獨家 | 關鍵人物反駁：「我很震驚……」（基因技術之爭2）

知識 08-21

?叢樂

編者按：

2016年8月19日，《知識分子》報道「CRISPR是否成為有史以來最大的生物學專利尚無定論，但它成為生物學有史以來最大爭議恐怕已經成為事實」。

加州大學伯克利分校杜德娜一方為專利爭議，公布了曾參與博德研究所張鋒實驗室研究的林帥亮2015年致杜德娜的電子郵件。8月17日《麻省理工科技評論》報道後，引起廣泛關注。

昨晚，《知識分子》收到關鍵人物之一的反駁。叢樂是張鋒當時的研究生、張鋒實驗室2013年發表CRISPR論文的第一作者（林帥亮是該文第四作者）、與張鋒共有CRISPR專利。為了保證準確性，我們全文發表。

《知識分子》不預設立場，保持公平公正，給不同意見的雙方或多方提供理性討論、爭議的平台。

請有興趣的讀者保持耐心，考慮事情的複雜性，與我們一道跟進，觀察事態發展，也許有朝一日能夠透過這一世界科學發現的爭議了解真相？

撰文 | 叢樂（麻省理工學院-哈佛大學聯合博德研究所）

●　●　●

這封郵件（編者註：系指美國專利與商標局本周公開的一封張鋒實驗室的前成員林帥亮發給加州大學伯克利分校的分子生物學家詹妮弗·杜德娜的一封求職信，標題是：「博德研究所的CRISPR專利以及申請貴實驗室的職位」。詳請參閱《知識分子》此前報道）對我博士期間在張鋒老師實驗室中針對CRISPR基因編輯工作的描述與事實完全不符。我很震驚林帥亮會做出這樣的錯誤描述。我和張鋒老師在2011年初開始開發CRISPR在哺乳動物細胞中的應用並獲得數據支持這個系統可以用來進行基因編輯。他在2011年10月作為訪問學生來實驗室進行輪轉。他來訪期間，我們實驗室成員在繼續開發CRISPR技術，作為他輪轉研究的一部分他也參與了其中部分工作。訪問期間我和張鋒老師付出時間傳授他我們所掌握的實驗技術並在科研方面對他進行指導，實驗室CRISPR課題組成員一起提供他作為輪轉學生被張鋒老師安排完成的實驗所需要的幫助和實驗材料。這段歷史和相關記錄都很清楚，我希望確保你（編者註：指《知識分子》撰稿人）看到了Broad Institute（博德研究所）對這一情況的回應，其中提供了幾項關鍵證據，鏈接是：

https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/journalists-statement-and-background-crispr-patent-interfer

（點擊文末「閱讀原文」可見）

英文版

Statement

I strongly disagree with the statements in the email as the description of my work in Dr. Feng Zhang"s lab is entirely incorrect. I am surprised he would make such misstatements. Dr. Feng Zhang and I started working on CRISPR in mammalian cells back in the beginning of 2011 and obtained positive data to support the system can be harnessed to perform gene editing. He was a visiting rotation student at the Broad from October 2011, and members of the lab continued to work on CRISPR while he was asked to participate as part of his rotation. During his time in the Zhang lab, Feng and I spent time teaching him how to perform experiments, providing guidance to him, and all lab members on the CRISPR team provided materials for him to use in experiments he was asked to run by Feng as a rotation student. The history and related documents are clear, and I wanted to be sure you had a copy of the Broad Institute"s response to this issue, which provides several key evidence and is available here: https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/journalists-statement-and-background-crispr-patent-interfer

同時，回應的英文原文中相關部分節錄如下：

Update: August 17, 2016

In its Opposition Document 2, posted August 16, the Regents of the University of California again claim Broad relied on Jinek 2012 to engineer a eukaryotic CRISPR-Cas9 gene editing system.

This is false, and has been demonstrated to be false numerous times in the public record.

In an attempt to strengthen its case, in Opposition Document 2 the UC Regents quote an excerpt from an email sent to Jennifer Doudna by a rotation student, who visited the Broad for a brief period from a Peking University/Tsinghua University joint program. This rotation student worked for Feng Zhang at the Broad on CRISPR projects from October 2011 to June 2012.

It is important to understand the context of the visiting student』s email, which the Regents omitted from the Opposition Document:

The student』s visa was scheduled to expire on March 1, 2015.

The student learned in late February that he could not be offered a position to return to the Broad Institute.

The student sent the email to Dr. Doudna on February 28, 2015 requesting a job and offering to share 「details and records」 about the Broad』s patent claims. The subject line was 「The Broad CRISPR patent and Apply for a position in your lab.」

The UC system, at UCSF, offered the student a position on March 2, 2015. He immediately requested a transfer of his visa to UCSF.

The complete email is available on the PTAB website as Exhibit 1475.

Although the rotation student』s email makes several claims, the Opposition Document does not include any evidence to support them.

Abundant evidence already shows that the student』s claims are false. Examples include email exchanges between the student and Zhang:

August 2011: Zhang introduces Cas9 for genome editing to the student.

October 2011: Zhang explains to the student the necessary role of tracrRNA in the duplex with crRNA to load onto the Cas9, writing, 「I don』t think transfecting crRNA alone will work. It is loaded onto csn-1 as duplex with the tracrRNA. You should read the tracrRNA Nature paper again…」

November 2011: The student recognizes that some of his experiments were not successful because he did not follow the guidance he had received from Zhang and other lab members. In addition the student indicates Zhang has been overseeing and guiding his work, writing 「When Feng wrote on the notebook, I knew what I should do.」.

There are numerous other examples that make clear that beginning in 2011, Zhang and other members of his lab were actively and successfully engineering a unique CRISPR-Cas9 eukaryotic genome editing system prior to and independent of what was later published in Jinek.

Indeed, contrary to the visiting student』s own current claim that there was no invention prior to Jinek 2012, the individual has previously asserted - in legal documents - that he had made contributions to an invention prior to June 2012. This is inconsistent with his current claim.

《知識分子》為本文提供的參考資料：

叢樂是2013年1月3日上線，2月15日紙質版《科學》論文的第一作者，林帥亮是第四作者，張鋒是通訊作者。

Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Luciano A. LA, Zhang F (2013).

Multiplex Genome Engineering Using CRISPR/Cas Systems. Science 339:819-823.

叢樂和張鋒於2014年4月23日申請的CRISPR專利，他們是這一專利的共有者。

Cong L, Zhang F: CRISPR-Cas component systems, methods and compositions for sequence manipulation, US 8871445 B2 (filing date: April 23, 2014)