人类生育方式的历史转变
三十万年来，人类历史上的每一位父母都递给孩子一副自己从未见过的基因牌。曾经根本没有办法知道里面有什么，无法提前做准备，也无法选择健康。基因彩票就这样转动，抽到什么就是什么。
英文原文
For 300,000 years, every parent in human history handed their child a genetic hand they'd never seen. There was no way to know what was in it. No way to prepare and no way to choose health. The genetic lottery ran, and you got what you got.那个时代已经结束了。我们繁衍后代的方式正在永远改变。
英文原文
That era is over. And the way that we have babies is changing forever.但在深入探讨之前，我想先从你以及你是如何来到这个世界讲起。你始于两个细胞：一颗卵子和一颗精子，各携带 23 条染色体。当卵子与精子相遇时，字面意义上的火花迸发了。一阵锌释放的火花开启了你的生命，而正是这个特定的瞬间，锁定了你一生的基因命运。
英文原文
But before we get into that, I want to start with you and how you got here. You began as two cells, an egg and a sperm, each carrying 23 chromosomes. When that egg and sperm met, sparks literally flew. A burst of zinc emerged to start your life. And this specific moment locked in your entire genetic destiny.你的母亲产生了两百万颗卵子，你的父亲产生了超过五千亿颗精子。构成你的这组特定的卵子与精子组合，概率仅为万亿分之一。你能够存在于世的几率，大致相当于从全地球所有海滩的所有沙粒中，挑选出某一颗特定的沙子。你能够存在本身，就是一个极低概率的奇迹。换一个夜晚，换另一天，出生的便不会是你。
英文原文
Your mother produced two million eggs. Your father produced over 500 billion sperm. And the specific combination of egg and sperm that make up you is a one in a trillion chance. The odds of you existing at all are about the same as picking one specific grain of sand out of all the grains of sand on all the beaches on the entire planet. You are wildly unlikely to exist at all. A different night, a different day, and it wouldn't have been you.基因疾病的沉重负担与个人痛点
然而，在数以亿计的人群中，这层奇迹之下潜藏着一种基因疾病，等待着夺走他们的某些东西。它们可能夺走心脏、视力或是孩子。无论他们多么被深爱，无论他们怎样努力抗争，有些厄运终会降临。
英文原文
Yet tucked inside that miracle for hundreds of millions of people is a genetic disease, waiting to take something from them. Their heart, their sight, their child. Something that will arrive regardless of how loved they are or how hard they fight.我是看着母亲逐渐失明长大的。仅仅为了确诊就花了好多年；在经历了所有的检测、所有的就诊和所有的不确定之后，得到的答复却是：“我们无能为力。”她先是失去了夜视力，接着是周边视野，最后，她的中心视力也慢慢丧失了。
英文原文
I grew up watching my mom go blind. It took years just to get the diagnosis, and after all the testing and all the office visits and all the uncertainty, the answer was, “There’s nothing we can do.” She lost her night vision first, then her peripheral vision, and then finally and slowly, her central vision too.那种无力感非常痛苦。眼睁睁看着自己深爱的人失去如此珍贵的东西，令人心痛。不幸的是，她并非个例。全球有 4 亿人饱受基因疾病折磨，这比整个美国的人口还要多。受影响的人群中有一半是儿童，其中 95% 没有获得 FDA 批准的治疗方案。科学家目前已经编目的基因疾病超过 3,000 种。大部分名字你甚至念不出来，你不知道它们叫什么，但那些受其影响、日复一日饱受煎熬的人们——他们绝不愿将这种痛苦施加给自己最痛恨的敌人身上。
英文原文
It sucks to be powerless. It sucks to watch someone you love so much lose something so precious. And unfortunately, she's not alone. Four hundred million people around the world suffer from genetic disease. That's more than the entire population of the United States. Half of those people that are affected are children. Ninety-five percent of those don't have an FDA-approved treatment. Scientists have now catalogued over 3,000 genetic diseases. You can’t pronounce most of them. You don’t know their names, but the people who are affected, who are living it day in and day out -- they wouldn't wish it on their worst enemies.我创立 Orchid 就是因为我的母亲。我依然无法接受这个事实：仅仅因为 DNA 中一个随机的基因印刷错误，她就将永远无法看到孙辈的容貌。我打造这项事业，是因为我不想让自己的孩子的生活也被一个随机的基因打印错误所绑架。
英文原文
I started Orchid because of my mom. I still can't accept the fact that she's not going to be able to see her grandkids' faces because of a random genetic typo in her DNA. I built this because I don't want my own kids to be stuck with their life getting hijacked by a random genetic typo.传统筛查的局限与全基因组测序突破
我们是世界上第一家能够对试管婴儿（IVF）培育的胚胎进行全基因组测序的公司。一个试管周期通常会产生 5 到 15 个胚胎。而在今天，这项极为关键的决策，要么就像选美比赛一样——完全看这些胚胎在显微镜下的外观——要么仅仅依赖实际可用的一小片基因信息来决定。
英文原文
We were the first company in the world to be able to sequence the entire genome of an embryo created during IVF. A round of IVF creates anywhere from five to 15 embryos. And today, that incredibly critical decision is made either by a beauty contest -- what these embryos look like under a microscope -- or they're made with a tiny slice of genetic information that's actually available.这就是如今试管婴儿门诊中检测的实际情形：他们放大观察某一条特定的染色体：两条染色体都在不在？如果缺失了，它会通知你；如果两条都在，它会告诉你一切正常。如果多了一条染色体，例如多了一条 21 号染色体，那就是 21-三体综合征，也就是唐氏综合征。
英文原文
So this is what testing looks like today in the IVF office. They zoom in on a specific chromosome: Are both chromosomes present or not? If they're missing, it'll let you know. And if both are present, it'll tell you you're all good. And if there's an extra chromosome, 21, for example, that's called trisomy 21 or Down syndrome.但你应当这样理解：你的基因组里有 30 亿个碱基，它的结构就像一本书。这 30 亿个碱基分布在 23 个不同的章节里。目前所有的染色体检测所能做到的，仅仅是告诉你每一个章节在不在。它根本没有去读任何一个章节里面的任何一个字母。所以，如果第 7 章或者说 7 号染色体里面有一个打字错误、一个拼写错误，它是根本找不出来的。它只会告诉你：“嘿，第 7 章一切正常，我只在章节层级做了检查。”
英文原文
But the way you need to think about this is that you have three billion bases in your genome, and it's organized like a book. So those three billion bases are in 23 different chapters. And all this chromosome testing is able to do is tell you if every chapter is present or not. It's not actually reading any of the letters in any of those chapters. So if in chapter seven or chromosome seven, there's a typo, there's a spelling error, it's not going to be able to find it. It's just going to tell you, hey, you know, "Chapter seven is all good. I only checked at the chapter level."这就是全基因组测序变得极其有价值的地方，因为它能切实去阅读每一个字母——整整 30 亿个。那么这到底是什么样子的呢？如果你放大到某一条特定的染色体，你会看到一堆字母。而在那 30 亿个字母中，可能隐藏着一个错误。不幸的是，仅仅几个字母的差异，就决定了一个孩子是永远无法开口说话，还是能够正常言语。所需的仅仅是：改变了几个字母。
英文原文
So that's where whole genome sequencing becomes incredibly valuable because it’s actually reading every single letter -- all three billion of them. So what does that actually look like? So if you zoom in to a specific chromosome, you're going to see a bunch of letters. And hidden in those three billion letters is a typo. And unfortunately, just a few letters can be the difference between a child that will never be able to talk and one that will. That’s all that it takes: is a few letters changed.这项技术之所以极难做到，而我们能成为全球首创，是因为胚胎所含的 DNA 数量极其微少。胚胎学家只送给我们 5 个细胞，而在这 5 个细胞中，只有 30 皮克的 DNA。一皮克是万亿分之一克。我们处理的材料量极小，因此我们不得不发明一种全新的技术，在不造成损坏的情况下，将这些 DNA 扩增复制数十万倍。
英文原文
The reason that it's really hard to do this, and we're the first to do it in the world, is because embryos have extremely small quantities of DNA. The embryologist only sends us five cells, and in those five cells there [are] 30 picograms of DNA. A picogram is a trillionth of a gram. So we're working with extremely tiny amounts of material. And we had to invent an entirely new technology to amplify or copy that DNA hundreds of thousands of times without corrupting it.现在我们知道它是行之有效的，因为我们拥有胚胎的数据，也拥有九个月后出生的婴儿数据，我们将两者进行比对，确认它们完全吻合。
英文原文
Now we know that it works because we have embryos, and we have the subsequent babies that were born nine months later, and we've matched them up and we know that they match.风险量化与从单基因到多基因的筛查
那么，这项很酷的技术到底能让父母做些什么呢？令人兴奋的是，在最基础的层面上，我们能够让父母了解并筛查我们前面谈到的那 3,000 种疾病：先天性缺陷、心脏缺陷、骨骼缺陷、神经发育障碍、基因突变导致的自闭症，所有这些都是现有检测完全遗漏的基因疾病。
英文原文
So, cool technology. What does it actually let parents do? So what's really exciting is that at the most basic level, what we're able to do is allow parents to understand and screen for those 3,000 diseases that we talked about. Birth defects, heart defects, skeletal defects, neurodevelopmental disorders, genetic forms of autism, all genetic diseases that are completely missed by existing testing.但我们还能走得更远。想想精神分裂症、双相情感障碍或心脏病。这些疾病是由数百万个变异共同作用的累积影响所致。有些人具有较高的遗传易感性，而另一些人则没有。如今令人瞩目且切实可行的是，我们拥有数十万个人的数据：我们拥有他们的测序数据，也拥有他们的医疗记录，因此我们能够建立在胚胎层面上量化疾病风险的模型。
英文原文
But we can go even further than that. Think about schizophrenia or bipolar disorder or heart disease. These are diseases that are driven by the cumulative impact of many millions of variants working together. Some people are at high genetic predisposition and other people aren't. So what's amazing and what's available now is that now we have data from hundreds of thousands of individuals. We have their sequenced data, and we have their medical records so we can build models that quantify disease risk at the embryo level.因此我们能够告诉父母：这个胚胎有较高的遗传易感性，而那个胚胎有较低的遗传易感性。尽管这些模型内部包含了数百万个变异，但对于一个正在进行试管周期且仅有 5 个胚胎的人来说，仅仅通过这 5 个胚胎，就可以预期实现 30% 到 50% 的风险降低。
英文原文
So we can tell parents, this embryo is at a high genetic predisposition, and this embryo is at a low genetic predisposition. And despite the fact that these models have millions of variants inside them, someone who's going through an IVF cycle who has only five embryos can expect to see anywhere from a 30 to 50 percent risk reduction with just those five embryos.而在今天，这些模型的表现还是它们有史以来最差的时候，因为我们目前拥有的数据是未来最少的状态。随着每年获得的数据越来越多，这些模型会变得越来越强大，这将转化为父母能够用更少的胚胎降低更多的风险。
英文原文
And today, the models are the worst they're ever going to perform because we have the least data that we're ever going to have. Every year, we're getting more and more data, and these models are getting more and more powerful, which is going to translate to parents being able to reduce more risk with fewer embryos.最棒的是，这并非科幻小说。这些婴儿实际上已经降生了。他们登上了《纽约时报》的版面，登上了国际新闻，因为他们的父母做成了以往绝不可能做到的事情。我们是第一代——也是第一种生命形态——能够阅读自身的源代码并切实选择下一代。我们是第一批得以去选择健康、而不仅仅是被动期盼健康的人。
英文原文
And the best part is this isn’t sci-fi. These babies are actually already here. They’re being photographed by “The New York Times,” and they're making international news because their parents have done something that has never been possible before. We are the first generation, the first life form, to be able to read its own source code and actually choose the next generation. We are the first to get to choose health, not just have to hope for it.很快，这将成为我们所有人繁衍后代的默认方式。有一点大多数人目前还没有意识到：性是为了快乐，而胚胎筛查是为了生孩子。
（笑声）
这两件事已经在悄然分离。一旦你从这个角度看待问题，问题就变成了：为什么还会有人以其他方式来孕育孩子？而不是为什么会有人主动选择试管婴儿。
英文原文
Soon this is going to be the default way we all have babies. And here's the thing most people don't realize yet: sex is for fun, and embryo screening is for babies. (Laughter) Those two things have quietly separated. And once you see it that way, the question [isn’t], Why would anyone do IVF electively? The question is, why would you do it any other way?临床案例与单碱基对的影响
我想让大家认识一个人。这是米娅（Mia）。米娅出生时患有无脑回畸形，一种致命的脑部疾病。大多数患有这种病症的儿童活不过 10 岁。这是一种基因突变，没有治疗方法，也没有任何先兆。米娅的母亲做过了大家听过的所有基因检测：携带者筛查、无创产前基因检测（NIPT）。由于这些检测评估的基因组范围还不到 1%，它们根本无法识别出我们讨论的绝大多数基因疾病。
英文原文
I want you to meet someone. This is Mia. Mia was born with lissencephaly, a terminal brain disorder. Most children with her condition don't make it to their 10th birthday. There was a genetic mutation, no cure and no warning. Mia's mom did all the genetic testing that you've heard of: carrier screening, NIPT. And because those tests only evaluate less than one percent of the genome, they're not able to identify the vast majority of these genetic diseases that we're talking about.所以她当时根本无从得知。后来她使用 Orchid 筛查了接下来的胚胎。她现在已经怀孕了。尽管承受着米娅确诊的悲痛，但面对这次新的怀孕，她能够更有信心，心里也多了一份踏实，确信下一个孩子不必再像米娅那样承受痛苦。同样的母亲，同样的爱，截然不同的结果。不是因为运气，而是因为一次选择。
英文原文
So there was no way for her to know. She used Orchid to screen her next embryos. She's pregnant now. And despite living with the tragedy of Mia's diagnosis, she's able to go into this next pregnancy more confident and with a little bit more security that her next child isn't going to have to suffer in the same way that Mia does. Same mother, same love, different outcome. Not because of luck. Because of a choice.单个碱基对的威力有多大，往往很难令人直观理解。想想世界上最高的女性——她身高超过 7 英尺；以及世界上最矮的女性——她身高只有刚过 2 英尺。最高的女性患有一种叫韦弗综合征（Weaver syndrome）的病症，而最矮的女性则患有软骨发育不全症（achondroplasia）。这两种疾病实际上都只是由 30 亿个字母中改变了一个字母引起的。我觉得这很不可思议，仅仅一个字母就能造成如此巨大的差异。
英文原文
It can be hard to understand just how powerful a single base pair can be. Think about the tallest woman on Earth -- she’s over seven feet tall -- and the shortest woman on Earth, she’s just over two feet tall. The tallest woman has a condition called Weaver syndrome, and the shortest woman has a condition called achondroplasia. Both of these diseases are actually caused by one letter changed in three billion letters. And I think that's miraculous, that one letter can have such a dramatic difference.并且它们都是自发突变。这意味着在她们的家族中没有其他人携带这些打印错误，她们是首个发生突变的人。女性常因卵子老化而饱受指责，但男性通常不知道的是，随着年龄增长，男性的精子其实也会累积突变。事实上有一整类基因疾病，仅仅是由精子中的突变引起的，而这些突变本身并不影响男性自身。其中一种就是软骨发育不全症，它是侏儒症最常见的病因之一。
英文原文
They're also both spontaneous mutations. So what that means is that there's no one else in their family that has these typos. They're the first ones to have them. You know, women get a lot of flak for their eggs aging, but something that men usually don't know is that sperm actually accumulates mutations as men age as well. And there's actually a whole category of genetic diseases that are just caused by mutations in sperm that don't affect men. And one of them is achondroplasia, one of the most common causes of dwarfism.基因变异的另一面与伦理探讨
所以基因彩票分发的并不只是风险，它有时也会分发某些“超能力”。这是一位芬兰奥运滑雪运动员。他控制红细胞生成的基因中存在一个单碱基对的变化。这意味着他的肌肉能比竞争对手获得多得多的氧气。他拥有极强的耐力，在统治赛场的时期几乎不可战胜。
英文原文
So the genetic lottery doesn't only deal risk. It also deals some superpowers. This is a Finnish Olympic skier. He has a single base-pair change in a gene that controls red blood cell production. So that means that his muscles get way more oxygen than his competitors'. He has way more endurance and was practically unbeatable during his reign.在美国中西部有一个家庭，其骨密度是有记录的人类的 8 倍，他们的骨骼几乎是不可折断的。你和我只有三种颜色感受器，但已经发现有女性拥有四种颜色感受器。因此，当你和我只能分辨 100 万种颜色时，她们可以看见 1 亿种颜色。她们生活在一个我们字面意义上根本无法想象的世界里。超强的耐力、不可折断的骨骼、1 亿种色彩——这些都不是科幻小说，它们已经真实存在，只不过目前是由基因彩票随机分发的。
英文原文
There's a family in the Midwest that has eight times the bone density of anyone else that has been documented, and their bones are virtually unbreakable. You and I have only three color receptors, but there have been women found to have four color receptors. So while you and I can only see a million colors, they can see 100 million. They're living in a world that we literally can't picture. Extra endurance, unbreakable bones, 100 million colors. These aren't science fiction. They're already here. They're just currently given out by a genetic lottery.我知道你们中有人在想：这是在扮演上帝，这不自然。但我其实认为恰恰相反。我想不出还有什么能比渴望保护自己的孩子、希望他们少受痛苦更为自然、更具人性的事了。我们过去只是从未拥有过这些信息，而现在我们拥有了。
英文原文
And I know what some of you are thinking: playing God, unnatural. But I actually think the exact opposite is true. I can't think of anything that's more natural and more human than wanting to protect your child and wanting them to suffer less. We've just never had the information before and now we do.我想让大家看最后一个家庭。这是莉迪亚（Lydia），罗汉（Rohan）和珍（Jen）的第一个孩子。她出生时患有非常严重的神经发育障碍，这是由名为 KCNQ2 的基因中单碱基对突变引起的。这就是她出生后头几周的生活状态。他们希望能为莉迪亚添一个妹妹，于是在下一次受孕时使用了 Orchid。
英文原文
I want to show you one last family. This is Lydia -- Rohan and Jen’s first child. She was born with a very serious neurodevelopmental disorder caused by a single-base-pair-mutation in a gene called KCNQ2. This is what the first few weeks of her life looked like. They wanted a sister for Lydia, and they used Orchid for their next pregnancy.这是莉迪亚刚出生的妹妹露西（Lucy）。同样的父母，同样的爱，截然不同的结果。不是因为运气，而是因为一次选择。露西不必在成为一个人之前先沦为一个病人。她只需要做个普通的孩子——而多亏了她父母在她出生前所做的事，她做到了。未来不是一种假设，它正在此时此刻诞生。这是第一代让基因胜率偏向自己这一边的人。谢谢大家。
（掌声）
英文原文
This is Lydia’s newly minted younger sister, Lucy. Same parents, same love, different outcome. Not because of luck. Because of a choice. Lucy won't become a patient before she becomes a person. She just gets to be a kid -- and because of what her parents did before she was born, she will. The future is not hypothetical. It is being born right now. This is the first generation who gets the genetic odds stacked in their favor. Thank you. (Applause)问答环节：资源倾斜与技术边界
萨尔·汗（Sal Khan）：我把两个我猜很多人都会问的问题合二为一。第一，这项技术不是免费的。你提到了基因彩票，但这是否会让天平向那些有资源能力的人倾斜？第二，界限划在哪里？你刚才在结尾暗示了超人的视力、骨骼或耐力。结合 CRISPR 以及其他所有技术，你会在哪里划定边界？
英文原文
Sal Khan: I'm going to put two questions into one that I'm guessing many people are asking. One, this isn't free. So you mention the genetic lottery, but does that stack the deck for those who have the ability for the resources? And then where do you draw the line? You kind of hinted in the end of superhuman sight or bones or endurance. Where would you draw that line with CRISPR and everything else?诺尔·西迪基（Noor Siddiqui）：我认为在成本方面，与这些疾病带来的代价相比，它实际上只是九牛一毛，对吧？比如我母亲患有的视网膜色素变性这种遗传病，第一款获批的基因疗法每只眼睛花费达一百万美元。相比之下，试管婴儿胚胎筛查是非常实惠的。但谈到技术未来的走向，这正是我来 TED 的原因。这真的取决于在座的各位：你们希望看到它走向何方？我认为这是一个需要展开重大社会讨论的话题，因为技术的发展极其迅速，各项能力演进得实在太快了。
英文原文
Noor Siddiqui: I think that in terms of cost, you know, in contrast to what these diseases cost, it's actually, you know, pennies on the dollar, right? So the genetic condition that my mom has, retinitis pigmentosa, the first gene therapy that was approved costs a million dollars per eye. So in comparison, IVF embryo screening is quite affordable. But yeah, in terms of where it goes, that's kind of why I'm here at TED. It’s really up to you guys: Where do you want to see it go? I think that's going to be a really big societal conversation that needs to be had, because the technology is moving so quickly and the capabilities are moving so quickly.萨尔·汗：确实有很多值得深思的内容。非常感谢你，诺尔，这场演讲太精彩了。
（掌声）