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2020-11-25 21:55:02

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 Harvards Dana-Farber Cancer Institute.) Mindful of his adopted citys 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?罗恩徳追薄肩负着一个愿景。虽然奇怪的是,他现在仍不确切他的愿景的清楚目标是什么。徳追薄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-法波尔癌症研究院辖下的贝尔佛研究所所长。徳追薄告诉,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。



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,人们之所以勇于谈论攻下癌症(即便是其中一种癌症),主要是因为一个取名为国际癌症基因图谱研究联盟的的组织。这个的组织还包括遍及四大洲的39个研究项目,该的组织的研究人员用于低流量的基因测序方法来检测50种有所不同的肿瘤。他们把每种肿瘤的众多基因突变案例展开较为,区分出对某种肿瘤来说,哪些变异是联合的(从而,估算是致病原因),哪些变异是无意间的(恶性细胞中的基因修缮机制常常错误,所以无意间变异是少见的事)。

The consortiums 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 infor 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 nucleuss 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迅速,早已得出结论了很多种肿瘤的可行性研究成果。但是,对病因的理解只有转化成为化疗方法才是确实简单的。

这正是徳追薄博士要做到的事,因为在他的职业生涯中,他既做到过医疗工作,也做到过经营管理工作。他是一个富有经验的企业家,参予创立过若干个公司,还包括:正在研制妨碍肿瘤中血管生长的药品的Aveo制药公司;研究癌症临床方法的Metamark遗传研究公司;还有Karyopharm 医疗研究所,这个所的研究方向是,通过掌控分子出入细胞核的方法来掌控细胞核的活动。

他说道,他来MD 安德森癌症研究中心的目的是,以低流量测序推展遗传研究的某种程度方式,用产业化的方法来推展生物学领域其它方面的研究。That will cost billions of dollars. Fortunately, the state of Texasno pushover when it comes to spending taxpayers cashis 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 2001and 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。幸运地的是,尽管德克萨斯州在花纳税者的钱上是十分慎重的,但早已创建了一个30亿美元的癌症研究基金来反对这个计划。

当地的慈善家,如T. Boone Pickens 和 Ross Perot等也给予了反对。他们的模式和原本的人类基因图谱项目完全相同,在那个项目中,单个DNA碱基的测序价格从1991年的10美元降至2001年的1毛钱,现在是3,000个碱基1钱。

他们期望,他们的资金将希望那些现在基本上是运用手工技术的研究人员,考虑到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 cancers genetic generals to be distinguished from the foot soldiers.对于这种产业化方式,若干技术显然早已非常成熟期。

例如,徳追薄博士很推崇运用基因被改建过的老鼠(他称作小患者),研究者把人类癌症的基因突变准确地读取这些老鼠身上,从而找到这些变异的基因图谱每一部分的形状。但是,基因突变的拷贝不能一次做到一个,他指出,如果这个过程可以成规模地来做到,就可以区分基因突变的主因和无意间事件。Another field that has great potential is imaging technologyin 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 bodys internal anatomy). Together these can show whether a treatment is reducing a cancers energy consumption, and thus its metabolism. This gives a good indication of how well that treatment is working.另一个很有期望的领域是光学技术,明确说道,这是两种技术的融合:正电子放射线层扫描术(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学结构)。两种技术一起运用,可以表明某种化疗方法否减少了肿瘤的能量消耗,从而否减慢了它的新陈代谢。

这对于评价化疗方法的有效性很有协助。A family businessDr 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 DePinhos 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.夫妻店做生意徳追薄博士在MD安德森的起到远不止确认哪五种肿瘤。创建肿瘤应用科学研究所(这是新的目标掌控机构的名称)的艰难工作是琳达秦的责任,她也曾在贝尔佛研究所工作。


徳追薄博士把此事戏称为细胞移往,因为他原本建构的研究机构的克隆物将在另一个地方恰下根来。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 stagethe 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2012年年中要求。一个关键因素是看对目标癌症的研究否能尽早超过概念检验的阶段,到了那个阶段,研究工作就可以在商业资本的反对下作为一个做生意来向前前进,而不是意味着是依赖科研经费。

这样,或者可以在研究所的基础上正式成立一个新的公司,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,很多大制药公司中止了他们的研究部。

部分原因是,这些研究部没有能研制出当初做到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期望徳追薄博士那样的小生物技术公司分担发明者新药的艰难工作,然后再行把这些小公司并购进去。Unfortunately, it hasnt 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 thatand 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.令人沮丧的是,事情并没像他们设想的那样发展。



这种药的效力是如此明显,以致一些人把它称作拉扎罗斯 那个被耶稣起死回生的麻风病人的名字。Crucially for Dr DePinhos 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.对徳追薄博士很有意义的是,vemurafenib的研发正是由于识别了经常出现在黑色素瘤中的一种突变基因所推展的。

徳追薄和同行们期望癌症基因图谱研究联盟需要找到几十种类似于的基因,从而需要为新药研发获取高效率的目标。Of course, if Dr DePinho had a penny for every time a cure for cancer headline proved premature, he wouldnt 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,过去早已有过于多关于攻下癌症的宣告最后被证明是为时过早。[录]但是,如果徳追薄博士的科研选题和运用商业方式的办法需要奏效,制药行业和数百万患者将不会获益。那推倒真为可以称作一个良性的细胞移往。



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