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<div class='syndicate'><h1>Our Stories</h1><div><p class="lead">NIH supports research in a wide variety of biomedical and behavioral research areas, advancing our knowledge of health and disease. NIH is an integral part of a biomedical and behavioral research ecosystem that includes universities, researchers, private companies, and other government agencies. The knowledge produced by NIH-supported research can take many years and pass through many organizations on its pathway toward improving health.</p>
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<p>Explore this page to look at a few stories of how NIH has contributed to successful health interventions, and how these interventions have made a difference in our lives.</p>
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<p>For a description of how these stories are put together, view the <a href="http://www.cambridge.org/core/journals/journal-of-clinical-and-translational-science/article/protocol-for-retrospective-translational-science-case-studies-of-health-interventions/A3C74BAA1F89943D8525CF140629B13C">published protocol</a> that describes a systematic way of linking the chain of events between scientific discoveries and the adoption of evidence-based health applications.</p>
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<h2>Protecting Children from Pesticides</h2>
|
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<p><a class="media-border no-tag" href="/sites/default/files/about-nih/impact/protecting-children-pesticides-case-study.pdf"><div class="media media-element-container media-featured_media"><div class="ds-1col file file-image file-image-jpeg view-mode-featured_media clearfix">
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-large/public/about-nih/impact/protecting-children-pesticides-case-study-spread-screenshot.jpg?itok=YdnjVmnG&timestamp=1695910779 1x" media="screen and (min-width: 960px)"></source>
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/about-nih/impact/protecting-children-pesticides-case-study-spread-screenshot.jpg?itok=8E3lEpfv&timestamp=1695910779 1x" media="screen and (min-width: 800px)"></source>
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-small/public/about-nih/impact/protecting-children-pesticides-case-study-spread-screenshot.jpg?itok=iqyonkBN&timestamp=1695910779 1x" media="screen and (min-width: 480px)"></source>
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<img class="media-element" src="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/about-nih/impact/protecting-children-pesticides-case-study-spread-screenshot.jpg?itok=8E3lEpfv&timestamp=1695910779" alt="Screenshot of Protecting Children from Pesticides case study" title="Screenshot of the Protecting Children from Pesticides case study" />
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<p>After identifying connections between poor housing conditions, pest infestations, and pesticide use, NIEHS grantees developed an intervention that uses integrated pest management (IPM), an environmentally sustainable approach for reducing pesticide use, to reduce children’s exposure to pesticide. <a href="/sites/default/files/about-nih/impact/protecting-children-pesticides-case-study.pdf">Read how informed by this work, New York implemented regulations to promote the use of IPM in residential and child care settings.</a></p>
|
||
|
||
<div class="collapsible">
|
||
<h4 class="collapsible-trigger">References</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<p class="footnote"><sup>1</sup>Brenner BL, Markowitz S, Rivera M, Romero H, Weeks M, Sanchez E, Deych E, Garg A, Godbold J, Wolff MS, Landrigan PJ, Berkowitz G. 2003. Integrated pest management in an urban community: a successful partnership for prevention. Environ Health Perspect. 111(13):1649-1653.</p>
|
||
|
||
<p class="footnote"><sup>2</sup>Phipatanakul W, Cronin B, Wood RA, Eggleston PA, Shih MC, Song L, Tachdjian R, Oettgen HC. 2004. Effect of environmental intervention on mouse allergen levels in homes of inner-city Boston children with asthma. Ann Allergy Asthma Immunol. 92(4):420-425.</p>
|
||
|
||
<p class="footnote"><sup>3</sup>Kass D, McKelvey W, Carlton E, Hernandez M, Chew G, Nagle S, Garfinkel R, Clarke B, Tiven J, Espino C, Evans D. 2009. Effectiveness of an integrated pest management intervention in controlling cockroaches, mice, and allergens in New York City public housing. Environ Health Perspect. 117(8):1219-1225.</p>
|
||
|
||
<p class="footnote"><sup>4</sup>Bradman A, Chevrier J, Tager I, Lipsett M, Sedgwick J, Macher J, Vargas AB, Cabrera EB, Camacho JM, Weldon R, Kogut K, Jewell NP, Eskenazi B. 2005. Association of housing disrepair indicators with cockroach and rodent infestations in a cohort of pregnant Latina women and their children. Environ Health Perspect 113(12):1795-801.</p>
|
||
|
||
<p class="footnote"><sup>5</sup>Chew GL, Carlton EJ, Kass D, Hernandez M, Clarke B, Tiven J, Garfinkel R, Nagle S, Evans D. 2006. Determinants of cockroach and mouse exposure and associations with asthma in families and elderly individuals living in New York City public housing. Ann Allergy Asthma Immunol. 97(4):502-513.</p>
|
||
|
||
<p class="footnote"><sup>6</sup>Williams MK, Barr DB, Camann DE, Cruz, LA, Carlton EJ, Borjas M, Reyes A, Evans D, Kinney PL, Whitehead Jr. RD, Perera FP, Matsoanne S, Whyatt RM. 2006. An intervention to reduce residential insecticide exposure during pregnancy among an inner-city cohort. Environ Health Perspect. 114(11):1684-1689.</p>
|
||
|
||
<p class="footnote"><sup>7</sup>Kinney PL, Northridge ME, Chew GL, Gronning E, Joseph E, Correa JC, Prakash S, Goldstein I. 2002. On the front lines: an environmental asthma intervention in New York City. Am J Public Health. 92(1):24-6.</p>
|
||
|
||
<p class="footnote"><sup>8</sup>University of California San Francisco California Childcare Health Program. 2011. Integrated Pest Management: A Curriculum for Early Care and Education Programs. <a href="http://cerch.berkeley.edu/sites/default/files/ipm_curriculum_final_10.2010.pdf">http://cerch.berkeley.edu/sites/default/files/ipm_curriculum_final_10.2010.pdf</a>.</p>
|
||
|
||
<p class="footnote"><sup>9</sup>University of California San Francisco California Childcare Health Program. 2013. Green Cleaning, Sanitizing, and Disinfecting: A Curriculum for Early Care and Education. <a href="http://cerch.berkeley.edu/sites/default/files/green_cleaning_toolkit.pdf">http://cerch.berkeley.edu/sites/default/files/green_cleaning_toolkit.pdf</a>.</p>
|
||
|
||
<p class="footnote"><sup>10</sup>University of California Statewide Integrated Pest Management Program. 2016. University of California Agriculture and Natural Resources. Available: <a href="http://ipm.ucanr.edu/training/">http://ipm.ucanr.edu/training/</a>)</p>
|
||
|
||
<p class="footnote"><sup>11</sup>California Healthy Schools Act. 2000. AB 2260, Statutes of 2000, Ch.718.</p>
|
||
|
||
<p class="footnote"><sup>12</sup>NYC Pesticide Reduction Law. 2007. Intro 329A, Local Law 37</p>
|
||
|
||
<p class="footnote"><sup>13</sup>Neighborhood Notification Law. 2007. Intro 328A</p>
|
||
|
||
<p class="footnote"><sup>14</sup>NYC Health Code. 2008. Article 151</p>
|
||
|
||
<p class="footnote"><sup>15</sup>National Institute of Environmental Health Sciences. (2017-2023). Reducing Pesticide Exposures to Preschool-age Children in California Child Care Centers. R01ES027134</p>
|
||
|
||
<p class="footnote"><sup>16</sup>Alkon A, Gunier R, Hazard, K, Castorina R, Hoffman R, Scott R, Anderson K, Bradman A. 2022. Preschool-age children’s pesticide exposures in child care centers and at home in northern California. Journal of Pediatric Health Care. 36(1): 34-45.</p>
|
||
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</div>
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||
|
||
<h2>Protecting Arctic Communities from Environmental Exposures</h2>
|
||
|
||
<p><a class="media-border no-tag" href="/sites/default/files/about-nih/impact/protecting-arctic-communities-case-study.pdf"><div class="media media-element-container media-featured_media"><div class="ds-1col file file-image file-image-jpeg view-mode-featured_media clearfix">
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<p>The Alaska Community Action on Toxics (ACAT) works to address health risks from contaminant chemicals by facilitating collaborations between academic environmental health researchers, scientists, health care professionals, students, teachers, and the indigenous Yupik people of Sivuqaq, Alaska — also known as St. Lawrence Island. <a href="/sites/default/files/about-nih/impact/protecting-arctic-communities-case-study.pdf">Read how this community-based participatory research project has identified significant contamination in the island and associated health effects and used these findings to inform state level policies to reduce exposure to PFAS chemicals.</a></p>
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<h4 class="collapsible-trigger">References</h4>
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<p class="footnote"><sup>1</sup>Anchorage School District. ASD MEMORANDUM #199. Available online at <a href="https://www.akaction.org/wp-content/uploads/ASD_pest_management_policy_02-14-2000.pdf">https://www.akaction.org/wp-content/uploads/ASD_pest_management_policy_02-14-2000.pdf</a>. Accessed May 2023.</p>
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<p class="footnote"><sup>2</sup>Miller PK, Waghiyi V, Welfinger-Smith G, Byrne SC, Kava J, Gologergen J, Eckstein L, Scrudato R, Chiarenzelli J, Carpenter DO, Seguinot-Medina S. 2013. Community-based participatory research projects and policy engagement to protect environmental health on St Lawrence Island, Alaska. International journal of circumpolar health, 72, 10.3402/ijch.v72i0.21656</p>
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<p class="footnote"><sup>3</sup>Carpenter DO, DeCaprio AP, O'Hehir D, Akhtar F, Johnson G, Scrudato RJ, Apatiki L, Kava J, Gologergen J, Miller PK, Eckstein L. 2005. Polychlorinated biphenyls in serum of the Siberian Yupik people from St. Lawrence Island, Alaska. Int J Circumpolar Health, 64(4), 322–335.</p>
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<p class="footnote"><sup>4</sup>Scrudato R, Chiarenzelli JR, Miller PK, Alexander CR, Arnason J, Zamzow K, Zweifel K, Kava J, Waghiyi V, Carpenter DO. 2012. Contaminants at Arctic formerly used defense sites. Journal of Local and Global Health Sciences, Vol. 2.</p>
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<p class="footnote"><sup>5</sup>Welfinger-Smith G, Minholz JL, Byrne S, Waghiyi V, Gologergen J, Kava J, Apatiki M, Ungott E, Miller PK, Arnason JG, Carpenter DO. 2011. Organochlorine and metal contaminants in traditional foods from St. Lawrence Island, Alaska. J Toxicol Environ Health A, 74(18):1195-214.</p>
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<p class="footnote"><sup>6</sup>Environmental Protection Agency. The Frank R. Lautenberg Chemical Safety for the 21st Century Act. Available online at <a href="https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/frank-r-lautenberg-chemical-safety-21st-century-act">https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/frank-r-lautenberg-chemical-safety-21st-century-act</a>. Accessed May 2023.</p>
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<p class="footnote"><sup>7</sup>Anchorage Municipal Assembly. Anchorage Ordinance No. 2017-59. Available online at <a href="https://www.akaction.org/wp-content/uploads/Ordinance-2017-59-Pesticide-Free-Anchorage-As-Introduced-3-21-17-1.pdf">https://www.akaction.org/wp-content/uploads/Ordinance-2017-59-Pesticide-Free-Anchorage-As-Introduced-3-21-17-1.pdf</a>. Accessed May 2023.</p>
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<p class="footnote"><sup>8</sup>Byrne, SC, PK Miller, S Seguinot-Medina, V. Waghiyi, CL Buck, FA von Hippel, DO Carpenter. 2017. Associations between serum polybrominated diphenyl ethers and thyroid hormones in a remote Alaska Native population. Environmental Pollution, 231 387-305.</p>
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<p class="footnote"><sup>9</sup>von Hippel FA, PK Miller, DO Carpenter, D Dillon, L Smayda, I Katsiadaki, T Titus, P Batzel, JH Postlethwait, CL Buck. 2018. Endocrine disruption and differential gene expression in sentinel fish on St. Lawrence Island, Alaska: health implications for indigenous residents. Environ Pollut, 234:279-287.</p>
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<p class="footnote"><sup>10</sup>Byrne S, Seguinot-Medina S, Miller P, Waghiyi V, von Hippel FA, Buck CL, Carpenter DO. 2017. Exposure to polybrominated diphenyl substances in a remote population of Alaska Natives. Environmental pollution (Barking, Essex : 1987), 231(Pt 1), 387–395.</p>
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<p class="footnote"><sup>11</sup>Babayev M, Capozzi SL, Miller P, McLaughlin KR, Medina SS, Byrne S, Zheng G, Salamova A. 2022. PFAS in drinking water and serum of the people of a southeast Alaska community: A pilot study. Environmental pollution (Barking, Essex : 1987), 305, 119246.</p>
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<p class="footnote"><sup>12</sup>Byrne S, Seguinot-Medina S, Waghiyi V, Apatiki E, Immingan T, Miller P, von Hippel FA, Buck CL, Carpenter DO. 2022. PFAS and PBDEs in traditional subsistence foods from Sivuqaq, Alaska. Environmental science and pollution research international, 29(51), 77145–77156.</p>
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<p class="footnote"><sup>13</sup>Alaska Community Action on Toxics. Alaska Community Water Quality Report: PFAS Contamination of Municipality of Anchorage and Fairbanks North Star Borough Waters. Available at <a href="https://www.akaction.org/publications/pfas/alaska-community-water-quality-report-pfas-contamination-of-municipality-of-anchorage-and-fairbanks-north-star-borough-waters/">https://www.akaction.org/publications/pfas/alaska-community-water-quality-report-pfas-contamination-of-municipality-of-anchorage-and-fairbanks-north-star-borough-waters/</a>. Accessed May 2023.</p>
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<p class="footnote"><sup>14</sup>Byrne SC, Miller P, Seguinot-Medina S, Waghiyi V, Buck CL, von Hippel FA, Carpenter DO. 2018. Exposure to perfluoroalkyl substances and associations with serum thyroid hormones in a remote population of Alaska Natives. Environmental research, 166, 537–543.</p>
|
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<p class="footnote"><sup>15</sup>Zheng G, Melo L, Chakraborty R, Klaunig JE, Salamova A. 2022. Biotransformation of 2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine (TTBP-TAZ) can contribute to high levels of 2,4,6-tribromophenol (2,4,6-TBP) in humans. Environment international, 158, 106943.</p>
|
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<p class="footnote"><sup>16</sup>Alaska State Legislature. Regulation for Flame Retardant Chemicals. Available online at <a href="https://www.akleg.gov/basis/Bill/Detail/31?Root=HB%20%2027">https://www.akleg.gov/basis/Bill/Detail/31?Root=HB%20%2027</a>. Accessed May 2023.</p>
|
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<p class="footnote"><sup>17</sup>National Academies of Sciences, Engineering, and Medicine. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Available online at <a href="https://nap.nationalacademies.org/catalog/26156/guidance-on-pfas-exposure-testing-and-clinical-follow-up">https://nap.nationalacademies.org/catalog/26156/guidance-on-pfas-exposure-testing-and-clinical-follow-up</a>. Accessed May 2023.</p>
|
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<p class="footnote"><sup>18</sup>Jordan-Ward R, von Hippel FA, Zheng G, Salamova A, Dillon D, Gologergen J, Immingan T, Dominguez E, Miller P, Carpenter D, Postlethwait JH, Byrne S, Buck CL. 2022. Elevated mercury and PCB concentrations in Dolly Varden (Salvelinus malma) collected near a formerly used defense site on Sivuqaq, Alaska. Science of the Total Environment 826:154067.</p>
|
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|
||
<p class="footnote"><sup>19</sup>Miller, P. 2023. Protecting the Health of Future Generations in the Arctic through Community-Based Participatory Research and Action. Explore (NY). 2023;19(2):271-272.</p>
|
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<p class="footnote"><sup>20</sup>Moran IL, Tidwell L, Barton M, Kile M, Miller P, Rohlman D, Seguinot-Medina S, Ungwiluk B, Waghiyi V, Anderson K. 2023. Diffusive fluxes of persistent organic pollutants between Arctic atmosphere, surface waters and sediments. Science of The Total Environment 892:164566.</p>
|
||
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</div>
|
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|
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<h2>Addressing Asthma and Air Pollution: NIEHS-Funded Researchers Bring Solutions to Children in Rural Agricultural Communities</h2>
|
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|
||
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|
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|
||
<p>Addressing Asthma and Air Pollution: NIEHS supported researchers developed an intervention to help reduce asthma in children from rural agricultural communities. <a href="/sites/default/files/about-nih/impact/asthma-case-study.pdf">Read how they engaged with communities to combine high-efficiency particulate air cleaners and a home-based education program to reduce children’s exposure to pollutants in the home and improve lung health.</a></p>
|
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<div class="collapsible">
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<h4 class="collapsible-trigger">References</h4>
|
||
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<div class="collapsible-content">
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<p class="footnote"><sup>1</sup>Mortimer KM, Neas LM, Dockery DW, Redline S, Tager IB. (2002). The effect of air pollution on inner-city children with asthma. European Respiratory Journal 19: 699-705 DOI: 10.1183/09031936.02.00247102</p>
|
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|
||
<p class="footnote"><sup>2</sup>Armstrong JL, Fitzpatrick CF, Loftus CT, Yost MG, Tchong-French MI, Karr CJ. 2013. Development of a unique multi-contaminant air sampling device for a childhood asthma cohort in an agricultural environment. Environmental Sci Process Impacts 15(9): 1760–1767. doi:10.1039/c3em00330b PMID:23896655Noss I, Doekes G, Sander I, Heederik DJJ, Thorne PS, Wouters IM. 2010. Passive airborne dust sampling with the electrostatic dustfall collector: Optimization of storage and extraction procedures for endotoxin and glucan measurement. Ann Occup Hyg 54(6):651-658. doi:10.1093/annhyg/meq026</p>
|
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||
<p class="footnote"><sup>3</sup>Noss I, Wouters IM, Bezemer G, Metwali N, Sander I, Raulf-Heimsoth M, Heederik DJ, Thorne PS, Doekes G. 2010. Beta-(1,3)-Glucan exposure assessment by passive airborne dust sampling and new sensitive immunoassays. Appl Environ Microbiol 76(4):1158-67. doi:10.1128/AEM.01486-09 PMID:20038709 PMCID:PMC2820944</p>
|
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<p class="footnote"><sup>4</sup>Noss I, Doekes G, Sander I, Heederik DJJ, Thorne PS, Wouters IM. 2010. Passive airborne dust sampling with the electrostatic dustfall collector: Optimization of storage and extraction procedures for endotoxin and glucan measurement. Ann Occup Hyg 54(6):651-658. doi:10.1093/annhyg/meq026</p>
|
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<p class="footnote"><sup>5</sup>Karr, C. 2009. Aggravating Factors of Asthma in a Rural Environment (AFARE). Available online at <a href="https://deohs.washington.edu/pnash/aggravating-factors-asthma-rural-environment-afare">https://deohs.washington.edu/pnash/aggravating-factors-asthma-rural-environment-afare</a>. Accessed October 2021.</p>
|
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<p class="footnote"><sup>6</sup>Loftus C, Yost M, Sampson P, Torres E, Arias G, Breckwich Vasquez V, Hartin K, Armstrong J, Tchong-French MI, Vedal S, Bhatti P, Karr CJ. 2015. Ambient ammonia exposures in an agricultural community and pediatric asthma morbidity. Epidemiology 26(6):794-801.</p>
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<p class="footnote"><sup>7</sup>Williams DL, Breysse PN, McCormack MC, Diette GB, McKenzie S, Geyh AS. 2011. Airborne cow allergen, ammonia and particulate matter at homes vary with distance to industrial scale dairy operations: An exposure assessment. Environ Health 10(72). doi:10.1186/1476-069X-10-72 PMID:21838896</p>
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<p class="footnote"><sup>8</sup>Rabinovitch N. 2007. Urinary leukotriene E4. Immunol Allergy Clin North Am 27(4):651-664. doi:10.1016/j.iac.2007.09.004 PMID:17996582</p>
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<p class="footnote"><sup>9</sup>Loftus C, Afsharinejad Z, Sampson P, Vedal S, Torres E, Arias G, Tchong-French MI, Karr CJ. 2020. Estimated time-varying exposures to air emissions from animal feeding operations and childhood asthma. Int J Hyg Environ Health 223(1):187-198. PMID:31543304</p>
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<p class="footnote"><sup>10</sup>Masterson EE, Younglove LB, Perez A, Torres E, Krenz JE, Tchong-French MI, Riederer AM, Sampson PD, Metwali N, Min E, Jansen KL, Aisenberg G, Babadi RS, Farquhar SA, Thorne PS, Karr CJ. 2020. The home air in agriculture pediatric intervention (HAPI) trial: Rationale and methods. Contemp Clin Trials 96:106085. PMID:32721578</p>
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<p class="footnote"><sup>11</sup>Jack DW, Asante KP, Wylie BJ, Chillrud SN, Whyatt RM, Ae-Ngibise KA, Quinn AK, Yawson AK, Boamah EA, Agyei O, Mujtaba M, Kaali S, Kinney P, Owusu-Agyei S. 2015. Ghana randomized air pollution and health study (GRAPHS): Study protocol for a randomized controlled trial. Trials 16:420. PMID:26395578</p>
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<p class="footnote"><sup>12</sup>Loftus C, Yost MG, Sampson P, Arias G, Torres E, Vasquez VB, Bhatti P, Karr CJ. 2015. Regional PM2.5 and asthma morbidity in an agricultural community: A panel study. Environ Res 136:505-12. PMID:25460673 PMCID:PMC4425279</p>
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<p class="footnote"><sup>13</sup>Benka-Coker W, Loftus C, Magzamen S, Karr CJ. 2019. Characterizing the joint effects of pesticide exposure and criteria ambient air pollutants on pediatric asthma morbidity in an agricultural community. Environ Epidemiol 3(3):e046. doi:10.1097/EE9.0000000000000046 PMID:31342006 PMCID:PMC6571181</p>
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<p class="footnote"><sup>14</sup>Benka-Coker W, Loftus C, Magzamen S, Karr CJ. 2019. Association of organophosphate pesticide exposure and a marker of asthma morbidity in an agricultural community. J Agromedicine 25:106-114. doi:10.1080/1059924X.2019.1619644 PMID:31130077 PMCID:PMC6875607</p>
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<p class="footnote"><sup>15</sup>Riederer AM, Krenz JE, Tchong-French MI, Torres E, Perez A, Younglove LR, Jansen KL, Hardie DC, Farquhar SA, Sampson PD, Metwali N, Thorne PS, Karr CJ. 2021. Effectiveness of portable HEPA air cleaners on reducing indoor endotoxin, PM10, and coarse particulate matter in an agricultural cohort of children with asthma: A randomized intervention trial. Indoor Air 31(6):1926-1939. doi:10.1111/ina.12858 PMID:34288127</p>
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<p class="footnote"><sup>16</sup>Riederer AM, Krenz JE, Tchong-French MI, Torres E, Perez A, Younglove LR, Jansen KL, Hardie DC, Farquhar SA, Sampson PD, Karr CJ. 2021. Effectiveness of portable HEPA air cleaners on reducing indoor PM2.5 and NH3 in an agricultural cohort of children with asthma: A randomized intervention trial. Indoor Air 31(2):454-466. doi:10.1111/ina.12753</p>
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<p class="footnote"><sup>17</sup>Drieling R, Sampson P, Krenz J, French MT, Jansen K, Massey A, Farquhar S, Min E, Perez A, Riederer A, Torres E, Younglove L, Aisenberg E, Andra S, Kim-Schulze S, Karr CJ. 2022. Randomized trial of a portable HEPA /air cleaner intervention to reduce asthma morbidity among Latino children in an agricultural community. Environmental Health. 21:1. doi:10.1186/s12940-021-00816-w</p>
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<p class="footnote"><sup>18</sup>Centers for Disease Control and Prevention. 2018. Asthma in children. [Website.] <a href="https://www.cdc.gov/vitalsigns/childhood-asthma/index.html">https://www.cdc.gov/vitalsigns/childhood-asthma/index.html</a>. [accessed October 28 2021]</p>
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<p class="footnote"><sup>19</sup>United States Environmental Protection Agency. 2014. Children’s environmental health disparities: Hispanic and Latino American children and asthma. Available from: <a href="https://www.epa.gov/sites/default/files/2014-05/documents/hd_hispanic_asthma.pdf">https://www.epa.gov/sites/default/files/2014-05/documents/hd_hispanic_asthma.pdf</a>.</p>
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<p class="footnote"><sup>20</sup>Centers for Disease Control and Prevention. 2020. Most Recent National Asthma Data. [Website.]<a href="https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm">https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm</a> [Accessed September 27, 2022]</p>
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|
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|
||
<h2>Reducing PFAS in Drinking Water</h2>
|
||
|
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<p>Reducing PFAS in Drinking Water: Researchers supported by NIEHS’s Breast Cancer and the Environment Program worked with city officials to implement water filtering practices that reduced PFAS exposures in communities in Ohio. <a href="/sites/default/files/about-nih/impact/pfas-case-study.pdf">Read about how they worked with local water departments to implement water filtering techniques that reduced exposure to harmful chemicals.</a></p>
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<h4 class="collapsible-trigger">References</h4>
|
||
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<p class="footnote"><sup>1</sup><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846284/">Pinney SM, Biro FM, Windham GC, Herrick RL, Yaghjyan L, Calafat AM, Succop P, Sucharew H, Ball KM, Kato K, Kushi LH, Bornschein R</a>. 2014. Serum biomarkers of polyfluoroalkyl compound exposure in young girls in Greater Cincinnati and the San Francisco Bay Area, USA. Environ Pollut. 184:327-34.</p>
|
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<p class="footnote"><sup>2</sup><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2072821/">Calafat AM, Wong L, Kuklenyik Z, Reidy JA, Needham LL</a>. Polyfluoroalkyl chemicals in the US population: Data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and comparisons with NHANES 1999–2000. Environ Health Perspect. 2007b;115(11):1596–1602.</p>
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<p class="footnote"><sup>3</sup><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018486/">Hernick AD, Brown MK, Pinney SM, Biro FM, Ball KM, Bornschein RL</a>. Sharing unexpected biomarker results with study participants. 2011. Environ Health Perspect. 119(1):1-5.</p>
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<p class="footnote"><sup>4</sup><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477546/">White SS, Kato K, Jia LT, Basden BJ, Calafat AM, Hines EP, Stanko JP, Wolf CJ, Abbott BD, Fenton SE</a>. 2009. Effects of perfluorooctanoic acid on mouse mammary gland development and differentiation resulting from cross-foster and restricted gestational exposures. Reprod Toxicol. 27(3-4):289-298.</p>
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<p class="footnote"><sup>5</sup><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855353/">Zhao, Y, Tan YS, Haslam, SZ, Yang C</a>. 2010. Perfluorooactanoic acid effects on steroid hormone and growth factor levels mediate stimulation of peripubertal mammary gland development in C57BL/6 mice. Toxicol Sci.115:214-224.</p>
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<p class="footnote"><sup>6</sup><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739850/">Pinney SM, Windham GC, Xie C, Herrick RL, Calafat AM, McWhorter K, Fassler CS, Hiatt RA, Kushi LH, Biro FM; Breast Cancer and the Environment Research Program</a>. 2019. Perfluorooctanoate and changes in anthropometric parameters with age in young girls in the Greater Cincinnati and San Francisco Bay Area. Int J Hyg Environ Health. 222(7):1038-1046.</p>
|
||
|
||
<p class="footnote"><sup>7</sup><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739842/">Fassler CS, Pinney SE, Xie C, Biro FM, Pinney SM</a>. Complex relationships between perfluorooctanoate, body mass index, insulin resistance and serum lipids in young girls. 2019. Environ Res. 176:108558.</p>
|
||
|
||
<p class="footnote"><sup>8</sup><a href="https://ehp.niehs.nih.gov/doi/abs/10.1289/isee.2020.virtual.O-OS-617">Pinney SM, Fassler CS, Windham GC, Herrick RL, Xie C, Kushi LH, Biro FM</a>. 2020. Exposure to perfluorooctanoic acid and effects on reproductive hormones and pubertal onset in a longitudinal study of young girls. Abstract presented at: Annual Meeting of the International Society for Environmental Epidemiology; 27 August 2020; Virtual conference; Oral session 35.</p>
|
||
|
||
<p class="footnote"><sup>9</sup>Water Quality Report. Northern Kentucky Water District. 2012. PWSID#KY0590220—32013. Available: <a href="https://nkywater.org/pdfs/CCRS/ccr2012.pdf">https://nkywater.org/pdfs/CCRS/ccr2012.pdf</a>. [Accessed 1 August 2022].</p>
|
||
|
||
<p class="footnote"><sup>10</sup><a href="https://pubmed.ncbi.nlm.nih.gov/28505513/">Herrick RL, Buckholz J, Biro FM, Calafat AM, Ye X, Xie C, Pinney SM</a>. 2017. Polyfluoroalkyl substance exposure in the Mid-Ohio River Valley, 1991-2012. Environ Pollut. 228:50-60.</p>
|
||
|
||
<p class="footnote"><sup>11</sup>PFAS, GenX, and Other Forever Chemicals: An Update for Clinicians. University of Cincinnati Center for Continuous Professional Development/CME. <a href="https://uc.cloud-cme.com/course/courseoverview?P=0&EID=29137">https://uc.cloud-cme.com/course/courseoverview?P=0&EID=29137</a>. [Accessed 1 August 2022].</p>
|
||
|
||
<p class="footnote"><sup>12</sup>Agency for Toxic Substances and Disease Registry: Per- and polyfluoroalkyl substances (PFAS) and your health. Available: <a href="https://www.atsdr.cdc.gov/pfas/">https://www.atsdr.cdc.gov/pfas/</a>. [Accessed 1 August 2022].</p>
|
||
|
||
<p class="footnote"><sup>13</sup><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799453/">Hiatt RA, Haslam SZ, Osuch J; Breast Cancer and the Environment Research Centers</a>. 2009. The breast cancer and the environment research center: transdisciplinary research on the role of the environment in breast cancer etiology. Environ Health Perspect. 117(12):1814-22.</p>
|
||
</div>
|
||
</div>
|
||
|
||
<h2>Rapid Translation of Science to Real-World Practice: Coordinated Specialty Care Treatment Programs for Early Schizophrenia</h2>
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||
|
||
<p><a class="media-border no-tag" href="/sites/default/files/about-nih/impact/raise-case-study.pdf"><div class="media media-element-container media-featured_media"><div class="ds-1col file file-image file-image-jpeg view-mode-featured_media clearfix">
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<picture title="Screenshot of the RAISE case study" class="media-element">
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-large-extra/public/about-nih/impact/raise-case-study-spread-screenshot_0.jpg?itok=Beokas8c&timestamp=1668785992 1x" media="screen and (min-width: 1100px)"></source>
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||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-large/public/about-nih/impact/raise-case-study-spread-screenshot_0.jpg?itok=ABOfB4YW&timestamp=1668785992 1x" media="screen and (min-width: 960px)"></source>
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/about-nih/impact/raise-case-study-spread-screenshot_0.jpg?itok=PPnfCRLh&timestamp=1668785992 1x" media="screen and (min-width: 800px)"></source>
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium-small/public/about-nih/impact/raise-case-study-spread-screenshot_0.jpg?itok=8mX1F0tE&timestamp=1668785992 1x" media="screen and (min-width: 600px)"></source>
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<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-small/public/about-nih/impact/raise-case-study-spread-screenshot_0.jpg?itok=fzTGweMR&timestamp=1668785992 1x" media="screen and (min-width: 480px)"></source>
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||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media__breakpoint-tiny_/public/about-nih/impact/raise-case-study-spread-screenshot_0.jpg?itok=vHoaMraj&timestamp=1668785992 1x" media="screen and (min-width: 0)"></source>
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<!--[if IE 9]></video><![endif]-->
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||
<img class="media-element" src="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/about-nih/impact/raise-case-study-spread-screenshot_0.jpg?itok=PPnfCRLh&timestamp=1668785992" alt="Screenshot of the RAISE case study" title="Screenshot of the RAISE case study" />
|
||
</picture></div>
|
||
|
||
</div></a></p>
|
||
|
||
<p>Schizophrenia is a serious mental illness and a leading cause of long-term disability. <a href="/sites/default/files/about-nih/impact/raise-case-study.pdf">Read the story of NIH’s strategic approach to disseminate and help to implement research findings on coordinated specialty care treatment programs into the standard of practice for early schizophrenia in the U.S., which substantially improves the quality of life for patients.</a></p>
|
||
|
||
<div class="collapsible">
|
||
<h3 class="collapsible-trigger">Additional materials</h3>
|
||
|
||
<div class="collapsible-content">
|
||
<h4 class="collapsible-trigger">References</h4>
|
||
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||
<div class="collapsible-content">
|
||
<p class="footnote"><sup>1</sup><a href="https://www.nimh.nih.gov/health/statistics/schizophrenia#part_2544">https://www.nimh.nih.gov/health/statistics/schizophrenia#part_2544</a>.</p>
|
||
|
||
<p class="footnote"><sup>2</sup><a href="https://www.nimh.nih.gov/health/statistics/schizophrenia">https://www.nimh.nih.gov/health/statistics/schizophrenia</a>.</p>
|
||
|
||
<p class="footnote"><sup>3</sup><a href="https://www.nimh.nih.gov/health/statistics/schizophrenia#part_2715">https://www.nimh.nih.gov/health/statistics/schizophrenia#part_2715</a>.</p>
|
||
|
||
<p class="footnote"><sup>4</sup>Simon GE, et al. <em>Psychiatric Services </em>2017;68(5):456-461. PMID: 28045349.</p>
|
||
|
||
<p class="footnote"><sup>5</sup><a href="https://www.nimh.nih.gov/health/topics/schizophrenia/raise">https://www.nimh.nih.gov/health/topics/schizophrenia/raise</a>.</p>
|
||
|
||
<p class="footnote"><sup>6</sup>Sullivan HS. <em>American Journal of Psychiatry</em> 1994;151,6 Sesquicentennial Supplement:135-9. PMID: 8192188.</p>
|
||
|
||
<p class="footnote"><sup>7</sup>Craig TK, et al. <em>British Medical Journal</em> 2004;329(7474):1067. PMID: 15485934.</p>
|
||
|
||
<p class="footnote"><sup>8</sup>Petersen L, et al. <em>British Medical Journal</em> 2005;331(7517):602. PMID: 16141449.</p>
|
||
|
||
<p class="footnote"><sup>9</sup>Kane JM, et al. <em>American Journal of Psychiatry </em>2016;173(4):362-72. PMID: 26481174.</p>
|
||
|
||
<p class="footnote"><sup>10</sup>Dixon LB, et al. Psychiatric Services 2015;66(7):691–98. PMID: 25772764.</p>
|
||
|
||
<p class="footnote"><sup>11</sup>Goldman HH. <em>Schizophrenia Bulletin</em> 2010;36(5):893–94. PMID: 20660023.</p>
|
||
|
||
<p class="footnote"><sup>12</sup>Public Law 113–76—Jan. 17, 2014, 113th Congress. Available at: <a href="https://www.govinfo.gov/content/pkg/PLAW-113publ76/pdf/PLAW-113publ76.pdf">https://www.govinfo.gov/content/pkg/PLAW-113publ76/pdf/PLAW-113publ76.pdf</a>.</p>
|
||
|
||
<p class="footnote"><sup>13</sup><a href="https://med.stanford.edu/peppnet">https://med.stanford.edu/peppnet</a>.</p>
|
||
|
||
<p class="footnote"><sup>14</sup>Correll CU, et al. <em>JAMA Psychiatry</em> 2014;71(12):1350–63. PMID: 25321337.</p>
|
||
|
||
<p class="footnote"><sup>15</sup><a href="https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-16-600.html">https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-16-600.html</a>.</p>
|
||
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||
<p class="footnote"><sup>16</sup><a href="https://www.hhs.gov/guidance/sites/default/files/hhs-guidance-documents/cib-10-16-2015_26.pdf">https://www.hhs.gov/guidance/sites/default/files/hhs-guidance-documents/cib-10-16-2015_26.pdf</a>.</p>
|
||
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||
<p class="footnote"><sup>17</sup>Srihari VH, et al. <em>Psychiatric Services</em> 2015;66(7): 705-12. PMID: 25639994.</p>
|
||
|
||
<p class="footnote"><sup>18</sup><a href="https://www.nimh.nih.gov/health/topics/schizophrenia/raise/state-health-administrators-and-clinics">https://www.nimh.nih.gov/health/topics/schizophrenia/raise/state-health-administrators-and-clinics</a>.</p>
|
||
|
||
<p class="footnote"><sup>19</sup>US Department of Health and Human Services. <em>Agency Priority Goal Action Plan: Serious Mental Illness.</em> 2018. Available at: <a href="https://assets.performance.gov/APG/HHS/FY2018_Q4_HHS_Serious_Mental_Illness.pdf">https://assets.performance.gov/APG/HHS/FY2018_Q4_HHS_Serious_Mental_Illness.pdf</a>.</p>
|
||
|
||
<p class="footnote"><sup>20</sup>Substance Abuse and Mental Health Services Administration. Snapshot of State Plans for Using the Community Mental Health Block Grant (MHBG) Ten Percent Set-Aside for Early Intervention Programs: Fiscal Years 2016 & 2017. 2016. Available at: <a href="https://www.nri-inc.org/media/1547/nri_2016_2017_snapshotpdf.pdf">https://www.nri-inc.org/media/1547/nri_2016_2017_snapshotpdf.pdf</a>.</p>
|
||
|
||
<p class="footnote"><sup>21</sup>Addington J, et al. <em>Psychiatric services</em> 2015;66(7):753–756. PMID: 25588418.</p>
|
||
|
||
<p class="footnote"><sup>22</sup><a href="https://grants.nih.gov/grants/guide/pa-files/PAR-16-264.html">https://grants.nih.gov/grants/guide/pa-files/PAR-16-264.html</a></p>
|
||
|
||
<p class="footnote"><sup>23</sup><a href="https://grants.nih.gov/grants/guide/pa-files/PAR-16-265.html">https://grants.nih.gov/grants/guide/pa-files/PAR-16-265.html</a></p>
|
||
|
||
<p class="footnote"><sup>24</sup><a href="https://www.congress.gov/114/plaws/publ255/PLAW-114publ255.pdf">https://www.congress.gov/114/plaws/publ255/PLAW-114publ255.pdf</a>.</p>
|
||
|
||
<p class="footnote"><sup>25</sup>Nossel N, et al. <em>Psychiatric Services</em> 2018; 69(8):863-70. PMID: 29759055.</p>
|
||
|
||
<p class="footnote"><sup>26</sup>Substance Abuse and Mental Health Services Administration. Snapshot of State Plans for Using the Community Mental Health Block Grant (MHBG) Ten Percent Set-Aside for Early Intervention Programs: Fiscal Year 2018. 2018. Available at: <a href="https://www.nasmhpd.org/sites/default/files/Snapshot_of_State_Plans.pdf">https://www.nasmhpd.org/sites/default/files/Snapshot_of_State_Plans.pdf</a></p>
|
||
|
||
<p class="footnote"><sup>27</sup>Substance Abuse and Mental Health Services Administration. 2019 Uniform Reporting System (URS) Output Tables. 2020. Available at: <a href="https://www.samhsa.gov/data/report/2019-uniform-reporting-system-urs-output-tables">https://www.samhsa.gov/data/report/2019-uniform-reporting-system-urs-output-tables</a>.</p>
|
||
|
||
<p class="footnote"><sup>28</sup>Department of Veterans Affairs, Veterans Health Administration, VHA Directive 1163.07, 2020. Available at: <a href="https://www.va.gov/vhapublications/publications.cfm?pub=1&order=asc&orderby=pub_Number">https://www.va.gov/vhapublications/publications.cfm?pub=1&order=asc&orderby=pub_Number</a>.</p>
|
||
|
||
<p class="footnote"><sup>29</sup>Substance Abuse and Mental Health Services Administration. 2020 Uniform Reporting System (URS) Output Tables. 2021. Available at <a href="https://www.samhsa.gov/data/report/2020-uniform-reporting-system-urs-output-tables">https://www.samhsa.gov/data/report/2020-uniform-reporting-system-urs-output-tables</a>.</p>
|
||
|
||
<p class="footnote"><sup>30</sup>Ho B, et al. <em>American Journal of Psychiatry</em> 2000;157:808-15. PMID: 10784476.</p>
|
||
|
||
<p class="footnote"><sup>31</sup>Correll CU, et al. <em>JAMA Psychiatry</em> 2018;75(6):555-565. PMID: 29800949.</p>
|
||
|
||
<p class="footnote"><sup>32</sup>Marino L, et al. <em>Early Intervention in Psychiatry</em> 2020;14(5):544–52. PMID: 31502409.</p>
|
||
|
||
<p class="footnote"><sup>33</sup>Keepers GA, et al. <em>American Journal of Psychiatry</em> 2020;177(9): 868-72. PMID: 32867516.</p>
|
||
|
||
<p class="footnote"><sup>34</sup>Societal Costs of Schizophrenia and Related Disorders, 2021. Available at <a href="https://sczaction.org/wp-content/uploads/2021/11/571-012_WhitePaper_Report_FINAL_updated_11.09.21.pdf">https://sczaction.org/wp-content/uploads/2021/11/571-012_WhitePaper_Report_FINAL_updated_11.09.21.pdf</a>.</p>
|
||
|
||
<p class="footnote"><sup>35</sup>Rosenheck R, et al. <em>Schizophrenia Bulletin</em> 2016;42(4):896-906. PMID: 26834024.</p>
|
||
</div>
|
||
|
||
<h4 class="collapsible-trigger">Related Resources on the Rapid Translation of Science to Real-World Practice: Coordinated Specialty Care Treatment Programs for Early Schizophrenia</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<ul>
|
||
<li><a href="https://www.nimh.nih.gov/research/research-funded-by-nimh/research-initiatives/recovery-after-an-initial-schizophrenia-episode-raise">Recovery After an Initial Schizophrenia Episode (RAISE)</a></li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<h2>The Framingham Heart Study: Laying the Foundation for Preventive Health Care</h2>
|
||
|
||
<p><a class="media-border no-tag" href="/sites/default/files/about-nih/impact/framingham-heart-study.pdf"><div class="media media-element-container media-featured_media"><div class="ds-1col file file-image file-image-jpeg view-mode-featured_media clearfix">
|
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||
|
||
<picture title="Screenshot of the Framingham Heart Study" class="media-element">
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||
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||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-large/public/about-nih/impact/framingham-heart-study-spread-screenshot.jpg?itok=Dg2jLdgT&timestamp=1517500832 1x" media="screen and (min-width: 960px)"></source>
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||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/about-nih/impact/framingham-heart-study-spread-screenshot.jpg?itok=9JlZAVGT&timestamp=1517500832 1x" media="screen and (min-width: 800px)"></source>
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||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium-small/public/about-nih/impact/framingham-heart-study-spread-screenshot.jpg?itok=lv9-we7V&timestamp=1517500832 1x" media="screen and (min-width: 600px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-small/public/about-nih/impact/framingham-heart-study-spread-screenshot.jpg?itok=XqHwshQ3&timestamp=1517500832 1x" media="screen and (min-width: 480px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media__breakpoint-tiny_/public/about-nih/impact/framingham-heart-study-spread-screenshot.jpg?itok=SXOhVl2e&timestamp=1517500832 1x" media="screen and (min-width: 0)"></source>
|
||
<!--[if IE 9]></video><![endif]-->
|
||
<img class="media-element" src="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/about-nih/impact/framingham-heart-study-spread-screenshot.jpg?itok=9JlZAVGT&timestamp=1517500832" alt="Screenshot of the Framingham Heart Study" title="Screenshot of the Framingham Heart Study" />
|
||
</picture></div>
|
||
|
||
</div></a></p>
|
||
|
||
<p>One of the first long-term cohort studies of its kind, the NIH's Framingham Heart Study is considered the crown jewel of epidemiology. Thanks to Framingham, we now know that most cardiovascular disease is caused by modifiable risk factors like smoking, high blood pressure, obesity, high cholesterol levels, and physical inactivity. <a href="/sites/default/files/about-nih/impact/framingham-heart-study.pdf">Read how this study, celebrating its 70th anniversary, changed the way we study health and disease.</a></p>
|
||
|
||
<div class="collapsible">
|
||
<h3 class="collapsible-trigger">Additional materials</h3>
|
||
|
||
<div class="collapsible-content">
|
||
<h4 class="collapsible-trigger">References</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<p class="footnote"><sup>1</sup>Centers for Disease Control and Prevention. Leading Causes of Death, 1900-1998. <em>Natl Vital Stat Rep</em>. 1998;48:1-67. <a href="http://www.cdc.gov/nchs/data/dvs/lead1900_98.pdf">http://www.cdc.gov/nchs/data/dvs/lead1900_98.pdf</a>.</p>
|
||
|
||
<p class="footnote"><sup>2</sup>Mahmood SS, Levy D, Vasan RS, Wang TJ. The Framingham Heart Study and the epidemiology of cardiovascular disease: a historical perspective. <em>Lancet (London, England)</em>. 2014;383(9921):999-1008. doi:10.1016/S0140-6736(13)61752-3.</p>
|
||
|
||
<p class="footnote"><sup>3</sup>Tsao CW, Vasan RS. The Framingham Heart Study: past, present and future. <em>Int J Epidemiol</em>. 2015;44(6):1763-1766. doi:10.1093/ije/dyv336.</p>
|
||
|
||
<p class="footnote"><sup>4</sup>Gordon T, Kannel W, Cole C, et al. The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease, Sections 1 and 2. 1968.</p>
|
||
|
||
<p class="footnote"><sup>5</sup>Framingham Heart Study (FHS) | National Heart, Lung, and Blood Institute (NHLBI). <a href="https://www.nhlbi.nih.gov/science/framingham-heart-study-fhs">https://www.nhlbi.nih.gov/science/framingham-heart-study-fhs</a>. Accessed September 22, 2017.</p>
|
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|
||
<p class="footnote"><sup>6</sup>Tsao CW, Vasan RS. Cohort Profile: The Framingham Heart Study (FHS): overview of milestones in cardiovascular epidemiology. doi:10.1093/ije/dyv337.</p>
|
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|
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<p class="footnote"><sup>7</sup>Levy D, Brink S. <em>A Change of Heart</em>. New York, N.Y.: Vintage Books; 2005.</p>
|
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|
||
<p class="footnote"><sup>8</sup>DAWBER TR, KANNEL WB, REVOTSKIE N, STOKES J, KAGAN A, GORDON T. Some factors associated with the development of coronary heart disease: six years’ follow-up experience in the Framingham study. <em>Am J Public Health Nations Health</em>. 1959;49:1349-1356.</p>
|
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|
||
<p class="footnote"><sup>9</sup>Kannel WB, Dawber TR, Kagan a, Revotskie N, Stokes J. Factors of risk in the development of coronary heart disease--six year follow-up experience. The Framingham Study. <em>Ann Intern Med</em>. 1961;55:33-50.</p>
|
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|
||
<p class="footnote"><sup>10</sup>Marshall TR. The 1964 Surgeon General’s report and Americans’ beliefs about smoking. <em>J Hist Med Allied Sci</em>. 2015;70(2):250-278. doi:10.1093/jhmas/jrt057.</p>
|
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|
||
<p class="footnote"><sup>11</sup>Kannel WB, LeBauer EJ, Dawber TR, McNamara PM. Relation of body weight to development of coronary heart disease. The Framingham study. <em>Circulation</em>. 1967;35(4):734-744.</p>
|
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|
||
<p class="footnote"><sup>12</sup>Kannel WB. Habitual level of physical activity and risk of coronary heart disease: the Framingham study. <em>Can Med Assoc J</em>. 1967;96(12):811-812.</p>
|
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|
||
<p class="footnote"><sup>13</sup>Sorlie PD, Sholinsky PD, Lauer MS, et al. Reinvestment in government-funded research: a great way to share. <em>Circulation</em>. 2015;131(1):17-18. doi:10.1161/CIRCULATIONAHA.114.014204.</p>
|
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|
||
<p class="footnote"><sup>14</sup>Kannel WB, Wolf PA, Verter J, McNamara PM. Epidemiologic assessment of the role of blood pressure in stroke. The Framingham study. <em>JAMA</em>. 1970;214(2):301-310.</p>
|
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|
||
<p class="footnote"><sup>15</sup>Feinleib M, Kannel WB, Garrison RJ, Mcnamara PM, Castelli WP. The Framingham Offspring Study. Design and Preliminary Data1. <em>Prev Med (Baltim)</em>. 1975;4(5):18-525.</p>
|
||
|
||
<p class="footnote"><sup>16</sup>Kannel WB, Hjortland MC, McNamara PM, Gordon T. Menopause and risk of cardiovascular disease: the Framingham study. <em>Ann Intern Med</em>. 1976;85(4):447-452.</p>
|
||
|
||
<p class="footnote"><sup>17</sup>Wolf PA, Kannel WB, McGee DL, Meeks SL, Bharucha NE, McNamara PM. Duration of atrial fibrillation and imminence of stroke: the Framingham study. <em>Stroke</em>. 14(5):664-667.</p>
|
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|
||
<p class="footnote"><sup>18</sup>Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. <em>Stroke</em>. 1991;22(8):983-988. doi:10.1161/01.STR.22.8.983.</p>
|
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||
<p class="footnote"><sup>19</sup>Lowering Blood Cholesterol To Prevent Heart Disease. NIH Consens Statement. <em>Arteriosclerosis</em>. 1985;5(4):404-12.</p>
|
||
|
||
<p class="footnote"><sup>20</sup>Hannan MT, Felson DT, Dawson-Hughes B, et al. Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. <em>J Bone Miner Res</em>. 2000;15(4):710-720. doi:10.1359/jbmr.2000.15.4.710.</p>
|
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<p class="footnote"><sup>21</sup>Farmer ME, White LR, Abbott RD, et al. Blood pressure and cognitive performance. The Framingham Study. <em>Am J Epidemiol</em>. 1987;126(6):1103-1114.</p>
|
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||
<p class="footnote"><sup>22</sup>Elias MF, D’Agostino RB, Elias PK, Wolf PA. Neuropsychological test performance, cognitive functioning, blood pressure, and age: the Framingham Heart Study. <em>Exp Aging Res</em>. 1995;21(4):369-391. doi:10.1080/03610739508253991.</p>
|
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||
<p class="footnote"><sup>23</sup>Elias PK, D’Agostino RB, Elias MF, Wolf PA. Blood pressure, hypertension, and age as risk factors for poor cognitive performance. <em>Exp Aging Res</em>. 1995;21(4):393-417. doi:10.1080/03610739508253992.</p>
|
||
|
||
<p class="footnote"><sup>24</sup>Levy D, Garrison R, et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. <em>New Engl J Med</em>. 1990;322(22):1561-6.</p>
|
||
|
||
<p class="footnote"><sup>25</sup>Benjamin EJ, Wolf PA, Agostino RBD, Silbershatz H, Kannel WB, Levy D. Clinical Investigation and Reports Impact of Atrial Fibrillation on the Risk of Death The Framingham Heart Study. <em>Circulation</em>. 1998;98(10):946-953.</p>
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||
<p class="footnote"><sup>26</sup>Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. <em>Circulation</em>. 1998;97(18):1837-1847.</p>
|
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||
<p class="footnote"><sup>27</sup>Splansky GL, Corey D, Yang Q, et al. The Third Generation Cohort of the National Heart, Lung, and Blood Institute’s Framingham Heart Study: Design, Recruitment, and Initial Examination. <em>Am J Epidemiol</em>. 2007;165(11):1328-1335. doi:10.1093/aje/kwm021.</p>
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<p class="footnote"><sup>28</sup>Speliotes EK, Willer CJ, Berndt SI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. <em>Nat Genet</em>. 2010;42(11):937-948. doi:10.1038/ng.686.</p>
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<p class="footnote"><sup>29</sup>Psaty BM, O ’donnell CJ, Gudnason V, et al. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from five cohorts. doi:10.1161/CIRCGENETICS.108.829747.</p>
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<p class="footnote"><sup>30</sup>Benjamin I, Brown N, Burke G, et al. American Heart Association Cardiovascular Genome-Phenome Study: Foundational Basis and Program. <em>Circulation</em>. 2015;131(1):100-112. doi:10.1161/CIRCULATIONAHA.114.014190.</p>
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<p class="footnote"><sup>31</sup>Trans-Omics for Precision Medicine (TOPMed) Program - NHLBI, NIH. <a href="https://www.nhlbi.nih.gov/research/resources/nhlbi-precision-medicine-initiative/topmed">https://www.nhlbi.nih.gov/research/resources/nhlbi-precision-medicine-initiative/topmed</a>. Accessed September 22, 2017.</p>
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<p class="footnote"><sup>32</sup>Epidemiological Background and Design: The Framingham Study. https://www.framinghamheartstudy.org/about-fhs/background.php. Accessed September 22, 2017.</p>
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<p class="footnote"><sup>33</sup>Ma J, Ward EM, Siegel RL, Jemal A. Temporal Trends in Mortality in the United States, 1969-2013. <em>JAMA</em>. 2015;314(16):1731-1739. doi:10.1001/jama.2015.12319.</p>
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<p class="footnote"><sup>34</sup>Centers for Disease Control and Prevention. Achievements in Public Health, 1900-1999: Decline in Deaths from Heart Disease and Stroke — United States, 1900–1999. <em>Morb Mortal Wkly Rep</em>. 1999;48(30):649-656.</p>
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<p class="footnote"><sup>35</sup>St. Sauver JL, Warner DO, Yawn BP, et al. Why Patients Visit Their Doctors: Assessing the Most Prevalent Conditions in a Defined American Population. <em>Mayo Clin Proc</em>. 2013;88(1):56-67. doi:10.1016/j.mayocp.2012.08.020.</p>
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<p class="footnote"><sup>36</sup>Saklayen MG, Deshpande N V. Timeline of History of Hypertension Treatment. <em>Front Cardiovasc Med</em>. 2016;3:3. doi:10.3389/fcvm.2016.00003.</p>
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<p class="footnote"><sup>37</sup>Remington PL, Brownson RC, Centers for Disease Control and Prevention (CDC). Fifty years of progress in chronic disease epidemiology and control. <em>MMWR Suppl</em>. 2011;60(4):70-77.</p>
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<p class="footnote"><sup>38</sup>Ford ES, Ajani U a, Croft JB, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980-2000. <em>N Engl J Med</em>. 2007;356(23):2388-2398. doi:10.1097/sa.0b013e31815c1098.</p>
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<p class="footnote"><sup>39</sup>Levy D. 60 years studying heart-disease risk. <em>Nat Rev Drug Discov</em>. 2008;7(9):715-715. doi:10.1038/nrd2667.</p>
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<p class="footnote"><sup>40</sup>Framingham Risk Functions. https://www.framinghamheartstudy.org/risk-functions/. Accessed September 22, 2017.</p>
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<p class="footnote"><sup>41</sup>Manton KG, Woodbury MA. Analysis of the Components of CHD Risk in the Framingham Study: New Multivariate Procedures for the Analysis of Chronic Disease Development. <em>Comput Biomed Res</em>. 1979;12:109-123.</p>
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<p class="footnote"><sup>42</sup>Murphy KM, Topel RH. The Value of Health and Longevity. <em>J Polit Econ</em>. 2006;114(5):871-904. doi:10.1086/508033.</p>
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<p class="footnote"><sup>43</sup>Cutler DM, Rosen AB, Vijan S. The Value of Medical Spending in the United States, 1960–2000. <em>N Engl J Med</em>. 2006;355(9):920-927. doi:doi:10.1056/NEJMsa054744.</p>
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<p class="footnote"><sup>44</sup>Bibliography | Framingham Heart Study. <a href="https://www.framinghamheartstudy.org/fhs-bibliography/index.php">https://www.framinghamheartstudy.org/fhs-bibliography/index.php</a>. Accessed September 22, 2017.</p>
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<p class="footnote"><sup>45</sup>dbGaP | phs000007.v29.p10 | Framingham Cohort. <a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000007.v29.p10">https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000007.v29.p10</a>. Accessed September 22, 2017.</p>
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<p class="footnote"><sup>46</sup>For Researchers | Framingham Heart Study. <a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000007.v29.p10">https://www.framinghamheartstudy.org/researchers/index.php</a>. Accessed September 22, 2017.</p>
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<p class="footnote"><sup>47</sup>Writing Group Members, Mozaffarian D, Benjamin EJ, et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. <em>Circulation</em>. 2016;133(4):e38-60. doi:10.1161/CIR.0000000000000350.</p>
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</div>
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<h4 class="collapsible-trigger">Related Resources on the Framingham Heart Study and Cardiovascular Disease</h4>
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<div class="collapsible-content">
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<ul>
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<li><a href="http://www.framinghamheartstudy.org">The Framingham Heart Study Website</a></li>
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<li><a href="https://www.nhlbi.nih.gov/science/framingham-heart-study-fhs">NHLBI — About the Framingham Heart Study</a></li>
|
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<li><a href="https://www.cdc.gov/heartdisease/index.htm">CDC — Heart Disease Information</a></li>
|
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<li><a href="https://www.cdc.gov/stroke/index.htm">CDC — Stroke Information</a></li>
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</ul>
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</div>
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</div>
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</div>
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<h2>Understanding Immune Cells and Inflammation: Opening New Treatment Avenues for Rheumatoid Arthritis and Other Conditions</h2>
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<p><a class="media-border no-tag" href="/sites/default/files/about-nih/impact/immune-cells-inflammation-case-study.pdf"><div class="media media-element-container media-featured_media"><div class="ds-1col file file-image file-image-jpeg view-mode-featured_media clearfix">
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</div></a></p>
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<p>Discovery of the JAK-STAT molecular pathway in the early 1990s was a landmark advance explaining how cells sense and respond to their immediate environment. <a href="/sites/default/files/about-nih/impact/immune-cells-inflammation-case-study.pdf">Read the story of how NIH research set a foundation for the development of a new family of drugs, one of which provides a new option for people with rheumatoid arthritis who aren’t helped by older drugs.</a></p>
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<div class="collapsible">
|
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<h3 class="collapsible-trigger">Additional materials</h3>
|
||
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||
<div class="collapsible-content">
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<h4 class="collapsible-trigger">References</h4>
|
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<div class="collapsible-content">
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||
<p class="footnote"><sup>1</sup><a href="http://www.ncbi.nlm.nih.gov/pubmed/1848670">Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase.</a> Wilks AF, Harpur AG, Kurban RR, Ralph SJ, Zürcher G, Ziemiecki A. Mol Cell Biol. 1991 Apr;11(4):2057-65. PMID: 1848670</p>
|
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|
||
<p class="footnote"><sup>2</sup>Examples include:</p>
|
||
|
||
<p class="footnote"><a href="http://www.ncbi.nlm.nih.gov/pubmed/1386289">A protein tyrosine kinase in the interferon alpha/beta signaling pathway.</a> Velazquez L, Fellous M, Stark GR, Pellegrini S. Cell. 1992 Jul 24;70(2):313-22. PMID: 1386289</p>
|
||
|
||
<p class="footnote"><a href="http://www.ncbi.nlm.nih.gov/pubmed/8272873">Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components.</a> Stahl N, Boulton TG, Farruggella T, Ip NY, Davis S, Witthuhn BA, Quelle FW, Silvennoinen O, Barbieri G, Pellegrini S, et al. Science. 1994 Jan 7;263(5143):92-5. PMID: 8272873</p>
|
||
|
||
<p class="footnote"><a href="http://www.ncbi.nlm.nih.gov/pubmed/7504784">Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins.</a> Shuai K, Ziemiecki A, Wilks AF, Harpur AG, Sadowski HB, Gilman MZ, Darnell JE. Nature. 1993 Dec 9;366(6455):580-3. PMID: 7504784</p>
|
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||
<p class="footnote"><sup>3</sup><a href="http://www.ncbi.nlm.nih.gov/pubmed/8143863">Molecular cloning of rat JAK3, a novel member of the JAK family of protein tyrosine kinases.</a> Takahashi T, Shirasawa T. FEBS Lett. 1994 Apr 4;342(2):124-8. PMID: 8143863</p>
|
||
|
||
<p class="footnote"><a href="http://www.ncbi.nlm.nih.gov/pubmed/8022790">Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes.</a> Kawamura M, McVicar DW, Johnston JA, Blake TB, Chen YQ, Lal BK, Lloyd AR, Kelvin DJ, Staples JE, Ortaldo JR, et al. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6374-8. PMID: 8022790</p>
|
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||
<p class="footnote"><a href="http://www.ncbi.nlm.nih.gov/pubmed/7518579">JAK3: a novel JAK kinase associated with terminal differentiation of hematopoietic cells.</a> Rane SG, Reddy EP. Oncogene. 1994 Aug;9(8):2415-23. PMID: 7518579</p>
|
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|
||
<p class="footnote"><a href="http://www.ncbi.nlm.nih.gov/pubmed/8022485">Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2.</a> Johnston JA, Kawamura M, Kirken RA, Chen YQ, Blake TB, Shibuya K, Ortaldo JR, McVicar DW, O'Shea JJ. Nature. 1994 Jul 14;370(6485):151-3. PMID: 8022485</p>
|
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|
||
<p class="footnote"><sup>4</sup><a href="http://www.ncbi.nlm.nih.gov/pubmed/7481768">Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development.</a> Russell SM, Tayebi N, Nakajima H, Riedy MC, Roberts JL, Aman MJ, Migone TS, Noguchi M, Markert ML, Buckley RH, O'Shea JJ, Leonard WJ. Science. 1995 Nov 3;270(5237):797-800. PMID: 7481768</p>
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|
||
<p class="footnote"><a href="http://www.ncbi.nlm.nih.gov/pubmed/7659163">Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID).</a> Macchi P, Villa A, Giliani S, Sacco MG, Frattini A, Porta F, Ugazio AG, Johnston JA, Candotti F, O'Shea JJ, et al. Nature. 1995 Sep 7;377(6544):65-8. PMID: 7659163</p>
|
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<p class="footnote"><sup>5</sup><a href="http://www.ncbi.nlm.nih.gov/pubmed/7594533">Regulation of JAK3 expression and activation in human B cells and B cell malignancies.</a> Tortolani PJ, Lal BK, Riva A, Johnston JA, Chen YQ, Reaman GH, Beckwith M, Longo D, Ortaldo JR, Bhatia K, McGrath I, Kehrl J, Tuscano J, McVicar DW, O'Shea JJ. J Immunol. 1995 Dec 1;155(11):5220-6. PMID: 7594533</p>
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<p class="footnote"><sup>6</sup><a href="http://www.ncbi.nlm.nih.gov/pubmed/9192665">The amino terminus of JAK3 is necessary and sufficient for binding to the common gamma chain and confers the ability to transmit interleukin 2-mediated signals.</a> Chen M, Cheng A, Chen YQ, Hymel A, Hanson EP, Kimmel L, Minami Y, Taniguchi T, Changelian PS, O'Shea JJ. Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6910-5. PMID: 9192665</p>
|
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<p class="footnote"><a href="http://www.ncbi.nlm.nih.gov/pubmed/9391116">Distinct tyrosine phosphorylation sites in JAK3 kinase domain positively and negatively regulate its enzymatic activity.</a> Zhou YJ, Hanson EP, Chen YQ, Magnuson K, Chen M, Swann PG, Wange RL, Changelian PS, O'Shea JJ. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13850-5. PMID: 9391116</p>
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<p class="footnote"><a href="http://www.ncbi.nlm.nih.gov/pubmed/11741532">Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases.</a> Zhou YJ, Chen M, Cusack NA, Kimmel LH, Magnuson KS, Boyd JG, Lin W, Roberts JL, Lengi A, Buckley RH, Geahlen RL, Candotti F, Gadina M, Changelian PS, O'Shea JJ. Mol Cell. 2001 Nov;8(5):959-69. PMID: 11741532</p>
|
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|
||
<p class="footnote"><a href="http://www.ncbi.nlm.nih.gov/pubmed/21383241">Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550).</a> Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW, Warner JD, Tanaka M, Steward-Tharp SM, Gadina M, Thomas CJ, Minnerly JC, Storer CE, LaBranche TP, Radi ZA, Dowty ME, Head RD, Meyer DM, Kishore N, O'Shea JJ. J Immunol. 2011 Apr 1;186(7):4234-43. doi: 10.4049/jimmunol.1003668. Epub 2011 Mar 7. PMID: 21383241</p>
|
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|
||
<p class="footnote"><sup>7</sup><a href="http://www.ncbi.nlm.nih.gov/pubmed/14593182">Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor.</a> Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH, Rizzuti BJ, Sawyer PS, Perry BD, Brissette WH, McCurdy SP, Kudlacz EM, Conklyn MJ, Elliott EA, Koslov ER, Fisher MB, Strelevitz TJ, Yoon K, Whipple DA, Sun J, Munchhof MJ, Doty JL, Casavant JM, Blumenkopf TA, Hines M, Brown MF, Lillie BM, Subramanyam C, Shang-Poa C, Milici AJ, Beckius GE, Moyer JD, Su C, Woodworth TG, Gaweco AS, Beals CR, Littman BH, Fisher DA, Smith JF, Zagouras P, Magna HA, Saltarelli MJ, Johnson KS, Nelms LF, Des Etages SG, Hayes LS, Kawabata TT, Finco-Kent D, Baker DL, Larson M, Si MS, Paniagua R, Higgins J, Holm B, Reitz B, Zhou YJ, Morris RE, O'Shea JJ, Borie DC. Science. 2003 Oct 31;302(5646):875-8. PMID: 14593182</p>
|
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|
||
<p class="footnote"><sup>8</sup><a href="http://www.ncbi.nlm.nih.gov/pubmed/25686607">Super-enhancers delineate disease-associated regulatory nodes in T cells.</a> Vahedi G, Kanno Y, Furumoto Y, Jiang K, Parker SC, Erdos MR, Davis SR, Roychoudhuri R, Restifo NP, Gadina M, Tang Z, Ruan Y, Collins FS, Sartorelli V, O'Shea JJ. Nature. 2015 Apr 23;520(7548):558-62. doi: 10.1038/nature14154. Epub 2015 Feb 16. PMID: 25686607</p>
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|
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<p class="footnote"><sup>9</sup>ClinicalTrials.gov Identifier: <a href="https://www.clinicaltrials.gov/ct2/show/NCT02535689">NCT02535689</a></p>
|
||
|
||
<p class="footnote"><sup>10</sup>Reviewed in <a href="http://www.ncbi.nlm.nih.gov/pubmed/25587654">The JAK-STAT pathway: impact on human disease and therapeutic intervention.</a> O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. Annu Rev Med. 2015;66:311-28. doi: 10.1146/annurev-med-051113-024537. Review. PMID: 25587654</p>
|
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|
||
<p class="footnote"><sup>11</sup><a href="http://www.ncbi.nlm.nih.gov/pubmed/26633291">Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases.</a> Schwartz DM, Bonelli M, Gadina M, O'Shea JJ. Nat Rev Rheumatol. 2016 Jan;12(1):25-36. doi: 10.1038/nrrheum.2015.167. Epub 2015 Dec 3. Review. PMID: 26633291</p>
|
||
</div>
|
||
|
||
<h4 class="collapsible-trigger">Related Resources on Rheumatoid Arthritis and Tofacitinib</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<ul>
|
||
<li><a href="https://www.niams.nih.gov/health_info/rheumatic_disease/rheumatoid_arthritis_ff.asp">What is Rheumatoid Arthritis?</a></li>
|
||
<li><a href="https://www.niams.nih.gov/Health_info/Rheumatic_Disease/">Handout on Health: Rheumatoid Arthritis</a></li>
|
||
<li><a href="https://www.niams.nih.gov/newsroom/research-briefs/tofacitinib-shows-potential-treating-lupus">Tofacitinib Shows Potential for Treating Lupus</a> (2017)</li>
|
||
<li><a href="https://www.niams.nih.gov/News_and_Events/Spotlight_on_Research/2016/drug_hair_growth.asp">Two Drugs That Treat Rheumatoid Arthritis and Blood Cancers Shown to Promote Hair Growth</a> (April 2016)</li>
|
||
<li><a href="https://www.niams.nih.gov/News_and_Events/Press_Releases/2015/2_17.asp">NIH researchers reveal link between powerful gene regulatory elements and autoimmune diseases: Findings point to potential drug targets</a> (February 2015)</li>
|
||
</ul>
|
||
</div>
|
||
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|
||
</div>
|
||
|
||
<h2>Rare Autoinflammatory Diseases Research: Saving Lives, Giving Hope to Families</h2>
|
||
|
||
<p><a class="media-border no-tag" href="/sites/default/files/about-nih/impact/rare-autoinflammatory-diseases-case-study.pdf"><div class="media media-element-container media-featured_media"><div class="ds-1col file file-image file-image-jpeg view-mode-featured_media clearfix">
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<p>Autoinflammatory diseases are a relatively new category of conditions that differ from autoimmune diseases. Although both kinds of illnesses happen when the immune system attacks the body’s own tissues, they occur by different processes. <a href="/sites/default/files/about-nih/impact/rare-autoinflammatory-diseases-case-study.pdf">Read the story of how NIH researchers played a vital role in differentiating between the two groups of diseases, discovering the molecular causes for different autoinflammatory diseases, and identifying life-saving treatments</a></p>
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<h3 class="collapsible-trigger">Additional materials</h3>
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<p class="footnote"><sup>1</sup>Examples include: Siegal S. <a href="http://annals.org/article.aspx?articleid=673191">Benign paroxysmal peritonitis.</a> <em>Ann Intern Med. </em>1945;23(1):1-21, as cited in Centola M, Aksentijevich I, Kastner DL. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9735379">The hereditary periodic fever syndromes: molecular analysis of a new family of inflammatory diseases.</a> <em>Hum Mol Genet</em>. 1998;7(10):1581-1588. PMID: 9735379 Reimann HA. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18920089">Periodic disease; a probable syndrome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia.</a> <em>J Am Med Assoc</em>. 1948;136(4):239-244. PMID: 18920089/p></p>
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<p class="footnote"><sup>2</sup>One of many examples: Wright DG, Wolff SM, Fauci AS, Alling DW. <a href="http://annals.org/article.aspx?articleid=690856">Efficacy of intermittent colchicine therapy in familial Mediterranean fever</a>. <em>Ann Intern Med</em>. 1977;86(2):162-165.</p>
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<p class="footnote"><sup>3</sup>Williamson LM, Hull D, Mehta R, Reeves WG, Robinson BH, Toghill PJ. <a href="http://www.ncbi.nlm.nih.gov/pubmed/7156325">Familial Hibernian fever.</a> <em>Q J Med</em>. 1982;51(204):469-480. PMID: 7156325</p>
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<p class="footnote"><sup>4</sup>Pras E, Aksentijevich I, Gruberg L, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/1579134">Mapping of a gene causing familial Mediterranean fever to the short arm of chromosome 16.</a> <em>N Engl J Med</em>. 1992 Jun 4;326(23):1509-1513. PMID: 1579134<br />
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International FMF Consortium. <a href="http://www.sciencedirect.com/science/article/pii/S0092867400805395">Ancient missense mutations in a new member of the <em>RoRet</em> gene family are likely to cause familial Mediterranean fever</a>. <em>Cell</em> 1997;90(4):797-807. PMID: 9288758<br />
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French FMF Consortium. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9288094">A candidate gene for familial Mediterranean fever.</a> <em>Nat Genet</em>. 1997;17(1):25-31. PMID: 9288094</p>
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<p class="footnote"><sup>5</sup>McDermott MF, Aksentijevich I, Galon J, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10199409">Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes.</a> <em>Cell</em>. 1999;97(1):133-144. PMID: 10199409</p>
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<p class="footnote"><sup>6</sup>Aksentijevich I, Nowak M, Mallah M, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12483741">De novo <em>CIAS1</em> mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases.</a> <em>Arthritis Rheum</em>. 2002;46(12):3340-3348. PMID: 12483741<br />
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Feldmann J, Prieur A-M, Quartier P, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12032915">Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in <em>CIAS1</em>, a gene highly expressed in polymorphonuclear cells and chondrocytes.</a> <em>Am J Hum Genet</em>. 2002;71(1):198-203. PMID: 12032915</p>
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<p class="footnote"><sup>7</sup>Goldbach-Mansky R, Dailey NJ, Canna SW, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16899778">Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition.</a> <em>N Engl J Med</em>. 2006;355(6):581-592. PMID: 16899778</p>
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<p class="footnote"><sup>8</sup>Booty MG, Chae JJ, Masters SL, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19479870">Familial Mediterranean fever with a single <em>MEFV</em> mutation: where is the second hit?</a> <em>Arthritis Rheum</em>. 2009;60(6):1851-1861. PMID: 19479870</p>
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<p class="footnote"><sup>9</sup>Aksentijevich I, Masters SL, Ferguson PJ, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19494218">An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist.</a> <em>N Engl J Med</em>. 2009;360(23):2426-2437. PMID: 19494218</p>
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<p class="footnote"><sup>10</sup>Liu Y, Ramot Y, Torrelo A, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21953331">Mutations in proteasome subunit β type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity.</a> <em>Arthritis Rheum</em>. 2012;64(3):895-907. PMID: 21953331</p>
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<p class="footnote"><sup>11</sup>Sibley CH, Plass N, Snow J, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/22294344">Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes.</a> <em>Arthritis Rheum</em>. 2012;64(7):2375-86. PMID: 22294344</p>
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<p class="footnote"><sup>12</sup>Jesus AA, Goldbach-Mansky R. <a href="http://www.ncbi.nlm.nih.gov/pubmed/24422572">IL-1 blockade in autoinflammatory syndromes.</a> <em>Annu Rev Med</em>. 2014;65:223-244. PMID: 24422572</p>
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<p class="footnote"><sup>13</sup>Liu Y, Jesus AA, Marrero B, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/25029335">Activated STING in a vascular and pulmonary syndrome.</a> <em>N Engl J Med</em>. 2014;371(6):507-518. PMID: 25029335</p>
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<p class="footnote"><sup>14</sup>De Jesus AA, Canna SW, Liu Y, Goldbach-Mansky R. <a href="http://www.ncbi.nlm.nih.gov/pubmed/25706096">Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling.</a> <em>Annu Rev Immunol</em>. 2015;33:823-874. PMID: 25706096</p>
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<p class="footnote"><sup>15</sup>De Jesus AA, Canna SW, Liu Y, Goldbach-Mansky R. <a href="http://www.ncbi.nlm.nih.gov/pubmed/25706096">Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling.</a> <em>Annu Rev Immunol</em>. 2015;33:823-874. PMID: 25706096</p>
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<p class="footnote"><sup>16</sup>National Institutes of Health. <a href="http://www.niams.nih.gov/News_and_Events/Press_Releases/2014/7_17.asp">NIH scientists identify gene linked to fatal inflammatory disease in children</a>. NIAMS Press Releases. Published July 17, 2014. Accessed August 1, 2016.</p>
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<p class="footnote"><sup>17</sup>National Institute of Arthritis and Musculoskeletal and Skin Diseases. <a href="http://www.niams.nih.gov/News_and_Events/Spotlight_on_Research/2013/anakinra_nomid.asp">NIH study contributes to approval of promising treatment for genetic inflammatory disorder</a>. Spotlight on Research. Published March 2013. Accessed August 1, 2016.</p>
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<p class="footnote"><sup>18</sup>National Institute of Arthritis and Musculoskeletal and Skin Diseases. <a href="http://www.niams.nih.gov/Health_Info/Autoinflammatory/default.asp#5">Deficiency of the Interleukin-1 Receptor Antagonist (DIRA)</a>. Autoinflammatory Diseases. Published March 2016. Accessed August 1, 2016.</p>
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<p class="footnote"><sup>19</sup>National Institutes of Health. <a href="http://www.niams.nih.gov/News_and_Events/Press_Releases/2011/10_31.asp">NIH scientists discover link among spectrum of childhood diseases</a>. NIAMS Press Releases. Published October 31, 2011. Accessed August 1, 2016.</p>
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<p class="footnote"><sup>20</sup>U.S. National Library of Medicine. <a href="https://ghr.nlm.nih.gov/condition/familial-mediterranean-fever#statistics">Familial Mediterranean fever: frequency</a>. Genetics Home Reference. Updated July 26, 2016. Accessed August 1, 2016.</p>
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<p class="footnote"><sup>21</sup>Jesus AA, Goldbach-Mansky R. <a href="http://www.ncbi.nlm.nih.gov/pubmed/24422572">IL-1 blockade in autoinflammatory syndromes.</a> <em>Annu Rev Med</em>. 2014;65:223-244. PMID: 24422572</p>
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<p class="footnote"><sup>22</sup>U.S. National Library of Medicine. <a href="https://ghr.nlm.nih.gov/condition/tumor-necrosis-factor-receptor-associated-periodic-syndrome#statistics">Tumor necrosis factor receptor-associated periodic syndrome: Frequency</a>. Genetics Home Reference. Updated July 26, 2016. Accessed August 1, 2016.</p>
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<p class="footnote"><sup>23</sup>Bulua AC, Simon A, Maddipati R, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21282379">Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS).</a> <em>J Exp Med</em>. 2011;208(3):519-533. PMID: 21282379</p>
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<p class="footnote"><sup>24</sup>U.S. National Library of Medicine. <a href="https://ghr.nlm.nih.gov/condition/neonatal-onset-multisystem-inflammatory-disease#statistics">Neonatal onset multisystem inflammatory disease: Frequency</a>. Genetics Home Reference. Updated July 26, 2016. Accessed August 1, 2016.<br />
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Collins F. <a href="https://directorsblog.nih.gov/2013/04/09/meet-alex-before-and-after-nih-clinical-trial/#more-1046">Meet Alex—Before and after NIH clinical trial</a>. NIH Director’s blog. Published April 9, 2013. Accessed May 23, 2016</p>
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<h4 class="collapsible-trigger">Related Resources on Rare Autoinflammatory Diseases Research</h4>
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<li><a href="http://www.niams.nih.gov/Health_Info/Autoinflammatory/">Understanding Autoinflammatory Diseases</a></li>
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<li><a href="http://directorsblog.nih.gov/2013/04/09/meet-alex-before-and-after-nih-clinical-trial/">NIH Director’s Blog: Meet Alex—Before and After NIH Clinical Trial</a></li>
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<li><a href="http://niams.nih.gov/Research/Ongoing_Research/Branch_Lab/Clinical_Director/default.asp#fever">Autoinflammatory Diseases Studies at the NIH Clinical Center</a></li>
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<li><a href="http://niams.nih.gov/Research/Ongoing_Research/Branch_Lab/Pediatric_Translational_Research/tads_areas.asp">Autoinflammatory Diseases Research at NIAMS</a></li>
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<h2>Neurostimulation Technologies: Harnessing Electricity To Treat Lost Neural Function</h2>
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<p>The human nervous system is so complex and fundamental, that until recently, it was believed that any damage to it was irreversible. NIH support and years of scientific effort, however, have begun to make it possible to compensate for lost function using electrical stimulation to enhance nervous system activity. <a href="/sites/default/files/about-nih/impact/neurostimulation-technologies-case-study.pdf">Read the story of how NIH-supported research helped harness the electrical nature of the nervous system to develop cutting-edge therapies</a></p>
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<h3 class="collapsible-trigger">Additional materials</h3>
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<h4 class="collapsible-trigger">References</h4>
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<p class="footnote"><sup>1</sup>Donald R. McNeal, “2000 years of electrical stimulation” in F. Terry Hambrecht and James B. Reswick, eds., <em>Functional Electrical StimulationApplications in Neural Prosthesis </em>(New York and BaselMacel Dekker, Inc., 1977) pp. 3-35.</p>
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<p class="footnote"><sup>2</sup>Thompson DM, Koppes AN, Hardy JG, Schmidt CE. <a href="https://www.ncbi.nlm.nih.gov/pubmed/25014787">Electrical stimuli in the central nervous system microenvironment</a>. <em>Annual review of biomedical engineering</em>. 2014;16:397-430.</p>
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<p class="footnote"><sup>3</sup>Aquilina O. <a href="https://www.ncbi.nlm.nih.gov/pubmed/22368662">A brief history of cardiac pacing</a>. <em>Images in paediatric cardiology.</em> 2006;8(2):17-81.</p>
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<p class="footnote"><sup>4</sup>FDA Premarket Approval P8300693M: Brand Cochlear Implant System/House Design</p>
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<p class="footnote"><sup>5</sup>FDA Premarket Approval P960009: Medtronic Activa Tremor Control System and Supplement S007: Medtronic Activa Parkinson’s Control System</p>
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<p class="footnote"><sup>6</sup><a href="http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm343162.htm">http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm343162.htm</a></p>
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<p class="footnote"><sup>7</sup>House WF, Urban J. <a href="https://www.ncbi.nlm.nih.gov/pubmed/4721186">Long term results of electrode implantation and electronic stimulation of the cochlea in man</a>. <em>The Annals of otology, rhinology, and laryngology.</em> 1973;82(4):504-517.</p>
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<p class="footnote"><sup>8</sup><a href="http://www.nidcd.nih.gov/health/hearing/pages/coch.aspx">http://www.nidcd.nih.gov/health/hearing/pages/coch.aspx</a></p>
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<p class="footnote"><sup>9</sup>Sekhon LH, Fehlings MG. <a href="https://www.ncbi.nlm.nih.gov/pubmed/11805601">Epidemiology, demographics, and pathophysiology of acute spinal cord injury</a>. <em>Spine</em>. 2001;26(24 Suppl):S2-12.</p>
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<p class="footnote"><sup>10</sup><a href="http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm343162.htm">http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm343162.htm</a></p>
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<p class="footnote"><sup>11</sup>Gerasimenko YP, Lu DC, Modaber M, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/26077679">Noninvasive Reactivation of Motor Descending Control after Paralysis</a>. <em>Journal of neurotrauma. </em>2015;32(24):1968-1980.</p>
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<p class="footnote"><sup>12</sup>Donald R. McNeal, “2000 years of electrical stimulation” in F. Terry Hambrecht and James B. Reswick, eds., Functional Electrical StimulationApplications in Neural Prosthesis (New York and BaselMacel Dekker, Inc., 1977) pp. 3-35.</p>
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<p class="footnote"><sup>13</sup>Penfield W. <a href="http://archneurpsyc.jamanetwork.com/article.aspx?articleid=646900">Epilepsy and surgical therapy</a>. <em>Archives of Neurology & Psychiatry. </em>1936;36(3):449-484.</p>
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<p class="footnote"><sup>14</sup>Aquilina O. <a href="https://www.ncbi.nlm.nih.gov/pubmed/22368662">A brief history of cardiac pacing</a>. <em>Images in paediatric cardiology.</em> 2006;8(2):17-81.</p>
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<p class="footnote"><sup>15</sup>Djourno A, Eyries C. <a href="http://www.ncbi.nlm.nih.gov/pubmed/13484817">Auditory prosthesis by means of a distant electrical stimulation of the sensory nerve with the use of an indwelt coiling</a>. <em>La Presse medicale. </em>1957;65(63):1417.</p>
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<p class="footnote"><sup>16</sup>Chatrian GE, Petersen MC, Uihlein A. <a href="http://www.ncbi.nlm.nih.gov/pubmed/13809433">Electrical stimulation of the human brain through implanted electrodespreliminary observations</a>. <em>Diseases of the nervous system. </em>1960;21:321-326.</p>
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<p class="footnote"><sup>17</sup>House WF, Urban J. <a href="https://www.ncbi.nlm.nih.gov/pubmed/4721186">Long term results of electrode implantation and electronic stimulation of the cochlea in man</a>. <em>The Annals of otology, rhinology, and laryngology.</em> 1973;82(4):504-517.</p>
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<p class="footnote"><sup>18</sup>Simmons FB, Mongeon CJ, Lewis WR, Huntington DA. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14135073">Electrical Stimulation of Acoustical Nerve and Inferior Colliculus</a>. <em>Archives of otolaryngology. </em>1964;79:559-568.</p>
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<p class="footnote"><sup>19</sup>Kumar K, Rizvi S. <a href="http://www.ncbi.nlm.nih.gov/pubmed/24338734">Historical and present state of neuromodulation in chronic pain</a>. <em>Current pain and headache reports. </em>2014;18(1):387.</p>
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<p class="footnote"><sup>20</sup>DeLong MR. <a href="http://www.ncbi.nlm.nih.gov/pubmed/4997823">Activity of pallidal neurons during movement</a>. <em>Journal of neurophysiology. </em>1971;34(3):414-427.</p>
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<p class="footnote"><sup>21</sup>DeLong MR. <a href="http://www.ncbi.nlm.nih.gov/pubmed/4624486">Activity of basal ganglia neurons during movement</a>. <em>Brain research. </em>1972;40(1):127-135.</p>
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<p class="footnote"><sup>22</sup>DeLong MR. <a href="http://www.ncbi.nlm.nih.gov/pubmed/4631890">Putamen: activity of single units during slow and rapid arm movements</a>. <em>Science. </em>1973;179(4079):1240-1242.</p>
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<p class="footnote"><sup>23</sup>House WF, Urban J. <a href="https://www.ncbi.nlm.nih.gov/pubmed/4721186">Long term results of electrode implantation and electronic stimulation of the cochlea in man</a>. <em>The Annals of otology, rhinology, and laryngology.</em> 1973;82(4):504-517.</p>
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<p class="footnote"><sup>24</sup>Hosobuchi Y, Adams JE, Rutkin B. <a href="http://www.ncbi.nlm.nih.gov/pubmed/4591720">Chronic thalamic stimulation for the control of facial anesthesia dolorosa</a>. <em>Archives of neurology. </em>1973;29(3):158-161., NIH training grant NS5593</p>
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|
||
<p class="footnote"><sup>25</sup>Mudry A, Mills M. <a href="http://www.ncbi.nlm.nih.gov/pubmed/23681026">The early history of the cochlear implant: a retrospective</a>. <em>JAMA otolaryngology-- head & neck surgery. </em>2013;139(5):446-453.</p>
|
||
|
||
<p class="footnote"><sup>26</sup>Clark G. <em>Cochlear Implants: Fundamentals and Applications.</em> Springer; 2003.</p>
|
||
|
||
<p class="footnote"><sup>27</sup>Clark G, Cowan RSC, Dowell RC. <em>Cochlear Implantation for Infants and Children: Advances.</em> Singular Publishing Group; 1997.</p>
|
||
|
||
<p class="footnote"><sup>28</sup>Davis GC, Williams AC, Markey SP, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/298352">Chronic Parkinsonism secondary to intravenous injection of meperidine analogues</a>. <em>Psychiatry research. </em>1979;1(3):249-254.</p>
|
||
|
||
<p class="footnote"><sup>29</sup>Langston JW, Ballard P, Tetrud JW, Irwin I. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6823561">Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis</a>. <em>Science. </em>1983;219(4587):979-980.</p>
|
||
|
||
<p class="footnote"><sup>30</sup>Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6192438">A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine</a>. <em>Proceedings of the National Academy of Sciences of the United States of America. </em>1983;80(14):4546-4550.</p>
|
||
|
||
<p class="footnote"><sup>31</sup>FDA Premarket Approvals P830069: 3M Brand Cochlear Implant System/House Design and P840024: Nucleus Multichannel Implantable Hearing Prosthesis</p>
|
||
|
||
<p class="footnote"><sup>32</sup>FDA Premarket Approval P890027: Nucleus 22 Channel Cochlear Implant Sys /Children</p>
|
||
|
||
<p class="footnote"><sup>33</sup>Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J. <a href="https://www.ncbi.nlm.nih.gov/pubmed/3329873">Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease</a>. <em>Applied neurophysiology. </em>1987;50(1-6):344-346.</p>
|
||
|
||
<p class="footnote"><sup>34</sup>Benabid AL, Pollak P, Gervason C, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/1671433">Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus</a>. <em>Lancet. </em>1991;337(8738):403-406.</p>
|
||
|
||
<p class="footnote"><sup>35</sup>Limousin P, Pollak P, Benazzouz A, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/7815888">Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation</a>. <em>Lancet. </em>1995;345(8942):91-95.</p>
|
||
|
||
<p class="footnote"><sup>36</sup>Limousin P, Krack P, Pollak P, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/9770557">Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease</a>. <em>The New England journal of medicine. </em>1998;339(16):1105-1111.</p>
|
||
|
||
<p class="footnote"><sup>37</sup><a href="http://professional.medtronic.com/pt/neuro/dbs-md/eff/data-and-clinical-outcomes/">Medtronic DBS Therapy for Parkinson's Disease and Essential Tremor Clinical Summary, 2013</a></p>
|
||
|
||
<p class="footnote"><sup>38</sup>Rise MT, W. KG, Inventors; Medtronic, Inc., assignee. <a href="http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=5716377.PN.&OS=PN/5716377&RS=PN/5716377">Method of treating movement disorders by brain stimulation</a>. US patent 5716377. February 10, 1998.</p>
|
||
|
||
<p class="footnote"><sup>39</sup>FDA Premarket Approval P960009, Supplement S007: Medtronic Activa Parkinson’s Control</p>
|
||
|
||
<p class="footnote"><sup>40</sup><a href="http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm125520.htm">http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm125520.htm</a></p>
|
||
|
||
<p class="footnote"><sup>41</sup>Harkema S, Gerasimenko Y, Hodes J, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/21601270">Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study</a>. <em>Lancet. </em>2011;377(9781):1938-1947.</p>
|
||
|
||
<p class="footnote"><sup>42</sup>Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. <a href="https://www.ncbi.nlm.nih.gov/pubmed/24713270">Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans</a>. <em>Brain: a journal of neurology. </em>2014;137(Pt 5):1394-1409.</p>
|
||
|
||
<p class="footnote"><sup>43</sup>Gerasimenko YP, Lu DC, Modaber M, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/26077679">Noninvasive Reactivation of Motor Descending Control after Paralysis</a>. <em>Journal of neurotrauma. </em>2015;32(24):1968-1980.</p>
|
||
|
||
<p class="footnote"><sup>44</sup><a href="http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm343162.htm">http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm343162.htm</a></p>
|
||
|
||
<p class="footnote"><sup>45</sup><a href="https://consensus.nih.gov/1995/1995CochlearImplants100html.htm">https://consensus.nih.gov/1995/1995CochlearImplants100html.htm</a></p>
|
||
|
||
<p class="footnote"><sup>46</sup><a href="http://www.nidcd.nih.gov/health/hearing/pages/coch.aspx">http://www.nidcd.nih.gov/health/hearing/pages/coch.aspx</a></p>
|
||
|
||
<p class="footnote"><sup>47</sup>Semenov YR, Yeh ST, Seshamani M, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/23558665">Age-dependent cost-utility of pediatric cochlear implantation</a>. <em>Ear and hearing. </em>2013;34(4):402-412.</p>
|
||
|
||
<p class="footnote"><sup>48</sup>Contrera KJ, Choi JS, Blake CR, Betz JF, Niparko JK, Lin FR. <a href="https://www.ncbi.nlm.nih.gov/pubmed/24518403">Rates of long-term cochlear implant use in children</a>. <em>Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. </em>2014;35(3):426-430.</p>
|
||
|
||
<p class="footnote"><sup>49</sup>Cheng AK, Rubin HR, Powe NR, Mellon NK, Francis HW, Niparko JK. <a href="https://www.ncbi.nlm.nih.gov/pubmed/10938174">Cost-utility analysis of the cochlear implant in children</a>. <em>Jama. </em>2000;284(7):850-856.</p>
|
||
|
||
<p class="footnote"><sup>50</sup>Semenov YR, Yeh ST, Seshamani M, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/23558665">Age-dependent cost-utility of pediatric cochlear implantation</a>. <em>Ear and hearing. </em>2013;34(4):402-412.</p>
|
||
|
||
<p class="footnote"><sup>51</sup><a href="http://www.laskerfoundation.org/awards/2014_c_description.htm">http://www.laskerfoundation.org/awards/2014_c_description.htm</a></p>
|
||
|
||
<p class="footnote"><sup>52</sup>Weaver FM, Follett K, Stern M, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/19126811">Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial</a>. <em>Jama. </em>2009;301(1):63-73.</p>
|
||
|
||
<p class="footnote"><sup>53</sup>ibid.</p>
|
||
|
||
<p class="footnote"><sup>54</sup>Rizzone MG, Fasano A, Daniele A, et al. <a href="https://www.ncbi.nlm.nih.gov/pubmed/24508574">Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: from the advanced phase towards the late stage of the disease?</a> <em>Parkinsonism & related disorders. </em>2014;20(4):376-381.</p>
|
||
|
||
<p class="footnote"><sup>55:</sup><a href="http://professional.medtronic.com/pt/neuro/dbs-md/eff/data-and-clinical-outcomes">http://professional.medtronic.com/pt/neuro/dbs-md/eff/data-and-clinical-outcomes</a></p>
|
||
|
||
<p class="footnote"><sup>56</sup><a href="http://www.laskerfoundation.org/awards/2014_c_description.htm">http://www.laskerfoundation.org/awards/2014_c_description.htm</a></p>
|
||
|
||
<p class="footnote"><sup>57</sup>Hariz M, Blomstedt P, Zrinzo L. <a href="https://www.ncbi.nlm.nih.gov/pubmed/24123327">Future of brain stimulation: new targets, new indications, new technology</a>. <em>Movement disorders: official journal of the Movement Disorder Society. </em>2013;28(13):1784-1792.</p>
|
||
|
||
<p class="footnote"><sup>58</sup><a href="http://braininitiative.nih.gov/about.htm">http://braininitiative.nih.gov/about.htm</a></p>
|
||
|
||
<p class="footnote"><sup>59</sup><a href="https://commonfund.nih.gov/sparc/index">https://commonfund.nih.gov/sparc/index</a></p>
|
||
|
||
<p class="footnote"><sup>60</sup>NIH Grant UH2NS095495, BRAIN initiative</p>
|
||
|
||
<p class="footnote"><sup>61</sup>NIH Grant U18EB021793, SPARC program</p>
|
||
|
||
<p class="footnote"><sup>62</sup><a href="http://news.berkeley.edu/2014/05/27/cnep-targets-brain-circuitry-to-treat-mental-disorders/">http://news.berkeley.edu/2014/05/27/cnep-targets-brain-circuitry-to-treat-mental-disorders/</a></p>
|
||
|
||
<p class="footnote"><sup>63</sup>NIH Grant UH3NS095554, BRAIN initiative</p>
|
||
</div>
|
||
|
||
<h4 class="collapsible-trigger">Appendix</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<p>The table below provides a more detailed list of selected milestones underlying this story’s “Research-to-Practice Milestones” (page 2 of the pdf), including the lead scientists, research institutions, funding sources, and scientific publications involved in each one.</p>
|
||
|
||
<p><strong>1950s–60s: Stimulating Nerves with Electricity</strong></p>
|
||
|
||
<table border="0" cellpadding="10" cellspacing="0" class="table-data-tight" summary=" Stimulating Nerves with Electricity">
|
||
<tbody>
|
||
<tr>
|
||
<th>Year</th>
|
||
<th>Description of Milestone</th>
|
||
<th>Primary Investigator(s)</th>
|
||
<th>Research Institution</th>
|
||
<th>Funding source (including NIH grant numbers where available)</th>
|
||
<th>Citation 1</th>
|
||
<th>Citation 2</th>
|
||
<th>Citation 3</th>
|
||
<th>Citation 4</th>
|
||
</tr>
|
||
<tr>
|
||
<td>1957</td>
|
||
<td>>Attempting to repair a facial nerve injury, scientists electrically stimulated the auditory nerve, causing the patient to perceive sounds and providing evidence that electrical stimulation might restore lost hearing.</td>
|
||
<td>Andre Djourno, Charles Eyries</td>
|
||
<td>Faculté de Médecine, Paris, France</td>
|
||
<td>Unknown, Not likely to be NIH</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/13484817">Djourno A, Eyries C. [Auditory prosthesis by means of a distant electrical stimulation of the sensory nerve with the use of an indwelt coiling]. La Presse medicale. 1957;65(63):1417.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1960</td>
|
||
<td>Researchers first tested the long-term safety and effectiveness of implanting electrodes in the human brain.</td>
|
||
<td>Alfred Uihlein</td>
|
||
<td>Mayo Clinic</td>
|
||
<td>Unknown, Not likely to be NIH</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/13809433">Chatrian GE, Petersen MC, Uihlein A. Electrical stimulation of the human brain through implanted electrodes: preliminary observations. Diseases of the nervous system. 1960;21:321-326.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1961</td>
|
||
<td>The first prototype single-channel cochlear implant is developed, and inserted into two subjects</td>
|
||
<td>William F. House and James Doyle</td>
|
||
<td>Private Practice, Los Angeles</td>
|
||
<td>Private</td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/4721186">House WF, Urban J. Long term results of electrode implantation and electronic stimulation of the cochlea in man. The Annals of otology, rhinology, and laryngology. 1973;82(4):504-517.</a></td>
|
||
<td>U.S. Patent 3449786 to James Doyle</td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1964</td>
|
||
<td>First NIH grant for cochlear implants funds a report on the effects of auditory nerve stimulation in a patient with normal hearing.</td>
|
||
<td>F. Blair Simmons</td>
|
||
<td>Stanford University</td>
|
||
<td>Funded by NIH grant NB 02167 from the National Institute of Neurological Diseases and Blindness (NINDB).</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/14135073">Simmons FB, Mongeon CJ, Lewis WR, Huntington DA. Electrical Stimulation of Acoustical Nerve and Inferior Colliculus. Archives of otolaryngology. 1964;79:559-568.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1968</td>
|
||
<td>Medtronic became the first company to introduce a spinal cord stimulation system as a treatment for chronic pain.</td>
|
||
<td>Unknown</td>
|
||
<td>Medtronic Corp</td>
|
||
<td>Private</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/24338734">Kumar K, Rizvi S. Historical and present state of neuromodulation in chronic pain. Current pain and headache reports. 2014;18(1):387.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
</tbody>
|
||
</table>
|
||
|
||
<p><strong>1970s–80s: Unlocking the Potential of Neurotechnology</strong></p>
|
||
|
||
<table border="0" cellpadding="10" cellspacing="0" class="table-data-tight" summary=" Unlocking the Potential of Neurotechnology">
|
||
<tbody>
|
||
<tr>
|
||
<th>Year</th>
|
||
<th>Description of Milestone</th>
|
||
<th>Primary Investigator(s)</th>
|
||
<th>Research Institution</th>
|
||
<th>Funding source (including NIH grant numbers where available)</th>
|
||
<th>Citation 1</th>
|
||
<th>Citation 2</th>
|
||
<th>Citation 3</th>
|
||
<th>Citation 4</th>
|
||
</tr>
|
||
<tr>
|
||
<td>1971-3</td>
|
||
<td>NIH researchers characterized the normal electrical function of deep brain areas involved in movement, which are affected in Parkinson’s</td>
|
||
<td>Mahlon DeLong</td>
|
||
<td>NIMH Laboratory of Neurophysiology</td>
|
||
<td>NIMH Intramural</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/4997823">DeLong MR. Activity of pallidal neurons during movement. Journal of neurophysiology. 1971;34(3):414-427.</a></td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/4624486">DeLong MR. Activity of basal ganglia neurons during movement. Brain research. 1972;40(1):127-135.</a></td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/4631890">DeLong MR. Putamen: activity of single units during slow and rapid arm movements. Science. 1973;179(4079):1240-1242.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1972</td>
|
||
<td>Early cochlear implants developed with a single electrode, and the first functional prototype implanted in a patient</td>
|
||
<td>William F. House</td>
|
||
<td>Private practice, Los Angeles</td>
|
||
<td>Private, included support from 3M</td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/4721186">House WF, Urban J. Long term results of electrode implantation and electronic stimulation of the cochlea in man. The Annals of otology, rhinology, and laryngology. 1973;82(4):504-517.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1973</td>
|
||
<td>Improving upon the pain relief provided by spinal cord stimulation, NIH-supported investigators developed the first long-term, implanted device to stimulate the brain</td>
|
||
<td>Yoshio Hosobuchi</td>
|
||
<td>UCSF</td>
|
||
<td>NIH training grant NS5593</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/4591720">Hosobuchi Y, Adams JE, Rutkin B. Chronic thalamic stimulation for the control of facial anesthesia dolorosa. Archives of neurology. 1973;29(3):158-161.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1976</td>
|
||
<td>The 1976 Bilger report suggests that cochlear implants could be a substantially more useful device for patients with hearing loss than traditional devices and methods.</td>
|
||
<td>Robert C. Bilger</td>
|
||
<td>Univ. of Pittsburgh</td>
|
||
<td>NIH Contract N01 NS-5-2331.</td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/405906">Bilger RC, Black FO, Hopkinson NT. Research plan for evaluating subjects presently fitted with implanted auditory prostheses. The Annals of otology, rhinology & laryngology. Supplement. 1977;86(3 Pt 2 Suppl 38):21-24.</a></td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/898520">Bilger RC, Black FO, Hopkinson NT, Myers EN. Implanted auditory prosthesis: an evaluation of subjects presently fitted with cochlear implants. Transactions. Section on Otolaryngology. American Academy of Ophthalmology and Otolaryngology. 1977;84(4 Pt 1):ORL-677-682.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1970s-80s</td>
|
||
<td>Several groups of academic researchers begin to partner with technology firms to form corporations in Australia, the U.S., and Europe focused on devices to restore hearing.Both industry and academic researchers focused on upgrading cochlear implants with even better resolution, using multiple electrodes (multi-channel).</td>
|
||
<td>Graeme Clark; Claude Chouard; F. Blair Simmons and Robert L. White; Michael Merzenich and Robin P. Michelson</td>
|
||
<td>Academia: Univ. of Melbourne, Australia; INSERM, France; Stanford; UCSF Industry: Nucleus Ltd. , MedEl</td>
|
||
<td>NIH Grants NS 10532, NS10414, NIH grant NS 11804, NIH Contracts N01-NS-5-2388,-2395,and -2396</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/23681026">Mudry A, Mills M. The early history of the cochlear implant: a retrospective. JAMA otolaryngology-- head & neck surgery. 2013;139(5):446-453.</a></td>
|
||
<td>Clark GM. Cochlear implants. New York: Springer Verlag; 2003</td>
|
||
<td>Clark GM, Cowan RSC, Dowell DC. Cochlear implantation for infants and children. Advances. San Diego: Singular Publishing Group; 1997.</td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1979-83</td>
|
||
<td>NIH-supported researchers used a new animal model for Parkinson’s disease, called the MPTP model, to identify the brain regions responsible for motor symptoms.</td>
|
||
<td>Irwin Kopin</td>
|
||
<td>NINDS and NIMH Intramural, Stanford</td>
|
||
<td>NIMH and NINDS Intramural, Santa Clara County Medical Services, NIMH Intramural</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/298352">Davis GC, Williams AC, Markey SP, et al. Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry research. 1979;1(3):249-254.</a></td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/6823561">Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219(4587):979-980.</a></td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/6192438">Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ. A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proceedings of the National Academy of Sciences of the United States of America. 1983;80(14):4546-4550.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1984, 1985</td>
|
||
<td>FDA Approval of first two cochlear implant devices</td>
|
||
<td>William F. House, Graeme Clark</td>
|
||
<td>3M/House Research Institute, Univ. of Melbourne/Cochlear Corp</td>
|
||
<td>Private--3M and Nucleus Ltd</td>
|
||
<td>FDA Premarket Approval P830069: 3M Brand Cochlear Implant System/House Design in citation 1</td>
|
||
<td>FDA Premarket Approval P840024: Nucleus Multichannel Implantable Hearing Prosthesis</td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
</tbody>
|
||
</table>
|
||
|
||
<p><strong>Late 1980s/1990s: Next Generation Devices and Applications</strong></p>
|
||
|
||
<table border="0" cellpadding="10" cellspacing="0" class="table-data-tight" summary="Late 1980s/1990s: Next Generation Devices and Applications">
|
||
<tbody>
|
||
<tr>
|
||
<th>Year</th>
|
||
<th>Description of Milestone</th>
|
||
<th>Primary Investigator(s)</th>
|
||
<th>Research Institution</th>
|
||
<th>Funding source (including NIH grant numbers where available)</th>
|
||
<th>Citation 1</th>
|
||
<th>Citation 2</th>
|
||
<th>Citation 3</th>
|
||
<th>Citation 4</th>
|
||
</tr>
|
||
<tr>
|
||
<td>1986</td>
|
||
<td>Publication of first model for parallel organization of circuits involved in both normal movement and Parkinson's</td>
|
||
<td>Garrett Alexander, Mahlon DeLong, and Peter Strick</td>
|
||
<td>Johns Hopkins University</td>
|
||
<td>NIH Grants NS00632 (G.A.), NS17678 (G.A.), NS16375 (Mahlon DeLong), NS02957 (P.S.), VA, private donations</td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/3085570">Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual review of neuroscience. 1986;9:357-381.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1986-1990</td>
|
||
<td>Studies in the MPTP primate model implcate dysfunction in two regions for movement symptoms in PD and related disorders</td>
|
||
<td>Mahlon DeLong; John Penney, Anne Young; David Sibley</td>
|
||
<td>Johns Hopkins University; University of Michigan, Ann Arbor; NINDS/NIMH Intramural</td>
|
||
<td>NIH Grants NS15655, NS19613, NS01300,NS015417 private donations</td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/2848190">Penney JB, Jr., Young AB. Striatal inhomogeneities and basal ganglia function. Movement disorders : official journal of the Movement Disorder Society. 1986;1(1):3-15.</a></td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/2479133">Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends in neurosciences. 1989;12(10):366-375.</a></td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/1695404">DeLong MR. Primate models of movement disorders of basal ganglia origin. Trends in neurosciences. 1990;13(7):281-285.</a></td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/2147780">Gerfen CR, Engber TM, Mahan LC, et al. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science. 1990;250(4986):1429-1432.</a></td>
|
||
</tr>
|
||
<tr>
|
||
<td>1990</td>
|
||
<td>The FDA approved cochlear implant use in children, providing an opportunity to restore hearing to children during their developmental years</td>
|
||
<td>Graeme Clark</td>
|
||
<td>Cochlear Corp</td>
|
||
<td>Private-Cochlear Corp</td>
|
||
<td>FDA Premarket Approval P890027: Nucleus 22 Channel Cochlear Implant Sys /Children</td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1990-91</td>
|
||
<td>Studies demonstrated that inactivation of one deep brain region in a primate model reduces tremor symptoms using the MPTP model for Parkinson's disease</td>
|
||
<td>Mahlon DeLong; Alan Crossman</td>
|
||
<td>Johns Hopkins University; University of Manchester Medical School, U.K.</td>
|
||
<td>NS15417, private funds from the E.K. Dunn family, UK Govt.</td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/2402638">Bergman H, Wichmann T, DeLong MR. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science. 1990;249(4975):1436-1438.</a></td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/1758446">Aziz TZ, Peggs D, Sambrook MA, Crossman AR. Lesion of the subthalamic nucleus for the alleviation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the primate. Movement disorders : official journal of the Movement Disorder Society. 1991;6(4):288-292.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1987-98</td>
|
||
<td>Studies in humans revealed that electrical stimulation of deep brain regions could quickly and reversibly reduce the tremors associated with Parkinson’s disease.</td>
|
||
<td>Alim-Louis Benabid</td>
|
||
<td>Joseph Fourier University of Grenoble, France</td>
|
||
<td>INSERM/French Govt</td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/3329873">Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Applied neurophysiology. 1987;50(1-6):344-346.</a></td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/1671433">Benabid AL, Pollak P, Gervason C, et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet. 1991;337(8738):403-406.</a></td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/7815888">Limousin P, Pollak P, Benazzouz A, et al. Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet. 1995;345(8942):91-95.</a></td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/9770557">Limousin P, Krack P, Pollak P, et al. Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. The New England journal of medicine. 1998;339(16):1105-1111.</a></td>
|
||
</tr>
|
||
<tr>
|
||
<td>1990s</td>
|
||
<td>Building on earlier research, Medtronic scientists performed clinical trials of deep brain stimulation for tremor and Parkinson’s disease.</td>
|
||
<td>N/A</td>
|
||
<td>Medtronic</td>
|
||
<td>Private-Medtronic</td>
|
||
<td><a href="http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=5716377.PN.&OS=PN/5716377&RS=PN/5716377">Rise MT, W. KG, Inventors; Medtronic, Inc., assignee. Method of treating movement disorders by brain stimulation. US patent 5716377. February 10, 1998.</a></td>
|
||
<td><a href="http://professional.medtronic.com/pt/neuro/dbs-md/eff/data-and-clinical-outcomes/">Medtronic DBS Therapy for Parkinson's Disease and Essential Tremor Data and Clinical Outcomes</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1997</td>
|
||
<td>Medtronic received the first FDA approval for deep brain stimulation to treat essential tremor, a common disorder with symptoms similar to Parkinson’s disease.</td>
|
||
<td>N/A</td>
|
||
<td>Medtronic</td>
|
||
<td>Private-Medtronic</td>
|
||
<td>FDA Premarket Approval P960009: Medtronic Activa Tremor Control System</td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
</tbody>
|
||
</table>
|
||
|
||
<p><strong>2000s-2010s: A Rapidly Growing Field Seeking New Targets</strong></p>
|
||
|
||
<table border="0" cellpadding="10" cellspacing="0" class="table-data-tight" summary=" A Rapidly Growing Field Seeking New Targets">
|
||
<tbody>
|
||
<tr>
|
||
<th>Year</th>
|
||
<th>Description of Milestone</th>
|
||
<th>Primary Investigator(s)</th>
|
||
<th>Research Institution</th>
|
||
<th>Funding source (including NIH grant numbers where available)</th>
|
||
<th>Citation 1</th>
|
||
<th>Citation 2</th>
|
||
<th>Citation 3</th>
|
||
<th>Citation 4</th>
|
||
</tr>
|
||
<tr>
|
||
<td>2002-03</td>
|
||
<td>The Medtronic deep brain stimulation device was approved by the FDA to treat symptoms of Parkinson’s disease</td>
|
||
<td>N/A</td>
|
||
<td>Medtronic</td>
|
||
<td>Private-Medtronic</td>
|
||
<td>FDA Premarket Approval P960009: Medtronic Activa Tremor Control System, Supplement S007: Medtronic Activa Parkinson’s Control System</td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>2009</td>
|
||
<td>A large clinical trial demonstrated that deep brain stimulation is superior to best medical therapy</td>
|
||
<td>Frances Weaver</td>
|
||
<td>Hines VA Hospital (and many others via the CSP 468 Study Group)</td>
|
||
<td>VA, NIH-NINDS, Medtronic</td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/19126811">Weaver FM, Follett K, Stern M, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. Jama. 2009;301(1):63-73.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>2009</td>
|
||
<td>FDA approves a humanitarian exemption for deep brain stimulation as a treatment for Obsessive-Compulsive Disorder</td>
|
||
<td>N/A</td>
|
||
<td>Medtronic</td>
|
||
<td>Private-Medtronic</td>
|
||
<td><a href="http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm125520.htm">FDA: Reclaim™ DBS™ Therapy for OCD - H050003</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>2011-14</td>
|
||
<td>NIH-funded researchers used electrical stimulation strategies to restore lost function in patients with spinal cord injury, who regained bladder control, blood pressure control, sexual function, and the ability to make small voluntary lower body movements and stand unaided for up to 20 minutes</td>
|
||
<td>V. Reggie Edgerton; Susan Harkema</td>
|
||
<td>University of California, Los Angeles; University of Louisville</td>
|
||
<td>NIH Grants EB007615 and GM103507, Reeve Foundation, Leona M. and Harry B. Helmsley Charitable Trust, Kessler Foundation, University of Louisville Foundation, and Jewish Hospital and St. Mary’s Foundation, Frazier Rehab Institute and University of Louisville Hospital</td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/21601270">Harkema S, Gerasimenko Y, Hodes J, et al. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet. 2011;377(9781):1938-1947.</a></td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/24713270">Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain : a journal of neurology. 2014;137(Pt 5):1394-1409.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>2014</td>
|
||
<td>The FDA approved a humanitarian exemption for the use of the first visual prosthesis,the Argus II, which allows patients with certain types of vision loss to perceive a small, low-resolution visual field.</td>
|
||
<td>Mark Humayan, Robert Jay Greenberg</td>
|
||
<td>Johns Hopkins University, Second Sight Medical Products, Inc.</td>
|
||
<td>NIH Grants: EY011888 and EY012893</td>
|
||
<td><a href="http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm343162.htm">FDA: Argus II Retinal Prosthesis System - H110002</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>2015</td>
|
||
<td>NIH-funded researchers stimulate the spinal cord through the skin, generating intentional step-like movements in patients with spinal cord injury</td>
|
||
<td>V. Reggie Edgerton</td>
|
||
<td>University of California, Los Angeles</td>
|
||
<td>NIH Grants EB15521, EB007615, TR000124, Reeve Foundation, Walkabout Foundation, F.M. Kirby Foundation</td>
|
||
<td><a href="https://www.ncbi.nlm.nih.gov/pubmed/26077679">Gerasimenko YP, Lu DC, Modaber M, et al. Noninvasive Reactivation of Motor Descending Control after Paralysis. Journal of neurotrauma. 2015;32(24):1968-1980.</a></td>
|
||
<td> </td>
|
||
<td> </td>
|
||
<td> </td>
|
||
</tr>
|
||
</tbody>
|
||
</table>
|
||
</div>
|
||
|
||
<h4 class="collapsible-trigger">Related Resources on Neurostimulation Technologies</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<ul>
|
||
<li><a href="https://www.nidcd.nih.gov/health/cochlear-implants">More on Cochlear Implants</a></li>
|
||
<li><a href="http://www.ninds.nih.gov/disorders/deep_brain_stimulation/deep_brain_stimulation.htm">More on Deep Brain Stimulation</a></li>
|
||
<li><a href="http://www.nimh.nih.gov/health/topics/brain-stimulation-therapies/brain-stimulation-therapies.shtml">More on Brain Stimulation Therapies</a></li>
|
||
<li><a href="https://www.nibib.nih.gov/science-education/bionic-man">Science Education: Bionic Man</a></li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<h2>Fighting Cancer: Ushering in a New Era of Molecular Medicine</h2>
|
||
|
||
<p><a class="media-border no-tag" href="/sites/default/files/about-nih/impact/fighting-cancer-case-study.pdf"><div class="media media-element-container media-featured_media"><div class="ds-1col file file-image file-image-jpeg view-mode-featured_media clearfix">
|
||
|
||
|
||
<picture title="Screenshot of the Fighting Cancer Case Study" class="media-element">
|
||
<!--[if IE 9]><video style="display: none;"><![endif]-->
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-large-extra/public/about-nih/impact/fighting-cancer-spread-screenshot.jpg?itok=aDswhNs6&timestamp=1459270377 1x" media="screen and (min-width: 1100px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-large/public/about-nih/impact/fighting-cancer-spread-screenshot.jpg?itok=hRSHEWHd&timestamp=1459270377 1x" media="screen and (min-width: 960px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/about-nih/impact/fighting-cancer-spread-screenshot.jpg?itok=S4AhsQ7n&timestamp=1459270377 1x" media="screen and (min-width: 800px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium-small/public/about-nih/impact/fighting-cancer-spread-screenshot.jpg?itok=gnbWRyWq&timestamp=1459270377 1x" media="screen and (min-width: 600px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-small/public/about-nih/impact/fighting-cancer-spread-screenshot.jpg?itok=NFoOFKzi&timestamp=1459270377 1x" media="screen and (min-width: 480px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media__breakpoint-tiny_/public/about-nih/impact/fighting-cancer-spread-screenshot.jpg?itok=icyDabG7&timestamp=1459270377 1x" media="screen and (min-width: 0)"></source>
|
||
<!--[if IE 9]></video><![endif]-->
|
||
<img class="media-element" src="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/about-nih/impact/fighting-cancer-spread-screenshot.jpg?itok=S4AhsQ7n&timestamp=1459270377" alt="Screenshot of the Fighting Cancer Case Study." title="Screenshot of the Fighting Cancer Case Study" />
|
||
</picture></div>
|
||
|
||
</div></a></p>
|
||
|
||
<p>Huge advances in our understanding of disease at a molecular level are paving the way for more effective, personalized treatments. Gleevec<sup>®</sup>, a drug used to treat chronic myelogenous leukemia (CML), was among the first successful molecular medicines developed. <a href="/sites/default/files/about-nih/impact/fighting-cancer-case-study.pdf">Read the story of how NIH-supported research helped create a revolutionary cancer drug that changed the way we think about designing new medicines</a></p>
|
||
|
||
<div class="collapsible">
|
||
<h3 class="collapsible-trigger">Additional materials</h3>
|
||
|
||
<div class="collapsible-content">
|
||
<h4 class="collapsible-trigger">References</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<p class="footnote"><sup>1</sup>A Story of Discovery: Gleevec Transforms Cancer Treatment for Chronic Myelogenous Leukemia. National Cancer Institute. Retrieved October 29, 2015, from <a href="http://www.cancer.gov/research/progress/discovery/gleevec">http://www.cancer.gov/research/progress/discovery/gleevec</a></p>
|
||
|
||
<p class="footnote"><sup>2</sup>Druker BJ, Guilhot F, O'Brien SG, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17151364">Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia</a>. <em>The New England journal of medicine. </em>2006;355(23):2408-2417.</p>
|
||
|
||
<p class="footnote"><sup>3</sup><a href="http://www.cancer.org/cancer/cancerbasics/thehistoryofcancer/the-history-of-cancer-cancer-treatment-targeted-therapy">http://www.cancer.org/cancer/cancerbasics/thehistoryofcancer/the-history-of-cancer-cancer-treatment-targeted-therapy</a></p>
|
||
|
||
<p class="footnote"><sup>4</sup><a href="https://www.jstage.jst.go.jp/article/kjm/59/1/59_1_1/_pdf">https://www.jstage.jst.go.jp/article/kjm/59/1/59_1_1/_pdf</a></p>
|
||
|
||
<p class="footnote"><sup>5</sup>Huang X, Cortes J, Kantarjian H. <a href="http://www.ncbi.nlm.nih.gov/pubmed/22294282">http://www.ncbi.nlm.nih.gov/pubmed/22294282</a> Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. <em>Cancer. </em>2012;118(12):3123-3127.</p>
|
||
|
||
<p class="footnote"><sup>6</sup><a href="http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf">http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf</a></p>
|
||
|
||
<p class="footnote"><sup>7</sup>A Decade of Innovation in Rare Diseases. PhRMA 2015. <a href="http://www.phrma.org/sites/default/files/pdf/PhRMA-Decade-of-Innovation-Rare-Diseases.pdf">http://www.phrma.org/sites/default/files/pdf/PhRMA-Decade-of-Innovation-Rare-Diseases.pdf</a></p>
|
||
|
||
<p class="footnote"><sup>8</sup>Boveri T. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18089652">Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris</a>. <em>Journal of cell science. </em>2008;121 Suppl 1:1-84.</p>
|
||
|
||
<p class="footnote"><sup>9</sup><a href="https://www.genome.gov/Pages/Education/GeneticTimeline.pdf">https://www.genome.gov/Pages/Education/GeneticTimeline.pdf</a></p>
|
||
|
||
<p class="footnote"><sup>10</sup>Nowell PC, Hungerford DA. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14427847">Chromosome studies on normal and leukemic human leukocytes</a>. <em>Journal of the National Cancer Institute. </em>1960;25:85-109.</p>
|
||
|
||
<p class="footnote"><sup>11</sup>Rowley JD. Letter: <a href="http://www.ncbi.nlm.nih.gov/pubmed/4126434">A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining</a>. <em>Nature. </em>1973;243(5405):290-293.</p>
|
||
|
||
<p class="footnote"><sup>12</sup>Heisterkamp N, Stephenson JR, Groffen J, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6316147">Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia</a>. <em>Nature. </em>1983;306(5940):239-242.</p>
|
||
|
||
<p class="footnote"><sup>13</sup>Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6319012">Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22</a>. <em>Cell. </em>1984;36(1):93-99.</p>
|
||
|
||
<p class="footnote"><sup>14</sup>Konopka JB, Watanabe SM, Singer JW, Collins SJ, Witte ON. <a href="http://www.ncbi.nlm.nih.gov/pubmed/3856862">Cell lines and clinical isolates derived from Ph1-positive chronic myelogenous leukemia patients express c-abl proteins with a common structural alteration</a>. <em>Proceedings of the National Academy of Sciences of the United States of America. </em>1985;82(6):1810-1814.</p>
|
||
|
||
<p class="footnote"><sup>15</sup>Druker BJ. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19812576">Perspectives on the development of imatinib and the future of cancer research</a>. <em>Nature medicine. </em>2009;15(10):1149-1152.</p>
|
||
|
||
<p class="footnote"><sup>16</sup>Ibid.</p>
|
||
|
||
<p class="footnote"><sup>17</sup>Hunter T. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17671637">Treatment for chronic myelogenous leukemia: the long road to imatinib</a>. <em>The Journal of clinical investigation. </em>2007;117(8):2036-2043.</p>
|
||
|
||
<p class="footnote"><sup>18</sup>Pray L. <a href="http://www.nature.com/scitable/topicpage/gleevec-the-breakthrough-in-cancer-treatment-565">Gleevec: the breakthrough in cancer treatment</a>. Nat Education. 2008;1(1):37.</p>
|
||
|
||
<p class="footnote"><sup>19</sup>Druker BJ, Tamura S, Buchdunger E, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8616716">Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells</a>. <em>Nature medicine. </em>1996;2(5):561-566.</p>
|
||
|
||
<p class="footnote"><sup>20</sup>Food and Drug Administration Modernization Act. S. 830. 105th Congress. (1997).</p>
|
||
|
||
<p class="footnote"><sup>21</sup>Fast Track. Food and Drug Administration. Updated 2014, September 15. Retrieved October 29, 2015, from <a href="http://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm">http://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm</a></p>
|
||
|
||
<p class="footnote"><sup>22</sup>Druker BJ, Talpaz M, Resta DJ, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11287972">Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia</a>. <em>The New England journal of medicine. </em>2001;344(14):1031-1037.</p>
|
||
|
||
<p class="footnote"><sup>23</sup>Waalen J. <a href="https://www.hhmi.org/sites/default/files/Bulletin/2001/December/dec2001_fulltext.pdf">Gleevec’s Glory Days</a>. Howard Hughes Medical Institute Bulletin. 2001 Dec;14(5):10-15.</p>
|
||
|
||
<p class="footnote"><sup>24</sup>Druker BJ, Guilhot F, O'Brien SG, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17151364">Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia</a>. <em>The New England journal of medicine. </em>2006;355(23):2408-2417.</p>
|
||
|
||
<p class="footnote"><sup>25</sup><a href="http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm110505.htm">http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm110505.htm</a></p>
|
||
|
||
<p class="footnote"><sup>26</sup>Cumulative number of publications containing the search term “imatinib” from 1996-2014 in the PubMed database.</p>
|
||
|
||
<p class="footnote"><sup>27</sup>A Decade of Innovation in Rare Diseases. PhRMA 2015. <a href="http://www.phrma.org/sites/default/files/pdf/PhRMA-Decade-of-Innovation-Rare-Diseases.pdf">http://www.phrma.org/sites/default/files/pdf/PhRMA-Decade-of-Innovation-Rare-Diseases.pdf</a></p>
|
||
|
||
<p class="footnote"><sup>28</sup>Ibid.</p>
|
||
|
||
<p class="footnote"><sup>29</sup><a href="https://www.jstage.jst.go.jp/article/kjm/59/1/59_1_1/_pdf">https://www.jstage.jst.go.jp/article/kjm/59/1/59_1_1/_pdf</a></p>
|
||
|
||
<p class="footnote"><sup>30</sup>Determined by searching clinicaltrials.gov for registered clinical trials using the term “imatinib,” “Gleevec,” or “Glivec.”</p>
|
||
|
||
<p class="footnote"><sup>31</sup><a href="http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021588s042lbl.pdf">http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021588s042lbl.pdf</a></p>
|
||
|
||
<p class="footnote"><sup>32</sup><a href="http://seer.cancer.gov/csr/1975_2012/browse_csr.php?sectionSEL=13&pageSEL=sect_13_table.16.html#table4">http://seer.cancer.gov/csr/1975_2012/browse_csr.php?sectionSEL=13&pageSEL=sect_13_table.16.html#table4</a></p>
|
||
|
||
<p class="footnote"><sup>33</sup><a href="https://www.jstage.jst.go.jp/article/kjm/59/1/59_1_1/_pdf">https://www.jstage.jst.go.jp/article/kjm/59/1/59_1_1/_pdf</a></p>
|
||
|
||
<p class="footnote"><sup>34</sup>Determined using data provided by FDA’s Center for Drug Evaluation and Research on mechanism of action of approved FDA drugs, 1999-2015.</p>
|
||
|
||
<p class="footnote"><sup>35</sup>Determined using data provided by FDA’s Center for Drug Evaluation and Research on the companies associated with approved FDA drugs.</p>
|
||
|
||
<p class="footnote"><sup>36</sup>DiMasi JA, Hansen RW, Grabowski HG. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12606142">The price of innovation: new estimates of drug development costs</a>. <em>Journal of health economics.</em> 2003;22(2):151-185.</p>
|
||
|
||
<p class="footnote"><sup>37</sup><a href="http://csdd.tufts.edu/files/uploads/Tufts_CSDD_briefing_on_RD_cost_study_-_Nov_18,_2014..pdf">http://csdd.tufts.edu/files/uploads/Tufts_CSDD_briefing_on_RD_cost_study_-_Nov_18,_2014..pdf</a></p>
|
||
</div>
|
||
|
||
<h4 class="collapsible-trigger">Appendix</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<p>The table below provides a more detailed list of selected milestones underlying this story’s “Research-to-Practice Milestones” (page 2 of the pdf), including the lead scientists, research institutions, funding sources, and scientific publications involved in each one.</p>
|
||
|
||
<p><strong>Identifying the Molecular Trigger of CML (1914–1990)</strong></p>
|
||
|
||
<table border="0" cellpadding="10" cellspacing="0" class="table-data-tight" summary="Identifying the Molecular Trigger of CML (1914-1990)">
|
||
<tbody>
|
||
<tr>
|
||
<th>Year</th>
|
||
<th>Description of Milestone</th>
|
||
<th>Primary Investigator(s)</th>
|
||
<th>Research Institution</th>
|
||
<th>Funding source (including NIH grant numbers where available)</th>
|
||
<th>Citation 1</th>
|
||
<th>Citation 2</th>
|
||
</tr>
|
||
<tr>
|
||
<td>1914</td>
|
||
<td>Biologist Theodor Boveri first hypothesized that chromosomal abnormalities may play a role in tumor development, but no tools existed at that time to test his theory.</td>
|
||
<td>Boveri</td>
|
||
<td>N/A</td>
|
||
<td>Unknown (Germany)</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/18089652">Boveri T. Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris. Journal of cell science. 2008;121 Suppl 1:1-84.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1950s</td>
|
||
<td>Using newly developed techniques to study cells and chromosomes, researchers began to link chromosomal abnormalities to specific human diseases.</td>
|
||
<td>None specific</td>
|
||
<td>N/A</td>
|
||
<td>N/A</td>
|
||
<td><a href="https://www.genome.gov/Pages/Education/GeneticTimeline.pdf">Genome.gov Timeline: From Darwin and Mendel to the Human Genome Project</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1960</td>
|
||
<td>Drs. Nowell and Hungerford studied cells from CML patients and discovered an atypical small chromosome in the cancer cells, called the Philadelphia chromosome.</td>
|
||
<td>Nowell and Hungerford</td>
|
||
<td>University of Pennsylvania</td>
|
||
<td>NIH (C-3562), American Cancer Society, US Public Health Service</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/14427847">Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. Journal of the National Cancer Institute. 1960;25:85-109.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1973</td>
|
||
<td>Dr. Rowley discovered that the Philadelphia chromosome results from a chromosomal translocation between chromosomes 9 and 22.</td>
|
||
<td>Rowley</td>
|
||
<td>University of Chicago</td>
|
||
<td>Unknown</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/4126434">Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973;243(5405):290-293.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1983</td>
|
||
<td>Researchers identified the genes involved in the Philadelphia chromosome, showing that the human oncogene c-abl is part of the translocation.</td>
|
||
<td>Heisterkamp</td>
|
||
<td>NIH (NCI intramural); Erasmus University</td>
|
||
<td>NIH (contract COI-CP-75380), Netherlands Cancer Society</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/6316147">Heisterkamp N, Stephenson JR, Groffen J, et al. Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature. 1983;306(5940):239-242.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1984</td>
|
||
<td>Scientists identified the breakpoint cluster region (bcr) on chromosome 22.</td>
|
||
<td>Groffen</td>
|
||
<td>NIH (NCI intramural); Erasmus University</td>
|
||
<td>NIH (contract COI-CP-75380), Netherlands Cancer Society</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/6319012">Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell. 1984;36(1):93-99.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1990</td>
|
||
<td>Researchers identified the function of the bcr-abl fusion gene, which prompts production of an improperly regulated abnormal tyrosine kinase protein.</td>
|
||
<td>Lugo</td>
|
||
<td>University of California, Los Angeles</td>
|
||
<td>NIH/NCI (T32GM08243 and T32GM07185), Howard Hughes Medical Institute, Leukemia Society of America</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/2408149">Lugo TG, Pendergast AM, Muller AJ, Witte ON. Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science. 1990;247(4946):1079-1082.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
</tbody>
|
||
</table>
|
||
|
||
<p><strong>Developing a targeted Bcr-abl kinase inhibitor (1990–1996)</strong></p>
|
||
|
||
<table border="0" cellpadding="10" cellspacing="0" class="table-data-tight" summary="Developing a targeted Bcr-abl kinase inhibitor (1990-1996)">
|
||
<tbody>
|
||
<tr>
|
||
<th>Year</th>
|
||
<th>Description of Milestone</th>
|
||
<th>Primary Investigator(s)</th>
|
||
<th>Research Institution</th>
|
||
<th>Funding source (including NIH grant numbers where available)</th>
|
||
<th>Citation 1</th>
|
||
<th>Citation 2</th>
|
||
</tr>
|
||
<tr>
|
||
<td>1990</td>
|
||
<td>Scientists at pharmaceutical company Ciba-Geigy (later became Novartis) began to refine a compound that blocks the enzyme that triggers CML without harming other kinases.</td>
|
||
<td>Nick Lydon</td>
|
||
<td>Ciba-Geigy (now Novartis)</td>
|
||
<td>Ciba-Geigy</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/19812576">Druker BJ. Perspectives on the development of imatinib and the future of cancer research. Nature medicine. 2009;15(10):1149-1152.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1990</td>
|
||
<td>Dr. Druker began developing model systems to study BCR-ABL signaling and outlined how to characterize BCR-ABL kinase inhibitors.</td>
|
||
<td>Brian Druker</td>
|
||
<td>Dana-Farber Cancer Institute</td>
|
||
<td>NIH/NCI (K08CA001422)</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/19812576">Druker BJ. Perspectives on the development of imatinib and the future of cancer research. Nature medicine. 2009;15(10):1149-1152.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1992</td>
|
||
<td>The compound that would become Gleevec was first synthesized, although many years of testing would be needed before its effectiveness was known.</td>
|
||
<td>N/A</td>
|
||
<td>Ciba-Geigy</td>
|
||
<td>Ciba-Geigy</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/17671637">Hunter T. Treatment for chronic myelogenous leukemia: the long road to imatinib. The Journal of clinical investigation. 2007;117(8):2036-2043.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1993</td>
|
||
<td>Dr. Druker started his own lab with the goal of finding a drug company that had a BCR-ABL kinase inhibitor that he could help move to the clinic. He partnered with Ciba-Geigy to screen their collection of synthesized compounds for signs of anticancer activity.</td>
|
||
<td>Brian Druker</td>
|
||
<td>Oregon Health & Sciences University; Ciba-Geigy</td>
|
||
<td>NIH/NCI (K08CA001422); Ciba-Geigy</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/19812576">Druker BJ. Perspectives on the development of imatinib and the future of cancer research. Nature medicine. 2009;15(10):1149-1152.</a></td>
|
||
<td><a href="http://www.nature.com/scitable/topicpage/gleevec-the-breakthrough-in-cancer-treatment-565">Pray L. Gleevec: the breakthrough in cancer treatment. Nat Education. 2008;1(1):37.</a></td>
|
||
</tr>
|
||
<tr>
|
||
<td>1996</td>
|
||
<td>One of the compounds showed promising results in cultured cells. The compound (ST1571) caused a 92-98% decrease in the number of bcr-abl colonies formed and did not appear to harm healthy cells.</td>
|
||
<td>Brian Druker</td>
|
||
<td>Oregon Health & Sciences University; Ciba-Geigy</td>
|
||
<td>NIH/NCI (K08CA001422); Ciba-Geigy</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/8616716">Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nature medicine. 1996;2(5):561-566.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
</tbody>
|
||
</table>
|
||
|
||
<p><strong>Testing and Approving a Life-changing Drug (1997–2015)</strong></p>
|
||
|
||
<table border="0" cellpadding="10" cellspacing="0" class="table-data-tight" summary="Testing and Approving a Life-changing Drug (1997-2015)">
|
||
<tbody>
|
||
<tr>
|
||
<th>Year</th>
|
||
<th>Description of Milestone</th>
|
||
<th>Primary Investigator(s)</th>
|
||
<th>Research Institution</th>
|
||
<th>Funding source (including NIH grant numbers where available)</th>
|
||
<th>Citation 1</th>
|
||
<th>Citation 2</th>
|
||
</tr>
|
||
<tr>
|
||
<td>1998</td>
|
||
<td>Ciba-Geigy helped develop the drug for patient use, and the first Phase I clinical trial of ST1571 (later renamed Gleevec) began. All 31 patients in the initial trial experienced complete remission with limited side effects.</td>
|
||
<td>Brian Druker</td>
|
||
<td>Ciba-Geigy; Oregon Health & Sciences University</td>
|
||
<td>NIH (R01CA65823 and P01CA032737); Novartis</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/11287972">Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. The New England journal of medicine. 2001;344(14):1031-1037.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>2001</td>
|
||
<td>Successful clinical trial results led the FDA to grant “fast track” designation for Gleevec, and it was approved only ten weeks after the New Drug Application was submitted.</td>
|
||
<td>N/A</td>
|
||
<td>Novartis</td>
|
||
<td>NIH, Novartis</td>
|
||
<td><a href="https://www.hhmi.org/sites/default/files/Bulletin/2001/December/dec2001_fulltext.pdf">Waalen J. Gleevec’s Glory Days. Howard Hughes Medical Institute Bulletin. 2001 Dec;14(5):10-15.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>2006</td>
|
||
<td>After five years of continuous follow-up treatment, patients receiving Gleevec continued to have a high response rate to the drug, and most remained cancer-free.</td>
|
||
<td>Druker</td>
|
||
<td>Novartis; Oregon Health & Sciences University</td>
|
||
<td>Novartis</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/17151364">Druker BJ, Guilhot F, O'Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. The New England journal of medicine. 2006;355(23):2408-2417.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
</tbody>
|
||
</table>
|
||
</div>
|
||
|
||
<h4 class="collapsible-trigger">Related Resources on Gleevec</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<ul>
|
||
<li><a href="http://www.cancer.gov/research/progress/discovery/gleevec">A Story of Discovery: Gleevec Transforms Cancer Treatment for Chronic Myelogenous Leukemia</a></li>
|
||
<li><a href="http://www.cancer.gov/about-cancer/treatment/drugs/imatinibmesylate">More on Gleevec (Imatinib Mesylate)</a></li>
|
||
<li><a href="http://www.cancer.gov/types/leukemia/patient/cml-treatment-pdq">More on CML Treatment</a></li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<h2>Childhood Hib Vaccines: Nearly Eliminating the Threat of Bacterial Meningitis</h2>
|
||
|
||
<p><a class="media-border no-tag" href="/sites/default/files/about-nih/impact/childhood-hib-vaccines-case-study.pdf"><div class="media media-element-container media-featured_media"><div class="ds-1col file file-image file-image-jpeg view-mode-featured_media clearfix">
|
||
|
||
|
||
<picture title="Screenshot of the Childhood Hib Vaccines Case Study" class="media-element">
|
||
<!--[if IE 9]><video style="display: none;"><![endif]-->
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-large-extra/public/about-nih/impact/childhood-hib-vaccines-case-study-spread-screenshot_0.jpg?itok=4sh_qxXH&timestamp=1464206255 1x" media="screen and (min-width: 1100px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-large/public/about-nih/impact/childhood-hib-vaccines-case-study-spread-screenshot_0.jpg?itok=7MmzbuYh&timestamp=1464206255 1x" media="screen and (min-width: 960px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/about-nih/impact/childhood-hib-vaccines-case-study-spread-screenshot_0.jpg?itok=BNxdAWwL&timestamp=1464206255 1x" media="screen and (min-width: 800px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium-small/public/about-nih/impact/childhood-hib-vaccines-case-study-spread-screenshot_0.jpg?itok=bPqwkWHG&timestamp=1464206255 1x" media="screen and (min-width: 600px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-small/public/about-nih/impact/childhood-hib-vaccines-case-study-spread-screenshot_0.jpg?itok=YbyTDSBY&timestamp=1464206255 1x" media="screen and (min-width: 480px)"></source>
|
||
<source srcset="https://www.nih.gov/sites/default/files/styles/featured_media__breakpoint-tiny_/public/about-nih/impact/childhood-hib-vaccines-case-study-spread-screenshot_0.jpg?itok=XqZmgO3B&timestamp=1464206255 1x" media="screen and (min-width: 0)"></source>
|
||
<!--[if IE 9]></video><![endif]-->
|
||
<img class="media-element" src="https://www.nih.gov/sites/default/files/styles/featured_media_breakpoint-medium/public/about-nih/impact/childhood-hib-vaccines-case-study-spread-screenshot_0.jpg?itok=BNxdAWwL&timestamp=1464206255" alt="Screenshot of the Childhood Hib Vaccines Case Study." title="Screenshot of the Childhood Hib Vaccines Case Study" />
|
||
</picture></div>
|
||
|
||
</div></a></p>
|
||
|
||
<p>NIH has contributed to the development of many important vaccines, including the vaccine against Haemophilus influenzae type b (Hib) infection. Once the leading cause of bacterial meningitis in children, Hib infection can result in serious, long-term disability and death. Today, Hib has been nearly eliminated. <a href="/sites/default/files/about-nih/impact/childhood-hib-vaccines-case-study.pdf">Read the story of how NIH-supported research helped create a vaccine that has nearly eliminated childhood meningitis</a></p>
|
||
|
||
<div class="collapsible">
|
||
<h3 class="collapsible-trigger">Additional materials</h3>
|
||
|
||
<div class="collapsible-content">
|
||
<h4 class="collapsible-trigger">References</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<p class="footnote"><sup>1</sup><a href="http://www.niaid.nih.gov/topics/vaccines/Pages/Default.aspx">NIAID Health and Research Topics: Vaccines</a> , <a href="http://www.cdc.gov/vaccines/vpd-vac/vaccines-list.htm">CDC Vaccines and Immunizations: List of Vaccines Used in United States</a></p>
|
||
|
||
<p class="footnote"><sup>2</sup><a href="http://www.niaid.nih.gov/topics/vaccines/Pages/vaccineBenefits.aspx">NIAID Health and Research Topics: Vaccine Benefits</a> , <a href="https://www.nichd.nih.gov/about/overview/mission/Pages/hib-vaccine.aspx">NICHD Mission and Scientific Accomplishments: Hib Vaccine</a>, and <a href="http://www.who.int/immunization/REH_47_8_pages.pdf?ua=1">WHO Position Paper on Haemophilus infl uenzae type b conjugate vaccines</a> <em>Weekly Epidemiological Record</em>. 2006;81(47):445.</p>
|
||
|
||
<p class="footnote"><sup>3</sup>Whitney CG, Zhou F, Singleton J, Schuchat A, Centers for Disease C, Prevention. <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6316a4.htm">Benefits from immunization during the vaccines for children program era - United States, 1994-2013</a>. MMWR. Morbidity and mortality weekly report. 2014;63(16):352-355.</p>
|
||
|
||
<p class="footnote"><sup>4</sup>Robbins JB, Schneerson R, Anderson P, Smith DH. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8827975">The 1996 Albert Lasker Medical Research Awards. Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines</a>. <em>Jama</em>. 1996;276(14):1181-1185.</p>
|
||
|
||
<p class="footnote"><sup>5</sup>Decker MD, Edwards KM. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9781742">Haemophilus influenzae type b vaccines: history, choice and comparisons</a>. <em>The Pediatric infectious disease journal</em>. 1998;17(9 Suppl):S113-116.</p>
|
||
|
||
<p class="footnote"><sup>6</sup><a href="http://www.cdc.gov/vaccines/vpd-vac/hib/downloads/dis-hib-color-office.pdf">CDC Diseases and the Vaccines that Prevent Them: Hib</a> and <a href="http://www.nichd.nih.gov/news/releases/pages/cviawar2.aspx">NICHD Press Release: NICHD Researchers Honored by WHO for Developing Vaccines Against Haemophilus Influenzae</a>, December 10, 1996.</p>
|
||
|
||
<p class="footnote"><sup>7</sup><a href="http://www.cdc.gov/vaccines/imz-managers/coverage/nis/child/data/tables-2013.html">Coverage with Individual Vaccines and Vaccination Series, by State and Local area</a>. In: CDC, ed. National Immunization Survey 2013.</p>
|
||
|
||
<p class="footnote"><sup>8</sup><a href="http://www.cdc.gov/vaccines/hcp/vis/vis-statements/hib.html">CDC Vaccine Information Statements: Hib</a></p>
|
||
|
||
<p class="footnote"><sup>9</sup><a href="http://www.niaid.nih.gov/topics/vaccines/Pages/vaccineBenefits.aspx">NIAID Health and Research Topics: Vaccine Benefits</a></p>
|
||
|
||
<p class="footnote"><sup>10</sup><a href="http://www.nichd.nih.gov/news/releases/pages/cviawar2.aspx">NICHD Press Release: NICHD Researchers Honored by WHO for Developing Vaccines Against Haemophilus Influenzae</a>, December 10, 1996.</p>
|
||
|
||
<p class="footnote"><sup>11</sup>Zhou F, Shefer A, Wenger J, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/24590750">Economic evaluation of the routine childhood immunization program in the United States, 2009</a>. <em>Pediatrics</em>. 2014;133(4):577-585.</p>
|
||
|
||
<p class="footnote"><sup>12</sup><a href="http://www.laskerfoundation.org/awards/show/vaccine-for-preventing-meningitis-in-children/">Albert Lasker Clinical Medical Research Award, 1996 Winners</a></p>
|
||
|
||
<p class="footnote"><sup>13</sup>Zhou F, Shefer A, Wenger J, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/24590750">Economic evaluation of the routine childhood immunization program in the United States, 2009</a>. <em>Pediatrics</em>. 2014;133(4):577-585.</p>
|
||
|
||
<p class="footnote"><sup>14</sup> Baker JP, Katz SL. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14630981">Childhood vaccine development: an overview</a>. <em>Pediatric research</em>. 2004;55(2):347-356. and <a href="http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/tetanus.pdf">CDC: The Pink Book: Tetanus Vaccine</a></p>
|
||
|
||
<p class="footnote"><sup>15</sup>Pittman M. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19869858">Variation and Type Specificity in the Bacterial Species Hemophilus Influenzae</a>.<em> The Journal of experimental medicine</em>. 1931;53(4):471-492. and Pittman M. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19870224">The Action of Type-Specific Hemophilus Influenzae Antiserum</a>. <em>The Journal of experimental medicine</em>. 1933;58(6):683-706.</p>
|
||
|
||
<p class="footnote"><sup>16</sup>Robbins JB, Schneerson R, Anderson P, Smith DH. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8827975">The 1996 Albert Lasker Medical Research Awards. Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines</a>. <em>Jama</em>. 1996;276(14):1181-1185. and Jin Z, Romero-Steiner S, Carlone GM, Robbins JB, Schneerson R. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17353280">Haemophilus influenzae type a infection and its prevention</a>. <em>Infection and immunity</em>. 2007;75(6):2650-2654.</p>
|
||
|
||
<p class="footnote"><sup>17</sup>Landsteiner K, van der Scheer J. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19870475">On Cross Reactions of Immune Sera to Azoproteins</a>. <em>The Journal of experimental medicine</em>. 1936;63(3):325-339. and Avery OT, Goebel WF. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19869645">Chemo-Immunological Studies on Conjugated Carbohydrate-Proteins : Ii. Immunological Specificity of Synthetic Sugar-Protein Antigens</a>. <em>The Journal of experimental medicine</em>. 1929;50(4):533-550.</p>
|
||
|
||
<p class="footnote"><sup>18</sup>Alexander DF. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21199851">Why should there be an NICHD?</a> <em>Pediatrics</em>. 2011;127(2):325-333, also <a href="http://www.laskerfoundation.org/awards/show/vaccine-for-preventing-meningitis-in-children/">Albert Lasker Clinical Medical Research Award, 1996 Winners</a>, and Rodrigues LP, Schneerson R, Robbins JB. <a href="http://www.ncbi.nlm.nih.gov/pubmed/4999258">Immunity to Hemophilus influenzae type b. I. The isolation, and some physicochemical, serologic and biologic properties of the capsular polysaccharide of Hemophilus influenzae type b</a>. <em>Journal of immunology</em>. 1971;107(4):1071-1080.</p>
|
||
|
||
<p class="footnote"><sup>19</sup>Smith DH, Peter G, Ingram DL, Harding AL, Anderson P. <a href="http://www.ncbi.nlm.nih.gov/pubmed/4542777">Responses of children immunized with the capsular polysaccharide of Hemophilus influenzae, type b</a>. <em>Pediatrics</em>. 1973;52(5):637-644. and Peltola H, Kayhty H, Sivonen A, Makela H. <a href="http://www.ncbi.nlm.nih.gov/pubmed/335348">Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland</a>. <em>Pediatrics</em>. 1977;60(5):730-737.</p>
|
||
|
||
<p class="footnote"><sup>20</sup><a href="http://www.laskerfoundation.org/awards/show/vaccine-for-preventing-meningitis-in-children/">Albert Lasker Clinical Medical Research Award, 1996 Winners</a> and <a href="https://www.rochester.edu/pr/Review/V70N1/gazette2.html">University of Rochester: Childhood Vaccine with Rochester Roots Recognized</a></p>
|
||
|
||
<p class="footnote"><sup>21</sup>Robbins JB, Schneerson R, Anderson P, Smith DH. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8827975">The 1996 Albert Lasker Medical Research Awards. Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines</a>. <em>Jama</em>. 1996;276(14):1181-1185.</p>
|
||
|
||
<p class="footnote"><sup>22</sup>ibid. and <a href="http://www.laskerfoundation.org/awards/show/vaccine-for-preventing-meningitis-in-children/">Albert Lasker Clinical Medical Research Award, 1996 Winners</a></p>
|
||
|
||
<p class="footnote"><sup>23</sup>Schneerson R, Barrera O, Sutton A, Robbins JB. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6967514">Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates</a>. <em>The Journal of experimental medicine</em>. 1980;152(2):361-376. and Robbins JB, Schneerson R, Anderson P, Smith DH. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8827975">The 1996 Albert Lasker Medical Research Awards. Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines</a>. <em>Jama</em>. 1996;276(14):1181-1185.</p>
|
||
|
||
<p class="footnote"><sup>24</sup>Schneerson R, Robbins JB, Chu C, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6332076">Serum antibody responses of juvenile and infant rhesus monkeys injected with Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-protein conjugates</a>. <em>Infection and immunity</em>. 1984;45(3):582-591.</p>
|
||
|
||
<p class="footnote"><sup>25</sup>Claesson BA, Schneerson R, Robbins JB, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/2783345">Protective levels of serum antibodies stimulated in infants by two injections of Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate</a>. <em>The Journal of pediatrics</em>. 1989;114(1):97-100. also Anderson P, Pichichero M, Edwards K, Porch CR, Insel R. <a href="http://www.ncbi.nlm.nih.gov/pubmed/3499499">Priming and induction of Haemophilus influenzae type b capsular antibodies in early infancy by Dpo20, an oligosaccharide-protein conjugate vaccine</a>. <em>The Journal of pediatrics</em>. 1987;111(5):644-650. and Anderson P, Pichichero ME, Insel RA. <a href="http://www.ncbi.nlm.nih.gov/pubmed/3875705">Immunization of 2-month-old infants with protein-coupled oligosaccharides derived from the capsule of Haemophilus influenzae type b</a>. The <em>Journal of pediatrics</em>. 1985;107(3):346-351</p>
|
||
|
||
<p class="footnote"><sup>26</sup>Decker MD, Edwards KM. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9781742">Haemophilus influenzae type b vaccines: history, choice and comparisons</a>. <em>The Pediatric infectious disease journal</em>. 1998;17(9 Suppl):S113-116.</p>
|
||
|
||
<p class="footnote"><sup>27</sup>ibid.</p>
|
||
|
||
<p class="footnote"><sup>28</sup><a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/00035471.htm">CDC Notice to Readers Recommended Childhood Immunization Schedule — United States, January 1995</a></p>
|
||
|
||
<p class="footnote"><sup>29</sup><a href="http://www.laskerfoundation.org/awards/show/vaccine-for-preventing-meningitis-in-children/">Albert Lasker Clinical Medical Research Award, 1996 Winners</a></p>
|
||
|
||
<p class="footnote"><sup>30</sup>Kelly DF, Moxon ER, Pollard AJ. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15379976">Haemophilus influenzae type b conjugate vaccines</a>. <em>Immunology</em>. 2004;113(2):163-174.</p>
|
||
|
||
<p class="footnote"><sup>31</sup><a href="http://www.cdc.gov/vaccines/imz-managers/coverage/nis/child/data/tables-2013.html">Coverage with Individual Vaccines and Vaccination Series, by State and Local area</a>. In: CDC, ed. National Immunization Survey 2013.</p>
|
||
|
||
<p class="footnote"><sup>32</sup><a href="http://www.niaid.nih.gov/topics/vaccines/Pages/vaccineBenefits.aspx">NIAID Health and Research Topics: Vaccine Benefits</a> and <a href="http://www.cdc.gov/vaccines/pubs/pinkbook/hib.html">CDC: The Pink Book: Course Textbook — 13th Edition (2015) — Hib</a> (graph adapted from “Secular Trends in the United States” section)</p>
|
||
|
||
<p class="footnote"><sup>33</sup>Briere EC, Rubin L, Moro PL, et al. <a href="http://www.cdc.gov/mmwr/PDF/rr/rr6301.pdf">Prevention and control of haemophilus influenzae type b disease: recommendations of the advisory committee on immunization practices (ACIP)</a>. MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 2014;63(RR-01):1-14.</p>
|
||
|
||
<p class="footnote"><sup>34</sup>Whitney CG, Zhou F, Singleton J, Schuchat A, Centers for Disease C, Prevention. <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6316a4.htm">Benefits from immunization during the vaccines for children program era — United States, 1994–2013</a>. MMWR. Morbidity and mortality weekly report. 2014;63(16):352-355.</p>
|
||
|
||
<p class="footnote"><sup>35</sup>Zhou F, Shefer A, Wenger J, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/24590750">Economic evaluation of the routine childhood immunization program in the United States, 2009</a>. <em>Pediatrics</em>. 2014;133(4):577-585.</p>
|
||
|
||
<p class="footnote"><sup>36</sup>Whitney CG, Zhou F, Singleton J, Schuchat A, Centers for Disease C, Prevention. <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6316a4.htm">Benefits from immunization during the vaccines for children program era — United States, 1994–2013</a>. MMWR. Morbidity and mortality weekly report. 2014;63(16):352-355. (see <a href="http://www.cdc.gov/vaccines/programs/vfc/pubs/methods/">Appendix Table 2</a>)</p>
|
||
|
||
<p class="footnote"><sup>37</sup><a href="http://www.laskerfoundation.org/awards/show/vaccine-for-preventing-meningitis-in-children/">Albert Lasker Clinical Medical Research Award, 1996 Winners</a></p>
|
||
|
||
<p class="footnote"><sup>38</sup>Robbins JB, Schneerson R, Anderson P, Smith DH. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8827975">The 1996 Albert Lasker Medical Research Awards. Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines</a>. <em>Jama</em>. 1996;276(14):1181-1185, also <a href="http://www.laskerfoundation.org/awards/show/vaccine-for-preventing-meningitis-in-children/">Albert Lasker Clinical Medical Research Award, 1996 Winners</a> and <a href="http://www.nichd.nih.gov/news/releases/pages/cviawar2.aspx">NICHD Press Release: NICHD Researchers Honored by WHO for Developing Vaccines Against Haemophilus Influenzae</a>, December 10, 1996.</p>
|
||
|
||
<p class="footnote"><sup>39</sup>Zhou F, Shefer A, Wenger J, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/24590750">Economic evaluation of the routine childhood immunization program in the United States, 2009</a>. <em>Pediatrics</em>. 2014;133(4):577-585.</p>
|
||
</div>
|
||
|
||
<h4 class="collapsible-trigger">Appendix</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<p>The table below provides a more detailed list of selected milestones underlying this story’s “Research-to-Practice Milestones” (page 2 of the pdf), including the lead scientists, research institutions, funding sources, and scientific publications involved in each one.</p>
|
||
|
||
<p><strong>Foundational Research</strong></p>
|
||
|
||
<table border="0" cellpadding="10" cellspacing="0" class="table-data-tight" summary="Foundational Research">
|
||
<tbody>
|
||
<tr>
|
||
<th>Year</th>
|
||
<th>Description of Milestone</th>
|
||
<th>Primary Investigator(s)</th>
|
||
<th>Research Institution</th>
|
||
<th>Funding source (including NIH grant numbers where available)</th>
|
||
<th>Citation 1</th>
|
||
<th>Citation 2</th>
|
||
</tr>
|
||
<tr>
|
||
<td>1892</td>
|
||
<td>Bacteria isolated in sputum of patients during an influenza outbreak – later named Haemophilus</td>
|
||
<td>Pfeiffer</td>
|
||
<td>N/A</td>
|
||
<td>N/A</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/17353280">Jin Z, Romero-Steiner S, Carlone GM, Robbins JB, Schneerson R. Haemophilus influenzae type a infection and its prevention. Infection and immunity. 2007;75(6):2650-2654</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1923</td>
|
||
<td>First diphtheria vaccine developed</td>
|
||
<td>Ramon</td>
|
||
<td>Pasteur Institute (France)</td>
|
||
<td>N/A</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/14630981">Baker JP, Katz SL. Childhood vaccine development: an overview. Pediatric research. 2004;55(2):347-356</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1924</td>
|
||
<td>First tetanus vaccine developed</td>
|
||
<td>Descombey</td>
|
||
<td>N/A</td>
|
||
<td>N/A</td>
|
||
<td><a href="http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/tetanus.pdf">CDC: The Pink Book: Tetanus Vaccine</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1929</td>
|
||
<td>The ability of the sugar coat surrounding some bacteria, called the capsular polysaccharide, to generate an immune response was enhanced.</td>
|
||
<td>Avery and Goebel</td>
|
||
<td>Rockefeller Institute</td>
|
||
<td>N/A</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/19869645">Avery OT, Goebel WF. Chemo-Immunological Studies on Conjugated Carbohydrate-Proteins : Ii. Immunological Specificity of Synthetic Sugar-Protein Antigens. The Journal of experimental medicine. 1929;50(4):533-550.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1930s</td>
|
||
<td>Hib was discovered and found to be the primary cause of bacterial meningitis. A unique feature of the type b strain is the structure of the sugar molecules on the bacterial coat, later known as the capsular polysaccharide.</td>
|
||
<td>Pittman</td>
|
||
<td>Rockefeller Institute</td>
|
||
<td>N/A</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/19869858">Pittman M. Variation and Type Specificity in the Bacterial Species Hemophilus Influenzae. The Journal of experimental medicine. 1931;53(4):471-492.</a></td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/19870224">Pittman M. The Action of Type-Specific Hemophilus Influenzae Antiserum. The Journal of experimental medicine. 1933;58(6):683-706.</a></td>
|
||
</tr>
|
||
<tr>
|
||
<td>1933</td>
|
||
<td>Determined that children develop systemic Hib infections when placental antibodies waned</td>
|
||
<td>Fothergill and Wright</td>
|
||
<td>Harvard University</td>
|
||
<td>Philip Ellis Stevens, Jr., Memorial Fund</td>
|
||
<td><a href="http://www.jimmunol.org/content/24/4/273.abstract">Fothergill L, Wright J. The Relation of Age Incidence to the Bactericidal Power of Blood Against the Causal Organism. J Immunol. 1933; 24(4): 273-284</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1936</td>
|
||
<td>A molecule’s ability to generate antibodies in animals is enhanced when bound to a more immune stimulating molecule</td>
|
||
<td>Landsteiner</td>
|
||
<td>Rockefeller Institute</td>
|
||
<td>N/A</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/19870475">Landsteiner K, van der Scheer J. On Cross Reactions of Immune Sera to Azoproteins. The Journal of experimental medicine. 1936;63(3):325-339.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
</tbody>
|
||
</table>
|
||
|
||
<p><strong>Early Hib Vaccine Development</strong></p>
|
||
|
||
<table border="0" cellpadding="10" cellspacing="0" class="table-data-tight" summary="Early Hib Vaccine Development">
|
||
<tbody>
|
||
<tr>
|
||
<th>Year</th>
|
||
<th>Description of Milestone</th>
|
||
<th>Primary Investigator(s)</th>
|
||
<th>Research Institution</th>
|
||
<th>Funding source (including NIH grant numbers where available)</th>
|
||
<th>Citation 1</th>
|
||
<th>Citation 2</th>
|
||
</tr>
|
||
<tr>
|
||
<td>1968</td>
|
||
<td>Hib polysaccharides were isolated, purified, and considered for clinical use</td>
|
||
<td>Smith and Anderson</td>
|
||
<td>Harvard Medical School</td>
|
||
<td>N/A</td>
|
||
<td><a href="http://www.laskerfoundation.org/awards/show/vaccine-for-preventing-meningitis-in-children/">Albert Lasker Clinical Medical Research Award, 1996 Winners</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1970s</td>
|
||
<td>Hib polysaccharides were recognized as the predominate bacterial substances that elicited immune responses, as opposed to proteins as widely believed.</td>
|
||
<td>Robbins and Schneerson</td>
|
||
<td>NIH</td>
|
||
<td>NICHD Intramural Research Program</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/21199851">Alexander DF. Why should there be an NICHD? Pediatrics. 2011;127(2):325-333</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1971</td>
|
||
<td>Hib polysaccharides were isolated and purified</td>
|
||
<td>Robbins and Schneerson</td>
|
||
<td>Albert Einstein College of Medicine</td>
|
||
<td>NIAID grant (R01AI8110), NICHD contract (69-2246), and NICHD grant (K03HD22856)</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/4999258">Rodrigues LP, Schneerson R, Robbins JB. Immunity to Hemophilus influenzae type b. I. The isolation, and some physicochemical, serologic and biologic properties of the capsular polysaccharide of Hemophilus influenzae type b. Journal of immunology. 1971;107(4):1071-1080.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1973</td>
|
||
<td>First purified Hib polysaccharide vaccine induced antibody responses in 87% of children over the age of two years, but only in a quarter of infants tested.</td>
|
||
<td>Smith and Anderson</td>
|
||
<td>Harvard Medical School</td>
|
||
<td>NIAID contract (71-2196), NIAID grants (AI20376, AI46905)</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/4542777">Smith DH, Peter G, Ingram DL, Harding AL, Anderson P. Responses of children immunized with the capsular polysaccharide of Hemophilus influenzae, type b. Pediatrics. 1973;52(5):637-644.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1977</td>
|
||
<td>A clinical trial assessed the effectiveness of the Hib polysaccharide vaccine in 100,000 children between three months to two years of age. The vaccine proved highly efficacious in those children over 18 months of age, as opposed to younger children.</td>
|
||
<td>Peltola</td>
|
||
<td>University of Helsinki & National Public Health Institute (Finland)</td>
|
||
<td>NIAID contract (AI52502)</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/335348">Peltola H, Kayhty H, Sivonen A, Makela H. Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland. Pediatrics. 1977;60(5):730-737.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1983</td>
|
||
<td>Praxis Biologics was founded to further develop childhood vaccines, including Hib.</td>
|
||
<td>Smith and Anderson</td>
|
||
<td>Praxis Biologics</td>
|
||
<td>N/A</td>
|
||
<td><a href="http://www.laskerfoundation.org/awards/show/vaccine-for-preventing-meningitis-in-children/">Albert Lasker Clinical Medical Research Award, 1996 Winners</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1984</td>
|
||
<td>When half of the children from the 1977 study were re-evaluated, the children who received the vaccine after 18 months of age continued to show good immune responses, while those vaccinated as infants only showed short-lived antibody responses.</td>
|
||
<td>Peltola</td>
|
||
<td>University of Helsinki & National Public Health Institute of Finland</td>
|
||
<td>NIAID contract (AI52502)</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/6610125?dopt=Abstract">Peltola H, Kayhty H, Virtanen M, Makela PH. Prevention of Hemophilus influenzae type b bacteremic infections with the capsular polysaccharide vaccine. The New England journal of medicine. 1984;310(24):1561-1566.</a></td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/6387614">Kayhty H, Karanko V, Peltola H, Makela PH. Serum antibodies after vaccination with Haemophilus influenzae type b capsular polysaccharide and responses to reimmunization: no evidence of immunologic tolerance or memory. Pediatrics. 1984;74(5):857-865.</a></td>
|
||
</tr>
|
||
<tr>
|
||
<td>1985</td>
|
||
<td>The FDA approved Hib polysaccharide vaccines from three companies (including Praxis Biologics) for use in children older than two years of age.</td>
|
||
<td>N/A</td>
|
||
<td>N/A</td>
|
||
<td>N/A</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/8827975">Robbins JB, Schneerson R, Anderson P, Smith DH. The 1996 Albert Lasker Medical Research Awards. Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines. Jama. 1996;276(14):1181-1185.</a></td>
|
||
<td><a href="http://www.laskerfoundation.org/awards/show/vaccine-for-preventing-meningitis-in-children/">Albert Lasker Clinical Medical Research Award, 1996 Winners</a></td>
|
||
</tr>
|
||
</tbody>
|
||
</table>
|
||
|
||
<p><strong>Protecting Infants with a Next-Generation Conjugate Vaccine</strong></p>
|
||
|
||
<table border="0" cellpadding="10" cellspacing="0" class="table-data-tight" summary="Protecting Infants with a Next-Generation Conjugate Vaccine">
|
||
<tbody>
|
||
<tr>
|
||
<th>Year</th>
|
||
<th>Description of Milestone</th>
|
||
<th>Primary Investigator(s)</th>
|
||
<th>Research Institution</th>
|
||
<th>Funding source (including NIH grant numbers where available)</th>
|
||
<th>Citation 1</th>
|
||
<th>Citation 2</th>
|
||
</tr>
|
||
<tr>
|
||
<td>1980</td>
|
||
<td>By applying the foundational early 20th century research highlighted above, Hib polysaccharides were linked to proteins shown to be effective vaccines against other bacteria (e.g., diphtheria), producing what is now known as a “conjugate vaccine."</td>
|
||
<td>Robbins and Schneerson</td>
|
||
<td>FDA</td>
|
||
<td>FDA</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/6967514">Schneerson R, Barrera O, Sutton A, Robbins JB. Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates. The Journal of experimental medicine. 1980;152(2):361-376.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1984</td>
|
||
<td>NIH and FDA scientists found that this conjugate vaccine triggered immune responses in appropriate animal models.</td>
|
||
<td>Robbins and Schneerson</td>
|
||
<td>NIH and FDA</td>
|
||
<td>NIH Intramural research programs at NICHD, National Institiute of Neurological and Commlunicative Disorders and Stroke, and National Instituite of Arthritis, Metabolism, and Digestive Diseases; FDA's Center for Drugs and Biologics</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/6332076">Schneerson R, Robbins JB, Chu C, et al. Serum antibody responses of juvenile and infant rhesus monkeys injected with Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-protein conjugates. Infection and immunity. 1984;45(3):582-591.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1986</td>
|
||
<td>Immune responses in infants could be enhanced if fewer sugar molecules were used with the Hib conjugate vaccine.</td>
|
||
<td>Smith and Anderson</td>
|
||
<td>University of Rochester, Praxis Biologics</td>
|
||
<td>NIAID grants (AI17938, AI12673, AI17217, AI02653)</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/3016088">Anderson PW, Pichichero ME, Insel RA, Betts R, Eby R, Smith DH. Vaccines consisting of periodate-cleaved oligosaccharides from the capsule of Haemophilus influenzae type b coupled to a protein carrier: structural and temporal requirements for priming in the human infant. Journal of immunology. 1986;137(4):1181-1186.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1986</td>
|
||
<td>The Hib polysaccharide vaccine linked to tetanus proteins elicited strong, protective immune responses in young adults.</td>
|
||
<td>Robbins and Schneerson</td>
|
||
<td>NIH, FDA, Uniformed Services University of the Health Sciences, Charlotte Memorial Hospital and Medical Center, State University of New York</td>
|
||
<td>NIH Intramural research programs at NICHD and National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/3516876?dopt=Abstract">Schneerson R, Robbins JB, Parke JC, Jr., et al. Quantitative and qualitative analyses of serum antibodies elicited in adults by Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-tetanus toxoid conjugates. Infection and immunit</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1987</td>
|
||
<td>Infants produced protective antibodies against Hib following vaccination with short segments of Hib sugars linked to diphtheria proteins.</td>
|
||
<td>Anderson</td>
|
||
<td>University of Rochester</td>
|
||
<td>NIAID grants (AI17938, AI02645, AI17217)</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/3499499">Anderson P, Pichichero M, Edwards K, Porch CR, Insel R. Priming and induction of Haemophilus influenzae type b capsular antibodies in early infancy by Dpo20, an oligosaccharide-protein conjugate vaccine. The Journal of pediatrics. 1987;111(5):644-650.</a></td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/3875705">Anderson P, Pichichero ME, Insel RA. Immunization of 2-month-old infants with protein-coupled oligosaccharides derived from the capsule of Haemophilus influenzae type b. The Journal of pediatrics. 1985;107(3):346-351</a></td>
|
||
</tr>
|
||
<tr>
|
||
<td>1988</td>
|
||
<td>Hib polysaccharides linked to tetanus proteins was safe and effective in 18- to 23-month old healthy children</td>
|
||
<td>Robbins and Schneerson</td>
|
||
<td>NIH, CDC, University of<br />
|
||
Gothenburg (Sweden)</td>
|
||
<td>NICHD Intramural Research Program</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/3361379">Claesson BA, Trollfors B, Lagergard T, et al. Clinical and immunologic responses to the capsular polysaccharide of Haemophilus influenzae type b alone or conjugated to tetanus toxoid in 18- to 23-month-old children. The Journal of pediatrics. 1988;112(5):695-702.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1989</td>
|
||
<td>A clinical study demonstrated infants produced protective antibodies following Hib polysaccharide-tetanus protein conjugate vaccination</td>
|
||
<td>Robbins and Schneerson</td>
|
||
<td>NIH, University of<br />
|
||
Gotheburg (Sweden)</td>
|
||
<td>NICHD Intramural Research Program</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/2783345">Claesson BA, Schneerson R, Robbins JB, et al. Protective levels of serum antibodies stimulated in infants by two injections of Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate. The Journal of pediatrics. 1989;114(1):97-100</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1987-1993</td>
|
||
<td>The FDA approved the first 4 Hib conjugate vaccines for use in infants.</td>
|
||
<td>N/A</td>
|
||
<td>N/A</td>
|
||
<td>N/A</td>
|
||
<td><a href="http://www.ncbi.nlm.nih.gov/pubmed/9781742">Decker MD, Edwards KM. Haemophilus influenzae type b vaccines: history, choice and comparisons. The Pediatric infectious disease journal. 1998;17(9 Suppl):S113-116.</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
<tr>
|
||
<td>1995</td>
|
||
<td>The CDC includes Hib conjugate vaccines in the first childhood vaccine schedule.</td>
|
||
<td>N/A</td>
|
||
<td>N/A</td>
|
||
<td>N/A</td>
|
||
<td><a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/00035471.htm">CDC Notice to Readers Recommended Childhood Immunization Schedule -- United States, January 1995</a></td>
|
||
<td> </td>
|
||
</tr>
|
||
</tbody>
|
||
</table>
|
||
</div>
|
||
|
||
<h4 class="collapsible-trigger">Related Resources on Hib and Other Vaccines</h4>
|
||
|
||
<div class="collapsible-content">
|
||
<ul>
|
||
<li><a href="http://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html">CDC’s Child, Adolescent, & “Catch-up” Immunization Schedules</a></li>
|
||
<li><a href="http://www.cdc.gov/vaccines/programs/vfc/index.html">CDC’s Vaccines for Children Program</a></li>
|
||
<li><a href="http://www.niaid.nih.gov/topics/vaccines/Pages/Default.aspx">NIAID Health and Research Topics: Vaccines</a></li>
|
||
</ul>
|
||
</div>
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||
</div>
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</div></div></div>
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</div>
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<div class="lastupdated">
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