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．德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。德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。德平厚知道，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。这正是德平厚博士要做的事，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，德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。