基因完美人離我們有多遠

So it begins. Nobody thought it would happen this fast, and now we are preparing to take a leap into the unknown. Not Brexit but Crispr gene-editing, a DNA-changing technology that can supposedly cure mice of liver disease and muscular dystrophy, render human cells resistant to HIV and create fungus-resistant wheat.

就這麼開始了。沒人想到這件事來得這麼快，現在我們正準備躍入未知之中。這裏說的不是英國退歐，而是“成簇規律間隔短迴文重複序列”(Crispr)基因編輯，一種據信能夠治癒小鼠的肝病和肌營養不良，讓人類細胞對艾滋病毒(HIV)產生抗性，培育出抗真菌小麥的DNA改造技術。

It has also been touted as a means of remaking humanity — and now it is about to progress from Petri dishes into people. An influential advisory panel at the US National Institutes of Health has unanimously approved the first clinical trial to use Crispr genome-editing (also known as gene-editing) on humans, to reboot immune cells in cancer patients. Researchers at the University of Pennsylvania will target patients with multiple myeloma, melanoma or sarcoma. The team will remove a class of immune cells called T-cells from patients, edit the genes of those T-cells so they are better able to “lock on” to tumour cells, and then restore the altered T-cells back into the bloodstream.

該技術也被吹捧爲一種再造人類的手段，現在這種技術即將從培養皿走向人類。美國國家衛生研究院(NIH)一個有影響力的顧問組已一致批准第一項對人類使用Crispr基因組編輯（也稱基因編輯）技術，以“重啓”癌症病人免疫細胞的臨牀試驗。賓夕法尼亞大學(University of Pennsylvania)的研究人員將以多發性骨髓瘤、黑色素瘤或肉瘤患者爲對象。該團隊將從患者體內取出被稱爲T細胞的一類免疫細胞，對這些T細胞的基因進行編輯，使它們能更好地“鎖定”癌細胞，然後將這些修改過的T細胞重新導入患者的血液循環系統。

With luck, the genetic edits should boost the patient’s immune system. The study, now expected to receive the blessing of federal regulators, will be funded by a cancer institute founded by Sean Parker of Napster and Facebook fame.

幸運的話，基因編輯應該能促進患者的免疫系統。預計將獲得聯邦監管機構的批准的這項研究，將由曾經創立Napster、並擔任Facebook首任總裁的肖恩•帕克(Sean Parker)創辦的一個癌症研究所資助。

The aim of this first in-human trial of Crispr is not to enhance therapeutic outcomes but to prove its safety. Other genetic technologies of great pro-mise cast long shadows. Gene therapy, which involves inserting copies of missing or defective genes into a patient, usually using a virus as a carrier, was nearly derailed at the turn of the millennium , when a child with a severe immune disorder developed leukaemia as a direct result of the treatment.

這個對人體進行的第一項Crispr實驗的目的，不是爲了改善治療結果，而是爲了證明其安全性。其他曾經大有希望的基因技術投下了長長的陰影。向患者體內注入缺失或者缺陷基因的副本（通常使用病毒作爲載體）的基因療法，在世紀之交的時候幾乎遭到毀滅性打擊，當時這種療法直接導致一名患有嚴重的免疫紊亂症的兒童罹患白血病。

The viruses chosen as carriers in some early trials wrought unforeseen damage. As a result the first European treatment using gene therapy, which has been around since 1990, was licensed only in 2012.

在一些早期的試驗中，被選爲載體的病毒造成了無法預見的傷害。其結果是，基因療法雖然從1990年起就存在了，但歐洲第一例使用這種療法的治療在2012年才獲得許可。

With gene-editing, the unintended consequence that most terrifies genetic researchers is “off-target effects”, in which untargeted genes are inadvertently snipped, deleted or altered. The technology uses enzymes to search for particular sequences of DNA — but, just as it is possible for a search facility in word-processing software to pick out a string of letters in an unexpected place, the enzymes might similarly latch on to the wrong stretch of DNA.

就基因編輯而言，最讓基因研究人員感到驚恐的意外後果是“脫靶效應”，也就是非靶向基因被不慎剪斷、移除或者修改。基因編輯技術利用酶來搜尋特定的DNA序列，但就像文字處理軟件的搜索功能可能在意想不到的地方挑出一串字符那樣，酶也可能以類似的方式附着於錯誤的DNA片段。

The risk, at least in this trial, is minimised by the gene-editing being done outside the body, allowing researchers to check the T-cells have been appropriately amended before being put back into the patient. Still, once the cutting enzyme is unleashed, there is a possibility it could continue operating inside the body to uncertain end.

至少在這次實驗中，這種風險被最小化——通過從人體外進行基因編輯，研究者能在檢查T細胞已被適當地修改之後，再將其導入患者體內。話雖如此，一旦剪切酶被釋放出來，其依然有可能在人體內發揮不確定的作用。

By next year we should have a hint of whether gene-editing really can fix deficient DNA in people. And that is when things get serious: why stop at correcting the human genome? Why not beautify it? That thought is preoccupying those in the field, who raised concerns at a Washington summit in December, organised by scientists from the UK, China and the US. Among those attending was Yale University’s Daniel Kevles, a historian of the eugenics movement.

到了明年，我們應該就能對基因編輯是否真的能修復人的缺陷DNA有所瞭解。這就是事情開始變嚴重的地方：爲何要止步於修正人類基因組呢？何不對其進行美化？這種想法讓該領域的人士憂心忡忡，在去年12月由英國、中國和美國科學家組織、在華盛頓舉行的一次峯會上，他們提出了這種擔憂。與會者包括來自耶魯大學(Yale University)的優生運動歷史學家丹尼爾•凱夫利斯(Daniel Kevles)。

The thing about Crispr genome-editing is this: it is fast, cheap and easy to do. Many countries, especially those that see themselves as future torchbearers for technology, such as China, are forging ahead; China holds the first claim to creating a (non-viable) gene-edited embryo. Regulation is patchy.

Crispr基因組編輯有這樣一個特點：這種技術快速、廉價和易行。許多國家，尤其是那些視自身爲這些技術未來旗手的國家，比如中國，正在大力推進；中國是第一個聲稱對（無法存活的）人類胚胎進行過基因編輯的的國家。相關法規還不健全。

No country endorses a genome-edited human embryo being implanted and being brought to term. Even so, gene-editing technology makes the prospect of a homo perfectus just slightly more probable — and, as a species, we have yet to fully grasp the implications of this brave and perfectly edited new world.

目前沒有哪個國家批准將經過基因組編輯的人類胚胎植入母體直至足月分娩。即使如此，基因編輯技術略微提高了實現“完美的人”(homo perfectus)的可能性——作爲一個物種，我們還沒有完全想好這個經過完美編輯的大膽新世界會有什麼影響。