未来目标 攻克五种癌症

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?

罗恩•徳平厚肩负着一个使命。虽然奇怪的是，他现在仍不清楚他的使命的确切目标是什么。徳平厚博士是德克萨斯州休斯顿市的MD •安德森癌症研究中心的新任主任，他此前是哈佛的丹娜-法波尔癌症研究院下属的贝尔佛研究所所长。徳平厚知道，休斯顿在科学领域最广为人知的，是其作为阿波罗登月计划的目标控制中心所在地。因此，他说他自己的目标也类似于登月。这就是，要找到攻克不仅一种，而是五种癌症的方法。他现在还没有决定的是哪五种癌症。

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.)

现在，人们之所以敢于谈论攻克癌症（即便是其中一种癌症），主要是因为一个名为国际癌症基因图谱研究联盟的组织。这个组织包括遍布四大洲的39个研究项目，该组织的研究人员使用高流量的基因测序方法来检测50种不同的肿瘤。他们把每种肿瘤的众多基因突变案例进行比较，区分出对某种肿瘤来说，哪些突变是共同的（从而，估计是致病原因），哪些突变是偶然的（恶性细胞中的基因修复机制经常出错，所以偶然突变是常见的事)。

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.

这个联盟的工作进展很快，已经得出了很多种肿瘤的初步研究成果。但是，对病因的认知只有转化为治疗方法才是真正有用的。这正是徳平厚博士要做的事，因为在他的职业生涯中，他既做过诊疗工作，也做过经营管理工作。他是一个富有经验的企业家，参与创建过若干个公司，包括：正在研制阻碍肿瘤中血管生长的药品的Aveo制药公司；研究癌症诊断方法的Metamark遗传研究公司；还有Karyopharm 诊疗研究所，这个所的研究方向是，通过控制分子进出细胞核的方法来控制细胞核的活动。他说，他来MD •安德森癌症研究中心的目的是，以高流量测序推动遗传研究的同样方式，用“产业化”的方法来推动生物学领域其它方面的研究。

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.

他的计划将花费数十亿美元。幸运的是，尽管德克萨斯州在花纳税者的钱上是非常谨慎的，但已经建立了一个30亿美元的癌症研究基金来支持这个计划。当地的慈善家，如T. Boone Pickens 和 Ross Perot等也给与了支持。他们的模式和原先的“人类基因图谱项目”相同，在那个项目中，单个DNA碱基的测序价格从1991年的10美元降到2001年的1毛钱，现在是3，000个碱基1分钱。他们希望，他们的资金将鼓励那些现在基本上是运用手工技术的研究人员，考虑如何把那些技术产业化的问题。

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.

对于这种产业化方式，若干技术看来已经相当成熟。例如，徳平厚博士很重视运用基因被改造过的老鼠（他称之为“小患者”），研究者把人类癌症的基因突变精确地复制到这些老鼠身上，从而发现这些突变的基因图谱每一部分的形状。但是，基因突变的复制只能一次做一个，他认为，如果这个过程可以成规模地来做，就可以区分基因突变的主因和偶然事件。

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.

另一个很有希望的领域是成像技术，具体说，这是两种技术的结合：正电子放射层扫描术（用放射性糖来测量细胞组织新陈代谢的活跃程度），和电脑化的体层摄影技术（用X-射线来绘制人体内部的解剖结构）。两种技术一起运用，可以显示某种治疗方法是否降低了肿瘤的能量消耗，从而是否减缓了它的新陈代谢。这对于评价治疗方法的有效性很有帮助。

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安德森的作用远不止确定哪五种肿瘤。建立肿瘤应用科学研究所（这是新的目标控制机构的名称）的艰苦工作是琳达•秦的责任，她也曾在贝尔佛研究所工作。她还是癌症图谱项目的国际科学指导委员会的成员，并且是徳平厚博士的妻子。55名科学工作者将和徳平厚夫妇一起从贝尔福来到德克萨斯，帮助秦博士工作。这种挖走人家整个团队的做法在投资银行界司空见惯，但是在学术研究界却不多见。徳平厚博士把此事戏称为“细胞转移”，因为他原先创造的研究机构的克隆物将在另一个地方扎下根来。

As to which five cancers to attack, that decision will be made by the middle of 2017. 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.

至于把哪五种癌症作为目标，将在2017年年中决定。一个关键因素是看对目标癌症的研究是否能尽快达到“概念验证”的阶段，到了那个阶段，研究工作就可以在商业资本的支持下作为一个生意来向前推进，而不是仅仅是依靠科研拨款。这样，或者可以在研究所的基础上成立一个新公司，或者可以和既有的制药公司合作，从而研发一种新药。

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.

最近这些年来，很多大制药公司取消了他们的研究部。部分原因是，这些研究部没能研制出当初做大这些大制药公司的拳头产品那种量级的新产品，部分原因是，那些大制药公司的老板们希望徳平厚博士那样的小生物技术公司承担发明新药的艰巨工作，然后再把这些小公司收购进来。

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，事情并没有像他们设想的那样发展。生物技术公司只有一些点滴的成果，没有产生什么大的成果。徳平厚博士指出，自2007年以来，这个领域是私募股份市场上表现最差的领域之一。他希望改变这个局面。而研制抗癌新药的科技看来正处于幸运期。例如，2011年8月，美国批准了一种名为vemurafenib的新药，它可以把最恶性的癌症之一黑色素瘤病人的生命延长数月。这种药的效力是如此显著，以致一些人把它称为“拉扎罗斯”—— 那个被耶稣起死回生的麻风病人的名字。

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.

对徳平厚博士很有意义的是，vemurafenib的研发正是由于辨识了经常出现在黑色素瘤中的一种突变基因所推动的。徳平厚和同行们希望癌症基因图谱研究联盟能够发现几十种类似的基因，从而能够为新药研发提供可控的目标。

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.

当然，过去已经有太多关于“攻克癌症”的宣告最终被证明是为时过早。[注]但是，如果徳平厚博士的科研选题和运用商业方式的办法能够奏效，制药行业和数百万患者将会受益。那倒真可以称之为一个良性的细胞转移。