In 2016, I called The Gene: An Intimate History one of my favorite books of the year. The book’s author, Siddhartha Mukherjee, decided to write it largely because of a huge advance that had received far less attention than it deserved: Biochemist Jennifer Doudna and microbiologist Emmanuelle Charpentier’s discovery of “genetic scissors” that allow scientists to cut any DNA sequence with incredible precision. Doudna and Charpentier’s discovery earned them the 2020 Nobel Prize in Chemistry.
2016年，我将《基因传：众生之源》列为当年最喜欢的书目之一。这本书的作者悉达多·慕克吉之所以决定写这本书，很大程度上是因为出现了一项巨大进步，但却没有得到应有的重视。生物化学家珍妮弗·道德纳和微生物学家埃玛纽埃勒·沙尔庞捷发明了“基因剪刀”，使得科学家能够以难以置信的精度切割任何脱氧核糖核酸（DNA）序列。道德纳和沙尔庞捷的发明为她们赢得了2020年诺贝尔化学奖。
The “scissors” Doudna and Charpentier discovered are known as CRISPR (pronounced like “crisper”), which stands for Clustered Regularly Interspaced Short Palindromic Repeat. The CRISPR system is a sophisticated defense that bacteria evolved to disarm invading viruses, similar to the way fungi developed penicillin to protect themselves against bacterial infection. The CRISPR system makes it much easier for scientists to alter human and other genomes in beneficial ways, such as repairing gene mutations that cause awful diseases like cystic fibrosis.
道德纳和沙尔庞捷发明的“剪刀”被称为CRISPR（与英文保鲜盒“crisper”一词同音），由“成簇的规律间隔的短回文重复序列”这一全称的英文首字母缩写而成。CRISPR系统是细菌为对抗入侵的病毒而进化出来的一种复杂的防御机制，类似于真菌为保护自己免受细菌感染而产生青霉素的机制。CRISPR系统使得科学家更容易以有益的方式来改变人类和其他基因组，如修复导致囊性纤维化等可怕疾病的基因突变。
In the five years since Mukherjee wrote his book, researchers have done a remarkable job of honing the CRISPR system for medical and agricultural applications, and my excitement about CRISPR has grown from super high to off the charts. CRISPR has fundamentally changed my thinking about what’s possible for improving the health and nutrition of families in poor countries—and how quickly. For example, it took more than 30 years to develop the first effective vaccine for malaria (which the Gates Foundation helped fund)—and that vaccine has an efficacy of only about 50 percent against severe malaria in the first year, dropping in subsequent years. Thanks to the CRISPR system, it’s very likely that our grantees will be able to develop much more effective vaccines in the next five years.
在穆克吉写下这本书后的五年里，研究人员做了出色的工作来完善CRISPR系统，使其得以在医疗和农业方面加以应用。我原就对CRISPR抱有很大兴趣，现在更是期待空前。CRISPR从根本上改变了我的看法，引我思考改善贫困国家家庭健康和营养状况的可能性——以及改善的速度会有多快。例如，人们花了30多年的时间才开发出第一种有效的疟疾疫苗（由盖茨基金会资助），而这种疫苗第一年对重症疟疾的有效性只有约50%，在随后的几年里有效性还会逐渐下降。由于CRISPR系统的存在，我们的受资助者很有可能在未来五年内开发出更有效的疫苗。
The foundation is investing in many other projects that use the CRISPR system, such as:
我们的基金会正在投资其他许多使用CRISPR系统的项目，如：
  • plant varieties that can withstand the effects of climate change.
  • a new suite of tools called programmable medical therapies, which could greatly speed up the development of treatments for new viruses and head off future pandemics.
  • quick, inexpensive ways of diagnosing diseases in poor countries.
  • monoclonal antibodies that could target and kill the pathogens that cause malaria and AIDS.
  • 能够抵御气候变化影响的植物品种。
  • 一套被称为可编程医学疗法的新工具，该工具可以大大加快新病毒治疗方法的开发进程，并阻止未来大流行的发生。
  • 贫困国家快速、廉价的疾病诊断方法。
  • 单克隆抗体，可以瞄准并杀死导致疟疾和艾滋病的病原体。
When I heard that one of my favorite authors, Walter Isaacson, was working on a book about CRISPR and its inventor, I was eager to read it. The title, The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race, suggests that the book is a biography of Doudna, but its scope is broader than that. In fact, Isaacson goes into detail about every CRISPR researcher the foundation is supporting (and many others as well). I found the book to be valuable on a number of levels.
当我听说我最喜欢的作家之一沃尔特·艾萨克森正在写一本关于CRISPR及其发明者的书时，我迫不及待地想读一读。这本书的书名是《密码破译者：珍妮弗·道德纳，基因编辑及人类未来》（ 中文名暂译），这似乎表明这本书是道德纳的传记，但其内容涵盖的范围却不止于此。事实上，艾萨克森详细地介绍了基金会正在支持的每一位CRISPR研究人员（以及许多其他研究人员）。我发现这本书在很多层面上都很有价值。
First, it’s great to read a story about scientific discovery with a woman at its center. As a dad, I was touched by the sections in which Doudna’s father, Martin, who was a professor, helps stoke his daughter’s passion for science and her confidence to pursue it at the highest levels. Unfortunately, Martin died of melanoma before his daughter achieved international fame.
首先，能读到一个围绕女性撰写的科学发现故事真是太棒了。书中一些章节讲述了道德纳的父亲马丁（曾是一位教授）如何激发了女儿对科学的热情和追求科学最高峰的信心。这些章节让同是父亲的我深受感动。不幸的是，马丁在女儿获得国际声誉之前，死于黑色素瘤。
Second, I thought Isaacson did a good job of highlighting the most important ethical questions that arise from the CRISPR revolution. Many applications of CRISPR are inarguably good, such as using it to cure blood diseases like sickle cell anemia and beta thalassemia. In these cases, scientists are alleviating human suffering in a way that does not alter the human germline. In other words, the edits affect only the person who receives them and do not get passed along to subsequent generations.
其次，我认为艾萨克森对CRISPR革命所带来的最重要的伦理问题方面强调的很好。CRISPR的许多应用毫无疑问是积极的，比如用来治疗镰状细胞贫血和β地中海贫血等血液疾病。在这些案例中，科学家们正在用一种不改变人类生殖系的方式来减轻人类的痛苦。换言之，基因编辑只影响接受改造的那个人，而不会遗传给后代。
But some scientists are not treating the germline as a red line. As Isaacson covers with nuance, three years ago a Chinese researcher named He Jiankui used CRISPR to edit the genomes of human embryos and then implanted these embryos in women who consented to carrying them to term. Two babies, named Nana and Lulu, have now been born from those embryos. If Nana and Lulu someday have babies of their own, their babies will inherit the genetic modifications Nana and Lulu received. The Chinese researcher’s intentions were good—helping HIV-positive couples give birth to children who had a gene that would confer resistance to infection with HIV—but he disregarded scientific guardrails established by Chinese and American authorities.
但是一些科学家并没有把生殖系视为一条红线。正如艾萨克森所述，三年前，一位名叫贺建奎的中国研究人员利用CRISPR技术编辑了人类胚胎的基因组，然后将这些胚胎植入同意孕育它们的妇女体内。两个婴儿，名为娜娜和露露，现在已经从这些胚胎中诞生。如果娜娜和露露有一天有了自己的孩子，他们的孩子将继承娜娜和露露接受的基因改造。这位中国研究人员的意图是好的——想要帮助艾滋病毒（HIV）阳性的夫妇生下具有抵抗HIV感染基因的孩子，但他无视了中美当局制定的科学红线。
While the foundation is not funding any CRISPR projects that involve germline editing, Doudna says it doesn’t make sense to ban germline editing outright. For one thing, she argues, editing that does not involve germline cells, known as “somatic editing,” has limitations. As I mentioned above, scientists are now able to cure sickle cell anemia, but that somatic approach is out of reach for the vast majority of the four million people who suffer from the disease, because it’s such a complex and expensive procedure and can only be done in top-tier hospitals. The germline version might be much less expensive and therefore much more accessible in low- and middle-income countries, which are home to most of the 300,000 babies born with sickle-cell disease each year.
虽然基金会没有资助任何涉及生殖系编辑的CRISPR项目，但道德纳表示，完全禁止生殖系编辑是没有意义的。她认为，首先，不涉及生殖系细胞的编辑，即所谓的“体细胞编辑”，有其局限性。正如我在上面提到的，科学家们现在能够治愈镰状细胞贫血症，但这种体细胞编辑方法对于400万患者中的绝大多数人来说是遥不可及的，因为这是一个非常复杂且昂贵的过程，只能在顶级医院进行。生殖系编辑可能要便宜得多，因此在低收入和中等收入国家更容易获得。（每年30万名出生时患有镰状细胞疾病的婴儿中，大多数出生于这些国家。）
But then another ethical dilemma arises. In Isaacson’s words, “Let’s suppose that researchers show that editing out the sickle-cell mutation is safe. Would there then be any reason to prohibit parents from having the gene edited out when they conceive children?” His answer: maybe. Isaacson introduces us to a California teen named David Sanchez, who gets sickle-cell crises so debilitating that he had to drop out of high school. When one of Sanchez’s doctors told him that “maybe one day with CRISPR they could go in and change the gene in the embryo so that the kid, when it’s born doesn’t have sickle cell,” Sanchez responded in a way you might not expect: “I think it should be up to the kid later,” he said. “There’s a lot of things that I learned having sickle cell. Because I had it, I learned patience with everyone.” The moral of the story: figuring out what’s right to edit into or out of a human genome is not clear cut.
但随后又出现了另一个伦理困境。用艾萨克森的话说，“让我们假设研究人员可以证明，编辑掉镰状细胞突变是安全的。那么，是否有任何理由禁止父母在孕育孩子时将这种基因编辑掉呢？" 他的答案是：也许有。艾萨克森向我们介绍了一个名为大卫·桑切斯的加州少年，他患有镰状细胞贫血，病情严重恶化，不得不从高中辍学。当桑切斯的一位医生告诉他，“也许有一天，他们可以用CRISPR来改变胚胎中的基因，这样孩子出生后就不会有镰状细胞了。”桑切斯的回答你大概不会料到：“我认为这应该由孩子以后自己决定。”他说，“我从镰状细胞病中学到了很多东西。因为我有这个病，我学会了对每个人都要有耐心。” 这个故事的寓意是：无论是编入还是删掉基因，在人类基因组上什么样的编辑是正确的，尚无明确界定。
The Code Breaker is highly accessible for non-scientists. And that’s super important, because the ethics of CRISPR’s use are not clear. Doudna is now spending a big portion of her time focused on these moral and ethical issues, especially the potential for genetic editing to exacerbate inequality. As she says to Isaacson, “If you think we face inequalities now, imagine what it would be like if society became genetically tiered along economic lines and we transcribed our financial inequality into our genetic code.”
《密码破译者》对非科学家来说是非常容易理解的。这一点非常重要，因为CRISPR使用的伦理规范并不明确。道德纳现在投入大部分精力来研究这些道德和伦理问题，特别是基因编辑加剧不平等的可能性。正如她对艾萨克森所说：“如果你认为我们现在面临着不平等，那么想象一下，如果社会的基因上沿着经济线分层，我们将财政上的不平等转录到我们的遗传密码中，那会是什么样子。”
As with artificial intelligence, facial recognition, and other digital technologies, the public should play an engaged role in drawing the ethical lines. That’s the best way to ensure that the world maximizes the potential for these remarkable innovations to improve the human condition.
与人工智能、面部识别和其他数字技术一样，公众应该在划定伦理底线方面发挥积极作用。这是最好的方法，以确保世界能够最大限度地发挥这些卓越创新的潜力来改善人类状况。
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