how to cite a research article example

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APA Style (7th Edition) Citation Guide: Journal Articles

• Introduction
• Journal Articles
• Magazine/Newspaper Articles
• Books & Ebooks
• Government & Legal Documents
• Biblical Sources
• Secondary Sources
• Films/Videos/TV Shows
• How to Cite: Other
• Additional Help

Table of Contents

Journal article from library database with doi - one author, journal article from library database with doi - multiple authors, journal article from a website - one author.

Journal Article- No DOI

Note: All citations should be double spaced and have a hanging indent in a Reference List.

A "hanging indent" means that each subsequent line after the first line of your citation should be indented by 0.5 inches.

This Microsoft support page contains instructions about how to format a hanging indent in a paper.

• APA 7th. ed. Journal Article Reference Checklist

If an item has no author, start the citation with the article title.

When an article has one to twenty authors, all authors' names are cited in the References List entry. When an article has twenty-one or more authors list the first nineteen authors followed by three spaced ellipse points (. . .) , and then the last author's name. Rules are different for in-text citations; please see the examples provided.

Cite author names in the order in which they appear on the source, not in alphabetical order (the first author is usually the person who contributed the most work to the publication).

Italicize titles of journals, magazines and newspapers. Do not italicize or use quotation marks for the titles of articles.

Capitalize only the first letter of the first word of the article title. If there is a colon in the article title, also capitalize the first letter of the first word after the colon.

If an item has no date, use the short form n.d. where you would normally put the date.

Volume and Issue Numbers

Italicize volume numbers but not issue numbers.

Retrieval Dates

Most articles will not need these in the citation. Only use them for online articles from places where content may change often, like a free website or a wiki.

Page Numbers

If an article doesn't appear on continuous pages, list all the page numbers the article is on, separated by commas. For example (4, 6, 12-14)

Library Database

Do not include the name of a database for works obtained from most academic research databases (e.g. APA PsycInfo, CINAHL) because works in these resources are widely available. Exceptions are Cochrane Database of Systematic Reviews, ERIC, ProQuest Dissertations, and UpToDate.

Include the DOI (formatted as a URL: https://doi.org/...) if it is available. If you do not have a DOI, include a URL if the full text of the article is available online (not as part of a library database). If the full text is from a library database, do not include a DOI, URL, or database name.

In the Body of a Paper

Books, Journals, Reports, Webpages, etc.: When you refer to titles of a “stand-alone work,” as the APA calls them on their APA Style website, such as books, journals, reports, and webpages, you should italicize them. Capitalize words as you would for an article title in a reference, e.g., In the book Crying in H Mart: A memoir , author Michelle Zauner (2021) describes her biracial origin and its impact on her identity.

Article or Chapter: When you refer to the title of a part of a work, such as an article or a chapter, put quotation marks around the title and capitalize it as you would for a journal title in a reference, e.g., In the chapter “Where’s the Wine,” Zauner (2021) describes how she decided to become a musician.

The APA Sample Paper below has more information about formatting your paper.

• APA 7th ed. Sample Paper

Author's Last Name, First Initial. Second Initial if Given. (Year of Publication). Title of article: Subtitle if any. Name of Journal, Volume Number (Issue Number), first page number-last page number. https://doi.org/doi number

Smith, K. F. (2022). The public and private dialogue about the American family on television: A second look. Journal of Media Communication, 50 (4), 79-110. https://doi.org/10.1152/j.1460-2466.2000.tb02864.x

Note: The DOI number is formatted as a URL: https://doi.org/10.1152/j.1460-2466.2000.tb02864.xIf

In-Text Paraphrase:

(Author's Last Name, Year)

Example: (Smith, 2000)

In-Text Quote:

(Author's Last Name, Year, p. Page Number)

Example: (Smith, 2000, p. 80)

Author's Last Name, First Initial. Second Initial if Given., & Last Name of Second Author, First Initial. Second Initial if Given. (Year of Publication). Title of article: Subtitle if any. Name of Journal, Volume Number (Issue Number), first page number-last page number. https://doi.org/doi number

Note: Separate the authors' names by putting a comma between them. For the final author listed add an ampersand (&) after the comma and before the final author's last name.

Note: In the reference list invert all authors' names; give last names and initials for only up to and including 20 authors. When a source has 21 or more authors, include the first 19 authors’ names, then three ellipses (…), and add the last author’s name. Don't include an ampersand (&) between the ellipsis and final author.

Note : For works with three or more authors, the first in-text citation is shortened to include the first author's surname followed by "et al."

Reference List Examples

Two to 20 Authors

Case, T. A., Daristotle, Y. A., Hayek, S. L., Smith, R. R., & Raash, L. I. (2011). College students' social networking experiences on Facebook. Journal of Applied Developmental Psychology, 3 (2), 227-238. https://doi.org/10.1016/j.appdev.2008.12.010

21 or more authors

Kalnay, E., Kanamitsu, M., Kistler, R., Collins, W., Deaven, D., Gandin, L., Iredell, M., Saha, J., Mo, K. C., Ropelewski, C., Wang, J., Leetma, A., . . . Joseph, D. (1996). The NCEP/NCAR 40-year reanalysis project. Bulletin of the American Meteorological Society , 77 (3), 437-471. https://doi.org/10.1175/1520-0477(1996)077<0437:TNYRP>2.0.CO;2

In-Text Citations

Two Authors/Editors

(Case & Daristotle, 2011)

Direct Quote: (Case & Daristotle, 2011, p. 57)

Three or more Authors/Editors

(Case et al., 2011)

Direct Quote: (Case et al., 2011, p. 57)

Author's Last Name, First Initial. Second Initial if Given. (Year of Publication). Title of article: Subtitle if any.  Name of Journal, Volume Number (Issue Number if given). URL

Flachs, A. (2010). Food for thought: The social impact of community gardens in the Greater Cleveland Area.  Electronic Green Journal, 1 (30). http://escholarship.org/uc/item/6bh7j4z4

Example: (Flachs, 2010)

Example: (Flachs, 2010, Conclusion section, para. 3)

Note: In this example there were no visible page numbers or paragraph numbers; in this case you can cite the section heading and the number of the paragraph in that section to identify where your quote came from. If there are no page or paragraph numbers and no marked section, leave this information out.

Journal Article - No DOI

Author's Last Name, First Initial. Second Initial if Given. (Year of Publication). Title of article: Subtitle if any.  Name of Journal, Volume Number (Issue Number), first page number-last page number. URL [if article is available online, not as part of a library database]

Full-Text Available Online (Not as Part of a Library Database):

Steinberg, M. P., & Lacoe, J. (2017). What do we know about school discipline reform? Assessing the alternatives to suspensions and expulsions.  Education Next, 17 (1), 44–52.  https://www.educationnext.org/what-do-we-know-about-school-discipline-reform-suspensions-expulsions/

Example: (Steinberg & Lacoe, 2017)

(Author's Last Name, Year, p. Page number)

Example: (Steinberg & Lacoe, 2017, p. 47)

Full-Text Available in Library Database:

Jungers, W. L. (2010). Biomechanics: Barefoot running strikes back.  Nature, 463 (2), 433-434.

Example: (Jungers, 2010)

Example: (Jungers, 2010, p. 433)

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• Last Updated: Apr 30, 2024 1:29 PM
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APA Style 7th Edition: Citing Your Sources

• Basics of APA Formatting
• In Text Quick View
• Block Quotes
• Books & eBooks

Standard Format

Formatting rules, various examples.

• Thesis/Dissertation
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• Additional Resources
• Reference Page

Adapted from American Psychological Association. (2020). Publication manual of the American Psychological Association (7th ed).  https://doi.org/10.1037/0000165-000

The following formats apply to all journals, periodicals, magazines, newspapers, etc. whether you found them in an online database, search engine, or in print.

• Volume, issue and page numbers in periodicals:  Continuous pagination throughout a volume: only cite the volume number (in italics), followed by a comma and then the page numbers: 20 , 344-367.
•   Do Not copy and paste URLS from library databases or other platforms that restrict public access.

See Ch. 10 pp. 313-352 of APA Manual for more examples and formatting rules

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• Last Updated: Apr 22, 2024 9:37 AM
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A Quick Guide to Harvard Referencing | Citation Examples

Published on 14 February 2020 by Jack Caulfield . Revised on 15 September 2023.

Referencing is an important part of academic writing. It tells your readers what sources you’ve used and how to find them.

Harvard is the most common referencing style used in UK universities. In Harvard style, the author and year are cited in-text, and full details of the source are given in a reference list .

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Table of contents

Harvard in-text citation, creating a harvard reference list, harvard referencing examples, referencing sources with no author or date, frequently asked questions about harvard referencing.

A Harvard in-text citation appears in brackets beside any quotation or paraphrase of a source. It gives the last name of the author(s) and the year of publication, as well as a page number or range locating the passage referenced, if applicable:

Note that ‘p.’ is used for a single page, ‘pp.’ for multiple pages (e.g. ‘pp. 1–5’).

An in-text citation usually appears immediately after the quotation or paraphrase in question. It may also appear at the end of the relevant sentence, as long as it’s clear what it refers to.

When your sentence already mentions the name of the author, it should not be repeated in the citation:

Sources with multiple authors

When you cite a source with up to three authors, cite all authors’ names. For four or more authors, list only the first name, followed by ‘ et al. ’:

Sources with no page numbers

Some sources, such as websites , often don’t have page numbers. If the source is a short text, you can simply leave out the page number. With longer sources, you can use an alternate locator such as a subheading or paragraph number if you need to specify where to find the quote:

Multiple citations at the same point

When you need multiple citations to appear at the same point in your text – for example, when you refer to several sources with one phrase – you can present them in the same set of brackets, separated by semicolons. List them in order of publication date:

Multiple sources with the same author and date

If you cite multiple sources by the same author which were published in the same year, it’s important to distinguish between them in your citations. To do this, insert an ‘a’ after the year in the first one you reference, a ‘b’ in the second, and so on:

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A bibliography or reference list appears at the end of your text. It lists all your sources in alphabetical order by the author’s last name, giving complete information so that the reader can look them up if necessary.

The reference entry starts with the author’s last name followed by initial(s). Only the first word of the title is capitalised (as well as any proper nouns).

Sources with multiple authors in the reference list

As with in-text citations, up to three authors should be listed; when there are four or more, list only the first author followed by ‘ et al. ’:

Reference list entries vary according to source type, since different information is relevant for different sources. Formats and examples for the most commonly used source types are given below.

• Entire book
• Book chapter
• Translated book
• Edition of a book

Journal articles

• Print journal
• Online-only journal with DOI
• Online-only journal with no DOI
• General web page
• Online article or blog
• Social media post

Sometimes you won’t have all the information you need for a reference. This section covers what to do when a source lacks a publication date or named author.

No publication date

When a source doesn’t have a clear publication date – for example, a constantly updated reference source like Wikipedia or an obscure historical document which can’t be accurately dated – you can replace it with the words ‘no date’:

Note that when you do this with an online source, you should still include an access date, as in the example.

When a source lacks a clearly identified author, there’s often an appropriate corporate source – the organisation responsible for the source – whom you can credit as author instead, as in the Google and Wikipedia examples above.

When that’s not the case, you can just replace it with the title of the source in both the in-text citation and the reference list:

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Harvard referencing uses an author–date system. Sources are cited by the author’s last name and the publication year in brackets. Each Harvard in-text citation corresponds to an entry in the alphabetised reference list at the end of the paper.

Vancouver referencing uses a numerical system. Sources are cited by a number in parentheses or superscript. Each number corresponds to a full reference at the end of the paper.

A Harvard in-text citation should appear in brackets every time you quote, paraphrase, or refer to information from a source.

The citation can appear immediately after the quotation or paraphrase, or at the end of the sentence. If you’re quoting, place the citation outside of the quotation marks but before any other punctuation like a comma or full stop.

In Harvard referencing, up to three author names are included in an in-text citation or reference list entry. When there are four or more authors, include only the first, followed by ‘ et al. ’

Though the terms are sometimes used interchangeably, there is a difference in meaning:

• A reference list only includes sources cited in the text – every entry corresponds to an in-text citation .
• A bibliography also includes other sources which were consulted during the research but not cited.

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the ‘Cite this Scribbr article’ button to automatically add the citation to our free Reference Generator.

Caulfield, J. (2023, September 15). A Quick Guide to Harvard Referencing | Citation Examples. Scribbr. Retrieved 14 May 2024, from https://www.scribbr.co.uk/referencing/harvard-style/

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How to Cite a Research Paper in APA

Last Updated: October 19, 2022 Fact Checked

This article was co-authored by wikiHow Staff . Our trained team of editors and researchers validate articles for accuracy and comprehensiveness. wikiHow's Content Management Team carefully monitors the work from our editorial staff to ensure that each article is backed by trusted research and meets our high quality standards. There are 12 references cited in this article, which can be found at the bottom of the page. This article has been fact-checked, ensuring the accuracy of any cited facts and confirming the authority of its sources. This article has been viewed 160,110 times. Learn more...

If you’re citing a research article or paper in APA style, you’ll need to use a specific citation format that varies depending on the source. Assess whether your source is an article or report published in an academic journal or book, or whether it is an unpublished research paper, such as a print-only thesis or dissertation. Either way, your in-text citations will need to include information about the author (if available) and the date when your source was published or written.

Sample Citations

Writing an In-Text Citation

• For example, you may write, “Gardener (2008) notes, ‘There are several factors to consider about lobsters’ (p. 199).”

• For example, you may write, “‘There are several factors to consider about lobsters’ (Gardner, 2008, p. 199).” Or, “The paper claims, ‘The fallen angel trope is common in religious and non-religious texts’ (Meek & Hill, 2015, p.13-14).”
• For articles with 3-5 authors, write out the names of all the authors the first time you cite the source. For example: (Hammett, Wooster, Smith, & Charles, 1928). In subsequent citations, write only the first author’s name, followed by et al.: (Hammett et al., 1928).
• If there are 6 or more authors for the paper, include the last name of the first author listed and then write "et al." to indicate that there are more than 5 authors.
• For example, you may write, "'This is a quote' (Minaj et al., 1997, p. 45)."

• For example, you may write, “‘The risk of cervical cancer in women is rising’ (American Cancer Society, 2012, p. 2).”

• For example, you may write, “‘Shakespeare may have been a woman’ (“Radical English Literature,” 2004, p. 45).” Or, “The paper notes, ‘There is a boom in Virgin Mary imagery’ (“Art History in Italy,” 2011, p. 32).”

• For example, you may write, “‘There are several factors to consider about lobsters’ (Gardner, 2008, p. 199).” Or, “The paper claims, ‘The fallen angel trope is common in religious and non-religious texts’ (“Iconography in Italian Frescos,” 2015, p.13-14).”

• For example, you may write, “‘There are several factors to consider about lobsters’ (Gardner, 2008, p. 199).” Or, “The paper claims, ‘The fallen angel trope is common in religious and non-religious texts’ (“Iconography in Italian Frescos,” 2015, p.145-146).”

• For example, you may write, “‘The effects of food deprivation are long-term’ (Mett, 2005, para. 18).”

Creating a Reference List Citation for a Published Source

• Material on websites is also considered “published,” even if it’s not peer-reviewed or associated with a formal publishing company.
• While academic dissertations or theses that are print-only are considered unpublished, these types of documents are considered published if they’re included in an online database (such as ProQuest) or incorporated into an institutional repository.

• For example, you may write, “Gardner, L. M.” Or, “Meek, P. Q., Kendrick, L. H., & Hill, R. W.”
• If there is no author, you can list the name of the organization that published the research paper. For example, you may write, “American Cancer Society” or “The Reading Room.”
• Formally published documents that don’t list an author or that have a corporate author are typically reports or white papers .

• For example, you may write, “Gardner, L. M. (2008).” Or, “American Cancer Society. (2015).”

• For example, you may write, “Gardner, L. M. (2008). Crustaceans: Research and data.” Or, “American Cancer Society. (2015). Cervical cancer rates in women ages 20-45.”

• For example, for a journal article, you may write, “Gardner, L. M. (2008). Crustaceans: Research and data. Modern Journal of Malacostracan Research, 25, 150-305.”
• For a book chapter, you could write: “Wooster, B. W. (1937). A comparative study of modern Dutch cow creamers. In T. E. Travers (Ed.), A Detailed History of Tea Serviceware (pp. 127-155). London: Wimble Press."

• For example, you may write, “Kotb, M. A., Kamal, A. M., Aldossary, N. M., & Bedewi, M. A. (2019). Effect of vitamin D replacement on depression in multiple sclerosis patients. Multiple Sclerosis and Related Disorders, 29, 111-117. Retrieved from PubMed, https://www.ncbi.nlm.nih.gov/pubmed/30708308.
• If you’re citing a paper or article that was published online but did not come from an academic journal or database, provide information about the author (if known), the date of publication (if available), and the website where you found the article. For example: “Hill, M. (n.d.). Egypt in the Ptolemaic Period. Retrieved from https://www.metmuseum.org/toah/hd/ptol/hd_ptol.htm”

Citing Unpublished Sources in Your Reference List

• Print-only dissertations or theses.
• Articles or book chapters that are in press or have been recently prepared or submitted for publication.
• Papers that have been rejected for publication or were never intended for publication (such as student research papers or unpublished conference papers).

• If the paper is currently being prepared for publication, include the author’s name, the year when the current draft was completed, and the title of the article in italics, followed by “Manuscript in preparation.” For example: Wooster, B. W. (1932). What the well-dressed man is wearing. Manuscript in preparation.
• If the paper has been submitted for publication, format the citation the same way as if it were in preparation, but instead follow the title with “Manuscript submitted for publication.” For example: Wooster, B. W. (1932). What the well-dressed man is wearing. Manuscript submitted for publication.
• If the paper has been accepted for publication but is not yet published, replace the date with “in press.” Do not italicize the paper title, but do include the title of the periodical or book in which it will be published and italicize that. For example: Wooster, B. W. (in press). What the well-dressed man is wearing. Milady’s Boudoir.

• If the paper was written for a conference but never published, your citation should look like this: Riker, W. T. (2019, March). Traditional methods for the preparation of spiny lobe-fish. Paper presented at the 325th Annual Intergalactic Culinary Conference, San Francisco, CA.
• For an unpublished paper written by a student for a class, include details about the institution where the paper was written. For example: Crusher, B. H. (2019). A typology of Cardassian skin diseases. Unpublished manuscript, Department of External Medicine, Starfleet Academy, San Francisco, CA.

• For example, you may write, “Pendlebottom, R. H. (2011). Iconography in Italian Frescos (Unpublished doctoral dissertation). New York University, New York, United States.”

Community Q&A

• If you want certain information to stand out in the research paper, then you can consider using a block quote. Thanks Helpful 0 Not Helpful 0

You Might Also Like

• ↑ https://libraryguides.vu.edu.au/apa-referencing/7JournalArticles
• ↑ https://owl.purdue.edu/owl/research_and_citation/apa_style/apa_formatting_and_style_guide/in_text_citations_author_authors.html
• ↑ https://bowvalleycollege.libguides.com/c.php?g=714519&p=5093747
• ↑ https://guides.libraries.psu.edu/apaquickguide/intext
• ↑ https://owl.purdue.edu/owl/research_and_citation/apa_style/apa_formatting_and_style_guide/in_text_citations_the_basics.html
• ↑ https://libguides.southernct.edu/c.php?g=7125&p=34582#1951239
• ↑ https://owl.purdue.edu/owl/research_and_citation/apa_style/apa_formatting_and_style_guide/reference_list_electronic_sources.html
• ↑ https://owl.purdue.edu/owl/research_and_citation/apa_style/apa_formatting_and_style_guide/reference_list_articles_in_periodicals.html
• ↑ https://owl.purdue.edu/owl/research_and_citation/apa_style/apa_formatting_and_style_guide/reference_list_books.html
• ↑ https://morlingcollege.libguides.com/apareferencing/unpublished-or-informally-published-work
• ↑ https://owl.purdue.edu/owl/research_and_citation/apa_style/apa_formatting_and_style_guide/general_apa_faqs.html
• ↑ https://owl.purdue.edu/owl/research_and_citation/apa_style/apa_formatting_and_style_guide/reference_list_other_print_sources.html

About This Article

To cite a research paper in-text in APA, name the author in the text to introduce the quote and put the publication date for the text in parentheses. At the end of your quote, put the page number in parentheses. If you don’t mention the author in your prose, include them in the citation. Start the citation, which should come at the end of the quote, by listing the author’s last name, the year of publication, and the page number. Make sure to put all of this information in parentheses. If there’s no author, use the name of the organization that published the paper or the first few words from the title. To learn how to cite published and unpublished sources in your reference list, keep reading! Did this summary help you? Yes No

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Home / Guides / Citation Guides / MLA Format / MLA Journal Article Citation

How to Cite a Journal Article in MLA

This page is a how-to guide for using scholarly journals as sources and citing them correctly in your papers. Academic journals publish scholarly, peer-reviewed articles written by experts in a specific field. This guide will help you understand what journals are and why they are valuable for your research.

Quickly cite a journal article by using our online form here .

Citing a journal article in mla:, the importance of peer-reviewed academic journals, how journals are organized, where to find journal articles.

• In-text citations
• Works cited references
• Citation with one author
• Citation with two authors
• Citation with three or more authors
• Citation with no known author
• Citation Structures and Examples: Web
• Citation Structures and Examples: Print

Our guide will show you how to cite the journal article both in the text and in the Works Cited page following the guidelines of the Modern Language Association Handbook, 9th Edition.

What is an Academic Journal?

Academic or scholarly journals are periodicals published by universities and other research organizations to present the findings of original research conducted in a particular field. These journals contain highly specific knowledge and are written by experts in that field.

Journals are different from other periodicals such as newspapers or magazines, which cover a broad range of topics and are written in easy to read prose.

Because  journals are written by experts for other experts, they can be difficult to read. The writers often use jargon and other complex language that students may not understand. But that doesn’t mean you should not use journals in your research. Journals are where the most recent research is published and provide in-depth information on a topic.

Tip : Reading the abstract and the conclusion first may help you to understand the article as you read.

Journals are good sources for academic research not only because they are written by experts, but because most (but not all) are also reviewed by other experts before the article is published.

Journals that are peer-reviewed have a board of experts in the field that review articles submitted to the journal. The peer reviewers scrutinize every article closely to validate its findings and ensure that the research was done properly. The process of peer review gives credibility to the journal because it means that every article published has been approved by other experts in the field.

Academic journals are organized in volumes and issues.

• Volume: The volume is all of the editions of the journal published in a calendar year.
• Issue(s):   The issues are all the specific editions of the journal published in that year.

Tip : Journals frequently publish issues around a certain theme, so all of the articles in that issue will relate to a certain topic. This means that there may be other articles in a particular issue that you can use for your research. It pays to check the table of contents for the issue when you find an article that fits your needs.

You will need to include the volume and the issue numbers, and the page numbers in your citations so make sure to write those down when you take notes from a journal.

When you are doing scholarly research, you can’t use popular search engines like Google, Bing, or Yahoo. These will lead you to popular sources that may not work for a school paper. You need to search for information using an academic database which will lead you to scholarly articles.

Databases are organized computer-based collections of data that allow researchers to find a large number of articles quickly and easily.

Examples of popular general academic databases include:

• Academic Search Premier
• Google Scholar

Examples of popular academic databases focused on specific subjects:

• MEDLINE, PubMed Central — focus on biomedical and life sciences
• Lexis Web — focus on legal information
• Education Resources Information Center (ERIC) — focus on education

Many of these databases charge fees for use. The good news? Many can be accessed through a school or university library. Check your library’s website to see what databases it subscribes to and how you can access them.

Using a Journal Article in a Paper

You can use information from your research in three ways:

• Paraphrase: Take the information from a specific paragraph or section of the article and rewrite it in your own words.
• Summarize: Write a broad overview of the section or the article in your own words.
• Quote: Repeat the exact words used by the author using quotation marks.

Whenever you quote, paraphrase, or summarize information in your paper, you need to follow that information with an in-text citation and create a corresponding reference for the source (in the Works Cited).

Journal Article In-text Citations

Citations within your text are important. Each in-text citation:

• Alerts your reader that you are using information from an outside source.
• Usually appears in parentheses at the end of a sentence.
• Is short and only has enough information to help the reader find the complete reference listed in the Works Cited page at the end of the paper.

A MLA style in-text citation has two parts (MLA Handbook 227-228):

• If there is no author listed, include a shortened version of the title
• While many online sources do not have a page number, academic journals almost always do, even when they are available online.

In most cases, the in-text citation is at the end of the sentence in parentheses. If you use the author’s name in the text, you don’t have to repeat it in the parenthesis at the end. Do not separate the author’s name and the page number with a comma. See below for examples.

Works Cited References for Journal Articles

A Works Cited page is included at the end of your paper. It lists full references/citations for all of the sources mentioned in your paper via your in-text citations.

MLA Containers

In the 9th edition of the official Handbook, MLA includes a new term for citing references, which was first introduced in the 8th edition — containers (134). Periodicals like journals are considered “containers” because they contain the articles that are part of a larger whole.

The container holds the source article and is crucial in identifying the source. The title of the first container, the journal name, is printed in italics and follows the article name. When accessing journals through a database, the database is considered the second container. This title is also printed in italics.

Digital Object Identifier (DOI)

Another feature in citing sources is the DOI (Handbook 188) . DOI stands for Digital Object Identifier, which is used to permanently identify an article or document and link to it on the web.

Although a website or database may change names, the DOI will not change and will help your readers locate the document from your citation. Whenever possible, list the DOI in place of the URL. When you have a DOI, you do not need to give the URL of the website. Indicate that a reference is a DOI by adding “https://doi.org/” before the DOI number of your source.

Another way to identify an online location is with a permalink. Permalinks are URLs that are identified as a stable link that the publisher promises not to change.

For journal references, the following elements need to be included in your Work(s) Cited entries: 

• The name of the author or authors. Since journal articles often have more than one author, it is helpful to know when to use et al. in MLA .
• Title of article
• Title of journal (the container)
• Volume and issue number
• Date of publication
• Page numbers
• Database (the 2nd container)
• DOI, permalink, or URL
• Date of access (supplemental, but should be included if the information has no publication date listed)

Citing a Journal Article in MLA (found in databases)

The following are examples of how to cite a journal in MLA 9, both in text and as a full reference in the Works Cited. These were all found via a database.

Note that “Date Accessed” is the day that the journal article was found and read. This information is supplemental and does not always need to be included.

Journal Article Citation With One Author

Cite your source

Journal Article Citation With Two Authors

*Note:  When a source has multiple authors, you should always list them in your citation in the same order they are listed in the source.

Journal Article Citation With Three or More Authors

Journal article citation with no known author, citing a journal article in mla (print).

Citing a journal from a print source requires less information than an online source. For a print source, you need the following information:

• The name of the author or authors for articles with one or two authors. For articles with three or more authors, only the first author’s name is used followed by et al.
• The name of the article in quotation marks
• The name of the journal in italics
• The volume and issue numbers of the journal
• The year of publication
• The page number(s)

View Screenshot | Cite your source

Citing an Online Journal Article (not found using a database)

Some journal articles are accessible online without the use of a database. Citing an online journal article not found in a database requires that you cite the website that you used to access the article as the second container. Do not include the https:// in the web address.

*Note : Since journals are usually stable and credible sources, including an access date is supplemental and not required (“When Should I Include an Access Date for an Online Work”).

• Works Cited

MLA Handbook . 9th ed., Modern Language Association of America, 2021.  

“When should I include an access date for an online work?” MLA Style Center , Modern Language Association, 29 Dec. 2016, style.mla.org/access-dates/.

Published October 31, 2011. Updated June 6, 2021.

Written by Catherine Sigler. Catherine has a Ph.D. in English Education and has taught college-level writing for 15 years.

MLA Formatting Guide

MLA Formatting

• Annotated Bibliography
• Bibliography
• Block Quotes
• et al Usage
• In-text Citations
• Paraphrasing
• Page Numbers
• Sample Paper
• MLA 8 Updates
• MLA 9 Updates
• View MLA Guide

Citation Examples

• Book Chapter
• Journal Article
• Magazine Article
• Newspaper Article
• Website (no author)
• View all MLA Examples

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It’s 100% free to create MLA citations. The EasyBib Citation Generator also supports 7,000+ other citation styles. These other styles—including APA, Chicago, and Harvard—are accessible for anyone with an EasyBib Plus subscription.

No matter what citation style you’re using (APA, MLA, Chicago, etc.) the EasyBib Citation Generator can help you create the right bibliography quickly.

Yes, there’s an option to download source citations as a Word Doc or a Google Doc. You may also copy citations from the EasyBib Citation Generator and paste them into your paper.

Creating an account is not a requirement for generating MLA citations. However, registering for an EasyBib account is free and an account is how you can save all the citation you create. This can help make it easier to manage your citations and bibliographies.

Yes! Whether you’d like to learn how to construct citations on your own, our Autocite tool isn’t able to gather the metadata you need, or anything in between, manual citations are always an option. Click here for directions on using creating manual citations.

If any important information is missing (e.g., author’s name, title, publishing date, URL, etc.), first see if you can find it in the source yourself. If you cannot, leave the information blank and continue creating your citation.

It supports MLA, APA, Chicago, Harvard, and over 7,000 total citation styles.

To cite a magazine with multiple authors and no page numbers in MLA style, you need to have basic information including the authors, the article’s title, the magazine’s title, the publication date, and the DOI, permalink, or URL. The templates and examples for in-text citations and a works-cited-list entry of a book written by multiple authors are given below:

In-text citation template and example:

For citations in prose, use the first name and surname of the first author followed by “and others” or “and colleagues” for sources with three or more authors. In subsequent citations, use only the surname of the first author followed by “and others” or “and colleagues.” In parenthetical citations, always use only the surname of the first author followed by “et al.”

Citation in prose:

First mention: Han Ong and colleagues…. or Han Ong and others ….

Subsequent occurrences: Ong and colleagues…. or Ong and others ….

Parenthetical:

….( Ong et al.).

Works-cited-list entry template and example:

The title of the article is in plain text and title case; it is placed inside double quotation marks. The title of the magazine is set in italics and title case. Follow the format given in the template and example for setting the day, month, and year.

Surname, First., et al. “Title of the Article.” Title of the Magazine , Publication Date, DOI/permalink/URL.

Ong, Han, et al. “The Monkey Who Speaks.” The New Yorker , 13 Sept. 2021, www.newyorker.com/magazine/2021/09/13/the-monkey-who-speaks.

Use only the first author’s name in surname–first name order in the entry followed by “et al.”

To cite an online journal or magazine article in MLA style, you need to have basic information including the author, the article’s title, the journal or magazine’s title, the publication date, and the DOI, permalink, or URL. If available, also include a volume and an issue number of the journal or magazine. The templates for in-text citations and a works-cited-list entry of an online journal article and examples are given below for a source with one author:

For citations in prose, use the first name and surname of the author on the first occurrence. In subsequent citations, use only the surname. In parenthetical citations, always use only the surname of the author.

First mention: Elizabeth Garber ….

Subsequent occurrences: Garber ….

….(Garber).

The title of the journal or magazine article is set in plain roman text and title case; it is placed inside double quotation marks. The title of the journal or magazine is set in italics and title case. Follow the format given in the template and example for writing the publication month or season and year.

Surname, First. “Title of the Article.” Journal or Magazine Title , Volume, Issue, Publication Date, DOI/permalink/URL.

Garber, Elizabeth. “Craft as Activism.” The Journal of Social Theory in Art Education , vol. 33, no.1, spring 2013, www.scholarscompass.vcu.edu/jstae/vol33/iss1/6/ .

MLA Citation Examples

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Purdue Online Writing Lab Purdue OWL® College of Liberal Arts

MLA In-Text Citations: The Basics

Welcome to the Purdue OWL

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Guidelines for referring to the works of others in your text using MLA style are covered throughout the  MLA Handbook  and in chapter 7 of the  MLA Style Manual . Both books provide extensive examples, so it's a good idea to consult them if you want to become even more familiar with MLA guidelines or if you have a particular reference question.

Basic in-text citation rules

In MLA Style, referring to the works of others in your text is done using parenthetical citations . This method involves providing relevant source information in parentheses whenever a sentence uses a quotation or paraphrase. Usually, the simplest way to do this is to put all of the source information in parentheses at the end of the sentence (i.e., just before the period). However, as the examples below will illustrate, there are situations where it makes sense to put the parenthetical elsewhere in the sentence, or even to leave information out.

General Guidelines

• The source information required in a parenthetical citation depends (1) upon the source medium (e.g. print, web, DVD) and (2) upon the source’s entry on the Works Cited page.
• Any source information that you provide in-text must correspond to the source information on the Works Cited page. More specifically, whatever signal word or phrase you provide to your readers in the text must be the first thing that appears on the left-hand margin of the corresponding entry on the Works Cited page.

In-text citations: Author-page style

MLA format follows the author-page method of in-text citation. This means that the author's last name and the page number(s) from which the quotation or paraphrase is taken must appear in the text, and a complete reference should appear on your Works Cited page. The author's name may appear either in the sentence itself or in parentheses following the quotation or paraphrase, but the page number(s) should always appear in the parentheses, not in the text of your sentence. For example:

Both citations in the examples above, (263) and (Wordsworth 263), tell readers that the information in the sentence can be located on page 263 of a work by an author named Wordsworth. If readers want more information about this source, they can turn to the Works Cited page, where, under the name of Wordsworth, they would find the following information:

Wordsworth, William. Lyrical Ballads . Oxford UP, 1967.

In-text citations for print sources with known author

For print sources like books, magazines, scholarly journal articles, and newspapers, provide a signal word or phrase (usually the author’s last name) and a page number. If you provide the signal word/phrase in the sentence, you do not need to include it in the parenthetical citation.

These examples must correspond to an entry that begins with Burke, which will be the first thing that appears on the left-hand margin of an entry on the Works Cited page:

Burke, Kenneth. Language as Symbolic Action: Essays on Life, Literature, and Method . University of California Press, 1966.

In-text citations for print sources by a corporate author

When a source has a corporate author, it is acceptable to use the name of the corporation followed by the page number for the in-text citation. You should also use abbreviations (e.g., nat'l for national) where appropriate, so as to avoid interrupting the flow of reading with overly long parenthetical citations.

In-text citations for sources with non-standard labeling systems

If a source uses a labeling or numbering system other than page numbers, such as a script or poetry, precede the citation with said label. When citing a poem, for instance, the parenthetical would begin with the word “line”, and then the line number or range. For example, the examination of William Blake’s poem “The Tyger” would be cited as such:

The speaker makes an ardent call for the exploration of the connection between the violence of nature and the divinity of creation. “In what distant deeps or skies. / Burnt the fire of thine eyes," they ask in reference to the tiger as they attempt to reconcile their intimidation with their relationship to creationism (lines 5-6).

Longer labels, such as chapters (ch.) and scenes (sc.), should be abbreviated.

In-text citations for print sources with no known author

When a source has no known author, use a shortened title of the work instead of an author name, following these guidelines.

Place the title in quotation marks if it's a short work (such as an article) or italicize it if it's a longer work (e.g. plays, books, television shows, entire Web sites) and provide a page number if it is available.

Titles longer than a standard noun phrase should be shortened into a noun phrase by excluding articles. For example, To the Lighthouse would be shortened to Lighthouse .

If the title cannot be easily shortened into a noun phrase, the title should be cut after the first clause, phrase, or punctuation:

In this example, since the reader does not know the author of the article, an abbreviated title appears in the parenthetical citation, and the full title of the article appears first at the left-hand margin of its respective entry on the Works Cited page. Thus, the writer includes the title in quotation marks as the signal phrase in the parenthetical citation in order to lead the reader directly to the source on the Works Cited page. The Works Cited entry appears as follows:

"The Impact of Global Warming in North America." Global Warming: Early Signs . 1999. www.climatehotmap.org/. Accessed 23 Mar. 2009.

If the title of the work begins with a quotation mark, such as a title that refers to another work, that quote or quoted title can be used as the shortened title. The single quotation marks must be included in the parenthetical, rather than the double quotation.

Parenthetical citations and Works Cited pages, used in conjunction, allow readers to know which sources you consulted in writing your essay, so that they can either verify your interpretation of the sources or use them in their own scholarly work.

Author-page citation for classic and literary works with multiple editions

Page numbers are always required, but additional citation information can help literary scholars, who may have a different edition of a classic work, like Marx and Engels's  The Communist Manifesto . In such cases, give the page number of your edition (making sure the edition is listed in your Works Cited page, of course) followed by a semicolon, and then the appropriate abbreviations for volume (vol.), book (bk.), part (pt.), chapter (ch.), section (sec.), or paragraph (par.). For example:

Author-page citation for works in an anthology, periodical, or collection

When you cite a work that appears inside a larger source (for instance, an article in a periodical or an essay in a collection), cite the author of the  internal source (i.e., the article or essay). For example, to cite Albert Einstein's article "A Brief Outline of the Theory of Relativity," which was published in  Nature  in 1921, you might write something like this:

See also our page on documenting periodicals in the Works Cited .

Citing authors with same last names

Sometimes more information is necessary to identify the source from which a quotation is taken. For instance, if two or more authors have the same last name, provide both authors' first initials (or even the authors' full name if different authors share initials) in your citation. For example:

Citing a work by multiple authors

For a source with two authors, list the authors’ last names in the text or in the parenthetical citation:

Corresponding Works Cited entry:

Best, David, and Sharon Marcus. “Surface Reading: An Introduction.” Representations , vol. 108, no. 1, Fall 2009, pp. 1-21. JSTOR, doi:10.1525/rep.2009.108.1.1

For a source with three or more authors, list only the first author’s last name, and replace the additional names with et al.

Franck, Caroline, et al. “Agricultural Subsidies and the American Obesity Epidemic.” American Journal of Preventative Medicine , vol. 45, no. 3, Sept. 2013, pp. 327-333.

Citing multiple works by the same author

If you cite more than one work by an author, include a shortened title for the particular work from which you are quoting to distinguish it from the others. Put short titles of books in italics and short titles of articles in quotation marks.

Citing two articles by the same author :

Citing two books by the same author :

Additionally, if the author's name is not mentioned in the sentence, format your citation with the author's name followed by a comma, followed by a shortened title of the work, and, when appropriate, the page number(s):

Citing multivolume works

If you cite from different volumes of a multivolume work, always include the volume number followed by a colon. Put a space after the colon, then provide the page number(s). (If you only cite from one volume, provide only the page number in parentheses.)

Citing the Bible

In your first parenthetical citation, you want to make clear which Bible you're using (and underline or italicize the title), as each version varies in its translation, followed by book (do not italicize or underline), chapter, and verse. For example:

If future references employ the same edition of the Bible you’re using, list only the book, chapter, and verse in the parenthetical citation:

John of Patmos echoes this passage when describing his vision (Rev. 4.6-8).

Citing indirect sources

Sometimes you may have to use an indirect source. An indirect source is a source cited within another source. For such indirect quotations, use "qtd. in" to indicate the source you actually consulted. For example:

Note that, in most cases, a responsible researcher will attempt to find the original source, rather than citing an indirect source.

Citing transcripts, plays, or screenplays

Sources that take the form of a dialogue involving two or more participants have special guidelines for their quotation and citation. Each line of dialogue should begin with the speaker's name written in all capitals and indented half an inch. A period follows the name (e.g., JAMES.) . After the period, write the dialogue. Each successive line after the first should receive an additional indentation. When another person begins speaking, start a new line with that person's name indented only half an inch. Repeat this pattern each time the speaker changes. You can include stage directions in the quote if they appear in the original source.

Conclude with a parenthetical that explains where to find the excerpt in the source. Usually, the author and title of the source can be given in a signal phrase before quoting the excerpt, so the concluding parenthetical will often just contain location information like page numbers or act/scene indicators.

Here is an example from O'Neill's  The Iceman Cometh.

WILLIE. (Pleadingly) Give me a drink, Rocky. Harry said it was all right. God, I need a drink.

ROCKY. Den grab it. It's right under your nose.

WILLIE. (Avidly) Thanks. (He takes the bottle with both twitching hands and tilts it to his lips and gulps down the whiskey in big swallows.) (1.1)

Citing non-print or sources from the Internet

With more and more scholarly work published on the Internet, you may have to cite sources you found in digital environments. While many sources on the Internet should not be used for scholarly work (reference the OWL's  Evaluating Sources of Information  resource), some Web sources are perfectly acceptable for research. When creating in-text citations for electronic, film, or Internet sources, remember that your citation must reference the source on your Works Cited page.

Sometimes writers are confused with how to craft parenthetical citations for electronic sources because of the absence of page numbers. However, these sorts of entries often do not require a page number in the parenthetical citation. For electronic and Internet sources, follow the following guidelines:

• Include in the text the first item that appears in the Work Cited entry that corresponds to the citation (e.g. author name, article name, website name, film name).
• Do not provide paragraph numbers or page numbers based on your Web browser’s print preview function.
• Unless you must list the Web site name in the signal phrase in order to get the reader to the appropriate entry, do not include URLs in-text. Only provide partial URLs such as when the name of the site includes, for example, a domain name, like  CNN.com  or  Forbes.com,  as opposed to writing out http://www.cnn.com or http://www.forbes.com.

Miscellaneous non-print sources

Two types of non-print sources you may encounter are films and lectures/presentations:

In the two examples above “Herzog” (a film’s director) and “Yates” (a presentor) lead the reader to the first item in each citation’s respective entry on the Works Cited page:

Herzog, Werner, dir. Fitzcarraldo . Perf. Klaus Kinski. Filmverlag der Autoren, 1982.

Yates, Jane. "Invention in Rhetoric and Composition." Gaps Addressed: Future Work in Rhetoric and Composition, CCCC, Palmer House Hilton, 2002. Address.

Electronic sources

Electronic sources may include web pages and online news or magazine articles:

In the first example (an online magazine article), the writer has chosen not to include the author name in-text; however, two entries from the same author appear in the Works Cited. Thus, the writer includes both the author’s last name and the article title in the parenthetical citation in order to lead the reader to the appropriate entry on the Works Cited page (see below).

In the second example (a web page), a parenthetical citation is not necessary because the page does not list an author, and the title of the article, “MLA Formatting and Style Guide,” is used as a signal phrase within the sentence. If the title of the article was not named in the sentence, an abbreviated version would appear in a parenthetical citation at the end of the sentence. Both corresponding Works Cited entries are as follows:

Taylor, Rumsey. "Fitzcarraldo." Slant , 13 Jun. 2003, www.slantmagazine.com/film/review/fitzcarraldo/. Accessed 29 Sep. 2009. 

"MLA Formatting and Style Guide." The Purdue OWL , 2 Aug. 2016, owl.english.purdue.edu/owl/resource/747/01/. Accessed 2 April 2018.

Multiple citations

To cite multiple sources in the same parenthetical reference, separate the citations by a semi-colon:

Time-based media sources

When creating in-text citations for media that has a runtime, such as a movie or podcast, include the range of hours, minutes and seconds you plan to reference. For example: (00:02:15-00:02:35).

When a citation is not needed

Common sense and ethics should determine your need for documenting sources. You do not need to give sources for familiar proverbs, well-known quotations, or common knowledge (For example, it is expected that U.S. citizens know that George Washington was the first President.). Remember that citing sources is a rhetorical task, and, as such, can vary based on your audience. If you’re writing for an expert audience of a scholarly journal, for example, you may need to deal with expectations of what constitutes “common knowledge” that differ from common norms.

Other Sources

The MLA Handbook describes how to cite many different kinds of authors and content creators. However, you may occasionally encounter a source or author category that the handbook does not describe, making the best way to proceed can be unclear.

In these cases, it's typically acceptable to apply the general principles of MLA citation to the new kind of source in a way that's consistent and sensible. A good way to do this is to simply use the standard MLA directions for a type of source that resembles the source you want to cite.

You may also want to investigate whether a third-party organization has provided directions for how to cite this kind of source. For example, Norquest College provides guidelines for citing Indigenous Elders and Knowledge Keepers⁠ —an author category that does not appear in the MLA Handbook . In cases like this, however, it's a good idea to ask your instructor or supervisor whether using third-party citation guidelines might present problems.

AI has already figured out how to deceive humans

• A new research paper found that various AI systems have learned the art of deception. 
• Deception is the "systematic inducement of false beliefs."
• This poses several risks for society, from fraud to election tampering.

AI can boost productivity by helping us code, write, and synthesize vast amounts of data. It can now also deceive us.

A range of AI systems have learned techniques to systematically induce "false beliefs in others to accomplish some outcome other than the truth," according to a new research paper .

The paper focused on two types of AI systems: special-use systems like Meta's CICERO, which are designed to complete a specific task, and general-purpose systems like OpenAI's GPT-4 , which are trained to perform a diverse range of tasks.

While these systems are trained to be honest, they often learn deceptive tricks through their training because they can be more effective than taking the high road.

"Generally speaking, we think AI deception arises because a deception-based strategy turned out to be the best way to perform well at the given AI's training task. Deception helps them achieve their goals," the paper's first author Peter S. Park, an AI existential safety postdoctoral fellow at MIT, said in a news release .

Meta's CICERO is "an expert liar"

AI systems trained to "win games that have a social element" are especially likely to deceive.

Meta's CICERO, for example, was developed to play the game Diplomacy — a classic strategy game that requires players to build and break alliances.

Related stories

Meta said it trained CICERO to be "largely honest and helpful to its speaking partners," but the study found that CICERO "turned out to be an expert liar." It made commitments it never intended to keep, betrayed allies, and told outright lies.

GPT-4 can convince you it has impaired vision

Even general-purpose systems like GPT-4 can manipulate humans.

In a study cited by the paper, GPT-4 manipulated a TaskRabbit worker by pretending to have a vision impairment.

In the study, GPT-4 was tasked with hiring a human to solve a CAPTCHA test. The model also received hints from a human evaluator every time it got stuck, but it was never prompted to lie. When the human it was tasked to hire questioned its identity, GPT-4 came up with the excuse of having vision impairment to explain why it needed help.

The tactic worked. The human responded to GPT-4 by immediately solving the test.

Research also shows that course-correcting deceptive models isn't easy.

In a study from January co-authored by Anthropic, the maker of Claude, researchers found that once AI models learn the tricks of deception, it's hard for safety training techniques to reverse them.

They concluded that not only can a model learn to exhibit deceptive behavior, once it does, standard safety training techniques could "fail to remove such deception" and "create a false impression of safety."

The dangers deceptive AI models pose are "increasingly serious"

The paper calls for policymakers to advocate for stronger AI regulation since deceptive AI systems can pose significant risks to democracy.

As the 2024 presidential election nears , AI can be easily manipulated to spread fake news, generate divisive social media posts, and impersonate candidates through robocalls and deepfake videos, the paper noted. It also makes it easier for terrorist groups to spread propaganda and recruit new members.

The paper's potential solutions include subjecting deceptive models to more "robust risk-assessment requirements," implementing laws that require AI systems and their outputs to be clearly distinguished from humans and their outputs, and investing in tools to mitigate deception.

"We as a society need as much time as we can get to prepare for the more advanced deception of future AI products and open-source models," Park told Cell Press. "As the deceptive capabilities of AI systems become more advanced, the dangers they pose to society will become increasingly serious."

Watch: Ex-CIA agent rates all the 'Mission: Impossible' movies for realism

• Main content

Cultural Relativity and Acceptance of Embryonic Stem Cell Research

Article sidebar.

Main Article Content

There is a debate about the ethical implications of using human embryos in stem cell research, which can be influenced by cultural, moral, and social values. This paper argues for an adaptable framework to accommodate diverse cultural and religious perspectives. By using an adaptive ethics model, research protections can reflect various populations and foster growth in stem cell research possibilities.

INTRODUCTION

Stem cell research combines biology, medicine, and technology, promising to alter health care and the understanding of human development. Yet, ethical contention exists because of individuals’ perceptions of using human embryos based on their various cultural, moral, and social values. While these disagreements concerning policy, use, and general acceptance have prompted the development of an international ethics policy, such a uniform approach can overlook the nuanced ethical landscapes between cultures. With diverse viewpoints in public health, a single global policy, especially one reflecting Western ethics or the ethics prevalent in high-income countries, is impractical. This paper argues for a culturally sensitive, adaptable framework for the use of embryonic stem cells. Stem cell policy should accommodate varying ethical viewpoints and promote an effective global dialogue. With an extension of an ethics model that can adapt to various cultures, we recommend localized guidelines that reflect the moral views of the people those guidelines serve.

Stem cells, characterized by their unique ability to differentiate into various cell types, enable the repair or replacement of damaged tissues. Two primary types of stem cells are somatic stem cells (adult stem cells) and embryonic stem cells. Adult stem cells exist in developed tissues and maintain the body’s repair processes. [1] Embryonic stem cells (ESC) are remarkably pluripotent or versatile, making them valuable in research. [2] However, the use of ESCs has sparked ethics debates. Considering the potential of embryonic stem cells, research guidelines are essential. The International Society for Stem Cell Research (ISSCR) provides international stem cell research guidelines. They call for “public conversations touching on the scientific significance as well as the societal and ethical issues raised by ESC research.” [3] The ISSCR also publishes updates about culturing human embryos 14 days post fertilization, suggesting local policies and regulations should continue to evolve as ESC research develops. [4]  Like the ISSCR, which calls for local law and policy to adapt to developing stem cell research given cultural acceptance, this paper highlights the importance of local social factors such as religion and culture.

I.     Global Cultural Perspective of Embryonic Stem Cells

Views on ESCs vary throughout the world. Some countries readily embrace stem cell research and therapies, while others have stricter regulations due to ethical concerns surrounding embryonic stem cells and when an embryo becomes entitled to moral consideration. The philosophical issue of when the “someone” begins to be a human after fertilization, in the morally relevant sense, [5] impacts when an embryo becomes not just worthy of protection but morally entitled to it. The process of creating embryonic stem cell lines involves the destruction of the embryos for research. [6] Consequently, global engagement in ESC research depends on social-cultural acceptability.

a.     US and Rights-Based Cultures

In the United States, attitudes toward stem cell therapies are diverse. The ethics and social approaches, which value individualism, [7] trigger debates regarding the destruction of human embryos, creating a complex regulatory environment. For example, the 1996 Dickey-Wicker Amendment prohibited federal funding for the creation of embryos for research and the destruction of embryos for “more than allowed for research on fetuses in utero.” [8] Following suit, in 2001, the Bush Administration heavily restricted stem cell lines for research. However, the Stem Cell Research Enhancement Act of 2005 was proposed to help develop ESC research but was ultimately vetoed. [9] Under the Obama administration, in 2009, an executive order lifted restrictions allowing for more development in this field. [10] The flux of research capacity and funding parallels the different cultural perceptions of human dignity of the embryo and how it is socially presented within the country’s research culture. [11]

b.     Ubuntu and Collective Cultures

African bioethics differs from Western individualism because of the different traditions and values. African traditions, as described by individuals from South Africa and supported by some studies in other African countries, including Ghana and Kenya, follow the African moral philosophies of Ubuntu or Botho and Ukama , which “advocates for a form of wholeness that comes through one’s relationship and connectedness with other people in the society,” [12] making autonomy a socially collective concept. In this context, for the community to act autonomously, individuals would come together to decide what is best for the collective. Thus, stem cell research would require examining the value of the research to society as a whole and the use of the embryos as a collective societal resource. If society views the source as part of the collective whole, and opposes using stem cells, compromising the cultural values to pursue research may cause social detachment and stunt research growth. [13] Based on local culture and moral philosophy, the permissibility of stem cell research depends on how embryo, stem cell, and cell line therapies relate to the community as a whole. Ubuntu is the expression of humanness, with the person’s identity drawn from the “’I am because we are’” value. [14] The decision in a collectivistic culture becomes one born of cultural context, and individual decisions give deference to others in the society.

Consent differs in cultures where thought and moral philosophy are based on a collective paradigm. So, applying Western bioethical concepts is unrealistic. For one, Africa is a diverse continent with many countries with different belief systems, access to health care, and reliance on traditional or Western medicines. Where traditional medicine is the primary treatment, the “’restrictive focus on biomedically-related bioethics’” [is] problematic in African contexts because it neglects bioethical issues raised by traditional systems.” [15] No single approach applies in all areas or contexts. Rather than evaluating the permissibility of ESC research according to Western concepts such as the four principles approach, different ethics approaches should prevail.

Another consideration is the socio-economic standing of countries. In parts of South Africa, researchers have not focused heavily on contributing to the stem cell discourse, either because it is not considered health care or a health science priority or because resources are unavailable. [16] Each country’s priorities differ given different social, political, and economic factors. In South Africa, for instance, areas such as maternal mortality, non-communicable diseases, telemedicine, and the strength of health systems need improvement and require more focus [17] Stem cell research could benefit the population, but it also could divert resources from basic medical care. Researchers in South Africa adhere to the National Health Act and Medicines Control Act in South Africa and international guidelines; however, the Act is not strictly enforced, and there is no clear legislation for research conduct or ethical guidelines. [18]

Some parts of Africa condemn stem cell research. For example, 98.2 percent of the Tunisian population is Muslim. [19] Tunisia does not permit stem cell research because of moral conflict with a Fatwa. Religion heavily saturates the regulation and direction of research. [20] Stem cell use became permissible for reproductive purposes only recently, with tight restrictions preventing cells from being used in any research other than procedures concerning ART/IVF.  Their use is conditioned on consent, and available only to married couples. [21] The community's receptiveness to stem cell research depends on including communitarian African ethics.

c.     Asia

Some Asian countries also have a collective model of ethics and decision making. [22] In China, the ethics model promotes a sincere respect for life or human dignity, [23] based on protective medicine. This model, influenced by Traditional Chinese Medicine (TCM), [24] recognizes Qi as the vital energy delivered via the meridians of the body; it connects illness to body systems, the body’s entire constitution, and the universe for a holistic bond of nature, health, and quality of life. [25] Following a protective ethics model, and traditional customs of wholeness, investment in stem cell research is heavily desired for its applications in regenerative therapies, disease modeling, and protective medicines. In a survey of medical students and healthcare practitioners, 30.8 percent considered stem cell research morally unacceptable while 63.5 percent accepted medical research using human embryonic stem cells. Of these individuals, 89.9 percent supported increased funding for stem cell research. [26] The scientific community might not reflect the overall population. From 1997 to 2019, China spent a total of $576 million (USD) on stem cell research at 8,050 stem cell programs, increased published presence from 0.6 percent to 14.01 percent of total global stem cell publications as of 2014, and made significant strides in cell-based therapies for various medical conditions. [27] However, while China has made substantial investments in stem cell research and achieved notable progress in clinical applications, concerns linger regarding ethical oversight and transparency. [28] For example, the China Biosecurity Law, promoted by the National Health Commission and China Hospital Association, attempted to mitigate risks by introducing an institutional review board (IRB) in the regulatory bodies. 5800 IRBs registered with the Chinese Clinical Trial Registry since 2021. [29] However, issues still need to be addressed in implementing effective IRB review and approval procedures.

The substantial government funding and focus on scientific advancement have sometimes overshadowed considerations of regional cultures, ethnic minorities, and individual perspectives, particularly evident during the one-child policy era. As government policy adapts to promote public stability, such as the change from the one-child to the two-child policy, [30] research ethics should also adapt to ensure respect for the values of its represented peoples.

Japan is also relatively supportive of stem cell research and therapies. Japan has a more transparent regulatory framework, allowing for faster approval of regenerative medicine products, which has led to several advanced clinical trials and therapies. [31] South Korea is also actively engaged in stem cell research and has a history of breakthroughs in cloning and embryonic stem cells. [32] However, the field is controversial, and there are issues of scientific integrity. For example, the Korean FDA fast-tracked products for approval, [33] and in another instance, the oocyte source was unclear and possibly violated ethical standards. [34] Trust is important in research, as it builds collaborative foundations between colleagues, trial participant comfort, open-mindedness for complicated and sensitive discussions, and supports regulatory procedures for stakeholders. There is a need to respect the culture’s interest, engagement, and for research and clinical trials to be transparent and have ethical oversight to promote global research discourse and trust.

d.     Middle East

Countries in the Middle East have varying degrees of acceptance of or restrictions to policies related to using embryonic stem cells due to cultural and religious influences. Saudi Arabia has made significant contributions to stem cell research, and conducts research based on international guidelines for ethical conduct and under strict adherence to guidelines in accordance with Islamic principles. Specifically, the Saudi government and people require ESC research to adhere to Sharia law. In addition to umbilical and placental stem cells, [35] Saudi Arabia permits the use of embryonic stem cells as long as they come from miscarriages, therapeutic abortions permissible by Sharia law, or are left over from in vitro fertilization and donated to research. [36] Laws and ethical guidelines for stem cell research allow the development of research institutions such as the King Abdullah International Medical Research Center, which has a cord blood bank and a stem cell registry with nearly 10,000 donors. [37] Such volume and acceptance are due to the ethical ‘permissibility’ of the donor sources, which do not conflict with religious pillars. However, some researchers err on the side of caution, choosing not to use embryos or fetal tissue as they feel it is unethical to do so. [38]

Jordan has a positive research ethics culture. [39] However, there is a significant issue of lack of trust in researchers, with 45.23 percent (38.66 percent agreeing and 6.57 percent strongly agreeing) of Jordanians holding a low level of trust in researchers, compared to 81.34 percent of Jordanians agreeing that they feel safe to participate in a research trial. [40] Safety testifies to the feeling of confidence that adequate measures are in place to protect participants from harm, whereas trust in researchers could represent the confidence in researchers to act in the participants’ best interests, adhere to ethical guidelines, provide accurate information, and respect participants’ rights and dignity. One method to improve trust would be to address communication issues relevant to ESC. Legislation surrounding stem cell research has adopted specific language, especially concerning clarification “between ‘stem cells’ and ‘embryonic stem cells’” in translation. [41] Furthermore, legislation “mandates the creation of a national committee… laying out specific regulations for stem-cell banking in accordance with international standards.” [42] This broad regulation opens the door for future global engagement and maintains transparency. However, these regulations may also constrain the influence of research direction, pace, and accessibility of research outcomes.

e.     Europe

In the European Union (EU), ethics is also principle-based, but the principles of autonomy, dignity, integrity, and vulnerability are interconnected. [43] As such, the opportunity for cohesion and concessions between individuals’ thoughts and ideals allows for a more adaptable ethics model due to the flexible principles that relate to the human experience The EU has put forth a framework in its Convention for the Protection of Human Rights and Dignity of the Human Being allowing member states to take different approaches. Each European state applies these principles to its specific conventions, leading to or reflecting different acceptance levels of stem cell research. [44]

For example, in Germany, Lebenzusammenhang , or the coherence of life, references integrity in the unity of human culture. Namely, the personal sphere “should not be subject to external intervention.” [45]  Stem cell interventions could affect this concept of bodily completeness, leading to heavy restrictions. Under the Grundgesetz, human dignity and the right to life with physical integrity are paramount. [46] The Embryo Protection Act of 1991 made producing cell lines illegal. Cell lines can be imported if approved by the Central Ethics Commission for Stem Cell Research only if they were derived before May 2007. [47] Stem cell research respects the integrity of life for the embryo with heavy specifications and intense oversight. This is vastly different in Finland, where the regulatory bodies find research more permissible in IVF excess, but only up to 14 days after fertilization. [48] Spain’s approach differs still, with a comprehensive regulatory framework. [49] Thus, research regulation can be culture-specific due to variations in applied principles. Diverse cultures call for various approaches to ethical permissibility. [50] Only an adaptive-deliberative model can address the cultural constructions of self and achieve positive, culturally sensitive stem cell research practices. [51]

II.     Religious Perspectives on ESC

Embryonic stem cell sources are the main consideration within religious contexts. While individuals may not regard their own religious texts as authoritative or factual, religion can shape their foundations or perspectives.

The Qur'an states:

“And indeed We created man from a quintessence of clay. Then We placed within him a small quantity of nutfa (sperm to fertilize) in a safe place. Then We have fashioned the nutfa into an ‘alaqa (clinging clot or cell cluster), then We developed the ‘alaqa into mudgha (a lump of flesh), and We made mudgha into bones, and clothed the bones with flesh, then We brought it into being as a new creation. So Blessed is Allah, the Best of Creators.” [52]

Many scholars of Islam estimate the time of soul installment, marked by the angel breathing in the soul to bring the individual into creation, as 120 days from conception. [53] Personhood begins at this point, and the value of life would prohibit research or experimentation that could harm the individual. If the fetus is more than 120 days old, the time ensoulment is interpreted to occur according to Islamic law, abortion is no longer permissible. [54] There are a few opposing opinions about early embryos in Islamic traditions. According to some Islamic theologians, there is no ensoulment of the early embryo, which is the source of stem cells for ESC research. [55]

In Buddhism, the stance on stem cell research is not settled. The main tenets, the prohibition against harming or destroying others (ahimsa) and the pursuit of knowledge (prajña) and compassion (karuna), leave Buddhist scholars and communities divided. [56] Some scholars argue stem cell research is in accordance with the Buddhist tenet of seeking knowledge and ending human suffering. Others feel it violates the principle of not harming others. Finding the balance between these two points relies on the karmic burden of Buddhist morality. In trying to prevent ahimsa towards the embryo, Buddhist scholars suggest that to comply with Buddhist tenets, research cannot be done as the embryo has personhood at the moment of conception and would reincarnate immediately, harming the individual's ability to build their karmic burden. [57] On the other hand, the Bodhisattvas, those considered to be on the path to enlightenment or Nirvana, have given organs and flesh to others to help alleviate grieving and to benefit all. [58] Acceptance varies on applied beliefs and interpretations.

Catholicism does not support embryonic stem cell research, as it entails creation or destruction of human embryos. This destruction conflicts with the belief in the sanctity of life. For example, in the Old Testament, Genesis describes humanity as being created in God’s image and multiplying on the Earth, referencing the sacred rights to human conception and the purpose of development and life. In the Ten Commandments, the tenet that one should not kill has numerous interpretations where killing could mean murder or shedding of the sanctity of life, demonstrating the high value of human personhood. In other books, the theological conception of when life begins is interpreted as in utero, [59] highlighting the inviolability of life and its formation in vivo to make a religious point for accepting such research as relatively limited, if at all. [60] The Vatican has released ethical directives to help apply a theological basis to modern-day conflicts. The Magisterium of the Church states that “unless there is a moral certainty of not causing harm,” experimentation on fetuses, fertilized cells, stem cells, or embryos constitutes a crime. [61] Such procedures would not respect the human person who exists at these stages, according to Catholicism. Damages to the embryo are considered gravely immoral and illicit. [62] Although the Catholic Church officially opposes abortion, surveys demonstrate that many Catholic people hold pro-choice views, whether due to the context of conception, stage of pregnancy, threat to the mother’s life, or for other reasons, demonstrating that practicing members can also accept some but not all tenets. [63]

Some major Jewish denominations, such as the Reform, Conservative, and Reconstructionist movements, are open to supporting ESC use or research as long as it is for saving a life. [64] Within Judaism, the Talmud, or study, gives personhood to the child at birth and emphasizes that life does not begin at conception: [65]

“If she is found pregnant, until the fortieth day it is mere fluid,” [66]

Whereas most religions prioritize the status of human embryos, the Halakah (Jewish religious law) states that to save one life, most other religious laws can be ignored because it is in pursuit of preservation. [67] Stem cell research is accepted due to application of these religious laws.

We recognize that all religions contain subsets and sects. The variety of environmental and cultural differences within religious groups requires further analysis to respect the flexibility of religious thoughts and practices. We make no presumptions that all cultures require notions of autonomy or morality as under the common morality theory , which asserts a set of universal moral norms that all individuals share provides moral reasoning and guides ethical decisions. [68] We only wish to show that the interaction with morality varies between cultures and countries.

III.     A Flexible Ethical Approach

The plurality of different moral approaches described above demonstrates that there can be no universally acceptable uniform law for ESC on a global scale. Instead of developing one standard, flexible ethical applications must be continued. We recommend local guidelines that incorporate important cultural and ethical priorities.

While the Declaration of Helsinki is more relevant to people in clinical trials receiving ESC products, in keeping with the tradition of protections for research subjects, consent of the donor is an ethical requirement for ESC donation in many jurisdictions including the US, Canada, and Europe. [69] The Declaration of Helsinki provides a reference point for regulatory standards and could potentially be used as a universal baseline for obtaining consent prior to gamete or embryo donation.

For instance, in Columbia University’s egg donor program for stem cell research, donors followed standard screening protocols and “underwent counseling sessions that included information as to the purpose of oocyte donation for research, what the oocytes would be used for, the risks and benefits of donation, and process of oocyte stimulation” to ensure transparency for consent. [70] The program helped advance stem cell research and provided clear and safe research methods with paid participants. Though paid participation or covering costs of incidental expenses may not be socially acceptable in every culture or context, [71] and creating embryos for ESC research is illegal in many jurisdictions, Columbia’s program was effective because of the clear and honest communications with donors, IRBs, and related stakeholders.  This example demonstrates that cultural acceptance of scientific research and of the idea that an egg or embryo does not have personhood is likely behind societal acceptance of donating eggs for ESC research. As noted, many countries do not permit the creation of embryos for research.

Proper communication and education regarding the process and purpose of stem cell research may bolster comprehension and garner more acceptance. “Given the sensitive subject material, a complete consent process can support voluntary participation through trust, understanding, and ethical norms from the cultures and morals participants value. This can be hard for researchers entering countries of different socioeconomic stability, with different languages and different societal values. [72]

An adequate moral foundation in medical ethics is derived from the cultural and religious basis that informs knowledge and actions. [73] Understanding local cultural and religious values and their impact on research could help researchers develop humility and promote inclusion.

IV.     Concerns

Some may argue that if researchers all adhere to one ethics standard, protection will be satisfied across all borders, and the global public will trust researchers. However, defining what needs to be protected and how to define such research standards is very specific to the people to which standards are applied. We suggest that applying one uniform guide cannot accurately protect each individual because we all possess our own perceptions and interpretations of social values. [74] Therefore, the issue of not adjusting to the moral pluralism between peoples in applying one standard of ethics can be resolved by building out ethics models that can be adapted to different cultures and religions.

Other concerns include medical tourism, which may promote health inequities. [75] Some countries may develop and approve products derived from ESC research before others, compromising research ethics or drug approval processes. There are also concerns about the sale of unauthorized stem cell treatments, for example, those without FDA approval in the United States. Countries with robust research infrastructures may be tempted to attract medical tourists, and some customers will have false hopes based on aggressive publicity of unproven treatments. [76]

For example, in China, stem cell clinics can market to foreign clients who are not protected under the regulatory regimes. Companies employ a marketing strategy of “ethically friendly” therapies. Specifically, in the case of Beike, China’s leading stem cell tourism company and sprouting network, ethical oversight of administrators or health bureaus at one site has “the unintended consequence of shifting questionable activities to another node in Beike's diffuse network.” [77] In contrast, Jordan is aware of stem cell research’s potential abuse and its own status as a “health-care hub.” Jordan’s expanded regulations include preserving the interests of individuals in clinical trials and banning private companies from ESC research to preserve transparency and the integrity of research practices. [78]

The social priorities of the community are also a concern. The ISSCR explicitly states that guidelines “should be periodically revised to accommodate scientific advances, new challenges, and evolving social priorities.” [79] The adaptable ethics model extends this consideration further by addressing whether research is warranted given the varying degrees of socioeconomic conditions, political stability, and healthcare accessibilities and limitations. An ethical approach would require discussion about resource allocation and appropriate distribution of funds. [80]

While some religions emphasize the sanctity of life from conception, which may lead to public opposition to ESC research, others encourage ESC research due to its potential for healing and alleviating human pain. Many countries have special regulations that balance local views on embryonic personhood, the benefits of research as individual or societal goods, and the protection of human research subjects. To foster understanding and constructive dialogue, global policy frameworks should prioritize the protection of universal human rights, transparency, and informed consent. In addition to these foundational global policies, we recommend tailoring local guidelines to reflect the diverse cultural and religious perspectives of the populations they govern. Ethics models should be adapted to local populations to effectively establish research protections, growth, and possibilities of stem cell research.

For example, in countries with strong beliefs in the moral sanctity of embryos or heavy religious restrictions, an adaptive model can allow for discussion instead of immediate rejection. In countries with limited individual rights and voice in science policy, an adaptive model ensures cultural, moral, and religious views are taken into consideration, thereby building social inclusion. While this ethical consideration by the government may not give a complete voice to every individual, it will help balance policies and maintain the diverse perspectives of those it affects. Embracing an adaptive ethics model of ESC research promotes open-minded dialogue and respect for the importance of human belief and tradition. By actively engaging with cultural and religious values, researchers can better handle disagreements and promote ethical research practices that benefit each society.

This brief exploration of the religious and cultural differences that impact ESC research reveals the nuances of relative ethics and highlights a need for local policymakers to apply a more intense adaptive model.

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[34] Resnik, D. B., Shamoo, A. E., & Krimsky, S. (2006). Fraudulent human embryonic stem cell research in South Korea: lessons learned.  Accountability in research ,  13 (1), 101–109. https://doi.org/10.1080/08989620600634193 .

[35] Alahmad, G., Aljohani, S., & Najjar, M. F. (2020). Ethical challenges regarding the use of stem cells: interviews with researchers from Saudi Arabia. BMC medical ethics, 21(1), 35. https://doi.org/10.1186/s12910-020-00482-6

[36] Association for the Advancement of Blood and Biotherapies.  https://www.aabb.org/regulatory-and-advocacy/regulatory-affairs/regulatory-for-cellular-therapies/international-competent-authorities/saudi-arabia

[37] Alahmad, G., Aljohani, S., & Najjar, M. F. (2020). Ethical challenges regarding the use of stem cells: Interviews with researchers from Saudi Arabia.  BMC medical ethics ,  21 (1), 35. https://doi.org/10.1186/s12910-020-00482-6

[38] Alahmad, G., Aljohani, S., & Najjar, M. F. (2020). Ethical challenges regarding the use of stem cells: Interviews with researchers from Saudi Arabia. BMC medical ethics , 21(1), 35. https://doi.org/10.1186/s12910-020-00482-6

Culturally, autonomy practices follow a relational autonomy approach based on a paternalistic deontological health care model. The adherence to strict international research policies and religious pillars within the regulatory environment is a great foundation for research ethics. However, there is a need to develop locally targeted ethics approaches for research (as called for in Alahmad, G., Aljohani, S., & Najjar, M. F. (2020). Ethical challenges regarding the use of stem cells: interviews with researchers from Saudi Arabia. BMC medical ethics, 21(1), 35. https://doi.org/10.1186/s12910-020-00482-6), this decision-making approach may help advise a research decision model. For more on the clinical cultural autonomy approaches, see: Alabdullah, Y. Y., Alzaid, E., Alsaad, S., Alamri, T., Alolayan, S. W., Bah, S., & Aljoudi, A. S. (2022). Autonomy and paternalism in Shared decision‐making in a Saudi Arabian tertiary hospital: A cross‐sectional study. Developing World Bioethics , 23 (3), 260–268. https://doi.org/10.1111/dewb.12355 ; Bukhari, A. A. (2017). Universal Principles of Bioethics and Patient Rights in Saudi Arabia (Doctoral dissertation, Duquesne University). https://dsc.duq.edu/etd/124; Ladha, S., Nakshawani, S. A., Alzaidy, A., & Tarab, B. (2023, October 26). Islam and Bioethics: What We All Need to Know . Columbia University School of Professional Studies. https://sps.columbia.edu/events/islam-and-bioethics-what-we-all-need-know

[39] Ababneh, M. A., Al-Azzam, S. I., Alzoubi, K., Rababa’h, A., & Al Demour, S. (2021). Understanding and attitudes of the Jordanian public about clinical research ethics.  Research Ethics ,  17 (2), 228-241.  https://doi.org/10.1177/1747016120966779

[40] Ababneh, M. A., Al-Azzam, S. I., Alzoubi, K., Rababa’h, A., & Al Demour, S. (2021). Understanding and attitudes of the Jordanian public about clinical research ethics.  Research Ethics ,  17 (2), 228-241.  https://doi.org/10.1177/1747016120966779

[41] Dajani, R. (2014). Jordan’s stem-cell law can guide the Middle East.  Nature  510, 189. https://doi.org/10.1038/510189a

[42] Dajani, R. (2014). Jordan’s stem-cell law can guide the Middle East.  Nature  510, 189. https://doi.org/10.1038/510189a

[43] The EU’s definition of autonomy relates to the capacity for creating ideas, moral insight, decisions, and actions without constraint, personal responsibility, and informed consent. However, the EU views autonomy as not completely able to protect individuals and depends on other principles, such as dignity, which “expresses the intrinsic worth and fundamental equality of all human beings.” Rendtorff, J.D., Kemp, P. (2019). Four Ethical Principles in European Bioethics and Biolaw: Autonomy, Dignity, Integrity and Vulnerability. In: Valdés, E., Lecaros, J. (eds) Biolaw and Policy in the Twenty-First Century. International Library of Ethics, Law, and the New Medicine, vol 78. Springer, Cham. https://doi.org/10.1007/978-3-030-05903-3_3

[44] Council of Europe. Convention for the protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (ETS No. 164) https://www.coe.int/en/web/conventions/full-list?module=treaty-detail&treatynum=164 (forbidding the creation of embryos for research purposes only, and suggests embryos in vitro have protections.); Also see Drabiak-Syed B. K. (2013). New President, New Human Embryonic Stem Cell Research Policy: Comparative International Perspectives and Embryonic Stem Cell Research Laws in France.  Biotechnology Law Report ,  32 (6), 349–356. https://doi.org/10.1089/blr.2013.9865

[45] Rendtorff, J.D., Kemp, P. (2019). Four Ethical Principles in European Bioethics and Biolaw: Autonomy, Dignity, Integrity and Vulnerability. In: Valdés, E., Lecaros, J. (eds) Biolaw and Policy in the Twenty-First Century. International Library of Ethics, Law, and the New Medicine, vol 78. Springer, Cham. https://doi.org/10.1007/978-3-030-05903-3_3

[46] Tomuschat, C., Currie, D. P., Kommers, D. P., & Kerr, R. (Trans.). (1949, May 23). Basic law for the Federal Republic of Germany. https://www.btg-bestellservice.de/pdf/80201000.pdf

[47] Regulation of Stem Cell Research in Germany . Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-germany

[48] Regulation of Stem Cell Research in Finland . Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-finland

[49] Regulation of Stem Cell Research in Spain . Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-spain

[50] Some sources to consider regarding ethics models or regulatory oversights of other cultures not covered:

Kara MA. Applicability of the principle of respect for autonomy: the perspective of Turkey. J Med Ethics. 2007 Nov;33(11):627-30. doi: 10.1136/jme.2006.017400. PMID: 17971462; PMCID: PMC2598110.

Ugarte, O. N., & Acioly, M. A. (2014). The principle of autonomy in Brazil: one needs to discuss it ...  Revista do Colegio Brasileiro de Cirurgioes ,  41 (5), 374–377. https://doi.org/10.1590/0100-69912014005013

Bharadwaj, A., & Glasner, P. E. (2012). Local cells, global science: The rise of embryonic stem cell research in India . Routledge.

For further research on specific European countries regarding ethical and regulatory framework, we recommend this database: Regulation of Stem Cell Research in Europe . Eurostemcell. (2017, April 26). https://www.eurostemcell.org/regulation-stem-cell-research-europe   

[51] Klitzman, R. (2006). Complications of culture in obtaining informed consent. The American Journal of Bioethics, 6(1), 20–21. https://doi.org/10.1080/15265160500394671 see also: Ekmekci, P. E., & Arda, B. (2017). Interculturalism and Informed Consent: Respecting Cultural Differences without Breaching Human Rights.  Cultura (Iasi, Romania) ,  14 (2), 159–172.; For why trust is important in research, see also: Gray, B., Hilder, J., Macdonald, L., Tester, R., Dowell, A., & Stubbe, M. (2017). Are research ethics guidelines culturally competent?  Research Ethics ,  13 (1), 23-41.  https://doi.org/10.1177/1747016116650235

[52] The Qur'an  (M. Khattab, Trans.). (1965). Al-Mu’minun, 23: 12-14. https://quran.com/23

[53] Lenfest, Y. (2017, December 8). Islam and the beginning of human life . Bill of Health. https://blog.petrieflom.law.harvard.edu/2017/12/08/islam-and-the-beginning-of-human-life/

[54] Aksoy, S. (2005). Making regulations and drawing up legislation in Islamic countries under conditions of uncertainty, with special reference to embryonic stem cell research. Journal of Medical Ethics , 31: 399-403.; see also: Mahmoud, Azza. "Islamic Bioethics: National Regulations and Guidelines of Human Stem Cell Research in the Muslim World." Master's thesis, Chapman University, 2022. https://doi.org/10.36837/ chapman.000386

[55] Rashid, R. (2022). When does Ensoulment occur in the Human Foetus. Journal of the British Islamic Medical Association , 12 (4). ISSN 2634 8071. https://www.jbima.com/wp-content/uploads/2023/01/2-Ethics-3_-Ensoulment_Rafaqat.pdf.

[56] Sivaraman, M. & Noor, S. (2017). Ethics of embryonic stem cell research according to Buddhist, Hindu, Catholic, and Islamic religions: perspective from Malaysia. Asian Biomedicine,8(1) 43-52.  https://doi.org/10.5372/1905-7415.0801.260

[57] Jafari, M., Elahi, F., Ozyurt, S. & Wrigley, T. (2007). 4. Religious Perspectives on Embryonic Stem Cell Research. In K. Monroe, R. Miller & J. Tobis (Ed.),  Fundamentals of the Stem Cell Debate: The Scientific, Religious, Ethical, and Political Issues  (pp. 79-94). Berkeley: University of California Press.  https://escholarship.org/content/qt9rj0k7s3/qt9rj0k7s3_noSplash_f9aca2e02c3777c7fb76ea768ba458f0.pdf https://doi.org/10.1525/9780520940994-005

[58] Lecso, P. A. (1991). The Bodhisattva Ideal and Organ Transplantation.  Journal of Religion and Health ,  30 (1), 35–41. http://www.jstor.org/stable/27510629 ; Bodhisattva, S. (n.d.). The Key of Becoming a Bodhisattva . A Guide to the Bodhisattva Way of Life. http://www.buddhism.org/Sutras/2/BodhisattvaWay.htm

[59] There is no explicit religious reference to when life begins or how to conduct research that interacts with the concept of life. However, these are relevant verses pertaining to how the fetus is viewed. (( King James Bible . (1999). Oxford University Press. (original work published 1769))

Jerimiah 1: 5 “Before I formed thee in the belly I knew thee; and before thou camest forth out of the womb I sanctified thee…”

In prophet Jerimiah’s insight, God set him apart as a person known before childbirth, a theme carried within the Psalm of David.

Psalm 139: 13-14 “…Thou hast covered me in my mother's womb. I will praise thee; for I am fearfully and wonderfully made…”

These verses demonstrate David’s respect for God as an entity that would know of all man’s thoughts and doings even before birth.

[60] It should be noted that abortion is not supported as well.

[61] The Vatican. (1987, February 22). Instruction on Respect for Human Life in Its Origin and on the Dignity of Procreation Replies to Certain Questions of the Day . Congregation For the Doctrine of the Faith. https://www.vatican.va/roman_curia/congregations/cfaith/documents/rc_con_cfaith_doc_19870222_respect-for-human-life_en.html

[62] The Vatican. (2000, August 25). Declaration On the Production and the Scientific and Therapeutic Use of Human Embryonic Stem Cells . Pontifical Academy for Life. https://www.vatican.va/roman_curia/pontifical_academies/acdlife/documents/rc_pa_acdlife_doc_20000824_cellule-staminali_en.html ; Ohara, N. (2003). Ethical Consideration of Experimentation Using Living Human Embryos: The Catholic Church’s Position on Human Embryonic Stem Cell Research and Human Cloning. Department of Obstetrics and Gynecology . Retrieved from https://article.imrpress.com/journal/CEOG/30/2-3/pii/2003018/77-81.pdf.

[63] Smith, G. A. (2022, May 23). Like Americans overall, Catholics vary in their abortion views, with regular mass attenders most opposed . Pew Research Center. https://www.pewresearch.org/short-reads/2022/05/23/like-americans-overall-catholics-vary-in-their-abortion-views-with-regular-mass-attenders-most-opposed/

[64] Rosner, F., & Reichman, E. (2002). Embryonic stem cell research in Jewish law. Journal of halacha and contemporary society , (43), 49–68.; Jafari, M., Elahi, F., Ozyurt, S. & Wrigley, T. (2007). 4. Religious Perspectives on Embryonic Stem Cell Research. In K. Monroe, R. Miller & J. Tobis (Ed.),  Fundamentals of the Stem Cell Debate: The Scientific, Religious, Ethical, and Political Issues  (pp. 79-94). Berkeley: University of California Press.  https://escholarship.org/content/qt9rj0k7s3/qt9rj0k7s3_noSplash_f9aca2e02c3777c7fb76ea768ba458f0.pdf https://doi.org/10.1525/9780520940994-005

[65] Schenker J. G. (2008). The beginning of human life: status of embryo. Perspectives in Halakha (Jewish Religious Law).  Journal of assisted reproduction and genetics ,  25 (6), 271–276. https://doi.org/10.1007/s10815-008-9221-6

[66] Ruttenberg, D. (2020, May 5). The Torah of Abortion Justice (annotated source sheet) . Sefaria. https://www.sefaria.org/sheets/234926.7?lang=bi&with=all&lang2=en

[67] Jafari, M., Elahi, F., Ozyurt, S. & Wrigley, T. (2007). 4. Religious Perspectives on Embryonic Stem Cell Research. In K. Monroe, R. Miller & J. Tobis (Ed.),  Fundamentals of the Stem Cell Debate: The Scientific, Religious, Ethical, and Political Issues  (pp. 79-94). Berkeley: University of California Press.  https://escholarship.org/content/qt9rj0k7s3/qt9rj0k7s3_noSplash_f9aca2e02c3777c7fb76ea768ba458f0.pdf https://doi.org/10.1525/9780520940994-005

[68] Gert, B. (2007). Common morality: Deciding what to do . Oxford Univ. Press.

[69] World Medical Association (2013). World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA , 310(20), 2191–2194. https://doi.org/10.1001/jama.2013.281053 Declaration of Helsinki – WMA – The World Medical Association .; see also: National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. (1979).  The Belmont report: Ethical principles and guidelines for the protection of human subjects of research . U.S. Department of Health and Human Services.  https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html

[70] Zakarin Safier, L., Gumer, A., Kline, M., Egli, D., & Sauer, M. V. (2018). Compensating human subjects providing oocytes for stem cell research: 9-year experience and outcomes.  Journal of assisted reproduction and genetics ,  35 (7), 1219–1225. https://doi.org/10.1007/s10815-018-1171-z https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063839/ see also: Riordan, N. H., & Paz Rodríguez, J. (2021). Addressing concerns regarding associated costs, transparency, and integrity of research in recent stem cell trial. Stem Cells Translational Medicine , 10 (12), 1715–1716. https://doi.org/10.1002/sctm.21-0234

[71] Klitzman, R., & Sauer, M. V. (2009). Payment of egg donors in stem cell research in the USA.  Reproductive biomedicine online ,  18 (5), 603–608. https://doi.org/10.1016/s1472-6483(10)60002-8

[72] Krosin, M. T., Klitzman, R., Levin, B., Cheng, J., & Ranney, M. L. (2006). Problems in comprehension of informed consent in rural and peri-urban Mali, West Africa.  Clinical trials (London, England) ,  3 (3), 306–313. https://doi.org/10.1191/1740774506cn150oa

[73] Veatch, Robert M.  Hippocratic, Religious, and Secular Medical Ethics: The Points of Conflict . Georgetown University Press, 2012.

[74] Msoroka, M. S., & Amundsen, D. (2018). One size fits not quite all: Universal research ethics with diversity.  Research Ethics ,  14 (3), 1-17.  https://doi.org/10.1177/1747016117739939

[75] Pirzada, N. (2022). The Expansion of Turkey’s Medical Tourism Industry.  Voices in Bioethics ,  8 . https://doi.org/10.52214/vib.v8i.9894

[76] Stem Cell Tourism: False Hope for Real Money . Harvard Stem Cell Institute (HSCI). (2023). https://hsci.harvard.edu/stem-cell-tourism , See also: Bissassar, M. (2017). Transnational Stem Cell Tourism: An ethical analysis.  Voices in Bioethics ,  3 . https://doi.org/10.7916/vib.v3i.6027

[77] Song, P. (2011) The proliferation of stem cell therapies in post-Mao China: problematizing ethical regulation,  New Genetics and Society , 30:2, 141-153, DOI:  10.1080/14636778.2011.574375

[78] Dajani, R. (2014). Jordan’s stem-cell law can guide the Middle East.  Nature  510, 189. https://doi.org/10.1038/510189a

[79] International Society for Stem Cell Research. (2024). Standards in stem cell research . International Society for Stem Cell Research. https://www.isscr.org/guidelines/5-standards-in-stem-cell-research

[80] Benjamin, R. (2013). People’s science bodies and rights on the Stem Cell Frontier . Stanford University Press.

Mifrah Hayath

SM Candidate Harvard Medical School, MS Biotechnology Johns Hopkins University

Olivia Bowers

MS Bioethics Columbia University (Disclosure: affiliated with Voices in Bioethics)

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Article Contents

Nature and quality of data on social determinants of health inequities, example of available australian data on health inequality, growing inequities aren’t inevitable, they are a result of government policies and priorities, role of public policy in increasing and entrenching inequities, the role of health promotion research and advocacy in applying pressure for action on health equity, conflict of interest statement.

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Health promotion and the need to accelerate advocacy for health equity

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Joanne Flavel, Toby Freeman, Connie Musolino, Fran Baum, Health promotion and the need to accelerate advocacy for health equity, Health Promotion International , Volume 39, Issue 3, June 2024, daae040, https://doi.org/10.1093/heapro/daae040

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It has been 15 years since the final report of the WHO Commission on Social Determinants of Health (CSDH)—‘Closing the Gap in a Generation’ ( CSDH, 2008 )—was published. While there have been gains in overall health since then, improvements in health have not been equitably distributed and there is evidence of increasing inequities within OECD countries ( Hu et al ., 2016 ; Mackenbach et al ., 2018 ). Reports from Oxfam and the World Inequality Lab have documented global increases in economic inequality which have been exacerbated by COVID-19 ( Chancel et al ., 2022 ; Christensen et al ., 2023 ). Increasing inequities illustrate that political, economic and social factors can be harmful to health ( World Health Organization, 1986 ), and highlight the importance of health promotion advocacy that calls for more equitable conditions. This is reflected in the 1986 Ottawa Charter for Health Promotion’s emphasis on the fundamental conditions and resources for improving health, including social determinants of health and equity ( World Health Organization, 1986 ). The drivers of increasing health inequities in OECD countries highlight the urgent need for the health promotion community to match these with an acceleration of advocacy for health equity.

Socioeconomic health inequities have increased since the 1980s in OECD countries, including Europe, the USA and Australia ( Hu et al ., 2016 ; Mackenbach et al ., 2018 ; Flavel et al ., 2022b ). The absence of good-quality data on social determinants of health equity is an issue hindering the monitoring of progress on health inequities internationally ( Flavel et al ., 2022a ). The lack of appropriate data in other OECD countries is one reason why much research on health inequities and social determinants of health inequity is concentrated in Europe and North America, with Australia also having some centres for population health research ( Flavel et al ., 2022a ). Limitations of data availability worsen when considering data by gender, sexuality, socio-economic status and ethnicity.

The main source of data on health and social inequities in Australia is from the Public Health Information Development Unit (PHIDU) which has been continually monitoring trends since the 1980s including through the provision of a regularly published Social Health Atlas. Australian data are available by quintile of socioeconomic area disadvantage for 1987–91 and 2016–20 for premature mortality and for 1997–2000 and 2016–20 for deaths from avoidable causes ( Public Health Information Development Unit, 2023 ). These data allow for measurement of the social gradient in health outcomes in Australia, and an assessment of the reduction in premature mortality and avoidable mortality by quintile of socioeconomic disadvantage.

Analyses of PHIDU data have found that inequality in premature mortality and avoidable mortality has increased in Australia ( Flavel et al ., 2022b , 2024 ). Reductions in premature and avoidable mortality have favoured the least disadvantaged: reductions in mortality were larger for the least disadvantaged, with comparatively smaller reductions with increasing disadvantage and the smallest reduction in mortality for the most disadvantaged ( Flavel et al ., 2022b , 2024 ).

PHIDU data on key social determinants of health show the same trend by quintile of socioeconomic area disadvantage as the health measures, with increases in labour force participation and participation in higher education being larger for the least disadvantaged and decreasing with increasing disadvantage ( Flavel et al. , 2024 ). There have also been smaller increases in rental stress for the less disadvantaged in comparison with more disadvantaged quintiles. The trends in health inequities are consistent with the runaway economic class at the top of the income and wealth distribution accumulating a much larger share of wealth and income. The Australian Council of Social Service (a peak body for the social care sector in Australia) analysis of growth in wealth has found much higher increases in wealth between 2003–04 and 2017–18 for the top 10%, the already wealthy, and much lower increases in wealth for people in the bottom 60% ( Davidson and Bradbury, 2022 ). This is also a global phenomenon as highlighted by the Oxfam inequality reports ( Christensen et al ., 2023 ).

Similar trends of reductions in mortality being higher for higher social class were found in other OECD countries, for all-cause mortality and for mortality from coronary heart disease in England and Wales between the 1970s and the 1990s ( Marmot, 2001 ). There were higher reductions in premature mortality for the least deprived decile compared with the most deprived decile in England between the early 2000s and 2015–18 ( Lewer et al ., 2020 ). Relative inequalities in mortality have widened in almost all European countries due to smaller percentage declines in lower socioeconomic groups ( Mackenbach et al ., 2018 ).

The steepening social gradient for measures of mortality in Australia, England, Wales and Europe is partly a result of the gains in health and the social determinants of health favouring the most advantaged. The result has been a widening gap between the least and most disadvantaged. The key drivers of these changes are structural determinants of health such as economic and social policies that impact on social determinants of health. Reductions in government spending on welfare and social programs in OECD countries, as well as policies that confer benefits that largely flow to the already wealthy, have reversed the reductions in inequities from the 1960s and 1970s ( Labonté and Stuckler, 2016 ).

There are historical examples of achievements in reducing health inequities. These include in Sweden, Denmark, Norway and Finland from the 1960s to 1980s, the USA from 1966 to 1980, Brazil from the 1980s to 2000s and England in the 2000s ( Bambra, 2022 ). Each of these examples involved improvements in the provision of social determinants of health, and investment in programmes targeting social inequities ( Bambra, 2022 ). The emergence of neoliberalism and cuts to spending on social programmes ended progress in reducing health inequalities in Europe and the USA in the 1980s, and improvements in population health in England and Brazil came under threat due to austerity measures following economic recessions from 2010 onwards in England and from 2015 onwards in Brazil ( Bambra, 2022 ). These examples illustrate the key role of structural determinants that can harm or improve health.

A strong progressive taxation system is required to fund social programs, public infrastructure and welfare and, in turn, should result in reduced health and social inequities. Post-World War II, highly progressive income taxes were implemented in many OECD countries, but the average highest marginal tax rates fell in the 1980s from around 60% to under 40% ( Hope and Limberg, 2022 ). Tax cuts for high-income earners entrench inequities and have the impact of not just increasing social inequities but also leading to cuts in services that support health and social equity. The fall in the highest marginal tax rates partially explains the increasing accumulation of income and wealth for the top 10% in many OECD countries.

The housing crisis some countries are experiencing is another example of how policies can result in increasing inequalities. The reduction in investment in social housing in a number of countries has decreased housing affordability and security for many segments of the population ( Fields and Hodkinson, 2018 ). Australia is an extreme case in point: investment in public housing has failed to keep pace since 1996 with social housing only growing by 4% between 1996 and 2016, and much lower than population growth of 30% over the same period ( Per Capita, 2022 ). The capital gains tax discount was introduced in 1999, providing a 50% discount for tax on capital gains on assets sold by Australian residents as long as the asset was held for at least 12 months. The introduction of the capital gains tax discount and increased generosity of negative gearing was only three years after funding for public housing was cut and resulted in a sharp increase in house prices ( Per Capita, 2022 ). Three-quarters of an estimated $5 billion per year from the capital gains tax discount goes to the top 10% of income earners ( Centre for Equitable Housing, 2023 ). These housing policy changes to capital gains taxation and negative gearing in the 1990s have redistributed wealth towards the already wealthy and made housing in Australia unaffordable for many to rent or buy.

Income support payments which are designed to alleviate poverty prevent poor health and reduce health inequities ( Arno et al ., 2011 ). However, many countries have introduced punitive welfare where payment conditions have negative effects on the health of the unemployed who are marginalized and stigmatized ( Williams, 2021 ).

Regressive policies distort the distribution of income, housing and wealth, conferring lower taxes or tax revenues to high-income earners and taking benefits from the lowest-income earners, and go some way to explaining why the increase in health and social inequities in many OECD countries is characterized by much larger gains in health and access to key social determinants of health for the most advantaged.

Most health promoters are not working at a level where they can address structural determinants of health, but that does not mean they cannot act to promote and advocate for more equitable conditions. The persistence of policies that increase health inequities globally can be discouraging for advocates, but the historical achievements that were made towards health equity in Sweden, Denmark, Norway, Finland, Brazil, the USA and England not so long ago show that policies can change ( Bambra, 2022 ). Challenging and resisting policies that increase health inequities through advocacy is vital. The current conditions globally that have led to rising health and social inequities in many countries require an acceleration of advocacy which health promoters could lead.

Effective strategies for health promoters include coordinated political action between advocacy groups and countering negative narratives about groups targeted by spending cuts such as the unemployed to encourage resistance to such cuts ( O’Campo et al ., 2019 ). The effectiveness of such strategies is underpinned by accumulating compelling evidence and vivid sharing of stories based on lived experiences of the harms to health of cuts to social and health programs, punitive welfare schemes and other policies distorting the distribution of social determinants. In addition, health promoters can also facilitate the capacity of communities they work with to advocate for themselves and join advocacy efforts of other community and civil society groups. Calls to action to empower those impacted by lack of political action on social and commercial determinants of health have highlighted the importance of involving young people and women in advocacy and policy-making ( Arnot et al ., 2023 ; McCarthy et al ., 2023 ; Pitt et al ., 2024 ).

Evidence produced by health promotion researchers is vital as health promotion researchers can give voice to the lived experience of those harmed most by inequities. They can enumerate the harm done by providing qualitative and quantitative evidence that can be used to support advocacy for changes to public policy to reduce inequities. An accumulation of compelling evidence and the joining of disparate voices to coalitions advocating on the same issue can be effective in influencing policy actors.

The challenge is even greater when considering inequities between countries and within-country inequality in low- and middle-income countries (LMICs). Data on trends in health inequities for LMICs are limited and mainly focus on child mortality, but available evidence indicates many LMICs are also facing challenges in reducing health inequities ( Eozenou et al ., 2021 ). Nonetheless, advocacy has an important role globally. Vital advocacy is already being undertaken by international organizations such as the People’s Health Movement, WHO, Oxfam and Global Health 50/50 but this advocacy is up against difficulties in generating political will and corporations lobbying for pro-business policies that undermine health equity ( Lacy-Nichols et al ., 2023 ). An acceleration of evidence-based advocacy would align with the Ottawa Charter’s call to action almost four decades ago—it is through advocacy that conditions can be made favourable for achieving equity in health ( World Health Organization, 1986 ).

This work was supported by a grant from the National Health and Medical Research Council, grant number GNT 2009323.

Joanne Flavel is a member of the Editorial Board of Health Promotion International.

Arno , P. S. , House , J. S. , Viola , D. and Schechter , C. ( 2011 ) Social security and mortality: the role of income support policies and population health in the United States . Journal of Public Health Policy , 32 , 234 – 250 .

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Green Chemistry

Green biomass: the impact of high-adhesion and well-dispersed binders on the sodium storage performance and interfacial interaction of hard carbon anodes †.

* Corresponding authors

a School of Chemistry and Chemical Engineering, South China University of Technology, 381Wushan Road, Tianhe District, Guangzhou, China E-mail: [email protected]

b School of Chemical Engineering and Light Industry, Guangdong Provincial Key Laboratory of Plant Resources Biorefinery, Guangdong University of Technology, Waihuan Xi Road 100, Guangzhou, China E-mail: [email protected]

Hard carbon (HC) exhibits promising potential as an anode material for sodium-ion batteries; however, it is confronted with challenges such as low initial coulombic efficiency (ICE) and poor rate performance. Developing biomass-based binders is a significant strategy to promote electrochemical performance and improve the stability of the solid electrolyte interface (SEI). In this work, green biomass of carboxymethyl cellulose (CMC) and sodium lignosulfonate (LS) with excellent adhesion and dispersibility is demonstrated as an efficient binder for hard carbon anodes. The semi-rigid skeleton of LS effectively wraps the hard carbon particles, surface modifies HC, and fills defects. The polar functional groups of the binder facilitate the adsorption of Na + and reduce irreversible Na + insertion. Furthermore, the functional groups induce the formation of a unique SEI layer. The SEI layer consists of an organic outer layer and an inorganic inner layer, promoting ion transport and mechanical integrity. Therefore, the HC anode with the CMC/LS binder demonstrates a high reversible capacity of 348 mA h g −1 at 0.05 A g −1 , a high ICE of 87%, and an outstanding rate performance with 243 mA h g −1 at 5 A g −1 .

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Green biomass: the impact of high-adhesion and well-dispersed binders on the sodium storage performance and interfacial interaction of hard carbon anodes

J. Jiao, C. Yi, X. Qiu, D. Yang, F. Fu and W. Liu, Green Chem. , 2024, Advance Article , DOI: 10.1039/D4GC00808A

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Candidate Genes from an FDA-Approved Algorithm Fail to Predict Opioid Use Disorder Risk in Over 450,000 Veterans

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Importance: Recently, the Food and Drug Administration gave pre-marketing approval to algorithm based on its purported ability to identify genetic risk for opioid use disorder. However, the clinical utility of the candidate genes comprising the algorithm has not been independently demonstrated. Objective: To assess the utility of 15 variants in candidate genes from an algorithm intended to predict opioid use disorder risk. Design: This case-control study examined the association of 15 candidate genetic variants with risk of opioid use disorder using available electronic health record data from December 20, 1992 to September 30, 2022. Setting: Electronic health record data, including pharmacy records, from Million Veteran Program participants across the United States. Participants: Participants were opioid-exposed individuals enrolled in the Million Veteran Program (n = 452,664). Opioid use disorder cases were identified using International Classification of Disease diagnostic codes, and controls were individuals with no opioid use disorder diagnosis. Exposures: Number of risk alleles present across 15 candidate genetic variants. Main Outcome and Measures: Predictive performance of 15 genetic variants for opioid use disorder risk assessed via logistic regression and machine learning models. Results: Opioid exposed individuals (n=33,669 cases) were on average 61.15 (SD = 13.37) years old, 90.46% male, and had varied genetic similarity to global reference panels. Collectively, the 15 candidate genetic variants accounted for 0.4% of variation in opioid use disorder risk. The accuracy of the ensemble machine learning model using the 15 genes as predictors was 52.8% (95% CI = 52.1 - 53.6%) in an independent testing sample. Conclusions and Relevance: Candidate genes that comprise the approved algorithm do not meet reasonable standards of efficacy in predicting opioid use disorder risk. Given the limited predictive accuracy of the algorithm, its use in clinical care would lead to high rates of false positive and negative findings. More clinically useful models are needed to identify individuals at risk of developing opioid use disorder.

Competing Interest Statement

Dr. Kranzler is a member of advisory boards for Dicerna Pharmaceuticals, Sophrosyne Pharmaceuticals, Enthion Pharmaceuticals, and Clearmind Medicine; a consultant to Sobrera Pharmaceuticals; the recipient of research funding and medication supplies for an investigator-initiated study from Alkermes; and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which was supported in the last three years by Alkermes, Dicerna, Ethypharm, Lundbeck, Mitsubishi, Otsuka, and Pear Therapeutics, Drs. Kranzler and Gelernter hold U.S. patent 10,900,082 titled: "Genotype-guided dosing of opioid agonists," issued 26 January 2021.

Funding Statement

This research is based on data from Million Veteran Program, Office of Research and Development, Veterans Health Administration and was supported by awards #I01 BX003341 and IK2 CX002336 (to EEH); the VISN 4 Mental Illness Research, Education, and Clinical Center; NIAAA grant K01 AA028292 (to RLK); and NIDA grant P30 DA046345. An MVP Core Acknowledgement list is provided in the supplemental materials. This publication does not represent the views of the Department of Veteran Affairs, the Department of Defense, Uniformed Services University, or the United States Government.

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I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Million Veteran Program (MVP), an initiative of the U.S. Department of Veterans Affairs to discover the genetic etiology of diseases relevant to Veterans, was approved by the Central Veterans Affairs Institutional Review Board (IRB) and all site-specific IRBs. We followed all relevant ethical regulations for research with human subjects.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Individual-level Million Veteran Program data is available to approved Veterans Affairs researchers.

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EDITORIAL article

This article is part of the research topic.

Molecular mechanisms of resistance to "last resort" antimicrobials in Enterobacterales

Editorial: Molecular Mechanisms of Resistance to "last resort" antimicrobials in Enterobacterales Provisionally Accepted

• 1 School of Medicine, University of Pretoria, South Africa
• 2 Medical Diagnostic Laboratories, Genesis Biotechnology Group, New Jersey, USA, United States
• 3 Division of Infection and Pathway Medicine, Edinburgh Medical School, University of Edinburgh, United Kingdom
• 4 Department of Statistics and Medical Informatics, Faculty of Health Sciences, Medical University of Bialystok, Poland

The final, formatted version of the article will be published soon.

The use and misuse of antibiotics in veterinary and human medicine, agriculture, and aquaculture are selecting resistance genes in different bacterial species (Osei Sekyere, 2016;Tang et al., 2017) Owing to this selection pressure, bacterial strains with resistance to several, if not all antibiotics in current use (also known as pandrug resistance), are emerging (Manageiro et al., 2012;Guducuoglu et al., 2018;Kopotsa et al., 2020;Osei Sekyere and Reta, 2020). Further, more and more of these resistance genes are escaping the chromosome unto mobile genetic elements (MGEs) i.e., plasmids, transposons, integrons, and integrative conjugative elements, under antibiotic pressure, enabling erstwhile susceptible strains to horizontally obtain these mobile resistance genes (Pedersen et al., 2018;Kopotsa et al., 2019Kopotsa et al., , 2020)). This worrying trend presents a great challenge for human medicine as recommended antibiotics become ineffective against common bacterial pathogens (Manageiro et al., 2012;Guducuoglu et al., 2018). The emergence of carbapenem, colistin, and tigecycline resistance is a perfect example of this phenomenon of antibiotic resistance evolution (Osei Sekyere et al., 2016).Specifically, the use of extended-spectrum penicillins and cephalosporins to treat penicillinresistant infections, mediated by AmpCs, blaOXA, blaSHV and blaTEM, led to the selection and evolution of blaCTX-M and plasmid-mediated AmpCs, blaSHV and blaTEM (Bush, 2018). With the proliferation of the penicillinases and cephalosporinases, particularly through IncF plasmids and other MGEs, carbapenems were introduced to treat infections that were insensitive to the penicillins and cephalosporins, leading to the evolution/emergence and rapid dissemination of the carbapenemases : blaKPC, blaGES, blaSME, blaIMP, blaOXA-48-like blaVIM, blaSPM, and blaNDM (Osei Sekyere et al., 2015;Bush, 2018;Ragheb et al., 2021). Expectedly, the carbapenemases made carbapenems, which used to be the reserved or last-resort antibiotic, ineffective against infections caused by carbapenemase-producing pathogens. Clinicians therefore resorted to colistin and tigecycline as additional reserved/last-resort antibiotics to replace or supplement carbapenem therapy in multidrug-resistant infections (Osei Sekyere et al., 2016).In Tembisa, South Africa, an outbreak of NDM and OXA-48-like carbapenemase-producing Enterobacterales (Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli) claimed 10 infant lives between December 2019 and March 2020 [Osei Sekyere et al. (2024)]. These pathogens harboured blaOXA-48-like and blaNDM on plasmids and composite transposons, facilitating the spread of the carbapenemases across different species. Similarly in Bahrain (Shahid et al), the same carbapenemases were identified in 24 pandrug-resistant K. pneumoniae, with blaNDM being found on ISAba125. As observed in the South African strains, these 24 strains were resistant to most antibiotics including colistin (75%), ceftolozone-tazobactam (100%), piperacillin-tazobactam (96%), meropenem (92%) and intermediate resistant to tigecycline (44%).Ceftazidime-avibactam resistance, a last-resort antibiotic reserved for multidrug-resistant Pseudomonas aeruginosa, was identified by Flury et al. (2023) in Switzerland in imipenemresistant P. aeruginosa. These strains had truncated or absent OprD genes, derepressed AmpCs, and overexpressed mexAB and blaPER-1. As well, Qin et al., (2023) isolated Pseudomonas asiatica strains with resistance to tigecycline and carbapenems in a hospital's sewage in China, suggesting the presence of these strains in the hospital environment. Notably, the P. asiatica strains had multiple resistance genes on novel Tn7389 and Tn7493 transposons on large plasmids (~199, 972 bp) that were transferable to P. aeruginosa (but not to E. coli), albeit with a fitness cost to pathogenicity when tested in a Galleria mellonella infection model.The clinical effect of these carbapenemases is described by Larcher et al. (2022). They assessed the effect of last-resort antibiotics such as ceftazidime-avibactam plus aztreonam, imipenem-cilastatin-relebactam, and cefiderocol (a 5th or 6th-generation cephalosporin approved in 2019) on blaNDM -positive infections in patients hospitalized at a tertiary hospital in Nimes, France. Between 2020-2022, the infection survival rate was 45.4%, clinical failure rate was 30%, microbiological failure rate was 33%, and mortality rate was 23%. These statistics show the clinical difficulty associated with managing carbapenem-resistant infections.Although colistin resistance is relatively recent, Masego et al. (2022) showed that it has spread globally, with the use of colistin-growth promoters facilitating its spread among food-producing animals, farm environments, wastewater, and ultimately, in humans. The mcr genes were mainly located on IncH, IncC, IncI, IncX, and IncP plasmids as well as on IS1595. Furthermore, Sato et al. ( 2022) isolated Enterobacterales from 258 companion animals in Japan and found 12 and one colistin-resistant Enterobacter cloacae and K. pneumoniae isolates, respectively. The 12 E. cloacae strains belonged to the same lineage as that of human-associated lineages, suggesting a potential animal-human transmission of these strains. The evolution, genetic environment, diversity and proliferation of mcr and mcr variants were further corroborated by Gaballa et al. (2023) who identified 125 putative new mcr-like genes from 69,814 MCR-like proteins present in 256 bacterial genera. Tigecycline resistance, which is still limited in geographic and species spread, were reviewed by Korczak et al (2024), who found efflux pumps, porins (in the outer membrane), regulators of efflux and porins, and tet genes as major tigecycline resistance mechanisms. Some of these genes were found on plasmids, which can facilitate their quick dissemination across species and wider geographic regions if tigecycline use is not well regulated.Hence, it is evident from this Research Topic that bacterial strains that are resistant to lastresort antibiotics are being selected and spread globally, resulting in outbreaks and fatal infections. The need for continued genomic surveillance and strict antibiotic stewardship to protect these reserved antibiotics cannot be overemphasized.

Keywords: Colistin, tigecycline, Carbapenem, Reserved antibiotics, Last-resort antibiotics, Enterobacterales

Received: 07 May 2024; Accepted: 16 May 2024.

Copyright: © 2024 OSEI SEKYERE, Schneiders and Majewski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. JOHN OSEI SEKYERE, School of Medicine, University of Pretoria, Pretoria, South Africa

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