科技資訊:未來目標 攻克五種癌症

RON DEPINHO is a man on a mission. Oddly, though, he does not yet know exactly what that mission is. Dr DePinho is the new president of the MD Anderson Cancer Centre in Houston, Texas. (He took over in September, having previously headed the Belfer Institute, part of Harvard's Dana-Farber Cancer Institute.) Mindful of his adopted city's most famous scientific role, as home to Mission Control for the Apollo project, he says his own mission is akin to a moon shot. He aims to cure not one but five varieties of cancer. What he has not yet decided is: which five?

羅恩•徳平厚肩負着一個使命。雖然奇怪的是，他現在仍不清楚他的使命的確切目標是什麼。徳平厚博士是德克薩斯州休斯頓市的MD •安德森癌症研究中心的新任主任，他此前是哈佛的丹娜-法波爾癌症研究院下屬的貝爾佛研究所所長。徳平厚知道，休斯頓在科學領域最廣爲人知的，是其作爲阿波羅登月計劃的目標控制中心所在地。因此，他說他自己的目標也類似於登月。這就是，要找到攻克不僅一種，而是五種癌症的方法。他現在還沒有決定的是哪五種癌症。

That it is possible to talk of curing even one sort of cancer is largely thanks to an outfit called the International Cancer Genome Consortium. Researchers belonging to this group, which involves 39 projects in four continents, are using high-throughput DNA-sequencing to examine 50 sorts of tumour. They are comparing the mutations in many examples of each type, to find which are common to a type (and thus, presumably, causative) and which are mere accidents. (The DNA-repair apparatus in malignant cells often goes wrong, so such accidents are common.)

現在，人們之所以敢於談論攻克癌症（即便是其中一種癌症），主要是因爲一個名爲國際癌症基因圖譜研究聯盟的組織。這個組織包括遍佈四大洲的39個研究項目，該組織的研究人員使用高流量的基因測序方法來檢測50種不同的腫瘤。他們把每種腫瘤的衆多基因突變案例進行比較，區分出對某種腫瘤來說，哪些突變是共同的（從而，估計是致病原因），哪些突變是偶然的（惡性細胞中的基因修復機制經常出錯，所以偶然突變是常見的事)。

The consortium's work is progressing fast, and preliminary results for many tumours are already in. But such knowledge is useless unless it can be translated into treatment. That is where Dr DePinho comes in—for his career has taken him into the boardroom as well as the clinic. He is a serial entrepreneur: he helped found Aveo Pharmaceuticals, which is developing a drug to block the growth of blood vessels in tumours, Metamark Genetics, which works on diagnosing cancers, and Karyopharm Therapeutics, which is trying to regulate the passage of molecules into and out of the cell nucleus, and thus control the nucleus's activities. His aim in coming to MD Anderson, he says, is to "industrialise" other aspects of biological research in the way that genetics has been pushed forward by high-throughput sequencing.

這個聯盟的工作進展很快，已經得出了很多種腫瘤的初步研究成果。但是，對病因的認知只有轉化爲治療方法纔是真正有用的。這正是徳平厚博士要做的事，因爲在他的職業生涯中，他既做過診療工作，也做過經營管理工作。他是一個富有經驗的企業家，參與創建過若干個公司，包括：正在研製阻礙腫瘤中血管生長的藥品的Aveo製藥公司；研究癌症診斷方法的Metamark遺傳研究公司；還有Karyopharm 診療研究所，這個所的研究方向是，通過控制分子進出細胞核的方法來控制細胞核的活動。他說，他來MD •安德森癌症研究中心的目的是，以高流量測序推動遺傳研究的同樣方式，用“產業化”的方法來推動生物學領域其它方面的研究。

That will cost billions of dollars. Fortunately, the state of Texas—no pushover when it comes to spending taxpayers' cash—is creating a $3 billion cancer-research fund to help pay for it. Local philanthropists, including T. Boone Pickens and Ross Perot, are chipping in, too. Their model is the original Human Genome Project, during which the cost of sequencing a single genetic "letter" (a DNA base pair) fell from $10 in 1991 to ten cents in 2001—and is now 3,000 base pairs a cent. They hope their dollars will encourage people working with what are now, essentially, craft technologies to think about how they might industrialise them.

他的計劃將花費數十億美元。幸運的是，儘管德克薩斯州在花納稅者的錢上是非常謹慎的，但已經建立了一個30億美元的癌症研究基金來支持這個計劃。當地的慈善家，如T. Boone Pickens 和 Ross Perot等也給與了支持。他們的模式和原先的“人類基因圖譜項目”相同，在那個項目中，單個DNA鹼基的測序價格從1991年的10美元降到2001年的1毛錢，現在是3，000個鹼基1分錢。他們希望，他們的資金將鼓勵那些現在基本上是運用手工技術的研究人員，考慮如何把那些技術產業化的問題。

Several techniques look ripe for such industrialisation. Dr DePinho sets great store, for example, by the use of genetically modified mice (he calls them "little patients") in which mutations found in human cancers can be replicated precisely, but one at a time, to discover the shape of each piece of the jigsaw. If this process can be scaled up it will, as he puts it, allow cancer's genetic generals to be distinguished from the foot soldiers.

對於這種產業化方式，若干技術看來已經相當成熟。例如，徳平厚博士很重視運用基因被改造過的老鼠（他稱之爲“小患者”），研究者把人類癌症的基因突變精確地複製到這些老鼠身上，從而發現這些突變的基因圖譜每一部分的形狀。但是，基因突變的複製只能一次做一個，他認爲，如果這個過程可以成規模地來做，就可以區分基因突變的主因和偶然事件。

Another field that has great potential is imaging technology—in particular, a combination of (which uses radioactive sugar to measure how metabolically active tissue is) and computerised tomography (which uses X-rays to map the body's internal anatomy). Together these can show whether a treatment is reducing a cancer's energy consumption, and thus its metabolism. This gives a good indication of how well that treatment is working.

另一個很有希望的領域是成像技術，具體說，這是兩種技術的結合：正電子放射層掃描術（用放射性糖來測量細胞組織新陳代謝的活躍程度），和電腦化的體層攝影技術（用X-射線來繪製人體內部的解剖結構）。兩種技術一起運用，可以顯示某種治療方法是否降低了腫瘤的能量消耗，從而是否減緩了它的新陳代謝。這對於評價治療方法的有效性很有幫助。

A family business

Dr DePinho himself will have more duties at MD Anderson than just dealing with the five chosen tumours. The donkey work of creating the Institute for Applied Cancer Science, as the new mission control is to be known, will be done by Lynda Chin. Dr Chin, too, worked at the Belfer Institute. She is part of the International Scientific Steering Committee of the cancer-genome project. And she is also Dr DePinho's wife. Dr Chin will be assisted by some 55 other scientists from the Belfer, who are making the journey to Texas with her and her husband. That sort of team poaching is common in investment banking but rarer in academic research. Dr DePinho refers to it, jokingly, as metastasis, since a clone of his primary creation will be taking root elsewhere in the country.

夫妻店生意

徳平厚博士在MD安德森的作用遠不止確定哪五種腫瘤。建立腫瘤應用科學研究所（這是新的目標控制機構的名稱）的艱苦工作是琳達•秦的責任，她也曾在貝爾佛研究所工作。她還是癌症圖譜項目的國際科學指導委員會的成員，並且是徳平厚博士的妻子。55名科學工作者將和徳平厚夫婦一起從貝爾福來到德克薩斯，幫助秦博士工作。這種挖走人家整個團隊的做法在投資銀行界司空見慣，但是在學術研究界卻不多見。徳平厚博士把此事戲稱爲“細胞轉移”，因爲他原先創造的研究機構的克隆物將在另一個地方紮下根來。

As to which five cancers to attack, that decision will be made by the middle of 2012. A crucial consideration will be how likely it looks that research into the tumour in question could get rapidly to the "proof of concept" stage—the point at which it could be taken forward by a business that relied on commercial sources of capital, rather than on the sorts of grants that usually propel academic research. At that moment a new firm might be spun out of the institute, or a deal might be done with an established pharmaceutical firm, to try to get a new drug developed.

至於把哪五種癌症作爲目標，將在2012年年中決定。一個關鍵因素是看對目標癌症的研究是否能儘快達到“概念驗證”的階段，到了那個階段，研究工作就可以在商業資本的支持下作爲一個生意來向前推進，而不是僅僅是依靠科研撥款。這樣，或者可以在研究所的基礎上成立一個新公司，或者可以和既有的製藥公司合作，從而研發一種新藥。

In recent years many big drug companies have gutted their research departments. This is partly because those departments have failed to come up with new "blockbuster" drugs of the sort that created Big Pharma in the first place, and partly because the big firms' bosses had hoped that smaller biotechnology companies, of the sort Dr DePinho has helped set up, would do the hard work of drug discovery instead, and then let themselves be bought by the big firms.

最近這些年來，很多大製藥公司取消了他們的研究部。部分原因是，這些研究部沒能研製出當初做大這些大製藥公司的拳頭產品那種量級的新產品，部分原因是，那些大製藥公司的老闆們希望徳平厚博士那樣的小生物技術公司承擔發明新藥的艱鉅工作，然後再把這些小公司收購進來。

Unfortunately, it hasn't quite worked out like that. The output of the biotech firms has been a trickle, rather than a torrent. They have been one of the worst-performing parts of the private-equity market since 2007, according to Dr DePinho. He hopes to change that—and in the matter of new anti-cancer drugs, the science is looking auspicious. For example, a drug called vemurafenib, which was approved for use in America in August 2011, gives months of extra life to people with metastasising melanoma, one of the deadliest cancers. Vemurafenib is so powerful that some people call it a "Lazarus" drug, after the chap Jesus is said to have raised from the dead.

令人失望的是，事情並沒有像他們設想的那樣發展。生物技術公司只有一些點滴的成果，沒有產生什麼大的成果。徳平厚博士指出，自2007年以來，這個領域是私募股份市場上表現最差的領域之一。他希望改變這個局面。而研製抗癌新藥的科技看來正處於幸運期。例如，2011年8月，美國批准了一種名爲vemurafenib的新藥，它可以把最惡性的癌症之一黑色素瘤病人的生命延長數月。這種藥的效力是如此顯著，以致一些人把它稱爲“拉扎羅斯”—— 那個被耶穌起死回生的麻風病人的名字。

Crucially for Dr DePinho's project, the development of vemurafenib was stimulated by the identification of a mutated gene often present in melanomas. He and others like him hope that the cancer-genome consortium will throw up dozens of similar genes, and that they, too, will prove tractable targets for drug development.

對徳平厚博士很有意義的是，vemurafenib的研發正是由於辨識了經常出現在黑色素瘤中的一種突變基因所推動的。徳平厚和同行們希望癌症基因圖譜研究聯盟能夠發現幾十種類似的基因，從而能夠爲新藥研發提供可控的目標。

Of course, if Dr DePinho had a penny for every time a "cure for cancer" headline proved premature, he wouldn't need munificent donors. But if his bets on the science and on adopting business methods pay off, the drug industry and millions of patients will benefit. That would be one benign sort of metastasis.

當然，過去已經有太多關於“攻克癌症”的宣告最終被證明是爲時過早。[注]但是，如果徳平厚博士的科研選題和運用商業方式的辦法能夠奏效，製藥行業和數百萬患者將會受益。那倒真可以稱之爲一個良性的細胞轉移。