贺建奎今天到底说了什么？真相在此！
“我不知道怎么回答这个问题。”
作者丨姜飞熊
来源丨医学界
今天下午，因“制造出基因编辑人类”而备受争议的贺建奎出现在第二届人类基因组编辑国际峰会，在演讲结束后，大会主办方给了他一个回答各方质问和疑问的机会。
主办方现已公布其演讲和问答的全部英文速记内容，现摘取一些大家比较关心的问题，进行翻译。
关于如何过伦理，如何获得许可的问题：
原文
Q: What did you to get feedback on the clinical trial design? What was the scope of the team and where did you go to get approvals?
A: I first talked with a couple of scientists and a doctor to find out whether CCR5 was the one recommended. Once we had some data, I presented at Cold Spring Harbor in 2017 and also at the Berkeley genome editing conference. Some of the others in that conference too. I received positive feedback and also some criticism and also some constructive advice. I continued to talk with not just scientists but also the top ethicists in the United States such as at Stanford and Harvard. I also showed my data to visiting scientists. When I started a clinical trial for the informed consent, we.. as a reference.. and drafted a consent form. The letter was reviewed by a US professor. ... Subsequent... follow-on plan.
译文：
Q：你临床试验设计的反馈是怎么来的？团队的范围是什么？你上哪得到批准的？
A ：我先是和几位科学家和一位医生讨论了一下，想了解他们是不是推荐CCR5。此后我获得了一些数据，并且在2017年在冷泉港和伯克利的基因编辑会议上进行了展示。会议中的其他一些人也是如此。我获得了正面的反馈，也有一些批评和建设性的意见。我继续与一些科学家讨论，同时也和一些美国顶级的伦理学家，比如来自哈佛和斯坦福的讨论这个问题。同时我也把数据给访问学者展示。当我们开始一项知情同意临床试验的时候，我们……作为参考……并起草了一份同意书。这封信由一名美国教授评议过……随后……后续计划。（此处翻译不通顺是因为速记原文在此处不完整）
原文
Q: I have a two-part ethical question. Could you slow down a little bit and talk about the institutional ethics process that you said you went through. Looking to the past. The second part is looking to the future- how do you understand your responsibility to these children? Your last slide indicated that you would be doing follow-up treatment. What is your responsibility towards the future as well?
A: Do you see your friends, your relatives who may have-- a genetic disease-- the way I see it, those people need help. There are millions of families with inherited diseases or or exposure to infectious disease. If we have the technology and can make it available, then this will help people. When we talk about the future, first it's a transparent open and share what knowledge I accumulate to society and to the world. It is up to society to decide what to do next.
译文：
Q：我有一个分两部分的伦理问题。首先，你慢一点，说一说你是怎么过机构制度伦理流程的。这部分是回首过去。第二部分是展望未来——你怎么理解你对那两个孩子的责任？你最后一张PPT说你会进行后续治疗。你对未来的责任是什么？
A：你看到你的亲朋好友有基因病——我是这样看的，你会觉得这些人需要帮助。有成千上万的家庭有遗传病或者暴露在感染病当中。如果我们有技术，而且能实现，那这就能够帮助他们。说到未来，首先，它是透明开放的，我将向社会和全世界分享我积累的知识。应该由社会来决定之后怎么做。
（这种回答没能让提问者满意，他追问了一个问题）
Q: What about the actual children? It was not an abstract question. Going forward with these born children, how do you understand your responsibility to them?
Q：我想问的是特指这个案例里的那两个孩子，这不是一个抽象的问题。这两个被生出来的孩子，你怎么理解自己对他们的责任？
（这个问题贺建奎并未作答）
关于知情同意的问题：
原文
Q: How did you convince the parents when you started this expeirment? Did you tell them about alternatives to avoid AIDS infection of their child? And how did you do the ethical review? How was the process? How many institutions?
A: So the first question regarding how we convinced the patient. These were volunteers. They all have good education background. They had a lot of information about HIV drugs and other approaches, and even some of the latest research articles published. They were usually in a social network together where the latest advancements in HIV treatment is available. The volunteers were given informed consent, and they already understood quite well about the gene editing technology and the potential effects and benefits. I think it's a mutual exchange of information.
译文：
Q：你在试验开始之前如何说服那些父母的？你有告诉他们其实还有其他方案可以避免感染AIDS吗？你是怎么过伦理审核的？流程是怎样的？有多少机构（参与）？
A：第一个问题是我们怎么说服患者。这些患者是志愿者。他们都有良好的受教育背景，同时也有许多关于HIV药物和其他治疗方案的知识，甚至还知道一些最新发表的研究成果。他们通常在一个社交网络中，在那个网络里能看到最新的HIV治疗进展。志愿者都被给予了知情同意，他们已经非常了解基因编辑技术和存在的潜在影响和好处。我想这是相互交换信息。（关于伦理审核的问题贺建奎未予回答）
Q: How many people reviewed the informed consent and felt it was appropriate?
A: About four people. ...
Q：有多少个人审核过你的知情同意书而且觉得它是可以的？
A：大概4个人……
原文
Q: I am very interested in informed consent process. You said there's a consent form that you are happy to share, it was reviewed by four people, and a ten minute conversation that happened with the patients. In the UK, the average reading age of the general public is around age 10. The vast majority of the UK public doesn't understand the word genome. I'm quite interested what happened in that conversation. How did you explain the risks? What was the evidence that they understood?
A: I did not say 10 minutes. I said 1 hour and 10 minutes. It happened in a conference room where the couples met and two observers. Printed copies were given to the couple before informed consent.
Q: Could they read them and understand them?
A: Yes. They were very well educated.
Q: Okay.
A: Yes. I explained from page 1 to page 20, line by line, paragraph by paragraph. And they had the right to ask any question during this informed consent process. Once we went through the entire informed consent, at the end I gave them time to private discussion so that they had some time to discuss as a couple. They also had the choice to decide to take it home and decide later.
Q: Were any of the team members trained in taking consent? Was this the first time? Were they trained at doing this?
A: I had two rounds of informed consent. The first round was informal and a team member from my lab. Just two hours to talk with them. The second one was more formal, and with me. I read guidelines from the NIH on informed consent when we drafted the informed consent.
译文：
Q：我对知情同意情况很感兴趣。你说你有一份你愿意公开的知情同意书，有4个人审查，而且你和患者谈了10分钟话。在英国，一般公众能够阅读的年龄是10岁，绝大部分英国公众不懂“基因编辑”这个词的意思。我对你和患者谈话的时候发生的情况很感兴趣，你是怎么给他们解释风险的？而他们能听明白的证据又是什么？
A：我说的不是10分钟，我说的是1小时10分钟。知情同意谈话在一个会议室里展开，有两夫妻参与，还有两个观察员。在进行谈话之前，我们预先给了他们纸质的知情同意书。
Q：他们能读懂知情同意书吗？
A：能的，他们有良好的受教育背景。
Q：好吧。
A：是这样，我从第1页到第20页，一行一行的，一段一段的解释。同时他们有权在此过程中问任何问题。在完成知情同意谈话之后，我会给他们时间进行私下商量，夫妻两会单独商量。他们也可以把知情同意书带回去商量，晚点再做决定。
Q：你的团队成员有人在“知情同意”这方面受过专业训练吗？这是头一回吗？他们为此受过训练吗？
A：我们进行了两轮知情同意。第一轮是我研究室的一名成员告知他们，就谈两个小时。第二次更正式，我会出马。我们起草知情同意书的时候，我是读过NIH的知情同意书指南的。
脱靶问题：
原文
Q: Regarding off-target assessment. You mentioned you did single cell whole genome sequencing. As far as I know, there is no reliable or mature technology to conduct single cell whole genome sequencing. So how did you do this? There's also consensus to not allow ... to conduct genome editing on germlines. This is the consensus of the international community including the Chinese community. I assume you were aware this was a red line. Why have you chosen to cross this red line? Why did you perform these clinical trials in secret?
A: First, regarding off-target by sequencing. Before implantation, we can biopsy only 3 to 5 cells from the blastocyte. From that, we amplify for single cell. We were able to get maybe 95% genome coverage for single cell. Or 80-85% coverage, current state of the art. There might be off-target effects missing, but it's not just looking at this embryo, we had many of them, and by many of them together we can understand how much off-target happens.
译文
Q：关于脱靶的评估。你提到你做了单细胞全基因组测序。 就我所知，现阶段没有可靠或成熟的技术能够进行单细胞全基因组测序。 那你是怎么做到的？同时现在的共识认为不应该对基因组进行基因编辑。这是包括华人社会在内的国际社会的共识。我想你应该知道这是一条红线。为什么你选择跨越这条红线，为什么要秘密进行这项临床试验。
A： 首先，关于脱靶问题。在植入胚胎之前，我们只能从胚细胞中活检到3-5个细胞。从这里，我们放大单个细胞。我们大致上能获得单个细胞95%的基因组覆盖率。或者以当前的技术，80%-85%。这可能会导致脱靶效应缺失，但是不要仅仅只看这个胚胎，我们有很多胚胎，通过检测这么多胚胎，我们把信息汇聚起来，就能知道脱靶发生的频率。
关于研究经费来源：
原文
Q: Question from the media, could you please explain the source of the funding for this work?
A: When I started this, I was a professor at a university. Three years ago, I began this work. I began that when the university was paying my salary. Medical care and expense for the patients was paid by myself. Some of the sequencing costs was covered by startup funding in the university.
Q: So there was no funding from industry or a company? Just to make it clear, you have involvement in a company, but that was not involved in this project?
A: Neither my company was involved in this project, neither people space or equipment.
Q: Did the families pay anything or did they pay anything? Was there any exchange of money?
A: We explained in the informed consent that we paid all the medical expense and they would not receive money for this.
译文：
Q：媒体提问，解释一下这项研究的经费来源？
A：我开始搞这个研究的时候，还是大学的教授。我三年前开始的这项研究。当时大学给我付薪水。患者的医疗花费是我自己出的。部分后续研究花费来自大学给我的启动资金。
Q：所以没有来自产业和公司的资金？说得清楚一点，你有一家公司，但是那家公司和这个项目无关？
A：我的公司没有参与这项研究，没有提供人员、场地和器材。
Q：那受试者家庭要付钱或者有人付钱给他们吗？这中间有金钱交易吗？
A：我们在知情同意中解释过，我们付所有的医疗花费。他们不会因此得到钱。
关于保密试验：
原文
Q: The second part of the question, was, why so much secrecy around this particularly when you know the general feeling among the scientists is that we shouldn't be doing this? Why so much secrecy from the Chinese authorities? You know the accusation now is that you have broken the law. If you had involved the Chinese authorities, they might have said you can't do it. That's how it seems, you went ahead anyway.
A: I have been engaged in the scientific community. I spoke at Cold Spring Harbor, Berkeley, and at an Asian conference. I consulted them for feedback. I moved on to clinical trials, and at that time I also consulted with experts in the United States about ethics.
译文：
Q：问题的第二部分是，你为什么搞得这么隐秘，尤其是当你知道科学家的总体态度是反对做这种事的时候？（此问题后面部分不做翻译）
A：我一直都有在科学界活动。我在冷泉港，伯克利和亚洲会议上都做过演讲。我也咨询科学圈寻求反馈意见。在我开始去进行临床试验的时候，在那个时候我也就伦理问题咨询过美国专家。
关于争议：
原文
Q: Did you expect all this reaction? Even if you had managed to succeed in having the paper reviewed and published first, there would have been a lot of fuss at that time as well. Did you anticipate this?
A: It's because the news leaked out. My original thinking was based on the survey of the United States or the US or the British ethics statement or the Chinese study that gave us the signal that the majority of the public is supporting human genome editing for treatment including HIV prevention.
译文：
Q：你预期过现在这样的反应吗？就算你成功通过审议把论文先发了，你同样也要面对一大堆争议的。你预期过这种情况吗？
A：现在这样是因为新闻提前走漏风声了。我原来的设想是，基于美国或者英国的伦理调查或者中国的调查，能给我们一个大部分公众支持人类基因编辑治疗疾病，包括预防艾滋的信号。
关于孩子的问题：
原文
Q: So there are two sisters, and one is refractory to HIV infection and that was a desired outcome from the parents or at least the father you specifically highlighted. Within the family dynamic, are these daughters going to be treated differently? The othe rside of that is the one girl that is refractory to HIV infection- is she now going to be desirable for breeding? Will this change her whole dynamic in terms of marriage and children because a spouse might be particularly interested in getting this mutation within the family? Even this very simple thing, with these two girls being different and the family and now this being something of an enhancement preventative trait not just a disease correction but now something new that could be introduced in the population.
A: I have reflected deeply on this. This is why I published the five code value for gene editing. First is respect for children's autonomy. These tools should not be used to control their future or make expectations about their future choices. They should be given the freedom of choice. The second one is-- the children, encourage them to explore their full potential and the pursuit of their own life.
Q: For 18 years though, they are children and they do not have that autonomy. Their genotype might quite affect their upbringing. Will this effect their perception, or their parents?
Q: Their parents will know they were edited.
A: I don't know how to answer this question.
译文：
Q: 现在有两姐妹，其中一个可以抵御HIV感染，你特别提到这是她们父亲特别期望的。在这样的家庭环境下，这两个孩子会被不同对待吗？问题的另一面是，那个能抵抗HIV感染的女孩，她自己会繁育后代吗？这会改变她整个的婚姻和繁育情况吗，因为有可能有人会特别希望这种变异出现在自己的家庭中？更别说还有一件很简单的事，这两个女孩现在与众不同了，而且现在不是治疗了疾病而是通过基因编辑进行了增强，有些新的东西被引入了总人群中。
A：我对此深有反思。这是我发布基因编辑的5个原则价值的原因。首先要尊重儿童的自主权。这些工具（基因编辑）不应该成为控制他们未来或给他们造成对未来的期许从而影响他们未来选择的东西。他们应该被给予选择的自由。第二件事，这些孩子们，应该鼓励他们去探索他们的全部潜力，追寻他们自己的生活。
Q：但是，在长达18岁的时间里，他们是小孩而且没有自主权。他们的基因型很可能影响他们的成长，这会不会影响他们的感知，或者影响他们的家长？他们的家长会知道他们被编辑过了。
A：我不知道怎么回答这个问题。
Q: The very final question is, if this was going to be your baby, would you have gone ahead with this?
A: That's a good question. If it was my baby, with the same situation, yes I would try first.
Q：最后一个问题，如果是你的孩子，你也会这么做吗？
A：这是个好问题。如果是我的孩子，在同样的情况下，我会先试试看。
速记出处
http://diyhpl.us/wiki/transcripts/human-genome-editing-summit/2018-hong-kong/jiankui-he-human-genome-editing/
https://twitter.com/kanzure/status/1067646854077325313
为了不在茫茫公众号里走失
三步"星标"医学界
和150万同行一起闯医道
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