Cited by 733CRISPR and Genetic EngineeringBiomedical Ethics and RegulationEthics and bioethics in healthcare

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index; 4 of the 8 sources its claims cite were checked for support.

A prudent path forward for genomic engineering and germline gene modification

Open access

Abstract

A framework for open discourse on the use of CRISPR-Cas9 technology to manipulate the human genome is urgently needed , Genome engineering technology offers unparalleled potential for modifying human and nonhuman genomes. In humans, it holds the promise of curing genetic disease, while in other organisms it provides methods to reshape the biosphere for the benefit of the environment and human societies. However, with such enormous opportunities come unknown risks to human health and well-being. In January, a group of interested stakeholders met in Napa, California ( 1 ), to discuss the scientific, medical, legal, and ethical implications of these new prospects for genome biology. The goal was to initiate an informed discussion of the uses of genome engineering technology, and to identify those areas where action is essential to prepare for future developments. The meeting identified immediate steps to take toward ensuring that the application of genome engineering technology is performed safely and ethically.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

A 2015 Science policy forum from the Napa meeting argues that CRISPR-Cas9 genome engineering offers major promise but also unknown risks, especially for human germline modification. It recommends broad open discussion and, in the near term, strongly discouraging clinical human germline genome modification while research and governance proceed.

Key findings

  • The Napa meeting concluded there is an urgent need for open discussion of the merits and risks of human genome modification by a broad cohort including scientists, clinicians, social scientists, the general public, and relevant public entities and interest groups.
  • Near-term recommendations include strongly discouraging germline genome modification for clinical application in humans, even in lax jurisdictions; creating expert forums for education; encouraging transparent research on efficacy and specificity in human and nonhuman model systems; and convening a globally representative group to consider policies.
  • The paper notes that human germline engineering methods have already been demonstrated in mice and monkeys, and it distinguishes mitochondrial transfer—which does not use CRISPR-Cas9 and was approved by the Human Fertilisation and Embryology Authority and by Parliament in the United Kingdom—from nuclear germline editing.
  • No quantitative data or effect sizes are reported; the text is a consensus policy commentary.

Methods

  • Design: policy forum/commentary reporting on a January 2015 Napa, California meeting of CRISPR-Cas9 developers and users and experts in genetics, law, and bioethics; all participants were from the United States.
  • Data or sample: no empirical dataset; discussion focused on human germline engineering and did not address mitochondrial transfer.
  • Main analysis: consensus discussion and recommendations for governance, risk assessment, public engagement, and research priorities.

Limitations

  • Stated: the Napa discussion did not address mitochondrial transfer; the group was all from the United States, and the paper calls for globally representative participation.
  • Stated: limits to knowledge of human genetics, gene-environment interactions, and disease pathways create uncertainty about unintended consequences of heritable germline modifications.
  • Evident from the text: the recommendations are not based on systematic data or quantitative risk assessment and are advisory rather than binding.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1126/science.aab1028

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

4 of 8 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured

  • Probably not a substantial claim. 2
  • It may state two separate claims as one. 3
5 of 5
  • The paper relies on this without support.

    There are limits to current knowledge of human genetics, gene-environment interactions, and disease pathways.

    “because there are limits to our knowledge of human genetics, gene-environment interactions, and the pathways of disease (including the interplay between one disease and other conditions or diseases in the same patient).”
  • The paper relies on this without support.

    In the United States, human research involving heritable germline modifications currently would require an Investigational New Drug exemption from the FDA.

    “In the United States, such human research currently would require an Investigational New Drug exemption from the Food and Drug Administration”
  • The paper relies on this without support.

    In countries with a highly developed bioscience capacity, germline genome modification in humans is currently illegal or tightly regulated.

    “(In countries with a highly developed bioscience capacity, germline genome modification in humans is currently illegal or tightly regulated.)”
  • The paper relies on this without support.

    Mitochondrial transfer does not use CRISPR-Cas9.

    “The Napa discussion did not address mitochondrial transfer (8, 9), a technique that does not use CRISPR-Cas9.”
  • The paper relies on this without support.

    Public trust in science ultimately begins with and requires ongoing transparency and open discussion.

    “At the dawn of the recombinant DNA era, the most important lesson learned was that public trust in science ultimately begins with and requires ongoing transparency and open discussion.”
  • The paper relies on this without support.

    CRISPR-Cas9 and other genome engineering methods can be used to change DNA in the nuclei of reproductive cells (germ line).

    “In addition to facilitating changes in differentiated somatic cells of animals and plants, CRISPR-Cas9 technology as well as other genome engineering methods can be used to change the DNA in the nuclei of reproductive cells that transmit information from one generation to the next (an organism’s “germ line”).”
  • The paper relies on this without support.

    Off-target alterations and on-target events with unintended consequences are possible with CRISPR-Cas9.

    “Considerations include the possibility of off-target alterations, as well as on-target events that have unintended consequences.”
  • The authors state this as an assumption.

    The safety and efficacy of genome engineering technology can be ensured.

    “Assuming the safety and efficacy of the technology can be ensured, a key point of discussion is whether the treatment or cure of severe diseases in humans would be a responsible use of genome engineering, and if so, under what circumstances.”
8 of 8

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Citations

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Metadata

Authors
Baltimore, D., Berg, P., Botchan, M., Carroll, D., Charo, R. A., Church, G., Corn, J. E., Daley, G. Q., Doudna, J. A., Fenner, M., Greely, H. T., Jinek, M., Martin, G. S., Penhoet, E., Puck, J., Sternberg, S. H., Weissman, J. S., & Yamamoto, K. R.
Affiliations
  • California Institute of Technology (US)
  • Stanford Medicine (US)
  • Innovative Genomics Institute (US)
  • University of Utah (US)
  • University of Wisconsin–Madison (US)
  • Harvard University (US)
  • Boston Children's Hospital (US)
  • Howard Hughes Medical Institute (US)
  • Stanford University (US)
  • Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
  • University of California, Berkeley (US)
  • Alta Partners, One Embarcadero Center, 37th Floor, San Francisco, CA 94111, USA.
  • University of California, San Francisco (US)
Corresponding author
Doudna, Jennifer A.
Venue
Science
Published
2015-04-03
Volume
348
Issue
6230
Pages
36-38
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1987739153
Cited by
733
References
7
Citations by year
2026: 37 · 2025: 28 · 2024: 48 · 2023: 34 · 2022: 52 · 2021: 46 · 2020: 77 · 2019: 74 · 2018: 75 · 2017: 96 · 2016: 80 · 2015: 84
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
Caribou Biosciences, Inc.
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Health Sciences › Nursing › Issues, ethics and legal aspects › Biomedical Ethics and Regulation
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics and bioethics in healthcare
Keywords
CRISPR/Cas9, germline editing, public discourse, genome editing regulation
MeSH terms
Biotechnology, Genetic Engineering, Germ Cells, Humans, Risk Management, Genome, Human, Genetic Predisposition to Disease, Gene Transfer, Horizontal, Genomics, Targeted Gene Repair, Clustered Regularly Interspaced Short Palindromic Repeats

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