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## You are here

HomeAbout NIHWhat We DoImpact of NIH Research

## Impact of NIH Research

### Impact of NIH Research

                - Improving Health
                - Revolutionizing Science
                - Serving Society
                - Our Stories

# Our Stories

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.

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 published protocol 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

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. http://cerch.berkeley.edu/sites/default/files/ipm_curriculum_final_10.2010.pdf.

9University of California San Francisco California Childcare Health Program. 2013. Green Cleaning, Sanitizing, and Disinfecting: A Curriculum for Early Care and Education. http://cerch.berkeley.edu/sites/default/files/green_cleaning_toolkit.pdf.

10University of California Statewide Integrated Pest Management Program. 2016. University of California Agriculture and Natural Resources. Available: http://ipm.ucanr.edu/training/)

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

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 https://www.akaction.org/wp-content/uploads/ASD_pest_management_policy_02-14-2000.pdf. 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 https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/frank-r-lautenberg-chemical-safety-21st-century-act. Accessed May 2023.

7Anchorage Municipal Assembly. Anchorage Ordinance No. 2017-59. Available online at https://www.akaction.org/wp-content/uploads/Ordinance-2017-59-Pesticide-Free-Anchorage-As-Introduced-3-21-17-1.pdf. 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 https://www.akaction.org/publications/pfas/alaska-community-water-quality-report-pfas-contamination-of-municipality-of-anchorage-and-fairbanks-north-star-borough-waters/. 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 https://www.akleg.gov/basis/Bill/Detail/31?Root=HB%20%2027. Accessed May 2023.

17National Academies of Sciences, Engineering, and Medicine. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. Available online at https://nap.nationalacademies.org/catalog/26156/guidance-on-pfas-exposure-testing-and-clinical-follow-up. 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

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 https://deohs.washington.edu/pnash/aggravating-factors-asthma-rural-environment-afare. 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.] https://www.cdc.gov/vitalsigns/childhood-asthma/index.html. [accessed October 28 2021]

19United States Environmental Protection Agency. 2014. Children’s environmental health disparities: Hispanic and Latino American children and asthma. Available from: https://www.epa.gov/sites/default/files/2014-05/documents/hd_hispanic_asthma.pdf.

20Centers for Disease Control and Prevention. 2020. Most Recent National Asthma Data. [Website.]https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm [Accessed September 27, 2022]

## Reducing PFAS in Drinking Water

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

1Pinney SM, Biro FM, Windham GC, Herrick RL, Yaghjyan L, Calafat AM, Succop P, Sucharew H, Ball KM, Kato K, Kushi LH, Bornschein R. 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.

2Calafat AM, Wong L, Kuklenyik Z, Reidy JA, Needham LL. 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.

3Hernick AD, Brown MK, Pinney SM, Biro FM, Ball KM, Bornschein RL. Sharing unexpected biomarker results with study participants. 2011. Environ Health Perspect. 119(1):1-5.

4White SS, Kato K, Jia LT, Basden BJ, Calafat AM, Hines EP, Stanko JP, Wolf CJ, Abbott BD, Fenton SE. 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.

5Zhao, Y, Tan YS, Haslam, SZ, Yang C. 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.

6Pinney 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. 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.

7Fassler CS, Pinney SE, Xie C, Biro FM, Pinney SM. Complex relationships between perfluorooctanoate, body mass index, insulin resistance and serum lipids in young girls. 2019. Environ Res. 176:108558.

8Pinney SM, Fassler CS, Windham GC, Herrick RL, Xie C, Kushi LH, Biro FM. 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: https://nkywater.org/pdfs/CCRS/ccr2012.pdf. [Accessed 1 August 2022].

10Herrick RL, Buckholz J, Biro FM, Calafat AM, Ye X, Xie C, Pinney SM. 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. https://uc.cloud-cme.com/course/courseoverview?P=0&EID=29137. [Accessed 1 August 2022].

12Agency for Toxic Substances and Disease Registry: Per- and polyfluoroalkyl substances (PFAS) and your health. Available: https://www.atsdr.cdc.gov/pfas/. [Accessed 1 August 2022].

13Hiatt RA, Haslam SZ, Osuch J; Breast Cancer and the Environment Research Centers. 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

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

1https://www.nimh.nih.gov/health/statistics/schizophrenia#part_2544.

2https://www.nimh.nih.gov/health/statistics/schizophrenia.

3https://www.nimh.nih.gov/health/statistics/schizophrenia#part_2715.

4Simon GE, et al. *Psychiatric Services*2017;68(5):456-461. PMID: 28045349.

5https://www.nimh.nih.gov/health/topics/schizophrenia/raise.

6Sullivan HS. *American Journal of Psychiatry* 1994;151,6 Sesquicentennial Supplement:135-9. PMID: 8192188.

7Craig TK, et al. *British Medical Journal* 2004;329(7474):1067. PMID: 15485934.

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.

12Public Law 113–76—Jan. 17, 2014, 113th Congress. Available at: https://www.govinfo.gov/content/pkg/PLAW-113publ76/pdf/PLAW-113publ76.pdf.

13https://med.stanford.edu/peppnet.

14Correll CU, et al. *JAMA Psychiatry* 2014;71(12):1350–63. PMID: 25321337.

15https://grants.nih.gov/grants/guide/rfa-files/RFA-MH-16-600.html.

16https://www.hhs.gov/guidance/sites/default/files/hhs-guidance-documents/cib-10-16-2015_26.pdf.

17Srihari VH, et al. *Psychiatric Services* 2015;66(7): 705-12. PMID: 25639994.

18https://www.nimh.nih.gov/health/topics/schizophrenia/raise/state-health-administrators-and-clinics.

19US Department of Health and Human Services. *Agency Priority Goal Action Plan: Serious Mental Illness.* 2018. Available at: https://assets.performance.gov/APG/HHS/FY2018_Q4_HHS_Serious_Mental_Illness.pdf.

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: https://www.nri-inc.org/media/1547/nri_2016_2017_snapshotpdf.pdf.

21Addington J, et al. *Psychiatric services* 2015;66(7):753–756. PMID: 25588418.

22https://grants.nih.gov/grants/guide/pa-files/PAR-16-264.html

23https://grants.nih.gov/grants/guide/pa-files/PAR-16-265.html

24https://www.congress.gov/114/plaws/publ255/PLAW-114publ255.pdf.

25Nossel N, et al. *Psychiatric Services* 2018; 69(8):863-70. PMID: 29759055.

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: https://www.nasmhpd.org/sites/default/files/Snapshot_of_State_Plans.pdf

27Substance Abuse and Mental Health Services Administration. 2019 Uniform Reporting System (URS) Output Tables. 2020. Available at: https://www.samhsa.gov/data/report/2019-uniform-reporting-system-urs-output-tables.

28Department of Veterans Affairs, Veterans Health Administration, VHA Directive 1163.07, 2020. Available at: https://www.va.gov/vhapublications/publications.cfm?pub=1&order=asc&orderby=pub_Number.

29Substance Abuse and Mental Health Services Administration. 2020 Uniform Reporting System (URS) Output Tables. 2021. Available at https://www.samhsa.gov/data/report/2020-uniform-reporting-system-urs-output-tables.

30Ho B, et al. *American Journal of Psychiatry* 2000;157:808-15. PMID: 10784476.

31Correll CU, et al. *JAMA Psychiatry* 2018;75(6):555-565. PMID: 29800949.

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 https://sczaction.org/wp-content/uploads/2021/11/571-012_WhitePaper_Report_FINAL_updated_11.09.21.pdf.

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

                          - Recovery After an Initial Schizophrenia Episode (RAISE)

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

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. http://www.cdc.gov/nchs/data/dvs/lead1900_98.pdf.

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). https://www.nhlbi.nih.gov/science/framingham-heart-study-fhs. 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.

19Lowering Blood Cholesterol To Prevent Heart Disease. NIH Consens Statement. *Arteriosclerosis*. 1985;5(4):404-12.

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. https://www.nhlbi.nih.gov/research/resources/nhlbi-precision-medicine-initiative/topmed. Accessed September 22, 2017.

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

33Ma J, Ward EM, Siegel RL, Jemal A. Temporal Trends in Mortality in the United States, 1969-2013. *JAMA*. 2015;314(16):1731-1739. doi:10.1001/jama.2015.12319.

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.

38Ford ES, Ajani U a, Croft JB, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980-2000. *N Engl J Med*. 2007;356(23):2388-2398. doi:10.1097/sa.0b013e31815c1098.

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.

44Bibliography | Framingham Heart Study. https://www.framinghamheartstudy.org/fhs-bibliography/index.php. Accessed September 22, 2017.

45dbGaP | phs000007.v29.p10 | Framingham Cohort. https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000007.v29.p10. Accessed September 22, 2017.

46For Researchers | Framingham Heart Study. https://www.framinghamheartstudy.org/researchers/index.php. 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

                          - The Framingham Heart Study Website
                          - NHLBI — About the Framingham Heart Study
                          - CDC — Heart Disease Information
                          - CDC — Stroke Information

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

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

1Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase. Wilks AF, Harpur AG, Kurban RR, Ralph SJ, Zürcher G, Ziemiecki A. Mol Cell Biol. 1991 Apr;11(4):2057-65. PMID: 1848670

2Examples include:

A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Velazquez L, Fellous M, Stark GR, Pellegrini S. Cell. 1992 Jul 24;70(2):313-22. PMID: 1386289

Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components. 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

Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Shuai K, Ziemiecki A, Wilks AF, Harpur AG, Sadowski HB, Gilman MZ, Darnell JE. Nature. 1993 Dec 9;366(6455):580-3. PMID: 7504784

3Molecular cloning of rat JAK3, a novel member of the JAK family of protein tyrosine kinases. Takahashi T, Shirasawa T. FEBS Lett. 1994 Apr 4;342(2):124-8. PMID: 8143863

Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes. 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

JAK3: a novel JAK kinase associated with terminal differentiation of hematopoietic cells. Rane SG, Reddy EP. Oncogene. 1994 Aug;9(8):2415-23. PMID: 7518579

Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2. 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

4Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. 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

Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). 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

5Regulation of JAK3 expression and activation in human B cells and B cell malignancies. 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

6The 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. 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

Distinct tyrosine phosphorylation sites in JAK3 kinase domain positively and negatively regulate its enzymatic activity. 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

Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases. 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

Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). 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

7Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. 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

8Super-enhancers delineate disease-associated regulatory nodes in T cells. 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

9ClinicalTrials.gov Identifier: NCT02535689

10Reviewed in The JAK-STAT pathway: impact on human disease and therapeutic intervention. 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

11Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. 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

                          - What is Rheumatoid Arthritis?
                          - Handout on Health: Rheumatoid Arthritis
                          - Tofacitinib Shows Potential for Treating Lupus  (2017)
                          - Two Drugs That Treat Rheumatoid Arthritis and Blood Cancers Shown to Promote Hair Growth  (April 2016)
                          - NIH researchers reveal link between powerful gene regulatory elements and autoimmune diseases: Findings point to potential drug targets  (February 2015)

## Rare Autoinflammatory Diseases Research: Saving Lives, Giving Hope to Families

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

1Examples include: Siegal S. Benign paroxysmal peritonitis.*Ann Intern Med.*1945;23(1):1-21, as cited in Centola M, Aksentijevich I, Kastner DL. The hereditary periodic fever syndromes: molecular analysis of a new family of inflammatory diseases.*Hum Mol Genet*. 1998;7(10):1581-1588. PMID: 9735379 Reimann HA. Periodic disease; a probable syndrome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia.*J Am Med Assoc*. 1948;136(4):239-244. PMID: 18920089/p>

2One of many examples: Wright DG, Wolff SM, Fauci AS, Alling DW. Efficacy of intermittent colchicine therapy in familial Mediterranean fever. *Ann Intern Med*. 1977;86(2):162-165.

3Williamson LM, Hull D, Mehta R, Reeves WG, Robinson BH, Toghill PJ. Familial Hibernian fever.*Q J Med*. 1982;51(204):469-480. PMID: 7156325

4Pras E, Aksentijevich I, Gruberg L, et al. Mapping of a gene causing familial Mediterranean fever to the short arm of chromosome 16.*N Engl J Med*. 1992 Jun 4;326(23):1509-1513. PMID: 1579134				International FMF Consortium. Ancient missense mutations in a new member of the *RoRet* gene family are likely to cause familial Mediterranean fever. *Cell* 1997;90(4):797-807. PMID: 9288758				French FMF Consortium. A candidate gene for familial Mediterranean fever.*Nat Genet*. 1997;17(1):25-31. PMID: 9288094

5McDermott MF, Aksentijevich I, Galon J, et al. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes.*Cell*. 1999;97(1):133-144. PMID: 10199409

6Aksentijevich I, Nowak M, Mallah M, et al. De novo *CIAS1* 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.*Arthritis Rheum*. 2002;46(12):3340-3348. PMID: 12483741				Feldmann J, Prieur A-M, Quartier P, et al. Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in *CIAS1*, a gene highly expressed in polymorphonuclear cells and chondrocytes.*Am J Hum Genet*. 2002;71(1):198-203. PMID: 12032915

7Goldbach-Mansky R, Dailey NJ, Canna SW, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition.*N Engl J Med*. 2006;355(6):581-592. PMID: 16899778

8Booty MG, Chae JJ, Masters SL, et al. Familial Mediterranean fever with a single *MEFV* mutation: where is the second hit?*Arthritis Rheum*. 2009;60(6):1851-1861. PMID: 19479870

9Aksentijevich I, Masters SL, Ferguson PJ, et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist.*N Engl J Med*. 2009;360(23):2426-2437. PMID: 19494218

10Liu Y, Ramot Y, Torrelo A, et al. Mutations in proteasome subunit β type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity.*Arthritis Rheum*. 2012;64(3):895-907. PMID: 21953331

11Sibley CH, Plass N, Snow J, et al. 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.*Arthritis Rheum*. 2012;64(7):2375-86. PMID: 22294344

12Jesus AA, Goldbach-Mansky R. IL-1 blockade in autoinflammatory syndromes.*Annu Rev Med*. 2014;65:223-244. PMID: 24422572

13Liu Y, Jesus AA, Marrero B, et al. Activated STING in a vascular and pulmonary syndrome.*N Engl J Med*. 2014;371(6):507-518. PMID: 25029335

14De Jesus AA, Canna SW, Liu Y, Goldbach-Mansky R. Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling.*Annu Rev Immunol*. 2015;33:823-874. PMID: 25706096

15De Jesus AA, Canna SW, Liu Y, Goldbach-Mansky R. Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling.*Annu Rev Immunol*. 2015;33:823-874. PMID: 25706096

16National Institutes of Health. NIH scientists identify gene linked to fatal inflammatory disease in children. NIAMS Press Releases. Published July 17, 2014. Accessed August 1, 2016.

17National Institute of Arthritis and Musculoskeletal and Skin Diseases. NIH study contributes to approval of promising treatment for genetic inflammatory disorder. Spotlight on Research. Published March 2013. Accessed August 1, 2016.

18National Institute of Arthritis and Musculoskeletal and Skin Diseases. Deficiency of the Interleukin-1 Receptor Antagonist (DIRA). Autoinflammatory Diseases. Published March 2016. Accessed August 1, 2016.

19National Institutes of Health. NIH scientists discover link among spectrum of childhood diseases. NIAMS Press Releases. Published October 31, 2011. Accessed August 1, 2016.

20U.S. National Library of Medicine. Familial Mediterranean fever: frequency. Genetics Home Reference. Updated July 26, 2016. Accessed August 1, 2016.

21Jesus AA, Goldbach-Mansky R. IL-1 blockade in autoinflammatory syndromes.*Annu Rev Med*. 2014;65:223-244. PMID: 24422572

22U.S. National Library of Medicine. Tumor necrosis factor receptor-associated periodic syndrome: Frequency. Genetics Home Reference. Updated July 26, 2016. Accessed August 1, 2016.

23Bulua AC, Simon A, Maddipati R, et al. Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS).*J Exp Med*. 2011;208(3):519-533. PMID: 21282379

24U.S. National Library of Medicine. Neonatal onset multisystem inflammatory disease: Frequency. Genetics Home Reference. Updated July 26, 2016. Accessed August 1, 2016.				Collins F. Meet Alex—Before and after NIH clinical trial. NIH Director’s blog. Published April 9, 2013. Accessed May 23, 2016

#### Related Resources on Rare Autoinflammatory Diseases Research

                          - Understanding Autoinflammatory Diseases
                          - NIH Director’s Blog: Meet Alex—Before and After NIH Clinical Trial
                          - Autoinflammatory Diseases Studies at the NIH Clinical Center
                          - Autoinflammatory Diseases Research at NIAMS

## Neurostimulation Technologies: Harnessing Electricity To Treat Lost Neural Function

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. Electrical stimuli in the central nervous system microenvironment. *Annual review of biomedical engineering*. 2014;16:397-430.

3Aquilina O. A brief history of cardiac pacing. *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

6http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm343162.htm

7House 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.

8http://www.nidcd.nih.gov/health/hearing/pages/coch.aspx

9Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. *Spine*. 2001;26(24 Suppl):S2-12.

10http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm343162.htm

11Gerasimenko YP, Lu DC, Modaber M, et al. Noninvasive Reactivation of Motor Descending Control after Paralysis. *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.

13Penfield W. Epilepsy and surgical therapy. *Archives of Neurology & Psychiatry.*1936;36(3):449-484.

14Aquilina O. A brief history of cardiac pacing. *Images in paediatric cardiology.* 2006;8(2):17-81.

15Djourno 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.

16Chatrian GE, Petersen MC, Uihlein A. Electrical stimulation of the human brain through implanted electrodespreliminary observations. *Diseases of the nervous system.*1960;21:321-326.

17House 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.

18Simmons FB, Mongeon CJ, Lewis WR, Huntington DA. Electrical Stimulation of Acoustical Nerve and Inferior Colliculus. *Archives of otolaryngology.*1964;79:559-568.

19Kumar K, Rizvi S. Historical and present state of neuromodulation in chronic pain. *Current pain and headache reports.*2014;18(1):387.

20DeLong MR. Activity of pallidal neurons during movement. *Journal of neurophysiology.*1971;34(3):414-427.

21DeLong MR. Activity of basal ganglia neurons during movement. *Brain research.*1972;40(1):127-135.

22DeLong MR. Putamen: activity of single units during slow and rapid arm movements. *Science.*1973;179(4079):1240-1242.

23House 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.

24Hosobuchi Y, Adams JE, Rutkin B. Chronic thalamic stimulation for the control of facial anesthesia dolorosa. *Archives of neurology.*1973;29(3):158-161., NIH training grant NS5593

25Mudry A, Mills M. The early history of the cochlear implant: a retrospective. *JAMA otolaryngology-- head & neck surgery.*2013;139(5):446-453.

26Clark G. *Cochlear Implants: Fundamentals and Applications.* Springer; 2003.

27Clark G, Cowan RSC, Dowell RC. *Cochlear Implantation for Infants and Children: Advances.* Singular Publishing Group; 1997.

28Davis GC, Williams AC, Markey SP, et al. Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. *Psychiatry research.*1979;1(3):249-254.

29Langston 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.

30Burns 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.

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

33Benabid 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.

34Benabid 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.

35Limousin P, Pollak P, Benazzouz A, et al. Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. *Lancet.*1995;345(8942):91-95.

36Limousin 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.

37Medtronic DBS Therapy for Parkinson's Disease and Essential Tremor Clinical Summary, 2013

38Rise MT, W. KG, Inventors; Medtronic, Inc., assignee. Method of treating movement disorders by brain stimulation. US patent 5716377. February 10, 1998.

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

40http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm125520.htm

41Harkema 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.

42Angeli 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.

43Gerasimenko YP, Lu DC, Modaber M, et al. Noninvasive Reactivation of Motor Descending Control after Paralysis. *Journal of neurotrauma.*2015;32(24):1968-1980.

44http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm343162.htm

45https://consensus.nih.gov/1995/1995CochlearImplants100html.htm

46http://www.nidcd.nih.gov/health/hearing/pages/coch.aspx

47Semenov YR, Yeh ST, Seshamani M, et al. Age-dependent cost-utility of pediatric cochlear implantation. *Ear and hearing.*2013;34(4):402-412.

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

49Cheng AK, Rubin HR, Powe NR, Mellon NK, Francis HW, Niparko JK. Cost-utility analysis of the cochlear implant in children. *Jama.*2000;284(7):850-856.

50Semenov YR, Yeh ST, Seshamani M, et al. Age-dependent cost-utility of pediatric cochlear implantation. *Ear and hearing.*2013;34(4):402-412.

51http://www.laskerfoundation.org/awards/2014_c_description.htm

52Weaver 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.

53ibid.

54Rizzone MG, Fasano A, Daniele A, et al. Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: from the advanced phase towards the late stage of the disease?*Parkinsonism & related disorders.*2014;20(4):376-381.

55:http://professional.medtronic.com/pt/neuro/dbs-md/eff/data-and-clinical-outcomes

56http://www.laskerfoundation.org/awards/2014_c_description.htm

57Hariz M, Blomstedt P, Zrinzo L. Future of brain stimulation: new targets, new indications, new technology. *Movement disorders: official journal of the Movement Disorder Society.*2013;28(13):1784-1792.

58http://braininitiative.nih.gov/about.htm

59https://commonfund.nih.gov/sparc/index

60NIH Grant UH2NS095495, BRAIN initiative

61NIH Grant U18EB021793, SPARC program

62http://news.berkeley.edu/2014/05/27/cnep-targets-brain-circuitry-to-treat-mental-disorders/

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**

**1970s–80s: Unlocking the Potential of Neurotechnology**

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

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

#### Related Resources on Neurostimulation Technologies

                          - More on Cochlear Implants
                          - More on Deep Brain Stimulation
                          - More on Brain Stimulation Therapies
                          - Science Education: Bionic Man

## Fighting Cancer: Ushering in a New Era of Molecular Medicine

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

1A Story of Discovery: Gleevec Transforms Cancer Treatment for Chronic Myelogenous Leukemia. National Cancer Institute. Retrieved October 29, 2015, from http://www.cancer.gov/research/progress/discovery/gleevec

2Druker 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.

3http://www.cancer.org/cancer/cancerbasics/thehistoryofcancer/the-history-of-cancer-cancer-treatment-targeted-therapy

4https://www.jstage.jst.go.jp/article/kjm/59/1/59_1_1/_pdf

5Huang X, Cortes J, Kantarjian H. http://www.ncbi.nlm.nih.gov/pubmed/22294282 Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. *Cancer.*2012;118(12):3123-3127.

6http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf

7A Decade of Innovation in Rare Diseases. PhRMA 2015. http://www.phrma.org/sites/default/files/pdf/PhRMA-Decade-of-Innovation-Rare-Diseases.pdf

8Boveri 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.

9https://www.genome.gov/Pages/Education/GeneticTimeline.pdf

10Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. *Journal of the National Cancer Institute.*1960;25:85-109.

11Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. *Nature.*1973;243(5405):290-293.

12Heisterkamp 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.

13Groffen 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.

14Konopka JB, Watanabe SM, Singer JW, Collins SJ, Witte ON. Cell lines and clinical isolates derived from Ph1-positive chronic myelogenous leukemia patients express c-abl proteins with a common structural alteration. *Proceedings of the National Academy of Sciences of the United States of America.*1985;82(6):1810-1814.

15Druker BJ. Perspectives on the development of imatinib and the future of cancer research. *Nature medicine.*2009;15(10):1149-1152.

16Ibid.

17Hunter T. Treatment for chronic myelogenous leukemia: the long road to imatinib. *The Journal of clinical investigation.*2007;117(8):2036-2043.

18Pray L. Gleevec: the breakthrough in cancer treatment. Nat Education. 2008;1(1):37.

19Druker 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.

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 http://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm

22Druker 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.

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

24Druker 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.

25http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm110505.htm

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. http://www.phrma.org/sites/default/files/pdf/PhRMA-Decade-of-Innovation-Rare-Diseases.pdf

28Ibid.

29https://www.jstage.jst.go.jp/article/kjm/59/1/59_1_1/_pdf

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

31http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021588s042lbl.pdf

32http://seer.cancer.gov/csr/1975_2012/browse_csr.php?sectionSEL=13&pageSEL=sect_13_table.16.html#table4

33https://www.jstage.jst.go.jp/article/kjm/59/1/59_1_1/_pdf

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. The price of innovation: new estimates of drug development costs. *Journal of health economics.* 2003;22(2):151-185.

37http://csdd.tufts.edu/files/uploads/Tufts_CSDD_briefing_on_RD_cost_study_-_Nov_18,_2014..pdf

#### 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)**

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

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

#### Related Resources on Gleevec

                          - A Story of Discovery: Gleevec Transforms Cancer Treatment for Chronic Myelogenous Leukemia
                          - More on Gleevec (Imatinib Mesylate)
                          - More on CML Treatment

## Childhood Hib Vaccines: Nearly Eliminating the Threat of Bacterial Meningitis

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

1NIAID Health and Research Topics: Vaccines , CDC Vaccines and Immunizations: List of Vaccines Used in United States

2NIAID Health and Research Topics: Vaccine Benefits , NICHD Mission and Scientific Accomplishments: Hib Vaccine, and WHO Position Paper on Haemophilus infl uenzae type b conjugate vaccines*Weekly Epidemiological Record*. 2006;81(47):445.

3Whitney CG, Zhou F, Singleton J, Schuchat A, Centers for Disease C, Prevention. Benefits from immunization during the vaccines for children program era - United States, 1994-2013. MMWR. Morbidity and mortality weekly report. 2014;63(16):352-355.

4Robbins 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.

5Decker MD, Edwards KM. Haemophilus influenzae type b vaccines: history, choice and comparisons. *The Pediatric infectious disease journal*. 1998;17(9 Suppl):S113-116.

6CDC Diseases and the Vaccines that Prevent Them: Hib and NICHD Press Release: NICHD Researchers Honored by WHO for Developing Vaccines Against Haemophilus Influenzae, December 10, 1996.

7Coverage with Individual Vaccines and Vaccination Series, by State and Local area. In: CDC, ed. National Immunization Survey 2013.

8CDC Vaccine Information Statements: Hib

9NIAID Health and Research Topics: Vaccine Benefits

10NICHD Press Release: NICHD Researchers Honored by WHO for Developing Vaccines Against Haemophilus Influenzae, December 10, 1996.

11Zhou F, Shefer A, Wenger J, et al. Economic evaluation of the routine childhood immunization program in the United States, 2009. *Pediatrics*. 2014;133(4):577-585.

12Albert Lasker Clinical Medical Research Award, 1996 Winners

13Zhou F, Shefer A, Wenger J, et al. Economic evaluation of the routine childhood immunization program in the United States, 2009. *Pediatrics*. 2014;133(4):577-585.

14 Baker JP, Katz SL. Childhood vaccine development: an overview. *Pediatric research*. 2004;55(2):347-356. and CDC: The Pink Book: Tetanus Vaccine

15Pittman M. Variation and Type Specificity in the Bacterial Species Hemophilus Influenzae.*The Journal of experimental medicine*. 1931;53(4):471-492. and Pittman M. The Action of Type-Specific Hemophilus Influenzae Antiserum. *The Journal of experimental medicine*. 1933;58(6):683-706.

16Robbins 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. and 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.

17Landsteiner K, van der Scheer J. On Cross Reactions of Immune Sera to Azoproteins. *The Journal of experimental medicine*. 1936;63(3):325-339. and 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.

18Alexander DF. Why should there be an NICHD?*Pediatrics*. 2011;127(2):325-333, also Albert Lasker Clinical Medical Research Award, 1996 Winners, and 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.

19Smith 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. and 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.

20Albert Lasker Clinical Medical Research Award, 1996 Winners and University of Rochester: Childhood Vaccine with Rochester Roots Recognized

21Robbins 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.

22ibid. and Albert Lasker Clinical Medical Research Award, 1996 Winners

23Schneerson 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. and 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.

24Schneerson 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.

25Claesson 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. also 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. and 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

26Decker MD, Edwards KM. Haemophilus influenzae type b vaccines: history, choice and comparisons. *The Pediatric infectious disease journal*. 1998;17(9 Suppl):S113-116.

27ibid.

28CDC Notice to Readers Recommended Childhood Immunization Schedule — United States, January 1995

29Albert Lasker Clinical Medical Research Award, 1996 Winners

30Kelly DF, Moxon ER, Pollard AJ. Haemophilus influenzae type b conjugate vaccines. *Immunology*. 2004;113(2):163-174.

31Coverage with Individual Vaccines and Vaccination Series, by State and Local area. In: CDC, ed. National Immunization Survey 2013.

32NIAID Health and Research Topics: Vaccine Benefits and CDC: The Pink Book: Course Textbook — 13th Edition (2015) — Hib (graph adapted from “Secular Trends in the United States” section)

33Briere EC, Rubin L, Moro PL, et al. Prevention and control of haemophilus influenzae type b disease: recommendations of the advisory committee on immunization practices (ACIP). 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. Benefits from immunization during the vaccines for children program era — United States, 1994–2013. MMWR. Morbidity and mortality weekly report. 2014;63(16):352-355.

35Zhou F, Shefer A, Wenger J, et al. Economic evaluation of the routine childhood immunization program in the United States, 2009. *Pediatrics*. 2014;133(4):577-585.

36Whitney CG, Zhou F, Singleton J, Schuchat A, Centers for Disease C, Prevention. Benefits from immunization during the vaccines for children program era — United States, 1994–2013. MMWR. Morbidity and mortality weekly report. 2014;63(16):352-355. (see Appendix Table 2)

37Albert Lasker Clinical Medical Research Award, 1996 Winners

38Robbins 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, also Albert Lasker Clinical Medical Research Award, 1996 Winners and NICHD Press Release: NICHD Researchers Honored by WHO for Developing Vaccines Against Haemophilus Influenzae, December 10, 1996.

39Zhou F, Shefer A, Wenger J, et al. Economic evaluation of the routine childhood immunization program in the United States, 2009. *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**

**Early Hib Vaccine Development**

**Protecting Infants with a Next-Generation Conjugate Vaccine**

#### Related Resources on Hib and Other Vaccines

                          - CDC’s Child, Adolescent, & “Catch-up” Immunization Schedules
                          - CDC’s Vaccines for Children Program
                          - NIAID Health and Research Topics: Vaccines

This page last reviewed on January 12, 2024

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