为什么大象很少得癌症

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Science & technology

科技板块

Oncology

肿瘤学

Protein shake-up

蛋白质重组

Why elephants so rarely get cancer

为什么大象很少患癌症

Elephants have always presented a paradox to biologists.

对于生物学家来说，大象一直是一个悖论。

They are much larger than humans and live for a similar length of time, yet they only rarely develop cancer.

它们比人类大得多，寿命也差不多，但它们很少患上癌症。

That is odd.

这很奇怪。

Cancer, after all, is something of a numbers game: the more cells, the more replications.

毕竟，在某种程度上癌症是一个数字游戏：细胞越多，复制就越多。

The more replications, the greater the likelihood of random dna damage and a cell going rogue, failing to be detected and ultimately starting the runaway process towards a tumour.

复制越多，随机DNA损伤和细胞失控的可能性就越大，无法被检测到，最终开始向肿瘤扩散的失控过程。

Work led by Konstantinos Karakostis of the Autonomous University of Barcelona and published in Molecular Biology and Evolution, points to an answer, for elephants at least, to Peto’s paradox.

巴塞罗那自治大学的Konstantinos Karakostis领导的研究发表在《分子生物学与进化》上，这项研究指出了皮托悖论的答案，至少对大象来说是这样。

This absence of size-to-cancer correlation is named after Sir Richard Peto, a British epidemiologist who first noted it in 1977.

大小与癌症之间没有相关性的现象，是以英国流行病学家理查德·皮托爵士的名字命名的，他在1977年首次发现这一现象。

Their investigations began with p53, a transcription factor.

他们的研究始于转录因子P53。

These are the proteins that are in attendance as dna is transcribed into rna, controlling which genes are switched on and for how long.

当DNA被转录成RNA时，这些蛋白质参与其中，控制着哪些基因被激活以及激活多长时间。

But p53 is also in the business of marshalling resources in the service of quality control.

但P53也在为质量控制服务中调集资源。

When it encounters damaged dna, it fails to bind to yet another protein called mdm2.

当它遇到受损的DNA时，它无法与另一种名为MDM2的蛋白质结合。

That in turn sets off a chain of events that stimulates a cell to repair any damage.

进而引发了一系列事件，刺激细胞修复任何损伤。

If that fails, p53 initiates a different chain that makes the cell destroy itself.

如果失败，p53会启动不同的链条，使细胞自我毁灭。

P53, then, is a potent anti-cancer agent in the body’s arsenal.

因此，p53是人体基因库中一种有效的抗癌剂。

But cancer, in many creatures, is a potent adversary.

但在许多生物体中，癌症是一个强劲的对手。

Cancer cells have damaged dna but have ways to ensure the binding to mdm2 happens without a hitch.

癌细胞破坏了DNA，但有办法确保与MDM2的结合顺利进行。

The first step in quality control is evaded, and the last steps -- repair or self-destruct -- are never reached.

逃避质量控制的第一步，而最后一步--修复或自毁--永远也达不到。

Most animals play host to but one type of p53.

大多数动物只有一种类型的p53。

So the discovery last year that elephants have 20, each subtly different, drew the attention of Dr Karakostis and his colleagues.

因此，去年发现大象有20种p53，每头大象略有不同，引起了卡拉科斯蒂斯博士和他的同事的注意。

Maybe the p53s provide one another with anti-cancer backup.

也许p53为彼此提供了抗癌的支援。

But how?

但如何做到呢？

They suspected that mdm2 was involved.

他们怀疑与MDM2有关。

Perhaps all those slightly different p53s latch onto it in slightly different ways.

也许所有这些略有不同的p53以略有不同的方式锁定在它上面。

It would be less likely, the idea goes, that cancer cells’ trickery could work in 20 altered arrangements.

这种想法认为，癌细胞的诡计不太可能在20种改变的排列中发挥作用。

If any failed, the chain of repair would still be triggered.

如果其中任何一个失败，修复链仍将被触发。

First the team took to their computers.

首先，团队开始使用他们的电脑模拟。

Extensive simulations of precisely how mdm2 binds at the molecular level to this plethora of p53s indicated their hunch might be right.

对MDM2如何在分子水平上与大量的p53结合的广泛模拟表明，他们的预感可能是正确的。

A trip to the laboratory, to study that binding in a dish, only confirmed things further.

去一趟实验室，在培养皿中研究这种结合，可能会进一步证实这一点。

Cancer cells might have defences clever enough to smooth the route to one kind of binding -- but not, it is now assumed, 20 of them.

癌细胞可能具有足够聪明的防御机制，能够使一种结合途径变得顺畅 --但现在人们认为，不是20种。

Peto's paradox lives on, however.

然而，皮托的悖论仍然存在。

Why have humans not evolved this variegated gang of anti-cancer proteins, or indeed the different suite of cellular protections enjoyed by blue whales, if they would confer such a clear-cut survival benefit?

如果能够带来如此明确的生存益处，为什么人类没有进化出这种五花八门的抗癌蛋白质，还是蓝鲸享有的不同的细胞保护呢？

Alas, a common refrain in matters scientific: more research is needed.

唉，在科学问题上有一个常见的问题：需要更多的研究。

But that is not to say this work is without potential relevance to humans.

但这并不是说这项工作与人类没有潜在的相关性。

Work reported in 2016 revealed that genetically engineering mice to have a few extra copies of p53 enhanced their cells’ ability to detect and repair dna damage.

2016年的研究报告显示，通过基因工程使小鼠拥有额外的几个p53，提高了它们的细胞检测和修复DNA损伤的能力。

This latest work suggests something many managers are belatedly finding out: success comes not just with a bigger team, but a more diverse one.

这项最新研究表明，许多管理者可以从中获得启发：成功不仅来自更大的团队，而且来自更多元化的团队。

来源：经济学人

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