TEDTalks2011.4.19---Susan Lim: 移植細胞，而不是器官

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http://dotsub.com/view/abd891c5-7f07-4516-a644-e4e350ba7322
Susan Lim: 移植細胞，而不是器官
我在两位伟大的外科先驱者 授权下训练移植手术： 他们是托马斯·斯塔齐尔， 世界上第一个成功完成肝脏移植手术的人 在1967年， 以及罗伊·卡恩爵士， 在英国第一个完成肝脏移植手术的人 在之后的那年（1978）。 我回到新加坡 然后，在1990年 完成了亚洲首例 尸肝移植手术， 尽管它极其的困难。 现在，当我回想起， 这次移植其实是最简单的一部分。 下一步，凑钱来资助手术。 但是可能最有挑战行的部分 是去说服那些立法者-- 一件在议会辩论过的事宜-- 关于一个年轻的女性外科医生 被给予机会 成为她的国家的先驱。 20年过去了， 我的病人，萨伦德， 是亚洲尸肝移植的 最长存活记录。 （掌声） 也许更重要的， 我有幸成为她 14岁儿子的教母。
（掌声）
但是不是所有在移植等待列表上的病人 都是这么幸运的。 现实是， 捐献的器官还是不够 周转。 当捐献器官的需求 持续的增加， 很多一部分是因为人口老龄化问题， 然而供应还是相对的保持稳定。 仅仅美国， 10万人，男人，女人还有小孩 在等待捐助的器官， 而且每天有十几人死亡 就因为缺少捐献的器官。 移植团体 活跃于器官捐献的活动中。 而且器官（捐赠范围） 已经被扩大化 从脑死亡的捐献者 到活体的亲属捐献者-- 亲属可能捐献整个器官 或者一部分器官， 比如劈裂式肝移植， 给亲属或者是所爱的人。
但是捐献器官还是十分短缺， 接着器官（捐赠范围）再一次扩大 从活体亲属捐献者 现在到了活体的非亲属捐献者。 然后这就引发了 未遇见和料想到的 道德纷争。 怎么才能辨别 捐献者是自愿和无私的 而不是被迫的或强制的 从，比如， 忠诚的伴侣，媳婿， 仆人，奴隶， 雇员？ 我们什么时候如何才能加以界限？ 在我的世界里， 很多人生活在贫困线之下。 而且有些地方， 用活体的非亲属的器官捐赠 来换取金钱上的回报 已经是一个兴旺 的行业。
在我完成第一例肝移植后不久， 我接到我下一个人物， 是步入监狱中 从死刑犯人身上 获取器官。 我当时怀孕了。 在任何女性的生命中 怀孕意味着 喜悦以及使命感。 但是我的这段喜悦的时间 却被严肃的病态的想法所摧毁-- 关于经过 最高安保的死刑囚犯的囚房， 就像这是唯一的道路 带我去那临时手术室的想法。 每当这时， 我就能感到那 跟随我的从死刑犯人眼中的冰冷的目光。 之后的2年， 我挣扎在这窘境中 早上4点30醒 每周五凌晨， 开车到监狱， 着手准备，戴上手套，消过毒， 准备接手 死刑犯人的尸体， 移出器官 然后到运送这些器官 到接受者的医院 然后当天下午 给接受者移植这些 毫无疑问的，我是被告知， 是获得了准许（捐赠器官）。
但是我一生， 现在真正感到冲突-- 冲突的范围 从清晨的极度悲伤和迷惑 到黄昏的庆祝 移植器官成功的喜悦。 我的团队中， 一两个我的同事的生活 也被这样的经历所困扰。 我们中一些已经看开了， 但是其实我们没有人还是原来的自己。 我很疑惑 从死刑囚犯取下器官 至少道德上是有争议的 就像从人类胚胎中 获取肝细胞。 并且我认为， 作为一个外科先锋人物 它让我想起 是否有更好的方法-- 一种规避死亡 同时获得器官 这样可能会影响到 全世界成千上万的病人。
现在就是时候， 外科手术的实行 正从大到小， 从大的开放性的切口 到孔洞式的 微开口。 而且移植手术的概念已经传遍 从完整器官到细胞。 1988年，在明尼苏达大学， 我参与了一系列 关于完整胰脏移植手术。 我见证此科技的困难性。 同时这激发了我的思考 一个转变从移植真个器官 也许到移植细胞。 我寻思着， 为什么不能把个体细胞 移出胰脏-- 那种分泌出胰岛素治疗糖尿病的细胞-- 并且移植这些细胞呢？-- 技术的角度讲这是更简单的过程 相比于克服移植 整个细胞的复杂程度。
那是， 肝细胞研究 已经有些许进展， 世界上首次分离出 人类胚胎肝细胞 在90年代。 观察表明肝细胞，也叫肥大细胞， 能发育成 所有种类的细胞-- 心肌细胞，肝细胞， 胰岛细胞-- 引起了医学界的关注 和公众的想象力。 我也被这种全新的 突破性的科技所吸引， 同时这激发了我思维上的转变， 从移植整个器官 到移植细胞。 我把我的研究集中在 可能成为 细胞移植的肝细胞中。
今天我们意识到 有很多种不同的肝细胞。 胚胎单细胞 已经占据了中心位置， 主要是因为他们的多能性-- 就是他们能轻松的分化成 不同种类的细胞。 但是道德上的争论 围绕着胚胎肝细胞-- 事实是这些细胞来源于 5天大的人类胚胎-- 激励研究 其他类型的肝细胞。 我激励我的实验组 集中研究我认为 是最没有争议的干细胞源 脂肪组织，或叫肥肉，对肥肉 现如今已经有着充足的可利用来源-- 你和我一样，我想，很乐意摆脱它。 脂肪源干细胞 是成体肝细胞。 成体干细胞 你和我身上都能找到-- 从我们血液中，从我们骨髓中 从我们脂肪，皮肤和其他器官中。 同时这也证明， 脂肪是一种最优来源的 成体干细胞。 但是成体干细胞 不是胚胎干细胞。 这有局限性： 成体干细胞是成熟的细胞， 就像成年的人类， 这些细胞局思维更加局限 行为更加局限 同时也不能像胚胎干细胞一样 分化成很多种 特定的细胞。
但是在2007年， 两位杰出的人， 日本的新古中山聪 和美国的杰米·汤普逊， 有了一项令人震惊的发现。 他们发现 成体细胞，从你我身上获取的， 可以重新的编辑 变回到类胚胎干细胞， 他们起名为IPS细胞，
因此猜测，在世界各地的科学家在实验室都在竞相转换成人细胞老化 - 成年细胞衰老从你和我 - 他们都在竞相重新编程回到更有用iPS细胞，这些细胞。而在我们实验室，我们致力于走脂肪细胞重新编程为青春喷泉的脂肪丘 - 细胞，那么我们可能会使用其他的形式，更专业，细胞，这一天可作为细胞移植使用。如果这项研究成功的话，那么可以减少需要研究和牺牲人类胚胎。
事实上，有很多的炒作，同时也希望干细胞的承诺，将一天的条件提供一整套的治疗方法。心脏病，中风，糖尿病，脊髓损伤，肌肉萎缩症，视网膜疾病 - 是这些条件的相关亲自告诉你们啊？
2006年5月，可怕的事情发生在我身上。我正要开始一个机器人操作，但加强对进入手术室的灯光明亮，耀眼的电梯时，我意识到我的左视场快速进入黑暗崩溃。本周早些时候，我采取了在晚春滑雪比较硬敲 - 是的，我摔倒。我开始看到漂浮物和星星，我随便过多高空晒太阳驳回。我怎么可能是灾难性的，如果不是事实，我在访问达到了良好的手术。而我有我的视力恢复，但在此之前长期的疗养 - 在头向下的位置 - 三个月。这次经历教会了我更多的同情，我的病人，特别是与视网膜疾病的。
全世界有3700万人失明，127多万患有视觉障碍。干细胞衍生的视网膜移植手术目前处于研究阶段，可能一天恢复视力，或与世界各地的数百万患者视网膜病变的部分视力。事实上，我们生活在充满挑战和激动人心的时刻。随着世界人口老龄化，科学家们正在争先恐后地发现新的方法来增强身体的力量，通过干细胞治疗本身。
这是一个事实，即当我们的器官或组织受伤，我们的骨髓干细胞释放到我们的循环细胞。而这些干细胞然后浮到受损的器官释放生长因子，修复受损组织的血液和家庭。干细胞可作为构建块来修复损坏我们的身体内支架，或提供新的肝细胞修复受损的肝脏。在我们发言，有117个左右的干细胞研究的肝脏疾病防治的临床试验。
是什么样的未来？心脏疾病是全球主要的死亡原因。 110万美国人患有心脏病的生产能力。 480万患有心力衰竭。干细胞可被用于运载生长因子，修复受损的心脏肌肉或肌肉细胞分化成心脏，恢复心脏功能。有170个调查干细胞在心脏疾病中的作用进行临床试验。虽然仍然在研究阶段，干细胞可能有一天预示着在心脏病学领域的飞跃。
干细胞为新的开端的希望 - 小，渐进的步骤，而不是器官的细胞修复，而不是替代。干细胞疗法可能有一天会减少对捐赠器官的需要。强大的新技术总是存在的谜团。在我们发言的时候，世界上第一个人类胚胎干细胞对脊髓损伤的研究已在进行继美国FDA的批准。而在英国，神经干细胞治疗中风正在试验中的第一阶段调查。
这项研究的成功，我们今天庆祝已经成为可能，好奇心和贡献，个别科学家和医疗先锋承诺。每个人都有自己的故事。我的故事一直对我的旅程从器官到细胞 - 通过争议的旅程中，希望启发 - 希望，随着年龄的增长，你和我可能一天庆祝提高生活质量的长寿。

谢谢。




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Susan Lim: Transplant cells, not organs
So I was privileged to train in transplantation under two great surgical pioneers: Thomas Starzl, who performed the world's first successful liver transplant in 1967, and Sir Roy Calne, who performed the first liver transplant in the U.K. in the following year. I returned to Singapore and, in 1990, performed Asia's first successful cadaveric liver transplant procedure, but against all odds. Now when I look back, the transplant was actually the easiest part. Next, raising the money to fund the procedure. But perhaps the most challenging part was to convince the regulators -- a matter which was debated in the parliament -- that a young female surgeon be allowed the opportunity to pioneer for her country. But 20 years on, my patient, Surinder, is Asia's longest surviving cadaveric liver transplant to date. (Applause) And perhaps more important, I am the proud godmother to her 14 year-old son.

(Applause)

But not all patients on the transplant wait list are so fortunate. The truth is, there are just simply not enough donor organs to go around. As the demand for donor organs continues to rise, in large part due to the aging population, the supply has remained relatively constant. In the United States alone, 100,000 men, women and children are on the waiting list for donor organs, and more than a dozen die each day because of a lack of donor organs. The transplant community has actively campaigned in organ donation. And the gift of life has been extended from brain-dead donors to living, related donors -- relatives who might donate an organ or a part of an organ, like a split liver graft, to a relative or loved one.

But as there was still a dire shortage of donor organs, the gift of life was then extended from living, related donors to now living, unrelated donors. And this then has given rise to unprecedented and unexpected moral controversy. How can one distinguish a donation that is voluntary and altruistic from one that is forced or coerced from, for example, a submissive spouse, an in-law, a servant, a slave, an employee? Where and how can we draw the line? In my part of the world, too many people live below the poverty line. And in some areas, the commercial gifting of an organ in exchange for monetary reward has led to a flourishing trade in living, unrelated donors.

Shortly after I performed the first liver transplant, I received my next assignment, and that was to go to the prisons to harvest organs from executed prisoners. I was also pregnant at the time. Pregnancies are meant to be happy and fulfilling moments in any woman's life. But my joyful period was marred by solemn and morbid thoughts -- thoughts of walking through the prison's high-security death row, as this was the only route to take me to the makeshift operating room. And at each time, I would feel the chilling stares of condemned prisoners' eyes follow me. And for two years, I struggled with the dilemma of waking up at 4:30 am on a Friday morning, driving to the prison, getting down, gloved and scrubbed, ready to receive the body of an executed prisoner, remove the organs and then transport these organs to the recipient hospital and then graft the gift of life to a recipient the same afternoon. No doubt, I was informed, the consent had been obtained.

But in my life, the one fulfilling skill that I had was now invoking feelings of conflict -- conflict ranging from extreme sorrow and doubt at dawn to celebratory joy at engrafting the gift of life at dusk. In my team, the lives of one or two of my colleagues were tainted by this experience. Some of us may have been sublimated, but really none of us remained the same. I was troubled that the retrieval of organs from executed prisoners was at least as morally controversial as the harvesting of stem cells from human embryos. And in my mind, I realized as a surgical pioneer that the purpose of my position of influence was surely to speak up for those who have no influence. It made me wonder if there could be a better way -- a way to circumvent death and yet deliver the gift of life that might exponentially impact millions of patients worldwide.

Now just about that time, the practice of surgery evolved from big to small, from wide open incisions to keyhole procedures, tiny incisions. And in transplantation, concepts shifted from whole organs to cells. In 1988, at the University of Minnesota, I participated in a small series of whole organ pancreas transplants. I witnessed the technical difficulty. And this inspired in my mind a shift from transplanting whole organs to perhaps transplanting cells. I thought to myself, why not take the individual cells out of the pancreas -- the cells that secrete insulin to cure diabetes -- and transplant these cells? -- technically a much simpler procedure than having to grapple with the complexities of transplanting a whole organ.

And at that time, stem cell research had gained momentum, following the isolation of the world's first human embryonic stem cells in the 1990's. The observation that stem cells, as master cells, could give rise to a whole variety of different cell types -- heart cells, liver cells, pancreatic islet cells -- captured the attention of the media and the imagination of the public. I too was fascinated by this new and disruptive cell technology, and this inspired a shift in my mindset, from transplanting whole organs to transplanting cells. And I focused my research on stem cells as a possible source for cell transplants.

Today we realize that there are many different types of stem cells. Embryonic stem cells have occupied center stage, chiefly because of their pluripotency -- that is their ease in differentiating into a variety of different cell types. But the moral controversy surrounding embryonic stem cells -- the fact that these cells are derived from five-day old human embryos -- has encouraged research into other types of stem cells.

Now to the ridicule of my colleagues, I inspired my lab to focus on what I thought was the most non-controversial source of stem cells, adipose tissue, or fat, yes fat -- nowadays available in abundant supply -- you and I, I think, would be very happy to get rid of anyway. Fat-derived stem cells are adult stem cells. And adult stem cells are found in you and me -- in our blood, in our bone marrow, in our fat, our skin and other organs. And as it turns out, fat is one of the best sources of adult stem cells. But adult stem cells are not embryonic stem cells. And here is the limitation: adult stem cells are mature cells, and, like mature human beings, these cells are more restricted in their thought and more restricted in their behavior and are unable to give rise to the wide variety of specialized cell types, as embryonic stem cells.

But in 2007, two remarkable individuals, Shinya Yamanaka of Japan and Jamie Thompson of the United States, made an astounding discovery. They discovered that adult cells, taken from you and me, could be reprogrammed back into embryonic-like cells, which they termed IPS cells, or induced pluripotent stem cells. And so guess what, scientists around the world and in the labs are racing to convert aging adult cells -- aging adult cells from you and me -- they are racing to reprogram these cells back into more useful IPS cells. And in our lab, we are focused on taking fat and reprogramming mounds of fat into fountains of youthful cells -- cells that we may use to then form other, more specialized, cells, which one day may be used as cell transplants. If this research is successful, it may then reduce the need to research and sacrifice human embryos.

Indeed, there is a lot of hype, but also hope that the promise of stem cells will one day provide cures for a whole range of conditions. Heart disease, stroke, diabetes, spinal cord injury, muscular dystrophy, retinal eye diseases -- are any of these conditions relevant personally to you?

In May 2006, something horrible happened to me. I was about to start a robotic operation, but stepping out of the elevator into the bright and glaring lights of the operating room, I realized that my left visual field was fast collapsing into darkness. Earlier that week, I had taken a rather hard knock during late spring skiing -- yes, I fell. And I started to see floaters and stars, which I casually dismissed as too much high-altitude sun exposure. What happened to me might have been catastrophic, if not for the fact that I was in reach of good surgical access. And I had my vision restored, but not before a prolonged period of convalescence -- three months -- in a head down position. This experience taught me to empathize more with my patients, and especially those with retinal diseases.

37 million people worldwide are blind, and 127 million more suffer from impaired vision. Stem cell-derived retinal transplants, now in a research phase, may one day restore vision, or part vision, to millions of patients with retinal diseases worldwide. Indeed, we live in both challenging as well as exciting times. As the world population ages, scientists are racing to discover new ways to enhance the power of the body to heal itself through stem cells.

It is a fact that when our organs or tissues are injured, our bone marrow releases stem cells into our circulation. And these stem cells then float in the bloodstream and home in to damaged organs to release growth factors to repair the damaged tissue. Stem cells may be used as building blocks to repair damaged scaffolds within our body, or to provide new liver cells to repair damaged liver. As we speak, there are 117 or so clinical trials researching the use of stem cells for liver diseases.

What lies ahead? Heart disease is the leading cause of death worldwide. 1.1 million Americans suffer heart attacks yearly. 4.8 million suffer cardiac failure. Stem cells may be used to deliver growth factors to repair damaged heart muscle or be differentiated into heart muscle cells to restore heart function. There are 170 clinical trials investigating the role of stem cells in heart disease. While still in a research phase, stem cells may one day herald a quantum leap in the field of cardiology.

Stem cells provide hope for new beginnings -- small, incremental steps, cells rather than organs, repair rather than replacement. Stem cell therapies may one day reduce the need for donor organs. Powerful new technologies always present enigmas. As we speak, the world's first human embryonic stem cell trial for spinal cord injury is currently underway following the USFDA approval. And in the U.K., neural stem cells to treat stroke are being investigated in a phase one trial.

The research success that we celebrate today has been made possible by the curiosity and contribution and commitment of individual scientists and medical pioneers. Each one has his story. My story has been about my journey from organs to cells -- a journey through controversy, inspired by hope -- hope that, as we age, you and I may one day celebrate longevity with an improved quality of life.

Thank you.