Our Stories

NIH supports research in a wide variety of biomedical and behavioral research areas, advancing our knowledge of health and disease. 鶹ý 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.

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.

For a description of how these stories are put together, view the that describes a systematic way of linking the chain of events between scientific discoveries and the adoption of evidence-based health applications.

Protecting Children from Pesticides

Screenshot of Protecting Children from Pesticides case study

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. Read how informed by this work, New York implemented regulations to promote the use of IPM in residential and child care settings.

References

1Brenner 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.

2Phipatanakul 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.

3Kass 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.

4Bradman 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.

5Chew 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.

6Williams 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.

7Kinney 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.

8University of California San Francisco California Childcare Health Program. 2011. Integrated Pest Management: A Curriculum for Early Care and Education Programs. .

9University of California San Francisco California Childcare Health Program. 2013. Green Cleaning, Sanitizing, and Disinfecting: A Curriculum for Early Care and Education. .

10University of California Statewide Integrated Pest Management Program. 2016. University of California Agriculture and Natural Resources. Available: )

11California Healthy Schools Act. 2000. AB 2260, Statutes of 2000, Ch.718.

12NYC Pesticide Reduction Law. 2007. Intro 329A, Local Law 37

13Neighborhood Notification Law. 2007. Intro 328A

14NYC Health Code. 2008. Article 151

15National Institute of Environmental Health Sciences. (2017-2023). Reducing Pesticide Exposures to Preschool-age Children in California Child Care Centers. R01ES027134

16Alkon 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.

Protecting Arctic Communities from Environmental Exposures

Screenshot of Protecting Arctic Communities case study

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. 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.

References

1Anchorage School District. ASD MEMORANDUM #199. Available online at . Accessed May 2023.

2Miller 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

3Carpenter 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.

4Scrudato 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.

5Welfinger-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.

6Environmental Protection Agency. The Frank R. Lautenberg Chemical Safety for the 21st Century Act. Available online at . Accessed May 2023.

7Anchorage Municipal Assembly. Anchorage Ordinance No. 2017-59. Available online at . Accessed May 2023.

8Byrne, 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.

9von 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.

10Byrne 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.

11Babayev 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.

12Byrne 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.

13Alaska Community Action on Toxics. Alaska Community Water Quality Report: PFAS Contamination of Municipality of Anchorage and Fairbanks North Star Borough Waters. Available at . Accessed May 2023.

14Byrne 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.

15Zheng 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.

16Alaska State Legislature. Regulation for Flame Retardant Chemicals. Available online at . Accessed May 2023.

17National Academies of Sciences, Engineering, and Medicine. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Available online at . Accessed May 2023.

18Jordan-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.

19Miller, 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.

20Moran 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.

Addressing Asthma and Air Pollution: NIEHS-Funded Researchers Bring Solutions to Children in Rural Agricultural Communities

Screenshot of the asthma case study

Addressing Asthma and Air Pollution: NIEHS supported researchers developed an intervention to help reduce asthma in children from rural agricultural communities. 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.

References

1Mortimer 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

2Armstrong 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

3Noss 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

4Noss 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

5Karr, C. 2009. Aggravating Factors of Asthma in a Rural Environment (AFARE). Available online at . Accessed October 2021.

6Loftus 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.

7Williams 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

8Rabinovitch N. 2007. Urinary leukotriene E4. Immunol Allergy Clin North Am 27(4):651-664. doi:10.1016/j.iac.2007.09.004 PMID:17996582

9Loftus 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

10Masterson 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

11Jack 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

12Loftus 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

13Benka-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

14Benka-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

15Riederer 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

16Riederer 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

17Drieling 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

18Centers for Disease Control and Prevention. 2018. Asthma in children. [Website.] . [accessed October 28 2021]

19United States Environmental Protection Agency. 2014. Children’s environmental health disparities: Hispanic and Latino American children and asthma. Available from: .

20Centers for Disease Control and Prevention. 2020. Most Recent National Asthma Data. [Website.] [Accessed September 27, 2022]

Reducing PFAS in Drinking Water

Screenshot of the PFAS case study

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. Read about how they worked with local water departments to implement water filtering techniques that reduced exposure to harmful chemicals.

References

1. 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.

2. 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.

3. Sharing unexpected biomarker results with study participants. 2011. Environ Health Perspect. 119(1):1-5.

4. 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.

5. 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.

6. 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.

7. Complex relationships between perfluorooctanoate, body mass index, insulin resistance and serum lipids in young girls. 2019. Environ Res. 176:108558.

8. 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.

9Water Quality Report. Northern Kentucky Water District. 2012. PWSID#KY0590220—32013. Available: . [Accessed 1 August 2022].

10. 2017. Polyfluoroalkyl substance exposure in the Mid-Ohio River Valley, 1991-2012. Environ Pollut. 228:50-60.

11PFAS, GenX, and Other Forever Chemicals: An Update for Clinicians. University of Cincinnati Center for Continuous Professional Development/CME. . [Accessed 1 August 2022].

12Agency for Toxic Substances and Disease Registry: Per- and polyfluoroalkyl substances (PFAS) and your health. Available: . [Accessed 1 August 2022].

13. 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.

Rapid Translation of Science to Real-World Practice: Coordinated Specialty Care Treatment Programs for Early Schizophrenia

Screenshot of the RAISE case study

Schizophrenia is a serious mental illness and a leading cause of long-term disability. 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.

Additional materials

References

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8Petersen L, et al. British Medical Journal 2005;331(7517):602. PMID: 16141449.

9Kane JM, et al. American Journal of Psychiatry 2016;173(4):362-72. PMID: 26481174.

10Dixon LB, et al. Psychiatric Services 2015;66(7):691–98. PMID: 25772764.

11Goldman HH. Schizophrenia Bulletin 2010;36(5):893–94. PMID: 20660023.

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20Substance 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: .

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26Substance 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:

27Substance Abuse and Mental Health Services Administration. 2019 Uniform Reporting System (URS) Output Tables. 2020. Available at: .

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32Marino L, et al. Early Intervention in Psychiatry 2020;14(5):544–52. PMID: 31502409.

33Keepers GA, et al. American Journal of Psychiatry 2020;177(9): 868-72. PMID: 32867516.

34Societal Costs of Schizophrenia and Related Disorders, 2021. Available at .

35Rosenheck R, et al. Schizophrenia Bulletin 2016;42(4):896-906. PMID: 26834024.

Related Resources on the Rapid Translation of Science to Real-World Practice: Coordinated Specialty Care Treatment Programs for Early Schizophrenia

The Framingham Heart Study: Laying the Foundation for Preventive Health Care

Screenshot of the Framingham Heart Study

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. Read how this study, celebrating its 70th anniversary, changed the way we study health and disease.

Additional materials

References

1Centers for Disease Control and Prevention. Leading Causes of Death, 1900-1998. Natl Vital Stat Rep. 1998;48:1-67. .

2Mahmood SS, Levy D, Vasan RS, Wang TJ. The Framingham Heart Study and the epidemiology of cardiovascular disease: a historical perspective. Lancet (London, England). 2014;383(9921):999-1008. doi:10.1016/S0140-6736(13)61752-3.

3Tsao CW, Vasan RS. The Framingham Heart Study: past, present and future. Int J Epidemiol. 2015;44(6):1763-1766. doi:10.1093/ije/dyv336.

4Gordon T, Kannel W, Cole C, et al. The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease, Sections 1 and 2. 1968.

5Framingham Heart Study (FHS) | National Heart, Lung, and Blood Institute (NHLBI). . Accessed September 22, 2017.

6Tsao CW, Vasan RS. Cohort Profile: The Framingham Heart Study (FHS): overview of milestones in cardiovascular epidemiology. doi:10.1093/ije/dyv337.

7Levy D, Brink S. A Change of Heart. New York, N.Y.: Vintage Books; 2005.

8DAWBER 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. Am J Public Health Nations Health. 1959;49:1349-1356.

9Kannel 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. Ann Intern Med. 1961;55:33-50.

10Marshall TR. The 1964 Surgeon General’s report and Americans’ beliefs about smoking. J Hist Med Allied Sci. 2015;70(2):250-278. doi:10.1093/jhmas/jrt057.

11Kannel WB, LeBauer EJ, Dawber TR, McNamara PM. Relation of body weight to development of coronary heart disease. The Framingham study. Circulation. 1967;35(4):734-744.

12Kannel WB. Habitual level of physical activity and risk of coronary heart disease: the Framingham study. Can Med Assoc J. 1967;96(12):811-812.

13Sorlie PD, Sholinsky PD, Lauer MS, et al. Reinvestment in government-funded research: a great way to share. Circulation. 2015;131(1):17-18. doi:10.1161/CIRCULATIONAHA.114.014204.

14Kannel WB, Wolf PA, Verter J, McNamara PM. Epidemiologic assessment of the role of blood pressure in stroke. The Framingham study. JAMA. 1970;214(2):301-310.

15Feinleib M, Kannel WB, Garrison RJ, Mcnamara PM, Castelli WP. The Framingham Offspring Study. Design and Preliminary Data1. Prev Med (Baltim). 1975;4(5):18-525.

16Kannel WB, Hjortland MC, McNamara PM, Gordon T. Menopause and risk of cardiovascular disease: the Framingham study. Ann Intern Med. 1976;85(4):447-452.

17Wolf PA, Kannel WB, McGee DL, Meeks SL, Bharucha NE, McNamara PM. Duration of atrial fibrillation and imminence of stroke: the Framingham study. Stroke. 14(5):664-667.

18Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983-988. doi:10.1161/01.STR.22.8.983.

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20Hannan MT, Felson DT, Dawson-Hughes B, et al. Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. J Bone Miner Res. 2000;15(4):710-720. doi:10.1359/jbmr.2000.15.4.710.

21Farmer ME, White LR, Abbott RD, et al. Blood pressure and cognitive performance. The Framingham Study. Am J Epidemiol. 1987;126(6):1103-1114.

22Elias MF, D’Agostino RB, Elias PK, Wolf PA. Neuropsychological test performance, cognitive functioning, blood pressure, and age: the Framingham Heart Study. Exp Aging Res. 1995;21(4):369-391. doi:10.1080/03610739508253991.

23Elias PK, D’Agostino RB, Elias MF, Wolf PA. Blood pressure, hypertension, and age as risk factors for poor cognitive performance. Exp Aging Res. 1995;21(4):393-417. doi:10.1080/03610739508253992.

24Levy D, Garrison R, et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. New Engl J Med. 1990;322(22):1561-6.

25Benjamin 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. Circulation. 1998;98(10):946-953.

26Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97(18):1837-1847.

27Splansky 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. Am J Epidemiol. 2007;165(11):1328-1335. doi:10.1093/aje/kwm021.

28Speliotes EK, Willer CJ, Berndt SI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010;42(11):937-948. doi:10.1038/ng.686.

29Psaty 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.

30Benjamin I, Brown N, Burke G, et al. American Heart Association Cardiovascular Genome-Phenome Study: Foundational Basis and Program. Circulation. 2015;131(1):100-112. doi:10.1161/CIRCULATIONAHA.114.014190.

31Trans-Omics for Precision Medicine (TOPMed) Program - NHLBI, NIH. . Accessed September 22, 2017.

32Epidemiological Background and Design: The Framingham Study. https://www.framinghamheartstudy.org/about-fhs/background.php. Accessed September 22, 2017.

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34Centers for Disease Control and Prevention. Achievements in Public Health, 1900-1999: Decline in Deaths from Heart Disease and Stroke — United States, 1900–1999. Morb Mortal Wkly Rep. 1999;48(30):649-656.

35St. Sauver JL, Warner DO, Yawn BP, et al. Why Patients Visit Their Doctors: Assessing the Most Prevalent Conditions in a Defined American Population. Mayo Clin Proc. 2013;88(1):56-67. doi:10.1016/j.mayocp.2012.08.020.

36Saklayen MG, Deshpande N V. Timeline of History of Hypertension Treatment. Front Cardiovasc Med. 2016;3:3. doi:10.3389/fcvm.2016.00003.

37Remington PL, Brownson RC, Centers for Disease Control and Prevention (CDC). Fifty years of progress in chronic disease epidemiology and control. MMWR Suppl. 2011;60(4):70-77.

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39Levy D. 60 years studying heart-disease risk. Nat Rev Drug Discov. 2008;7(9):715-715. doi:10.1038/nrd2667.

40Framingham Risk Functions. https://www.framinghamheartstudy.org/risk-functions/. Accessed September 22, 2017.

41Manton KG, Woodbury MA. Analysis of the Components of CHD Risk in the Framingham Study: New Multivariate Procedures for the Analysis of Chronic Disease Development. Comput Biomed Res. 1979;12:109-123.

42Murphy KM, Topel RH. The Value of Health and Longevity. J Polit Econ. 2006;114(5):871-904. doi:10.1086/508033.

43Cutler DM, Rosen AB, Vijan S. The Value of Medical Spending in the United States, 1960–2000. N Engl J Med. 2006;355(9):920-927. doi:doi:10.1056/NEJMsa054744.

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46For Researchers | Framingham Heart Study. . Accessed September 22, 2017.

47Writing Group Members, Mozaffarian D, Benjamin EJ, et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016;133(4):e38-60. doi:10.1161/CIR.0000000000000350.

Related Resources on the Framingham Heart Study and Cardiovascular Disease

Understanding Immune Cells and Inflammation: Opening New Treatment Avenues for Rheumatoid Arthritis and Other Conditions

Screenshot of the Understanding Immune Cells and Inflammation Case Study

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. 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.

Additional materials

References

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9ClinicalTrials.gov Identifier:

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11 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

Related Resources on Rheumatoid Arthritis and Tofacitinib

  • (2017)
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Rare Autoinflammatory Diseases Research: Saving Lives, Giving Hope to Families

Screenshot of the Rare Autoinflammatory Diseases Case Study.

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. 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

Additional materials

References

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Neurostimulation Technologies: Harnessing Electricity To Treat Lost Neural Function

Screenshot of the Neurostimulation Technologies Case Study.

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. Read the story of how NIH-supported research helped harness the electrical nature of the nervous system to develop cutting-edge therapies

Additional materials

References

1Donald 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.

2Thompson DM, Koppes AN, Hardy JG, Schmidt CE. . Annual review of biomedical engineering. 2014;16:397-430.

3Aquilina O. . Images in paediatric cardiology. 2006;8(2):17-81.

4FDA Premarket Approval P8300693M: Brand Cochlear Implant System/House Design

5FDA Premarket Approval P960009: Medtronic Activa Tremor Control System and Supplement S007: Medtronic Activa Parkinson’s Control System

6

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11Gerasimenko YP, Lu DC, Modaber M, et al. . Journal of neurotrauma. 2015;32(24):1968-1980.

12Donald 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.

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31FDA Premarket Approvals P830069: 3M Brand Cochlear Implant System/House Design and P840024: Nucleus Multichannel Implantable Hearing Prosthesis

32FDA Premarket Approval P890027: Nucleus 22 Channel Cochlear Implant Sys /Children

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37

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39FDA Premarket Approval P960009, Supplement S007: Medtronic Activa Parkinson’s Control

40

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43Gerasimenko YP, Lu DC, Modaber M, et al. . Journal of neurotrauma. 2015;32(24):1968-1980.

44

45

46

47Semenov YR, Yeh ST, Seshamani M, et al. . Ear and hearing. 2013;34(4):402-412.

48Contrera KJ, Choi JS, Blake CR, Betz JF, Niparko JK, Lin FR. . Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2014;35(3):426-430.

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53ibid.

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55:

56

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59

60NIH Grant UH2NS095495, BRAIN initiative

61NIH Grant U18EB021793, SPARC program

62

63NIH Grant UH3NS095554, BRAIN initiative

Appendix

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.

1950s–60s: Stimulating Nerves with Electricity

Year Description of Milestone Primary Investigator(s) Research Institution Funding source (including NIH grant numbers where available) Citation 1 Citation 2 Citation 3 Citation 4
1957 >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. Andre Djourno, Charles Eyries Faculté de Médecine, Paris, France Unknown, Not likely to be NIH
1960 Researchers first tested the long-term safety and effectiveness of implanting electrodes in the human brain. Alfred Uihlein Mayo Clinic Unknown, Not likely to be NIH
1961 The first prototype single-channel cochlear implant is developed, and inserted into two subjects William F. House and James Doyle Private Practice, Los Angeles Private U.S. Patent 3449786 to James Doyle
1964 Firsr 鶹ý grant for cochlear implants funds a report on the effects of auditory nerve stimulation in a patient with normal hearing. F. Blair Simmons Stanford University Funded by NIH grant NB 02167 from the National Institute of Neurological Diseases and Blindness (NINDB).
1968 Medtronic became the first company to introduce a spinal cord stimulation system as a treatment for chronic pain. Unknown Medtronic Corp Private

1970s–80s: Unlocking the Potential of Neurotechnology

Year Description of Milestone Primary Investigator(s) Research Institution Funding source (including NIH grant numbers where available) Citation 1 Citation 2 Citation 3 Citation 4
1971-3 NIH researchers characterized the normal electrical function of deep brain areas involved in movement, which are affected in Parkinson’s Mahlon DeLong NIMH Laboratory of Neurophysiology NIMH Intramural
1972 Early cochlear implants developed with a single electrode, and the first functional prototype implanted in a patient William F. House Private practice, Los Angeles Private, included support from 3M
1973 Improving upon the pain relief provided by spinal cord stimulation, NIH-supported investigators developed the first long-term, implanted device to stimulate the brain Yoshio Hosobuchi UCSF NIH training grant NS5593
1976 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. Robert C. Bilger Univ. of Pittsburgh NIH Contract N01 NS-5-2331.
1970s-80s 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). Graeme Clark; Claude Chouard; F. Blair Simmons and Robert L. White; Michael Merzenich and Robin P. Michelson Academia: Univ. of Melbourne, Australia; INSERM, France; Stanford; UCSF Industry: Nucleus Ltd. , MedEl NIH Grants NS 10532, NS10414, NIH grant NS 11804, NIH Contracts N01-NS-5-2388,-2395,and -2396 Clark GM. Cochlear implants. New York: Springer Verlag; 2003 Clark GM, Cowan RSC, Dowell DC. Cochlear implantation for infants and children. Advances. San Diego: Singular Publishing Group; 1997.
1979-83 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. Irwin Kopin NINDS and NIMH Intramural, Stanford NIMH and NINDS Intramural, Santa Clara County Medical Services, NIMH Intramural
1984, 1985 FDA Approval of first two cochlear implant devices William F. House, Graeme Clark 3M/House Research Institute, Univ. of Melbourne/Cochlear Corp Private--3M and Nucleus Ltd FDA Premarket Approval P830069: 3M Brand Cochlear Implant System/House Design in citation 1 FDA Premarket Approval P840024: Nucleus Multichannel Implantable Hearing Prosthesis

Late 1980s/1990s: Next Generation Devices and Applications

Year Description of Milestone Primary Investigator(s) Research Institution Funding source (including NIH grant numbers where available) Citation 1 Citation 2 Citation 3 Citation 4
1986 Publication of first model for parallel organization of circuits involved in both normal movement and Parkinson's Garrett Alexander, Mahlon DeLong, and Peter Strick Johns Hopkins University NIH Grants NS00632 (G.A.), NS17678 (G.A.), NS16375 (Mahlon DeLong), NS02957 (P.S.), VA, private donations
1986-1990 Studies in the MPTP primate model implcate dysfunction in two regions for movement symptoms in PD and related disorders Mahlon DeLong; John Penney, Anne Young; David Sibley Johns Hopkins University; University of Michigan, Ann Arbor; NINDS/NIMH Intramural NIH Grants NS15655, NS19613, NS01300,NS015417 private donations
1990 The FDA approved cochlear implant use in children, providing an opportunity to restore hearing to children during their developmental years Graeme Clark Cochlear Corp Private-Cochlear Corp FDA Premarket Approval P890027: Nucleus 22 Channel Cochlear Implant Sys /Children
1990-91 Studies demonstrated that inactivation of one deep brain region in a primate model reduces tremor symptoms using the MPTP model for Parkinson's disease Mahlon DeLong; Alan Crossman Johns Hopkins University; University of Manchester Medical School, U.K. NS15417, private funds from the E.K. Dunn family, UK Govt.
1987-98 Studies in humans revealed that electrical stimulation of deep brain regions could quickly and reversibly reduce the tremors associated with Parkinson’s disease. Alim-Louis Benabid Joseph Fourier University of Grenoble, France INSERM/French Govt
1990s Building on earlier research, Medtronic scientists performed clinical trials of deep brain stimulation for tremor and Parkinson’s disease. N/A Medtronic Private-Medtronic
1997 Medtronic received the first FDA approval for deep brain stimulation to treat essential tremor, a common disorder with symptoms similar to Parkinson’s disease. N/A Medtronic Private-Medtronic FDA Premarket Approval P960009: Medtronic Activa Tremor Control System

2000s-2010s: A Rapidly Growing Field Seeking New Targets

Year Description of Milestone Primary Investigator(s) Research Institution Funding source (including NIH grant numbers where available) Citation 1 Citation 2 Citation 3 Citation 4
2002-03 The Medtronic deep brain stimulation device was approved by the FDA to treat symptoms of Parkinson’s disease N/A Medtronic Private-Medtronic FDA Premarket Approval P960009: Medtronic Activa Tremor Control System, Supplement S007: Medtronic Activa Parkinson’s Control System
2009 A large clinical trial demonstrated that deep brain stimulation is superior to best medical therapy Frances Weaver Hines VA Hospital (and many others via the CSP 468 Study Group) VA, NIH-NINDS, Medtronic
2009 FDA approves a humanitarian exemption for deep brain stimulation as a treatment for Obsessive-Compulsive Disorder N/A Medtronic Private-Medtronic
2011-14 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 V. Reggie Edgerton; Susan Harkema University of California, Los Angeles; University of Louisville 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
2014 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. Mark Humayan, Robert Jay Greenberg Johns Hopkins University, Second Sight Medical Products, Inc. NIH Grants: EY011888 and EY012893
2015 NIH-funded researchers stimulate the spinal cord through the skin, generating intentional step-like movements in patients with spinal cord injury V. Reggie Edgerton University of California, Los Angeles NIH Grants EB15521, EB007615, TR000124, Reeve Foundation, Walkabout Foundation, F.M. Kirby Foundation

Related Resources on Neurostimulation Technologies

Fighting Cancer: Ushering in a New Era of Molecular Medicine

Screenshot of the Fighting Cancer Case Study.

Huge advances in our understanding of disease at a molecular level are paving the way for more effective, personalized treatments. Gleevec®, a drug used to treat chronic myelogenous leukemia (CML), was among the first successful molecular medicines developed. Read the story of how NIH-supported research helped create a revolutionary cancer drug that changed the way we think about designing new medicines

Additional materials

References

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19Druker BJ, Tamura S, Buchdunger E, et al. . Nature medicine. 1996;2(5):561-566.

20Food and Drug Administration Modernization Act. S. 830. 105th Congress. (1997).

21Fast Track. Food and Drug Administration. Updated 2014, September 15. Retrieved October 29, 2015, from

22Druker BJ, Talpaz M, Resta DJ, et al. . The New England journal of medicine. 2001;344(14):1031-1037.

23Waalen J. . Howard Hughes Medical Institute Bulletin. 2001 Dec;14(5):10-15.

24Druker BJ, Guilhot F, O'Brien SG, et al. . The New England journal of medicine. 2006;355(23):2408-2417.

25

26Cumulative number of publications containing the search term “imatinib” from 1996-2014 in the PubMed database.

27A Decade of Innovation in Rare Diseases. PhRMA 2015.

28Ibid.

29

30Determined by searching clinicaltrials.gov for registered clinical trials using the term “imatinib,” “Gleevec,” or “Glivec.”

31

32

33

34Determined using data provided by FDA’s Center for Drug Evaluation and Research on mechanism of action of approved FDA drugs, 1999-2015.

35Determined using data provided by FDA’s Center for Drug Evaluation and Research on the companies associated with approved FDA drugs.

36DiMasi JA, Hansen RW, Grabowski HG. . Journal of health economics. 2003;22(2):151-185.

37

Appendix

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.

Identifying the Molecular Trigger of CML (1914–1990)

Year Description of Milestone Primary Investigator(s) Research Institution Funding source (including NIH grant numbers where available) Citation 1 Citation 2
1914 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. Boveri N/A Unknown (Germany)
1950s Using newly developed techniques to study cells and chromosomes, researchers began to link chromosomal abnormalities to specific human diseases. None specific N/A N/A
1960 Drs. Nowell and Hungerford studied cells from CML patients and discovered an atypical small chromosome in the cancer cells, called the Philadelphia chromosome. Nowell and Hungerford University of Pennsylvania NIH (C-3562), American Cancer Society, US Public Health Service
1973 Dr. Rowley discovered that the Philadelphia chromosome results from a chromosomal translocation between chromosomes 9 and 22. Rowley University of Chicago Unknown
1983 Researchers identified the genes involved in the Philadelphia chromosome, showing that the human oncogene c-abl is part of the translocation. Heisterkamp NIH (NCI intramural); Erasmus University NIH (contract COI-CP-75380), Netherlands Cancer Society
1984 Scientists identified the breakpoint cluster region (bcr) on chromosome 22. Groffen NIH (NCI intramural); Erasmus University NIH (contract COI-CP-75380), Netherlands Cancer Society
1990 Researchers identified the function of the bcr-abl fusion gene, which prompts production of an improperly regulated abnormal tyrosine kinase protein. Lugo University of California, Los Angeles NIH/NCI (T32GM08243 and T32GM07185), Howard Hughes Medical Institute, Leukemia Society of America

Developing a targeted Bcr-abl kinase inhibitor (1990–1996)

Year Description of Milestone Primary Investigator(s) Research Institution Funding source (including NIH grant numbers where available) Citation 1 Citation 2
1990 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. Nick Lydon Ciba-Geigy (now Novartis) Ciba-Geigy
1990 Dr. Druker began developing model systems to study BCR-ABL signaling and outlined how to characterize BCR-ABL kinase inhibitors. Brian Druker Dana-Farber Cancer Institute NIH/NCI (K08CA001422)
1992 The compound that would become Gleevec was first synthesized, although many years of testing would be needed before its effectiveness was known. N/A Ciba-Geigy Ciba-Geigy
1993 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. Brian Druker Oregon Health & Sciences University; Ciba-Geigy NIH/NCI (K08CA001422); Ciba-Geigy
1996 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. Brian Druker Oregon Health & Sciences University; Ciba-Geigy NIH/NCI (K08CA001422); Ciba-Geigy

Testing and Approving a Life-changing Drug (1997–2015)

Year Description of Milestone Primary Investigator(s) Research Institution Funding source (including NIH grant numbers where available) Citation 1 Citation 2
1998 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. Brian Druker Ciba-Geigy; Oregon Health & Sciences University NIH (R01CA65823 and P01CA032737); Novartis
2001 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. N/A Novartis NIH, Novartis
2006 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. Druker Novartis; Oregon Health & Sciences University Novartis

Related Resources on Gleevec

Childhood Hib Vaccines: Nearly Eliminating the Threat of Bacterial Meningitis

Screenshot of the Childhood Hib Vaccines Case Study.

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. Read the story of how NIH-supported research helped create a vaccine that has nearly eliminated childhood meningitis

Additional materials

References

1 ,

2 , , and Weekly Epidemiological Record. 2006;81(47):445.

3Whitney CG, Zhou F, Singleton J, Schuchat A, Centers for Disease C, Prevention. . MMWR. Morbidity and mortality weekly report. 2014;63(16):352-355.

4Robbins JB, Schneerson R, Anderson P, Smith DH. . Jama. 1996;276(14):1181-1185.

5Decker MD, Edwards KM. . The Pediatric infectious disease journal. 1998;17(9 Suppl):S113-116.

6 and , December 10, 1996.

7. In: CDC, ed. National Immunization Survey 2013.

8

9

10, December 10, 1996.

11Zhou F, Shefer A, Wenger J, et al. . Pediatrics. 2014;133(4):577-585.

12

13Zhou F, Shefer A, Wenger J, et al. . Pediatrics. 2014;133(4):577-585.

14 Baker JP, Katz SL. . Pediatric research. 2004;55(2):347-356. and

15Pittman M. . The Journal of experimental medicine. 1931;53(4):471-492. and Pittman M. . The Journal of experimental medicine. 1933;58(6):683-706.

16Robbins JB, Schneerson R, Anderson P, Smith DH. . Jama. 1996;276(14):1181-1185. and Jin Z, Romero-Steiner S, Carlone GM, Robbins JB, Schneerson R. . Infection and immunity. 2007;75(6):2650-2654.

17Landsteiner K, van der Scheer J. . The Journal of experimental medicine. 1936;63(3):325-339. and Avery OT, Goebel WF. . The Journal of experimental medicine. 1929;50(4):533-550.

18Alexander DF. Pediatrics. 2011;127(2):325-333, also , and Rodrigues LP, Schneerson R, Robbins JB. . Journal of immunology. 1971;107(4):1071-1080.

19Smith DH, Peter G, Ingram DL, Harding AL, Anderson P. . Pediatrics. 1973;52(5):637-644. and Peltola H, Kayhty H, Sivonen A, Makela H. . Pediatrics. 1977;60(5):730-737.

20 and

21Robbins JB, Schneerson R, Anderson P, Smith DH. . Jama. 1996;276(14):1181-1185.

22ibid. and

23Schneerson R, Barrera O, Sutton A, Robbins JB. . The Journal of experimental medicine. 1980;152(2):361-376. and Robbins JB, Schneerson R, Anderson P, Smith DH. . Jama. 1996;276(14):1181-1185.

24Schneerson R, Robbins JB, Chu C, et al. . Infection and immunity. 1984;45(3):582-591.

25Claesson BA, Schneerson R, Robbins JB, et al. . The Journal of pediatrics. 1989;114(1):97-100. also Anderson P, Pichichero M, Edwards K, Porch CR, Insel R. . The Journal of pediatrics. 1987;111(5):644-650. and Anderson P, Pichichero ME, Insel RA. . The Journal of pediatrics. 1985;107(3):346-351

26Decker MD, Edwards KM. . The Pediatric infectious disease journal. 1998;17(9 Suppl):S113-116.

27ibid.

28

29

30Kelly DF, Moxon ER, Pollard AJ. . Immunology. 2004;113(2):163-174.

31. In: CDC, ed. National Immunization Survey 2013.

32 and (graph adapted from “Secular Trends in the United States” section)

33Briere EC, Rubin L, Moro PL, et al. . MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 2014;63(RR-01):1-14.

34Whitney CG, Zhou F, Singleton J, Schuchat A, Centers for Disease C, Prevention. . MMWR. Morbidity and mortality weekly report. 2014;63(16):352-355.

35Zhou F, Shefer A, Wenger J, et al. . Pediatrics. 2014;133(4):577-585.

36Whitney CG, Zhou F, Singleton J, Schuchat A, Centers for Disease C, Prevention. . MMWR. Morbidity and mortality weekly report. 2014;63(16):352-355. (see )

37

38Robbins JB, Schneerson R, Anderson P, Smith DH. . Jama. 1996;276(14):1181-1185, also and , December 10, 1996.

39Zhou F, Shefer A, Wenger J, et al. . Pediatrics. 2014;133(4):577-585.

Appendix

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.

Foundational Research

Year Description of Milestone Primary Investigator(s) Research Institution Funding source (including NIH grant numbers where available) Citation 1 Citation 2
1892 Bacteria isolated in sputum of patients during an influenza outbreak – later named Haemophilus Pfeiffer N/A N/A
1923 First diphtheria vaccine developed Ramon Pasteur Institute (France) N/A
1924 First tetanus vaccine developed Descombey N/A N/A
1929 The ability of the sugar coat surrounding some bacteria, called the capsular polysaccharide, to generate an immune response was enhanced. Avery and Goebel Rockefeller Institute N/A
1930s 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. Pittman Rockefeller Institute N/A
1933 Determined that children develop systemic Hib infections when placental antibodies waned Fothergill and Wright Harvard University Philip Ellis Stevens, Jr., Memorial Fund
1936 A molecule’s ability to generate antibodies in animals is enhanced when bound to a more immune stimulating molecule Landsteiner Rockefeller Institute N/A

Early Hib Vaccine Development

Year Description of Milestone Primary Investigator(s) Research Institution Funding source (including NIH grant numbers where available) Citation 1 Citation 2
1968 Hib polysaccharides were isolated, purified, and considered for clinical use Smith and Anderson Harvard Medical School N/A
1970s Hib polysaccharides were recognized as the predominate bacterial substances that elicited immune responses, as opposed to proteins as widely believed. Robbins and Schneerson NIH NICHD Intramural Research Program
1971 Hib polysaccharides were isolated and purified Robbins and Schneerson Albert Einstein College of Medicine NIAID grant (R01AI8110), NICHD contract (69-2246), and NICHD grant (K03HD22856)
1973 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. Smith and Anderson Harvard Medical School NIAID contract (71-2196), NIAID grants (AI20376, AI46905)
1977 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. Peltola University of Helsinki & National Public Health Institute (Finland) NIAID contract (AI52502)
1983 Praxis Biologics was founded to further develop childhood vaccines, including Hib. Smith and Anderson Praxis Biologics N/A
1984 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. Peltola University of Helsinki & National Public Health Institute of Finland NIAID contract (AI52502)
1985 The FDA approved Hib polysaccharide vaccines from three companies (including Praxis Biologics) for use in children older than two years of age. N/A N/A N/A

Protecting Infants with a Next-Generation Conjugate Vaccine

Year Description of Milestone Primary Investigator(s) Research Institution Funding source (including NIH grant numbers where available) Citation 1 Citation 2
1980 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." Robbins and Schneerson FDA FDA
1984 NIH and FDA scientists found that this conjugate vaccine triggered immune responses in appropriate animal models. Robbins and Schneerson NIH and FDA 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
1986 Immune responses in infants could be enhanced if fewer sugar molecules were used with the Hib conjugate vaccine. Smith and Anderson University of Rochester, Praxis Biologics NIAID grants (AI17938, AI12673, AI17217, AI02653)
1986 The Hib polysaccharide vaccine linked to tetanus proteins elicited strong, protective immune responses in young adults. Robbins and Schneerson NIH, FDA, Uniformed Services University of the Health Sciences, Charlotte Memorial Hospital and Medical Center, State University of New York NIH Intramural research programs at NICHD and National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases
1987 Infants produced protective antibodies against Hib following vaccination with short segments of Hib sugars linked to diphtheria proteins. Anderson University of Rochester NIAID grants (AI17938, AI02645, AI17217)
1988 Hib polysaccharides linked to tetanus proteins was safe and effective in 18- to 23-month old healthy children Robbins and Schneerson NIH, CDC, University of
Gothenburg (Sweden)		 NICHD Intramural Research Program
1989 A clinical study demonstrated infants produced protective antibodies following Hib polysaccharide-tetanus protein conjugate vaccination Robbins and Schneerson NIH, University of
Gotheburg (Sweden)		 NICHD Intramural Research Program
1987-1993 The FDA approved the first 4 Hib conjugate vaccines for use in infants. N/A N/A N/A
1995 The CDC includes Hib conjugate vaccines in the first childhood vaccine schedule. N/A N/A N/A

Related Resources on Hib and Other Vaccines

This page last reviewed on January 12, 2024