英語閱讀雙語新聞

詹妮弗·A·杜德納 一位女科學家的兩個戰場

本文已影響 3.2W人 

BERKELEY, Calif. — As a child in Hilo, one of the less touristy parts of Hawaii, Jennifer A. Doudna felt out of place. She had blond hair and blue eyes, and she was taller than the other kids, who were mostly of Polynesian and Asian descent.

加利福尼亞州伯克利——在遊客稀少的夏威夷城市希洛(Hilo),孩提時的詹妮弗·A·杜德納(Jennifer A. Doudna)感覺自己和這個地方格格不入。她擁有一頭金髮,藍色的眼睛,又比其他孩子高出一截,周圍的孩子大部分是波利尼西亞裔或亞裔。

“I think to them I looked like a freak,” she recently recalled. “And I felt like a freak.”

“我想在他們看來我像是一個怪胎,”不久前杜德納回憶道,“而且我感覺自己也像是個怪胎。”

詹妮弗·A·杜德納 一位女科學家的兩個戰場

Her isolation contributed to a kind of bookishness that propelled her toward science. Her upbringing “toughened her up,” said her husband, Jamie Cate. “She can handle a lot of pressure.”

與外界的隔閡帶給她的是促使她走向科學的一種書卷氣。這樣的生長環境“讓她在磨礪中成長”,她的丈夫傑米·凱特(Jamie Cate)說。“她能夠應對巨大的壓力。”

These days, that talent is being put to the test.

近來,這位才女正面臨着考驗。

Three years ago, Dr. Doudna, a biochemist at the University of California, Berkeley, helped make one of the most monumental discoveries in biology: a relatively easy way to alter any organism’s DNA, just as a computer user can edit a word in a document.

杜德納博士是加州大學伯克利分校的生物化學家。3年前,她幫助完成了生物學界堪稱不朽的一項發現:用一種比較簡單的方法來改變任何生物體的DNA,猶如電腦使用者可以在文檔中編輯一個單詞一樣。

The discovery has turned Dr. Doudna (the first syllable rhymes with loud) into a celebrity of sorts, the recipient of numerous accolades and prizes. The so-called Crispr-Cas9 genome editing technique is already widely used in laboratory studies, and scientists hope it may one day help rewrite flawed genes in people, opening tremendous new possibilities for treating, even curing, diseases.

這一發現讓杜德納成爲名人,她獲得了無數的榮譽和獎項。這一被稱爲Crispr-Cas9的基因組編輯技術已經被廣泛應用於實驗室研究,科學家們希望,未來它可以幫助重新編寫人類有缺陷的基因,爲治療甚至是治癒疾病帶來新的、巨大的可能性。

But now Dr. Doudna, 51, is battling on two fronts to control what she helped create.

不過現在,51歲的杜德納正奮戰在兩個戰場,來控制她幫助發明的Crispr-Cas9技術。

While everyone welcomes Crispr-Cas9 as a strategy to treat disease, many scientists are worried that it could also be used to alter genes in human embryos, sperm or eggs in ways that can be passed from generation to generation. The prospect raises fears of a dystopian future in which scientists create an elite population of designer babies with enhanced intelligence, beauty or other traits.

就在每個人都樂見Crispr-Cas9成爲治療疾病的一種策略時,許多科學家擔憂,它可能會被用於改變人類胚胎、精子或卵子中的基因,如此一來,這些基因改變可以被遺傳給一代又一代人。這樣的前景讓我們對未來充滿恐懼:在這個反烏托邦的未來,科學家制造出一個精英羣體,經過設計的嬰兒擁有增強的智力、美貌或其他特性。

Scientists in China reported last month that they had already used the technique in an attempt to change genes in human embryos, though on defective embryos and without real success.

上個月,中國科學家宣稱,他們已經使用這項技術嘗試改變人類胚胎的基因,這個實驗是在有缺陷的胚胎上進行,並沒有成功。

Dr. Doudna has been organizing the scientific community to prevent this ethical line from being crossed. “The idea that you would affect evolution is a very profound thing,” she said.

杜德納博士一直在組織科學界人士防止倫理底線遭到破壞。“影響進化的想法是一件非常嚴重的事。”她說。

She is also fighting for control of what could be hugely lucrative intellectual property rights to the genome editing technique. To the surprise of many, the first sweeping patents for the technology were granted not to her, but to Feng Zhang, a scientist at the Broad Institute and M.I.T.

杜德納同時也在爭取控制這項基因編輯技術的知識產權,它可能會帶來巨大的財富。令人驚訝的是,與這項技術相關的第一批專利並沒有授予她,而是授予麻省理工學院和布羅德研究所(Broad Institute)的科學家張鋒。

The University of California is challenging the decision, and the nasty skirmish has cast a bit of a pall over the field.

加州大學對這一決議提出了質疑。因爲巨大的爭議,基因編輯技術籠罩在陰雲之中。

“I really want to see this technology used to help people,” Dr. Doudna said. “It would be a shame if the I.P. situation would block that.”

“我真的希望看到這項技術用於幫助人類。”杜德納博士說,“如果知識產權機構阻止這麼做,這將令人遺憾。”

The development of the Crispr-Cas9 technique is a story in which obscure basic biological research turned out to have huge practical implications. For Dr. Doudna, though, it is only one accomplishment in a stellar career.

Crispr-Cas9技術的發展,可以被認爲是一個鮮爲人知的基礎生物學研究發展爲巨大應用價值的故事。不過,對杜德納博士來說,Crispr-Cas9只是她輝煌職業生涯中的一項成就而已。

“She’s been a high-impact scientist from the time she was a graduate student,” said Thomas Cech, a Nobel laureate and professor of chemistry and biochemistry at the University of Colorado, for whom Dr. Doudna was a postdoctoral researcher. “New topics, new fields of science, but she just has a knack for discovery.”

“從研究生時代開始,她就一直是個具有高度影響力的科學家。”諾貝爾獎得主托馬斯·切赫(Thomas Cech)說,他是科羅拉多州大學化學和生物化學教授,杜德納曾跟隨他做博士後研究。“新的主題,新的科學領域,但是她就是有發現的技能。”

Dr. Doudna was 7 when she moved to Hilo, where her father taught literature at the University of Hawaii campus there, and her mother lectured on history at a community college. Their daughter loved exploring the rain forests and was fascinated by how things worked. She found her calling in high school after hearing a lecture by a scientist about her research into how normal cells became cancerous.

杜德納7歲時,全家搬到希洛。父親在夏威夷大學教文學,母親在一個社區大學講授歷史,他們的女兒喜歡探索熱帶雨林,對事物如何運行很着迷。在高中時期,她聽了一個科學家的講座,這位科學家講解了自己是怎樣研究正常的細胞如何變成癌細胞的。因爲這次講座, 杜德納找到了自己的使命。

“I was just dumbstruck,” Dr. Doudna recalled. “I wanted to be her.”

“我當時目瞪口呆。”杜德納回憶道,“我希望自己成爲像她那樣的科學家。”

After studying biochemistry at Pomona College in California, she went to Harvard for graduate school. There her adviser, the future Nobel laureate Jack Szostak, was doing research on RNA. Some scientists believe that RNA, not DNA, was the basis of early life, since the molecule can both store genetic information and catalyze chemical reactions.

在加州的波莫納學院(Pomona College)學習生物化學後,她去了哈佛的研究生院。她的導師、2009年諾貝爾生理學或醫學獎獲得者傑克·紹斯塔克(Jack Szostak)當時在做RNA的研究。一些科學家相信,RNA是早期生命的基礎,而不是DNA,因爲RNA分子可以同時存儲遺傳信息,又能催化化學反應。

Dr. Doudna earned her doctoral degree by engineering a catalytic RNA that could self-replicate, adding evidence to that theory. But her inability to visualize this catalytic RNA hindered her work.

杜德納憑藉改造催化性RNA使之具有自我複製能力獲得博士學位,這也爲RNA是早期生命基礎的理論增加了證據。但是,無法使這種催化性RNA可視化阻礙了她的研究。

So as a postdoctoral researcher in Colorado, she decided to try to determine the three-dimensional atomic structure of RNA using X-ray diffraction — and succeeded, though she had had no formal training in the technique. Structural and biochemical studies of RNA in action have been her forte ever since.

因此,在科羅拉多州從事博士後研究時,她決定嘗試使用X射線衍射確定RNA的三維原子結構並且取得了成功,儘管她沒有經過正規的技術訓練。自那之後,RNA結構和生物化學研究成爲她的特長。

In 2000, while on the faculty at Yale, she won the Alan T. Waterman Award, given each year by the National Science Foundation to an exceptional young scientist. She moved to Berkeley in 2002.

2000年,還是耶魯教員的杜德納獲得艾倫·沃特曼獎(Alan T. Waterman Award),這一獎項由美國國家科學基金每年授予一位傑出的青年科學家。2002年,她赴伯克利任職。

In 2005, Dr. Doudna was approached by Jillian Banfield, an environmental researcher at Berkeley who had been sequencing the DNA of unusual microbes that lived in a highly acidic abandoned mine. In the genomes of many of these microbes were unusual repeating sequences called “clustered regularly interspaced short palindromic repeats,” or Crispr.

2005年, 伯克利大學的一位環境科學的研究者吉利安·班菲爾德(Jillian Banfield)找到杜德納,班菲爾德當時正在對高度酸性的廢氣礦井中的罕見微生物進行DNA測序。許多這些微生物的基因組存在罕見的重複序列,被稱作“規律成簇的間隔短迴文重複”,即Crispr。

No one was quite sure what they did, though over the next few years scientists elsewhere established that these sequences were part of a bacterial immune system. Between the repeated sequences were stretches of DNA taken from viruses that had previously infected the bacteria — genetic most-wanted posters, so to speak.

即便在此後的幾年時間裏,沒有人確定它們的功能,直到其他地方的科學家證實,這些序列是細菌免疫系統的一部分。這些重複序列之間的DNA片段源自於曾經侵染細菌的病毒——可以這麼說,這是細菌最想得到的遺傳標識。

If the same virus invaded again, these stretches of DNA would permit the bacteria to recognize it and destroy it by slicing up its genetic material. Dr. Doudna was trying to figure out exactly how this happened.

如果相同的病毒再次入侵,這些DNA片段將允許細菌識別這一病毒並通過切割它的遺傳物質摧毀它。杜德納試圖弄清楚這到底是如何發生的。

“I remember thinking this is probably the most obscure thing I ever worked on,” she said.

“我記得,我當時認爲這可能是我研究過的最難懂的東西。”她說。

It would prove to have wide use. At a conference in early 2011, she met Emmanuelle Charpentier, a French microbiologist at Umea University in Sweden, who had already made some fundamental discoveries about the relatively simple Crispr system in one bacterial species.

日後它將被證明有着廣泛的用途。在2011年初的一個會議上,她遇到了瑞典于默奧大學(Umea University)的法國微生物學家埃馬紐埃爾·卡彭蒂耶(Emmanuelle Charpentier),她已經在一個細菌物種中發現了一個相對簡單的Crispr系統。

The bacterial expert and the structural biologist decided to work together.

細菌專家和結構生物學家決定聯手研究。

“It was very enjoyable, because we were complementary,” said Dr. Charpentier, who recalled sitting in her office near the North Pole while Dr. Doudna regaled her with stories about Hawaii.

“合作很愉快,因爲我們剛好互補。”卡彭蒂耶博士說。她坐在靠近北極的辦公室回憶起,杜德納講述的關於夏威夷的故事讓她樂不可支。

Along with postdoctoral researchers Martin Jinek and Krzysztof Chylinski, the two scientists eventually figured out how two pieces of RNA join up with a protein made by the bacteria called Cas9 to cut DNA at a specific spot. The researchers also found that the two RNA pieces could be combined into one and still function.

杜德納的兩個博士後馬丁·伊內克(Martin Jinek)和剋日什托夫·黑林斯基(Krzysztof Chylinski),最終找到了兩段RNA以及由細菌產生的蛋白質系統,又被稱爲Cas9蛋白系統,它可以在DNA特定位置進行剪切。研究人員還發現,這兩個RNA片段可組合成一個片段,並仍能發揮作用。

In a eureka moment, the scientists realized that this cellular defense system might be used to edit genomes, not just kill viruses.

在這靈光閃現的時刻,科學家們意識到,這種細菌防禦系統不僅可用來殺死病毒,也可用來編輯基因組。

A specific sequence of guide RNA could be made to attach to a spot virtually anywhere on the genome, and the Cas9 protein would cleave the DNA at that spot. Then pieces of the DNA could be deleted or added, just as a film editor might cut a film and splice in new frames.

Cas9蛋白系統中一個特定的嚮導RNA 序列可附着在基因組上幾乎任何一個位置, Cas9蛋白會切開DNA序列的特定位點,然後在這個位點添加或刪除特定的DNA片段,如同電影剪輯那樣,刪掉或拼接上一個新的電影片段。

The researchers demonstrated this using DNA in a test tube. While there were other genome editing techniques, they found that Crispr-Cas9 was much simpler.

研究人員在試管中演示了DNA編輯這一操作過程。雖然目前還有其他的基因組編輯技術,但是他們發現Crispr-Cas9技術要簡單得多。

The paper describing the technique, published by the journal Science in June 2012, set off a race to see if it would work in human, plant and animal cells.

對這項技術的最早研究發表在2012年6月的《科學》雜誌上,隨後引發了一場對該技術是否可應用於人類、植物和動物細胞的爭論。

Dr. Doudna, whose expertise was in working with molecules, not cells, reported such a demonstration in human cells in January 2013. But her report came four weeks after two papers were published simultaneously, one by George Church at Harvard and the other by the Broad Institute’s Dr. Zhang.

杜德納博士的專業知識是在分子生物學領域,而不是細胞生物學領域。2013年1月,她在開放期刊eLife上發表了這項技術在人類細胞中的應用,就在4周之前,哈佛大學的喬治·切奇(George Church)以及布羅德研究所的張鋒博士分別發表了一篇論文。

Now the University of California and the Broad Institute are arguing before the federal patent office over whether Dr. Doudna or Dr. Zhang, who last year received the Waterman Award for young scientists that Dr. Doudna had won years earlier, was the first to invent the genome editing technique. So far, the patents have gone to Dr. Zhang.

Crispr-Cas9技術專利之戰悄然打響,現在,加州大學和布羅德研究所在美國聯邦專利局就Crispr-Cas9技術專利應授予誰而爭論不休。張鋒博士去年也獲得了杜德納多年前獲得過的沃特曼獎。不過,到目前爲止,張鋒博士仍是Crispr-Cas9技術專利的擁有者。

The Broad Institute claims that the paper by Dr. Doudna and Dr. Charpentier in 2012 did not demonstrate how to alter DNA in cells with nuclei, including human cells, something requiring the inventive steps that Dr. Zhang took. His patent application included pages from a lab notebook he said demonstrated that he was doing Crispr genome editing even before the 2012 paper was published.

布羅德研究所稱,杜德納博士和卡彭蒂耶博士2012年的那篇論文,並沒有說明這項技術在包括人類細胞在內的有核細胞中如何改變DNA, 而張鋒的工作則闡明瞭這一點。在Crispr-Cas9技術的專利申請材料中,包含有張鋒的實驗記錄,顯示他在2012年杜德納的研究發表之前, 就在使用 Crispr編輯技術。

The University of California says it filed for a patent months before Dr. Zhang did, though the Broad Institute says that initial application lacked necessary details. The university’s request to the patent office says that once the 2012 paper laid out the recipe, it was obvious how to use it in cells. The university also says Dr. Zhang’s notebook does not prove he could edit genomes before the 2012 paper.

儘管布羅德研究所認爲,最初的申請材料缺乏必要的細節,加州大學表示,他們提出專利申請的時間比張鋒早幾個月。加州大學還向美國專利局表示,杜德納博士2012年的這篇論文一經發表,在細胞中如何使用它就變得顯而易見,還說,張鋒的實驗記錄材料並不能證明他在杜德納發表論文之前就能編輯基因組。

Patent disputes are often settled in time. In any event, Dr. Church of Harvard said, before Crispr-Cas9 could be used to treat disease, it would need important refinements from many other researchers.

解決專利糾紛通常需要時日。哈佛大學切奇教授稱,無論如何,在Crispr-Cas9技術可用來治療疾病之前,還需要許多研究者對其加以改進。

“It’s going to be hard to use Feng’s without Jennifer’s, and it would be hard to use either of them without further improvements,” he said.

“如果沒有杜德納的發現,張鋒的發明很難得到應用,而(這項技術)如果沒有進一步的改進,他們二人的方法都難以應用。” 切奇教授說。

The scientists have formed competing companies with rights to their patents and pending patents. Dr. Doudna co-founded Caribou Biosciences to work on research uses of Crispr-Cas9, and more recently, Intellia Therapeutics to work on disease treatments.

此後,兩位科學家憑藉已有的專利以及申請中的專利分別成立了自己的公司。杜德納博士與其他人共同創立Caribou Biosciences公司來繼續Crispr-Cas9技術的研究,最近則成立了另一家公司Intellia Therapeutics,專注於疾病治療。

Dr. Church and Dr. Zhang are co-founders of Editas Medicine, which Dr. Doudna also helped start but then withdrew from. Dr. Charpentier, who is now at the Helmholtz Center for Infection Research in Germany, helped start Crispr Therapeutics. She and Dr. Doudna remain friends, but no longer collaborate on research.

張鋒與切奇教授聯合創立了Editas Medicine公司,杜德納博士也參與了公司的創建,但是之後她退出了。在德國亥姆霍茲感染研究中心(Helmholtz Center for Infection Research)工作的卡彭蒂耶博士幫助創建了Crispr Therapeutics公司。儘管她和杜德納仍是朋友,但是她們兩人不再合作研究。

Even before the dust settles, researchers are moving ahead. While contending with the patents, Dr. Doudna began hearing reports that researchers were trying to use Crispr-Cas9 to make inheritable DNA changes in embryos. Genetically altered monkeys had already been created in China using the technique.

在專利歸屬塵埃落定之前,研究人員仍在繼續探索Crispr-Cas9技術。不過,最近杜德納博士開始注意到,有研究者開始利用這一技術修飾人類胚胎細胞DNA的報告。去年,中國研究者就利用這一技術讓基因編輯猴子成爲現實。

“It’s very far afield from the kind of chemistry I think about and know about,” she said. Still, she felt it would be irresponsible to ignore the rumors.

“這和我所理解以及思考的化學領域相距甚遠。”杜德納說。但是她認爲如果自己忽視這一傳言,將是不負責任的。

She organized a meeting of leading biologists in Napa, Calif., in January. In a subsequent commentary published in Science, the group called for a moratorium on attempts to create altered babies, though they said basic research on inheritable changes should still be done.

今年1月,杜德納在加利福尼亞納帕(Napa)地區組織了一場由頂尖生物學家參加的會議。隨後,這一羣體有關呼籲暫停嘗試創造基因改造的嬰兒的評論發表在《科學》雜誌上,儘管他們認爲,關於人類遺傳物質改變的基礎研究仍可以進行 。

Dr. Doudna said it was not practical to prohibit basic research. “You can’t really put a lid on it, even if you wanted to,” she said. She and others are trying to organize a bigger international meeting with participants from companies and governments as well as universities, possibly to set new guidelines.

杜德納博士稱,禁止這一領域的基礎研究工作並不現實。“即使你想要禁止,絕對的禁止顯然是不可能的。”她說。目前,她正與其他研究者組織一個更大的國際會議,其中包括企業、大學以及政府的代表,將共同制定新的指導方針。

She is also trying to cope with her newfound quasi-celebrity status. She has been invited to hobnob with entrepreneurs in Silicon Valley, to speak to science fiction writers, to advise Hollywood on science-themed movies. The garden, her hobby, has had to wait.

杜德納正在努力地適應她的準名人生活。她經常被企業家們邀請去硅谷演講,參與科幻小說作家的暢談,以及爲好萊塢科學電影提供科學諮詢。而她卻無瑕顧及自己對花園種植的愛好 。

In November, Dr. Doudna and Dr. Charpentier were each awarded $3 million Breakthrough Prizes, endowed by leading Internet entrepreneurs. They accepted their awards at an Oscars-like black-tie affair attended by movie stars like Cameron Diaz and Benedict Cumberbatch. Recently Time magazine listed the two scientists among the 100 most influential people in the world.

2014年11月,杜德納博士和卡彭蒂耶博士共同獲得了生命科學突破獎(Breakthrough Prizes),每人獲得300萬美元的獎金,該獎項由互聯網領域的巨頭企業家們創立。生命科學突破獎授獎儀式就如同奧斯卡獎一樣隆重,參加者身着盛裝,電影明星卡梅隆·迪亞茲(Cameron Diaz)和本尼迪克特·康伯巴奇(Benedict Cumberbatch)也受邀出席。同年,這兩位女科學家被美國《時代》雜誌評選爲世界上100位最有影響力的人物。

Dr. Doudna, who has a 12-year-old son, Andrew, also finds herself a role model for women in science. Her secret: “I have a great partner,” with whom she shares the chores.

杜德納有一個12歲的兒子,名叫安德魯(Andrew)。杜德納也深知自己成爲女性科學家的榜樣,而她的祕訣是,“有一個偉大的伴侶”,幫她分擔家務活。

Her husband, Dr. Cate, is also a professor at Cal-Berkeley. The couple have adjacent offices, with views of the Golden Gate Bridge in the distance. Dr. Cate also studies RNA; there is some overlap, but mostly they do their own research. Andrew walks to their office from his middle school each afternoon and hangs out until his parents are ready to go home.

她的丈夫凱特博士,也是加州大學伯克利分校的一名教授。這對夫婦的辦公室相鄰,都可以遠眺到金門大橋。凱特博士也研究RNA,儘管研究上有一些重疊,但是他們主要還是做各自的研究。每個下午,安德魯從學校步行到他們的辦公室,會一直待到這對夫婦準備回家。

“I don’t think of myself as a role model, but I can see that I am,” Dr. Doudna said. “I still think of myself as that person back in Hawaii.”

“我不把自己看做是別人的榜樣,但是我知道我的確如此 。”杜德納博士說,“我認爲自己還是夏威夷的那個我。”

猜你喜歡

熱點閱讀

最新文章