2013年5月19日 星期日

Osamu Shimomura下村修


For Witness to Nagasaki, a Life Focused on Science


LOS ALAMOS, N.M. —-- Sixty-eight years ago, Osamu Shimomura was a 16-year-old high school student working in a factory seven and a half miles from Nagasaki, Japan. Sitting down to work, a light flashed, briefly blinding him, and the pressure wave from an explosion came rolling through.
On his walk home from the factory, he was drenched with a black rain. His grandmother immediately had him bathe, most likely saving him from radiation-related illness.
 Osamu Shimomura, an emeritus professor at the Marine Biological Laboratory in Woods Hole, Mass., won a Nobel Prize in Chemistry in 2008 for taking the ability of some jellyfish to glow green and transforming it into a ubiquitous tool of molecular biology.
Josh Reynolds/Associated Press
Osamu Shimomura, an emeritus professor at the Marine Biological Laboratory in Woods Hole, Mass., won a Nobel Prize in Chemistry in 2008 for taking the ability of some jellyfish to glow green and transforming it into a ubiquitous tool of molecular biology.

His future wife, Akemi, was not as lucky. She was just over a mile from the blast and, though sheltered by a small hill, suffered for years from the effects of radiation poisoning.
In the aftermath of World War II and the dropping of the atomic bomb on Hiroshima and Nagasaki, Dr. Shimomura, now a Nobel Prize-winning chemist, said he largely put the events out of his mind.
But here he was last month, in the birthplace of the atomic era, to deliver a lecture at the monthly Director’s Symposium. Nearby was a museum with Manhattan Project artifacts, and surrounding him were Los Alamos scientists who were curious about how this man, now 84 and a professor emeritus at the Marine Biological Laboratory in Woods Hole, Mass., felt about the bombings in 1945.
That is not, though, what he chose to address in his talk to about 100 Los Alamos scientists and lab workers.

Instead, he recounted the discovery and development of one of the most significant tools for modern biotechnology: the green fluorescent protein, or G.F.P., used widely in cell and molecular biology as a visual tracer. The discovery, which has deepened the understanding of a wide range of fundamental biological processes, brought him the Nobel Prize in Chemistry in 2008, along with Martin Chalfie and Roger Y. Tsien.
“I decided to focus on the science,” he said.

So it has been for Dr. Shimomura since shortly after Japan’s surrender. In the chaos after the war, he spent two years “idling,” he said, before enrolling in pharmacy school, a path that was not his first choice. But not long after, during a sabbatical in the 1950s, he began his life’s work, the study of bioluminescence.

He chose as his subject a crustacean sometimes known as seed shrimp that emits a striking blue light and is plentiful in the waters around Japan. His focus was on a class of compounds, luciferin, that are bioluminescent. After years of research at Princeton, they had still never been purified.

For 10 months he struggled in his laboratory, until one night, instead of heating the mixture as he usually did, he “accidentally” left the compound in a strong acid.

“Next morning, I found the dark red mixture was turned into a colorless transparent solution,” he recalled. And when he looked with a microscope, he realized that the solvent had crystallized in pure, fine red crystals.

“I was very happy by the success of crystallization,” he said. “It was probably the happiest moment of my life.”

The discovery led to an invitation in 1959 from the marine biologist Frank Johnson to work in his Princeton laboratory. There he focused his days on studying a jellyfish, Aequorea victoria, whose edge glows green. In 1961 he and his family, with Dr. Johnson, set off for the Friday Harbor Laboratories at the University of Washington.

Ultimately the small team, including Dr. Shimomura’s family members, would collect a quarter million jellyfish, all in the hunt for the elusive green fluorescent protein.

Sitting in a rowboat one day, he said, he had an insight.

“It was a very simple idea: Luminescence probably involves a protein. If so, luminescence might be reversibly inhibited at a certain pH,” he recalled.

His breakthrough came in the form of a bright blue flash, produced when he threw his extract into a sink where seawater from an aquarium had just been poured. That led to a successful strategy for extracting the luminescent substance, and ultimately to a deeper understanding of G.F.P.

Decades later, the fluorescent markers have become a standard laboratory technique used by scientists to visualize biological activity.

“It’s really changed biological and medical research,” said Marc Zimmer, a computational chemist at Connecticut College who maintains an introductory Web site on the technology. “It allows us to see things we couldn’t have imagined seeing in the 1990s.” It was 50 years before Dr. Shimomura even addressed the topic of the atomic bombings, in an article for a Japanese newspaper.
“No one wanted to remember,” he said.

But in 2008, in his Nobel acceptance essay, he made his feelings about the bombings clear.

“Even if the use of the Hiroshima bomb was justifiable in order to precipitate an end to the war, the bomb dropped on Nagasaki three days later was clearly a test of new arms,” he wrote. “It cannot be justified.”

In Los Alamos on April 18, he seemed content to leave it at that. But his hosts could not.
At a dinner, Bette Korber, a theoretical biologist at the Los Alamos National Laboratory, told of how her father had been on a troop ship preparing for the invasion of Japan. For years, she said, he had credited the decision to drop the bombs with sparing his life. Years later, however, when declassified documents reopened questions about whether the Nagasaki bomb had been necessary to end the war, he was in despair, she said.
Gary Doolen, a physicist who had been a weapon designer at the lab, said there was evidence that the second bomb had been dropped as a demonstration of American power to Russians, who were then massing troops in East Asia.

Dr. Shimomura, tall and stooped, mostly listened.

After the lecture, he toured a Los Alamos museum, where full-size models of the Hiroshima and Nagasaki bombs are on display. His wife, Akemi Shimomura, also a chemist by training and his longtime research collaborator, said that the Japanese government had been stupid to not surrender immediately after the Hiroshima bomb.

“Starting the war was stupid,” Dr. Shimomura replied.

The next day, they returned. Something was on his mind. The day before the Nagasaki bombing, Dr. Shimomura had seen a B-29 bomber drop three parachutes. The drop had puzzled him. He would later learn that they carried instruments for data transmission and measurement.

He asked John E. Pearson, the Los Alamos physicist who had invited him to lecture, about the instruments. After some hunting they found models of the original parachute payloads.
“Some guy came up and started explaining what we were looking at,” said Dr. Pearson. “Osamu said, ‘Yes. I watched them falling.’ I don’t think I’ve ever seen anyone quite as stunned as that guy.”


新墨西哥州洛斯阿拉莫斯——68年前,下村修(Osamu Shimomura)還是個16歲的高中生,在離日本長崎7.5英里(約合12公里)的一家工廠兼職。剛坐下工作,一道強光閃過,導致他短暫失明,爆炸的衝擊波隨之襲來。
  • 檢視大圖 2008年,馬薩諸塞州伍茲霍爾海洋生物學實驗室的榮譽退休教授下村修獲得了諾貝爾化學獎,獲獎理由是研究了某些水母能發綠光的原理,並將之轉化為分子生物學中一種普遍應用的工具。
    Josh Reynolds/Associated Press

不過上個月,他來到原子時代的誕生地洛斯阿拉莫斯國家實驗 室,受邀在每月一次的「實驗室主任研討會」(Director』s Symposium)上演講。不遠處的一座博物館裡,安放着「曼哈頓計劃」(Manhattan Project)的各種裝置。現年84歲的下村修還是馬薩諸塞州伍茲霍爾海洋生物學實驗室(Marine Biological Laboratory)的榮譽退休教授,而圍繞在他身邊的這群洛斯阿拉莫斯科學家很想知道,他對1945年的爆炸做何感想。
他轉而回憶了如何發現並擴展現代生物技術中最重要的工具之 一:被廣泛用於細胞和分子生物學研究的示蹤劑綠色熒光蛋白(green fluorescent protein,簡稱GFP)。這一發現加深了人類對一大批基本生物過程的理解,使得下村修與馬丁·沙爾菲(Martin Chalfie)和錢永健(Roger Y. Tsien)共同獲得了2008年的諾貝爾化學獎。
他選擇的研究對象是一種甲殼綱動物,別名「種子蝦」,它們能發出一種美麗的藍光,在日本附近的水域里數量龐大。他研究的重點是一組化合物,也就是能發出生物光的熒光素。普林斯頓大學(Princeton University)已對此研究多年,但一直未能提純熒光素。
這一發現令普林斯頓的海洋生物學家弗蘭克·約翰遜 (Frank Johnson)在1959年發出邀請,讓下村修到他的實驗室工作。在那裡,下村修專註於研究一種邊緣發出綠光的水母,它的名字叫做「維多利亞多管發光水 母」(Aequorea victoria)。1961年,他和家人以及約翰遜博士一起前往華盛頓大學的星期五港實驗室(Friday Harbor Laboratories at the University of Washington)。
「這真的改變了生活和醫學研究,」康涅狄格學院的計算化學 家(Connecticut College)馬克·齊默爾(Marc Zimmer)說。「它讓我們看到在20世紀90年代所無法能看到的東西。」齊默爾管理着一個針對該技術的介紹性網站。50年後,在發表在日本報紙上的一 篇文章里,下村修才談到了原子彈轟炸問題。
一次晚飯間,洛斯阿拉莫斯國家實驗室(Los Alamos National Laboratory)的理論生物學家貝蒂·科貝爾(Bette Korber)談到她父親如何一直待在一個運兵船上準備入侵日本。她說,數年來,父親一直認為,投放原子彈的決定使自己免於一死。然而,多年後,被解封的 秘密文件重新引起人們的疑問:投向長崎的原子彈對於結束戰爭來說是否真的必要,科貝爾說,那時,父親陷入了絕望。
此前一直在該實驗室作武器設計師的物理學家加里·杜蘭(Gary Doolen)說,有證據表明,投下第二顆炸彈是為了向俄國人展示美國的實力,當時,俄國正在東亞集結大量兵力。
下村修向邀請他去演講的洛斯阿拉莫斯實驗室的物理學家約翰·E·皮爾遜(John E. Pearson)問起這些裝置。經過一番搜尋後,他們找到了原始的降落傘所載裝置的模型。