2017.06.23 摩门教家谱告诉我们有关癌症的情况

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WHAT MORMON FAMILY TREES TELL US ABOUT CANCER
By searching the church's famed family trees, scientists have tracked down a cancer-causing mutation that came west with a pioneer couple—just in time to save the lives of their great-great-great-great grandchildren.

By Sarah Zhang
JUNE 23, 2017

Nobody knew it then, but the genetic mutation came to Utah by wagon with the Hinman family. Lyman Hinman found the Mormon faith in 1840. Amid a surge of religious fervor, he persuaded his wife, Aurelia, and five children to abandon their 21-room Massachusetts house in search of Zion. They went first to Nauvoo, Illinois, where the faith’s prophet and founder, Joseph Smith, was holding forth—until Smith was murdered by a mob and his followers were run out of town. They kept going west and west until there were no towns to be run out of. Food was scarce. They boiled elk horns.The children’s mouths erupted in sores from scurvy.  Aurelia lost all her teeth. But they survived. And so did the mutation.


Earlier this year, I met Gregg Johnson, Lyman and Aurelia’s great-great-great-great grandson. The genetic mutation that had traveled the Mormon Trail was now in Gregg, one of hundreds of the Hinmans’ descendants in the Utah area. Gregg is 61, with blue eyes and a white goatee. He frequently travels for his job as a craftsman for Mormon temples, but Utah is still home. “I’m just a Salt Lake City boy,” he says.

The mutation that came with the Hinmans turns out to be a troublesome one. It lies dormant just long enough for people to have children and pass the mutation along, but not long enough to watch their children start their own lives. Gregg’s mother died of colon cancer at age 47. Her mother also died early of colon cancer, as did her mother. And who knows how many other relatives succumbed, stretching all the way back when the Hinmans came to Utah.

Gregg knows the history of this mutation in a gene called APC because he’s spent more than 30 years in a series of studies at the University of Utah—made possible by a vast trove of Mormon genealogy records. Detailed family trees make it easier to trace genes that cause disease. After the Hinmans and other pioneers settled in the state, the Mormon church kept records that over time became an unusually detailed and complete genealogy. In the 1970s, university researchers had the foresight to combine these genealogy records with the state cancer registry to create what ultimately became the Utah Population Database. So when scientists began suspecting a genetic cause for cancer, they went hunting through the Mormon family trees.


They found patterns of deadly inheritance:  BRCA1, one of the infamous cancer mutations, as well as mutations for cardiac arrhythmia and melanoma. And of course, they found the APC mutation behind the colon cancer in Gregg’s family. Utah became an accidental genetics laboratory. When Lyman hitched his wagon for Utah a century and a half ago, he ended up setting a course for colon cancer research.

The church of Jesus Christ of Latter-day Saints, or the Mormon church, has one of the largest genealogy databases in the world. Today, it operates a family-history library just steps from the  temple in downtown Salt Lake City, where banks of computers await visitors interested in digital genealogy records. The Church has physical records, too. They are stored on microfilm under 700 feet of rock in the climate-controlled Granite Mountain Records Vault, secured with doors so heavy they’re supposed to withstand a nuclear blast. Mormons are, by stereotype, family oriented, and this intense interest in family trees is a matter of theology.

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Mormons believe in baptism of the dead—including, in some cases, the long-dead. The baptisms are meant to give those who did not find the gospel of Jesus Christ in their mortal lives a chance at salvation, so that entire families stretching back generations might be reunited, forever together in Heaven. (This practice has attracted controversy, especially when the dead have included Holocaust victims.) The actual ceremonies are performed by proxy in temples. Members of the church line up and step forward for baptism as the name of an ancestor appears on a screen.

But first, you need names. So the Church sends crews around the world to collect records of the dead. In the 1970s, one such genealogy team looking for old parish records arrived in Parma, Italy, where a young American named Mark Skolnick was working on his Ph.D. thesis.

As luck would have it, Skolnick was using parish records to construct a genealogy database of his own. His thesis looked at how genes spread as people from different Italian villages moved and intermarried. The study was a nice “theoretical exercise,” he says, but nothing practical really came of it. Meanwhile, because he spoke Italian, Skolnick helped translate for the Mormon team that came to microfilm parish records. “I was a lowly gofer,” he says. A great many things, however, would come out of this.

When Lyman hitched his wagon for Utah a century and a half ago, he ended up setting a course for colon cancer research.
The Mormon church, Skolnick realized, was sitting on a vast trove of population genetics data. After finishing his thesis, he got a job at the University of Utah, where he set out to combine Mormon church records and cancer registry data into what would become the Utah Population Database. The genealogies and cancer records were a daunting amount of data, especially in an era when money was tight and computers were still the size of refrigerators. “It was like going from one year to the next to try to get the funding,” recalls Lisa Cannon-Albright, one of Skolnick’s graduate students at the time. They worked out of an old VA hospital building, infested with bats and painted an awful pale green.

Getting all that data into the computer was a low-tech slog. Skolnick convinced the church to let him copy 186,000 pages of family records covering all the pioneers who came on the Mormon trail. The records went back eight generations and comprised about 1.6 million people in total. A team of typists, many of them genealogy enthusiasts, turned the handwritten records into a digital database. The data entry took the equivalent of 15 person-years.

As Skolnick was casting around for projects that could use the database, he met a young gastroenterologist named Randall Burt. Having grown up in Salt Lake City, Burt had recently returned to take up a fellowship at the University of Utah. He’s a gregarious guy, with a knack for putting patients facing colonoscopies at ease. “I just think of him as a big teddy bear,” one of his former patients told me. Gregg’s mother was one of Burt’s patients. By the time of her diagnosis, it was already too late to cure her colon cancer. She died a year later.

Burt and his colleagues were seeing other families like Gregg’s, where colon cancer had cut down whole branches of the family tree. What’s more, when you looked at the young, still-healthy members of these families, their colons were also strange—covered in dozens of mushroom-like growths called polyps that can turn cancerous. The doctors called it attenuated familial adenomatous polyposis. They didn’t yet know what caused the profusion of polyps, but they reasoned if they could trace it through the family trees, they could identify who had the mutation and eventually the mutation itself.

“I can’t tell you how many reunions where I’ve been to eating corn and potato salad and talking polyps.”
In retrospect, finding a mutation whose effects are so stark does not sound difficult. And indeed, today it isn’t especially difficult. But in the early 1980s, still two decades away from the first draft of a human genome, finding a gene was hard—especially if you weren’t so sure the gene even existed. Perhaps, as many thought at the time, cancer is simply a product of lifestyle or other environmental factors. Tracing a genetic mutation back to a common ancestor is no easy task either. Family trees get exponentially bigger as you go back in time: You have two parents, four grandparents, eight great grandparents, and so on. Eight generations back, you have hundreds of ancestors. A family tree for the Mormon pioneers is more like a tangled bush.

To prove that the polyps were hereditary—rather than just the unfortunate result of say, a family living in the same house drinking the same toxic water—the researchers needed to find more families elsewhere that looked like Gregg’s.  So they went looking through the Utah Population Database. With the family trees and cancer registry data, they could identify clusters of colon cancer. Then Burt and his team hit the road with his colon screening scopes—driving through Utah but also Idaho and Wyoming, where descendants of Mormon pioneers had settled. They set up in local hospitals and spent a day looking for colon polyps in the local population. “These dairymen would come in between milking the cows, and the next day cowboys would come in,” he says. And they went to family reunions. “I can’t tell you how many reunions where I’ve been to eating corn and potato salad and talking polyps,” says Burt. They took blood for genetic tests and invited patients to schedule future colon screenings.


(Lisk Feng)
It helped that the Mormons they were studying lived up to their reputation for friendliness. “I don’t know if people told you how receptive they are to research,” says Cannon-Albright, who herself comes from a Mormon background. “People recognize what you're doing. ‘It won’t help me but it’ll help my kids and kids’ kids,’ and they were in just like that.” Participating in the study required an invasive colon screening and a blood draw. Still, she says, “Nobody ever said no.”


Slowly, after hundreds of colon screenings and blood draws, a picture began to emerge. All of the families with this profusion of polyps seemed to have the exact same mutation, which pointed to a common ancestor. Those common ancestors, we now know, are Lyman and Aurelia. It’s not clear which one of the couple had the gene, but they passed it along to at least two of their five children. In 1991, research groups in Utah and at Johns Hopkins simultaneously discovered the gene, which became known as APC.

In the decades since, this colon cancer research has kept going at University of Utah. Deborah Neklason, who took over Burt’s research after he retired, keeps a large white roll of paper in her office. She took it out when I visited and motioned me over to the big wood conference table, where she unfurled it and kept unfurling it, until half of it ran off the edge. It was the Hinmans’ pedigree on paper. Actually it was only part of it. The family had five branches: A, B, C, D, E, corresponding to each of Hinmans’ children, and this pedigree covered just branch E. Neklason found that she wanted to show me: a square with a black dot in the middle. It was Gregg—square for male, a dot to mark him as a carrier.

Neklason’s office is in the university’s Huntsman Cancer Institute, a hospital and research center founded by businessman Jon Huntsman Sr. The Huntsmans wield unusual influence even for wealthy donors—hence a recent and ugly power struggle with university administrators—and this influence is apparent even in campus geography. The university’s building climbs up the foothills on Salt Lake City’s eastern edge, and the Huntsman Cancer Institute, wrapped in green glass, sits at the campus’s highest elevation. It’s more alpine ski resort than hospital. Huntsman jokes that when cancer is cured, he’s turning it into a Ritz-Carlton. The Utah Population Database, which began in the bat-infested old VA hospital, is set to move into the Huntsman’s new wing later this year.


Last february, then Vice President Joe Biden spoke at the Huntsman to promote his cancer moonshot. The event took place in the institute’s cafeteria, though calling it a hospital cafeteria is a bit of a disservice. Bon Appetit named it one of the world’s “coolest workplace cafeterias,” thanks to the floor-to-ceiling glass that overlook the mountains around Salt Lake City. On that day though, the windows were blacked out, per the request of the Secret Service.

Gregg spoke at the event, too, and he was starstruck. (“Joe is Joe. He’s cool. I would have voted for him in a heartbeat.”) He swallowed his nervousness and began telling his family’s story, starting with his mother’s diagnosis.

After his mother’s death, Gregg began seeing Burt for regular colonoscopies. Polyps, if removed early enough, never become cancerous. Each time Gregg had a colonoscopy, he got hundreds of polyps snipped off. He’s been doing this long enough that he can hold forth about how it used to be. “It used be,” he says, “you had to drink an Imperial gallon, five quarts of saline solution, within an hour and keep it down.” He paused to grimace. “Just thinking about it now makes my skin crawl.” The prep for colonoscopies requires much less liquid now, and it tastes a lot better. Stop putting off your colonoscopy, he added, slipping into the role he often plays for his family and friends, encouraging people to get tested.


Gregg has two sons, Dan and Patrick. The mutation has a 50-50 chance of being passed on, and the laws of chance were followed perfectly in this case: Dan, the older son, has the mutation, and Patrick does not. Dan is 32 now, at the point where he’s thinking about having kids. Having watched his father live a pretty much normal life despite this ticking time bomb of a mutation has given him an equanimous outlook. “That doesn’t affect my decision at all,” he says.

In the future, Dan might not need such regular colonoscopies either. Gregg participated in a recent clinical trial using two drugs called sulindac and erlotinib to prevent polyps in the duodenum, a section of the small intestine that is difficult to reach with a scope. It worked beautifully for shrinking polyps, though it did have some side effects that are being ironed out in a follow-up trial. Gregg’s digestive tract was the “poster child” for the initial study. “The advancements are amazing,” says Dan, “It's so cool, even in the time that Dad's started with this.” In this era of hype about precision medicine, Gregg’s family shows its power—as it’s already being applied.

The particular mutation in Gregg’s family only accounts for a tiny sliver of colon cancers in the U.S., but the research on his family may have a much larger impact. The APC gene is known as a tumor suppressor gene. Gregg’s family members are born with a mutation in APC, but it is also possible and common to acquire a mutation in the APC gene over one’s lifetime, through random chance or environmental exposure. Eighty percent of all colon cancers have such a mutation. “It’s such an early step in colon cancer, it’s perfect target for prevention,” says Neklason. If something can prevent colon cancer in this high-risk family, then perhaps it could prevent it in the rest of us too. That’s in part why the clinical trial results were so exciting.


The early successes of the Utah Population Database with cancer demonstrated the power of genealogy. Geneticists elsewhere have since used family trees to study other inherited diseases. In Iceland, where the population is small and isolated and ancestry can be traced back hundreds of years, a 20-year-old company called deCODE has collected samples from about half of all Icelanders and published a suite of papers. Researchers have also recently started exploring the massive crowdfunded genealogies that are so popular online.

The Utah Population Database is growing, too. It now has medical records from Utah’s two major healthcare providers as well as state birth and death records. More recently, it inked a deal with the Mormon church to add 100 million new records from the church’s genealogy into the database. Neklason hopes to use those records to go even further back and find connections between the Hinmans and a dozen or so families  in New York, Texas, and other states that have since been discovered  with the same colon cancer mutation. But it’s difficult work, because older pre-Mormon pioneer records are less reliable. Husbands, for example, often remarried after their first or even second wives died and it can be difficult to tell who gave birth to which child. (Mothers are well-documented in the Mormon records, and the researchers tracing the Hinmans’ descendants did not actually encounter polygamy, which was practiced by only a minority of men in the 19th century.) A connection Neklason originally thought she found between the Utah and New York families is ambiguous because of conflicting information over which of two wives is the mother of a child that could have linked the two branches.

“I feel like a bit of an insider even though I’m just a lab rat.”
Thirty years into the university’s colon cancer research, Gregg can tell the story as well as anyone. He’s seen its entire arc. Skolnick and Burt are both retired now. Skolnick spends half his time in San Diego and the other half in Parma, Italy—where he met those Mormon genealogy hunters and his Italian wife. Burt is retired, too. He’s currently living in Frankfurt, Germany, where he advises on the medical care of Mormon missionaries in Europe. Gregg has been around as long as anyone.“I feel like a bit of an insider even though I’m just a lab rat,” says Gregg. That’s why he was speaking in front of Biden that day.

The event’s organizers had blown up part of his family tree on the screen behind him, a small section of what Neklason had showed me in her office. His mother and grandmother’s generations were full of black squares and circles, indicating deaths from colon cancer. His generation, now reaching their 60s, were all still alive and cancer-free thank to their colonoscopies. “Right there just seeing the chart, it was like holy cow it really does work,” Gregg later recalled to me in his living room.

His mother, Sandra, died in 1983—before genetic testing, before anyone knew anything about the APC mutation lurking in her family for so long. Gregg had gotten married just a few months before. She was already sick at his wedding. She would not get to see her grandsons, the first of whom was born a year later. “From my standpoint,” he told me, “I’ve outlived her by about 15 years.” He said this as he leaned back into his chair, his grandson’s train tracks sprawled on the coffee table in front of us.

Sarah Zhang is a staff writer at The Atlantic.








摩门教家谱告诉我们有关癌症的情况
通过搜索教会著名的家谱，科学家们追踪到了一种致癌突变，这种突变随着一对先锋夫妇来到了西部--正好可以挽救他们的曾曾曾孙的生命。

作者：莎拉-张
2017年6月23日
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当时没有人知道，但这种基因突变是随着欣曼家族的马车来到犹他州的。莱曼-辛曼在1840年发现了摩门教信仰。在一股宗教热潮中，他说服他的妻子奥蕾莉亚和五个孩子放弃他们在马萨诸塞州有21个房间的房子，去寻找锡安。他们首先去了伊利诺伊州的纳乌，那里是该信仰的先知和创始人约瑟夫-斯密的聚集地--直到斯密被暴徒杀害，他的追随者被赶出小镇。他们一直向西走，直到没有城镇可以被赶走。食物很匮乏。他们煮麋鹿角。孩子们的嘴因坏血病而长出了溃疡。 奥瑞莉娅的牙齿都掉光了。但他们活了下来。这种突变也是如此。


今年早些时候，我见到了格雷格-约翰逊，莱曼和奥蕾莉亚的曾曾曾曾孙。曾经走过摩门径的基因突变现在出现在格雷格身上，他是犹他州地区数百名欣曼家族的后裔之一。格雷格今年61岁，蓝眼睛，留着白色山羊胡。他经常为摩门教寺庙的工匠工作而出差，但犹他州仍然是他的家。"我只是一个盐湖城的男孩，"他说。

伴随着Hinmans家族而来的突变被证明是一个麻烦的突变。它休眠的时间刚好够人们生孩子并把突变传给他们，但还不够长，不能看着他们的孩子开始自己的生活。格雷戈的母亲在47岁时死于结肠癌。她的母亲也早早死于结肠癌，她的母亲也是如此。谁也不知道还有多少其他的亲戚屈服了，一直延伸到欣曼家族来到犹他州的时候。

格雷格知道这种叫做APC的基因突变的历史，因为他花了30多年时间在犹他大学进行了一系列研究，这是由大量的摩门教家谱记录促成的。详细的家谱使我们更容易追踪导致疾病的基因。在辛曼家族和其他拓荒者在该州定居后，摩门教会保留了一些记录，随着时间的推移，这些记录变成了异常详细和完整的家谱。在20世纪70年代，大学研究人员有远见，将这些家谱记录与州癌症登记处结合起来，创建了最终成为犹他州人口数据库。因此，当科学家们开始怀疑癌症的遗传原因时，他们就去寻找摩门教的家谱。


他们发现了致命的遗传模式。 BRCA1，臭名昭著的癌症突变之一，以及心律失常和黑色素瘤的突变。当然，他们还发现了格雷戈家族中结肠癌背后的APC突变。犹他州成为一个意外的遗传学实验室。一个半世纪前，当莱曼搭上他的马车前往犹他州时，他最终为结肠癌研究设定了一个方向。

耶稣基督末世圣徒教会，即摩门教会，拥有世界上最大的家谱数据库之一。今天，它经营着一个家族历史图书馆，离盐湖城市中心的圣殿只有几步之遥，那里有几台电脑等待着对数字家谱记录感兴趣的访客。教会也有实体记录。它们被储存在700英尺高的岩石下的微缩胶片上，存放在气候控制的花岗岩山记录库中，库门很重，应该可以抵御核爆炸。按照惯例，摩门教徒是以家庭为导向的，这种对家谱的强烈兴趣是一个神学问题。

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摩门教徒相信对死者进行洗礼--在某些情况下，包括长期死亡的人。这种洗礼是为了给那些在凡人生活中没有找到耶稣基督福音的人一个得救的机会，这样整个家庭几代人就可以团聚，永远在天堂相聚。(这种做法引起了争议，特别是当死者中包括大屠杀受害者时）。实际的仪式是在寺庙中通过代理进行的。当祖先的名字出现在屏幕上时，教会成员排队向前接受洗礼。

但首先，你需要名字。所以教会派人到世界各地收集死者的记录。20世纪70年代，一个寻找旧教区记录的家谱小组来到意大利帕尔马，一位名叫马克-斯科尔尼克的年轻美国人正在那里撰写他的博士论文。

幸运的是，斯科尔尼克正在使用教区记录来构建他自己的家谱数据库。他的论文研究了基因如何随着来自不同意大利村庄的人的迁移和通婚而传播。他说，这项研究是一项很好的 "理论练习"，但没有什么实际的成果。同时，由于会说意大利语，斯科尼克为前来拍摄教区记录缩微胶片的摩门教团队提供翻译服务。"他说："我是一个卑微的走卒。然而，许多事情将由此产生。

一个半世纪前，当莱曼搭上他的马车前往犹他州时，他最终为结肠癌研究设定了一个方向。
斯科尼克意识到，摩门教会正坐在一个巨大的人口遗传学数据库中。完成论文后，他在犹他大学找到了一份工作，在那里他开始将摩门教教会记录和癌症登记数据结合起来，成为后来的犹他人口数据库。家谱和癌症记录是一个令人生畏的数据量，特别是在一个资金紧张、电脑还只有冰箱大小的时代。"丽莎-坎农-奥尔布赖特（Lisa Cannon-Albright）回忆说，她是斯科尼克当时的研究生之一。"这就像从一年到另一年，试图获得资金。他们在退伍军人医院的一栋旧楼里工作，那里有蝙蝠出没，被漆成可怕的淡绿色。

将所有数据输入计算机是一项低技术含量的工作。斯科尼克说服教会让他复制186,000页的家庭记录，包括所有沿着摩门教路线来的先驱者。这些记录可以追溯到八代以前，总共包括大约160万人。一组打字员，其中许多是家谱爱好者，将手写的记录变成了一个数字数据库。数据输入花费了相当于15个人年的时间。

当斯科尼克四处寻找可以使用该数据库的项目时，他遇到了一位名叫兰德尔-伯特的年轻胃肠病学家。伯特在盐湖城长大，最近回到犹他大学担任研究员。他是一个热情洋溢的人，善于让面临结肠镜检查的病人感到安心。"他的一位前病人告诉我："我只是把他当作一个大泰迪熊。格雷格的母亲也是伯特的病人之一。当她被诊断出结肠癌时，已经为时已晚，无法治愈。她在一年后去世。

伯特和他的同事们还看到了其他像格雷格这样的家庭，结肠癌已经切断了整个家谱的分支。更重要的是，当你看到这些家庭中年轻的、仍然健康的成员时，他们的结肠也很奇怪--覆盖着几十个蘑菇状的生长物，称为息肉，可以变成癌症。医生称其为减弱的家族性腺瘤性息肉病。他们还不知道是什么原因导致了大量的息肉，但是他们推断如果他们能够通过家谱来追踪它，他们就可以确定谁有这种突变，并最终确定突变本身。

"我无法告诉你我参加了多少次团聚，在那里我吃着玉米和土豆沙拉，谈论着息肉。"
现在回想起来，找到一个影响如此明显的突变并不难。事实上，今天它也不是特别困难。但是在20世纪80年代初，距离人类基因组的第一份草案还有20年的时间，找到一个基因是很难的，特别是如果你不太确定这个基因是否存在的话。也许，正如当时许多人认为的那样，癌症只是生活方式或其他环境因素的产物。将一个基因突变追溯到一个共同的祖先也不是一件容易的事。随着时间的推移，家谱会呈指数级增长。你有两个父母，四个祖父母，八个曾祖父母，以此类推。往前追溯八代，你有数百个祖先。摩门教先驱者的家谱更像是一个纠结的灌木丛。

为了证明这些息肉是遗传性的--而不仅仅是住在同一所房子里的一家人喝了同样的有毒水的不幸结果--研究人员需要在其他地方找到更多像格雷戈的家庭。 所以他们通过犹他州的人口数据库来寻找。通过家谱和癌症登记数据，他们可以确定结肠癌的集群。然后伯特和他的团队带着结肠筛查镜上路了--开车穿过犹他州，还有爱达荷州和怀俄明州，那里有摩门教先驱者的后代定居。他们在当地医院设点，用一天时间在当地人中寻找结肠息肉。"他说："这些乳品商会在挤牛奶的间隙过来，第二天牛仔就会过来。而且他们还去参加家庭团聚。"伯特说："我无法告诉你我参加过多少次团聚，在那里吃着玉米和土豆沙拉，谈论着息肉。他们抽血进行基因测试，并邀请病人安排未来的结肠筛查。


(Lisk Feng)
他们所研究的摩门教徒没有辜负他们友善的名声，这对他们很有帮助。坎农-奥尔布赖特说："我不知道人们是否告诉过你他们对研究的接受程度，"她自己也有摩门教背景。"人们认识到你在做什么。'它不会帮助我，但它会帮助我的孩子和孩子的孩子'，他们就这样加入了。" 参加这项研究需要进行侵入性结肠检查和抽血。但她说，"没有人说不。


慢慢地，在进行了数百次结肠筛查和抽血后，开始出现了一个画面。所有有这种大量息肉的家庭似乎都有完全相同的突变，这表明了一个共同的祖先。我们现在知道，这些共同的祖先是莱曼和奥里利亚。目前还不清楚这对夫妇中的哪一个有这种基因，但他们至少把这种基因传给了他们五个孩子中的两个。1991年，犹他州和约翰霍普金斯大学的研究小组同时发现了这个基因，它被称为APC。

在此后的几十年里，犹他大学的这项结肠癌研究一直在进行。伯特退休后接手他的研究工作的黛博拉-内克拉森（Deborah Neklason）在她的办公室里放着一大卷白纸。当我访问时，她把它拿出来，并示意我到大的木制会议桌前，在那里她展开它，不断地展开它，直到它的一半跑出边缘。这是在纸上的Hinmans家的血统。事实上，这只是其中的一部分。这个家族有五个分支。内克拉森找到了她想给我看的东西：一个中间有一个黑点的正方形。这是代表男性的格雷格方块，这个点标志着他是一个携带者。

尼克拉森的办公室位于该大学的亨茨曼癌症研究所，这是一个由商人乔恩-亨茨曼（Jon Huntsman Sr.）创建的医院和研究中心。亨茨曼家族即使对富有的捐赠者来说也具有不同寻常的影响力--因此最近与大学管理人员发生了一场丑陋的权力斗争--这种影响力甚至在校园地理上也很明显。大学的建筑沿着盐湖城东边的山麓攀升，被绿色玻璃包裹的亨茨曼癌症研究所位于校园的最高海拔。它与其说是医院，不如说是高山滑雪场。亨茨曼开玩笑说，当癌症被治愈后，他将把这里变成丽思卡尔顿酒店。犹他州人口数据库开始于蝙蝠出没的老退伍军人医院，今年晚些时候将迁入亨茨曼的新翼。


去年2月，当时的副总统乔-拜登在亨茨曼发表演讲，宣传他的癌症月票。该活动是在该研究所的食堂进行的，尽管称其为医院食堂有点不合适。Bon Appetit将其命名为世界上 "最酷的工作场所食堂 "之一，因为从落地玻璃可以俯瞰盐湖城周围的山脉。但在那一天，根据特勤局的要求，窗户被拉黑了。

格雷格也在活动中发表了讲话，他也是个追星族。("乔就是乔，他很酷，我恨不得把票投给他。")他忍住紧张，开始讲述他家的故事，从他母亲的诊断开始。

在他母亲去世后，格雷格开始定期找伯特做结肠镜检查。息肉如果足够早地被切除，就不会变成癌症。每次格雷格做结肠镜检查时，他都会被剪掉数百个息肉。他这样做的时间已经够长了，以至于他可以说说以前的情况。"他说："过去，你必须在一小时内喝下一加仑，即五夸脱的盐水，并保持下去。他停顿了一下，面无表情。"现在只要一想到这个，我的皮肤就会爬行。" 现在结肠镜检查的准备工作需要的液体要少得多，而且味道好得多。他补充说，不要再拖延你的结肠镜检查了，他进入了他经常为家人和朋友扮演的角色，鼓励人们接受检查。


格雷格有两个儿子，丹和帕特里克。这种突变有50％的机会被遗传，在这种情况下，机会法则被完美地遵循。大儿子丹有这种突变，而帕特里克则没有。丹现在32岁了，正处于考虑要孩子的阶段。看着他的父亲在这种突变的定时炸弹下仍然过着几乎正常的生活，使他有了一种平和的心态。"他说："这一点也不影响我的决定。

在未来，丹可能也不需要这样定期的结肠镜检查了。格雷格参加了最近的一项临床试验，使用两种叫做舒林酸和厄洛替尼的药物来预防十二指肠的息肉，十二指肠是小肠的一个部分，用窥镜很难到达。它在缩小息肉方面效果很好，尽管它确实有一些副作用，正在后续试验中得到解决。格雷格的消化道是最初研究的 "海报儿童"。"进步是惊人的，"丹说，"这太酷了，即使是在爸爸开始做这个的时候。" 在这个关于精准医疗的炒作时代，格雷格的家庭显示了它的力量--因为它已经被应用了。

格雷格家族的特定突变只占美国结肠癌的一小部分，但对他家族的研究可能会产生更大的影响。APC基因被称为一种肿瘤抑制基因。格雷格的家庭成员出生时就带有APC的突变，但在一个人的一生中，通过随机的机会或环境接触，获得APC基因的突变也是可能的和常见的。所有结肠癌中的80%都有这样的突变。"内克拉森说："这是结肠癌的一个早期步骤，它是预防的完美目标。如果有什么东西能在这个高危家庭中预防结肠癌，那么也许它也能在我们其他人中预防它。这就是为什么临床试验的结果如此令人兴奋的部分原因。


犹他州人口数据库在癌症方面的早期成功表明了家谱的力量。此后，其他地方的遗传学家也利用家谱来研究其他遗传性疾病。在冰岛，人口少且与世隔绝，祖先可以追溯到几百年前，一家名为deCODE的20岁公司已经收集了所有冰岛人中约一半的样本，并发表了一系列论文。研究人员最近也开始探索在网上非常流行的大规模众筹家谱。

犹他州的人口数据库也在增长。它现在拥有犹他州两个主要医疗机构的医疗记录，以及该州的出生和死亡记录。最近，它与摩门教会签订了一项协议，将该教会的家谱中的1亿条新记录添加到数据库中。内克拉森希望利用这些记录进一步追溯，找到欣曼家族与纽约、德克萨斯和其他州的十几个家庭之间的联系，这些家庭后来被发现有相同的结肠癌突变。但这是一项困难的工作，因为较早的前摩门教先驱者记录不太可靠。例如，丈夫们往往在他们的第一任甚至第二任妻子去世后再婚，因此很难分辨谁生了哪个孩子。(母亲在摩门教记录中得到了很好的记载，而且追踪欣曼家族后裔的研究人员实际上并没有遇到一夫多妻制，因为在19世纪只有少数男子实行这种制度）。内克拉森原本认为她在犹他州和纽约州家庭之间发现的一种联系是模棱两可的，因为关于两个妻子中哪个是孩子的母亲的信息是相互矛盾的，这可能把这两个分支联系起来。

"我觉得自己有点像内部人士，尽管我只是一只实验室的老鼠。"
大学的结肠癌研究已经进行了30年，格雷格可以像其他人一样讲述这个故事。他已经看到了它的整个弧线。斯科尔尼克和伯特现在都已经退休了。斯科尼克一半时间在圣地亚哥，另一半时间在意大利的帕尔马--他在那里遇到了那些摩门教族谱的猎人和他的意大利妻子。伯特也已经退休了。他目前住在德国的法兰克福，在那里他为欧洲的摩门教传教士提供医疗方面的建议。格雷格和其他人一样在这里呆了很久。"虽然我只是一只实验室的老鼠，但我觉得自己有点像内部人士，"格雷格说。这就是为什么他那天要在拜登面前发言。

活动的组织者在他身后的屏幕上放大了他的部分家谱，这是尼克拉森在她办公室给我看的一小部分。他的母亲和祖母那一代充满了黑色的方块和圆圈，表示死于结肠癌。他这一代人，现在已经60多岁了，由于做了结肠镜检查，他们都还活着，没有患癌症。"格雷格后来在他的客厅里对我回忆说："就在那里看到这个图表，我就觉得天哪，这真的很有效。

他的母亲桑德拉于1983年去世，当时还没有进行基因测试，也没有人知道她的家族中长期潜伏着APC突变。Gregg在几个月前刚刚结婚。在他的婚礼上，她已经生病了。她将无法看到她的孙子，其中第一个孙子是一年后出生的。"从我的角度来看，"他告诉我，"我比她多活了大约15年。" 他说这话时靠在椅子上，他孙子的火车轨道铺在我们面前的茶几上。

萨拉-张是《大西洋》杂志的一名工作人员。