Seth Berkley:艾滋病毒和禽流感 - 疫苗战略

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http://dotsub.com/view/fb1ca34c-b863-44c7-b673-9c52d01b7fd7
Seth Berkley:艾滋病毒和禽流感 - 疫苗战略
你是否曾经担心过什么将置于你于死地？ 心脏病或者癌症 还是车祸呢？ 我们大多数担心一些我们无法控制的事情 比如战争、恐怖主义、 或者是刚刚在海地发生的悲惨的地震。 那么到底是什么真正地威胁着我们人类呢？ 几年前，Vaclav Smil教授 就试图结算一种可能性来自于® 突发性大灾难。 这种灾难足使人类的历史得以改变。 他称其这类灾难为 “大规模致命间断性灾难” 其意思就是它们将会造成 超过一亿人的死亡。 这将发生在在将来50年里。 他观察到另一场世界大战 大规模火山爆发 甚至是小行星撞击地球的某种可能会发生的机会。 他对比所有可能相似的事件 从所有的事件当中，其中 最为接近可能发生的事件就是 严重的流感大流行。 尽管你们可能认为流感 只是很严重的感冒罢啦。 但是它是致命的。 每年在美国有36000人 死于季节性流感。 在发展中国家，这个数据更为高一些， 其死亡的总数应该 高出美国的死亡人数一大节。 所存在的问题就是 如果病毒偶尔变异 甚至更为急剧的变异， 从根本上来说，它就是一个新的病毒。 那么之后，我们又将迎来新的流感大流行。
在1989年，一种新的病毒出现 这种病毒已经夺走了5000万到1亿人的性命。 它的传播就像死野火一样迅速。 一些人的流感症状正出现不久就死掉了。 难道我们今天更为安全了吗？ 然而，我们看起来似乎逃过了一劫—— 发生在今年的致命性大流感。 却让我们极为恐惧。 这样流感会在任何时候再次爆发。 有一个好消息是： 我们在一个新的时代 这个时代聚合了科学、技术、全球化 创造了史无前例的可能性。 这种可能性就是创造历史 通过阻止传染病得以实现。 然而由传染病造成的死亡人数占全球总死亡人数的五分之一， 它还将在我们这个星球上创造无数悲剧。 我们所要做的就是这些。 我们正在阻止这几百人死去， 运用现有的疫苗。 如果我们可以让更多的人接种疫苗的话， 我们当然肯定可以挽救更多人的生命。 但是我们要是能使用最新的、更好的疫苗 来预防疟疾、肺结核、艾滋病、 肺炎、痢疾、流感， 我们结束这种苦难。 这种困难一直存在我们之上。
所以我在这里向你们介绍一下疫苗。 第一点，我得解释为什么它们这么对我们如此之重要。 因为疫苗的威力 正如低声细语一般。 它们起作用的时候，它们正在改变着历史。 可是之后 你们几乎很难听见它们了。 现在，我们中一些在年龄够大的人 手臂上会留下一个小的、圆形的小疤痕。 这是因为我们在小时候接种疫苗时候留下的印记。 你最后一次担心天花疾病的时候， 这种疾病在上个世纪已经夺走了近5亿人的性命。 但现在难道已经不存在我们身边了吗？ 或者说小儿麻痹症——有多少人还记得铁肺？ 我们从没有看到这样的现象。 是因为疫苗的出现。
现在你会感觉着挺有趣。 因为新的30种奇特病毒 已经能被疫苗预防住了。 但是我们仍然受到艾滋病毒和流感的威胁。 这又是为什么呢？ 这里我想让你们知道一个小小的但是有些肮脏的秘密。 直到如今，我们从没有去了解过 疫苗到底是怎样起作用的。 我们所知道的是它们是通过旧式的反复试验得以实现其作用的。 你得到一个病原体，你改良它。 之后你把它注入人体或者动物身体里， 这时你会看到发生什么。 这个可以对付大多数的病原体， 即使是一些狡诈的病原体，像流感病毒。 但是对付艾滋病毒就不行了。 因为人类对艾滋病毒没有天然的免疫性。
所以我们探索疫苗的起作用的方式。 基本上来说，它们是创造一个 为你的免疫系统武器的隐藏所之类的东西。 当你需要的时候，你就可以通过它来部署武器。 现在，当你病毒感染了， 一切正常运转的是它会用几天或者几周的时间 为你的身体奋力还击， 它们会全力以赴去做。 也许这太晚了些。 如果你提前免疫的话， 那么你将增强你身体的实力 预先训练识别、 并且击败这些诡异的病毒。 这就是疫苗怎样起作用的。 现在，让我们来看看一段视频 这是我们在TED上初次亮相。 将向你们展示感染性艾滋病毒怎样发生的。
（音乐）
叙述者：疫苗预先训练我们身体 怎样识别和压制 特殊的入侵者。 一旦艾滋病毒穿过身体黏膜障碍， 它就开始破坏免疫细胞不断进行自我复制。 入侵者会吸引 人体免疫系统“前线部队”的注意力。 如：树突细胞、巨噬细胞， 抓住病毒，同时展现它的每一部分。 艾滋病毒产生的记忆细胞 一旦他们学会了，就会被激活。 艾滋病病毒碰到人体的“前线部队” 艾滋病病毒的记忆细胞迅速分派 适当的武器。 记忆细胞B变成血浆细胞， 而血浆细胞会产生一波又一波 特殊抗体。 这些抗体将会抓住艾滋病病毒 以其组织艾滋病病毒感染其他的细胞。 杀手T细胞中队 会寻找并破坏 被艾滋病病毒感染的细胞。 病毒就这样被打败了。 如果没有疫苗， 我们身体可能会要一周多时间才会对病毒作出反应。 到那时，与艾滋病病毒的战斗 必然是失败的了。
Seth Berkley：非常酷的视频，难道不是吗？ 你们刚刚所看到视频里的抗体的行为 那就是大部分疫苗起作用的过程。 所以真正的问题就是： 我们怎眼确保我们的身体能产生 我们所需要的抗体 抵抗流感和艾滋病病毒呢？ 面对大部分病毒最大的挑战就是 病毒总是在变换。 我们一起来看一看流感病毒。 在这个流感病毒示意图中， 那些不同颜色尖状物就是病毒用来感染你的身体的。 同样也是抗体用来 抓住并且压制这些病毒。 一旦病毒开始变异，它们开始改变自己形状， 抗体这时候就难以识别这些病毒。 所以这就是每一年，为什么 你总是感染这些与众不同的流感病毒的原因了。 这也就是，为什么每年春天 我们可以做好的设想一下， 至少三类病毒会在明年流行的原因。 我们把这些病毒制作出一种疫苗， 在秋季加紧投入生产。
可是更糟糕的是， 大部分流感病毒，流感病毒A 会感染动物。 而那些动物就是生活在人类身边。 病毒会在 这些动物中再次 重组。 还有就是，野生水生鸟类 会携带众所周知 多种流行性感冒病毒。 你们已经处在这种情况当中了。 2003年， 我们遭遇一种H5N1病毒。 它能从鸟类传染到人类 在一些个例中出现这种情况。 这种病毒造成了70%的死亡率。 现在幸运的是尽管一些特殊的病毒 在一段时间令人恐惧害怕， 但是它们不会在人与人之间传播 那样轻易地传播。 今年的H1N1病毒 其实是人类、飞禽、猪的混合病毒。 这种病毒首先在墨西哥产生。 这种病毒很容易传播， 但幸运的是，它传染性并没有那没强。 所以，在某种意义上， 我们仍是很幸运的， 但是你们知道，在任何时候，另一只鸟就从天空飞过。
现在我们来看看艾滋病病毒。 正如流感一样多变的 艾滋病毒让流感病毒 相形见绌就像直布罗陀海峡的岩石不起眼。 艾滋病毒 是最狡猾，最难缠的病毒 也是科学家面对的最难对付的病毒。 艾滋病毒急剧变异。 它甚至可以躲骗过免疫系统。 它会攻击那些抗击它的免疫细胞。 之后它会迅速的隐藏自己。 艾滋病毒隐藏在你的基因组里。 这里幻灯片向我们展示的是 流感基因多变性 相比艾滋病毒， 艾滋病毒是一个更为使人迷惑的目标。 在之前你们在视频中 看到从感染细胞中产生出一组新的病毒。 现在我们意识到这样的情形发生在每一个感染的人身体内， 它们有成千上百万个， 但是每一个都稍有不同。 所以要寻找到识别 并且击败所有的病毒的有效的武器 这是一件更为艰难的事。
自从艾滋病毒被确认为 引起艾滋病的原凶以来，已经有27年了。 我们已经研制了越来越多的药物来治疗艾滋病 然而艾滋病毒会所有的病毒聚集起来。 这使这些药物难以达到治疗效果。 但是这已经表明我们科学的（在对艾滋病毒的战斗中） 巨大的胜利 因为这些药物让艾滋病不再等同于 宣判死刑 至少对于那些能接触到药物的人来说 尽管疫苗的作用实际上完全不同。 一些大公司也不再做疫苗之类， 因为他们认为科学如此艰难 而做疫苗却又是这样不赚钱的业务。 很多人都认为研制出艾滋病毒的疫苗简直是天方夜谭。 但是现在，证据显示这是有可能的。
今年九月， 我们有一个令人惊奇和令人兴奋的发现。 在泰国的临床实验中得以这一发现的。 这是我们第一次发现艾滋病毒在人体中怎样进行的， 尽管我们的发现是有限的。 一种特殊的疫苗在十多年前 就研制出来了。 更新的理念和最近的测试 显示在动物样本中有着很好的前景。 但是在过去的几个月中，研究人员已经从 感染艾滋病毒个体的血液中分离出 新的一种有着明显的防御能力的抗体。 那这意味着什么呢？ 早些时候我们看到艾滋病毒是 急剧变化的病毒。 这种具有广泛中和能力的抗体 能依附并并且破坏 病毒的多种变化能力。 如果你取得这样疫苗并且把它注入 猴子样本中， 抗体应对感染提供全面的保护。 另外，这些研究院发现 艾滋病毒新的点 抗体抓住的地方。 这一点特别就是 抗体不会改变 在病毒变异的时候。 这就好像 尽管 病毒换了自己衣服， 但是它仍然穿着同样的短袜。 现在我们的工作就是 让我们的身体厌恶这些短袜。
这就是我们现在处境。 泰国实验结果告诉我们 我们能研制出艾滋病毒疫苗。 抗体的发现 告诉我们我们能做到。 这样的策略，我们返回我们之前工作 从抗体到制造出预选疫苗。 在疫苗研究之前这从未这样做过。 我们称这一过程为还原接种疫苗学。 这一理论的应用 已经超出艾滋病领域。 所以我们想到这中方法。 我们已经取得了这些我们确认的新的抗体 我们知道这些疫苗能抓住很多多变的病毒。 我们知道疫苗能抓住特殊的病毒。 所以我们能构想出这些病毒更为精确的结构 通过疫苗就可以做到。 我们希望我们能促使 你们的免疫系统产生相匹配的抗体。 这样能将产生 一种通用的艾滋病毒疫苗。 现在，这听起来挺容易的。 因为它的结构的确看起来像 这种蓝色抗体简图一样 粘附在黄色节点。 正如你们可以想象的，这些三位结构图 是非常更为难以制作的。 如果你们能有想法帮助我们解决这问题， 我们很愿意听听你的想法。
但是，现在，我们对艾滋病研究 的确帮助我们发明其他病毒的疫苗。 例如，一个生物科技公司 现在已经发现对付流感 广泛中和能力的抗体。 以及针对流感病毒的新的抗体。 他们正在研制一种鸡尾酒 一种鸡尾酒类型的抗体。这种能抗体能治疗 严重的流感例子。 现在，长远来看，我们能做的 使用还原接种技术 来生产防御性流感疫苗。 现在，还原接种技术是一种 在所谓理性疫苗设计范围内的技术。
我再给你另一个例子。 我们之前所说到 在流感病毒表面 的H和M的刺突。 注意看到这些其他的更小的突起物。 这些突起物都隐藏在疫苗系统里。 现在结果证明的这些节点 在病毒变异之时并没有改变。 如果你的身体特定的抗体能损害这些病毒， 那么你的身体就能抵抗所有这类的流感。 到现在为止，动物测试显示 这样一种疫苗能抵抗预防这些病毒。 尽管你会感染一些轻微的流感。 如果这些疫苗子运用在人身体中， 我们说道的就是一种通用的疫苗。 这样我们不要每年在去研制改变。 最终我们会抹掉这种死亡威胁。 实际上，我们认为这样流感 就仅仅是一次重感冒。
当然，可以想象的最好的疫苗 在某种程度上是有价值的。 我们给疫苗给那些需要的每一个人。 所以为了达到这样目的，我们不得不 把巧妙的疫苗设计与精细生产方法以及 聪明的销售方式相结合。 你们回想几个月前。 六月份，世界卫生组织 宣布41年来第一个 全球流感病毒。 美国政府承诺 15亿剂疫苗将会 在10月15日生产出来以应对流感高峰。 同样也承诺会向发展中国家提供这些疫苗。 数亿美元将会花费在 提高疫苗的产量上。 在之前我们又是怎样的？
那时我们首先想到 怎样研制疫苗，怎样生产这些疫苗。 那是在20世纪40年代初期。 那是一段缓慢而复杂的过程。 因为我们整个过程都要依赖鸡蛋， 上百万的活鸡蛋。 病毒只能通过这样活鸡蛋才能生长。 的确最后也证明这一点。 对于流感，鸡蛋相当有用。 对于大部分种类病毒，你可能每个鸡蛋 会产出一到两剂疫苗。 我们是幸运的。 我们生活在 生物医药飞速发展的时代。 即使是今天，我们的流感疫苗也是来自 这些鸡蛋。 （笑声） 来自这些数以亿计的鸡蛋。 这些几乎没有改变过。 系统是可靠的。 但是现在问题是，你们不知道 一种病毒是怎样生产的。 今年猪流感病毒 在早期生产中很难生产 基本上，每只蛋产6剂疫苗。 这可是一种令人害怕的想法。 如果野生飞禽又飞回来，那又会怎么样呢？ 你可能都知道禽流感病毒 能感染家禽。 那时，我们就没有生产疫苗的鸡蛋了。 Dan，如果你想 要上百亿个鸡蛋 来自你们的农场。 我知道哪里可以得到这些鸡蛋。 现在全球能生产 3.5亿剂 3种流感病毒的疫苗。 我们能提产到12亿剂疫苗。 如果我们只生产一类病毒的疫苗 例如猪流感。 但是我们想到我们的工厂正在热火生产 因为，2004年， 美国产量减产一般 是由于一种疫苗受到污染。 这一生产过程需要 半年多的时间。
我们现在是否比 我们1918年那时准备更好吗？ 当然，随着新科技兴起， 我希望我们可以确定的说“是”。 想象一下，如果我们能为全球 生产足够的流感疫苗。 但是我们只要花费 现在在美国疫苗生产费用一半还好少。 我们运用新技术这是可以实现的。 这里有一个例子。 我之前工作过家公司已经发现 一种H刺突流感病毒。 这种病毒能激发免疫系统。 如果你能消除这种病毒，并且把它 粘附在另一种不同细菌的尾巴上。 这样就可以激起免疫系统的反应。 他们已经研制出一种强有力的流感病毒战士。 这种疫苗相当的微小。 这种疫苗能普通的细菌中就能产生。 现在这种细菌繁殖非常快速。 这就好像制造酸奶一样。 所以我们能在几个工厂就能 在几周内生产猪流感病毒。 但是我们并不需要使用鸡蛋。 而且我们只要花费现在生产方式的费用的一小部分就可以了。
（鼓掌）
这只是几种疫苗新科技的比较。 除了根本上提高产量和 大幅度节约生产成本之外， 就我们刚才说道的E.coli方法， 这种方法还节约了时间，这就意味着拯救更多生命。 发展中国家 大部分发展中国家脱离了时代的潮流， 他们却看到了这种替代技术的巨大潜力。 他们正在超越西方的发达国家。 印度、墨西哥以及其他发展中国家 正在做流感疫苗的实验。 他们也许处于领先地位。 我们看到这种疫苗的用途性 因为这些技术如此高效率 而且相对便宜。 那么几十亿的普通大众也能接种这种救命的疫苗。 如果我们构想出销售这些疫苗方式。
最近我们在想我们在研究的 新的感染性的疾病 一次又一次的出现。 每隔几年都会出现。 某一天，也许很快 又会出现一种威胁我们的新的病毒。 然而这次我们将最快作出反应 在百万人逝去之前，我们将做到。 幸运的是，今年的流感病毒相对微弱。 我刚说“幸运” 因为在过去发展中国家几乎没有一人 接种过疫苗。 如果那些有着政治和金融远见的投资者 来持续我们对疫苗生产的投资。 我们将掌握疫苗技术的新工具。 运用这些新工具，我们能 生产出低廉的，普通大众都买得起的疫苗。 这样可以保障那些健康而充实有效的生命。 每年流感不会再夺走50多万的生命了。 每年艾滋病也不会再 夺走200多万的生命。 不论是贫穷或嬴弱的人们 也不会在受到感染性疾病的威胁饿了。 的确，不会威胁到任何人。 然而不会再有Vaclav Smil’s 这样的大规模非持续性致命疾病了。 我们能保证 生命的延续。 现在世界需要的就是这些新的疫苗， 我们能生产出来。
非常感谢！
（掌声）
Chris Anderson ：谢谢。 （掌声） 谢谢 科学日新月异变化着。 在你看来，我的意思是，你在想 什么时候， 就拿艾滋病毒来说， 我们会使用上这种已经存在的游戏替换式疫苗呢？
SB：任何时候游戏不断替换。 因为我们现在的面对的问题是 正如我们刚才向你们展现疫苗在人体如何工作的。 我们需要更好的一种。 人类的身体可以使用这类抗体就可以对抗病毒。 如果我们知道它们怎么工作的， 之后我们就研制出疫苗。 正真有趣的是 有些迹象证明我们已经开始解决这些问题。 所以研制速度仍是我们的一大挑战。
CA：在你开来，你是否认为还要五年的时间才研制出下一种疫苗呢？
SB：每个人都说要十年， 但是几十年已经过去了。 我个人不喜欢给 科学发明一种时间限制。 那是那些投入研究的资金正在用于支付股东红利。
CA：它们与通用的流感疫苗是同样的吗？
SB：我认为流感是不同的。 一旦我们遇到一大股的流感时——正如我们刚刚展示的， 我们有一批相当酷而且非常有用的技术已经准备好了。 它们看起来不错。还有一个问题 我们过去投资在传统技上。 因为那是过去合适的方式。 你也能用一种你混合化学用品的佐剂。 这也正是欧洲国家在做的，要是我们能稀释出 我们提供的流感病毒，然后研制出更多的。 但是，说道MichaelSpecter 说的话， 抗疫苗的病毒可不希望这样的事 发生。
CA：疟疾疫苗实现当落后了吧？
SB：不，疟疾， 我们已经早期试验中发现一种疟疾疫苗候选者表现非常有效。 现在已经进入了第三阶段的实验。 它现在可能不是那没完美的疫苗，但是它正在改进中。
CA：Seth，像我们大家一样每个月工作 像我们一样，制作一些东西。 我们会感到非常快乐。 你们已经投入研究这一领域有十多年了。 我得向你和你的同事致敬，以及你们的研究成果。 这个世界需要像你们这样的一类人。谢谢你们！
SB：谢谢。
（掌声）


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Seth Berkley: HIV and flu -- the vaccine strategy
Do you worry about what is going to kill you? Heart disease, cancer, a car accident? Most of us worry about things we can't control like war, terrorism, the tragic earthquake that just occurred in Haiti. But what really threatens humanity? A few years ago, Professor Vaclav Smil tried to calculate the probability of sudden disasters large enough to change history. He called these "massively fatal discontinuities," meaning that they could kill up to 100 million people in the next 50 years. He looked at the odds of another world war, of a massive volcanic eruption, even of an asteroid hitting the Earth. But he placed the likelihood of one such event above all others, at close to 100 percent, and that is a severe flu pandemic. Now, you might think of flu as just a really bad cold. But it can be a death sentence. Every year, 36,000 people in the United States die of seasonal flu. In the developing world, the data is much sketchier, but the death toll is almost certainly higher. You know, the problem is if this virus occasionally mutates so dramatically, it essentially is a new virus. And then we get a pandemic.

In 1918, a new virus appeared that killed some 50 to 100 million people. It spread like wildfire. And some died within hours of developing symptoms. Are we safer today? Well, we seem to have dodged the deadly pandemic this year that most of us feared, but this threat could reappear at any time. The good news is that we're at a moment in time when science, technology, globalization is converging to create an unprecedented possibility, the possibility to make history by preventing infectious diseases that still account for one-fifth of all deaths and countless misery on Earth. We can do this. We're already preventing millions of deaths with existing vaccines. And if we get these to more people, we can certainly save more lives. But with new or better vaccines for malaria, TB, HIV, pneumonia, diarrhea, flu, we could end suffering that has been on the Earth since the beginning of time.

So I'm here to trumpet vaccines for you. But first, I have to explain why they're important. Because vaccines, the power of them, is really like a whisper. When they work, they can make history, but after awhile, you can barely hear them. Now, some of us are old enough to have a small, circular scar on our arms from an inoculation we received as children. But when was the last time you worried about smallpox, a disease that killed half a billion people last century and no longer is with us? Or polio -- how many of you remember the iron lung? We don't see scenes like this anymore because of vaccines.

Now, you know, it's interesting because there are 30-odd diseases that can be treated with vaccines now, but we're still threatened by things like HIV and flu. Why is that? Well, here's the dirty little secret. Until recently, we haven't had to know exactly how a vaccine worked. We knew they worked through old-fashioned trial and error. You took a pathogen, you modified it, you injected it into a person or an animal, and you saw what happened. This worked well for most pathogens, somewhat well for crafty bugs like flu, but not at all for HIV, for which humans have no natural immunity.

So let's explore how vaccines work. They basically create a cache of weapons for your immune system which you can deploy when needed. Now, when you get a viral infection, what normally happens is it takes days or weeks for your body to fight back at full strength, and that might be too late. When you're pre-immunized, what happens is you have forces in your body pre-trained to recognize and defeat specific foes. So that's really how vaccines work. Now, let's take a look at a video that we're debuting at TED, for the first time, on how an effective HIV vaccine might work.

(Music)

Narrator: A vaccine trains the body in advance how to recognize and neutralize a specific invader. After HIV penetrates the body's mucosal barriers, it infects immune cells to replicate. The invader draws the attention of the immune system's front-line troops. Dendritic cells, or macrophages, capture the virus and display pieces of it. Memory cells generated by the HIV vaccine are activated when they learn HIV is present from the front line troops. These memory cells immediately deploy the exact weapons needed. Memory B cells turn into plasma cells, which produce wave after wave of specific antibodies that latch on to HIV to prevent it from infecting cells while squadrons of killer T cells seek out and destroy cells that are already HIV infected. The virus is defeated. Without a vaccine, these responses would have taken more than a week. By that time, the battle against HIV would already have been lost.

Seth Berkley: Really cool video, isn't it? The antibodies you just saw in this video, in action, are the ones that make most vaccines work. So the real question then is: How do we insure that your body makes the exact ones that we need to protect against flu and HIV? The principal challenge for both of these viruses is that they're always changing. So let's take a look at the flu virus. In this rendering of the flu virus, these different colored spikes are what is uses to infect you. And also, what the antibodies use is a handle to essentially grab and neutralize the virus. When these mutate, they change their shape, and the antibodies don't know what they're looking at anymore. So that's why, every year, you can catch a slightly different strain of flu. It's also why, in the spring, we have to make a best guess at which three strains are going to prevail the next year, put those into a single vaccine and rush those into production for the fall.

Even worse, the most common influenza, influenza A, also infects animals that live in close proximity to humans, and they can recombine in those particular animals. In addition, wild aquatic birds carry all known strains of influenza. So, you've got this situation. In 2003, we had an H5N1 virus that jumped from birds into humans in a few isolated cases with an apparent mortality rate of 70 percent. Now luckily, that particular virus, although very scary at the time, did not transmit from person to person very easily. This year's H1N1 threat was actually a human, avian, swine mixture that arose in Mexico. It was easily transmitted, but luckily, was pretty mild. And so, in a sense, our luck is holding out, but you know, another wild bird could fly over at anytime.

Now let's take a look at HIV. As variable as flu is, HIV makes flu look like the Rock of Gibraltar. The virus that causes AIDS is the trickiest pathogen scientists have ever confronted. It mutates furiously. It has decoys to evade the immune system. It attacks the very cells that are trying to fight it. And it quickly hides itself in your genome. Here's a slide looking at the genetic variation of flu and comparing that to HIV, a much wilder target. In the video a moment ago, you saw fleets of new viruses launching from infected cells. Now realize that in a recently infected person, there are millions of these ships, each one is just slightly different. Finding a weapon that recognizes and sinks all of them makes the job that much harder.

Now, in the 27 years since HIV was identified as the cause of AIDS, we've developed more drugs to treat HIV than all other viruses put together. These drugs aren't cures, but they represent a huge triumph of science, because they take away the automatic death sentence from a diagnosis of HIV, at least for those who can access them. The vaccine effort though is really quite different. Large companies moved away from it because they thought the science was so difficult and vaccines were seen as poor business. Many thought that it was just impossible to make an AIDS vaccine, but today, evidence tells us otherwise.

In September, we had surprising, but exciting findings from a clinical trial that took place in Thailand. For the first time, we saw an AIDS vaccine work in humans, albeit, quite modestly. And that particular vaccine was made almost a decade ago. Newer concepts and early testing now show even greater promise in the best of our animal models. But in the past few months, researchers have also isolated several new broadly neutralizing antibodies from the blood of an HIV infected individual. Now, what does this mean? We saw earlier that HIV is highly variable, that a broad neutralizing antibody latches on and disables multiple variations of the virus. If you take these and you put them in the best of our monkey models, they provide full protection from infection. In addition, these researchers found a new site on HIV where the antibodies can grab onto. And what's so special about this spot is that it changes very little as the virus mutates. It's like, as many times as the virus changes its clothes, it's still wearing the same socks, and now our job is to make sure we get the body to really hate those socks.

So what we've got is a situation. The Thai results tell us we can make an AIDS vaccine. And the antibody findings tell us how we might do that. This strategy, working backwards from an antibody to create a vaccine candidate, has never been done before in vaccine research. It's called retro-vaccinology, and its implications extend way beyond that of just HIV. So think of it this way. We've got these new antibodies we've identified, and we know that they latch on to many, many variations of the virus. We know that they have to latch on to a specific part, so if we can figure out the precise structure of that part, present that through a vaccine, what we hope is we can prompt your immune system to make these matching antibodies. And that would create a universal HIV vaccine. Now, it sounds easier than it is because the structure actually looks more like this blue antibody diagram attached to its yellow binding site. And as you can imagine, these three-dimensional structures are much harder to work on. And if you guys have ideas to help us solve this, we'd love to hear about it.

But, you know, the research that has occurred from HIV, now, has really helped with innovation for other diseases. So for instance, a biotechnology company has now found broadly neutralizing antibodies to influenza as well as a new antibody target on the flu virus. They're currently making a cocktail, an antibody cocktail, that can be used to treat severe, overwhelming cases of flu. Now, in the longer term, what they can do is use these tools of retro-vaccinology to make a preventive flu vaccine. Now, retro-vaccinology is just one technique within the ambit of so-called rational vaccine design.

Let me give you another example. We talked about before the H and M spikes on the surface of the flu virus. Notice these other, smaller protuberances. These are largely hidden from the immune system. Now it turns out that these spots also don't change much when the virus mutates. If you can cripple these with specific antibodies, you could cripple all versions of the flu. So far, animal tests indicate that such a vaccine could prevent severe disease, although you might get a mild case. So if this works in humans, what we're talking about is a universal flu vaccine, one that doesn't need to change every year and would remove the threat of death. We really could think of flu then as just a bad cold.

Of course, the best vaccine imaginable is only valuable to the extent we get it to everyone who needs it. So to do that, we have to combine smart vaccine design with smart production methods and, of course, smart delivery methods. So I want you to think back a few months ago. In June, the World Health Organization declared the first global flu pandemic in 41 years. The U.S. government promised 150 million doses of vaccine by October 15th for the flu peak. Vaccines were promised to developing countries. Hundreds of millions of dollars were spent and flowed to accelerating vaccine manufacturing. So what happened?

Well, we first figured out how to make flu vaccines, how to produce them, in the early 1940s. It was a slow, cumbersome process that depended on chicken eggs, millions of living chicken eggs. Viruses only grow in living things, and so it turned out that, for flu, chicken eggs worked really well. For most strains, you could get one to two doses of vaccine per egg. Luckily for us, we live in an era of breathtaking biomedical advances. So today, we get our flu vaccines from ... ... chicken eggs, (Laughter) hundreds of millions of chicken eggs. You know, almost nothing has changed. You know, the system is reliable. But the problem is, you never know how well a strain is going to grow. This year's swine flu strain grew very poorly in early production, basically .6 doses per egg. So here's an alarming thought. What if that wild bird flies by again? You could see an avian strain that would infect the poultry flocks, and then we would have no eggs for our vaccines. So, Dan [Barber], if you want billions of chicken pellets for your fish farm, I know where to get them. So right now, the world can produce about 350 million doses of flu vaccine for the three strains. And we can up that to about 1.2 billion doses, if we want to target a single variant like swine flu. But this assumes that our factories are humming because, in 2004, the U.S. supply was cut in half by contamination at one single plant. And the process still takes more than half a year.

So are we better prepared than we were in 1918? Well, with the new technologies emerging now, I hope we can say definitively, "Yes." Imagine if we could produce enough flu vaccine for everyone in the entire world for less that half of what we're currently spending now in the United States. With a range of new technologies, we could. Here's an example. A company I'm engaged with has found a specific piece of the H spike flu that sparks the immune system. If you lop this off and attach it to the tail of a different bacterium which creates a vigorous immune response, they've created a very powerful flu fighter. This vaccine is so small, it can be grown in a common bacteria, E. coli. Now, as you know, bacteria reproduce quickly. It's like making yogurt. And so we could produce enough swine origin flu for the entire world in a few factories, in a few weeks with no eggs for a fraction of the cost of current methods.

(Applause)

So here's a comparison of several of these new vaccine technologies. And, aside from the radically increased production and huge cost savings, for example, the E. coli method I just talked about, look at the time saved -- this would be lives saved. The developing world, mostly left out of the current response, sees the potential of these alternate technologies, and they're leapfrogging the West. India, Mexico and others are already making experimental flu vaccines, and they may be the first place we see these vaccines in use. Because these technologies are so efficient and relatively cheap, billions of people can have access to lifesaving vaccines, if we can figure out how to deliver them.

Now think of where this leads us. New infectious diseases appear or reappear every few years. Some day, perhaps soon, we'll have a virus that is going to threaten all of us. Will we be quick enough to react before millions die? Luckily, this year's flu was relatively mild. I say, "luckily" in part because virtually no one in the developing world was vaccinated. So if we have the political and financial foresight to sustain our investments, we will master these and new tools of vaccinology. And with these tools, we can produce enough vaccine for everyone at low cost and insure healthy productive lives. No long must flu have to kill half a million people a year. No longer does AIDS need to kill two million a year. No longer do the poor and vulnerable need to be threatened by infectious diseases or, indeed, anybody. Instead of having Vaclav Smil's "massively fatal discontinuity" of life, we can ensure the continuity of life. What the world needs now are these new vaccines, and we can make it happen.

Thank you very much.

(Applause)

Chris Anderson: Thank you. (Applause) Thank you. So, the science is changing. In your mind, Seth -- I mean, you must dream about this -- what is the kind of time scale on, let's start with HIV, for a game-changing vaccine that's actually out there and usable?

SB: The game change can come at any time because the problem we have now is we've shown we can get a vaccine to work in humans, we just need a better one. And with these types of antibodies, we know humans can make them. So, if we can figure out how to do that, then we have the vaccine. And what's interesting is there already is some evidence that we're beginning to crack that problem. So the challenge is full speed ahead.

CA: In your gut, do you think it's probably going to be at least another five years?

SB: You know, everybody says it's 10 years, but it's been 10 years every 10 years. So I hate to put a time line on scientific innovation, but the investments that have occurred are now paying dividends.

CA: And that's the same with universal flu vaccine, the same kind of thing?

SB: I think flu is different. I think what happened with flu is we've got a bunch -- I just showed some of this -- a bunch of really cool and useful technologies that are ready to go now. They look good. The problem has been that, what we did was we invested in traditional technologies because that's what we were comfortable with. You also can use adjuvants, which are chemicals you mix. And that's what Europe is doing, so we could have diluted out our supply of flu and made more available, but, going back to what Michael Specter said, the antivaccine crowd didn't really want for that to happen.

CA: And malaria's even further behind?

SB: No, malaria, there is a candidate that actually showed efficacy in an earlier trial and is currently in phase three trials now. It probably isn't the perfect vaccine, but it's moving along.

CA: Seth, most of us do work where every month we kind of, you know, we produce something, we get that kind of gratification. You've been slaving away at this for more than a decade, and I salute you and your colleagues for what you do. The world needs people like you. Thank you.

SB: Thank you.

(Applause)