如何防止基因編輯嬰兒事件重演？

A year ago, Dr. Matthew Porteus, a genetics researcher at Stanford, received an out-of-the-blue email from a young Chinese scientist, asking to meet.

一年前，斯坦福大學的遺傳學研究員馬修·波特斯(Matthew Porteus)博士突然收到了一位年輕中國科學家的來函，要求與他見面。

A few weeks later, the scientist, He Jiankui, arrived in his office and dropped a bombshell. He said he had approval from a Chinese ethics board to create pregnancies using human embryos that he had genetically edited, a type of experiment that had never been carried out before and is illegal in many countries.

幾周后，這位名叫賀建奎的科學家來到他的辦公室，拋出一個驚人的消息。他說，他已獲得中國一個倫理委員會的批準，可以將經(jīng)他進行基因編輯的人類胚胎用于妊娠，這是一種以前從未進行過的實驗，在許多國家都是非法的。

“I spent probably 40 minutes or so telling him in no uncertain terms how wrong that was, how reckless,” Dr. Porteus said in a recent interview.

“我花了大約40分鐘，用十分明確的語言來告訴他，這種做法是多么錯誤，多么魯莽，”波特斯在最近的一次采訪中說。

Dr. Porteus did not report Dr. He’s intentions to anyone, because he thought he’d talked him out of it and it wasn’t clear where to report the plans of a scientist in China. Neither did two other American scientists Dr. He confided in.

波特斯并沒有將賀建奎的意圖告訴任何人，因為他認為自己已經(jīng)說服賀不再這么做，并且他也不清楚該如何舉報一名中國科學家的計劃。得到賀建奎透露信息的其他兩位美國科學家也沒有將這件事告訴任何人。

Now, nearly two months after Dr. He shook the scientific world by announcing he had created the first genetically edited babies — twins, born in November — the world’s major science and medical institutions are urgently trying to come up with international safeguards to keep such rogue experiments from happening again.

現(xiàn)在，在賀建奎宣布創(chuàng)造首例基因編輯嬰兒——一對于11月出生的雙胞胎——并震驚科學界近兩個月后，世界上的主要科學和醫(yī)學機構都迫切地試圖出臺國際保障措施來防止這樣任意妄為的實驗再次發(fā)生。

But while scientists around the world agree the nightmare scenario must be stopped, they disagree about how to do it. Even inventors of Crispr, the gene-editing tool Dr. He used, differ on the best approach.

然而，雖然全世界的科學家都同意這種恐怖景象必須加以制止，但在如何制止上卻意見不一。即便是賀建奎所使用的基因編輯工具Crispr的發(fā)明者們，在怎樣才是最佳方法的問題上都有不同看法。

Some scientists want a yearslong moratorium on creating pregnancies with gene-edited human embryos. Others say a moratorium would be too restrictive, or unenforceable. Some think scientific journals should agree not to publish embryo-editing research. Others consider that misguided or ineffective.

一些科學家希望頒布持續(xù)數(shù)年的暫止禁令來制止將經(jīng)基因編輯的人類胚胎用于妊娠。另一些認為禁令限制性過強，或者不可執(zhí)行。一些認為，科學期刊應該同意不發(fā)表胚胎編輯研究。另一些人則認為那是具有誤導性的，或者是徒勞的。

But most agree major health and science institutions should act quickly. The World Health Organization is assembling a panel to develop global standards for governments to follow. Leaders of the National Academy of Medicine and the National Academy of Sciences in the United States, along with the Chinese Academy of Sciences, have jointly proposed a commission with academies in other countries to develop criteria so scientists can’t “seek out convenient locales for conducting dangerous and unethical experimentation.” The proposal included establishing “an international mechanism that would enable scientists to raise concerns.” The World Economic Forum in Davos has scheduled a discussion of the issue on Thursday. Enforcement would need to be done by individual countries, many of which already have relevant laws and regulations. But global standards set by scientists could give countries a big push.

但多數(shù)人同意，主要的健康和科學機構應迅速采取行動。世界衛(wèi)生組織正在召集小組討論會，制定全球標準供各國政府遵循。美國國家醫(yī)學院(National Academy of Medicine)和美國國家科學院(National Academy of Sciences)的負責人已聯(lián)合提議，與其他國家的學術機構成立委員會，制定標準，這樣科學家就無法“尋找方便的地點開展危險、不符合倫理的實驗”。該提議包括建立“一項國際機制，使科學家能夠提出他們的擔憂”。周四，達沃斯的世界經(jīng)濟論壇安排了該議題的討論環(huán)節(jié)。執(zhí)行將需要各個國家去做，許多國家已經(jīng)有相關的法律法規(guī)。但由科學家制定的全球標準可以給各國一個有力的推動。

The fear isn’t just that genetically-edited babies could develop unintended health problems that could be inherited by subsequent generations, or that there could be attempts to produce designer babies, genetically altered for physical features, intelligence or athletic prowess.擔憂不只在于基因編輯嬰兒會導致意想不到的健康問題，還可能遺傳給后代，或可能會有人企圖生育經(jīng)過設計的嬰兒，通過基因改變獲得身體特征、智力或運動能力。

Rice is investigating. Lawyers for Dr. Deem, who also told the A.P. he had “a small stake” in Dr. He’s genomics companies, said: “Michael does not do human research and he did not do human research on this project.”

萊斯大學正在展開調(diào)查。迪恩的律師也曾告訴美聯(lián)社，他在賀建奎的基因組學公司里有“少數(shù)股權”，他說：“邁克爾不做人類研究，他也沒有做這個項目的人類研究。”

Dr. He and Dr. Deem haven’t responded to emails from The New York Times. A Rice spokesman declined to offer any information on the university’s investigation.

賀建奎和迪恩尚未回復《紐約時報》的郵件。萊斯大學發(fā)言人拒絕提供關于調(diào)查的任何信息。

Dr. He, who is in his mid-30s, went public about his work in a video announcement in November, after it was revealed by MIT Technology Review just before a conference on genome editing in Hong Kong.

《麻省理工科技評論》(MIT Technology Review)在香港舉行的一場基因組編輯大會召開前披露了此事，而后年齡在35歲上下的賀建奎于11月通過一則視頻聲明對外公布了他的研究。

“I was just horrified; I felt kind of physically sick,” said Jennifer Doudna, a Crispr inventor, who first learned what Dr. He had done when he emailed her on Thanksgiving with the subject line “Babies Born."

“我被嚇壞了，能感到某種身體上的不適，”Crispr發(fā)明者之一詹妮弗·達奧納(Jennifer Doudna)說。賀建奎在感恩節(jié)發(fā)給過她一封題為“嬰兒已出生”的郵件，這是她第一次得知他在做什么。

Dr. He said he had disabled a gene in the embryos that allows people to become infected with H.I.V., something medically unnecessary because simpler and safer ways exist for preventing H.I.V.

賀建奎說，他使胚胎中一個會讓人感染HIV的基因失了效，但這在醫(yī)學上是沒有必要的，因為預防HIV還有更簡便、更安全的方式。

Data he presented suggests the editing might have caused unintended genetic alterations with unknown health implications. There are serious doubts that Dr. He, who said he also created a second pregnancy that Chinese authorities said is still underway, ensured the babies’ parents understood the risks of the editing.

他給出的數(shù)據(jù)表明，基因編輯無意間可能已導致帶有未知健康問題的基因轉(zhuǎn)變。對于賀建奎是否確保嬰兒父母理解了基因編輯的風險，仍存在很大懷疑。他說他還完成了第二個妊娠，對此中國當局表示尚在進行中。

Dr. Porteus says he now wishes he’d consulted with colleagues after he learned about Dr. He’s plans and emailed a senior Chinese ethicist while Dr. He was in his office.

波特斯稱，他現(xiàn)在覺得自己當初在了解到賀建奎的計劃后應該和同事們商議，并在他仍在自己辦公室時，就寫封郵件給中國的一位資深倫理學家。

Another American Dr. He spoke to, Dr. William Hurlbut, a Stanford ethics professor, said he expressed strong opposition to the work in discussions with Dr. He in 2017 and 2018, warning him that, among other things, “‘This could hurt you, this could humiliate you.’”

另一位與賀建奎交談過的美國人、斯坦福大學倫理學教授威廉·赫爾伯特(William Hurlbut)博士說，2017至2018年，他曾在與賀的討論中對他的工作表示過強烈反對，包括警告他“‘這會害了你，會讓你蒙羞。’”

As of last October, Dr. Hurlbut said, “I was personally convinced that he had either implanted or had live births.”

赫爾伯特說，截止去年10月，“我個人確信他要么已經(jīng)植入，要么已經(jīng)有了活產(chǎn)兒。”

He said he didn’t notify anyone because “I decided it wasn’t like I knew somebody was going to murder somebody; it was a fait accompli. I didn’t feel like there was either any moral obligation or practical benefit to my raising it.”

他說他沒有告知任何人，因為“當時我的想法是，這又不是說我知道某人要去殺人了;這是個既成事實。我沒覺得自己有任何道德義務或?qū)嶋H的好處要去把這件事說出來。”

Mark DeWitt at University of California, Berkeley, declined to be interviewed, but has said he also tried to dissuade Dr. He.

加州大學伯克利分校的馬克·德威特(Mark DeWitt)拒絕接受采訪，但他說他也曾試圖勸阻賀建奎。

All three American scientists noted Dr. He spoke to them expecting confidentiality, which is how scientists commonly share preliminary research.

所有三位美國科學家都指出，賀建奎告知他們時期望他們能保密，這也是科學家通常分享初步研究的方式。

If Dr. He had been working through American universities or funding institutions, scientists could have alerted those, said Dr. Francis Collins, director of the National Institutes of Health, which doesn’t fund human embryo editing. China’s system is so complex that American scientists might not know “exactly what kind of alarm bells they should be ringing and who they should be ringing them to,” he said.

美國國家衛(wèi)生研究院(National Institutes of Health)院長弗朗西斯·柯林斯(Francis Collins)博士說，如果賀建奎是在美國的大學或資助機構完成工作，科學家們可能已經(jīng)就此事發(fā)出了警報。他所在的這個機構不資助人類胚胎編輯研究。中國的體制太過復雜，美國科學家可能不了解“究竟他們該敲響什么樣的警鐘，該向誰敲響警鐘，”他說。

Efforts to come up with a coordinated international response gained momentum this week when Chinese authorities, often perceived to be more laissez-faire about reining in unorthodox scientific experiments, indicated that an initial government investigation found that Dr. He “seriously violated” state regulations, according to Chinese state media.

一般認為中國當局對遏制非正統(tǒng)的科學實驗更多是持自由放任態(tài)度，而在據(jù)中國國有媒體報道，當局表明政府初步調(diào)查發(fā)現(xiàn)賀建奎“嚴重違反”了國家有關規(guī)定后，國際社會開始加緊行動，就此事給出一個協(xié)調(diào)一致的對策。

The findings — that he forged ethics documents, used unsafe and ineffective gene-editing methods and intentionally evaded supervision — suggest that he could face criminal charges. Dr. He’s academic home, Southern University of Science and Technology in Shenzhen, rescinded his contract.

調(diào)查結果——即他偽造了倫理文書，使用了安全性、有效性不確切的基因編輯方法，有意逃避監(jiān)管——表明他可能面臨刑事指控。賀建奎的學術單位深圳南方科技大學解除了他的聘用合同。

“It is clear that the Chinese government is taking this issue seriously,” said Dr. Victor Dzau, president of the National Academy of Medicine in Washington.

“顯然，中國政府在嚴肅對待這件事情，”華盛頓的國家醫(yī)學科學院院長曹文凱(Victor Dzau)博士說。

Initially it was unknown whether Dr. He would face consequences. In recent years, China has invested millions aiming to become a scientific powerhouse, including money to lure back to China scientists like Dr. He, who did doctoral and postdoctoral work in the United States. Eye-popping experiments, like a proposal to transplant a head to another body, have not been discouraged.

賀建奎是否會遭到處罰，在一開始是不明朗的。近年來，中國大舉投資，旨在成為科技大國，包括出資吸引賀建奎這樣的科學家回到中國，他在美國完成了博士和博士后工作。一些令人大為震驚的實驗，如將頭部移植給另一個身體的想法，并未被阻攔。

“It was vital for this dangerous and unwarranted work to be officially acknowledged and deemed illegal,” said Dr. Doudna after the announcement of the preliminary findings. “This announcement confirms an international ‘red line’ of ethical and scientific conduct to help ensure that this type of radical, medically unnecessary and negligent work does not happen again.”

“這種危險且無正當理由的研究，一定要得到正式承認并被判定為非法，”在初步結果公布后，達奧納說。“這一公布確認了一道倫理和科學行為的國際‘紅線’，以幫助確保這類激進的、無醫(yī)學必要性的、疏于管束的研究不再發(fā)生。”

While under investigation, Dr. He has been in faculty housing, able to roam campus, go to the gym and communicate with some Western scientists. Dr. Hurlbut has spoken to him by phone and email and said that in those conversations, Dr. He had sounded “hopeful that he can have a contributory future.”

在接受調(diào)查期間，賀建奎一直住在職工宿舍，能夠在校園走動，去健身房，并與一些西方的科學家溝通。赫爾伯特已和他通過電話和郵件，他說在那些談話中，賀聽起來“對自己將來能有所貢獻仍抱有希望”。

Asked if Dr. He, who initially said he was “proud” of what he had done, had expressed regret, Dr. Hurlbut replied: “He really regrets the way it was revealed to the world, the timing.”

賀建奎起初說過，他對自己所做之事感到“自豪”，在被問及是否表達過悔意時，赫爾伯特回復道：“他對這件事披露給世界的方式和時機真的感到后悔。”

Dr. He also recently emailed a British geneticist, Robin Lovell-Badge, saying: “I fully agree that ‘scientists should draw up a clear set of dos and don’ts for those who want to perform human gene editing.’”

賀建奎近期還給英國遺傳學家羅賓·洛維爾-巴奇(Robin Lovell-Badge)發(fā)過郵件，稱：“我完全同意，‘對于那些想開展人類基因編輯的人，科學家應該劃分出一套明確的‘該做’和‘不該做’的事項準則。’”

At least one major journal decided against publishing Dr. He’s research before the Hong Kong announcement, and scientists have debated whether it should be published.

至少有一份重要期刊在香港的聲明之前就決定不發(fā)表賀建奎的研究，科學家們也在就是否要發(fā)表展開爭論。

Dr. Porteus said he initially thought it should be posted on a forum that accepts early, not-yet-peer-reviewed research because “we could go through it with a fine tooth comb so we understand every detail.” But now, he said, “I don’t even think that would be appropriate. It’s so out of bounds, it can’t be given any stamp of approval.”

波特斯說，他最初認為，應該把它貼在一個接受未經(jīng)同行評審的早期研究的論壇上，因為“我們可以進行一次徹底的梳理，以便了解每一個細節(jié)。”但現(xiàn)在，他說，“我不再認為這樣做是合適的。這種行為太過分了，不能獲得任何形式的認可。”

Although Dr. He has said his motivation was protecting people from H.I.V., he also clearly wanted leading scientists’ approval. Several months before the twins’ birth, he asked to visit Feng Zhang, another Crispr inventor. At Dr. Zhang’s Broad Institute lab in Boston, Dr. He showed data from his gene-editing of human embryos in laboratory dishes, which didn’t alarm Dr. Zhang because it had already been done by several scientists. But Dr. Zhang sharply criticized “big problems” with Dr. He’s gene-editing results.

盡管賀建奎說他的動機是保護人們不感染艾滋病毒，顯然他也希望得到權威科學家的認可。在這對雙胞胎出生前的幾個月，他要求會見Crispr的另一位發(fā)明者張鋒。在張鋒位于波士頓博德研究所(Broad Institute)的實驗室，賀建奎展示了他在實驗室培養(yǎng)皿中對人類胚胎進行基因編輯時獲得的數(shù)據(jù)，這并沒有讓張鋒感到警覺，因為已經(jīng)有幾位科學家這么做了。但張鋒尖銳地批評了賀建奎的基因編輯結果中的“大問題”。

Dr. He didn’t say anything about implanting embryos. “Maybe I shouldn’t have been so critical and he would have revealed more,” Dr. Zhang said.

賀建奎完全沒有提及植入胚胎的事情。“也許我不應該挑那么多毛病，這樣他就會透露更多信息，”張鋒說。

Some experts say the best way to block misguided uses of embryo editing is coordinated action by all public and private players involved in new scientific technologies, including regulatory agencies, patent offices, funding organizations and liability insurers. In a recent New England Journal of Medicine article, R. Alta Charo, a bioethicist at University of Wisconsin-Madison, recommended a “comprehensive ecosystem of public and private entities that can restrain the rogues among us.”

一些專家說，阻止錯誤使用胚胎編輯的最佳方法是由所有新科學技術的公共和私人參與者協(xié)調(diào)行動，包括監(jiān)管機構、專利局、資助組織和責任保險公司。威斯康星大學麥迪遜分校(University of Wisconsin-Madison)的生物倫理學家R·奧塔·查洛(R. Alta Charo)最近在《新英格蘭醫(yī)學雜志》(New England Journal of Medicine)上發(fā)表的文章中提議，建立一個“由公共和私人實體組成的綜合生態(tài)系統(tǒng)，可以約束我們當中的任意妄為者”。

The first step may be an international commission, led by the American academies of science and medicine, which many countries have now agreed to form, said Dr. Dzau, the academy of medicine president. It would produce a report this year setting detailed guidelines.

第一步可能是成立一個由美國科學與醫(yī)學研究院牽頭的國際委員會。美國國家醫(yī)學科學院院長曹文凱說，許多國家現(xiàn)在已經(jīng)同意成立這個委員會。它將在今年發(fā)布一份報告，制定詳細的指導方針。

Current standards, reflected in a 2017 National Academies report, say edited embryos should only be used in human pregnancies to prevent or treat “serious diseases or disabilities” with no “reasonable alternative” treatment. Dr. Dzau wants more specifics, like which diseases are dire enough to justify the risks, which risks are acceptable, and how much preliminary testing is required.

目前的標準反映在2017年美國國家科學院的一份報告中，稱只有在預防或治療“嚴重疾病或殘疾”，且沒有“合理替代方案”時，才可以將經(jīng)過編輯的胚胎用于人類妊娠。曹文凱希望更加細化，比如哪些疾病嚴重到足以證明風險是合理的，哪些風險是可以接受的，以及需要多少初步測試。

He said the commission might recommend a moratorium on implanting edited human embryos until it issues its report. Some leading scientists want a longer hiatus.

他說，委員會可能會建議對植入編輯過的人類胚胎的行為實施暫止禁令，直到報告得以發(fā)表。一些頂尖科學家希望有更長的暫止期。

Dr. Zhang said a five-year moratorium would allow for necessary public discussion.

張鋒說，五年的暫止禁令將允許科學家展開必要的公開討論。

Dr. Doudna disagrees and instead supports developing “very strict international criteria” and getting journals “to say they will not publish work like this.”

達奧納不同意這種觀點，她支持制定“非常嚴格的國際標準”，讓期刊“聲明它們不會發(fā)表這樣的作品”。

She’s been jousting over email with the N.I.H’s Dr. Collins, who leans toward a moratorium.

她一直在和美國國家衛(wèi)生研究院的柯林斯在電子郵件中爭吵，后者傾向于暫禁。

“If you use the m-word, it has a little more clout,” Dr. Collins said, noting that international agreement would be required to lift it, discouraging individual countries from deciding, “‘We think it’s O.K. now.’”

“如果你使用‘暫禁’這么嚴重的字眼，它的影響力就會大一些，”柯林斯說。他指出，要想實現(xiàn)它，就需要達成國際協(xié)議，打消個別國家那種“我們覺得現(xiàn)在沒問題了”的念頭。