《优雅的守卫者：人类免疫系统的故事》

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The COVID-19 pandemic has sparked intense interest in and great questions about the immune system. Why would a virus kill some people while having little or no apparent effect on others—even those of similar age and background? What’s happening inside the body when it gets exposed to a novel virus? What happens when a vaccine gets injected into the arm? What is herd immunity? And so on.
新冠肺炎大流行引发了人们对免疫系统的强烈兴趣和巨大疑问。为什么一种病毒可以杀死一些人，而对其他人（即使是年龄和背景相似的人）几乎零影响或没有明显影响？当人体接触到一种新型病毒时，体内会发生什么？当疫苗注射到手臂上时会发生什么？什么是群体免疫？诸如此类。
If you’re asking these kinds of questions, you should pick up An Elegant Defense: The Extraordinary New Science of the Immune System, by Pulitzer Prize–winning New York Times reporter Matt Richtel. He wrote the book before the pandemic, which means there’s nothing here about COVID-19 or the virus that causes it. Nonetheless, Richtel’s timing was good, because his book gives you all the context you need to understand the science of immunity.
如果你在问这些问题，你应该读一读《优雅的守卫者：人类免疫系统的故事》。一本由获得普利策奖的《纽约时报》记者马特·里克特所写的书。他在新冠疫情之前就完成了这本书，这意味着本书里没有任何关于新冠疫情或导致疫情的病毒的内容。尽管如此，里克特出版此书的时机很好，因为这本书为你提供了理解免疫科学所需的所有背景知识。

Even though I dropped out of college, I really enjoy reading textbooks. But I know most people who don’t have a degree in immunology prefer books with a story that brings scientific concepts to life. That’s exactly how Richtel constructs this book. He anchors it in the tales of four real people whose health challenges illustrate the immune system’s features and bugs. The most poignant of these is the story of Richtel’s lifelong friend Jason Greenstein, a traveling salesman who was diagnosed with Hodgkin’s lymphoma. (I came to know this form of cancer all too well when my friend and Microsoft co-founder, Paul Allen, was diagnosed with it while we were working together. He died in October 2018 of a different form of cancer.)

尽管我从大学退学了，我还是很喜欢阅读课本。但我知道大多数没有免疫学学位的人更喜欢能够把科学概念以故事形式鲜活呈现出来的书。里克特就是用这样的形式构建这本书的。他的书围绕四个真实人物的故事，他们各自健康所受到的挑战阐明了免疫系统的特点和缺陷。其中最令人心酸的故事来自里克特一生的好朋友杰森·格林斯坦（Jason Greenstein）。他是一名经常出差的推销员，被诊断出患有霍奇金淋巴瘤。（我对这种癌症的认识已经非常透彻，因为我的朋友、也是微软的联合创始人保罗·艾伦，在我们一起工作时就被诊断出患有这种癌症。他于2018年10月因另一种癌症去世。）

In the process of reading about the four people in An Elegant Defense, you absorb quite a lot of useful and interesting science. For example, you’ll learn about all the key components of the immune response … the ways pathogens can outsmart our defenses … how women’s heightened immune systems lead to longer life on average … how sleep, meditation, and exercise improve immune function … why the pursuit of immortality is a fool’s errand … and why following the “five second rule” for eating food that falls on the floor is actually a healthy thing to do.

在阅读《优雅的守卫者》四人故事的过程中，你将吸收不少有用且有趣的科学知识。例如，你将了解免疫反应的所有关键组成部分；病原体如何战胜我们的防御系统；女性更强大的免疫系统如何使其平均寿命更长；睡眠、冥想和运动如何能改善免疫功能；为什么追求永生是一件傻事；以及为什么遵循“五秒法则”吃掉在地上的食物实际上是一个健康的选择。

Most important, you’ll come away with a much better understanding of our immune system’s awesome complexity—and the delicate, even precarious, tradeoffs inherent in its workings.

最重要的是，你会更好地理解人体免疫系统惊人的复杂性，及其运转过程中微妙的、甚至不稳定的内在平衡。

Millions of years of evolution have produced an immune system with multiple ingenious mechanisms for detecting and killing invaders, even ones it has never seen before. But seek and destroy is less than half of the story. Since the 1980s, immunologists have learned that the immune system is tuned to find a balance “between attacking and neutralizing real dangers and showing sufficient restraint such that its potency didn’t destroy the body,” Richtel writes. “This is what makes our defense so elegant.” In other words, evolution found a Goldilocks set point for the human immune system. When it’s working well, it’s aggressive enough to fend off most invaders but not so powerful that it’s constantly attacking its own cells.

数百万年的进化已经产生出一个利用多种巧妙机制探测并杀死入侵者的免疫系统，它甚至可以消灭自己从未见过的入侵者。但寻找和毁灭的功能还不到故事的一半。自20世纪80年代以来，免疫学家已经认识到，免疫系统已经调试到可以“在攻击与中和真正的危险之间找到一个平衡点，并显示出足够的克制，使其力量不会造成对身体的破坏”。里克特写道：“这就是为什么我们的免疫系统如此优雅。”换句话说，进化为人类的免疫系统找到了一个黄金平衡点。当它运作良好时，它的攻击性足以抵御大多数入侵者，但它不会强大到持续攻击自身的细胞。

One of the most exciting developments in all of science and medicine is our growing ability to tweak this balance in precise ways—an area I track closely and that Richtel covers well. In the course of telling the story of his friend Jason Greenstein’s cancer, Richtel describes effective new treatments that help our immune systems target our own cells that have gone rogue. Through the stories of lupus patient Merredith Branscombe and rheumatoid arthritis patient Linda Segre, Richtel helps us understand new drugs that tamp down the immune system for those who suffer from debilitating autoimmune disorders.

在所有科学和医学领域中，最令人兴奋的发展之一是我们不断提高精确调整这一平衡的能力——这是我密切跟踪的一个领域，也是里克特颇有建树的领域。在讲述他的朋友杰森·格林斯坦患癌故事的过程中，里克特描述了一些有效的可以帮助免疫系统瞄准已失控细胞的新疗法。通过狼疮患者梅雷迪思·布兰斯科姆（Merredith Branscombe）和类风湿性关节炎患者琳达·塞格（Linda Segre）的故事，里克特帮助我们认识了一些新的药物，这些药物可以为那些患有致衰性自身免疫紊乱症的患者抑制免疫系统。

These treatments fall into a class of drugs known as “biologics,” which now make up more than a quarter of the entire pharmaceutical market. Traditional medicines are based on small molecules with relatively simple chemical structures. Biologics, in contrast, are derived from living cells and are much more complex in structure, making them expensive to manufacture and a big factor in the rising costs of health care. What makes them so appealing to doctors and patients is that they don’t go everywhere in the body; they target and modulate specific chemicals or cells at the core of the immune system’s responses. Therefore, they’re usually less toxic and more effective than traditional drugs.

这些疗法属于一类被称为“生物制剂”的药物，目前占整个医药市场的四分之一以上。传统药物以小分子为基础，化学结构相对简单。相比之下，生物制剂是从活细胞中提取出来的，结构复杂得多，制造成本昂贵，也是导致医疗成本上升的一个重要因素。它们对医生和病人有如此吸引力的原因是，它们不会进入身体里的每个部分，而是瞄准并调节对免疫系统反应起核心作用的特定化学物质或细胞。因此，它们通常比传统药物毒性更小、疗效更好。

The best-known example of this type of drug is Humira. I have friends who take it and describe it in glowing terms compared to other treatments they’ve been prescribed. It’s made up of synthetic antibodies that dial down the production of a protein that’s thought to be at the root of a dozen major autoimmune disorders, including Crohn’s disease and ulcerative Colitis. (Incidentally, the term monoclonal antibody, which includes drugs like Humira, is abbreviated “mab,” which is why the generic name of so many new drugs ends in that suffix. You’ll notice it in most of the pharmaceutical ads you see on TV or in print.)

这类药物中最有名的一例药品叫做修美乐（Humira）。我有些朋友服用过这种药物，与他们曾遵医嘱接受的其他治疗方法相比，他们唯独对它赞不绝口。它由合成抗体组成，这些抗体可以减少一种蛋白质的产生，这种蛋白质被认为导致了一些主要的自身免疫疾病，包括克罗恩病和溃疡性结肠炎。（顺便说一句，单克隆抗体这一术语，其中包括诸如修美乐等药物，缩写为“mab”，这就是为什么这么多新药的通用名都以这个后缀结尾。在电视或印刷品上看到的大多数药品广告中，你都会注意到这一点。）

We’re just at the beginning of the mab revolution. For example, as scientists develop ways to make monoclonal antibodies cheaper and easier to administer, they could help fight diseases that disproportionately affect people in poor countries. I’m also excited about their potential for sparking advances in treatments for Alzheimer’s disease, which my dad had for years before he died  last fall. The immune system and the inflammation that it produces may well play key roles in neurodegenerative disease.

我们才刚刚开始单克隆抗体革命。例如，随着科学家们研究出使单克隆抗体更便宜且更易于使用的方法，它们可能有助于抗击那些着重影响贫困国家人口的疾病。我也对它们在治疗阿尔茨海默症方面的潜力感到兴奋，我父亲在去年秋天去世前已患这种疾病很多年。免疫系统及其产生的炎症反应，在神经退行性疾病中很可能起着关键作用。

Back in simpler, pre-COVID-19 times, I read and reviewed Dr. Siddhartha Mukherjee’s The Gene: An Intimate History. An Elegant Defenseleft me with the same sense of awe I had when I read The Gene. I marvel over the intricacy and sophistication of the systems that make up the human body. Now that I’ve read An Elegant Defense, I have a deeper, more nuanced appreciation for the system that is at the core of humanity’s fight against COVID-19 and everything our foundation’s Global Health program is trying to do.

在更简单的前新冠疫情时代，我阅读了悉达多·穆克吉博士的《基因传：众生之源》并写了书评。《优雅的守卫者》让我有了读《基因传》时的那种敬畏感。我不禁惊叹于人体系统构成的错综复杂。读完《优雅的守卫者》之后，对于人类对抗新冠病毒的这一核心系统，以及对于我们基金会全球健康项目正在做的一切工作，我都有了更深刻、更细致入微的理解。