这种治疗艾滋病的基因疗法不是一般的对体细胞进行修改，而是对胚胎细胞进行基因编辑修改。它与体细胞基因疗法的最大区别在于，如果失败，将影响到下一代，甚至子子孙孙。因为，它们会随胚胎基因遗传下去，无穷匮也。
南方科技大学副教授贺建奎在第二届人类基因组编辑峰会召开前一天（11月26日）宣布：一对基因编辑婴儿于2018年11月在中国健康诞生。这是一对双胞胎姐妹——露露和娜娜，她们在胚胎形成时经过基因剪刀CRISPR/Cas9对其生殖细胞核中一个基因（CCR5）进行了编辑修改，使得她们出生后即能天然抵抗艾滋病。这是世界首例免疫艾滋病的基因编辑婴儿。
现在，全球已经有122位科学家公开发表声明，集体谴责这一试验，称这是打开了“潘多拉魔盒”。而且，还有科学家认为，基因编辑婴儿危及科学与社会的关系，损害中国的国际科学声誉，并可能使全球基因疗法的发展倒退多年。
深圳市医学伦理专家委员会也发表声明，已启动对深圳和美妇儿科医院伦理问题的调查。南方科技大学同时发表声明称，贺建奎副教授将基因编辑技术用于人体胚胎研究，生物系学术委员会认为其严重违背了学术伦理和学术规范。
多变的艾滋病病毒
国际国内一致地批评和指责基因编辑婴儿，问题的核心在什么地方呢？如果我们把眼光放到艾滋病的形成、治疗、预防的历史，以及目前的现状来看，并且从基因编辑婴儿的核心来观察，可能会获得一些答案。
1981年6月5日，美国疾病控制和预防中心（CDC）报道，洛杉矶地区5名健康的男同性恋者患了卡氏肺囊虫肺炎（PCP），这就是人类最早发现的艾滋病，只是当时人们并不知道，而称其为卡氏肺囊虫肺炎。
不过，多年来，人们已经知道，艾滋病病毒（HIV）依靠几种手段侵犯人类。
一是借助人类免疫T细胞上的分子标记，这些标记也像是门把手或支点，如CD4分子和CCR5趋化因子。二是采用寄生的方式，一旦入侵T细胞后，HIV分子就把自己的一段基因塞入T细胞的DNA中，跟随T细胞的DNA进行复制，然后再释放到血液中感染更多的T细胞。三是HIV有多种类型，并且可以随时变化自己的分子结构，以躲避T细胞识别和攻击。
仅在类型上，HIV就拥有了类似孙悟空72变的本领。分子生物学家的检测发现，HIV可以分为两大类，HIV-1T和HIV-2，但是，仅在HIV-1中，中国就是世界上HIV亚型种类最多的国家之一，共有A、B（欧美B）、B’（泰国B）、C、D、E、F、G8种，以B’和C型居多，B’型占47.5%，C型占34.3%，E型占9.6%，其他亚型分别占5.7%~0.3%。
同时，一些研究人员对广西HIV-1感染者的HIV-1膜蛋白基因C2-V3区核酸片段并提纯回收，进行核苷酸序列测定与亚型分析，发现广西HIV-1流行毒株的基因变异程度较大。14份HIV-1核苷酸序列测定与亚型分析结果表明，9份为B亚型，5份为E亚型。另外，对贵州11例感染HIV-1的病人分析，B亚型有7例，C、E亚型各2例。因此，只要沾上HIV，凭HIV的诡计多端和神秘变化，人们就很难脱身。不过，T细胞上的分子受体CCR5可能是HIV更喜欢的“帮凶”。就像HIV多变一样，CCR5也有基因变异性，如果它一变异，艾滋病病毒就无法识别它，也无法借助这个帮手进入T细胞。
▲艾滋病病毒（图/图虫创意）
研究人员是在对各个国家和民族的人感染HIV时发现这一秘密的。美国黑人比白人容易患艾滋病，因此有研究人员推测，是不是他们性乱程度高造成的？在进行实际调查时发现，黑人的CCR5基因变异率较低，他们体内的CCR5不太会装扮改变自己，也就不能阻止艾滋病病毒的入侵。
再对其他人种进行调查发现，黑人的CCR5变异率仅为1.6%，美国白人的CCR5基因变异率为10%，欧洲人则为8%。只有俄罗斯人的CCR5基因变异率最高，为12%。显而易见，黑人的艾滋病易感率高与CCR5变异率的大小有重要关系。不幸的是，中国人身上的CCR5基因的变异率可能是世界上所有人种中最低的。中国研究人员王福生和蒋建东在国内各地随机抽取1300人的基因，经测定表明，只有3人的CCR5基因有突变。这说明，中国人的CCR5基因变异率比黑人还低，也意味着中国人比黑人更容易感染艾滋病。
于是，针对CCR5基因的研究和治疗就成为征服艾滋病的一个重要方向。不过，在贺建奎团队之前，世界各国的研究人员还进行了其他研究，主要是治疗（包括移植干细胞治疗、药物治疗）和疫苗研发。神秘的柏林病人。
在世人的眼中，艾滋病是不可治愈的。但是，世界上第一位被专家认可治愈了艾滋病的病人是“柏林病人”，这是最早的称呼，为的是保密，同时人们当初也对他的治疗效果表示怀疑，希望用时间来检验。后来，他的真名实姓才被公布，是美国人蒂莫西·雷·布朗（Timothy Ray Brown）。
2000年，在德国任翻译的布朗患上了白血病和艾滋病两种病。2007年，当时在柏林的布朗求医于肿瘤病和血液病专家胡特。经过胡特诊断，发现布朗的白血病比艾滋病更严重。胡特决定先全力治疗布朗的白血病，方法是进行骨髓移植。经过3年的治疗，没想到，不仅治愈了布朗的白血病，还连同他的艾滋病也治愈了，标志是，布朗的血液中查不出HIV了。而且，多年后，柏林病人身上也几乎查不到HIV，说明他已经摆脱了常人不可能摆脱的艾滋病魔鬼。原因何在呢？治疗柏林病人的医生首先想到的是，柏林病人接受过他人的骨髓移植治疗白血病，于是决定检测柏林病人的血液和干细胞成分。这一检测，获得了惊人的发现，柏林病人在移植骨髓干细胞时意外地获得了变异的CCR5基因，这种变异基因编码产生的CCR5趋化因子让HIV难以识别并无法利用CCR5因子进入T细胞。
图/图虫创意
这就证明，以前对不同种族的人的研究结果至少是部分正确，变异的CCR5基因的确有减少HIV感染的效果。但是，CCR5基因变异是天生的，在不同种族人身上比例不同，尤其在中国人和黑人身上较少，想要利用这种变异基因来治疗艾滋病就像中大奖一样，不具有普遍性。而且，骨髓干细胞移植的费用高昂，技术比较复杂，治疗过程也充满风险。
更重要的是，如果能找到有CCR5基因变异的人，而且人家也愿意成为供者，提供骨髓或血液干细胞给病人，在治疗时也首先要与患者（受者）白细胞表面抗原相匹配，才能进行移植。虽然CCR5基因变异的人在俄罗斯和北欧人体内存在的比例较高，但要找到供者和受者的白细胞表面抗原相匹配也很难。也就是说，同时符合这两个条件很难，因此治疗柏林病人的骨髓干细胞移植只是一种奢侈的试验性疗法，无法飞入寻常百姓家。现在的基因编辑婴儿显然是受到CCR5基因变异的启发。既然无法获得自然变异的CCR5基因，而且移植他人的变异CCR5基因又昂贵，何不采用基因编辑的方法让正常的CCR5基因变异来抗御艾滋病呢？有这个想法的不止是中国科学家，世界各国的科学家都在探索，但是由于技术的不成熟，以及建立在技术保障之上的伦理规章，让全球的科学家都不愿也不敢轻举妄动。
图/东方IC
最重要的原因在于，这种治疗艾滋病的基因疗法不是一般的对体细胞进行修改，而是对胚胎细胞进行基因编辑修改。它与体细胞基因疗法的最大区别在于，如果失败，将影响到下一代，甚至子子孙孙，无穷匮也。因为，它们会随胚胎基因遗传下去。但是，体细胞基因疗法如果失败，伤害的也就是一个人，即患者本人，不会伤及他/她的后代。
对这一点上，以及多种伦理规定和技术缺陷，贺建奎团队认识得非常清楚。贺建奎在2017年2月发表的，题为《人类胚胎基因编辑的安全性尚待解决》的文章中指出，尽管美国科学院在2017年2月发布报告称，编辑人类胚胎DNA以阻止婴儿疾病在伦理上或许可被接受，相当于为人类基因编辑开黄灯，但还是有很多伦理和技术难题需要首先解决。这些问题都涉及到安全。
一是基因编辑技术还未经过完备的模式动物（如猴子）及细胞系安全性评估；二是人类基因编辑后可能出现脱靶效应，需要建立质量控制流程来加以规避；三是在进行胚胎基因组编辑时，嵌合体问题还未解决，可能带来的影响还未厘清；四是胚胎发育会受到怎样的影响，需要在分子水平或功能水平得到详尽研究；五是经过基因编辑的人类，在繁衍多代以后会不会有影响？需要由动物模型得到验证。
而且，贺建奎也清楚，CRISPR-Cas9基因剪刀是一种新技术，需要进行更深入的研究和了解。不论是从科学还是社会伦理的角度考虑，在没有解决这些重要的安全问题之前，任何进行生殖细胞系编辑或制造基因编辑的人类的行为都是极其不负责任的。
图/图虫创意
换句话说，在没有解决这些问题之前，任何用基因剪刀编辑婴儿的行为都是人类社会不接受的。这也是基因编辑婴儿必须受到严格的伦理审批的原因。现在，在编辑和创造婴儿方面走在世界前列的英国，如果要编辑胚胎，需要获得英国卫生部和英国人类生育与胚胎学管理局(HFEA)的批准，并且需要专门的伦理审核通过后才可进行研究。同时，英国严格规定，编辑胚胎基因可以，但要求所有试验胚胎在发育第14天销毁，禁止移植入母体，也就根本不可能让基因编辑婴儿出生。后果
并非说，其他国家没有批准的研究中国就不可以做，而是这样的试验性治疗研究是否能保证后代的安全。一些基因编辑和遗传的后果已经通过科幻作品告诉人们了，较早的有《弗兰肯斯坦》，后来的有《绿巨人》。
《绿巨人》的主人公浩克是世界著名的物理学家，在一次意外中受到了被自己制造出的伽玛炸弹的放射线大量辐射，身体产生异变，后来，每当他情绪激动心跳加速的时候就会变成名为浩克的绿色怪物。由于变身后往往不受控制，伤害他人。为了不伤害自己周围的人，浩克游走于世界各地寻找控制愤怒的方法，即便如此他也会造成毁灭性的破坏，因此他成为警方与有关单位追捕的对象。
▲绿巨人浩克（图/图虫创意）
然而，基因编辑婴儿的后果可能比绿巨人还要严重。已经有研究人员进一步发现，有“基因魔剪”之称的CRISPR-Cas9基因组编辑技术并不精准，脱靶率较高。英国《自然·生物技术》杂志发表英国维康桑格研究所艾兰·布拉德雷等人的一项研究，指出CRISPR-Cas9会在靶点附近引起DNA删除或重排，结果比此前预期的要严重。对小鼠和人类的实验室细胞系研究发现，除了已知的伴随DNA双链断裂修复发生的小规模DNA错误外，CRISPR-Cas9技术还可能在靶点附近导致大规模的DNA删除，在部分情况下，甚至引起复杂的DNA重排，导致临近基因或调控序列受到影响，并改变细胞功能。
一个简单的情况是，如果后代的基因重排，后果可能是龙不生龙，凤不生凤；也可能是后代变成比弗兰肯斯坦还要奇怪和厉害的怪物，如古希腊神话中的喀迈拉（Chimera），即母山羊，它拥有羊身、狮头（赫西奥德的《神谱》中记载有说它有三个头）和蛇尾，会喷火。这就是基因编辑之后的嵌合体问题，即不同的基因嵌合，形成非人非马，非牛非猪的生物。
图/东方IC
也因此，世界主流科学家极力反对在安全问题尚未解决之前，进行人的胚胎基因编辑，即便需要如此做来让人改头换面，以治愈艾滋病，也首先得经过动物试验，例如对非人灵长类（猴子）的试验，才能过渡到人。
全球科学家的反对不是没有理由的。
（冰川思享号特约撰稿 | 张田勘）
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