Avery–MacLeod–McCarty experiment

<h2 id="background">Background</h2>
With the development of <a href="/facts/Quellung_reaction/FvxLlVjr">serological typing</a>, medical researchers were able to sort bacteria into different <a href="/facts/Strain_(biology)/xFv4QWjN">strains</a>, or types. When a person or test animal (e.g., a <a href="/facts/Mouse/6m1X7m0g">mouse</a>) is <a href="/facts/Inoculation/M2LPGM66">inoculated</a> with a particular type, an <a href="/facts/Immune_response/dtLulqIy">immune response</a> ensues, generating <a href="/facts/Antibodies/MX8pdTdP">antibodies</a> that react specifically with <a href="/facts/Antigens/9JlAernG">antigens</a> on the bacteria. <a href="/facts/Blood_serum/a22tvug9">Blood serum</a> containing the antibodies can then be extracted and applied to <a href="/facts/Cultured_bacteria/y3VaXn9Q">cultured bacteria</a>. The antibodies will react with other bacteria of the same type as the original inoculation. <a href="/facts/Fred_Neufeld/jM1HS8pR">Fred Neufeld</a>, a German bacteriologist, had discovered the pneumococcal types and serological typing; until <a href="/facts/Frederick_Griffith/96eJ7d7a">Frederick Griffith</a>'s studies bacteriologists believed that the types were fixed and unchangeable from one generation to the next.<a class="footnote-ref" id="fnref:3" href="#fn:3">3</a>
<a href="/facts/Griffith%2527s_experiment/RwWbSCTD">Griffith's experiment</a>, reported in 1928,<a class="footnote-ref" id="fnref:4" href="#fn:4">4</a> identified that some "transforming principle" in pneumococcal bacteria could transform them from one type to another. Griffith, a British medical officer, had spent years applying serological typing to cases of <a href="/facts/Pneumonia/Jw0KquTA">pneumonia</a>, a frequently fatal disease in the early 20th century. He found that multiple types—some virulent and some non-virulent—were often present over the course of a clinical case of pneumonia, and thought that one type might change into another (rather than simply multiple types being present all along). In testing that possibility, he found that transformation could occur when dead bacteria of a virulent type and live bacteria of a non-virulent type were both injected in mice: the mice would develop a fatal infection (normally only caused by live bacteria of the virulent type) and die, and virulent bacteria could be isolated from such infected mice.<a class="footnote-ref" id="fnref:5" href="#fn:5">5</a>
The findings of Griffith's experiment were soon confirmed, first by <a href="/facts/Fred_Neufeld/jM1HS8pR">Fred Neufeld</a><a class="footnote-ref" id="fnref:6" href="#fn:6">6</a> at the <a href="/facts/Robert_Koch_Institute/aP9mDvMs">Koch Institute</a> and by <a href="/facts/Martin_Henry_Dawson/Yep2Iu9B">Martin Henry Dawson</a> at the Rockefeller Institute.<a class="footnote-ref" id="fnref:7" href="#fn:7">7</a> A series of Rockefeller Institute researchers continued to study transformation in the years that followed. With Richard H. P. Sia, Dawson developed a method of transforming bacteria <a href="/facts/In_vitro/evp3hAX6">in vitro</a> (rather than <a href="/facts/In_vivo/kWcWyl6f">in vivo</a> as Griffith had done).<a class="footnote-ref" id="fnref:8" href="#fn:8">8</a> After Dawson's departure in 1930, James Alloway took up the attempt to extend Griffith's findings, resulting in the extraction of <a href="/facts/Aqueous_solution/eRNr3MH2">aqueous solutions</a> of the transforming principle by 1933. Colin MacLeod worked to purify such solutions from 1934 to 1937, and the work was continued in 1940 and completed by Maclyn McCarty.<a class="footnote-ref" id="fnref:9" href="#fn:9">9</a><a class="footnote-ref" id="fnref:10" href="#fn:10">10</a>

<h2 id="experimental-work">Experimental work</h2>
Pneumococcus is characterized by smooth colonies which have a polysaccharide capsule that induces <a href="/facts/Antibody/MX8pdTdP">antibody</a> formation; the different types are classified according to their immunological specificity.<a class="footnote-ref" id="fnref:11" href="#fn:11">11</a>
The purification procedure Avery undertook consisted of first killing the bacteria with heat and <a href="/facts/Leaching_(chemical_science)/hQ5JQhpF">extracting</a> the <a href="/facts/Saline_water/Tgw5AgL8">saline</a>-soluble components. Next, the protein was <a href="/facts/Precipitation_(chemistry)/s3BgsLLY">precipitated</a> out using <a href="/facts/Chloroform/gvzuJMXa">chloroform</a> and the polysaccharide capsules were <a href="/facts/Hydrolysis/JTvwIHPs">hydrolyzed</a> with an <a href="/facts/Enzyme/DSI1Fh7y">enzyme</a>. An immunological precipitation caused by type-specific antibodies was used to verify the complete destruction of the capsules. Then, the active portion was precipitated out by alcohol <a href="/facts/Fractionation/85wUlYTN">fractionation</a>, resulting in fibrous strands that could be removed with a stirring rod.<a class="footnote-ref" id="fnref:12" href="#fn:12">12</a>
Chemical analysis showed that the proportions of carbon, hydrogen, nitrogen, and phosphorus in this active portion were consistent with the chemical composition of DNA. To show that it was DNA rather than some small amount of <a href="/facts/RNA/HxPeNfNj">RNA</a>, <a href="/facts/Protein/Jxmagu3E">protein</a>, or some other cell component that was responsible for transformation, Avery and his colleagues used a number of biochemical tests. They found that <a href="/facts/Trypsin/wrwS23rh">trypsin</a>, <a href="/facts/Chymotrypsin/hht9v7eG">chymotrypsin</a> and <a href="/facts/Ribonuclease/Fod4qUu5">ribonuclease</a> (enzymes that break apart proteins or RNA) did not affect it, but an enzyme preparation of "deoxyribonucleodepolymerase" (a crude preparation, obtainable from a number of animal sources, that could break down DNA) destroyed the extract's transforming power.<a class="footnote-ref" id="fnref:13" href="#fn:13">13</a>
Follow-up work in response to criticism and challenges included the purification and crystallization, by <a href="/facts/Moses_Kunitz/d6om5ekr">Moses Kunitz</a> in 1948, of a DNA depolymerase (<a href="/facts/Deoxyribonuclease_I/bufblJqf">deoxyribonuclease I</a>), and precise work by <a href="/facts/Rollin_Hotchkiss/3TgeIvgf">Rollin Hotchkiss</a> showing that virtually all the detected nitrogen in the purified DNA came from <a href="/facts/Glycine/3nXI1hqW">glycine</a>, a breakdown product of the <a href="/facts/Nucleotide_base/zj1Vl9Qh">nucleotide base</a> <a href="/facts/Adenine/PSeDFBnl">adenine</a>, and that undetected protein contamination was at most 0.02% by Hotchkiss's estimation.<a class="footnote-ref" id="fnref:14" href="#fn:14">14</a><a class="footnote-ref" id="fnref:15" href="#fn:15">15</a>

<h2 id="reception-and-legacy">Reception and legacy</h2>
The experimental findings of the Avery–MacLeod–McCarty experiment were quickly confirmed, and extended to other hereditary characteristics besides polysaccharide capsules. However, there was considerable reluctance to accept the conclusion that DNA was the genetic material. According to <a href="/facts/Phoebus_Levene/zzkyqUV1">Phoebus Levene</a>'s influential "<a href="/facts/Tetranucleotide_hypothesis/sHh5askI">tetranucleotide hypothesis</a>", DNA consisted of repeating units of the four nucleotide bases and had little biological specificity. DNA was therefore thought to be the structural component of <a href="/facts/Chromosome/FRGf11FC">chromosomes</a>, whereas the genes were thought likely to be made of the protein component of chromosomes.<a class="footnote-ref" id="fnref:16" href="#fn:16">16</a><a class="footnote-ref" id="fnref:17" href="#fn:17">17</a> This line of thinking was reinforced by the 1935 crystallization of <a href="/facts/Tobacco_mosaic_virus/36sVcLw2">tobacco mosaic virus</a> by <a href="/facts/Wendell_Stanley/V7wL3p9j">Wendell Stanley</a>,<a class="footnote-ref" id="fnref:18" href="#fn:18">18</a> and the parallels among viruses, genes, and enzymes; many biologists thought genes might be a sort of "super-enzyme", and viruses were shown according to Stanley to be proteins and to share the property of <a href="/facts/Autocatalysis/2eGCpunY">autocatalysis</a> with many enzymes.<a class="footnote-ref" id="fnref:19" href="#fn:19">19</a> Furthermore, few biologists thought that genetics could be applied to bacteria, since they lacked <a href="/facts/Chromosome/FRGf11FC">chromosomes</a> and <a href="/facts/Sexual_reproduction/hmsXy53s">sexual reproduction</a>. In particular, many of the geneticists known informally as the <a href="/facts/Phage_group/P9dWfcUE">phage group</a>, which would become influential in the new discipline of <a href="/facts/Molecular_biology/YgqU35ub">molecular biology</a> in the 1950s, were dismissive of DNA as the genetic material (and were inclined to avoid the "messy" biochemical approaches of Avery and his colleagues). Some biologists, including fellow Rockefeller Institute Fellow <a href="/facts/Alfred_Mirsky/9AnUhCMK">Alfred Mirsky</a>, challenged Avery's finding that the transforming principle was pure DNA, suggesting that protein contaminants were instead responsible.<a class="footnote-ref" id="fnref:20" href="#fn:20">20</a><a class="footnote-ref" id="fnref:21" href="#fn:21">21</a> Although transformation occurred in some kinds of bacteria, it could not be replicated in other bacteria (nor in any higher organisms), and its significance seemed limited primarily to medicine.<a class="footnote-ref" id="fnref:22" href="#fn:22">22</a><a class="footnote-ref" id="fnref:23" href="#fn:23">23</a>
Scientists looking back on the Avery–MacLeod–McCarty experiment have disagreed about just how influential it was in the 1940s and early 1950s. <a href="/facts/Gunther_Stent/6fH0a5Sr">Gunther Stent</a> suggested that it was largely ignored, and only celebrated afterwards—similarly to <a href="/facts/Gregor_Mendel/4UpILWAz">Gregor Mendel</a>'s work decades before the rise of <a href="/facts/Genetics/bu8wne0A">genetics</a>. Others, such as <a href="/facts/Joshua_Lederberg/do1uFsb1">Joshua Lederberg</a> and <a href="/facts/Leslie_C._Dunn/BTh6FD9R">Leslie C. Dunn</a>, attest to its early significance and cite the experiment as the beginning of <a href="/facts/Molecular_genetics/Q8wsm0FE">molecular genetics</a>.<a class="footnote-ref" id="fnref:24" href="#fn:24">24</a>
A few microbiologists and geneticists had taken an interest in the physical and chemical nature of genes before 1944, but the Avery–MacLeod–McCarty experiment brought renewed and wider interest in the subject. While the original publication did not mention genetics specifically, Avery as well as many of the geneticists who read the paper were aware of the genetic implications—that Avery may have isolated the gene itself as pure DNA. Biochemist <a href="/facts/Erwin_Chargaff/fc55NAAv">Erwin Chargaff</a>, geneticist <a href="/facts/H._J._Muller/vmQSDmDC">H. J. Muller</a> and others praised the result as establishing the biological specificity of DNA and as having important implications for genetics if DNA played a similar role in higher organisms. In 1945, the <a href="/facts/Royal_Society/KI5yXCuV">Royal Society</a> awarded Avery the <a href="/facts/Copley_Medal/bBwd6QzN">Copley Medal</a>, in part for his work on bacterial transformation.<a class="footnote-ref" id="fnref:25" href="#fn:25">25</a>
Between 1944 and 1954, the paper was cited at least 239 times (with citations spread evenly through those years), mostly in papers on microbiology, immunochemistry, and biochemistry. In addition to the follow-up work by McCarty and others at the Rockefeller Institute in response to Mirsky's criticisms, the experiment spurred considerable work in microbiology, where it shed new light on the analogies between bacterial heredity and the genetics of sexually-reproducing organisms.<a class="footnote-ref" id="fnref:26" href="#fn:26">26</a> French microbiologist André Boivin claimed to extend Avery's bacterial transformation findings to <a href="/facts/Escherichia_coli/nR4Gvl56">Escherichia coli</a>,<a class="footnote-ref" id="fnref:27" href="#fn:27">27</a> although this could not be confirmed by other researchers.<a class="footnote-ref" id="fnref:28" href="#fn:28">28</a> In 1946, however, Joshua Lederberg and <a href="/facts/Edward_Tatum/1XnD76Ab">Edward Tatum</a> demonstrated <a href="/facts/Bacterial_conjugation/WfeyKYC4">bacterial conjugation</a> in E. coli and showed that genetics could apply to bacteria, even if Avery's specific method of transformation was not general.<a class="footnote-ref" id="fnref:29" href="#fn:29">29</a> Avery's work also motivated <a href="/facts/Maurice_Wilkins/nT5vv4Tu">Maurice Wilkins</a> to continue <a href="/facts/X-ray_Crystallography/WtI0F5DN">X-ray crystallographic</a> studies of DNA, even as he faced pressure from funders to focus his research on whole cells, rather than biomolecules.<a class="footnote-ref" id="fnref:30" href="#fn:30">30</a>
Despite the significant number of citations to the paper and positive responses it received in the years following publication, Avery's work was largely neglected by much of the scientific community. Although received positively by many scientists, the experiment did not seriously affect mainstream genetics research, in part because it made little difference for classical genetics experiments in which genes were defined by their behavior in breeding experiments rather than their chemical makeup. H. J. Muller, while interested, was focused more on physical rather than chemical studies of the gene, as were most of the members of the <a href="/facts/Phage_group/P9dWfcUE">phage group</a>. Avery's work was also neglected by the <a href="/facts/Nobel_Foundation/xAYmymTr">Nobel Foundation</a>, which later expressed public regret for failing to award Avery a <a href="/facts/Nobel_Prize/3z1Y3oFL">Nobel Prize</a>.<a class="footnote-ref" id="fnref:31" href="#fn:31">31</a>
By the time of the 1952 <a href="/facts/Hershey%25E2%2580%2593Chase_experiment/kJJpIHIE">Hershey–Chase experiment</a>, geneticists were more inclined to consider DNA as the genetic material, and <a href="/facts/Alfred_Hershey/lAEvkfBe">Alfred Hershey</a> was an influential member of the phage group.<a class="footnote-ref" id="fnref:32" href="#fn:32">32</a><a class="footnote-ref" id="fnref:33" href="#fn:33">33</a> Erwin Chargaff had shown that the base composition of DNA varies by species (contrary to the tetranucleotide hypothesis),<a class="footnote-ref" id="fnref:34" href="#fn:34">34</a> and in 1952 Rollin Hotchkiss published his experimental evidence both confirming Chargaff's work and demonstrating the absence of protein in Avery's transforming principle.<a class="footnote-ref" id="fnref:35" href="#fn:35">35</a> Furthermore, the field of <a href="/facts/Bacterial_genetics/Gy7pNIKF">bacterial genetics</a> was quickly becoming established, and biologists were more inclined to think of heredity in the same terms for bacteria and higher organisms.<a class="footnote-ref" id="fnref:36" href="#fn:36">36</a><a class="footnote-ref" id="fnref:37" href="#fn:37">37</a> After Hershey and Chase used <a href="/facts/Radioactive_isotope/5WpCfbdq">radioactive isotopes</a> to show that it was primarily DNA, rather than protein, that entered bacteria upon infection with <a href="/facts/Bacteriophage/L2Ll0T3q">bacteriophage</a>,<a class="footnote-ref" id="fnref:38" href="#fn:38">38</a> it was soon widely accepted that DNA was the material. Despite the much less precise experimental results (they found a not-insignificant amount of protein entering the cells as well as DNA), the Hershey–Chase experiment was not subject to the same degree of challenge. Its influence was boosted by the growing network of the phage group and, the following year, by the publicity surrounding the DNA structure proposed by <a href="/facts/James_D._Watson/TnXJ7GCp">Watson</a> and <a href="/facts/Francis_Crick/AG05HNKI">Crick</a> (Watson was also a member of the phage group). Only in retrospect, however, did either experiment definitively prove that DNA is the genetic material.<a class="footnote-ref" id="fnref:39" href="#fn:39">39</a><a class="footnote-ref" id="fnref:40" href="#fn:40">40</a>

<h2 id="notes">Notes</h2>

<ul><li>Deichmann, UTE (2004). "Early responses to Avery et al.'s paper on DNA as hereditary material". Historical Studies in the Physical and Biological Sciences. 34 (2): 207–32. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1525%2Fhsps.2004.34.2.207">10.1525/hsps.2004.34.2.207</a>.</li>
<li>Fruton, Joseph S. (1999). Proteins, enzymes, genes: the interplay of chemistry and biology. New Haven, Conn: Yale University Press. <a href="/facts/ISBN_(identifier)/15AdSPa9">ISBN</a> 978-0-300-07608-0.</li>
<li><a href="/facts/Matthew_Cobb/sPYU3SQk">Cobb, Matthew</a>; Morange, Michel (1998). A history of molecular biology. Cambridge: Harvard University Press. <a href="/facts/ISBN_(identifier)/15AdSPa9">ISBN</a> 978-0-674-00169-5.</li>
<li>Lehrer, Steven (2006). <a href="https://books.google.com/books?id=iwDn7ubDO2kC">Explorers of the Body: Dramatic Breakthroughs in Medicine from Ancient Times to Modern Science</a>. United States: iUniverse. <a href="/facts/ISBN_(identifier)/15AdSPa9">ISBN</a> 978-0-595-40731-6.</li>
<li>Fry, Michael (2016) Landmark Experiments in Molecular Biology; Elsevier-Academic Press, United States, <a href="/facts/ISBN_(identifier)/15AdSPa9">ISBN</a> 9780128020746</li></ul>
<h2 id="further-reading">Further reading</h2>
<ul><li>Lederberg J (February 1994). <a href="http://www.genetics.org/cgi/pmidlookup?view=long&pmid=8150273">"The transformation of genetics by DNA: an anniversary celebration of Avery, MacLeod and McCarty (1944)"</a>. Genetics. 136 (2): 423–6. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1093%2Fgenetics%2F136.2.423">10.1093/genetics/136.2.423</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1205797">1205797</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8150273">8150273</a>.</li>
<li>McCarty, Maclyn (1986). The transforming principle: discovering that genes are made of DNA. New York: Norton. <a href="/facts/ISBN_(identifier)/15AdSPa9">ISBN</a> 978-0-393-30450-3.</li>
<li>Stegenga, Jacob (2011). <a href="https://www.academia.edu/2310188">"The chemical characterization of the gene: vicissitudes of evidential assessment"</a>. History and Philosophy of the Life Sciences. 33 (1): 105–127. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/21789957">21789957</a>.</li></ul>
<h2 id="external-links">External links</h2>
<ul><li><a href="https://profiles.nlm.nih.gov/spotlight/cc">Profiles in Science: The Oswald T. Avery Collection</a></li></ul>

<h2 id="references">References</h2>

<ol>
<li id="fn:1">Avery, Oswald T.; Colin M. MacLeod; Maclyn McCarty (1944-02-01). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Deoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III". Journal of Experimental Medicine. 79 (2): 137–158. doi:10.1084/jem.79.2.137. PMC 2135445. PMID 19871359. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135445" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135445</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></li>
<li id="fn:2">Fruton (1999), pp. 438–440 <a href="#fnref:2" class="footnote-back-ref">↩</a></li>
<li id="fn:3">Lehrer, Steven. Explorers of the Body. 2nd edition. iuniverse 2006 p 46 [1] <a href="https://books.google.com/books?id=iwDn7ubDO2kC" target="_blank">https://books.google.com/books?id=iwDn7ubDO2kC</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></li>
<li id="fn:4">Griffith, Frederick (January 1928). "The Significance of Pneumococcal Types". The Journal of Hygiene. 27 (2): 113–159. doi:10.1017/S0022172400031879. JSTOR 4626734. PMC 2167760. PMID 20474956. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2167760" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2167760</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></li>
<li id="fn:5">Dawes, Heather (August 2004). "The quiet revolution". Current Biology. 14 (15): R605 – R607. doi:10.1016/j.cub.2004.07.038. PMID 15296771. <a href="https://doi.org/10.1016%2Fj.cub.2004.07.038" target="_blank">https://doi.org/10.1016%2Fj.cub.2004.07.038</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></li>
<li id="fn:6">Neufeld, Fred; Levinthal, Walter (1928). "Beitrage zur Variabilitat der Pneumokokken". Zeitschrift für Immunitätsforschung. 55: 324–340. <a href="https://profiles.nlm.nih.gov/101584575X28" target="_blank">https://profiles.nlm.nih.gov/101584575X28</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></li>
<li id="fn:7">Dawson, MH (1 January 1930). "The transformation of pneumococcal types: II. The interconvertibility of type-specific S pneumococci". The Journal of Experimental Medicine. 51 (1): 123–47. doi:10.1084/jem.51.1.123. PMC 2131805. PMID 19869670. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2131805" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2131805</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></li>
<li id="fn:8">Dawson, Martin H.; Sia, Richard H. P. (1930). "The Transformation of Pneumococcal Types In Vitro". Proceedings of the Society for Experimental Biology and Medicine. 27 (9): 989–990. doi:10.3181/00379727-27-5078. S2CID 84395600. <a href="https://journals.sagepub.com/doi/abs/10.3181/00379727-27-5078" target="_blank">https://journals.sagepub.com/doi/abs/10.3181/00379727-27-5078</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></li>
<li id="fn:9">Fruton (1999), p. 438 <a href="#fnref:9" class="footnote-back-ref">↩</a></li>
<li id="fn:10">The Oswald T. Avery Collection: "Shifting Focus: Early Work on Bacterial Transformation, 1928–1940." Profiles in Science. U.S. National Library of Medicine. Accessed February 25, 2009. <a href="https://profiles.nlm.nih.gov/CC/Views/Exhibit/narrative/shifting.html" target="_blank">https://profiles.nlm.nih.gov/CC/Views/Exhibit/narrative/shifting.html</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></li>
<li id="fn:11">Avery, Oswald T.; Colin M. MacLeod; Maclyn McCarty (1944-02-01). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Deoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III". Journal of Experimental Medicine. 79 (2): 137–158. doi:10.1084/jem.79.2.137. PMC 2135445. PMID 19871359. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135445" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135445</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></li>
<li id="fn:12">Avery, Oswald T.; Colin M. MacLeod; Maclyn McCarty (1944-02-01). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Deoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III". Journal of Experimental Medicine. 79 (2): 137–158. doi:10.1084/jem.79.2.137. PMC 2135445. PMID 19871359. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135445" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135445</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></li>
<li id="fn:13">Avery, Oswald T.; Colin M. MacLeod; Maclyn McCarty (1944-02-01). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Deoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III". Journal of Experimental Medicine. 79 (2): 137–158. doi:10.1084/jem.79.2.137. PMC 2135445. PMID 19871359. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135445" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135445</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></li>
<li id="fn:14">Fruton (1999), p. 439 <a href="#fnref:14" class="footnote-back-ref">↩</a></li>
<li id="fn:15">Witkin EM (August 2005). "Remembering Rollin Hotchkiss (1911–2004)". Genetics. 170 (4): 1443–7. doi:10.1093/genetics/170.4.1443. PMC 1449782. PMID 16144981. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1449782" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1449782</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></li>
<li id="fn:16">Morange (1998), pp. 30–39 <a href="#fnref:16" class="footnote-back-ref">↩</a></li>
<li id="fn:17">Fruton (1999), pp. 440–441 <a href="#fnref:17" class="footnote-back-ref">↩</a></li>
<li id="fn:18">Stanley, Wendell M. (1935-06-28). "Isolation of a Crystalline Protein Possessing the Properties of Tobacco-Mosaic Virus" (PDF). Science. New Series. 81 (2113): 644–645. Bibcode:1935Sci....81..644S. doi:10.1126/science.81.2113.644. JSTOR 1658941. PMID 17743301. Archived from the original (PDF) on September 27, 2006. Retrieved 2009-02-26. <a href="https://web.archive.org/web/20060927230511/http://www.asm.org/ASM/files/CCLIBRARYFILES/FILENAME/0000000268/1935p160.pdf" target="_blank">https://web.archive.org/web/20060927230511/http://www.asm.org/ASM/files/CCLIBRARYFILES/FILENAME/0000000268/1935p160.pdf</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></li>
<li id="fn:19">On the intersecting theories of viruses, genes and enzymes in this period, see: Creager, Angela N. H. The Life of a Virus: Tobacco Mosaic Virus as an Experimental Model, 1930–1965. University of Chicago Press: Chicago, 2002. ISBN 0-226-12025-2 <a href="/wiki/ISBN_(identifier)" target="_blank">/wiki/ISBN_(identifier)</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></li>
<li id="fn:20">Morange (1998), pp. 30–39 <a href="#fnref:20" class="footnote-back-ref">↩</a></li>
<li id="fn:21">Fruton (1999), pp. 440–441 <a href="#fnref:21" class="footnote-back-ref">↩</a></li>
<li id="fn:22">Morange (1998), pp. 30–39 <a href="#fnref:22" class="footnote-back-ref">↩</a></li>
<li id="fn:23">Deichmann, pp. 220–222 <a href="#fnref:23" class="footnote-back-ref">↩</a></li>
<li id="fn:24">Deichmann, pp. 207–209 <a href="#fnref:24" class="footnote-back-ref">↩</a></li>
<li id="fn:25">Deichmann, pp. 215–220 <a href="#fnref:25" class="footnote-back-ref">↩</a></li>
<li id="fn:26">Deichmann, pp. 220–222 <a href="#fnref:26" class="footnote-back-ref">↩</a></li>
<li id="fn:27">Boivin; Boivin, André; Vendrely, Roger; Lehoult, Yvonne (1945). "L'acide thymonucléique hautement polymerise, principe capable de conditioner la spécificité sériologique et l'équipement enzymatique des Bactéries. Conséquences pour la biochemie de l'hérédité". Comptes Rendus. 221: 646–648. <a href="#fnref:27" class="footnote-back-ref">↩</a></li>
<li id="fn:28">Deichmann, pp. 220–222 <a href="#fnref:28" class="footnote-back-ref">↩</a></li>
<li id="fn:29">Lederberg, Joshua; Edward L. Tatum (1946-10-19). "Gene Recombination in Escherichia Coli". Nature. 158 (4016): 558. Bibcode:1946Natur.158..558L. doi:10.1038/158558a0. PMID 21001945. S2CID 1826960. <a href="https://doi.org/10.1038%2F158558a0" target="_blank">https://doi.org/10.1038%2F158558a0</a> <a href="#fnref:29" class="footnote-back-ref">↩</a></li>
<li id="fn:30">Deichmann, pp. 220–222 <a href="#fnref:30" class="footnote-back-ref">↩</a></li>
<li id="fn:31">Deichmann, pp. 227–231 <a href="#fnref:31" class="footnote-back-ref">↩</a></li>
<li id="fn:32">Morange (1998), pp. 44–50 <a href="#fnref:32" class="footnote-back-ref">↩</a></li>
<li id="fn:33">Fruton (1999), pp. 440–442 <a href="#fnref:33" class="footnote-back-ref">↩</a></li>
<li id="fn:34">Chargaff E (June 1950). "Chemical specificity of nucleic acids and mechanism of their enzymatic degradation". Experientia. 6 (6): 201–9. doi:10.1007/BF02173653. PMID 15421335. S2CID 2522535. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:34" class="footnote-back-ref">↩</a></li>
<li id="fn:35">Hotchkiss, Roland D. "The role of deoxyribonucleotides in bacterial transformations". In W. D. McElroy; B. Glass (eds.). Phosphorus Metabolism. Baltimore: Johns Hopkins University Press. pp. 426–36. <a href="#fnref:35" class="footnote-back-ref">↩</a></li>
<li id="fn:36">Morange (1998), pp. 44–50 <a href="#fnref:36" class="footnote-back-ref">↩</a></li>
<li id="fn:37">Fruton (1999), pp. 440–442 <a href="#fnref:37" class="footnote-back-ref">↩</a></li>
<li id="fn:38">Hershey AD, Chase M (May 1952). "Independent functions of viral protein and nucleic acid in growth of bacteriophage". The Journal of General Physiology. 36 (1): 39–56. doi:10.1085/jgp.36.1.39. PMC 2147348. PMID 12981234. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2147348" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2147348</a> <a href="#fnref:38" class="footnote-back-ref">↩</a></li>
<li id="fn:39">Morange (1998), pp. 44–50 <a href="#fnref:39" class="footnote-back-ref">↩</a></li>
<li id="fn:40">Fruton (1999), pp. 440–442 <a href="#fnref:40" class="footnote-back-ref">↩</a></li>
</ol>

Avery–MacLeod–McCarty experiment open-in-new

Avery–MacLeod–McCarty experiment