癌症的新想法

世界自然保护协会(WCS)的一组科学家发表的一项研究表明，似乎伐木公司开辟森林的道路可能导致西非森林象的灭绝。他们在非洲森林中跋涉了8000多公里，对大象的数量进行了普查。

清点森林象并不是一件容易的事——部分原因是茂密的森林意味着你不能像它们生活在大草原上的表亲那样飞过该地区去发现和计数它们，还有一个原因是你不想太靠近大象，因为它们是出了名的具有攻击性。因此，研究小组转而寻找大象留在森林里的线索——最可靠的是它们的粪便。

令人担忧的是，他们发现大象的数量非常少，每平方公里森林中不到一头大象。更令人担忧的是，他们在靠近公路的地方发现的粪便更少。这些道路已经越来越深入森林，使木材公司能够获得宝贵的树木。他们没有在公路附近找到活象的证据，而是发现了更多被拔掉象牙的大象尸体。这表明，这些公路带来的不仅是伐木公司，还有为象牙和肉而来的大象偷猎者。

象牙贸易是被禁止的濒危物种国际贸易公约(CITES)但自2004年以来，价格翻了两番，现在每公斤超过850美元。可悲的是，对象牙的持续需求可能会导致这些令人难以置信的生物灭绝。

据美国科学家称，座头鲸是打破纪录的游泳健将——它们的迁徙距离比其他任何哺乳动物都要远。他们记录了这些鲸鱼从中美洲的哥斯达黎加到南极洲的觅食地旅行了5100多英里。

他们使用传统的方法来收集数据，而不是复杂的卫星跟踪——通过尾巴的形状和颜色来识别单个鲸鱼。随着鲸鱼年龄的增长，它巨大的尾巴上会有小的裂痕和切口，藤壶等物种也会在它身上定居。这意味着可以通过拍照和研究尾巴的差异来区分个体。研究人员收集了哥斯达黎加和南极洲的鲸鱼的照片，并在这两个地区识别出了相同的鲸鱼。

除了鲸鱼迁徙到目前为止的事实之外，这项研究的另一个有趣的部分是，它证明了座头鲸确实会在冬天迁徙到温暖的水域。他们还利用海洋表面温度的卫星数据显示，在哥斯达黎加温度较低的年份，鲸鱼实际上会向北移动，远离南极洲，到更温暖的地区度过冬天，然后在春天一直游回觅食地。

我们在生活中获得的技能是遗传的这一观点被称为拉马克主义，尽管这一度被广泛接受，但现在被认为是错误的。技能和能力的发展很可能是你成长环境的结果，这是后天培养的，而不是天生的。一些基因数据表明，某些能力，比如识别“完美音高”的能力，有基因成分。这并不意味着你天生就有音乐才能，但能够比大多数人更准确地再现音乐可能会让你更有可能决定进入音乐领域，并发展你的音乐技能。

萨宾娜:为了开始探索干细胞在癌症中的作用，我想我应该弄清楚干细胞是什么;所以我去了威康干细胞研究中心，问了一位干细胞研究人员。杰森·雷:干细胞是一种非常神奇的细胞类型，它们有两个非常特殊的特性;第一个是自我更新，即复制相同的自身的能力，第二个定义干细胞的特性是分化成更专门的细胞类型的能力。我们把干细胞分成两类:胚胎干细胞，它有能力制造任何类型的组织，以及更特化的干细胞，我们称之为成体干细胞，它仅限于一种特定类型的组织，比如脑组织、皮肤组织等等。Sabina——我要去见剑桥大学病理科的乳腺癌专家John Stingl，问他什么是癌症以及干细胞是如何参与的。约翰·斯廷格:实际上，我们认为癌症是一种干细胞疾病。干细胞通常参与器官的形成，而癌症就是器官的形成出了问题。癌症是一种需要多种基因突变才能产生肿瘤的疾病。例如，你不会因为一个突变就得了肿瘤，因为如果是这样的话，我们都会死。我们发现我们需要5-7个突变。细胞发生突变的概率实际上非常低，只有百万分之一，就像试图中彩票一样。然而，如果你有一个细胞有能力产生很多子细胞，比如干细胞，如果你能使一个干细胞发生突变，那么这个干细胞就会产生一百万个子细胞，现在你有一百万个细胞已经有了一个基因突变。其中一个细胞发生另一个突变的概率实际上是相当高的，然后发生突变的细胞会产生一百万个子细胞其中一个会发生突变，以此类推。 That's how you can acquire five mutations.Sabina - A lot of research is being conducted to look at how stem cells work and what their role in cancer is. Brian Huntley is an expert in stem cell self renewal and he's working with leukaemia at the Cambridge Institute for Medical Research. I asked him how current research is directed by a need for cancer treatment.Brian Huntley: Treatment of malignant disease is still very ineffective and most patients have relapse and progressional disease, many still die from malignant disorders. However when you initially have a tumour, regardless of the tumour type and regardless of the therapy; whether that be chemotherapy, radiotherapy or some of the newer immunotherapies, there is usually a reduction in the size of the tumour mass. Sometimes it's very dramatic and sometimes it actually disappears. However we know that the vast majority of patients have re-growth of that tumour, either in the same place of what's known as a metastasis, growth in another place. That would suggest, following on from the cancer stem cell hypothesis, that we are killing the cells that form the bulk of the tumour, but are not able to re-grow it, whilst we are sparing the cancer stem cells. We would ideally want to target the critical cells which cause the propagation and the re-growth of the tumour. We need to know more about these cancer stem cells and how they differ from normal stem cells, and we need to be specifically targeting them to show improvements in cancer therapy.

安德鲁:我们开始做的是试图了解在所有个体的基因组中出现的一组特定的基因，称为激酶，在疾病(癌症)的进展中起什么作用。这些细胞非常有趣，因为它们控制着细胞中的大部分分子过程。它们就像分子开关，开启和关闭物质。癌细胞是那些在不应该生长的时候生长，在不应该生长的地方生长以及不应该生长的方式几乎所有的这些过程都有一个激酶参与到控制这个过程的途径中。我们很想知道哪些基因可以作为药物靶点。我们还从过去20年的研究中了解到，如果你观察已知的突变基因，蛋白质激酶比目前任何其他基因家族出现的频率都要高。凯特-所以他们才是真正的坏人?目前看来，他们似乎是我们最了解的坏人。在人类基因组中存在的两万多个基因中，决定研究这些基因的关键，是我们知道如何制造药物的一个基因家族。有几个令人吃惊的例子，通过突变的蛋白激酶来了解肿瘤的遗传学，并开发出一种对患者具有高水平疗效的小分子。所以我们想要了解癌症的基因，并建立一个家庭，如果我们发现了一些东西，就会有更短的途径转化为患者的利益。凯特:你已经研究了200种癌症的500个基因。你如何从这么多基因中获取这么多信息呢?安德鲁:我们使用了几年后将被称为“石器时代”的技术，与我们用于人类基因组测序的技术相同;叫做毛细管基因测序。在这500个基因中，我们观察了所有编码它们的比特，用聚合酶链反应从这500个基因的所有200个样本中扩增它们，每个样本大约有10,000个片段，并从两端对它们进行测序。凯特-那是很多工作!你怎么处理这么多信息? Presumably you have incredible computers to process it all.Andrew - Yes, we have an excellent group of 14 people in the cancer genome project who are bioinformatitians. They are a brilliant group who organise the data and give it to us in terms we can understand. They actually allow us to find a single experiment amongst the millions that have been done, which is very important. It's collaboration between lab scientists, computer scientists and the people who integrate the information between the two.Kat - So what were you expecting to find?Andrew - Well, from the work that we had done earlier we found a frequently mutated Kinase called B-raf in the tumor type called melanoma. This particular Kinase is mutated in about 60% to 70% of this lethal disease. We were hoping to find the same sort of pattern when we look at Kinases across a broader set of cancers. If 60% of a gene is mutated in a tumour it would make a good drug target, if you can make a molecule to turn that gene off.So we when we started looking at these 200 cancers we quickly began to understand that this particular example looks like the exception rather than the rule. The rule looks like a more widely distributed set of mutations across a larger number of genes, so we found about 1000 mutations in 200 samples, and we believe about 100 of those are driving cancers in that group of 200.Kat - So this is more than you expected?Andrew - It's quite a bit more than I would have expected. We hoped it would be lots of spikes rather than this rumble of noise, because it's more tractable to deal with spikes in terms of therapeutic development.Kat - So do you think that means you've potentially more targets to have a go at?Andrew - I think that's exactly right. What it does is it opens up a window into understanding just how complex the disease is and that's a daunting prospective. I think what it also does is allow you to begin to integrate this information into understanding what processes, pathways and signalling circuitry is turned on or off in particular cancers, it may give you the opportunity to not only go after the gene itself but also the pathway.Cancer is a complex disease we can't get away from that so we're going to get in there, roll up our sleeves and get to grips with the ugly reality of it.Kat - So you've looked at Kinases, this particular group of signalling molecules. Are there any other molecules or family of molecules that are next on your hit list?Andrew - We started a study running towards the end of the Kinase study looking at another group of about 4000 genes. We're also going to use a larger number of tumours, about 100 cancers per set. This is comprised of essentially any gene family where there is already one member known to be mutated in cancer, promoting the idea that they may be clustered by family or by function. For example we know that DNA repair is not working particularly well in a lot of cancers. This would involve things like phosphatase, which turns things back off after Kinases turn them on, or other gene families that are involved in signalling pro-growth or pro-apoptosis cell growth division. These are all the usual suspects or at least as good as we can come up with on that list at the time.Kat - so that's going to keep you busy for a while!Andrew - Yes, sadly, I don't think we'll be working our way out of a job anytime soon.

非黑色素瘤癌症(不影响黑色素细胞或皮肤色素细胞的皮肤癌)是迄今为止西方世界最常见的癌症。这主要是因为皮肤是保护你不受环境影响的屏障。暴露在阳光下，如果不加控制，可能会破坏你皮肤中的DNA，导致癌症。其他可能导致癌症的损害包括接触有害化学物质。黑色素瘤(影响黑色素细胞或皮肤色素细胞的皮肤癌)的发病率在过去几十年里几乎增加了两倍，尤其是在年轻人中。这可能是因为人们在阳光下度假，使用日光浴床，在短时间内过度暴露在辐射中。