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.”


長崎原子彈親歷者,諾貝爾獎化學家


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。
從工廠回家的路上,他淋了一身「黑雨」(即放射性塵埃——譯註)。祖母立即讓他洗了澡,這一舉動很可能讓他免於罹患輻射病。
  • 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
    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。

將來成為他妻子的明美(Akemi)則沒那麼幸運。她當時離爆炸地僅一英里,儘管有一座小山的阻擋,後來仍受到輻射病的多年折磨。
二戰及廣島和長崎原子彈爆炸的硝煙散盡之後,下村博士成為了一名諾貝爾獎化學家,他說自己基本上已將這些事拋諸腦後。
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。
不過,面對約100名洛斯阿拉莫斯的科學家和實驗室員工,這並不是他選擇的演講主題。
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。
「我決定把重點放在科學上,」他說。
自日本投降後不久,下村博士就是一直這麼做的。他說,戰後的混亂期里自己有兩年「無所事事」,然後進了藥學院學習,而這也不是他首選的人生道路。不過,不久之後的20世紀50年代,他在休假期間開始研究生物發光現象,而這成為了他的終生事業。
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。
下村修在實驗室里苦苦折騰了10個月,直到某天晚上,他沒有遵循慣常的做法將混合物加熱,而是「不小心」將該化合物加到了一種強酸中。
「第二天早上,我發現原本暗紅色的混合物變成了無色透明溶液,」他回憶道。把該物質放到顯微鏡下之後,他意識到溶液已經結晶為細微的紅色純晶體。
他說:「我對成功結晶喜出望外。那很可能是我一生中最高興的時刻。」
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)。
最終,包括下村博士家人在內這一小組人員搜集了25萬隻水母,只是為了找到這種不易獲取的綠色熒光蛋白。
下村修說,有天坐在一艘小船里,他忽然有了靈感。
「當時我想的很簡單:發光物質中可能有蛋白質。如果是這樣,在某一pH值之下,該發光物質是會被抑制的,但這一抑制又是可逆的,」下村修回憶道。
當時,他把自己提取的物質扔到一個水池,水池裡剛倒入了來自魚池的海水,結果就出現了亮藍色光,而這就是下村修研究的突破。該突破產生了一個成功提取發光物質的方法,並最終加深了人們對GFP的認識。
數十年後,熒光標記成為科學家們用來檢測生物活動的一種標準實驗室技術。
「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。
「沒人願意記得那件事,」他說。
然而在2008年,下村在他的諾貝爾獲獎辭中袒露了自己對轟炸的看法。
「即便為了加速結束戰爭而向廣島投放原子彈可以算正當的理由,三天後將炸彈投向長崎,就明顯是在試驗新武器了,」他寫道,「這種做法是沒有正當性的。」
4月18日,在洛斯阿拉莫斯,下村修似乎覺得說這麼多已經夠了。但邀請他演講的人卻不這麼認為。
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。
個子高高有些駝背的下村修大部分時間只是聽着。
演講結束後,下村修參觀了洛斯阿拉莫斯的一個博物館,那裡展示着廣島、長崎原子彈的全尺寸模型。他的妻子下村明美也是一名受過專業訓練的化學家,並是下村修的長期研究夥伴,下村明美說,之前日本政府十分愚蠢,沒有在美國向廣島投下原子彈後立即投降。
「發動戰爭本身就很愚蠢,」下村修回應道。
第二天,他們回來了。但下村修在想着一些事情。在長崎遭轟炸的前一天,下村修看到一輛B-29轟炸機投下三個降落傘。這讓他很困惑。後來他會了解到,這些降落傘上載有數據傳輸和測量的裝置。
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。
「一個人走過來,開始向我們解釋我們正在看的是什麼,」皮爾遜說,「下村修說,『是的,我是看着它們落下去的。』那個人吃驚極了,我從來見過有人那麼吃驚。」
本文最初發表於2013年5月12日。
翻譯:黃錚、谷菁璐

沒有留言:

張貼留言