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TED演讲:从演化的观点来看人类的健康与疾病

你的基因遗传、文化、历史会如何影响你的健康?生物人类学家Lara Durgavich在这场演说中讨论了演化医学的领域,透过演化医学来了解人类生物学的突然转变,包括为什么基因突变有时会有益处,为什么了解你自己的演化过往,能够让你对现在及未来的健康有更清楚的洞见。

演讲者:Lara Durgavich

生物人类学家,将历史因素融入人类生物学,分享了进化医学在个人生活和其他方面的重要性


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When I was approximately nine weeks pregnant with my first child, I found out I'm a carrier for a fatal genetic disorder called Tay-Sachs disease. What this means is that one of the two copies of chromosome number 15 that I have in each of my cells has a genetic mutation. 

当我怀第一胎大约九周的时候,我发现我带有泰萨氏症的隐性基因,一种致命的遗传性疾病。意思就是说,我每个细胞中的两条十五号染色体其中有一条发生了基因突变。


Because I still have one normal copy of this gene, the mutation doesn't affect me. But if a baby inherits this mutation from both parents, if both copies of this particular gene don't function properly, it results in Tay-Sachs, an incurable disease that progressively shuts down the central nervous system and causes death by age five.

因为我仍然有一个正常的这种基因,突变并不会影响我。但如果宝宝从双亲遗传到了这种突变,如果两个这种基因都无法发挥正常功能,就会造成泰萨氏症,这种疾病无法治愈,会渐渐让中枢神经系统停摆,造成病人在五岁时就死亡。


For many pregnant women, this news might produce a full-on panic. But I knew something that helped keep me calm when I heard this bombshell about my own biology. 

这种消息可能会让许多怀孕的女性极度慌张。但,当我听到这个关于我自身生物学的震撼弹时,因为我知道一件事,让我能保持冷静。


I knew that my husband, whose ancestry isn't Eastern European Jewish like mine, had a very low likelihood of also being a carrier for the Tay-Sachs mutation. 

我知道我的丈夫不像我有东欧犹太血统,因此他几乎不可能同时也带有泰萨氏症的突变基因。


While the frequency of heterozygotes, individuals who have one normal copy of the gene and one mutated copy, is about one out of 27 people among Jews of Ashkenazi descent, like me, in most populations, only one in about 300 people carry the Tay-Sachs mutation. 

所谓的异型合子指的是一对基因中有一个正常另一个突变,在像我这种阿什肯纳兹犹太裔身上发生的频率约为二十七分之一,在大部分的人口中,只有三百分之一的人带有突变的泰萨氏症基因。


Thankfully, it turned out I was right not to worry too much. My husband isn't a carrier, and we now have two beautiful and healthy children.

谢天谢地,结果的确是不需要我太担心。我先生没有突变基因,现在我们育有两个健康的好孩子。


As I said, because of my Jewish background, I was aware of the unusually high rate of Tay-Sachs in the Ashkenazi population. But it wasn't until a few years after my daughter was born when I created and taught a seminar in evolutionary medicine at Harvard, that I thought to ask, and discovered a possible answer to, the question "why?" 

如我所言,因为我的犹太背景,我知道在阿什肯纳兹族群当中有异常高的泰萨氏症比率。但,一直到我女儿出生的几年后,我在哈佛设计并教授一场关于演化医学的研讨会时,我才想到要问「为什么?」


The process of evolution by natural selection typically eliminates harmful mutations. So how did this defective gene persist at all? And why is it found at such a high frequency within this particular population?

并去寻找可能的答案。天择的演化过程通常会让有害的突变消失。所以,这个瑕疵的基因怎么能够留存下来?且为什么在这个特定的族群中发生的比率特别高?


The perspective of evolutionary medicine offers valuable insight, because it examines how and why humans' evolutionary past has left our bodies vulnerable to diseases and other problems today. 

演化医学的观点能提供很有价值的洞见,因为它在探究「如何」及「为什么」人类过去的演化造成我们的身体很难抵抗现今的疾病和其他问题。


In doing so, it demonstrates that natural selection doesn't always make our bodies better. It can't necessarily. But as I hope to illustrate with my own story, understanding the implications of your evolutionary past can help enrich your personal health.

透过这样的探究,可以发现天择不一定会让我们的身体变得更好。不见得。但,我希望能用我自己的故事来说明:了解你过去的演化有什么意涵,便能协助充实你的个人健康。


When I started investigating Tay-Sachs using an evolutionary perspective, I came across an intriguing hypothesis. The unusually high rate of the Tay-Sachs mutation in Ashkenazi Jews today may relate to advantages the mutation gave this population in the past. 

当我开始从演化的观点研究泰萨氏症时,我偶然发现一个有趣的假设。现今的阿什肯纳兹犹太人具有泰萨氏症突变的比率高到不寻常,可能和过去这项突变带给这个族群的优势有关。


Now I'm sure some of you are thinking, "I'm sorry, did you just suggest that this disease-causing mutation had beneficial effects?" Yeah, I did. Certainly not for individuals who inherited two copies of the mutation and had Tay-Sachs. 

我相信在座有人在想:「抱歉,你刚刚的意思是这种会造成疾病的突变也有有益的效应?」是的,没错。当然我指的不是遗传到两个突变基因且患有泰萨氏症的那些人。


But under certain circumstances, people like me, who had only one faulty gene copy, may have been more likely to survive, reproduce and pass on their genetic material, including that mutated gene.

但在某些情况下,像我这样的人,只有一个基因有缺陷的人,可能在过去比较容易生存、繁殖,并将遗传物质传下去,包括那个突变的基因。


This idea that there can be circumstances in which heterozygotes are better off might sound familiar to some of you. Evolutionary biologists call this phenomenon heterozygote advantage. And it explains, for example, why carriers of sickle cell anemia are more common among some African and Asian populations or those with ancestry from these tropical regions. 

在某些情况下异型合子会比较好,在座有人可能很熟悉这个想法。演化生物学家把这个现象称为「异型合子优势」。比如,它可以解释为什么镰刀型红血球贫血症比较常出现在一些非洲和亚洲人的族群中,或者祖先来自这些热带地区的族群中。


In these geographic regions, malaria poses significant risks to health. The parasite that causes malaria, though, can only complete its life cycle in normal, round red blood cells. By changing the shape of a person's red blood cells, the sickle cell mutation confers protection against malaria. 

在这些地理区域,疟疾对健康是很重大的风险。不过,造成疟疾的寄生虫只能在正常、圆形的红血球细胞中完成它的生命循环。镰刀型红血球细胞突变能够改变人类红血球细胞的形状,进而保护人类,抵抗疟疾。


People with the mutation aren't less likely to get bitten by the mosquitoes that transmit the disease, but they are less likely to get sick or die as a result. Being a carrier for sickle cell anemia is therefore the best possible genetic option in a malarial environment. 

有这种突变基因的人并不是比较不会被传播疟疾的蚊子叮咬,但他们比较不会因为被叮咬而生病或死亡。因此,有镰刀型红血球贫血症反而是在疟疾环境中最好的遗传选项。


Carriers are less susceptible to malaria, because they make some sickled red blood cells, but they make enough normal red blood cells that they aren't negatively affected by sickle cell anemia.

这种人比较不会得到疟疾,因为他们会制造一些镰刀型红血球细胞,但他们也会制造足够的正常红血球细胞,所以他们不会受到镰刀型红血球贫血症的负面影响。


Now in my case, the defective gene I carry won't protect me against malaria. But the unusual prevalence of the Tay-Sachs mutation in Ashkenazi populations may be another example of heterozygote advantage. In this case, increasing resistance to tuberculosis. 

在我的例子中,我身上的基因缺陷并不会保护我抵抗疟疾。但在阿什肯纳兹族群中泰萨氏症突变的比率高到不寻常的现象可能是另一个异型合子优势的例子。在这个例子中,增强的是对结核病的抵抗力。


The first hint of a possible relationship between Tay-Sachs and tuberculosis came in the 1970s, when researchers published data showing that among the Eastern European-born grandparents of a sample of American Ashkenazi children born with Tay-Sachs, tuberculosis was an exceedingly rare cause of death. 

点出泰萨氏症和结核病之间可能有关联的第一个暗示出现在 1970 年代,当时研究者公布的数据显示美国的阿什肯纳兹孩童若在出生时就有泰萨氏症,他们在东欧出生的祖父母因为结核病而死的比率低得惊人。


In fact, only one out of these 306 grandparents had died of TB, despite the fact that in the early 20th century, TB caused up to 20 percent of deaths in large Eastern European cities.

事实上,306名祖父母中,只有一名因结核病而死,但在二十世纪初期在东欧的大型城市中结核病的致死率高达两成。


Now on the one hand, these results weren't surprising. People had already recognized that while Jews and non-Jews in Europe had been equally likely to contract TB during this time, the death rate among non-Jews was twice as high. 

一方面,这些结果很让人惊讶。大家公认在欧洲,虽然犹太人和非犹太人在这段时期得到结核病的机率差不多,但非犹太人的死亡率却是两倍高。



But the hypothesis that these Ashkenazi grandparents had been less likely to die of TB specifically because at least some of them were Tay-Sachs carriers was novel and compelling. 

但,假设这些阿什肯纳兹祖父母比较不可能死于结核病,就是因为他们当中至少有些人带有泰萨氏症的基因,这个假设很新颖且引人注目。


The data hinted that the persistence of the Tay-Sachs mutation among Ashkenazi Jews might be explained by the benefits of being a carrier in an environment where tuberculosis was prevalent.

数据暗示,阿什肯纳兹犹太人中泰萨氏症突变一直存在,这个现象的原因可能是在流行结核病的环境中带有这种基因是有益处的。


You'll notice, though, that this explanation only fills in part of the puzzle. Even if the Tay-Sachs mutation persisted because carriers were more likely to survive, reproduce and pass on their genetic material, why did this resistance mechanism proliferate among the Ashkenazi population in particular? 

但可以注意到,这种解释只解开了拼图的一部分。即使泰萨氏症突变一直存在是因为带有这种基因比较有机会生存、繁殖,再把遗传物质传下去,那为什么这种机制在阿什肯纳兹人口中特别明显?


One possibility is that the genes and health of Eastern European Jews were affected not simply by geography but also by historical and cultural factors. At various points in history this population was forced to live in crowded urban ghettos with poor sanitation. Ideal conditions for the tuberculosis bacterium to thrive. 

一个可能性是,东欧犹太人的基因和健康不仅受到地理的影响,还会受到历史和文化因素的影响。在历史上许多时点,这个族群都被迫要住在拥挤且卫生很差的都市犹太区。这些条件相当适合结核菌生长茁壮。


In these environments, where TB posed an especially high threat, those individuals who were not carriers of any genetic protection would have been more likely to die. 

在这些环境中,结核病是特别大的威胁,没有任何基因保护,不带有突变基因的人,更有可能会死亡。


This winnowing effect together with a strong cultural predilection for marrying and reproducing only within the Ashkenazi community, would have amplified the relative frequency of carriers, boosting TB resistance but increasing the incidence of Tay-Sachs as an unfortunate side effect.

这种筛选效应再加上阿什肯纳兹人强烈偏好只和同族群结婚生子,就有可能放大带有突变基因者的相对数目,促进对抗结核病的能力,但不幸的副作用就是泰萨氏症的发生率会增加。


Studies from the 1980s support this idea. The segment of the American Jewish population that had the highest frequency of Tay-Sachs carriers traced their descent to those European countries where the incidence of TB was highest. 

1980 年代的研究支持这个想法。美国犹太人人口中这个族群带有泰萨氏症基因的人数最多,他们追溯自己的世系到结核病发病率最高的欧洲国家。


The benefits of being a Tay-Sachs carrier were highest in those places where the risk of death due to TB was greatest. And while it was unclear in the 1970s or '80s how exactly the Tay-Sachs mutation offered protection against TB, recent work has identified how the mutation increases cellular defenses against the bacterium. 

在这些地方,因为结核病而死的风险最高,因此带有泰萨氏症基因的益处也最大。虽然我们不清楚在 1970 或 1980 年代时泰萨氏症突变基因到底如何提供对抗结核病的保护,近期有研究发现突变如何增加细胞对抗细菌的防御能力。


So heterozygote advantage can help explain why problematic versions of genes persist at high frequencies in certain populations.

所以,异型合子可以解释为什么在某些族群中有问题的基因会大量延续下去。


But this is only one of the contributions evolutionary medicine can make in helping us understand human health. As I mentioned earlier, this field challenges the notion that our bodies should have gotten better over time. An idea that often stems from a misconception of how evolution works. 

但,在协助我们了解人类健康上,演化医学的贡献不只如此。如先前所言,这个领域在挑战我们认为人类身体会随时间变更好的观念。这个想法通常源自对演化功能的误解。


In a nutshell, there are three basic reasons why human bodies, including yours and mine, remain vulnerable to diseases and other health problems today. Natural selection acts slowly, there are limitations to the changes it can make and it optimizes for reproductive success, not health.

概括来说,有三个理由可以说明为什么人类的身体,包括你我的身体,现今仍然很难抵抗疾病和其他问题。天择的速度很慢,天择能做的改变有限,且天择的目标是繁殖成功率而非健康。


The way the pace of natural selection affects human health is probably most obvious in people's relationship with infectious pathogens. We're in a constant arms race with bacteria and viruses. Our immune system is continuously evolving to limit their ability to infect, and they are continuously developing ways to outmaneuver our defenses.

若想知道天择影响人类健康的步调有多缓慢,最明显的地方就是人类和传染病病原体的关系。我们和细菌及病毒经常在做军备竞赛。我们的免疫系统持续演化,限制细菌及病毒的感染力,它们则持续发展新策略来击败我们的防御。


And our species is at a distinct disadvantage due to our long lives and slow reproduction. In the time it takes us to evolve one mechanism of resistance, a pathogenic species will go through millions of generations, giving it ample time to evolve, so it can continue using our bodies as a host.

因为我们的寿命很长且繁殖缓慢,人类这个物种明显占劣势。我们演化出一种对抗机制所需要花的时间,病原体物种就已经经过了数百万个世代,有很充裕的时间演化,所以能够持续用我们的身体当作宿主。


Now what does it mean that there are limitations to the changes natural selection can make? Again, my examples of heterozygote advantage offer a useful illustration. In terms of resisting TB and malaria, the physiological effects of the Tay-Sachs and sickle cell anemia mutations are good. 

天择能做的改变有限是什么意思?同样可以用我的异型合子例子来做说明。在抵抗结核病和疟疾方面,泰萨氏症和镰刀型红血球贫血症突变的生理效应是很好的。


Taken to their extremes, though, they cause significant problems. This delicate balance highlights the constraints inherent in the human body, and the fact that the evolutionary process must work with the materials already available. 

不过,在最极端的状况,它们会造成重大的问题。这种脆弱的平衡强调出人类身体的天生限制,以及演化过程一定得使用既有的可得素材。


In many instances, a change that improves survival or reproduction in one sense may have cascading effects that carry their own risk. Evolution isn't an engineer that starts from scratch to create optimal solutions to individual problems. Evolution is all about compromise.

在许多例子中,改善生存或繁殖能力的改变,在某种意义上,可能会有一连串的效应,带有它们自己的风险。演化并不像是工程师从零开始,针对个别问题去创造解决方案。演化完全是妥协。


It's also important to remember, when considering our bodies' vulnerabilities, that from an evolutionary perspective, health isn't the most important currency. Reproduction is. 

还有一点也很重要,在考虑到我们身体的弱点时,从演化的角度,健康并不是最重要的货币。繁殖才是。


Success is measured not by how healthy an individual is, or by how long she lives, but by how many copies of her genes she passes to the next generation.

判断成功与否,看的不是一个人有多健康,或者寿命多长,而是这个人的基因能复制多少份到下一代。


This explains why a mutation like the one that causes Huntington's disease, another degenerative neurological disorder, hasn't been eliminated by natural selection. 

这就说明了为什么突变,比如造成另一种神经退化障碍亨丁顿舞蹈症的突变,并没有被天择给淘汰。


The mutation's detrimental effects usually don't appear until after the typical age of reproduction, when affected individuals have already passed on their genes.

这类突变的有害效应通常要到一般的生育年龄之后才会出现,此时被影响的人也已经把基因传给下一代了。


As a whole, the biomedical community focuses on proximate explanations and uses them to shape treatment approaches. Proximate explanations for health conditions consider the immediate factors: What's going on inside someone's body right now that caused a particular problem.

总的来说,生物医学领域的焦点是在「近因解释」,并用它们来发展治疗方法。对于健康状况的近因解释会考虑立即性的因素:现在这个人的体内有什么现象会造成某个特定问题。


Nearsightedness, for example, is usually the result of changes to the shape of the eye and can be easily corrected with glasses. But as with the genetic conditions I've discussed, a proximate explanation only provides part of the bigger picture. 

以近视为例,通常是眼睛形状改变的结果,很容易就用眼镜来校正。但换成是我刚才讨论的基因状况,近因解释就只能提供全貌的一部分。


Adopting an evolutionary perspective to consider the broader question of why do we have this problem to begin with -- what evolutionary medicine calls the ultimate perspective -- can give us insight into nonimmediate factors that affect our health. 

采用演化的视角,更广泛来思考我们一开始为什么会有这个问题——演化医学所谓的「终极观点」——让我们能去洞察影响健康的非立即性因素。


This is crucial, because it can suggest ways by which you can mitigate your own risk or that of friends and family.

这很重要,因为从中可以找出一些方法来将帮你自己或朋友家人将风险降到最低。


In the case of nearsightedness, some research suggests that one reason it's becoming more common in some populations is that many people today, including most of us in this room, spend far more time reading, writing and engaging with various types of screen than we do outside, interacting with the world on a bigger scale. 

在近视的例子中,有些研究指出,在某些族群中近视更普遍的其中一个理由就是现今有很多人,包括在座的大部分人,花在阅读、书写,和接触各种屏幕的时间,远多于我们花在外面,和更大的世界互动的时间。


In evolutionary terms, this is a recent change. For most of human evolutionary history, people used their vision across a broader landscape, spending more time in activities like hunting and gathering. 

在演化方面,这算是近期的改变。人类演化史上大部分的时间,人们都把视力用在更广大的地景上,花更多时间从事如打猎和采集等活动。


The increase in recent years in what's termed "near work," focusing intensely on objects directly in front of us for long periods of time, strains our eyes differently and affects the physical shape of the eye. 

近年来,所谓的「近距离工作」增加,聚焦在我们面前的物品上,且持续很长的时间,用不同的方式让眼睛疲惫,影响眼睛的实体形状。


When we put all these pieces together, this ultimate explanation for nearsightedness -- that environmental and behavioral change impact the way we use our eyes -- helps us better understand the proximate cause. 

当我们把所有这些拼图拼起来,这个近视的终极解释——即:环境和行为的改变影响了我们使用眼睛的方式——能协助我们更了解近因。


And an inescapable conclusion emerges -- my mother was right, I probably should have spent a little less time with my nose in a book.

而必然的结论就浮现了——我母亲是对的——我应该少花点时间埋头读书。


This is just one of many possible examples. So the next time you or a loved one are faced with a health challenge, whether it's obesity or diabetes, an autoimmune disorder, or a knee or back injury, I encourage you to think about what an ultimate perspective can contribute. 

这只是许多可能例子中的一个。下次,当你或你亲爱的人面临健康上的难题时,不论是肥胖或糖尿病、自体免疫疾病,或膝盖或背部受伤,我都鼓励你去想想最终观点能提供什么见解。


Understanding that your health is affected not just by what's going on in your body right now, but also by your genetic inheritance, culture and history, can help you make more informed decisions about predispositions, risks and treatments.

若你能知道你的健康不仅会受到你的身体现状所影响,也会受到基因遗传、文化、历史的影响,也许你就能根据更多信息来做出和体质、风险,及治疗相关的决策。


As for me, I won't claim that an evolutionary medicine perspective has always directly influenced my decisions, such as my choice of spouse. It turned out, though, that not following the traditional practice of marrying within the Jewish community ultimately worked in my favor genetically, reducing the odds of me having a baby with Tay-Sachs. 

至于我,我不会宣称演化医学观点向来都会直接影响我的决策,比如我对配偶的选择。不过,结果发现,不遵循传统做法嫁给犹太族群的人,最终反而在基因方面对我有好处,减少我生出泰萨氏症宝宝的机率。


It's a great example of why not every set of Ashkenazi parents should hope that their daughter marries "a nice Jewish boy."

这是个很好的例子,说明为什么阿什肯纳兹父母不应该希望他们的女儿嫁给「一个犹太好男孩」。


More importantly, though, the experience of learning about my own genes taught me to think differently about health in the long run, and I hope sharing my story inspires you to do the same.

不过,更重要的是,了解我自己基因的这段经历教导我如何用不同的方式看待长期的健康,希望藉由分享我的故事,也能鼓舞大家这么做。


Thank you.

谢谢


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