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2009年诺贝尔医学奖问世

来源:天星 更新日期:2009-10-10 点击:

The 2009 Nobel Prize in medicine has been awarded to Elizabeth Blackburn, Carol Greider and Jack Szostak for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase.

Australian-born Elizabeth Blackburn, British-born Jack Szostak and Carol Greider won the prize of 10 million Swedish crowns ($1.42 million).

The scientists have solved a major problem in biology: how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes the telomeres - and in an enzyme that forms them - telomerase.

The long, threadlike DNA molecules that carry our genes are packed into chromosomes, the telomeres being the caps on their ends. Elizabeth Blackburn and Jack Szostak discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation. Carol Greider and Blackburn identified telomerase, the enzyme that makes telomere DNA. These discoveries explained how the ends of the chromosomes are protected by the telomeres and that they are built by telomerase.

If the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed. This is the case in cancer cells, which can be considered to have eternal life. Certain inherited diseases, in contrast, are characterized by a defective telomerase, resulting in damaged cells. The award of the Nobel Prize recognizes the discovery of a fundamental mechanism in the cell, a discovery that has stimulated the development of new therapeutic strategies.

In conclusion, the discoveries by Blackburn, Greider and Szostak have added a new dimension to our understanding of the cell, shed light on disease mechanisms, and stimulated the development of potential new therapies.

Medicine is traditionally the first of the Nobel prizes awarded each year. The prizes for achievement in science, literature and peace were first awarded in 1901 accordance with the will of dynamite inventor and businessman Alfred Nobel.

Q. What are telomeres and telomerase?

A. Telomeres are the protective caps at the ends of chromosomes in cells. Chromosomes carry the genetic information. Telomeres are buffers. They are like the tips of shoelaces. If you lose the tips, the ends start fraying.

Telomerase is an enzyme. In cells, it restores the length of the telomeres when they get worn. As the ends of the chromosomes wear down, the telomerase comes in and builds them back up.

In humans, the thing is that as we mature, our telomeres slowly wear down. So the question has always been: did that matter? Well, more and more, it seems like it matters.

Q. Is there a link between telomere length and stress?

A. In my lab, we’re finding that psychological stress actually ages cells, which can be seen when you measure the wearing down of the tips of the chromosomes, those telomeres.

A few years ago, Dr. Elissa Epel, a psychologist who studies chronic stress, came to see me. She asked, ‘Does stress have any effect on cell aging?’ There’s always been this observation that people under great stress appear to be care-worn. They look haggard, right?

So Elissa designed this study where we looked at two groups of mothers. One had normal, healthy children. The other group had a child with a chronic illness. Physiological and psychological measurements were done on everyone. With the stressed group, we found that the longer the mothers had been caring for their chronically ill child, the less their telomerase and the shorter their telomeres.

This was the first time you could clearly see cause and effect from a nongenetic influence. Genes play a role in telomerase levels, but this was not genes. This was something impacting the body that came from the outside and affecting its ability to repair itself. By the way, we found similar effects in women who were primary caregivers for partners with dementia.

Q. Is this scientific proof of the mind-body connection?

A. It’s a proof. There have been others. Researchers have found that the brain definitely sends nerves directly to organs of the immune system and not just to the heart and the lower gut. In that way, too, the brain is influencing the body.

One of the things that came out of our study of these mothers is a link between low telomerase and stress-related diseases. We looked at the measures for cardiovascular disease — bad lipid profiles, obesity, all that stuff. The women with those had low telomerase.

We also looked at low telomeres and cancer. We wondered if a cell with worn down chromosome tips might divide in some abnormal way. Our findings have yet to be published, so I can’t tell you much here, but we think we’re onto something.

2009年诺贝尔生理学或医学奖揭晓:共有三名获奖者,分别是:伊丽莎白 H. 布莱克本(Elizabeth H. Blackburn)、卡罗尔·W. 葛莱德尔(Carol W. Greider)和杰克 W. 卓斯塔克(Jack W. Szostak),他们的功绩是发现了染色体端粒及端粒酶对染色体的保护机制。

出生于澳大利亚的伊丽莎白·布莱克本、出生于英国的杰克·卓斯塔克和卡罗尔·葛莱德尔共同夺得这笔1000万瑞典法兰(约合142万美元)的奖项。

这三位科学家解决了生物学的重大问题:在细胞过程中,染色体是如何完整复制、又是如何避免自身退化的?这几位获奖者已经证明,染色体解决上述问题的奥妙就在于染色体末端的端粒(telomer)以及形成端粒的酶——端粒酶。

承载着各种基因的DNA分子就象一根长长的细线,并依一定规则扭曲成染色体,而端粒就象一顶帽子那样覆盖在染色体末端。伊丽莎白·布莱克本和杰克·卓斯塔克发现,由于端粒上有独特的DNA序列,从而能防止染色体的退化。卡罗尔·葛莱德尔和布莱克本还分离出端粒酶,即合成端粒DNA所需要的一种酶。他们的发现解释了染色体末端是怎样得到端粒的保护,而端粒是在端粒酶的作用下形成的。

当端粒变短的时候,细胞就开始老化。相反,如果端粒酶一直保持较高的活力,则端粒的长度就能保持下去,而细胞衰老的进程就会被推迟,这种情形可见于癌细胞:一类属于永生的细胞。相比之下,某些遗传病的机制正是因为端粒酶有缺陷、从而导致细胞受损的缘故。本届诺贝尔生理学及医学奖对此予以奖励,等于宣布人类发现了细胞生长的基本机理,这一科学发现,将加快人类研究全新的疾病治疗方案的步伐。

用一句话说,布莱克本、葛莱德尔和卓斯塔克三位科学家所取得的科学发现,让我们得以从新的角度去了解细胞,进一步阐明了产生疾病的机理,加快了人类研发新的疾病治疗方案的进程。

医学奖一直都是诺贝尔奖第一个颁发的奖项,这是诺贝尔奖的传统,而科学奖、文学奖和和平奖则是1901年才开始设立的,是火药发明家及商人阿尔弗雷德·诺贝尔本人的遗愿。

知识链接:从染色体末端不断磨损的现象中寻找衰老的线索

(《纽约时报》记者采访布莱克本的部分对话,原文刊登于2007年7月3日《纽约时报》)

问:端粒和端粒酶都是些什么东西?

答:端粒就是细胞内的染色体上的一个保护罩。染色体包含有遗传信息。端粒就是一种缓冲地带,就象鞋带扣一样,如果这个部分松脱了,鞋带也就更容易磨损。

端粒酶就是一种酶,其作用就是负责修复端粒,使其保持一定的长度,不至于因磨损而逐渐变短。当染色体末端出现磨损的时候,端粒酶就开始发挥作用,对磨损的部分加以修复。

在人类体内,随着人的长大成熟,端粒就会开始慢慢老化,这样一来,问题就变成了:这要紧吗?是的,这个问题确实很要紧,而且我们已经越来越深刻地认识到,这个问题很要紧。

问:端粒长度和人的精神压力两者有没有什么关系?

答:我在我的实验室里已经发现,人的心理压力确实会加快细胞的老化,这从染色体末端即端粒的损耗程度上可以看出来。

几年前我就和专门研究长期精神压力问题的心理学家艾丽莎·爱佩尔博士座谈过,她问过我:“精神压力对细胞老化有影响吗?”长期以来,人们总能观察到这样的现象:经受强大精神压力的人都容易疲劳,看起来也很憔悴,对吧?

于是,艾丽莎就设计了这么个实验,试验中我们把那些做妈妈的女人分成两组,其中一组女人的孩子身体健康,各方面都正常,另一组女人的孩子患有慢性病。实验过程中这两组女人的生理指标和心理指标都有专门监测,结果我们发现,在那组经受着精神压力的女人里面,照顾慢性病孩子的时间越长,端粒酶水平就越低,且端粒就越短。

这是我们第一次清清楚楚地看到非遗传因素所带来的因果关系。基因对端粒酶水平是起了一定作用,但这个实验所观察的并非基因的问题,这完全是身体以外的因素对身体带来的影响,其影响的结果就是端粒的自我修复水平。顺便说一点,我们也看到那些需要照料痴呆性丈夫的女人有类似情况。

问:这能作为身、心两者存在关系的证据吗?

答:这确是证据,除此以外还有别的证据。科研人员已经发现,大脑不仅会直接把某些神经信号发送到心脏和其他内脏,还会送给体内的免疫器官,这是千真万确的事实。这种情况也同样说明大脑对身体是有影响的。

发现端粒酶水平与精神压力性疾病之间的关系,只是我们对这些做妈妈的人的研究结果之一。我们对心血管疾病的某些指标——包括血脂水平、肥胖证等等——也进行过分析,结果发现患有这些病症的女性,其端粒酶水平也较低。

我们还考察过端粒与癌症之间的关系,当染色体末端开始出现损毁的时候,含有受损染色体的细胞是否还能正常复制呢?对此我们还没有弄清楚。我们已获得的一些发现还没有公开发表,因此这里不方便透露什么,不过我们确实已经发现了某些端倪。

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