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(xué)的遺傳學(xué)研究員馬修·波特斯(Matthew Porteus)博士突然收到了一位年輕中國(guó)科學(xué)家的來(lái)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(xué)家來(lái)到他的辦公室，拋出一個(gè)驚人的消息。他說(shuō)，他已獲得中國(guó)一個(gè)倫理委員會(huì)的批準(zhǔn)，可以將經(jīng)他進(jìn)行基因編輯的人類胚胎用于妊娠，這是一種以前從未進(jìn)行過(guò)的實(shí)驗(yàn)，在許多國(guó)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(yǔ)言來(lái)告訴他，這種做法是多么錯(cuò)誤，多么魯莽，”波特斯在最近的一次采訪中說(shuō)。

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(méi)有將賀建奎的意圖告訴任何人，因?yàn)樗J(rèn)為自己已經(jīng)說(shuō)服賀不再這么做，并且他也不清楚該如何舉報(bào)一名中國(guó)科學(xué)家的計(jì)劃。得到賀建奎透露信息的其他兩位美國(guó)科學(xué)家也沒(méi)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(duì)于11月出生的雙胞胎——并震驚科學(xué)界近兩個(gè)月后，世界上的主要科學(xué)和醫(yī)學(xué)機(jī)構(gòu)都迫切地試圖出臺(tái)國(guó)際保障措施來(lái)防止這樣任意妄為的實(shí)驗(yàn)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(xué)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(wèn)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(xué)家希望頒布持續(xù)數(shù)年的暫止禁令來(lái)制止將經(jīng)基因編輯的人類胚胎用于妊娠。另一些認(rèn)為禁令限制性過(guò)強(qiáng)，或者不可執(zhí)行。一些認(rèn)為，科學(xué)期刊應(yīng)該同意不發(fā)表胚胎編輯研究。另一些人則認(rèn)為那是具有誤導(dǎo)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(xué)機(jī)構(gòu)應(yīng)迅速采取行動(dòng)。世界衛(wèi)生組織正在召集小組討論會(huì)，制定全球標(biāo)準(zhǔn)供各國(guó)政府遵循。美國(guó)國(guó)家醫(yī)學(xué)院(National Academy of Medicine)和美國(guó)國(guó)家科學(xué)院(National Academy of Sciences)的負(fù)責(zé)人已聯(lián)合提議，與其他國(guó)家的學(xué)術(shù)機(jī)構(gòu)成立委員會(huì)，制定標(biāo)準(zhǔn)，這樣科學(xué)家就無(wú)法“尋找方便的地點(diǎn)開展危險(xiǎn)、不符合倫理的實(shí)驗(yàn)”。該提議包括建立“一項(xiàng)國(guó)際機(jī)制，使科學(xué)家能夠提出他們的擔(dān)憂”。周四，達(dá)沃斯的世界經(jīng)濟(jì)論壇安排了該議題的討論環(huán)節(jié)。執(zhí)行將需要各個(gè)國(guó)家去做，許多國(guó)家已經(jīng)有相關(guān)的法律法規(guī)。但由科學(xué)家制定的全球標(biāo)準(zhǔn)可以給各國(guó)一個(gè)有力的推動(dòng)。

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(dān)憂不只在于基因編輯嬰兒會(huì)導(dǎo)致意想不到的健康問(wèn)題，還可能遺傳給后代，或可能會(huì)有人企圖生育經(jīng)過(guò)設(shè)計(jì)的嬰兒，通過(guò)基因改變獲得身體特征、智力或運(yùn)動(dòng)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(xué)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(xué)公司里有“少數(shù)股權(quán)”，他說(shuō)：“邁克爾不做人類研究，他也沒(méi)有做這個(gè)項(xiàng)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(fù)《紐約時(shí)報(bào)》的郵件。萊斯大學(xué)發(fā)言人拒絕提供關(guān)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(píng)論》(MIT Technology Review)在香港舉行的一場(chǎng)基因組編輯大會(huì)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(guò)一則視頻聲明對(duì)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(dá)奧納(Jennifer Doudna)說(shuō)。賀建奎在感恩節(jié)發(fā)給過(guò)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(shuō)，他使胚胎中一個(gè)會(huì)讓人感染HIV的基因失了效，但這在醫(yī)學(xué)上是沒(méi)有必要的，因?yàn)轭A(yù)防HIV還有更簡(jiǎn)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(wú)意間可能已導(dǎo)致帶有未知健康問(wèn)題的基因轉(zhuǎn)變。對(duì)于賀建奎是否確保嬰兒父母理解了基因編輯的風(fēng)險(xiǎn)，仍存在很大懷疑。他說(shuō)他還完成了第二個(gè)妊娠，對(duì)此中國(guó)當(dāng)局表示尚在進(jìn)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(jué)得自己當(dāng)初在了解到賀建奎的計(jì)劃后應(yīng)該和同事們商議，并在他仍在自己辦公室時(shí)，就寫封郵件給中國(guó)的一位資深倫理學(xué)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(guò)的美國(guó)人、斯坦福大學(xué)倫理學(xué)教授威廉·赫爾伯特(William Hurlbut)博士說(shuō)，2017至2018年，他曾在與賀的討論中對(duì)他的工作表示過(guò)強(qiáng)烈反對(duì)，包括警告他“‘這會(huì)害了你，會(huì)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(shuō)，截止去年10月，“我個(gè)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(shuō)他沒(méi)有告知任何人，因?yàn)?ldquo;當(dāng)時(shí)我的想法是，這又不是說(shuō)我知道某人要去殺人了;這是個(gè)既成事實(shí)。我沒(méi)覺(jué)得自己有任何道德義務(wù)或?qū)嶋H的好處要去把這件事說(shuō)出來(lái)。”

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(xué)伯克利分校的馬克·德威特(Mark DeWitt)拒絕接受采訪，但他說(shuō)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(guó)科學(xué)家都指出，賀建奎告知他們時(shí)期望他們能保密，這也是科學(xué)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(guó)國(guó)家衛(wèi)生研究院(National Institutes of Health)院長(zhǎng)弗朗西斯·柯林斯(Francis Collins)博士說(shuō)，如果賀建奎是在美國(guó)的大學(xué)或資助機(jī)構(gòu)完成工作，科學(xué)家們可能已經(jīng)就此事發(fā)出了警報(bào)。他所在的這個(gè)機(jī)構(gòu)不資助人類胚胎編輯研究。中國(guó)的體制太過(guò)復(fù)雜，美國(guó)科學(xué)家可能不了解“究竟他們?cè)撉庙懯裁礃拥木?，該向誰(shuí)敲響警鐘，”他說(shuō)。

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(rèn)為中國(guó)當(dāng)局對(duì)遏制非正統(tǒng)的科學(xué)實(shí)驗(yàn)更多是持自由放任態(tài)度，而在據(jù)中國(guó)國(guó)有媒體報(bào)道，當(dāng)局表明政府初步調(diào)查發(fā)現(xiàn)賀建奎“嚴(yán)重違反”了國(guó)家有關(guān)規(guī)定后，國(guó)際社會(huì)開始加緊行動(dòng)，就此事給出一個(gè)協(xié)調(diào)一致的對(duì)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(jié)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(xué)術(shù)單位深圳南方科技大學(xué)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(guó)政府在嚴(yán)肅對(duì)待這件事情，”華盛頓的國(guó)家醫(yī)學(xué)科學(xué)院院長(zhǎng)曹文凱(Victor Dzau)博士說(shuō)。

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(huì)遭到處罰，在一開始是不明朗的。近年來(lái)，中國(guó)大舉投資，旨在成為科技大國(guó)，包括出資吸引賀建奎這樣的科學(xué)家回到中國(guó)，他在美國(guó)完成了博士和博士后工作。一些令人大為震驚的實(shí)驗(yàn)，如將頭部移植給另一個(gè)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(xiǎn)且無(wú)正當(dāng)理由的研究，一定要得到正式承認(rèn)并被判定為非法，”在初步結(jié)果公布后，達(dá)奧納說(shuō)。“這一公布確認(rèn)了一道倫理和科學(xué)行為的國(guó)際‘紅線’，以幫助確保這類激進(jìn)的、無(wú)醫(yī)學(xué)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(dòng)，去健身房，并與一些西方的科學(xué)家溝通。赫爾伯特已和他通過(guò)電話和郵件，他說(shuō)在那些談話中，賀聽起來(lái)“對(duì)自己將來(lái)能有所貢獻(xiàn)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(shuō)過(guò)，他對(duì)自己所做之事感到“自豪”，在被問(wèn)及是否表達(dá)過(guò)悔意時(shí)，赫爾伯特回復(fù)道：“他對(duì)這件事披露給世界的方式和時(shí)機(jī)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(guó)遺傳學(xué)家羅賓·洛維爾-巴奇(Robin Lovell-Badge)發(fā)過(guò)郵件，稱：“我完全同意，‘對(duì)于那些想開展人類基因編輯的人，科學(xué)家應(yīng)該劃分出一套明確的‘該做’和‘不該做’的事項(xiàng)準(zhǔn)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(xué)家們也在就是否要發(fā)表展開爭(zhēng)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(shuō)，他最初認(rèn)為，應(yīng)該把它貼在一個(gè)接受未經(jīng)同行評(píng)審的早期研究的論壇上，因?yàn)?ldquo;我們可以進(jìn)行一次徹底的梳理，以便了解每一個(gè)細(xì)節(jié)。”但現(xiàn)在，他說(shuō)，“我不再認(rèn)為這樣做是合適的。這種行為太過(guò)分了，不能獲得任何形式的認(rèn)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(shuō)他的動(dòng)機(jī)是保護(hù)人們不感染艾滋病毒，顯然他也希望得到權(quán)威科學(xué)家的認(rèn)可。在這對(duì)雙胞胎出生前的幾個(gè)月，他要求會(huì)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(shí)驗(yàn)室，賀建奎展示了他在實(shí)驗(yàn)室培養(yǎng)皿中對(duì)人類胚胎進(jìn)行基因編輯時(shí)獲得的數(shù)據(jù)，這并沒(méi)有讓張鋒感到警覺(jué)，因?yàn)橐呀?jīng)有幾位科學(xué)家這么做了。但張鋒尖銳地批評(píng)了賀建奎的基因編輯結(jié)果中的“大問(wèn)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(méi)有提及植入胚胎的事情。“也許我不應(yīng)該挑那么多毛病，這樣他就會(huì)透露更多信息，”張鋒說(shuō)。

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(shuō)，阻止錯(cuò)誤使用胚胎編輯的最佳方法是由所有新科學(xué)技術(shù)的公共和私人參與者協(xié)調(diào)行動(dòng)，包括監(jiān)管機(jī)構(gòu)、專利局、資助組織和責(zé)任保險(xiǎn)公司。威斯康星大學(xué)麥迪遜分校(University of Wisconsin-Madison)的生物倫理學(xué)家R·奧塔·查洛(R. Alta Charo)最近在《新英格蘭醫(yī)學(xué)雜志》(New England Journal of Medicine)上發(fā)表的文章中提議，建立一個(gè)“由公共和私人實(shí)體組成的綜合生態(tài)系統(tǒng)，可以約束我們當(dāng)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(gè)由美國(guó)科學(xué)與醫(yī)學(xué)研究院牽頭的國(guó)際委員會(huì)。美國(guó)國(guó)家醫(yī)學(xué)科學(xué)院院長(zhǎng)曹文凱說(shuō)，許多國(guó)家現(xiàn)在已經(jīng)同意成立這個(gè)委員會(huì)。它將在今年發(fā)布一份報(bào)告，制定詳細(xì)的指導(dǎo)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(biāo)準(zhǔn)反映在2017年美國(guó)國(guó)家科學(xué)院的一份報(bào)告中，稱只有在預(yù)防或治療“嚴(yán)重疾病或殘疾”，且沒(méi)有“合理替代方案”時(shí)，才可以將經(jīng)過(guò)編輯的胚胎用于人類妊娠。曹文凱希望更加細(xì)化，比如哪些疾病嚴(yán)重到足以證明風(fēng)險(xiǎn)是合理的，哪些風(fēng)險(xiǎn)是可以接受的，以及需要多少初步測(cè)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(shuō)，委員會(huì)可能會(huì)建議對(duì)植入編輯過(guò)的人類胚胎的行為實(shí)施暫止禁令，直到報(bào)告得以發(fā)表。一些頂尖科學(xué)家希望有更長(zhǎng)的暫止期。

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

張鋒說(shuō)，五年的暫止禁令將允許科學(xué)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(dá)奧納不同意這種觀點(diǎn)，她支持制定“非常嚴(yán)格的國(guó)際標(biāo)準(zhǔn)”，讓期刊“聲明它們不會(huì)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(guó)國(guó)家衛(wèi)生研究院的柯林斯在電子郵件中爭(zhēng)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(yán)重的字眼，它的影響力就會(huì)大一些，”柯林斯說(shuō)。他指出，要想實(shí)現(xiàn)它，就需要達(dá)成國(guó)際協(xié)議，打消個(gè)別國(guó)家那種“我們覺(jué)得現(xiàn)在沒(méi)問(wèn)題了”的念頭。