授予在認識和精神分裂症研究方面的傑出人物。莊明哲博士以他在大腦與行為研究方面的許 多成就、包括確定精神分裂症等精神疾病的根本原因而獲得此獎。

NARSAD總裁兼首席執行官貝妮塔•肖貝 (Benita Shobe) 說: NARSAD很高興表彰莊博士和他在精神分裂症研究上的突破,「他的成就和正在進行的工作，對240萬患有精神分裂症美國人的恢復，具有里程碑的意義」。

莊 明哲博士是加州大學聖地亞哥分校（UCSD）醫學院傑出的精神病學教授和行為基因組中心主任。他1957年獲國立台灣大學醫學學位，1965年在倫敦大學 獲得博士學位, 他的博士論文是關於有精神疾病的兄弟姐妹的研究。他推測精神分裂症是多基因因素造成，現在已經是被廣泛接受的理論。他接著又發展出了世界上最大的遺傳學研 究兄弟姐妹樣品比對，領導了40年的該方面研究，提供了一個與精神分裂症和情感性精神障礙的區別的第一個證據，以及精神分裂症亞型的臨床標準。他目前的任 務是確定精神分裂症易感特質，以期在事前阻止精神分裂症發生。

莊明哲教授主持全美心理健康遺傳學國家研究委員會，該委員會研究精神分裂症，雙相情感障礙和阿茲海默氏病等；開創用越南退伍軍人雙胞胎登記來研究藥物濫用造成的長期後果，並曾擔任衛生與人類服務部心理健康局國家諮詢官員。他還指導哈佛大學的精神病流行病學和遺傳學研究所。

NARSAD 是領先的捐助者支持組織，致力於尋找精神疾病的原因，改進治療方法和治癒方法。自1987年以來，已有3832個課題，有3,132名世界各地的科學家榮 獲NARSAD贈款2.6億美元。10月29日，莊明哲博士將與其他5名研究人員參加在NARSAD的全國頒獎晚宴。

Ming T. Tsuang recognized with NARSAD outstanding achievement award for schizophrenia research

Date:10/13/2010[] []

 

Ming T. Tsuang, MD, PhD, DSc, Behavioral Genomics Endowed Chair and Distinguished Professor of Psychiatry at the University of California, San Diego School of Medicine, and director of its Center for Behavioral Genomics, has been awarded the Lieber Prize for Outstanding Achievement in Schizophrenia Research by NARSAD. The Lieber Prize is given annually to recognize and award extraordinary leadership in schizophrenia research. The award recognizes Tsuang's many accomplishments in brain and behavior research, including identifying underlying causes of mental illnesses such as schizophrenia.

"NARSAD is pleased to recognize Dr. Tsuang and his breakthrough schizophrenia research," said Benita Shobe, NARSAD president and CEO. "His accomplishments and ongoing research are remarkable points along the pathway to recovery for the 2.4 million Americans suffering from schizophrenia."

"Dr. Tsuang is a world-renowned leader in the genetics of schizophrenia, bipolar disorder and substance abuse, and we are extremely proud of his many accomplishments, including this prestigious honor," said Lewis L. Judd, MD, Mary Gilman Marston Professor and chair of the UCSD Department of Psychiatry.

After earning a medical degree from National Taiwan University in 1957, Tsuang completed PhD and DSc degrees at the University of London. His 1965 PhD thesis, a study of siblings with psychiatric disorders, postulated multiple-gene causality for schizophrenia, a theory that is now widely accepted. He went on to develop some of the world's largest samples of sibling pairs for genetics research leading a 40-year study that provided the first evidence of a distinction between schizophrenia and affective disorders, as well as clinical criteria for subtypes of schizophrenia. His current quest is to identify predisposing traits for schizophrenia toward the ultimate goal of learning how to stop psychiatric disorders before they start.

On the national stage, Tsuang chaired the steering committee of the National Institute of Mental Health genetics initiative on schizophrenia, bipolar disorders and Alzheimer's disease; pioneered the use of the Veterans Affairs' Vietnam Twin Registry to study long-term consequences of drug abuse; and served on the National Advisory Mental Health Council of the Department of Health and Human Services. He also directs the Harvard Institute of Psychiatric Epidemiology and Genetics in Boston.