Understanding Diabetes—and Paying for It
By Jerome Groopman 杰罗姆·格鲁普曼
Advances in our knowledge of the causes of diabetes, and in our ability to treat the disease, have long been hampered by racial prejudice and exorbitant drug prices.
我们对糖尿病病因的认识和治疗能力的进步长期以来受到种族偏见和过高的药物价格的阻碍。
On April 9 of this year, The New York Times featured an obituary for Arthur D. Riggs, a scientist likely unknown to most readers. Riggs’s career was largely spent at the City of Hope National Medical Center in Duarte, California, where he discovered how to use recombinant DNA technology—which brings together genetic sequences from multiple sources—to convert bacteria into factories that produce hormones for clinical use. Among his notable successes was the creation of artificial human insulin. “We chose insulin because it looked doable, and there was a need,” Riggs recalled in an interview last year. “At the time, diabetics were being treated with cow insulin because there was no source of human insulin. And cow insulin resulted in a high rate of allergic reactions.” 今年4月9日，《纽约时报》刊登了一篇关于亚瑟·D·里格斯的讣告，他是一位大多数读者可能不熟悉的科学家。里格斯的职业生涯主要在加利福尼亚州杜阿尔特市的希望之城国家医疗中心度过，他在那里发现了如何利用重组DNA技术（将来自多个来源的基因序列结合在一起）将细菌转化为生产临床用激素的工厂。他的一项显著成就是人工合成人胰岛素。“我们选择胰岛素是因为它看起来可行，而且有需求，”里格斯在去年的一次采访中回忆道。“当时，糖尿病患者使用的是牛胰岛素，因为没有人胰岛素的来源。而牛胰岛素会导致高发生率的过敏反应。”
Hormones regulate our growth and development as well as metabolism. They may act locally on the tissue that makes them, on nearby tissues, or on distant tissues after entering the bloodstream. When we’re healthy, hormone production is controlled through feedback loops in the body, which prevents either a deficiency or an excess. The disruption of these loops can lead to disease. 激素调节我们的生长发育和新陈代谢。它们可以在产生它们的组织上发挥局部作用，也可以在附近的组织或进入血液后对远处的组织产生作用。当我们身体健康时，激素的产生通过身体内的反馈环路来控制，以防止缺乏或过量。这些环路的紊乱可能导致疾病的发生。
Insulin is made in the pancreas and secreted into the bloodstream to promote the absorption of glucose by various tissues, which use it immediately for energy or convert the glucose to glycogen (for short-term storage) or fat (for long-term storage). Insufficient insulin or bodily resistance to it causes high levels of glucose to remain in the blood, a condition formally known as diabetes mellitus. It’s believed that more than 400 million people worldwide suffer from diabetes, which can lead to blindness, nerve damage, tissue necrosis necessitating amputation, kidney failure, and stroke. Every year about four million people die from complications of the disease. 胰岛素是由胰腺产生并分泌到血液中，以促进各种组织对葡萄糖的吸收，这些组织会立即将其用作能量或将葡萄糖转化为糖原（用于短期储存）或脂肪（用于长期储存）。胰岛素不足或对其的抵抗会导致血液中葡萄糖水平升高，这种情况被正式称为糖尿病。据信全球有超过4亿人患有糖尿病，这可能导致失明、神经损伤、组织坏死导致截肢、肾功能衰竭和中风。每年约有400万人死于该疾病的并发症。
The race to produce human insulin started in the mid-1970s. Riggs and his team at City of Hope partnered with scientists at the biotech company Genentech, which had just been founded. They first attempted to synthesize somatostatin—a hormone about one tenth the size of insulin—but as soon as the bacteria produced the hormone, it fell apart. Riggs’s seminal insight was to link it to a larger protein molecule while still in the bacteria to stabilize it, and only later separate the two. Within a year of conquering somatostatin in 1977, Riggs’s group did the same with human insulin. In 1982 a commercial product, Humulin, was approved by the Food and Drug Administration. 人类胰岛素的生产竞赛始于20世纪70年代中期。里格斯和他在希望城市的团队与刚刚成立的生物技术公司Genentech的科学家合作。他们最初尝试合成生长抑素——一种比胰岛素小十分之一的激素——但是一旦细菌产生了这种激素，它就会分解。里格斯的重要发现是在细菌中将其与一个较大的蛋白质分子连接起来以稳定它，然后再将两者分离。在1977年征服生长抑素的一年内，里格斯的团队也成功合成了人类胰岛素。1982年，一种商业产品Humulin获得了美国食品和药物管理局的批准。
“The discovery made Genentech, and Dr. Riggs, rich,” the Times obituary noted. “But unlike many of his fellow biotech pioneers, he declined the opportunity to make even more money working in the for-profit sector; he was under contract to Genentech, but after that arrangement ended in 1984, he returned to City of Hope full time.” For fifty years he lived in the same modest house. Last year, when he announced a $100 million donation to City of Hope, it was revealed that he had already given $210 million to the hospital anonymously. 《时代》的讣告指出：“这一发现使得吉尼泰克公司和里格斯博士致富。但与许多同行的生物技术先驱不同的是，他拒绝了在营利部门工作赚更多钱的机会；他与吉尼泰克公司签有合同，但在1984年合同结束后，他全职回到了希望之城医院。”五十年来，他一直住在同一所朴素的房子里。去年，当他宣布向希望之城医院捐赠1亿美元时，人们才知道他已经匿名捐赠了2.1亿美元给这家医院。
Perhaps Riggs’s humble origins shaped his values. He was born in 1939 in Modesto, California. His family lost their farm in the Depression, and his father, who had only an eighth-grade education, moved them to San Bernardino, where he built and operated a trailer park. Riggs’s mother, a nurse, encouraged her son’s interest in science, buying him a chemistry set and ensconcing him in the library. He didn’t feel the need to seek the spotlight with his philanthropy. Gratification came from improving the lives of people through science. 或许里格斯的卑微出身塑造了他的价值观。他于1939年出生在加利福尼亚州莫德斯托市。他的家庭在大萧条中失去了农场，他的父亲只受过八年级的教育，将他们搬到圣贝纳迪诺市，建立并经营一个拖车公园。里格斯的母亲是一名护士，鼓励儿子对科学的兴趣，给他买了一个化学实验箱，并让他沉浸在图书馆中。他并不觉得有必要通过慈善事业来追求名利。他从改善人们的生活中获得满足感，而这是通过科学实现的。
Riggs is one of the many researchers discussed in Insulin—The Crooked Timber, Kersten Hall’s comprehensive account of the modern medical history of the hormone, which was first isolated in 1921. Originally trained as a molecular biologist, Hall now teaches the history of science at Leeds University. He has a personal stake in the story. During “middle age,” he writes, he began to feel lethargic and irritable, then rapidly lost weight and developed “raging thirst and a ravenous craving for sugar”: 里格斯是《胰岛素——歪曲的木材》中讨论的众多研究者之一，这是科尔斯顿·霍尔对这种激素的现代医学历史的全面描述，该激素于1921年首次被分离出来。霍尔最初接受的是分子生物学的训练，现在在利兹大学教授科学史。他对这个故事有个人的利害关系。他写道，在“中年”时，他开始感到疲倦和烦躁，然后迅速减重，并出现“极度口渴和对糖的狂热渴望”。
A series of blood tests at the hospital confirmed my hunch. There was so much sugar in my blood it was if it had turned to treacle. Poisonous compounds called ketones were raging through my system which, if untreated, would acidify my blood and eventually put me potentially into a permanent coma. My body was in a state of metabolic meltdown—brought on by the onset of diabetes. 在医院进行了一系列的血液检查后，我的直觉得到了证实。我的血液中含有大量的糖分，就像变成了糖浆一样。一种名为酮体的有毒化合物正在我的体内肆虐，如果不加以治疗，它们会使我的血液酸化，最终可能导致我陷入永久性昏迷。我的身体处于代谢崩溃的状态，这是由糖尿病的发作引起的。
There are two forms of diabetes. In type 1 diabetes, the immune system destroys beta cells, which are found in the pancreas and synthesize and secrete insulin. In type 2 diabetes, beta cells still produce insulin, but its effectiveness is compromised. Type 1 diabetes used to be called “juvenile” diabetes and type 2 “adult-onset” diabetes, though it’s now known that the former does not only appear in childhood, while young people can develop the latter. 有两种形式的糖尿病。在1型糖尿病中，免疫系统破坏了胰腺中合成和分泌胰岛素的β细胞。在2型糖尿病中，β细胞仍然产生胰岛素，但其效力受到损害。过去将1型糖尿病称为“少年”糖尿病，2型糖尿病称为“成人发病”糖尿病，但现在已知前者不仅出现在儿童时期，而年轻人也可能患上后者。
Hall assumed that, as an adult, he must have type 2, “the one which, were I to eat slightly less, drink slightly less, and run a bit more, might have some chance of being brought under control.” But he was mistaken. It was type 1: “From now on, insulin would be my constant companion—the biochemical crutch on which I would need to lean.” While patients with type 1 and type 2 diabetes both are at risk for serious health complications, type 1 diabetes can be especially hard to control without constant vigilance. Hall quotes a patient who compares it to living with a tiger: “If you look after it, and never turn your back on it, you can live with a tiger. If you neglect it, it will pounce on you and rip you to shreds.”
Little more is said about his experience with the disease. 霍尔认为，作为一个成年人，他一定是2型糖尿病，“只要我稍微少吃一点，少喝一点，多运动一些，或许有一些机会控制住它。”但他错了。他得的是1型糖尿病：“从现在开始，胰岛素将成为我不离不弃的伴侣，我需要依赖它的生化拐杖。”虽然1型和2型糖尿病患者都面临严重的健康并发症风险，但1型糖尿病在没有持续警惕的情况下特别难以控制。霍尔引用了一位患者的话，将其比喻为与老虎共同生活：“如果你照顾好它，永远不要背对它，你可以与老虎共存。如果你忽视它，它会扑向你，撕碎你。”关于他对这种疾病的经历没有多少提及。
Although Hall structures his narrative as a series of biographies of researchers, he rejects the view of scientific progress as linear, without detours and blind alleys: 虽然霍尔将他的叙述构建成一系列研究者的传记，但他拒绝了科学进步是一条直线、没有弯路和死胡同的观点
Alongside ignorance of the history of science, the particular way in which it is remembered can also be problematic. It is tempting to lay the blame for this on Sir Isaac Newton…. Newton famously said that “If I have seen further it is by standing on the shoulders of Giants.” …It conjures up an image that scientific progress is achieved by a succession of either lone geniuses or unsung pioneers far ahead of their time, whose work marks out a smooth, steady triumphant ascent to the lofty pinnacles of present-day knowledge. 除了对科学历史的无知外，对其记忆方式的特定问题也可能引发困扰。很容易将这归咎于艾萨克·牛顿爵士……牛顿曾经著名地说过：“如果我看得更远，那是因为我站在巨人的肩膀上。”……这种说法让人联想到科学进步是由一系列孤独的天才或超前时代的无名先驱所取得的，他们的工作标志着通往当今知识高峰的平稳、稳定而胜利的攀登。
I concur with Hall that “the real workings of science” are better captured by Immanuel Kant, who gives this book its subtitle: “Out of the crooked timber of humanity, no straight thing was ever made.”
In Insulin, Hall does not present 我同意霍尔的观点，他认为“科学的真正运作方式”更好地被伊曼纽尔·康德所捕捉，正是他给这本书起了副标题：“从人类扭曲的木材中，从未制造出直的东西。”在《胰岛素》中，霍尔没有提出
a tale of bold, lone geniuses or saints who set to work on improving the lot of humanity. Instead, it is a story of monstrous egos, toxic insecurities, and bitter career rivalry that at times resembles “Game of Thrones” but enacted with lab coats and pipettes, rather than chain mail and poisoned daggers. 这不是一个关于勇敢、孤独的天才或圣人努力改善人类命运的故事。相反，这是一个关于巨大的自我、有毒的不安全感和激烈的职业竞争的故事，有时候看起来更像是《权力的游戏》，只不过换成了实验室白大褂和移液管，而不是锁子甲和毒匕首。
While the discovery that diabetes is a malady of the pancreas related to the hormone insulin dates to the modern era, its symptoms have been recognized since antiquity. The Ebers Papyrus, written around 1550 BCE, refers to a therapy “to drive away the too much emptying of urine,” presumably due to excess sugar. The second-century CE physician Aretaeus of Cappadocia termed this condition “diabetes,” from an ancient Greek word that means “to siphon” or “to flow.” At the turn of the nineteenth century John Rollo, a Scottish doctor, appended mellitus to “diabetes,” from the Greek and Latin words for honey. He had been anticipated by the Hindu physician Charaka, who in the third century BCE recorded that his patients’ urine tasted sweet and that ants were attracted to what he referred to as Madhumeha, or “urine of honey.” (Diabetics’ excess glucose is excreted through the urine.) 尽管糖尿病与胰腺激素胰岛素有关的发现可以追溯到现代时代，但其症状自古代就被认识到了。公元前1550年左右写成的埃伯斯纸草提到了一种治疗方法，用于“驱散过多的尿液排出”，可能是由于多余的糖分引起的。公元二世纪的医生阿雷塔约斯·卡帕多西亚将这种病状称为“糖尿病”，源自古希腊语中的一个词，意为“倒吸”或“流动”。19世纪初，苏格兰医生约翰·罗洛在“糖尿病”后加上了“mellitus”，源自希腊语和拉丁语中的蜜糖一词。他之前已经被印度医生查拉卡预见到了，公元前三世纪，查拉卡记录下他的病人尿液味道甜，并且蚂蚁被吸引到他所称的“蜜尿”上。（糖尿病患者的多余葡萄糖通过尿液排出。）
In the nineteenth century the pathologist Paul Langerhans found clusters of cells in the pancreas that resembled small islands; they later were named islets of Langerhans. The Belgian scientist Jean de Meyer postulated that these clusters created a substance he called insuline, from the Latin for island. “The hunt was now on to demonstrate its existence,” Hall writes. “The medical rewards of isolating insulin and then applying it in therapy were boundless, for the current methods of treating diabetes did little more than delay a slow and painful death.” 在19世纪，病理学家保罗·朗格汉斯（Paul Langerhans）在胰腺中发现了一些类似小岛的细胞团，后来被命名为朗格汉斯岛。比利时科学家让·德·梅耶（Jean de Meyer）假设这些细胞团产生了一种他称之为胰岛素的物质，源自拉丁语中的“岛屿”。霍尔（Hall）写道：“现在人们开始寻找证明其存在的方法。分离胰岛素并将其应用于治疗的医学价值无限，因为目前治疗糖尿病的方法只能延缓缓慢而痛苦的死亡。”
Unlike Riggs, the Canadian Frederick Banting, who helped discover a breakthrough treatment for diabetes, is likely to be familiar to many readers. But I, for one, was not aware of his team’s contentious backstory, which contrasts sharply with that of Riggs and his cohorts at City of Hope and Genentech. Like Riggs, Banting had grown up on a farm, in rural Ontario. He first enrolled in a course in general arts at Victoria College at the University of Toronto in 1910, but he failed his French exam at the end of the academic year and soon had to abandon the arts to pursue medicine instead. Banting’s signature hypothesis was that the antidiabetic substance in the pancreas “was being destroyed by digestive enzymes,” Hall writes, which frustrated efforts to identify it. If you could isolate the islet cells and protect the insulin from the destructive enzymes, Banting posited, you could successfully extract it. 与里格斯不同，加拿大的弗雷德里克·班廷是许多读者熟悉的人物，他帮助发现了糖尿病的突破性治疗方法。但是，我个人对他的团队的争议背景并不了解，这与里格斯及其在希望之城和基因泰克的同事们形成了鲜明对比。和里格斯一样，班廷在农场长大，在安大略农村长大。他于1910年首次在多伦多大学维多利亚学院修读通识艺术课程，但在学年末他的法语考试不及格，不得不放弃艺术而转而追求医学。班廷的核心假设是胰腺中的抗糖尿病物质“被消化酶破坏”，这使得鉴定它的努力受挫。班廷提出，如果能够分离出胰岛细胞并保护胰岛素免受破坏性酶的影响，就能成功提取出胰岛素。
In 1920 Banting approached John J. R. Macleod, a professor of physiology at the University of Toronto and an authority on carbohydrate metabolism and diabetes, with his hypothesis. Macleod, as the senior clinician-scientist, appropriately offered numerous criticisms about Banting’s initial experiment. Most importantly, it lacked rigorous controls. This is how good science should work: frank challenges to experimental methods are vital to avoid misleading results. 1920年，班廷向多伦多大学的生理学教授、碳水化合物代谢和糖尿病专家约翰·J·R·麦克劳德提出了他的假设。作为资深的临床科学家，麦克劳德对班廷最初的实验提出了许多批评，这是合理的。最重要的是，实验缺乏严格的对照组。这就是良好科学的工作方式：对实验方法的坦诚挑战对于避免误导性结果至关重要。
But Banting, insecure and suspicious, took Macleod’s suggestions as personal slights. When, in 1923, the two were awarded the Nobel Prize for their discovery, Banting was enraged that Macleod was included, viewing it as “nothing short of a travesty,” Hall writes. Like the Nobel Committee, Hall sees both as responsible for the discovery and quotes Macleod’s own account of it: 但班廷不安和多疑，将麦克劳德的建议视为个人侮辱。1923年，当两人因他们的发现而获得诺贝尔奖时，班廷对麦克劳德的包括感到愤怒，认为这是“一种荒谬的行为”，霍尔写道。与诺贝尔委员会一样，霍尔认为两人都对这一发现负有责任，并引用了麦克劳德自己的描述：
Dr. Banting deserves complete credit; if he had not contributed this idea and undertaken to test it experimentally, the discovery of Insulin would probably not as yet have been made. On the other hand, with the knowledge which he possessed of the methods for attacking such a problem he could certainly not have made such rapid progress without careful guidance and assistance. 班廷博士应该得到完全的赞誉；如果他没有贡献这个想法并进行实验测试，胰岛素的发现可能至今仍未实现。另一方面，凭借他对解决这类问题的方法的了解，如果没有仔细的指导和协助，他肯定无法取得如此快速的进展。
Banting’s resentment of the older scientist was misconceived. “But for Macleod,” Hall writes, “Banting may have remained a struggling GP in provincial Ontario and never taken those first steps on the road to the Nobel Prize.” 班廷对那位年长科学家的怨恨是误解的。霍尔写道：“如果没有麦克劳德，班廷可能仍然是安大略省一个辛苦奋斗的普通医生，从未踏上通往诺贝尔奖的第一步。”
Further advances in our understanding of insulin were made in the 1940s, when the Cambridge-trained chemists Archer Martin and Richard Synge were recruited by a branch of the British government to decipher the protein composition of wool, an important economic resource for the United Kingdom. Working in a converted stable in West Yorkshire, they developed a method to separate proteins known as partition chromatography. Their methodological breakthrough led to the discovery that all proteins, including those found in wool, are composed of ordered sequences of amino acids. Later, Hall writes, the method was used to show that insulin had a precise chemical structure; it also laid the foundation for modern molecular biology by offering “the first hint at how DNA carries the genetic message,” since DNA codes for the ordered sequence of amino acids. Martin and Synge were awarded the Nobel Prize in Chemistry for their development of partition chromatography in 1952 and, unlike Banting and Macleod, seem to have had an amicable partnership. Hall offers many details about Martin’s eccentric personality: a creative genius who ate only certain foods (never fish, no fruit besides apples), he enjoyed sunbathing nude with his girlfriend on Synge’s balcony, drawing complaints from neighbors and a visit from the local constabulary. 在20世纪40年代，我们对胰岛素的理解取得了进一步的进展。当时，剑桥培养的化学家阿彻·马丁和理查德·辛奇被英国政府的一个部门招募，以解析羊毛的蛋白质组成，这对于英国来说是一个重要的经济资源。他们在西约克郡的一个改造过的马厩里工作，开发出了一种称为分区色谱的蛋白质分离方法。他们的方法突破了方法论，发现了所有蛋白质，包括羊毛中的蛋白质，都由有序的氨基酸序列组成。霍尔后来写道，这种方法被用来显示胰岛素具有精确的化学结构；它还为现代分子生物学奠定了基础，因为DNA编码了有序的氨基酸序列，这是“关于DNA如何携带遗传信息的第一个线索”。马丁和辛奇因为他们在1952年开发分区色谱技术而获得了诺贝尔化学奖，并且与邦丁和麦克劳德不同，他们似乎有着友好的合作关系。 霍尔提供了许多关于马丁古怪个性的细节：他是一个创造天才，只吃特定的食物（从不吃鱼，除了苹果之外不吃水果），他喜欢和女友在辛格的阳台上裸晒，引起了邻居的抱怨和当地警察的拜访。
Hall notes that when, in the 1970s, Riggs partnered with the ambitious cloning maven David Goeddel at Genentech to be the first to synthesize human insulin, they faced “vocal protest and opposition from a public and media frightened by this new technology.” Indeed, activists were filled with the delusional belief that modern-day Frankensteins, not lifesaving hormones, would be cloned from recombinant DNA laboratories. Fortunately, this delusion has evaporated, and the technology is widely used to produce not only insulin but humanized growth hormone and follicle-stimulating hormone, as well as clotting proteins to treat hemophilia. 霍尔指出，在20世纪70年代，里格斯与雄心勃勃的克隆专家大卫·戈德尔合作，成为首批合成人类胰岛素的人，他们面临着“公众和媒体对这项新技术感到恐惧的强烈抗议和反对。”的确，活动人士满怀幻想地认为，现代版的弗兰肯斯坦将从重组DNA实验室中克隆出来，而不是拯救生命的激素。幸运的是，这种幻想已经消失，这项技术被广泛用于生产胰岛素、人源生长激素、促卵泡激素以及治疗血友病的凝血蛋白。
Efforts are underway to replace injected insulin with insulin-producing cells created from human embryonic stem cells, which could then be transplanted into patients. This would allow the body to resume producing its own insulin, and essentially be a cure for type 1 diabetes. Douglas Melton, a developmental biologist at Vertex Pharmaceuticals whose two children have type 1 diabetes, is refining the process in anticipation of clinical trials. A single patient treated this way has had excellent control of his blood glucose levels for more than a year without any insulin injections. The use of sources like discarded embryos from in vitro fertilization treatment, however, could become restricted, depending on Supreme Court rulings and which party controls Congress. 正在努力将注射胰岛素替换为由人类胚胎干细胞制造的胰岛素产生细胞，然后将其移植到患者体内。这将使身体能够恢复自己产生胰岛素，从而基本上治愈1型糖尿病。道格拉斯·梅尔顿是一位发育生物学家，就职于维特克斯制药公司，他的两个孩子患有1型糖尿病，他正在完善这一过程以准备进行临床试验。以此方式治疗的单个患者已经在一年多的时间里完全控制了血糖水平，而无需注射任何胰岛素。然而，根据最高法院的裁决和哪个政党控制国会，使用类似体外受精治疗中废弃的胚胎等资源可能会受到限制。
Amemorable scene in the Woody Allen movie Annie Hall depicts a Jewish family in Brooklyn sitting around the dinner table fixating on illness—“His wife has diabetes!” “Diabetes! Is that an excuse?” “Old Moskowitz, he had a coronary”—satirically invoking a stereotype of Jews as prone to the malady and dilating on its consequences. But as Arleen Marcia Tuchman convincingly shows in her illuminating book Diabetes: A History of Race and Disease, what the film casts as humor, lampooning supposedly neurotic American Jews, has deep roots in the medical establishment’s dark bigotry concerning the origins of the disorder. And the bigotry directed at Jews was redirected in various ways over the past century, making diabetes a case study in how societal prejudice distorts medical science. 在伍迪·艾伦的电影《安妮·霍尔》中，有一个令人难忘的场景描绘了一个犹太家庭在布鲁克林的餐桌旁围坐在一起，专注于疾病问题——“他妻子得了糖尿病！”“糖尿病！那是借口吗？”“老莫斯科维茨，他得了冠心病”——讽刺地揭示了犹太人易患这种疾病的刻板印象，并详细阐述了其后果。然而，正如阿琳·玛西娅·图赫曼在她的启发性著作《糖尿病：种族与疾病的历史》中所表明的那样，电影所描绘的幽默，嘲笑所谓神经质的美国犹太人，实际上深深扎根于医学界对这种疾病起源的黑暗偏见。而针对犹太人的偏见在过去一个世纪中以各种方式得到了转移，使得糖尿病成为了一个研究社会偏见如何扭曲医学科学的案例。
Tuchman notes that Germany at the turn of the twentieth century was the acme of clinical science, and its medical literature termed diabetes Judenkrankheit, or a “Jewish disease.” In 1916 Elliott P. Joslin, the leading diabetes specialist in the US, wrote that “the frequency with which diabetes occurs in the Jewish race is proverbial.” Was this in fact true? “Perhaps,” Tuchman answers. “Jewish immigrants who had fled poverty and hunger in Eastern Europe tended to eat better in their new land, and this may have increased their chances of putting on a lot of weight and thus of developing the disease.” While extreme obesity is a clear major risk factor, she cautions that an ample diet does not necessarily result in diabetes, and most overweight individuals are not diabetic. In addition, diabetes has a strong familial incidence, indicating a genetic predisposition to it. 图奇曼指出，二十世纪初的德国是临床科学的巅峰，其医学文献将糖尿病称为“犹太病”。1916年，美国领先的糖尿病专家埃利奥特·P·乔斯林写道，“糖尿病在犹太人种中的发生频率是众所周知的。”这是事实吗？图奇曼回答说：“也许是的。逃离东欧的贫困和饥饿的犹太移民在新的土地上往往吃得更好，这可能增加了他们发胖和患病的机会。”虽然极度肥胖是明显的主要风险因素，但她警告说，丰盛的饮食并不一定导致糖尿病，大多数超重的人并不患糖尿病。此外，糖尿病具有很强的家族发病率，表明存在遗传易感性。
Indeed, there was a dearth of evidence to support claims connecting Jews and diabetes. Instead, Tuchman writes, physicians “simply repeated what everyone else was saying. And those who did offer up numbers and patterns offered statistics that were often unreliable.” Furthermore, the definition of “Jew” was usually ambiguous. Did it include the Sephardim who originated from Spain and Portugal? Or only Ashkenazi Jews? If the latter, were they the German Ashkenazi, who first arrived in America in the 1830s and were generally wealthy by the end of that century? Or the millions of Eastern European Ashkenazi Jews, primarily from the Russian Empire, who began to arrive in the 1880s and were poor? “It is…impossible to answer the question of whether Jews had a higher rate of the disease,” Tuchman concludes. 事实上，缺乏证据来支持将犹太人与糖尿病联系起来的说法。图赫曼写道，医生们“只是简单地重复着其他人的说法。而那些提供数字和模式的人所提供的统计数据往往不可靠。”此外，“犹太人”的定义通常含糊不清。它是否包括起源于西班牙和葡萄牙的西班牙犹太人？还是只包括亚述犹太人？如果是后者，是指最早在19世纪30年代抵达美国并且到世纪末通常富有的德国亚述犹太人吗？还是指从19世纪80年代开始抵达美国并且贫穷的数百万东欧亚述犹太人，主要来自俄罗斯帝国？“无法回答犹太人是否患病率更高的问题，”图赫曼得出结论。
But we can explore why, despite the highly ambiguous nature of the data—an ambiguity acknowledged at the time—virtually no one questioned the fundamental link between Jews and diabetes during the first three decades of the [twentieth] century. 但是我们可以探讨一下为什么在20世纪的前三十年间，尽管数据的高度模糊性被当时承认，几乎没有人对犹太人和糖尿病之间的基本联系提出质疑。
It came down to negative stereotypes of the “Hebrew race” as loving “high living” and parties where they “congregate together and have frequent and irregular meals.” William Osler, often called the father of modern medicine, added that Jews had a “neurotic temperament,” which he claimed made them vulnerable to the disease, whether because of, Tuchman writes, “nervous strain, nervous temperament, nervous derangements, nervous tension, or the nerve-shattering aspects of city life.” Haven Emerson, a professor of preventive medicine at Columbia’s College of Physicians and Surgeons and a former commissioner of health for the city of New York, “put the onus on Jews for spreading what he called ‘this great luxury disease.’” Here Tuchman links the characterization to “negative images of the Jew as the embodiment of much that was wrong with modernity.” Even Jewish doctors, who denied racial traits, anticipated the Annie Hall scene as they ascribed unbridled nervousness to Jews, drawing on the Oslerian belief that diabetes and the nervous system were intimately connected. This “labile nervous system” was postulated to be an outgrowth of “the long history of suffering, which the Jewish people have had to endure over thousands of years.” 这归结于对“希伯来种族”的负面刻板印象，认为他们喜欢“奢华生活”和“聚集在一起，频繁而不规律地进餐的派对。”被誉为现代医学之父的威廉·奥斯勒还称犹太人具有“神经质的气质”，他声称这使得他们易受疾病侵袭，可能是因为“神经紧张、神经质、神经紊乱、神经紧张或城市生活中令人神经崩溃的方面”，如图曼所写。哥伦比亚大学医学院的预防医学教授、纽约市前卫生专员哈文·爱默生将“这种豪华病”传播的责任归咎于犹太人。图曼在这里将这种描述与“犹太人被负面形象所代表，成为现代性的诸多问题的体现”联系起来。即使是犹太医生也否认种族特征，但他们也预见到了《安妮·霍尔》中的场景，将无节制的神经紧张归因于犹太人，借鉴了奥斯勒的观点，即糖尿病和神经系统密切相关。 这个“易变的神经系统”被认为是“犹太人民在几千年的历史中所遭受的长期苦难的产物。”请将文本翻译成简体中文： “Translate the text to Simplified Chinese.”
Blacks were also victims of bigotry on the part of the medical establishment and its understanding of diabetes. First they were believed immune to the disorder, which was deemed a “disease of civilization”; African Americans, Tuchman writes, were stereotyped by prominent American physicians as “dull” and “happy” (when not violent) and thus distinctly “uncivilized.” Poor Blacks were thought not “advanced” enough to suffer from diabetes, and middle-class Blacks supposedly “did not exist.” While Tuchman doesn’t offer statistics on how this belief in “racial immunity” to diabetes affected the care African American patients received, we can presume they suffered as a result of it. Only later in the twentieth century, when data on the malady were derived from epidemiological studies in northern cities, did the medical establishment abandon the bigoted view that Black people were somehow immune to diabetes. 黑人也是医疗机构对糖尿病的偏见的受害者。首先，他们被认为对这种疾病免疫，被视为“文明病”。托奇曼写道，美国著名医生将非裔美国人刻板地刻画为“迟钝”和“快乐”（当然不是暴力），因此明显“未开化”。穷黑人被认为不足以“进步”到患糖尿病的程度，而中产阶级黑人据说“不存在”。尽管托奇曼没有提供关于这种“种族免疫力”对非裔美国人患者护理的统计数据，但我们可以推断他们因此而受苦。直到20世纪后期，当关于这种疾病的数据来自北方城市的流行病学研究时，医疗机构才放弃了黑人对糖尿病有某种免疫力的偏见。
Athird group whose relationship to diabetes was distorted by prejudice was the diverse peoples known collectively as Native Americans. In 1962 the geneticist James Neel hypothesized the existence of a “thrifty gene,” which offered an evolutionary explanation for how a negative trait might persist at a high frequency in the human gene pool. Neel posited that a “thrifty genotype” might have helped early humans survive periods of feast and famine by increasing their ability to store fat when sufficient food was available. In the modern era, with ready access to food no longer an issue for most people, this efficient storage of fat fostered disease. 一个被偏见扭曲了与糖尿病关系的第三个群体是被统称为美洲原住民的多样人群。1962年，遗传学家詹姆斯·尼尔提出了“节俭基因”的存在假设，为负面特征在人类基因库中高频率存在的进化解释提供了依据。尼尔假设，“节俭基因型”可能帮助早期人类在丰饶和饥荒时期存活下来，通过增加他们在有足够食物时储存脂肪的能力。在现代社会，对于大多数人来说，食物的便利获取已不再是问题，这种高效的脂肪储存反而促进了疾病的发生。
By the late 1970s the thrifty gene, Tuchman writes, “acquired the status of a highly plausible explanation, occasionally referred to as a theory, about why Native Americans had some of the highest rates of diabetes not only in the United States, but also in the world.” She adds, “What often goes unnoticed is that Neel did not offer his hypothesis as a way of explaining high rates of diabetes among Native Americans; in fact, he did not even mention them in his 1962 article.” Rather, he aimed to explain the nearly global distribution of diabetes. While Neel was referring to “all the peoples of the world” in his hypothesis on the origin of diabetes in early humans, 到了20世纪70年代末，节俭基因“成为了一个高度可信的解释，有时被称为理论，解释了为什么美国原住民不仅在美国，而且在全世界范围内患糖尿病的比率如此之高。”她补充道，“往往被忽视的是，尼尔并没有将他的假设作为解释美国原住民糖尿病高发率的方式；事实上，在他1962年的文章中，他甚至没有提到他们。”相反，他的目的是解释糖尿病几乎全球分布的现象。虽然尼尔在他关于早期人类糖尿病起源的假设中提到了“全世界的所有民族”，
the idea of a close link between thrifty genes and indigenous peoples has persisted until today, despite Neel’s abandonment of his own theory before his death in 1999, and despite the lack of any concrete evidence. A belief in racial difference keeps it alive. 尽管尼尔在1999年去世前放弃了自己的理论，并且缺乏任何具体证据，但关于节俭基因与土著民族之间紧密联系的观念一直持续至今。种族差异的信念使其得以延续。
Tuchman points out that while there are high rates of diabetes among the Akimel O’odham (Pima), Cherokee, and several other native populations, there are comparatively low rates among other tribes, such as the Athapascan Indians, Eskimos, and Diné (Navajo). Yet both professional and popular writers continue to assert that whites and Native Americans differ in their “experiences of the disease.” Tuchman指出，尽管Akimel O'odham（Pima）族群、切罗基族和其他几个土著人口中糖尿病的发病率很高，但与其他部落相比，如阿萨帕斯坎印第安人、爱斯基摩人和Diné（纳瓦霍族），糖尿病的发病率相对较低。然而，无论是专业作家还是大众作家都继续声称白人和美洲原住民在“患病经历”上存在差异。
Tuchman ends her book by emphasizing that, most recently, diabetes has become associated with poverty and class. Appalachia, a predominantly white region, is particularly hard-hit. The rate of diabetes in West Virginia, for example, is 10.2 percent, 3.5 percent above the national average. The recognition that diabetes is disproportionately affecting poor populations highlights how social factors as well as genetic predisposition strongly contribute to its development. That poor whites are afflicted further belies the benighted racial stereotypes that have long characterized the disorder. Since the genetic predispositions are not yet addressed by treatment, there is an opportunity to stem the rising incidence of diabetes by tackling the social factors involved. 图奇曼在她的书中强调，最近，糖尿病与贫困和阶级有关。阿巴拉契亚地区，一个以白人为主的地区，受到了特别严重的影响。例如，西弗吉尼亚州的糖尿病发病率为10.2％，比全国平均水平高出3.5％。认识到糖尿病对贫困人口的不成比例影响，突显了社会因素和遗传倾向对其发展的强烈影响。贫困的白人受到病痛的折磨，进一步证明了长期以来对这种疾病的愚昧种族刻板印象是错误的。由于目前治疗尚未解决遗传倾向的问题，因此通过解决涉及的社会因素，有机会遏制糖尿病发病率的上升趋势。
Riggs wasn’t interested in reaping money for himself from his success with humanized insulin. But since his discovery, money has become a flashpoint in the story of diabetes and insulin, which now extends from science and bigotry to the perverse realities of drug pricing and patents in the United States. The most common forms of insulin can cost ten times more in America than in any other developed country. The price of insulin has nearly tripled over the last fifteen years, according to research cited by the Endocrine Society in a 2021 statement calling for more affordable options for patients. At the outset of the Covid-19 pandemic, the American Diabetes Association found, one quarter of patients with diabetes reported self-rationing medical supplies to reduce the cost of their treatment. 里格斯对于自己在人体胰岛素方面的成功并不感兴趣于从中获利。但自从他的发现以来，金钱已经成为糖尿病和胰岛素故事中的一个争议点，这个故事从科学和偏见延伸到了美国药品定价和专利的扭曲现实。根据内分泌学会在2021年的一份呼吁提供更实惠选择给患者的声明中引用的研究，美国最常见的胰岛素种类的价格比其他发达国家高出十倍。根据美国糖尿病协会在新冠疫情爆发初期的调查，四分之一的糖尿病患者报告称他们自行限制医疗用品的使用以减少治疗费用。在过去的十五年里，胰岛素的价格几乎翻了两番。
A single vial of Humalog (insulin lispro, or fast-acting insulin), which cost $21 in 1999, cost $332 in 2019, a price increase of more than 1,500 percent. In contrast, insulin prices in neighboring Canada didn’t budge. Why? Because there’s neither a real free market nor government price controls for insulin in the United States. Rather, there is a presumed oligopoly of three drug companies—Eli Lilly, Novo Nordisk, and Sanofi—that appear to set prices in sync, with a vulnerable population of diabetics forced to pay whatever they charge for a lifesaving treatment. Our arcane patent laws allow for extended protection of insulin products without significant innovations, thereby blocking competition. The middlemen who negotiate with the drug companies, insurers, and pharmacies—so-called benefit managers—are enriched by keeping the prices high at the expense of patients. And the insulin manufacturers have a powerful lobbying arm that has kept Congress from taking action. 1999年，一支Humalog（速效胰岛素）的小瓶售价为21美元，而2019年的售价为332美元，涨幅超过1500%。相比之下，邻国加拿大的胰岛素价格没有变动。为什么呢？因为在美国，胰岛素既没有真正的自由市场，也没有政府对其价格进行控制。相反，有三家制药公司——礼来、诺和诺德和赛诺菲——被认为是寡头垄断，他们似乎协调定价，而糖尿病患者这个弱势群体被迫支付任何他们所要求的挽救生命的治疗费用。我们过时的专利法允许对胰岛素产品进行长时间的保护，而没有实质性的创新，从而阻碍了竞争。与制药公司、保险公司和药店进行谈判的中间商，即所谓的福利管理者，通过保持高价使自己获利，而患者则承担了这些费用。而胰岛素制造商则拥有强大的游说机构，使得国会无法采取行动。
The issue may be coming to a head, with the Biden administration’s Federal Trade Commission looking into price fixing and Congress asking the Government Accountability Office to investigate pharmacy benefit managers. Governor Gavin Newsom of California recently announced a $100 million initiative to produce generic insulin at cost for patients in his state; whether drug companies will seek to block this by invoking patent protection, as they have done with privately manufactured generic insulin, remains to be seen. The recently passed Inflation Reduction Act limits the monthly cost of insulin to thirty-five dollars for Medicare patients, but Republicans blocked a provision that would have done the same for privately insured diabetics, who are at grave risk of having to ration their insulin unless a remedy is implemented quickly. 问题可能即将达到顶峰，拜登政府的联邦贸易委员会正在调查价格垄断问题，国会要求政府问责办公室调查药店福利管理人。加利福尼亚州州长加文·纽森最近宣布了一个1亿美元的计划，以成本生产通用胰岛素，供其州的患者使用；药企是否会通过援引专利保护来阻止此举，就像他们对私人生产的通用胰岛素所做的那样，还有待观察。最近通过的通胀削减法案将医疗保险患者的胰岛素月费用限制在35美元，但共和党阻止了一项同样适用于私人保险糖尿病患者的规定，这些患者面临着严重的胰岛素配给风险，除非迅速采取措施，否则将不得不限制使用胰岛素。
Diabetes is a biological illness, but it should also be understood as sociological, economic, and political. Treatment is incomplete unless each dimension is addressed. 糖尿病是一种生物性疾病，但也应该从社会学、经济学和政治学的角度来理解。除非每个维度都得到关注，否则治疗是不完整的。