21.4: MLA Documentation and Format
MLA style is the preferred form for documenting research sources in English and other humanities disciplines. The following are general features of MLA style:
- All material borrowed from sources is cited in the text of a paper by the author’s name and page number (if available).
- A works-cited list at the end of a paper provides full publication data for each source cited in the text of the paper.
- Additional explanatory information provided by the writer (but not from external sources) goes in either footnotes or endnotes. These notes are optional.
MLA In-Text Citations
In-text citations feature author names, page numbers, and sometimes titles, depending on what information is available. The Index located in H12 provides a listing of the models that are included below.
- One Author
When you quote, paraphrase, or summarize a source, include the last name of the source’s author, if known, in a signal phrase or in parentheses at the end of your sentence. Provide the page or pages on which the original material appeared. Do not include the word page or the abbreviations p. or pp. Use a hyphen [-] to indicate a number range (See Spotlight on … Citation for more on quoting, paraphrasing, and summarizing sources):
Becker points out that Joe Biden’s views on same-sex marriage changed during a personal visit to a family while he was vice president (285-86).
While he was vice president, Joe Biden’s views on same-sex marriage changed during a personal visit with a family (Becker 285-86).
- Two or more works by the same author
If you cite two or more works by the same author in your paper, give the title of the specific work in your sentence or a short version of the title in parentheses:
According to Lewis Thomas in Lives of a Cell , many bacteria become dangerous only if they manufacture exotoxins (76).
According to Lewis Thomas, many bacteria become dangerous only if they manufacture exotoxins ( Lives 76).
Many bacteria become dangerous only if they manufacture exotoxins (Thomas, Lives 76).
See Model 18 for how to cite two works by the same author in the works-cited list.
- Two authors
If you cite a work with two authors, include both authors’ names in a signal phrase or in parentheses:
In the preface to Half the Sky , Kristof and WuDunn explain their focus on the issues of sex trafficking and sex work, violence against women, and maternal mortality (xxi).
In the preface to Half the Sky , the authors explain their focus on the issues of sex trafficking and sex work, violence against women, and maternal mortality (Kristof and WuDunn xxi).
- Three or more authors
For works with more than two authors, give the last name of the first author followed by “et al.”:
Of the survey respondents, twenty-two percent described themselves as concerned about future job prospects (Pronkowski et al. 9).
- Authors with the same last name
When authors of different sources have the same last name, include their initials:
Since the legalization of marijuana for recreational use, frequent use among adults has risen (J. T. Greene 21; M. Greene 30).
- Organization, government, corporation, or association as author
When no author is given for a work published by a corporation, a government, an organization, or an association, indicate the group’s name in a signal phrase or in parentheses:
The United States Forest Service describes its mission as “sustain[ing] the health, diversity, and productivity of the nation’s forests and grasslands to meet the needs of present and future generations” (8).
- Unknown author
When the author of a work is unknown, use the work’s title in a signal phrase or a shortened version of the title in parentheses and a page number if available. Put quotation marks around article titles, and put book or journal titles in italics:
In a pointed 2020 editorial, “Don’t Let the Games Begin,” The New York Times argued that college athletic departments should support public health by canceling sports seasons until athletes and the public were vaccinated.
In a pointed 2020 editorial, The New York Times argued that college athletic departments should support public health by canceling sports seasons until athletes and the public were vaccinated (“Don’t Let”).
- Work in more than one volume
If you cite only one volume of a multivolume work, give the page number in parentheses. If you cite more than one volume of a multivolume work, give the volume number for each citation before the page number, and follow it with a colon and one space:
Hill notes that Sir Arthur Conan Doyle’s The Adventure of the Dancing Men was first published in the Strand Magazine and later in Collier’s Weekly (1: 332).
- Work with no page or other reference numbers
When the work has no page numbers, give the author’s name in a signal phrase or in parentheses. If the source has paragraph, chapter, or section numbers, use them with the abbreviations par. , ch. , or sec. :
Chen reports that the number of Americans seeking help with mental health rose during the pandemic that began in 2020. (ch. 2)
The number of Americans seeking help with mental health rose during the pandemic that began in 2020 (Chen, ch. 2).
For an audio or a video recording, give the start and stop times for the segment you are citing shown on the player in hours (if available), minutes, and seconds:
It is well known that maternity leave is available in countries around the world, including Norway, which popularized its policy in a comic YouTube video showing a pregnant woman on skis announcing the start of her one-year paid leave (01:48-02:07).
- One-page work or entire work
When you cite a work that is one page long or an entire work, such as a book, website, single-page article, tweet, video, or film, you do not need to cite a page or give a reference number:
In Da 5 Bloods , director Spike Lee connects the Civil Rights movement to the war in Vietnam through the music, montages of the era, and characters’ stories.
- Source quoted in another source (indirect quotation)
When a quotation or any information in your source is originally from another source, try to track down the original source. If you cannot find it, use the abbreviation “qtd. in”:
The group, which has researched global health including access to food, sounded the alarm about a potential “worldwide food crisis” in the early 2000s (qtd. in Sing 32).
- Literacy works
-
Poetry and verse plays
For poems, provide line numbers for reference, and include line or lines in the first reference:
In “The Character,” Aphra Behn describes a lovely young woman, starting with her eyes: “Her Eyes all sweet, and languishingly move” (line 4).
Cite verse plays using act, scene, and line numbers, separated by periods: ( Hamlet 4.4.31-39) -
Fiction and prose plays
When citing a prose literary work available in various editions, provide additional information after the page number, such as the chapter, act, or scene number, for readers who may be consulting a different edition. Use a semicolon to separate the page number from this additional information: (331; ch. 5) or (78; act 2).
- Two or more works in the same citation
When you cite more than one work in parentheses, use a semicolon between them:
Americans who resisted or ignored civil defense are often portrayed as heroic people who chose not to build fallout shelters or as marginalized people who could not afford them (Garrison 57; Mechling and Mechling 109).
- Sacred text
When you cite passages from the Bible or another sacred text such as the Qur’an, give the title of the edition you are consulting the first time you refer to it. Then give the book (abbreviate the title if it is longer than four letters), chapter, and verse, separated by periods:
Several times in the New Testament of the Bible, Jesus comments on wealth, telling his disciples, “And again I say unto you, It is easier for a camel to go through the eye of a needle, than for a rich man to enter into the kingdom of God” ( King James Version , Matt. 19.24).
Endnotes and Footnotes
Writers use notes to offer comments, explanations, or additional information that cannot easily be integrated into the rest of a paper. Use notes to cite several sources within a single context if a series of in-text citations will detract from the readability of the text.
Text with Superscript
The standard ingredients for guacamole include avocados, lemon juice, onion, tomatoes, coriander, salt, and pepper. 1 Hurtado’s poem, however, gives this traditional dish a whole new twist.
Note
- For variations see Beard 314, Egerton 197, Eckhardt 92, and Kafka 26. Beard’s version, which includes olives and green peppers, is the most unusual.
A note may be placed as a footnote at the bottom of the page on which the in-text citation appears or on a separate page of endnotes at the end of the paper. This should be titled “Notes” or “Endnotes” and appear between the last page of the paper and the works-cited list. Include all sources given in notes in the works-cited list.
MLA Works Cited
Each source cited in the text of your paper refers readers to the list of works cited, a complete list of all the sources you quoted, paraphrased, or summarized. Every source cited in the text of your paper must be included in the works-cited list, and every source in the works-cited list must be cited in the text of your paper.
Format of the List of Works Cited (MLA)
After the last page of the paper, start a new page with the centered title “Works Cited” at the top. Create an entry for each source using the following guidelines and examples:
- Begin each entry at the left margin, and indent subsequent lines one-half inch. (In Microsoft Word, you can also highlight the entire page when you are finished and select “Hanging” from the Special options on the Indentation section of the Paragraph menu.)
- Alphabetize the entries according to authors’ last names. If two or more authors have the same last name, alphabetize by first name or initial. Alphabetize sources with unknown authors by the first word of the title, excluding a , an , or the .
- Double-space the entire page.
Core Elements (MLA)
Each entry in the list of works cited consists of core elements:
- Author. Who is responsible for the work?
- Title. What is the work called?
-
Publication information.
Where can the work be found so that others can consult it?
Publication information includes the date of publication and any larger work, which MLA calls a “container,” in which a shorter work is published, such as a journal, magazine, newspaper, database, streaming service, and so on.
A note on access dates. Although access dates for online sources are not required, MLA acknowledges that an access date can indicate the version of a source you consulted. If you add an access date, place it at the end of the works-cited entry in this format: “Accessed 4 Apr. 2020.”
Authors and Contributors for Books and Articles (MLA)
- Authors. Give the author’s last name, a comma, the author’s first name and any middle name or middle initial, and then a period. For works with more than one author, an organization as an author, or an unknown author, see the models below.
- Contributors. People who contributed to the work in addition to the author are called contributors. Refer to them by their role in a phrase such as “adapted by,” “directed by,” “edited by,” “illustrated by,” “introduction by,” “narrated by,” “performance by,” and “translated by.” (See Models 19, 20, 21, 30, and 58 for examples.)
- Book: one author
Sotomayor, Sonia. My Beloved World . Vintage Books, 2013.
- Book: two atuhors
Kristoff, Nicholas D., and Sheryl WuDunn. H alf the Sky: Turning Oppression into Opportunity for Women Worldwide . Alfred A. Knopf, 2009.
- Book: three or more authors
Barlow, David H., et al. Abnormal Psychology: An Integrative Approach . 8th ed., Cengage Learning, 2017.
- Book: two or more works by the same author
When you cite two works by the same author, use three hyphens in place of the author’s name, and alphabetize the works by title:
Trethewey, Natasha. Memorial Drive: A Daughter’s Memoir . Ecco, 2020.
---. Native Guard: Poems . Mariner Books, 2007.
- Book author and editor
Add the editor’s name after the title:
Hemingway, Ernest. Conversations with Ernest Hemingway , edited by Matthew J. Bruccoli, UP of Mississippi, 1986.
- Book author and translator
Add the translator’s name after the title:
Ferrante, Elena. My Brilliant Friend . Translated by Ann Goldstein, Europa Editions, 2012.
If you are citing the work of the translator, place the translator’s name in the author position:
Goldstein, Ann, translator. My Brilliant Friend . By Elena Ferrante, Europa Editions, 2012.
- Book author and illustrator
Add the illustrator’s name after the title. If you are citing the work of the illustrator, place the illustrator’s name in the author position, as shown in the preceding example:
Fasler, Joe. Light in the Dark: Writers on Creativity, Inspiration, and the Artistic Process . Illustrated by Doug McLean, Penguin Books, 2017.
- Work by an organization, a government, a corporation, or an association
If the author and publisher are not the same, start with the author:
United States Department of Veterans Affairs, Veterans Health Administration. Healthy Living Resource Guide . Government Printing Office, 2020.
If the author and the publisher are the same, give the title of the work in place of the author, and list the organization as the publisher:
MLA Handbook . 8th ed., Modern Language Association of America, 2016.
“This Is Who We Are.” U.S. Forest Service , United States Department of Agriculture, Mar. 2019, www.fs.usda.gov/sites/default/files/This-is-Who-We-Are.pdf.
- Unknown author
If no author is given, start with the title.
“The Most Beautiful Battalion in the Army.” Grunt Magazine , 1968, pp. 12-15.
Articles in Journals, Magazines, and Newspaper (MLA)
Articles, reviews, editorials, and other short works are published in journals, newspapers, and magazines. They appear in print, on databases, and on websites (though often through a paywall). As a student, you are likely to access many articles and other short research sources primarily through databases available through your library.
- Basic format for a journal article in a database
Author’s Last Name, First Name. “Title of Article.” Title of Journal , volume number, issue number, Date of Publication, page numbers. Title of Database , DOI or URL.
- Author. Give the last name, a comma, the first name, and any middle name or initial. Do not list an author’s professional title, such as Dr. or PhD. End with a period.
- Title of the article. Give the full title and any subtitle, separating them with a colon. Capitalize all significant words in the title. Put the title of the article in quotation marks. End with a period inside the closing quotation mark.
- Title of the journal. Put the title of the journal in italics. Capitalize all significant words in the title. End the title with a comma.
- Volume and issue numbers. Use the abbreviations vol. and no. followed by the number and a comma.
- Publication date. Give the month or season and the year of publication, if available. Use the following abbreviations for months: Jan. , Feb. , Mar. , Apr. , Aug. , Sept. , Oct. , Nov. , and Dec. Do not abbreviate May, June, or July.
- Page numbers. Give p. (singular) or pp. (plural) and the page number or numbers of the article, followed by a period.
- Title of the database. Put the database title in italics, followed by a comma.
- Location. Give a DOI if available, and end with a period. If there is no DOI, give a URL, preferably a permalink, without http://.
- Article in an academic journal
-
Database
Daddis, Gregory A. “Out of Balance: Evaluating American Strategy in Vietnam, 1968–72.” War & Society , vol. 32, no. 3, Oct. 2013, pp. 252-70. EBSCOhost, doi:10.1179/0729247313Z.00000000026. -
Print
Daddis, Gregory A. “Out of Balance: Evaluating American Strategy in Vietnam, 1968–72.” War & Society , vol. 32, no. 3, Oct. 2013, pp. 252-70. -
Online
Squires, Scot. “Do Generations Differ When It Comes to Green Values and Products?” Electronic Green Journal , no. 42, 2019, escholarship.org/uc/item/6f91213q.
The journal in the example numbers issues only, so no volume number is given.
- Article in a weekly or biweekly magazine
To cite an article in a weekly or biweekly magazine, give the author, title of the article, title of the magazine, publication date (day, month, year), and page numbers. If you found the article through a database, add the title of the database and a DOI or URL. If you found the article online, add the URL.
-
Database
Sanneh, Kelefa. “The Color of Money.” The New Yorker , 8 Feb. 2021, pp. 26-31. EBSCOhost , search.ebscohost.com/login.aspx?direct=true&AuthType=aph&AN=148411685&site=ehost-live&scope=site. -
Print
Sanneh, Kelefa. “The Color of Money.” The New Yorker , 8 Feb. 2021, pp. 26-31. -
Online
Ferrer, Ada. “My Brother’s Keeper.” The New Yorker , 22 Feb. 2021, www.newyorker.com/magazine/2021/ 03/01/my-brothers-keeper.
- Article in a monthly or bimonthly magazine
To cite an article in a monthly or bimonthly magazine, give the author, title of the article, title of the magazine, publication month and year, and page numbers. If you found the article through a database, add the title of the database and a DOI or URL. If you found the article online, add the URL.
-
Database
Sneed, Annie. “Giant Shape-Shifters.” Scientific American , Sept. 2017, pp. 20-22. EBSCOhost , doi:10.1038/ scientificamerican1017-20 . -
Print
Sneed, Annie. “Giant Shape-Shifters.” Scientific American , Sept. 2017, pp. 20-22. -
Online
Stewart, Jamila. “A Look Inside the Black Designers of Canada Initiative.” Essence , July 2020, www.essence.com/fashion/black-designers-of-canada-digital-index/.
To cite a comment on an article, see Model 54.
- Article in a newspaper
To cite an article in a newspaper, give the author, title of the article, title of the newspaper, publication date (day, month, year), and the page numbers. If you found the article through a database, add the title of the database and a DOI or a URL. If you found the article online, add the URL.
-
Database
Krueger, Alyson. “When Mom Knows Best, on Instagram.” The New York Times , 27 Nov. 2019, pp. B1-B4. EBSCOhost , search.ebscohost.com/login.aspx?direct=true&AuthType =aph&AN=139891108&site=ehost-live&scope=site. -
Print
Krueger, Alyson. “When Mom Knows Best, on Instagram.” The New York Times , 27 Nov. 2019, pp. B1-B4. -
Online
Smith, Doug. “They’re Building Affordable Housing for the Homeless—Without Government Help.” Los Angeles Times , 10 Feb. 2021, www.latimes.com/california/story/2021-02-10/theyre-building-affordable-housing-for-the-homeless-without-government-help.
To cite a comment on an article, see Model 54.
- Editorial or letter to the editor
An editorial may or may not have an author’s name attached to it. If it does, give the author’s name first. If it does not, start with the title. In both situations, add the designation Editorial or Letter to the Editor after the title.
“For Better Elections, Copy the Neighbors.” Editorial. The Wall Street Journal, 16 Feb. 2021, www.wsj.com/ articles/for-better-elections-copy-the-neighbors-11613518448.
- Review
To cite a review of a book, film, television show, or other work, give the name of the reviewer and title of the review, add Review of before the title of work being reviewed, and give the name of the work’s author, director, or creator after the title.
Girish, Devika. “Refocusing the Lens on Race and Gender.” Review of Test Pattern , directed by Shatara Michelle Ford. The New York Times , 18 Feb. 2021, www.nytimes.com/2021/02/18/movies/test-pattern-review.html.
Books and Parts of Books (MLA)
Use the following guidelines for books and parts of books, such as a selection from an anthology, an article in a collection, a published letter, and so on.
- Basic entry for a book
Author’s Last Name, First Name. Title of Book . Publisher, Year of Publication.
- Author. Give the last name, a comma, the first name, and any middle name or initial. Do not list an author’s professional title, such as Dr. or PhD. End with a period.
- Title of the book. Put the book’s title in italics. Give the full title and any subtitle, separating them with a colon. Capitalize all significant words in the title, even if the book’s cover does not use conventional capitalization. End the title with a period.
- Publisher. List the publisher’s name without words such as “Inc.” or “Company.” Shorten “University Press” to “UP.” End with a comma.
- Year of publication. Provide the publication date, and end with a period.
- Print book
Wilkerson, Isabel. The Warmth of Other Suns: The Epic Story of America’s Great Migration . Vintage Books, 2010.
- E-book formatted for a specific reader device or service
Wilkerson, Isabel. The Warmth of Other Suns: The Epic Story of America’s Great Migration . Kindle ed., Vintage Books, 2010.
- Book, anthology, or collection with an editor
Add the abbreviation ed. or eds. (if more than one) after the editor’s first name:
Lunsford, Andrea, ed. Reclaiming Rhetorica: Women in the Rhetorical Tradition . U of Pittsburgh P, 1995.
- Work in an anthology or chpater in an edited collection
After the author and title of the work, give the title of the anthology or edited collection, name of the editor, publication information, and page numbers of the work:
Royster, Jacqueline Jones. “To Call a Thing by Its True Name: The Rhetoric of Ida B. Wells.” Reclaiming Rhetorica: Women in the Rhetorical Tradition , edited by Andrea Lunsford, U of Pittsburgh P, 1995, pp. 167-84.
- Two or more works in an anthology or edited collection
When you cite two or more selections from the same anthology or edited collection, list the anthology separately under the editor’s name. In the entries for the selections you cite, include the editor’s name and the page numbers on which the selections appear:
Lipscomb, Drema R. “Sojourner Truth: A Practical Public Discourse." Lunsford, pp. 227-46.
Lunsford, Andrea, ed. Reclaiming Rhetorica: Women in the Rhetorical Tradition . U of Pittsburgh P, 1995.
Royster, Jacqueline Jones. “To Call a Thing by Its True Name: The Rhetoric of Ida B. Wells.” Lunsford, pp. 167-84.
- Revised or later edition
For a book published in an edition other than the first, give the edition number after the title:
Strunk, William, Jr., and E. B. White. The Elements of Style , 4th ed., Pearson, 2019.
- Multivolume work
For a book published in more than one volume, give the total number of volumes after the title:
Klinger, Leslie S. The New Annotated Sherlock Holmes . 2 vols., W. W. Norton, 2005.
- One volume of a multivolume work
Klinger, Leslie S. The New Annotated Sherlock Holmes . Vol. 2, W. W. Norton, 2005.
When each volume of a multivolume set has an individual title, list the volume’s full publication information first, followed by series information (number of volumes, dates). When separate volumes were published in different years, give inclusive dates:
Churchill, Winston S. Triumph and Tragedy . Houghton Mifflin, 1953. Vol. 6 of The Second World War . 6 vols. 1948-53.
However, if the volume you are using has its own title, you may cite the book without referring to the other volumes as if it were an independent publication.
- Book in a series
Add the title of the series at the end of the entry:
Thaiss, Christopher. Language across the Curriculum in the Elementary Grades . WAC Clearinghouse, 2011, wac.colostate.edu/books/landmarks/thaiss/. Landmark Publications in Writing Studies.
- Republished book
Give the original publication date after the title and the date the book was republished after the publisher:
Evans, Elizabeth E. G. The Abuse of Maternity . 1875. Arno, 1974.
- Sacred text
Give the complete title of the version you consulted followed by the name of the editor and/or translator, the edition, the publisher, and the publication date:
The Bible . Authorized King James Version. Edited by Robert Carroll and Stephen Prickett, Oxford UP, 2008.
The Koran . Translated by N. J. Dawood, rev. ed., Penguin Books, 2015.
- Introduction, preface, foreword, or afterword
Start with the author of the introduction, preface, foreword, or afterword, followed by a description of the work you are citing, such as “Foreword.” Give the author of the work after the title:
Offill, Jenny. Foreword. Mrs. Dalloway , by Virginia Woolf, Penguin Classics, 2021, pp. vii-xiv.
- Published letter
Roosevelt, Theodore. Letter to Upton Sinclair. 15 Mar. 1906. Theodore Roosevelt: Letters and Speeche s, edited by Louis Auchincloss, 2004, pp. 310-11.
- Conference paper
Killi, Stainer, and Andrew Morrison. “Could the Food Market Pull 3D Printing Appetites Further?” Industry 4.0—Shaping the Future of the Digital World: Proceedings of the 2nd International Conference on Sustainable & Smart Manufacturing , edited by Paulo Bartolo et al., CRC Press, 2021, pp. 197-203.
Websites and Parts of Websites (MLA)
Use the following guidelines for works that are published only online and do not have an overarching publication, such as a journal, newspaper, magazine, or database.
- Basic format for a short work or page on a website
Author’s Last Name, First Name. “Title of Short Work.” Title of Website , Publisher, Publication Date, URL.
- Author. Give the last name, a comma, the first name, and any middle name or initial. Do not list an author’s professional title, such as Dr. or PhD. End with a period.
- Title of the short work. Put the title in quotation marks. Give the full title and any subtitle, separating them with a colon. Capitalize all significant words in the title. End with a period inside the closing quotation mark.
- Title of the website. Put the title of the website in italics. Capitalize all significant words in the title. End the title with a comma.
- Publisher. If the publisher of the website is different from the title of the website (as shown in Model 48), give it next, followed by a comma. If they are the same (as shown in Model 47), give only the title of the website.
- Publication date. Give the day, month, and year the work was posted, if available. Use the following abbreviations for months: Jan. , Feb. , Mar. , Apr. , Aug. , Sept. , Oct. , Nov. , and Dec. Do not abbreviate May, June, and July.
- URL. Give the URL, without “http://.”
- Short work or page on a website
Shetterly, Margot Lee. “Katherine Johnson Biography.” NASA , 24 Feb. 2020, www.nasa.gov/content/katherine-johnson-biography.
If the source you are citing has no author listed, start with the title. If the page has no title, give the name of the site and a descriptive label, such as “Home page” or “Blog post.”
- Blog post
Blazich, Frank A. “The Cold Morning of the Day After.” Smithsonian Voices, Smithsonian Magazine , 5 Feb. 2021, www.smithsonianmag.com/blogs/national-museum-american-history/2021/02/05/cold-morning-day-after/.
- Entire website
Beinecke Rare Book and Manuscript Library . Yale U, 2021, beinecke.library.yale.edu/.
If the website lists an editor, give the person’s name as you would an author, followed by a comma and ed.
- Wiki
“Coronavirus.” Wikipedia . Wikimedia Foundation, 22 Feb. 2021, en.Wikipedia.org/wiki/Coronavirus.
Social Media (MLA)
- Basic format for a social media post
Author. “Text of untitled post” or “Title of post” or Descriptive label. Title of Site , Date of Post, Time of Post, URL.
- Author. Give the author’s handle and name. End with a period.
- Text, title, or description of post. Match the capitalization exactly, add quotation marks, and end with a period inside the closing quotation mark.
- Title of the social media site. Put the title of the site in italics, ending with a comma.
- Publication date and time. Give the day, month, year, and time of the post. Use the following abbreviations for months: Jan. , Feb. , Mar ., Apr. , Aug. , Sept. , Oct. , Nov. , and Dec. Do not abbreviate May, June, and July.
- URL. Give the URL, without “http://.”
- Social media post
@Holleratcha (James Holler). “People go out and vote tomorrow!” Twitter , 2 Nov. 2020, 2:08 p.m., twitter.com/ holleratcha/status/1270432672544784384.
Death Valley National Park. “What does it mean to protect something you love?” Facebook , 23 Feb. 2021, 5:01 p.m., www.facebook.com/DeathValleyNPS/posts/4108808255810092.
See Model 54 for how to cite a comment.
- Online forum post
@Duckpond318. “Turkeys in the arboretum.” Reddit , 15 Mar. 2021, 11:22 a.m., www.reddit.com/r/Wildlife/ comments/lqlbo3/turkeys_in_the_arboretum/. Accessed 4 Feb. 2021.
- Online comment
AKJersey. Comment on “Can We Stop Fighting about Charter Schools?” The New York Times , 22 Feb. 2021, www.nytimes.com/2021/02/22/opinion/charter-schools-democrats.html#commentsContainer.
Personal Communication (MLA)
Use the following guidelines to cite email, text messages, and letters that you sent or received.
Roberts, Jeffrey. “Study results.” Received by Kenneth Berg, 21 Oct. 2020.
- Text message
Roberts, Jeffrey. “Study results.” Received by Kenneth Berg, 21 Oct. 2020.
- Personal letter
Atwood, Margaret. Letter to the author. 11 Mar. 2007.
Video, Audio, and Other Media Sources (MLA)
Use the following guidelines to cite various media sources.
- Film
Begin with the title, followed by the director, the studio, and the year released.
Casablanca . Directed by Michael Curtiz, Warner Brothers, 1942.
You may also cite other contributors and their roles after the title (as illustrated below). If your paper is concerned with a particular person’s work on a film, such as the director, an actor, or someone else, begin with that person’s name and arrange all other information accordingly. For a film you stream, add the title of the streaming service and the URL:
Moonlight . Directed by Barry Jenkins, performances by Mahershala Ali, Naomie Harris, and Trevante Rhodes. A24, 2016. Netflix , www.netflix.com/watch/80121348?trackId=13752289&tctx=8%2C.
- Online video
NASA. “Apollo 11 Moonwalk – Original NASA EVA Mission Video.” 20 July 1969. YouTube , 17 July 2014, www.youtube.com/watch?v=S9HdPi9Ikhk.
- Television series or episode
-
TV Series
The Good Place . Michael Schur, creator. NBC, 2016-20. -
Streamed TV episode
“Jason Mendoza.” The Good Place , season 1, episode 4, NBC, 2016. Netflix , www.netflix.com/watch/ 80191852?trackId=13752289&tctx=%2C%2C.
- Advertisement
-
Print
XOFLUZA. Flu medication advertisement. The New Yorker , 8. Feb. 2021, pp. 5-6. -
Online
General Motors. “Will Ferrell Super Bowl Ad.” YouTube , 3 Feb. 2021, www.youtube.com/ watch?v=mdsPvbSpB2Y&t=24s.
- Cartoon or comic
-
Print
Davis, Jim. “Garfield.” Cartoon. Courier [Findlay, OH], 17 May 1996, p. 18.
If the source you cite appears in a local newspaper, as it does here, give the city and state in brackets after the name of the newspaper if the city is not part of the newspaper’s name. -
Online
Gauld, Tom. “Waiting for Godot to Join the Zoom Meeting.” You’re All Just Jealous of My Jetpack , 31 Jan. 2021, myjetpack.tumblr.com/.
- Painting or other visual artwork
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Original work
Rivera, Diego. Detroit Industry Murals . 1932-33. Detroit Institute of Art.
If the city is not part of the name of the museum, add it after museum. For example, if the work you viewed was at the Museum of Modern Art in New York City, you would end the entry as follows: Museum of Modern Art, New York. -
Reproduction
Neel, Alice. Elenka . 1936. Alice Neel: People Come First , by Kelly Baum and Randall Griffey, The Metropolitan Museum of Art, 2021, p. 142. -
Online
Basquiat, Jean-Michel. Untitled . 1983. Museum of Modern Art , www.moma.org/collection/works/ 63997?artist_id=370&page=1&sov_referrer=artist. Accessed 24 Sept. 2020.
- Map, chart, or diagram
-
Print
Everglades National Park . National Geographic Society Maps, 2019. -
Online
“Map: Expedition of Lewis and Clark.” National Park Service , 2 Jan. 2018, nps.gov/subjects/ travellewisandclark/map.htm.
- Sound recording
Sound recordings include songs, albums, and spoken word. If you stream a sound recording or watch a performance online, add the name of the streaming service, such as Spotify, Apple Music, or Amazon Music, after the date. If you access the recording online, add the name of the website and the URL after the date.
-
Album
Prince. Purple Rain . Warner Brothers, 1984. -
Song
The Supremes. “Baby Love.” Where Did Our Love Go , Motown, 1964. Spotify. -
Online
Gorman, Amanda. “The Hill We Climb.” 20 Jan. 2021, YouTube , www.youtube.com/watch?v=LZ055ilIiN4.
- Radio
The Road to Higher Ground . Hosted by Jonathan Overby. WPR, 9 Jan. 2021.
If you listened to the radio program online, add the URL after the date.
- Podcast
McEvers, Kelly, host. “This Is Not a Joke.” Embedded , season 9, episode 2, NPR, 7 Nov. 2019, Apple Podcasts.
If you listened to the podcast on the web, add the URL instead of the podcast service.
- Interview
-
Broadcast
Wilkerson, Isabel. Interview. Fresh Air , NPR, 4 Aug. 2020. -
Online
Sowell, Thomas. Interview. Hoover Institution , 3 Jan. 2015, www.wsj.com/video/uncommon-knowledg-thomas-sowell-basic-economics/51837CB6-9FF2-305AE55D179A.html. -
Personal interview
Wong, Diana. Personal interview. 12 Sept. 2020.
- Video game, software, or app
Houser, Dan, et al., writers. Grand Theft Auto V . Rockstar Games, 2013. Xbox 360.
Other Sources (MLA)
- Live lecture, speech, address, or reading
Diaz, Shanna. “Your Dazzling Brain: The Symphony of Sleep.” Community Lecture Series, University of New Mexico Health Science and the City of Albuquerque, 13 Mar. 2018, Albuquerque Academy.
- Live performance
Hamilton . By Lin-Manuel Miranda, directed by Thomas Kail, 11 Mar. 2018, CIBC Theater, Chicago.
If you watch a video of a performance online, cite it as you would cite an online video.
- Letter in an archive
Mucklestone, Ada. Letter to Maj. Gen. Ralph J. Olson. 6 Nov. 1958. Wisconsin Historical Society, Madison, Alphabetical Subject File, 1950-66, 1715, Box 13.
- Dissertation
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Database
Park, Eun Jung. Korean American Artists and the 1992 Los Angeles Riots . 2013. U of California, San Diego, PhD dissertation. ProQuest, www.proquest.com/doc-view/1425303659. -
Print
Boothby, Daniel W. The Determinants of Earnings and Occupation for Young Women . 1978. U of California, Berkeley, PhD dissertation.
- Pamphlet
“Facts about Fallout.” Civil Defense Administration, 1961.
MLA Paper Format
Follow your instructor’s formatting guidelines or those indicated here. For sample papers with MLA format and works-cited pages, visit this site ( https://openstax.org/r/this-site1 ) .
- Margins. Use one-inch margins on all sides.
- Spacing. Double-space throughout the paper, including the works-cited page.
- Paragraph format. Indent paragraphs one-half inch.
- Page numbers. Start numbering on the first page of your paper and continue to the end of the works-cited page. Place page numbers in the upper-right corner, and add your last name before the page number: “Coleman 3.”
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- Long quotations and quotations from poetry. See Quotations for how to cite long quotations and poetry quotations.


5.2: Structure and Replication of DNA
- Describe the biochemical structure of deoxyribonucleotides
- Identify the base pairs used in the synthesis of deoxyribonucleotides
- Explain why the double helix of DNA is described as antiparallel
- Explain the meaning of semiconservative DNA replication
- Explain why DNA replication is bidirectional and includes both a leading and lagging strand
- Explain why Okazaki fragments are formed
- Describe the process of DNA replication and the functions of the enzymes involved
- Identify the differences between DNA replication in bacteria and eukaryotes
- Explain the process of rolling circle replication
Like other macromolecules, nucleic acids are composed of monomers, called nucleotides, which are polymerized to form large strands. Each nucleic acid strand contains certain nucleotides that appear in a certain order within the strand, called its base sequence. The base sequence of deoxyribonucleic acid (DNA) is responsible for carrying and retaining the hereditary information in a cell. Now, we will discuss in detail the ways in which DNA uses its own base sequence to direct its own synthesis, as well as the synthesis of RNA and proteins, which, in turn, gives rise to products with diverse structure and function. In this section, we will discuss the basic structure and function of DNA.
DNA Nucleotides
The building blocks of nucleic acids are nucleotides. Nucleotides that compose DNA are called deoxyribonucleotides. The three components of a deoxyribonucleotide are a five-carbon sugar called deoxyribose, a phosphate group, and a nitrogenous base, a nitrogen-containing ring structure that is responsible for complementary base pairing between nucleic acid strands (Figure \(\PageIndex{1}\)). The carbon atoms of the five-carbon deoxyribose are numbered 1ʹ, 2ʹ, 3ʹ, 4ʹ, and 5ʹ (1ʹ is read as “one prime”).
The deoxyribonucleotide is named according to the nitrogenous bases (Figure \(\PageIndex{2}\)). The nitrogenous bases adenine (A) and guanine (G) are the purines; they have a double-ring structure with a six-carbon ring fused to a five-carbon ring. The pyrimidines, cytosine (C) and thymine (T), are smaller nitrogenous bases that have only a six-carbon ring structure.
Individual nucleotides with three phosphates combine with each other by covalent bonds known as 5ʹ-3ʹ phosphodiester bonds, or linkages whereby the phosphate group attached to the 5ʹ carbon of the sugar of one nucleotide bonds to the hydroxyl group of the 3ʹ carbon of the sugar of the next nucleotide. Phosphodiester bonding between nucleotides forms the sugar-phosphate backbone, the alternating sugar-phosphate structure composing the framework of a nucleic acid strand (Figure \(\PageIndex{3}\)). During the polymerization process, deoxynucleotide triphosphates (dNTP) are used. To construct the sugar-phosphate backbone, the two terminal phosphates are released from the dNTP as a pyrophosphate. The resulting strand of nucleic acid has a free phosphate group at the 5ʹ carbon end and a free hydroxyl group at the 3ʹ carbon end. The two unused phosphate groups from the nucleotide triphosphate are released as pyrophosphate during phosphodiester bond formation. Pyrophosphate is subsequently hydrolyzed, releasing the energy used to drive nucleotide polymerization.
What is meant by the 5ʹ and 3ʹ ends of a nucleic acid strand?
Discovering the Double Helix
By the early 1950s, considerable evidence had accumulated indicating that DNA was the genetic material of cells, and now the race was on to discover its three-dimensional structure. Around this time, Austrian biochemist Erwin Chargaff 1 (1905–2002) examined the content of DNA in different species and discovered that adenine, thymine, guanine, and cytosine were not found in equal quantities, and that it varied from species to species, but not between individuals of the same species. He found that the amount of adenine was very close to equaling the amount of thymine, and the amount of cytosine was very close to equaling the amount of guanine, or A = T and G = C. These relationships are also known as Chargaff’s rules.
Other scientists were also actively exploring this field during the mid-20th century. In 1952, American scientist Linus Pauling (1901–1994) was the world’s leading structural chemist and odds-on favorite to solve the structure of DNA. Pauling had earlier discovered the structure of protein α helices, using X-ray diffraction, and, based upon X-ray diffraction images of DNA made in his laboratory, he proposed a triple-stranded model of DNA. 2 At the same time, British researchers Rosalind Franklin (1920–1958) and her graduate student R.G. Gosling were also using X-ray diffraction to understand the structure of DNA (Figure \(\PageIndex{4}\)). It was Franklin’s scientific expertise that resulted in the production of more well-defined X-ray diffraction images of DNA that would clearly show the overall double-helix structure of DNA.
James Watson (1928–), an American scientist, and Francis Crick (1916–2004), a British scientist, were working together in the 1950s to discover DNA’s structure. They used Chargaff’s rules and Franklin and Wilkins’ X-ray diffraction images of DNA fibers to piece together the purine-pyrimidine pairing of the double helical DNA molecule (Figure \(\PageIndex{5}\)). In April 1953, Watson and Crick published their model of the DNA double helix in Nature . 3 The same issue additionally included papers by Wilkins and colleagues, 4 as well as by Franklin and Gosling, 5 each describing different aspects of the molecular structure of DNA. In 1962, James Watson, Francis Crick, and Maurice Wilkins were awarded the Nobel Prize in Physiology and Medicine. Unfortunately, by then Franklin had died, and Nobel prizes at the time were not awarded posthumously. Work continued, however, on learning about the structure of DNA. In 1973, Alexander Rich (1924–2015) and colleagues were able to analyze DNA crystals to confirm and further elucidate DNA structure. 6
Which scientists are given most of the credit for describing the molecular structure of DNA?
DNA Structure
Watson and Crick proposed that DNA is made up of two strands that are twisted around each other to form a right-handed helix. The two DNA strands are antiparallel, such that the 3ʹ end of one strand faces the 5ʹ end of the other (Figure \(\PageIndex{6}\)). The 3ʹ end of each strand has a free hydroxyl group, while the 5ʹ end of each strand has a free phosphate group. The sugar and phosphate of the polymerized nucleotides form the backbone of the structure, whereas the nitrogenous bases are stacked inside. These nitrogenous bases on the interior of the molecule interact with each other, base pairing.
Analysis of the diffraction patterns of DNA has determined that there are approximately 10 bases per turn in DNA. The asymmetrical spacing of the sugar-phosphate backbones generates major grooves (where the backbone is far apart) and minor grooves (where the backbone is close together) (Figure \(\PageIndex{6}\)). These grooves are locations where proteins can bind to DNA. The binding of these proteins can alter the structure of DNA, regulate replication, or regulate transcription of DNA into RNA.
Base pairing takes place between a purine and pyrimidine. In DNA, adenine (A) and thymine (T) are complementary base pairs, and cytosine (C) and guanine (G) are also complementary base pairs, explaining Chargaff’s rules (Figure \(\PageIndex{7}\)). The base pairs are stabilized by hydrogen bonds; adenine and thymine form two hydrogen bonds between them, whereas cytosine and guanine form three hydrogen bonds between them.
In the laboratory, exposing the two DNA strands of the double helix to high temperatures or to certain chemicals can break the hydrogen bonds between complementary bases, thus separating the strands into two separate single strands of DNA (single-stranded DNA [ssDNA]). This process is called DNA denaturation and is analogous to protein denaturation. The ssDNA strands can also be put back together as double-stranded DNA (dsDNA), through reannealing or renaturing by cooling or removing the chemical denaturants, allowing these hydrogen bonds to reform. The ability to artificially manipulate DNA in this way is the basis for several important techniques in biotechnology (Figure \(\PageIndex{8}\)). Because of the additional hydrogen bonding between the C = G base pair, DNA with a high GC content is more difficult to denature than DNA with a lower GC content.
View an animation on DNA structure from the DNA Learning Center to learn more.
What are the two complementary base pairs of DNA and how are they bonded together?
Historically, women have been underrepresented in the sciences and in medicine, and often their pioneering contributions have gone relatively unnoticed. For example, although Rosalind Franklin performed the X-ray diffraction studies demonstrating the double helical structure of DNA, it is Watson and Crick who became famous for this discovery, building on her data. There still remains great controversy over whether their acquisition of her data was appropriate and whether personality conflicts and gender bias contributed to the delayed recognition of her significant contributions. Similarly, Barbara McClintock did pioneering work in maize (corn) genetics from the 1930s through 1950s, discovering transposons (jumping genes), but she was not recognized until much later, receiving a Nobel Prize in Physiology or Medicine in 1983 (Figure \(\PageIndex{9}\)).
Today, women still remain underrepresented in many fields of science and medicine. While more than half of the undergraduate degrees in science are awarded to women, only 46% of doctoral degrees in science are awarded to women. In academia, the number of women at each level of career advancement continues to decrease, with women holding less than one-third of the positions of Ph.D.-level scientists in tenure-track positions, and less than one-quarter of the full professorships at 4-year colleges and universities. 7 Even in the health professions, like nearly all other fields, women are often underrepresented in many medical careers and earn significantly less than their male counterparts, as shown in a 2013 study published by the Journal of the American Medical Association . 8
Why do such disparities continue to exist and how do we break these cycles? The situation is complex and likely results from the combination of various factors, including how society conditions the behaviors of girls from a young age and supports their interests, both professionally and personally. Some have suggested that women do not belong in the laboratory, including Nobel Prize winner Tim Hunt, whose 2015 public comments suggesting that women are too emotional for science 9 were met with widespread condemnation.
Perhaps girls should be supported more from a young age in the areas of science and math (Figure \(\PageIndex{9}\)). Science, technology, engineering, and mathematics (STEM) programs sponsored by the American Association of University Women (AAUW) 10 and National Aeronautics and Space Administration (NASA) 11 are excellent examples of programs that offer such support. Contributions by women in science should be made known more widely to the public, and marketing targeted to young girls should include more images of historically and professionally successful female scientists and medical professionals, encouraging all bright young minds, including girls and women, to pursue careers in science and medicine.
Based upon his symptoms, Alex’s physician suspects that he is suffering from a foodborne illness that he acquired during his travels. Possibilities include bacterial infection (e.g., enterotoxigenic E. coli , Vibrio cholerae , Campylobacter jejuni , Salmonella ), viral infection (rotavirus or norovirus), or protozoan infection ( Giardia lamblia , Cryptosporidium parvum , or Entamoeba histolytica ).

Alex’s stool sample showed neither blood nor cysts. Following analysis of his stool sample and based upon his recent travel history, the hospital physician suspected that Alex was suffering from traveler’s diarrhea caused by enterotoxigenic E. coli (ETEC), the causative agent of most traveler’s diarrhea. To verify the diagnosis and rule out other possibilities, Alex’s physician ordered a diagnostic lab test of his stool sample to look for DNA sequences encoding specific virulence factors of ETEC. The physician instructed Alex to drink lots of fluids to replace what he was losing and discharged him from the hospital.
ETEC produces several plasmid-encoded virulence factors that make it pathogenic compared with typical E. coli . These include the secreted toxins heat-labile enterotoxin (LT) and heat-stabile enterotoxin (ST), as well as colonization factor (CF). Both LT and ST cause the excretion of chloride ions from intestinal cells to the intestinal lumen, causing a consequent loss of water from intestinal cells, resulting in diarrhea. CF encodes a bacterial protein that aids in allowing the bacterium to adhere to the lining of the small intestine.
Why did Alex’s physician use genetic analysis instead of either isolation of bacteria from the stool sample or direct Gram stain of the stool sample alone?
DNA Function
DNA stores the information needed to build and control the cell. The transmission of this information from mother to daughter cells is called vertical gene transfer and it occurs through the process of DNA replication. DNA is replicated when a cell makes a duplicate copy of its DNA, then the cell divides, resulting in the correct distribution of one DNA copy to each resulting cell. DNA can also be enzymatically degraded and used as a source of nucleotides for the cell. Unlike other macromolecules, DNA does not serve a structural role in cells.
The elucidation of the structure of the double helix by James Watson and Francis Crick in 1953 provided a hint as to how DNA is copied during the process of replication. Separating the strands of the double helix would provide two templates for the synthesis of new complementary strands, but exactly how new DNA molecules were constructed was still unclear. In one model, semiconservative replication, the two strands of the double helix separate during DNA replication, and each strand serves as a template from which the new complementary strand is copied; after replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. There were two competing models also suggested: conservative and dispersive, which are shown in Figure \(\PageIndex{10}\).
Matthew Meselson (1930–) and Franklin Stahl (1929–) devised an experiment in 1958 to test which of these models correctly represents DNA replication. They grew E. coli for several generations in a medium containing a “heavy” isotope of nitrogen ( 15 N) that was incorporated into nitrogenous bases and, eventually, into the DNA. This labeled the parental DNA. The E. coli culture was then shifted into a medium containing 14 N and allowed to grow for one generation. The cells were harvested and the DNA was isolated. The DNA was separated by ultracentrifugation, during which the DNA formed bands according to its density. DNA grown in 15 N would be expected to form a band at a higher density position than that grown in 14 N. Meselson and Stahl noted that after one generation of growth in 14 N, the single band observed was intermediate in position in between DNA of cells grown exclusively in 15 N or 14 N. This suggested either a semiconservative or dispersive mode of replication. Some cells were allowed to grow for one more generation in 14 N and spun again. The DNA harvested from cells grown for two generations in 14 N formed two bands: one DNA band was at the intermediate position between 15 N and 14 N, and the other corresponded to the band of 14 N DNA. These results could only be explained if DNA replicates in a semiconservative manner. Therefore, the other two models were ruled out. As a result of this experiment, we now know that during DNA replication, each of the two strands that make up the double helix serves as a template from which new strands are copied. The new strand will be complementary to the parental or “old” strand. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells. This means the middle explanation from Figure \(\PageIndex{10}\) is correct.
DNA Replication in Bacteria
DNA replication has been well studied in bacteria primarily because of the small size of the genome and the mutants that are available. E. coli has 4.6 million base pairs (Mbp) in a single circular chromosome and all of it is replicated in approximately 42 minutes, starting from a single origin of replication and proceeding around the circle bidirectionally (i.e., in both directions). This means that approximately 1000 nucleotides are added per second. The process is quite rapid and occurs with few errors.
DNA replication uses a large number of proteins and enzymes (Table \(\PageIndex{1}\)). One of the key players is the enzyme DNA polymerase, also known as DNA pol. In bacteria, three main types of DNA polymerases are known: DNA pol I, DNA pol II, and DNA pol III. It is now known that DNA pol III is the enzyme required for DNA synthesis; DNA pol I and DNA pol II are primarily required for repair. DNA pol III adds deoxyribonucleotides each complementary to a nucleotide on the template strand, one by one to the 3’-OH group of the growing DNA chain. The addition of these nucleotides requires energy. This energy is present in the bonds of three phosphate groups attached to each nucleotide (a triphosphate nucleotide), similar to how energy is stored in the phosphate bonds of adenosine triphosphate (ATP) (Figure \(\PageIndex{11}\)). When the bond between the phosphates is broken and diphosphate is released, the energy released allows for the formation of a covalent phosphodiester bond by dehydration synthesis between the incoming nucleotide and the free 3’-OH group on the growing DNA strand.
Initiation
The initiation of replication occurs at specific nucleotide sequence called the origin of replication, where various proteins bind to begin the replication process. E. coli has a single origin of replication (as do most prokaryotes), called oriC , on its one chromosome. The origin of replication is approximately 245 base pairs long and is rich in adenine-thymine (AT) sequences.
Some of the proteins that bind to the origin of replication are important in making single-stranded regions of DNA accessible for replication. Chromosomal DNA is typically wrapped around histones (in eukaryotes and archaea) or histone-like proteins (in bacteria), and is supercoiled, or extensively wrapped and twisted on itself. This packaging makes the information in the DNA molecule inaccessible. However, enzymes can change the shape and supercoiling of the chromosome. For bacterial DNA replication to begin, the supercoiled chromosome is relaxed. An enzyme called helicase then separates the DNA strands by breaking the hydrogen bonds between the nitrogenous base pairs. Recall that AT sequences have fewer hydrogen bonds and, hence, have weaker interactions than guanine-cytosine (GC) sequences. These enzymes require ATP hydrolysis. As the DNA opens up, Y-shaped structures called replication forks are formed. Two replication forks are formed at the origin of replication, allowing for bidirectional replication and formation of a structure that looks like a bubble when viewed with a transmission electron microscope; as a result, this structure is called a replication bubble. The DNA near each replication fork is coated with single-stranded binding proteins to prevent the single-stranded DNA from rewinding into a double helix.
Once single-stranded DNA is accessible at the origin of replication, DNA replication can begin. However, DNA pol III is able to add nucleotides only in the 5’ to 3’ direction (a new DNA strand can be only extended in this direction). This is because DNA polymerase requires a free 3’-OH group to which it can add nucleotides by forming a covalent phosphodiester bond between the 3’-OH end and the 5’ phosphate of the next nucleotide. This also means that it cannot add nucleotides if a free 3’-OH group is not available, which is the case for a single strand of DNA. The problem is solved with the help of an RNA sequence that provides the free 3’-OH end. Because this sequence allows the start of DNA synthesis, it is appropriately called the primer. The primer is five to 10 nucleotides long and complementary to the parental or template DNA. It is synthesized by RNA primase, which is an RNA polymerase. Unlike DNA polymerases, RNA polymerases do not need a free 3’-OH group to synthesize an RNA molecule. Now that the primer provides the free 3’-OH group, DNA polymerase III can now extend this RNA primer, adding DNA nucleotides one by one that are complementary to the template strand.
Elongation
During elongation in DNA replication, the addition of nucleotides occurs at its maximal rate of about 1000 nucleotides per second. DNA polymerase III can only extend in the 5’ to 3’ direction, which poses a problem at the replication fork. The DNA double helix is antiparallel; that is, one strand is oriented in the 5’ to 3’ direction and the other is oriented in the 3’ to 5’ direction. During replication, one strand, which is complementary to the 3’ to 5’ parental DNA strand, is synthesized continuously toward the replication fork because polymerase can add nucleotides in this direction. This continuously synthesized strand is known as the leading strand. The other strand, complementary to the 5’ to 3’ parental DNA, grows away from the replication fork, so the polymerase must move back toward the replication fork to begin adding bases to a new primer, again in the direction away from the replication fork. It does so until it bumps into the previously synthesized strand and then it moves back again (Figure \(\PageIndex{12}\)). These steps produce small DNA sequence fragments known as Okazaki fragments, each separated by RNA primer. Okazaki fragments are named after the Japanese research team and married couple Reiji and Tsuneko Okazaki, who first discovered them in 1966. The strand with the Okazaki fragments is known as the lagging strand, and its synthesis is said to be discontinuous.
The leading strand can be extended from one primer alone, whereas the lagging strand needs a new primer for each of the short Okazaki fragments. The overall direction of the lagging strand will be 3’ to 5’, and that of the leading strand 5’ to 3’. A protein called the sliding clamp holds the DNA polymerase in place as it continues to add nucleotides. The sliding clamp is a ring-shaped protein that binds to the DNA and holds the polymerase in place. As synthesis proceeds, the RNA primers are replaced by DNA by the exonuclease activity of DNA polymerase I, and the gaps are filled in. Any nicks that remain between the newly synthesized DNA (that replaced the RNA primer) and the previously synthesized DNA are sealed by the enzyme DNA ligase, stabilizing the sugar-phosphate backbone of the DNA molecule.
Termination
Once the complete chromosome has been replicated, termination of DNA replication must occur. Although much is known about initiation of replication, less is known about the termination process. Following replication, the resulting complete circular genomes of prokaryotes are concatenated, meaning that the circular DNA chromosomes are interlocked and must be separated from each other. This is accomplished through the activity of bacterial topoisomerase IV, which introduces double-stranded breaks into DNA molecules, allowing them to separate from each other; the enzyme then reseals the circular chromosomes. The resolution of concatemers is an issue unique to prokaryotic DNA replication because of their circular chromosomes. Because both bacterial DNA gyrase and topoisomerase IV are distinct from their eukaryotic counterparts, these enzymes serve as targets for a class of antimicrobial drugs called quinolones.
- Which enzyme breaks the hydrogen bonds holding the two strands of DNA together so that replication can occur?
- Is it the lagging strand or the leading strand that is synthesized in the direction toward the opening of the replication fork?
- Which enzyme is responsible for removing the RNA primers in newly replicated bacterial DNA?
DNA Replication in Eukaryotes
Eukaryotic genomes are much more complex and larger than prokaryotic genomes and are typically composed of multiple linear chromosomes (Table \(\PageIndex{2}\)). The human genome, for example, has 3 billion base pairs per haploid set of chromosomes, and 6 billion base pairs are inserted during replication. There are multiple origins of replication on each eukaryotic chromosome (Figure \(\PageIndex{13}\)); the human genome has 30,000 to 50,000 origins of replication. The rate of replication is approximately 100 nucleotides per second—10 times slower than prokaryotic replication.
The essential steps of replication in eukaryotes are the same as in prokaryotes. Before replication can start, the DNA has to be made available as a template. Eukaryotic DNA is highly supercoiled and packaged, which is facilitated by many proteins, including histones. At the origin of replication, a prereplication complex composed of several proteins, including helicase, forms and recruits other enzymes involved in the initiation of replication, including topoisomerase to relax supercoiling, single-stranded binding protein, RNA primase, and DNA polymerase. Following initiation of replication, in a process similar to that found in prokaryotes, elongation is facilitated by eukaryotic DNA polymerases. The leading strand is continuously synthesized by the eukaryotic polymerase enzyme pol δ, while the lagging strand is synthesized by pol ε. A sliding clamp protein holds the DNA polymerase in place so that it does not fall off the DNA. The enzyme ribonuclease H (RNase H), instead of a DNA polymerase as in bacteria, removes the RNA primer, which is then replaced with DNA nucleotides. The gaps that remain are sealed by DNA ligase.
Because eukaryotic chromosomes are linear, one might expect that their replication would be more straightforward. As in prokaryotes, the eukaryotic DNA polymerase can add nucleotides only in the 5’ to 3’ direction. In the leading strand, synthesis continues until it reaches either the end of the chromosome or another replication fork progressing in the opposite direction. On the lagging strand, DNA is synthesized in short stretches, each of which is initiated by a separate primer. When the replication fork reaches the end of the linear chromosome, there is no place to make a primer for the DNA fragment to be copied at the end of the chromosome. These ends thus remain unpaired and, over time, they may get progressively shorter as cells continue to divide.
The ends of the linear chromosomes are known as telomeres and consist of noncoding repetitive sequences. The telomeres protect coding sequences from being lost as cells continue to divide. In humans, a six base-pair sequence, TTAGGG, is repeated 100 to 1000 times to form the telomere. The discovery of the enzyme telomerase clarified our understanding of how chromosome ends are maintained. Telomerase contains a catalytic part and a built-in RNA template. It attaches to the end of the chromosome, and complementary bases to the RNA template are added on the 3’ end of the DNA strand. Once the 3’ end of the lagging strand template is sufficiently elongated, DNA polymerase can add the nucleotides complementary to the ends of the chromosomes. In this way, the ends of the chromosomes are replicated. In humans, telomerase is typically active in germ cells and adult stem cells; it is not active in adult somatic cells and may be associated with the aging of these cells. Eukaryotic microbes including fungi and protozoans also produce telomerase to maintain chromosomal integrity. For her discovery of telomerase and its action, Elizabeth Blackburn (1948–) received the Nobel Prize for Medicine or Physiology in 2009.
- How does the origin of replication differ between eukaryotes and prokaryotes?
- What polymerase enzymes are responsible for DNA synthesis during eukaryotic replication?
- What is found at the ends of the chromosomes in eukaryotes and why?
Key Concepts and Summary
- Nucleic acids are composed of nucleotides , each of which contains a pentose sugar, a phosphate group, and a nitrogenous base . Deoxyribonucleotides within DNA contain deoxyribose as the pentose sugar.
- DNA contains the pyrimidines cytosine and thymine , and the purines adenine and guanine .
- Nucleotides are linked together by phosphodiester bonds between the 5ʹ phosphate group of one nucleotide and the 3ʹ hydroxyl group of another. A nucleic acid strand has a free phosphate group at the 5ʹ end and a free hydroxyl group at the 3ʹ end.
- Chargaff discovered that the amount of adenine is approximately equal to the amount of thymine in DNA, and that the amount of the guanine is approximately equal to cytosine . These relationships were later determined to be due to complementary base pairing.
- Watson and Crick, building on the work of Chargaff, Franklin and Gosling, and Wilkins, proposed the double helix model and base pairing for DNA structure.
- DNA is composed of two complementary strands oriented antiparallel to each other with the phosphodiester backbones on the exterior of the molecule. The nitrogenous bases of each strand face each other and complementary bases hydrogen bond to each other, stabilizing the double helix.
- Heat or chemicals can break the hydrogen bonds between complementary bases, denaturing DNA. Cooling or removing chemicals can lead to renaturation or reannealing of DNA by allowing hydrogen bonds to reform between complementary bases.
- DNA stores the instructions needed to build and control the cell. This information is transmitted from parent to offspring through vertical gene transfer .
- The DNA replication process is semiconservative , which results in two DNA molecules, each having one parental strand of DNA and one newly synthesized strand.
- In bacteria, the initiation of replication occurs at the origin of replication , where supercoiled DNA is unwound by DNA gyrase , made single-stranded by helicase , and bound by single-stranded binding protein to maintain its single-stranded state. Primase synthesizes a short RNA primer , providing a free 3’-OH group to which DNA polymerase III can add DNA nucleotides.
- During elongation , the leading strand of DNA is synthesized continuously from a single primer. The lagging strand is synthesized discontinuously in short Okazaki fragments , each requiring its own primer. The RNA primers are removed and replaced with DNA nucleotides by bacterial DNA polymerase I , and DNA ligase seals the gaps between these fragments.
- Termination of replication in bacteria involves the resolution of circular DNA concatemers by topoisomerase IV to release the two copies of the circular chromosome.
- Eukaryotes typically have multiple linear chromosomes, each with multiple origins of replication. Overall, replication in eukaryotes is similar to that in prokaryotes.
- The linear nature of eukaryotic chromosomes necessitates telomeres to protect genes near the end of the chromosomes. Telomerase extends telomeres, preventing their degradation, in some cell types.
Footnotes
- N. Kresge et al. “Chargaff's Rules: The Work of Erwin Chargaff.” Journal of Biological Chemistry 280 (2005):e21.
- L. Pauling, “A Proposed Structure for the Nucleic Acids.” Proceedings of the National Academy of Science of the United States of America 39 no. 2 (1953):84–97.
- J.D. Watson, F.H.C. Crick. “A Structure for Deoxyribose Nucleic Acid.” Nature 171 no. 4356 (1953):737–738.
- M.H.F. Wilkins et al. “Molecular Structure of Deoxypentose Nucleic Acids.” Nature 171 no. 4356 (1953):738–740.
- R. Franklin, R.G. Gosling. “Molecular Configuration in Sodium Thymonucleate.” Nature 171 no. 4356 (1953):740–741.
- R.O. Day et al. “A Crystalline Fragment of the Double Helix: The Structure of the Dinucleoside Phosphate Guanylyl-3',5'-Cytidine.” Proceedings of the National Academy of Sciences of the United States of America 70 no. 3 (1973):849–853.
- N.H. Wolfinger “For Female Scientists, There's No Good Time to Have Children.” The Atlantic July 29, 2013. www.theatlantic.com/sexes/arc...ildren/278165/.
- S.A. Seabury et al. “Trends in the Earnings of Male and Female Health Care Professionals in the United States, 1987 to 2010.” Journal of the American Medical Association Internal Medicine 173 no. 18 (2013):1748–1750.
- E. Chung. “Tim Hunt, Sexism and Science: The Real 'Trouble With Girls' in Labs.” CBC News Technology and Science , June 12, 2015. http://www.cbc.ca/news/technology/ti...labs-1.3110133 . Accessed 8/4/2016.
- American Association of University Women. “Building a STEM Pipeline for Girls and Women.” www.aauw.org/what-we-do/stem-education/. Accessed June 10, 2016.
- National Aeronautics and Space Administration. “Outreach Programs: Women and Girls Initiative.” http://women.nasa.gov/outreach-programs/ . Accessed June 10, 2016.
Contributors and Attributions
-
Nina Parker, (Shenandoah University), Mark Schneegurt (Wichita State University), Anh-Hue Thi Tu (Georgia Southwestern State University), Philip Lister (Central New Mexico Community College), and Brian M. Forster (Saint Joseph’s University) with many contributing authors. Original content via Openstax (CC BY 4.0; Access for free at https://openstax.org/books/microbiology/pages/1-introduction )


5.7: Icons in Word
Learning Outcomes
- Create a Word document with inserted icon.
There is one more thing Rosamine wishes to incorporate into her document—a final icon.
Rosamine’s GM has a good sense of humor, so Rosamine chooses a different icon to end with in each of her reports. This time she wants a little piggy bank icon. To do this, she puts her cursor where she wants the icon to go, clicks on the Insert tab, and selects the Icon button. After scrolling down, she finds the piggy bank icon, selects it, and clicks the Insert button.
The little piggy is now in the document but needs a bit of adjusting. Like she can with the table and chart, Rosamine can drag the little image circle boarder to make the icon smaller. She also selects the button to have the icon move behind the text.
Now the little piggy bank is in place, and Rosamine has finished her report. She makes sure to save her file where she can easily find it again and emails it to her General Manager. Well done, Rosamine!
Contributors and Attributions
- Icons in Word. Authored by : Sherri Pendleton. Provided by : Lumen Learning. License : CC BY: Attribution


6.1: Energy and Metabolism - The Role of Energy and Metabolism
- Explain the importance of metabolism
Energy and Metabolism
All living organisms need energy to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is the set of life-sustaining chemical processes that enables organisms transform the chemical energy stored in molecules into energy that can be used for cellular processes. Animals consume food to replenish energy; their metabolism breaks down the carbohydrates, lipids, proteins, and nucleic acids to provide chemical energy for these processes. Plants convert light energy from the sun into chemical energy stored in molecules during the process of photosynthesis.
Bioenergetics and Chemical Reactions
Scientists use the term bioenergetics to discuss the concept of energy flow through living systems such as cells. Cellular processes such as the building and breaking down of complex molecules occur through step-by-step chemical reactions. Some of these chemical reactions are spontaneous and release energy, whereas others require energy to proceed. All of the chemical reactions that take place inside cells, including those that use energy and those that release energy, are the cell’s metabolism.
Cellular Metabolism
Every task performed by living organisms requires energy. Energy is needed to perform heavy labor and exercise, but humans also use a great deal of energy while thinking and even while sleeping. For every action that requires energy, many chemical reactions take place to provide chemical energy to the systems of the body, including muscles, nerves, heart, lungs, and brain.
The living cells of every organism constantly use energy to survive and grow. Cells break down complex carbohydrates into simple sugars that the cell can use for energy. Muscle cells may consumer energy to build long muscle proteins from small amino acid molecules. Molecules can be modified and transported around the cell or may be distributed to the entire organism. Just as energy is required to both build and demolish a building, energy is required for both the synthesis and breakdown of molecules.
Many cellular process require a steady supply of energy provided by the cell’s metabolism. Signaling molecules such as hormones and neurotransmitters must be synthesized and then transported between cells. Pathogenic bacteria and viruses are ingested and broken down by cells. Cells must also export waste and toxins to stay healthy, and many cells must swim or move surrounding materials via the beating motion of cellular appendages like cilia and flagella.
Key Points
- All living organisms need energy to grow and reproduce, maintain their structures, and respond to their environments; metabolism is the set of the processes that makes energy available for cellular processes.
- Metabolism is a combination of chemical reactions that are spontaneous and release energy and chemical reactions that are non-spontaneous and require energy in order to proceed.
- Living organisms must take in energy via food, nutrients, or sunlight in order to carry out cellular processes.
- The transport, synthesis, and breakdown of nutrients and molecules in a cell require the use of energy.
Key Terms
- metabolism : the complete set of chemical reactions that occur in living cells
- bioenergetics : the study of the energy transformations that take place in living organisms
- energy : the capacity to do work


4.3: The SIR Epidemic Disease Model
The SIR model, first published by Kermack and McKendrick in 1927, is undoubtedly the most famous mathematical model for the spread of an infectious disease. Here, people are characterized into three classes: susceptible \(S\) , infective \(I\) and removed R. Removed individuals are no longer susceptible nor infective for whatever reason; for example, they have recovered from the disease and are now immune, or they have been vaccinated, or they have been isolated from the rest of the population, or perhaps they have died from the disease. As in the SIS model, we assume that infectives leave the \(I\) class with constant rate \(\gamma\) , but in the SIR model they move directly into the \(R\) class. The model may be diagrammed as
\[S \stackrel{\beta S I}{\longrightarrow} I \stackrel{\gamma I}{\longrightarrow} R, \nonumber \]
and the corresponding coupled differential equations are
\[\frac{d S}{d t}=-\beta S I, \quad \frac{d I}{d t}=\beta S I-\gamma I, \quad \frac{d R}{d t}=\gamma I, \nonumber \]
with the constant population constraint \(S+I+R=N\) . For convenience, we nondimensionalize (4.3.2) using \(N\) for population size and \(\gamma^{-1}\) for time; that is, let
\[\hat{S}=S / N, \quad \hat{I}=I / N, \quad \hat{R}=R / N, \quad \hat{t}=\gamma t \nonumber \]
and define the dimensionless basic reproductive ratio as
\[\mathcal{R}_{0}=\frac{\beta N}{\gamma} \nonumber \]
The dimensionless SIR equations are then given by
\[\frac{d \hat{S}}{d \hat{t}}=-\mathcal{R}_{0} \hat{S} \hat{I}, \quad \frac{d \hat{I}}{d \hat{t}}=\mathcal{R}_{0} \hat{S} \hat{I}-\hat{I}, \quad \frac{d \hat{R}}{d \hat{t}}=\hat{I}, \nonumber \]
with dimensionless constraint \(\hat{S}+\hat{I}+\hat{R}=1\) .
We will use the SIR model to address two fundamental questions: (1) Under what condition does an epidemic occur? (2) If an epidemic occurs, what fraction of a well-mixed population gets sick?
Let \(\left(\hat{S}_{*}, \hat{I}_{*}, \hat{R}_{*}\right)\) be the fixed points of (4.3.5). Setting \(d \hat{S} / d \hat{t}=d \hat{I} / d \hat{t}=d \hat{R} / d \hat{t}=0\) , we immediately observe from the equation for \(d \hat{R} / d \hat{t}\) that \(\hat{I}=0\) , and this value forces all the time-derivatives to vanish for any \(\hat{S}\) and \(\hat{R}\) . Since with \(\hat{I}=0\) , we have \(\hat{R}=1-\hat{S}\) , evidently all the fixed points of (4.3.5) are given by the one parameter family \(\left(\hat{S}_{*}, \hat{I}_{*}, \hat{R}_{*}\right)=\left(\hat{S}_{*}, 0,1-\hat{S}_{*}\right) .\)
An epidemic occurs when a small number of infectives introduced into a susceptible population results in an increasing number of infectives. We can assume an initial population at a fixed point of \((4.3.5)\) , perturb this fixed point by introducing a small number of infectives, and determine the fixed point’s stability. An epidemic occurs when the fixed point is unstable. The linear stability problem may be solved by considering only the equation for \(d \hat{I} / d \hat{t}\) in (4.3.5). With \(\hat{I} \ll 1\) and \(\hat{S} \approx \hat{S}_{0}\) , we have
\[\frac{d \hat{I}}{d \hat{t}}=\left(\mathcal{R}_{0} \hat{S}_{0}-1\right) \hat{I} \nonumber \]
so that an epidemic occurs if \(\mathcal{R}_{0} \hat{S}_{0}-1>0\) . With the basic reproductive ratio given by (4.3.4), and \(S_{0}=S_{0} / N\) , where \(S_{0}\) is the number of initial susceptible individuals, an epidemic occurs if
\[\mathcal{R}_{0} \hat{S}_{0}=\frac{\beta S_{0}}{\gamma}>1 \nonumber \]
which could have been guessed. An epidemic occurs if an infective individual introduced into a population of \(S_{0}\) susceptible individuals infects on average more than one other person. If an epidemic occurs, then initially the number of infective individuals increases exponentially with growth rate \(\beta S_{0}-\gamma\) .
which upon integration and simplification, results in the following transcendental equation for \(\hat{R}_{\infty}\) :
\[1-\hat{R}_{\infty}-e^{-\mathcal{R}_{0} \hat{R}_{\infty}}=0, \nonumber \]
an equation that can be solved numerically using Newton’s method. We have
\[\begin{aligned} &F\left(\hat{R}_{\infty}\right)=1-\hat{R}_{\infty}-e^{-\mathcal{R}_{0} \hat{R}_{\infty}} \\[4pt] &F^{\prime}\left(\hat{R}_{\infty}\right)=-1+\mathcal{R}_{0} e^{-\mathcal{R}_{0} \hat{R}_{\infty}} \end{aligned} \nonumber \]
and Newton’s method for solving \(F\left(\hat{R}_{\infty}\right)=0\) iterates
\[\hat{R}_{\infty}^{(n+1)}=\hat{R}_{\infty}^{n}-\frac{F\left(\hat{R}_{\infty}^{(n)}\right)}{F^{\prime}\left(\hat{R}_{\infty}^{(n)}\right)} \nonumber \]
for fixed \(\mathcal{R}_{0}\) and a suitable initial condition for \(R_{\infty}^{(0)}\) , which we take to be unity. My code for computing \(R_{\infty}\) as a function of \(\mathcal{R}_{0}\) is given below, and the result is shown in Fig. 4.1. There is an explosion in the number of infections as \(\mathcal{R}_{0}\) increases from unity, and this rapid increase is a classic example of what is known more generally as a threshold phenomenon.


1.1: Why It Matters- Types of Statistical Studies and Producing Data
Why learn about the various types of statistical studies and how data is produced?
We organized this course around the Big Picture of Statistics. As we learn new material, we will always look at how these new ideas relate to the Big Picture. In this way the Big Picture is a diagram that will help us organize and understand the material we will learn throughout the course.
The Big Picture summarizes the steps in a statistical investigation.
We begin a statistical investigation with a research question. The research question is frequently something we want to know about a population . The population can be people or other things, such as animals or objects. For example, we might want to know the answer to questions such as:
- What percentage of U.S. adults supports the death penalty? (Population: U.S. adults)
- Do cell phones affect bees? (Population: bees)
- Do cars get better gas mileage with a new gasoline additive? (Population: cars)
The population is the entire group that we want to know something about:
In most cases, the population is a large group. Often, the population is so large that we cannot collect information from every individual in the population. So we select a sample from the population. Then we collect data from this sample. This is the first step in the statistical investigation. We call this step producing data .
Of course, we need a sample that represents the population well. This involves careful planning but also involves chance. For example, if our goal is to determine the percentage of U.S. adults who favor the death penalty, we do not want our sample to contain only Democrats or only Republicans. So we can give everyone the same opportunity to be in the sample, but we will let chance select the sample.
At this step of the investigation we also carefully define what kind of information we plan to gather. Then we collect the data.
Data is often a long list of information. To make sense of the data, we explore it and summarize it using graphs and different numerical measures, such as percentages or averages. We call this step exploratory data analysis .
Remember, our goal is to answer a question about a population based on a sample. Of course, samples will vary due to chance, and we will need to answer our question in spite of this variability. So we need to understand how sample results will vary and how sample results relate to the population as a whole when chance is involved. This is where probability comes in.
Probability is the “machinery” behind the last step in the process called inference . We infer something about a population based on a sample. This inference is the conclusion we reach from our sample data that answers our original question about the population.
Example – The big picture of statistics
At the end of April 2005, ABC News and the Washington Post conducted a poll to determine the percentage of U.S. adults who support the death penalty.
Research question : What percentage of U.S. adults support the death penalty?
Steps in the statistical investigation:
-
Produce Data
:
Determine what to measure, then collect the data.
The poll selected 1,082 U.S. adults at random. Each adult answered this question: “Do you favor or oppose the death penalty for a person convicted of murder?” -
Explore the Data
:
Analyze and summarize the data.
In the sample, 65% favored the death penalty. -
Draw a Conclusion
:
Use the data, probability, and statistical inference to draw a conclusion about the population.
Our goal is to determine the percentage of the U.S. adult population that supports the death penalty. We know that different samples will give different results. What are the chances that our sample reflects the opinions of the population within 3%? Probability describes the likelihood that our sample is this accurate. So we can say with 95% confidence that between 62% and 68% of the population favor the death penalty.
Let’s Summarize
A statistical investigation with a research question. Then the investigation proceeds with the following steps:
- Produce Data: Determine what to measure, then collect the data.
- Explore the Data: Analyze and summarize the data (also called exploratory data analysis ).
- Draw a Conclusion: Use the data, probability, and statistical inference to draw a conclusion about the population.
Types of Statistical Studies and Producing Data
In this first module, we focus on the produce data step in a statistical investigation. We discuss two types of statistical investigations: the observational study and the experiment. Each type of investigation involves a different approach to collecting data. We will also see that our approach to collecting data determines what we can conclude from the data.
Contributors and Attributions
- Concepts in Statistics. Provided by : Open Learning Initiative. Located at : http://oli.cmu.edu . License : CC BY: Attribution


32.1: Medical Imaging and Diagnostics
Learning Objectives
By the end of this section, you will be able to:
- Explain the working principle behind an anger camera.
- Describe the SPECT and PET imaging techniques.
A host of medical imaging techniques employ nuclear radiation. What makes nuclear radiation so useful? First, \(\gamma\) radiation can easily penetrate tissue; hence, it is a useful probe to monitor conditions inside the body. Second, nuclear radiation depends on the nuclide and not on the chemical compound it is in, so that a radioactive nuclide can be put into a compound designed for specific purposes. The compound is said to be tagged . A tagged compound used for medical purposes is called a radiopharmaceutical . Radiation detectors external to the body can determine the location and concentration of a radiopharmaceutical to yield medically useful information. For example, certain drugs are concentrated in inflamed regions of the body, and this information can aid diagnosis and treatment as seen in Figure \(\PageIndex{1}\). Another application utilizes a radiopharmaceutical which the body sends to bone cells, particularly those that are most active, to detect cancerous tumors or healing points. Images can then be produced of such bone scans. Radioisotopes are also used to determine the functioning of body organs, such as blood flow, heart muscle activity, and iodine uptake in the thyroid gland.
Medical Application
Table \(\PageIndex{1}\) lists certain medical diagnostic uses of radiopharmaceuticals, including isotopes and activities that are typically administered. Many organs can be imaged with a variety of nuclear isotopes replacing a stable element by a radioactive isotope. One common diagnostic employs iodine to image the thyroid, since iodine is concentrated in that organ. The most active thyroid cells, including cancerous cells, concentrate the most iodine and, therefore, emit the most radiation. Conversely, hypothyroidism is indicated by lack of iodine uptake. Note that there is more than one isotope that can be used for several types of scans. Another common nuclear diagnostic is the thallium scan for the cardiovascular system, particularly used to evaluate blockages in the coronary arteries and examine heart activity. The salt TlCl can be used, because it acts like NaCl and follows the blood. Gallium-67 accumulates where there is rapid cell growth, such as in tumors and sites of infection. Hence, it is useful in cancer imaging. Usually, the patient receives the injection one day and has a whole body scan 3 or 4 days later because it can take several days for the gallium to build up.
| Isotope | Typical activity (mCi), where \(1 \, mCi = 3.7 \times 10^7 \, Bq\) |
|---|---|
| Brain scan | |
| \(^{88m}Tc\) | 7.5 |
| \(^{113m}In\) | 7.5 |
| \(^{11}C\space (PET)\) | 20 |
| \(^{13}N \, (PET)\) | 20 |
| \(^{15}O \, (PET)\) | 50 |
| \(^{18}F \, (PET)\) | 10 |
| Lung scan | |
| \(^{99m}Tc\) | 2 |
| \(^{133}Xe\) | 7.5 |
| Cardiovascular blood pool | |
| \(^{131}I\) | 0.2 |
| \(^{99}Tc\) | 2 |
| Cardiovascular arterial flow | |
| \(^{201}Tl\) | 3 |
| \(^{24}Na\) | 7.5 |
| Thyroid scan | |
| \(^{131}I\) | 0.05 |
| \(^{123}I\) | 0.07 |
| Liver scan | |
|
\(^{198}Au\) (colloid) \(^{99m}Tc\) (colloid) |
0.1 2 |
| Bone scan | |
| \(^{85}Sr\) | 0.1 |
| \(^{99m}Tc\) | 10 |
| Kidney scan | |
| \(^{197}Hg\) | 0.1 |
| \(^{99m}Tc\) | 1.5 |
Note that Table \(\PageIndex{1}\) lists many diagnostic uses for \(^{99m}Tc\), where “m” stands for a metastable state of the technetium nucleus. Perhaps 80 percent of all radiopharmaceutical procedures employ \(^{99m}Tc\) because of its many advantages. One is that the decay of its metastable state produces a single, easily identified 0.142-MeV \(\gamma\) ray. Additionally, the radiation dose to the patient is limited by the short 6.0-h half-life of \(^{99m}Tc\). And, although its half-life is short, it is easily and continuously produced on site. The basic process for production is neutron activation of molybdenum, which quickly \(\beta\) decays into \(^{99m}Tc\). Technetium-99m can be attached to many compounds to allow the imaging of the skeleton, heart, lungs, kidneys, etc.
Figure \(\PageIndex{2}\) shows one of the simpler methods of imaging the concentration of nuclear activity, employing a device called an Anger camera or gamma camera . A piece of lead with holes bored through it collimates \(\gamma\) rays emerging from the patient, allowing detectors to receive \(\gamma\) rays from specific directions only. The computer analysis of detector signals produces an image. One of the disadvantages of this detection method is that there is no depth information (i.e., it provides a two-dimensional view of the tumor as opposed to a three-dimensional view), because radiation from any location under that detector produces a signal.
Imaging techniques much like those in x-ray computed tomography (CT) scans use nuclear activity in patients to form three-dimensional images. Figure \(\PageIndex{3}\) shows a patient in a circular array of detectors that may be stationary or rotated, with detector output used by a computer to construct a detailed image. This technique is called single-photon-emission computed tomography(SPECT) or sometimes simply SPET. The spatial resolution of this technique is poor, about 1 cm, but the contrast (i.e. the difference in visual properties that makes an object distinguishable from other objects and the background) is good.
Images produced by \(\beta^+\) emitters have become important in recent years. When the emitted positron (\(\beta^+\)) encounters an electron, mutual annihilation occurs, producing two \(\gamma\) rays. These \(\gamma\) rays have identical 0.511-MeV energies (the energy comes from the destruction of an electron or positron mass) and they move directly away from one another, allowing detectors to determine their point of origin accurately, as shown in Figure \(\PageIndex{4}\). The system is called positron emission tomography (PET) . It requires detectors on opposite sides to simultaneously (i.e., at the same time) detect photons of 0.511-MeV energy and utilizes computer imaging techniques similar to those in SPECT and CT scans. Examples of \(\beta^+\)-emitting isotopes used in PET are \(^{11}O\), \(^{13}N\), \(^{15}O\) and \(^{18}F\), as seen in Table \(\PageIndex{1}\). This list includes C, N, and O, and so they have the advantage of being able to function as tags for natural body compounds. Its resolution of 0.5 cm is better than that of SPECT; the accuracy and sensitivity of PET scans make them useful for examining the brain’s anatomy and function. The brain’s use of oxygen and water can be monitored with \(^{15}O\). PET is used extensively for diagnosing brain disorders. It can note decreased metabolism in certain regions prior to a confirmation of Alzheimer’s disease. PET can locate regions in the brain that become active when a person carries out specific activities, such as speaking, closing their eyes, and so on.
PHET EXPLORATIONS: SIMPLIFIED MRI
Is it a tumor? Magnetic Resonance Imaging (MRI) can tell.  In an MRI unit, these little radios can be made to broadcast their positions, giving a detailed picture of the inside of your head.
Summary
- Radiopharmaceuticals are compounds that are used for medical imaging and therapeutics.
- The process of attaching a radioactive substance is called tagging.
- Table lists certain diagnostic uses of radiopharmaceuticals including the isotope and activity typically used in diagnostics.
- One common imaging device is the Anger camera, which consists of a lead collimator, radiation detectors, and an analysis computer.
- Tomography performed with \(\gamma\) -emitting radiopharmaceuticals is called SPECT and has the advantages of x-ray CT scans coupled with organ- and function-specific drugs.
- PET is a similar technique that uses \(\beta^+\) emitters and detects the two annihilation \(\gamma\) rays, which aid to localize the source.
Glossary
- Anger camera
- a common medical imaging device that uses a scintillator connected to a series of photomultipliers
- gamma camera
- another name for an Anger camera
- positron emission tomography (PET)
- tomography technique that uses \(\beta^+\) emitters and detects the two annihilation \(\gamma\) rays, aiding in source localization
- radiopharmaceutical
- compound used for medical imaging
- single-photon-emission computed tomography (SPECT)
- tomography performed with \(\gamma\)-emitting radiopharmaceuticals
- tagged
- process of attaching a radioactive substance to a chemical compound