挑戰禁忌的中國克隆技術 The clone factory

In Chinese mythology, the Monkey King is a beast with magical fur. All he has to do is pull out a hair, blow on it and it is instantly transformed into a clone of himself.

在中國的神話故事裏，孫悟空身上的猴毛有着巨大的魔力。他只需拔下一根，吹口氣，瞬間就能變出一隻跟他一模一樣的猴子。

Xu Xiaochun, chief executive of BoyaLife, says the fable is not far from reality, as far as his Chinese biotechnology company is concerned. This week he announced an investment of $31m in a joint venture with South Korea’s Sooam Biotech that aims to clone 1m cows a year from their hair cells.

博雅(BoyaLife)首席執行官許曉椿表示，對於他執掌的這家中國生物技術公司，這種神話並非可望不可即。上週他宣佈投資3100萬美元與韓國秀巖生命工學研究院(Sooam Biotech)組建一家合資公司，計劃通過克隆毛髮細胞每年生產100萬頭牛。

The Monkey King “sounds like a fairy tale but we are really doing the same thing”, he says. “We pull out 200 hairs, blow on them — and boom!”

他表示，孫悟空“聽上去像是一個神話故事，但我們確實在做同樣的事情”，他表示，“我們拔下200根牛毛，吹一口氣，然後就會變出很多頭牛！”

Sometime next year, researchers in BoyaLife’s laboratory on the outskirts of the coastal city of Tianjin will take skin cells from a few carefully chosen cattle (Kobe beef is Mr Xu’s favourite). The scientists will extract the nucleus from each cell and place it into an unfertilised egg from another cow. The cloned embryos will then be implanted in surrogate dairy cows housed on cattle ranches throughout China.

明年某個時候，位於沿海城市天津郊區的博雅實驗室的研究人員，將從幾頭精心挑選的牛提取皮膚細胞（神戶牛肉是許曉椿的最愛）。這些科學家將從每個細胞中提取細胞核，將其置入另一頭牛的還未受精的卵細胞。接着克隆胚胎將被植入中國各地養牛場的代孕奶牛體內。

His ambition is staggering. Starting with 100,000 cloned cattle embryos a year in “phase one”, Mr Xu envisages 1m annually at some point in the future. That would make BoyaLife by far the largest clone factory in the world.

他的遠大理想是驚人的。他計劃“一期”每年生產10萬個克隆牛胚胎，未來將每年生產100萬個。這將令博雅成爲全球遙遙領先的最大克隆工廠。

Mr Xu says the latest techniques enable cloning to be carried out in an “assembly line format” at a rate of less than 1 minute per cell. Based on a four- hour shift and 250 working days a year, a proficient cloner would “manufacture” 60,000 cloned cow embryos a year, he says, adding that a team of 50 will be sufficient for the planned scale of the project. Mr Xu plans to have a staff of 300 and eventual total investment is estimated at $500m.

許曉椿表示，最新技術意味着，能夠按照“生產線模式”以每個細胞不到1分鐘的速度進行克隆。他表示，根據每4個小時倒一次班、每年250個工作日計算，一個熟練的克隆者每年可“生產”出6萬個克隆牛胚胎。他補充稱，按照項目的計劃規模，有一個50人的團隊就夠了。許曉椿計劃員工總數將達到300人，最終的投資總額預計將達到5億美元。

If the venture comes anywhere near achieving its goal, it will be another example of the recent surge of path-breaking, taboo-busting biotechnology research, with China introducing mass production and commercialisation of projects that are still in the experimental and clinical stages elsewhere.

如果該項目接近達到其目標，它將代表着近期一連串突破禁忌的開創性生物技術研究的又一例，在此類項目中，中國將其他國家仍處於試驗和臨牀階段的技術投入量產和商業化。

China’s flag-bearer in biotech is BGI, formerly known as Beijing Genomics Institute and now based in Shenzhen. BGI has grown into the world’s biggest genomics organisation, with a huge capacity to read, analyse and alter DNA from plants, microbes, people and animals. It employs more than 2,000 PhD-level scientists and 200 top-of-the-range gene-sequencing machines.

中國在生物技術領域的另一個旗手是總部位於深圳的華大基因(BGI)，該公司的前身是北京基因組研究所(Beijing Genomics Institute)。華大基因已發展成爲全球最大基因組組織，擁有從植物、微生物、人類和動物身上讀取、分析和改變DNA的強大能力。該公司聘用2000多名博士級別的科學家和200臺頂級基因測序設備。

In September BGI captured the public imagination with an announcement that “micropigs”, originally developed for biomedical research through gene editing and cloning, would be sold as pets.

今年9月，華大基因宣佈將銷售通過基因編輯和克隆開發的“迷你豬”（最初用於生物醫學研究）寵物，此舉抓住了公衆的想象力。

Chinese scientists are enthusiastic adopters of a “gene editing” technology called Crispr, invented in the US about three years ago, which greatly accelerates the insertion and deletion of DNA in any type of living cell.

中國科學家對於採用“成簇規律間隔短迴文重複序列”(Crispr)的“基因編輯”技術充滿熱情，該技術於大約3年前在美國發明，它大大加快了對任何活體細胞插入和刪除DNA的速度。

In September researchers from several Chinese universities published a study of Shanbei cashmere goats, whose genes were edited to produce larger muscles and longer hair, making them potentially more valuable as sources of meat and textile fibres.

今年9月，來自中國多所大學的研究人員發表了一項有關陝北絨山羊的研究，這些山羊經過基因編輯後，長出更大塊的肌肉和更長的毛，潛在讓它們作爲肉和紡織纖維的來源具有更高價值。

“The results showed that simultaneous editing of several [DNA] sites was achieved in large animals, demonstrating that the Crispr system has the potential to become a robust and efficient gene engineering tool in farm animals and therefore will be critically important and applicable for breeding,” they wrote in Scientific Reports, a leading western journal.

他們在西方領先刊物《科學報道》(Scientific Reports)上寫道：“結果表明，已在大型動物體內實現多處DNA同時編輯，這表明Crispr體系有望成爲牲畜領域一件強大且高效率的基因工程工具，因而將至關重要，而且適用於繁殖。”

But the most controversial application of gene editing is in human cells. In April scientists from Sun Yat-sen University in Guangzhou used Crispr to modify the genomes of 85 non-viable human embryos, despite a number of pre-emptive articles in western medical journals urging them not to do it. Although the experiment failed, it provoked an outcry from scientific peers and ominous headlines about the risks to passing on genetic changes to future human generations.

但最具爭議的基因編輯應用是人體細胞。今年4月，廣州中山大學(Sun Yat-sen University)的科學家利用Crispr技術修改了85個無法存活的人類胚胎的基因組，儘管西方醫學期刊上很多文章事先敦促他們不要這麼做。儘管這項實驗失敗了，但它引發了科學界同行的強烈抗議以及媒體的不祥頭條，稱風險在於把基因變化傳遞給人類後代。

While China’s biotech sector overall is small in financial terms — a study by McKinsey last month found that Chinese biotech companies account for less than 3 per cent of global revenues in the sector worldwide — they aspire to be world leaders in some of the most advanced and controversial biotech. Critics say this is partly due to looser regulations and a more relaxed treatment in China of some of the ethical issues involved.

總體而言，從收入來看，中國生物技術領域規模很小（麥肯錫(McKinsey) 10月的一項研究發現，中國生物技術公司佔該行業全球營收的不到3%），但他們希望在一些最先進和最具爭議的生物技術領域成爲全球領袖。批評者表示，部分原因是中國的法規較爲寬鬆，對涉及的一些道德問題態度也比較隨便。

In contrast, cloning of farm animals is effectively outlawed in Europe, which is where the technology started with the birth in 1996 of Dolly the sheep at the Roslin Institute in Edinburgh. Roslin has moved away from cloning to other areas of animal research, and today its scientists are reluctant to talk about the issue.

相比之下，在歐洲，克隆牲畜實際上已被界定爲非法。1996年，愛丁堡的羅斯林研究所(Roslin Institute)克隆出多利羊，爲全球首例克隆動物。該研究所已從克隆轉向其他動物研究領域，如今該所的科學家不願談論克隆話題。

The European Parliament voted by a large majority in September to ban agricultural cloning and the sale of cloned livestock on the grounds that cloned offspring suffer more health problems than conventional animals.

歐盟議會(European Parliament)今年9月高票通過禁止農業克隆和銷售克隆牲畜，理由是克隆的後代比常規繁衍的動物存在更多健康問題。

In the US, on the other hand, cattle have been cloned successfully for several years. In 2008 the US Food and Drug Administration ruled that the practice was safe; the leading livestock cloning company ViaGen, a subsidiary of Intrexon, says it “has successfully delivered thousands of healthy cloned animals to clients”.

另一方面，美國已經連續好幾年成功克隆牛。2008年，美國食品藥品監督管理局(FDA)裁定克隆牛的做法安全。Intrexon的子公司、領先牲畜克隆公司ViaGen表示，它“已經成功地向客戶交付數千頭健康的克隆動物”。

Mr Xu says people may be applying double standards when they judge China. “We are [cloning] on a scale of millions, and suddenly people say, ‘Gee, do they have a lower standard of ethics?’ We do not. We just do things on a massive scale,” he says. “If we made a factory that produces 10 cows a year rather than a million, no one would even blink.”

許曉椿表示，在評判中國的事務時，人們可能在運用雙重標準。“我們要以數百萬的規模（進行克隆），突然間人們說，‘呀，他們的道德標準是不是比較低？’我們的標準並不低。我們只是規模更大而已，”他表示，“如果我們建造一家每年只出產10頭牛而不是100萬頭牛的工廠，人們連眼睛都不會眨一下。”

However, according to Yusheng Wei, researcher at Peking University’s School of Life Sciences, unclear and incomplete rules make it easier to push ethical boundaries in China. “It’s not so much that we have a different ethical system but that China is relatively new to this field, and there are not enough laws and restrictions in place,” he says. “China's rapid progress in gene technology does have something to do with loose regulations. It’s hard for regulations to keep up with the development.”

然而，根據北京大學生命科學學院研究者韋玉生的說法，相關規則的不清晰和不完備，使得中國的科學家更容易逾越道德底線。“與其說我們有一套不同的道德體系，不如說中國在這個領域相對較新，相關的法律和限制不足，”他說，“中國在基因技術方面的快速進步的確和寬鬆的法規有關。法規難以跟上發展。”

Mr Wei says there is disagreement even within the Chinese scientific establishment over some aspects of gene modification. “There are no ethical debates over cloning,” he adds. “It’s just that everything is being drowned out by the debate over gene modification.”

韋玉生表示，即使是在中國科學界的體制內部，對於基因修飾的某些方面也存在分歧。“沒有關於克隆的道德辯論，”他補充道，“一切都被有關基因修飾的辯論淹沒了。”

If there is an ethical gap between Chinese and western research, as some believe, it is narrowing as “Chinese scientists are being brought into the global scientific community”, says Peter Mills, assistant director of the Nuffield Council on Bioethics in London.

如果的確像某些人所認爲的那樣，中國和西方的研究之間存在道德差距，那麼據倫敦納菲爾德生命倫理委員會(Nuffield Council on Bioethics)副主任彼得猠爾斯(Peter Mills)表示，這個差距也正因“中國科學家逐漸被融入全球科學界”而縮小。

An encouraging sign of this process is the key role played by the Chinese Academy of Sciences in organising a meeting on gene editing in Washington next week, along with the US National Academy of Sciences and UK’s Royal Society.

這一進程中一個令人鼓舞的跡象是，中國科學院與美國國家科學院(National Academy of Sciences)及英國皇家學會(Royal Society)下週將在華盛頓共同主辦一場基因編輯會議，中科院在其中發揮了關鍵作用。

“We would like to work together with international communities for the proper regulation and application of such technology,” says Bai Chunli, president of the Chinese Academy.

“我們希望與國際社會合作，對這類技術進行妥善監管和應用，”中國科學院院長白春禮表示。

Mr Xu points out that the FDA last week approved transgenic salmon, the first genetically engineered animal to be permitted for sale as food. Chinese regulators have not approved any GM animal to be used as food, nor have they approved GM crops to be planted in China for human consumption, with some minor exceptions. They do allow the import of a number of GM strains, notably soya beans used in cooking oil and animal feed.

許曉椿指出，上週FDA批准了轉基因三文魚，這是第一種被批准作爲食物銷售的基因工程動物。中國監管機構尚未批准任何轉基因動物被用作食品，也沒有批准在中國種植供人食用的轉基因作物（有少數例外）。中國監管機構允許進口幾種轉基因品種，主要是用於食用油和動物飼料的轉基因大豆。

While scientists have generally welcomed the FDA approval of GM salmon, there may be consumer resistance to the fish in the US, where environmental groups are pushing retailers to boycott the product. This week Friends of the Earth called on supporters to “celebrate” as Costco “joined more than 60 grocery store chains nationwide, including Kroger, Safeway, Trader Joe’s, Target and Whole Foods, that listened to the science and consumers and made commitments to not sell this unnecessary, risky and unlabelled ‘frankenfish’.”

儘管科學家普遍歡迎FDA批准轉基因三文魚，但這種魚可能會遭到美國消費者的抵制，美國的一些環保組織正在呼籲零售商抵制這種產品。最近，地球之友(Friends of the Earth)呼籲支持者“歡慶”，因爲好事多(Costco)“加入克羅格超市(Kroger)、Safeway、Trader Joe’s、Target、Whole Foods等全國60餘家連鎖生鮮超市的行列，聽取科學家和消費者的意見，承諾不銷售這種無必要、有風險和未經標記的‘科學怪魚’。”

When it comes to scientifically enhanced food, Mr Xu says Chinese consumers are more conservative than their American counterparts. So cloned beef may be a tough sell. “It’s always hard to get people to try new things. It’s hard to get them to trust science.”

對於用科學手段增強的食物，許曉椿表示，中國消費者比美國消費者更保守。因此銷售克隆牛肉可能比較困難。“讓人們嘗試新事物總是很困難。很難讓他們信任科學。”

Mr Xu uses an analogy to illustrate why cloned meat is intrinsically safe. “If you have a glass of water and you pour half into another glass, that would be cloning. If you add a drop of ink into a glass of water, that would be genetically modifying. The determining factor is whether you change the species.”

許曉椿用一個類比來說明爲何克隆肉從本質上說是安全的。“如果你有一杯水，你把其中半杯倒進另一個杯子裏，這就是克隆。如果你往這杯水裏加一滴墨水，這就是基因修飾。決定因素是你是否改變了物種。”

That is true in theory, but in practice there are obstacles to creating a perfect replica, says Kehkooi Kee of Tsinghua University. “There are risks because it won’t be an exact copy,” he says.

清華大學的紀家葵(Kehkooi Kee)表示，理論上這是正確的，但在實踐中，創造完美的複製品是有障礙的，“因爲不會是完全一樣的複製，所以這是有風險的。”

But Mr Xu says cloning is the best way to produce enough elite calves to satisfy growing demand for the meat that China is consuming in greater quantities as incomes rise. “Cloned beef is the tastiest beef I’ve had,” he says.

但徐曉椿表示，隨着收入增長，中國人的肉類消費量不斷上升，克隆是供應足夠的優質牛犢，以滿足日益增長的需求的最佳辦法。“克隆牛肉是我吃過的最美味的牛肉，”他說。