第二屆國際人類基因組編輯峰會組委會聲明

今天，第二屆國際人類基因組編輯峰會組委會發布聲明，指出「在臨床進行任何生殖系細胞的編輯仍然是不負責任的」，並呼籲對相關試驗制定嚴格、負責任的轉化途徑。以下為組委會聲明全文翻譯，原文參見文末。

來源 第二屆國際人類基因組編輯峰會組委會

翻譯 科研圈

時間 2018 年 11 月 29 日

2015 年 12 月，美國國家科學院、美國國家醫學院，英國皇家學會和中國科學院在華盛頓特區舉辦了一次國際峰會，討論與人類基因組編輯相關的科學、倫理和監管問題。作為峰會議程的結果，組委會發布了一份聲明，確定了在當前監管和政府規章的範圍內，可進行的研究和臨床應用領域。組委會還表示，彼時，在臨床進行任何可遺傳的生殖系細胞編輯，都是不負責任的。此外，聲明呼籲繼續就這一快速發展的技術的潛在利益、風險和監督進行國際討論。

為促進人類基因組編輯的深入、國際性討論，香港科學院、英國皇家學會、美國國家科學院和美國國家醫學院在香港組織了第二屆國際人類基因組編輯峰會，以評估這一議題在科學上的不斷發展、可能的臨床應用，以及社會由此對人類基因組編輯產生的反應。雖然第二次峰會的組委會對體細胞基因編輯在臨床試驗中的迅速發展表示讚賞，但我們仍然認為，在臨床進行任何生殖系細胞的編輯，仍然是不負責任的。

人類基因組編輯研究

基礎和臨床前研究，正在迅速推動體細胞和生殖系細胞基因組編輯的科學進步。對基因組編輯技術——包括鹼基編輯（base editing）進行更好的理解與設計，已經顯著提高了技術的效率和精確度，同時大大減少了脫靶。正如所預期的那樣，我們目前正在對患者進行體細胞基因組編輯的測試。

改變胚胎或配子的 DNA，可以讓攜帶致病突變的父母擁有健康的後代。然而，我們仍然難以評估胚胎或配子的可遺傳基因組編輯帶來的風險。人們擔心，基因編輯只能改變早期胚胎中某些細胞的基因，而其他未經編輯的細胞仍會導致長期的疾病。生殖系細胞的編輯不僅會對個體產生意想不到的有害影響，也會對個體的後代產生意想不到的有害影響；其對一種特定特徵的改變，可能對其他特徵帶來無法預估的作用，這種不確定性可能因人而異，且會受環境因素的影響。

遺傳改變所產生的影響的可變性，使得我們難以對利益和風險進行全面評估。然而，如果這些風險得以解決，並且符合多種其他標準，生殖系基因組編輯在未來可能會被接受。這些標準包括：嚴格的獨立監督、存在迫切的醫療需求、無合理的替代方案、有長期隨訪計劃，以及關注對社會的影響。即便如此，公眾對此的接受程度可能因司法管轄區而異，帶來不同的響應政策。

組委會總結，由於臨床實踐所需的科學理解和技術要求仍然過於不確定，風險太大，目前仍不允許進行生殖系基因組編輯的臨床試驗。 然而，過去三年的進展以及本次峰會的討論表明，當前應該為這些試驗確定嚴格、負責任的轉化途徑。

可能的轉化路徑

生殖系細胞編輯的轉化途徑需要遵守被廣泛接受的臨床研究標準，包括過去三年發表的基因組編輯指導文件中闡明的標準[1]。 這樣的途徑將需要建立一系列相關標準，包括臨床前證據和基因修飾準確性的標準、臨床試驗從業者的能力評估、可執行的專業行為標準，也需要與患者及患者倡導團體建立強有力的夥伴關係。

生殖系細胞編輯臨床應用報告

在這次峰會上，我們聽到一個出人意料且令人深感不安的消息：已有人類胚胎經過編輯和植入，導致懷孕和雙胞胎的誕生。我們建議進行獨立評估驗證，並確定所聲稱的 DNA 修飾是否已發生。即使基因修飾有效，該程序也是不負責任的，且不符合國際規範。該程序的缺陷包括醫學指征不足、研究方案設計不合理，未能達到保護研究對象福利的倫理標準，以及臨床程序的制定、審查和實施方面的缺乏透明度。

持續的國際論壇

組委會呼籲建立一個持續的國際論壇，以促進廣泛的公眾對話，制定相關的公平性戰略以滿足服務不足人口的需求，加快監管科學的發展，提供有關治理方案信息的交流中心，促進建立共同的監管標準，並通過對全球計劃和正在進行的實驗的進行登記，加強研究和臨床應用的協調。

除了建立國際論壇外，組委會還呼籲世界各國的科學院和科學、醫療學術團體繼續舉辦國際峰會，以便審核基因組編輯的臨床應用，收集不同觀點，對政策制定者的決策提供信息，制定建議和指導方針，以及促進國家和司法管轄區之間的協調。

[1] See, for example, National Academies of Sciences, Engineering, and Medicine, Human Genome Editing: Science, Ethics, and Governance (Washington, DC: The National Academies Press, 2017) and Nuffield Council on Bioethics, Genome Editing and Human Reproduction (London: Nuffield Council on Bioethics, 2018).

On Human Genome Editing II

Statement by the Organizing Committee of the

Second International Summit on Human Genome Editing

November 29, 2018

In December 2015, the U.S. National Academy of Sciences and U.S. National Academy of Medicine, the Royal Society of the United Kingdom, and the Chinese Academy of Sciences hosted an international summit in Washington, D.C., to discuss scientific, ethical, and governance issues associated with human genome editing. At its conclusion, the summit organizing committee released a statement identifying areas of research and clinical use that could proceed within current regulatory and governance protocols. The committee also stated that it would be irresponsible to proceed with any clinical use of heritable "germline" editing at that time. Further, it called for continued international discussion of potential benefits, risks, and oversight of this rapidly advancing technology.

As part of their commitment to fostering in-depth and international discussion about human genome editing, the Academy of Sciences of Hong Kong, the Royal Society of the United Kingdom, and the U.S. National Academy of Sciences and U.S. National Academy of Medicine organized the Second International Summit on Human Genome Editing in Hong Kong to assess the evolving scientific landscape, possible clinical applications, and attendant societal reactions to human genome editing. While we, the organizing committee of the second summit, applaud the rapid advance of somatic gene editing into clinical trials, we continue to believe that proceeding with any clinical use of germline editing remains irresponsible at this time.

Human Genome Editing Research

Basic and preclinical research is rapidly advancing the science of somatic and germline genome editing. Better understanding and design of genome editing techniques, including base editing, have produced significant increases in efficiency and precision while greatly reducing off-target events. As was anticipated, somatic genome editing is now being tested in patients.

Making changes in the DNA of embryos or gametes could allow parents who carry disease-causing mutations to have healthy, genetically related children. However, heritable genome editing of either embryos or gametes poses risks that remain difficult to evaluate. Concerns persist that changes may be made in only some cells of early-stage embryos, leaving unedited cells to perpetuate a disease. Germline editing could produce unintended harmful effects for not just an individual but also for that individual』s descendants. Changes to a particular trait may have unanticipated effects on other traits that could vary from person to person and in response to environmental influences.

The variability of effects produced by genetic changes makes it difficult to conduct a thorough evaluation of benefits and risks. Nevertheless, germline genome editing could become acceptable in the future if these risks are addressed and if a number of additional criteria are met. These criteria include strict independent oversight, a compelling medical need, an absence of reasonable alternatives, a plan for long-term follow-up, and attention to societal effects. Even so, public acceptability will likely vary among jurisdictions, leading to differing policy responses.

The organizing committee concludes that the scientific understanding and technical requirements for clinical practice remain too uncertain and the risks too great to permit clinical trials of germline editing at this time. Progress over the last three years and the discussions at the current summit, however, suggest that it is time to define a rigorous, responsible translational pathway toward such trials.

A Proposed Translational Pathway

A translational pathway to germline editing will require adhering to widely accepted standards for clinical research, including criteria articulated in genome editing guidance documents published in the last three years.[1]Such a pathway will require establishing standards for preclinical evidence and accuracy of gene modification, assessment of competency for practitioners of clinical trials, enforceable standards of professional behavior, and strong partnerships with patients and patient advocacy groups.

Report of Clinical Use of Germline Editing

At this summit we heard an unexpected and deeply disturbing claim that human embryos had been edited and implanted, resulting in a pregnancy and the birth of twins. We recommend an independent assessment to verify this claim and to ascertain whether the claimed DNA modifications have occurred. Even if the modifications are verified, the procedure was irresponsible and failed to conform with international norms. Its flaws include an inadequate medical indication, a poorly designed study protocol, a failure to meet ethical standards for protecting the welfare of research subjects, and a lack of transparency in the development, review, and conduct of the clinical procedures.

An Ongoing International Forum

The organizing committee calls for an ongoing international forum to foster broad public dialogue, develop strategies for increasing equitable access to meet the needs of underserved populations, speed the development of regulatory science, provide a clearinghouse for information about governance options, contribute to the development of common regulatory standards, and enhance coordination of research and clinical applications through an international registry of planned and ongoing experiments.

In addition to the establishment of an international forum, the organizing committee calls upon national academies and learned societies of science and medicine around the world to continue the practice of holding international summits to review clinical uses of genome editing, to gather diverse perspectives, to inform decisions by policymakers, to formulate recommendations and guidelines, and to promote coordination among nations and jurisdictions.

[1]See, for example, National Academies of Sciences, Engineering, and Medicine,Human Genome Editing: Science, Ethics, and Governance(Washington, DC: The National Academies Press, 2017) and Nuffield Council on Bioethics,Genome Editing and Human Reproduction(London:Nuffield Council on Bioethics, 2018).

Organizing Committee

David Baltimore1,2(committee chair)

President Emeritus and Robert Andrews Millikan Professor of Biology

California Institute of Technology

United States

Alta Charo2

Warren P. Knowles Professor of Law and Bioethics

University of Wisconsin, Madison

United States

George Q. Daley2

Dean of the Faculty of Medicine and Caroline Shields Walker Professor of Medicine

Harvard Medical School

United States

Jennifer A. Doudna1,2

Investigator, Howard Hughes Medical Institute; and

Professor, Department of Molecular and Cell Biology and Department of Chemistry

University of California, Berkeley

United States

Kazuto Kato

Professor of Biomedical Ethics and Public Policy

Graduate School of Medicine

Osaka University

Japan

Jin-Soo Kim

Director of Center for Genome Engineering

Institute for Basic Science

Seoul National University

South Korea

Robin Lovell-Badge3

Senior Group Leader

The Francis Crick Institute; and

Special Visiting Professor

University of Hong Kong

United Kingdom

Jennifer Merchant

Professor of Legal and Political Institutions

Université de Paris II (Panthéon-Assas)

France

Indira Nath

Visiting Professor, Bio-Support Unit

Department of Biotechnology

All India Institute of Medical Sciences (AIIMS); and

Former Raja Ramanna Fellow and Emeritus Professor

National Institute of Pathology

India

Duanqing Pei

Professor and Director General

Guangzhou Institutes of Biomedicine and Health

Chinese Academy of Sciences

China

Matthew Porteus

Associate Professor of Pediatrics

Division of Stem Cell Transplantation and Regenerative Medicine

Stanford University

United States

John Skehel3

Emeritus Scientist

The Francis Crick Institute

United Kingdom

Patrick Tam3

Deputy Director and Head, Embryology Research Unit

Children"s Medical Research Institute;

Senior Principal Research Fellow

National Health and Medical Research Council (NHMRC) of Australia;

Professor, School of Medical Sciences, Faculty of Medicine and Health

The University of Sydney; and

Mok Hing-Yiu Distinguished Visiting Professor

School of Biomedical Sciences

University of Hong Kong

Australia

Xiaomei Zhai

Professor and Executive Director, Centre for Bioethics

Chinese Academy of Medical Sciences and Peking Union Medical College

China

______________________________________

1Member, U.S. National Academy of Sciences

2Member, U.S. National Academy of Medicine

3Fellow, The Royal Society

喜歡這篇文章嗎？立刻分享出去讓更多人知道吧！