3

NIH Bethesda Campus: Facilities and Activities

OVERVIEW OF MISSION (INTRAMURAL, EXTRAMURAL)

Among its tasks, the committee has been asked to identify potential factors and approaches that the National Institutes of Health (NIH) should consider in developing a comprehensive capital strategy for its main campus portfolio of facilities to span from 5 to 20 years into the future. To respond to this task, it is important to review in some detail the history and culture of NIH and of the Bethesda Campus in particular. The administrative heart of the entire NIH is located there, as well as the largest dedicated research hospital in the world, in addition to acres of research space and research support services.

Mission of NIH

The 27 institutes and centers (ICs) that comprise NIH have diverse missions and areas of focus. The NIH leadership expresses the collective goal of these organizations in broad terms as follows:¹

• To foster fundamental creative discoveries, innovative research strategies, and their applications as a basis for ultimately protecting and improving health;
• To develop, maintain, and renew scientific human and physical resources that will ensure the nation’s capability to prevent disease;
• To expand the knowledge base in medical and associated sciences in order to enhance the nation’s economic well-being and ensure a continued high return on the public investment in research; and
• To exemplify and promote the highest level of scientific integrity, public accountability, and social responsibility in the conduct of science.

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¹ P.A. Sieving, National Eye Institute, and D. Wheeland, NIH Office of Research Facilities, 2018, “Orientation to the NIH,” presentation to the committee on March 20.

History and Description of the NIH Bethesda Campus

The NIH Bethesda Campus (NIH-BC) includes a large intramural research program nested within an administrative structure that offers central oversight over all NIH activities, including intramural and extramural programs. The intramural programs are located on the campus and sites nearby (with a few exceptions), whereas the extramural programs, which constitute most of NIH’s research expenditures, are not performed by NIH and are located nationwide.

In fiscal year (FY) 2018, NIH had total budget authority of $37.3 billion, about one-tenth of which supports its own intramural research laboratories, most of which are in Bethesda.² Of the nearly 6,000 scientists who work at NIH, some 1,117 are principal investigators (PIs; FY 2018) and over 4,000 are postdoctoral fellows who are both conducting research and honing their research skills. The role of NIH over the years in the creation of well-trained bench and clinical scientists has been profound. When one studies the background sketches of members in the National Academies of Science, Engineering, and Medicine, early experiences at NIH and its Clinical Center are frequently noted.

In colloquial language, most of the ICs relate to the study of body parts or conditions such as cancer, eye and heart disease, aging, allergies and infectious diseases, and neurological disorders. Other ICs such as the National Institute of Nursing Research, National Institute of Biomedical Imaging and Bioengineering, Institute of General Medical Sciences, National Library of Medicine, and Fogarty International Center have a broader focus. Eleven percent of the budget supports the intramural programs that are located largely on the Bethesda Campus; the remaining 89 percent supports the extramural research activities conducted at diverse locations across the nation and world.

The Bethesda Campus consists of 310 acres of land in Montgomery County, Maryland, just north of the downtown area of the unincorporated city of Bethesda. The Walter Reed National Medical Military Center is located immediately across Wisconsin Avenue at the eastern boundary of the campus. Animal facilities are located on campus, as well as at Poolesville, Maryland. Some campus facilities house administrative activities that support the research programs; other administrative activities are housed in leased space in the Washington, D.C., metropolitan area but are considered part of the NIH Bethesda Campus. While the bulk of the intramural investigators and postdoctoral fellows are located on the Bethesda Campus, the Intramural Research Program (IRP) also has facilities at the Research Triangle Park in North Carolina; the Bayview Campus in Baltimore, Maryland; the Frederick National Laboratory for Cancer Research in Frederick, Maryland; Rocky Mountain Laboratories in Hamilton, Montana; and the Phoenix Environmental and Clinical Research Branch in Phoenix, Arizona (Figure 3.1).³

Starting with the Ransdell Act in 1930,⁴ which changed the name of the Hygienic Laboratory to the National Institutes of Health, research fellowships have been supported. The NCI was designated as a component of NIH in 1944, and between 1947 and 1966, its budget grew from $8 million to over $1 billion. The NIH Clinical Center opened in 1953 with 540 beds (now 200 beds) and is the largest hospital in the world dedicated solely to biomedical and health research. Today, the Clinical Center includes an 870,000 square foot (SF) newer facility with 200 inpatient beds and 93 day-hospital stations, with some departments and ambulatory care in parts of the original 14-story Warren G. Magnuson Clinical Center. About 1,600 clinical research studies are in progress today at the Clinical Center, of which about half are devoted to rare human conditions that are often not studied anywhere else. Conducting clinical trials is a major part of the Clinical Center’s work, focusing predominately on first-in-human studies that test the safety and efficacy of potential new treatments. See Appendix D for additional statistics relating to inpatient clinical volumes and outpatient activities.

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² Overall, NIH is comprised of 27 ICs whose annual budgets range from the National Cancer Institute (NCI) with nearly $6 billion in FY 2018 down to a couple who each receive less than $100 million.

³ NIH Intramural Research Program, “Research Campus Locations,” https://irp.nih.gov/about-us/research-campus-locations, accessed March 20, 2018.

⁴ Public Law 71-251; codified as 42 U.S.C. § 21 et seq.

How the Organization Addresses the Needs of the Facilities

Organizational Structure

The structure and organization of NIH, in comparison to most biomedical research organizations, is driven by some of its peculiar features (e.g., being entirely government funded, its political as well as policy support particularly within the legislative branch) and strong external public advocacy groups. While there is an NIH Director who is presidentially appointed and Senate confirmed, he or she oversees a confederation of variably independently operated ICs rather than exercises central control. Perhaps, the most compelling example is the NCI, whose Director is a presidential appointee. This stature gives the NCI virtually total control over its operations and planning. While the institute directors have a weekly hour-and-a-half meeting with the Director, most planning and facilities issues reside within each IC. To some extent, an NIH resource committee and an institute directors’ “executive committee” also consider physical resources. All of this results in a very complicated structure for planning and managing facilities.

Most ICs at NIH relate to organs or body systems and specific diseases, while others relate to disciplines or areas of interest. For example, with the exception of research in the Clinical Center, the NCI does its research in facilities located at the Frederick National Laboratory located 50 miles northwest of Washington, D.C., and the Shady Grove Campus (see Figure 3.1); NCI made that decision more or less independently. The activities of the National Institute of Allergy and Infectious Diseases (NAIAD) are of similar scope and scale and, recently, the Institute on Aging has begun assuming this status.

Expansions to the research mission of NIH or for new facilities on the NIH campus have resulted at times from effective advocacy from external persons or organizations working in concert with NIH units to influence prominent members of the Congress to support NIH. Once it becomes apparent that Congress does want to move an area of investigation forward or add a facility on the NIH Bethesda Campus, the Director then becomes supportive and plans move forward (Smith, 2008).

Funding for Buildings and Facilities

As will be discussed further in Chapter 4, money spent on facilities addresses construction, repairs and improvements, and maintenance. Funds come from a number of sources including the Buildings and Facilities line item in the congressional appropriation, a nonrecurring expense fund (from the Department of Health and Human Services [HHS]), and one-time appropriations. A small allocation can come from individual institute operating funds (known as special authority, a reference to its origin in the appropriations bills) or from centrally administered funds such as the Capital Improvement Fund using deposits from the IC’s appropriated funds.

Maintaining the condition of facilities is a complex enterprise. An impression exists within a number of NIH ICs that in-house maintenance cannot be depended upon to fix problems within buildings, so the ICs hire special contractors to do some needed work. The waitlist for alterations or repairs is frequently a year or two even for small changes such as redesigning or building small offices. The basement in the Lister Hill Center, part of the National Library of Medicine, has sustained water leaks on at least four separate occasions over the years. The committee witnessed similar leaks in laboratories in the new Porter Neuroscience Research Center.

Perhaps a larger problem is the scale and management of leased buildings across Montgomery County in particular. Approximately thirty buildings are rented, and a number are either miles from the Metro, the Washington-area subway system, or have limited parking and transportations. A few are in transportation oases. One at 6100 Executive Boulevard suffered a recent major structural issue. A supporting column suffered a rust collapse of approximately an inch (NIH, 2014a). The building was evacuated, and the county essentially determined it uninhabitable for some weeks while remediation was done. At present, the building is in foreclosure, with only three of eight floors occupied. Apparently, the current plan is to move the remaining NIH staff to the Rockledge area of leased space in Rockville in 2020.

Additionally, the Bethesda Campus is challenged by the dearth of all-weather connectors among the buildings at NIH above ground and connectors for people to walk below grade. Such connectors are common in other biomedical research complexes and are a cost-effective way to promote collaboration.

Where growth has exceeded available land, new large parcels of land have been obtained. Excellent transportation mechanisms have been established to minimize the disconnections. At NIH, the various individual ICs have leased property throughout Montgomery County with radically varying transportation options among them. The committee was unable to determine the rationale behind this artificial separation of the various NIH units on the Bethesda Campus and believes it warrants reconsideration to achieve greater productivity.

Funding and Personnel

In assessing current and future space requirements in size and nature, it is of course relevant to consider the resources available for salaries and the size and distribution of personnel on the NIH campus needed to meet its mission. What follows here is a description of this matter, including how the current configuration of space and also access to facilities on the campus influence meeting the mission of NIH as a premier research campus.

Funding

The budget authority (appropriated funds) for NIH in FY 2018 totaled $37.3 billion (see Figure 3.2), with close to 90 percent for extramural programs. Not every one of the 27 ICs receives a line-item appropriation; in fact, three of the centers are funded by the NIH Management Fund, which receives

deposits from the various institutes from their appropriation accounts.⁵ The Clinical Center was thus funded in FY 2018 at $495 million and the Center for Scientific Review at $140 million (HHS, 2019).

Over the decades, the NIH campus has been a leader in developing the nation’s biomedical research workforce. During the 1960s, 1970s, and 1980s, clinical associates trained at NIH went into academic medical careers across the nation. Some stayed at NIH for their entire career or were recruited back to NIH to be investigators. Today, while there are still large numbers of personnel of differing categories, the challenge of attracting and keeping top-flight talent is much more difficult owing to, among other things, less than competitive salaries, deteriorating facilities, greater philanthropic support at private centers, and the rise of competitive international research centers.

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⁵ For example, the National Cancer Institute provided $137.4 million in FY 2018 for the Management Fund (NIH NCI, 2018b).

TABLE 3.1 NIH Full-Time Equivalent Employees by Institute or Center for Fiscal Year (FY) 2017

NOTE: IC, institute or center; NCI, National Cancer Institute; NHLBI, National Heart, Lung, and Blood Institute; NIAID, National Institute of Allergy and Infectious Diseases; NIEHS, National Institute of Environmental Health Sciences; NLM, National Library of Medicine; OD, Office of the Director.

SOURCE: NIH, “Full-Time Equivalents by Institute and Center (IC): FY 2000 to FY 2017,” https://officeofbudget.od.nih.gov/pdfs/FY19/FTEs by IC FY 2000 – FY 2017 (V).pdf, accessed January 30, 2019.

Workforce

In FY 2017, NIH had over 18,000 full-time equivalent (FTE) employees, with 26 percent assigned to NIH General Services (such as the Office of Research Facilities and Office of Research Services [ORS]), 17 percent assigned to NCI, and 11 percent to NIAID (see Table 3.1).

Approximately 21,000 staff, counting those who are not federal full-time equivalent employees, work on the NIH Bethesda Campus (Neibauer, 2015; NIH, 2015a); this is expected to increase to 23,000 according to the document 2013 Comprehensive Master Plan—Bethesda Campus (NIH ORF, 2013). Some of these additional personnel will be existing staff who currently work in off-campus leased space.

The IRP in FY 2018 employed 3,454 full-time equivalent research professionals and hosted over 5,500 non-FTE trainees. Of the full-time research professionals, 1,117 are principal investigators (32 percent of total Intramural Professional Designation), of which 28 percent are women (see Table 3.2). Of the 2,487 research personnel that are not designated as principal investigators, 42 percent are women. In FY 2017, 1 percent of the principal investigators were foreign nationals, with 9 percent of foreign nationals as research personnel not designated PIs, and 28 percent of the non-FTE trainees.

Today, the mix of personnel engaged in the IRP is changing in a way that deserves attention. All categories of staff have been on a slow downward trend over the past 8 years except for staff scientists, who have been sharply increasing, essentially doubling during this period (see Figure 3.3). Complete data are not available.

According to the NIH description of staff scientists, they are doctoral-level scientists selected to support the long-term research of a PI or as a member or head of a core facility. As such, “staff scientists do not receive independent research resources, although they often work independently and have sophisticated skills and knowledge essential to the work of the laboratory. Staff Scientists are capable of independently designing experiments, but do not have responsibilities for initiating new research programs.”⁶ It would be helpful to know if such a dramatic shift has been seen at other biomedical research institutions or if the IRP experience is an outlier.

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⁶ NIH Office of Intramural Research, “IPDs and Appointment Mechanisms,” https://oir.nih.gov/sourcebook/personnel/ipds-appointment-mechanisms, accessed October 18, 2018.

TABLE 3.2 Intramural Research Personnel Demographics, Fiscal Year 2018

NOTE: FTE, full-time equivalent; IPD, Intramural Professional Designation; NA, not applicable; PI, principal investigator.

SOURCE: National Institutes of Health, Office of Intramural Research, “IRP Demographics,” https://oir.nih.gov/sourcebook/personnel/irp-demographics, accessed January 30, 2019.

From 2005 to 2018, the number of senior investigators has decreased from 937 to 817, a drop of 15 percent. An even larger decrease in investigators has occurred—from 273 to 214, a 27 percent drop. Clinical fellows are doctoral-level health professionals with an interest in biomedical research relevant to NIH program needs who are employed on a time-limited appointment. Clinical fellows participate in protocol-based clinical research, as well as laboratory research. Scientists with considerable experience beyond postdoctoral training (PGY-9 equivalent or beyond) may be designated senior clinical fellow,⁷ if they fulfill

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⁷ See http://sourcebook.od.nih.gov/prof-desig/DDM%20memo%20re%20NIH%20T42%20Pay%20Model%20Modification.pdf.

the competitive selection requirements. Clinical and senior clinical fellows have dropped from 342 to 279, a decrease of over 20 percent. Postdoctoral fellows have gone from 1,765 to 1,517, a decrease of 15 percent. Staff clinicians have increased somewhat, while the numbers of predoctoral IRTA/CRTAs (Intramural Research Training Award, denominated CRTA at NCI) is stable and postdoctoral IRTA/CRTAs have gone down nearly 20 percent. Post-baccalaureate IRTA/CRTAs have increased by nearly 50 percent. Clearly, there are reasons underlying these workforce trends, but determining such reasons was beyond the committee’s charge.

NIH, NATIONAL SECURITY, AND THE BETHESDA CAMPUS

NIH Contributions to the Nation’s Health Security

The NIH is a vital element in the nation’s health security.⁸ The Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) is led by the HHS Office of the Assistant Secretary for Preparedness and Response and coordinates federal efforts to enhance preparedness and response from a medical countermeasure prospective to chemical, biological, radiological, and nuclear threats and emerging infectious diseases. The Centers for Disease Control and Prevention, the Food and Drug Administration, and NIH are the primary internal HHS partners working in close collaboration with numerous interagency partners including the Departments of Defense, Veterans Affairs, and Homeland Security, and the U.S. Department of Agriculture to support the PHEMCE mission (Figure 3.4).⁹

In this national security effort, NIH is focused on early-stage research to better understand the threats to civilian public health and to identify strategies to develop new treatments, medical products, and ways to diagnose, treat, and hopefully prevent health threats.¹⁰ In FY 2017, the largest proportion of multiple-hazard and preparedness funding in HHS was provided to Biodefense and Emerging Infectious Disease Research ($1.74 billion of combined intramural and extramural funding) at NIH (Boddie et al., 2016). As demonstrated during the 2014 Ebola outbreak, NIH is uniquely positioned to partner with industry and other stakeholders during times of national emergencies and to conduct essential clinical trials needed to accelerate the development of new treatments to fight epidemics and new infectious diseases. The NIH Mark O. Hatfield Clinical Research Center on the Bethesda Campus remains one of a few global research facilities with the ready capacity to isolate patients to control the further spread of a disease, prepare novel therapies, and conduct clinical trials in a controlled and safe environment (NASEM, 2016).

NIH Contributions to the Nation’s Economic Security

In addition to reducing the economic and social burdens of illness and disability, NIH research funding continues to sustain significant contributions to direct research and related job creation, as well as economic impacts delivered through the commericialization of biomedical innovation and resulting products development and distribution, as follows:¹¹

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⁸ National health security is defined as a state in which the country and its people prepare for, protect from, and become resilient to incidents that have the potential to cause extensive disruption and damage to the public health and to U.S. and global economies. See HHS (2014); HHS Public Health Emergency, “PHEMCE Mission Components,” updated February 27, 2015, https://www.phe.gov/Preparedness/mcm/phemce/Pages/mission.aspx; Watson (2017); and Boddie et al. (2016).

⁹ HHS Public Health Emergency, “PHEMCE Mission Components,” updated February 27, 2015, https://www.phe.gov/Preparedness/mcm/phemce/Pages/mission.aspx.

¹⁰ Ibid.

¹¹ See Ehrlich (2018) and NIH, “Our Society,” reviewed May 1, 2018, https://www.nih.gov/about-nih/what-wedo/impact-nih-research/our-society.

• “NIH investments in research focused on a particular area stimulate increased private investment in the same area” (Azouly, 2015). “A $1.00 increase in public basic research stimulates an additional $8.38 of industry R&D investment after 8 years. A $1.00 increase in public clinical research stimulates an additional $2.35 of industry R&D [research and development] investment after 3 years” (Toole, 2007).
• “NIH-funded basic research fuels the entry of new drugs into the market and provides a positive return to public investment of 43%, by some estimates” (Toole, 2007, 2012).
• “Using the Regional Input-Output Modeling System (RIMS II) developed by the Department of Commerce, United for Medical Research calculated the impact of NIH research funding in 2017 on jobs and the economy . . . NIH research funding in 2017 directly and indirectly supported 402,816 jobs nationwide. Thirteen states have employment of 10,000 or more supported by NIH research funding and the median state has 4,014 jobs due to NIH activity. Additionally, the income generated by these jobs, as well as by the purchase of research

• related equipment, services and materials, when cycled through the economy, produced $68.795 billion in new economic activity in 2017” (United for Medical Research, 2018).

Security Considerations and Access to the NIH Bethesda Campus

Until 9/11, the NIH Bethesda Campus was open and freely accessible. Security was building- or use-specific with a focus primarily on the central vivarium, smaller vivaria embedded in institutes, and certain laboratory facilities with functions and missions that required secure environments. The campus enjoyed access by vehicles and pedestrians from all surrounding campus streets with no discrimination between visitors, researchers, staff, patients, and vendors. The most pressing vehicular issue was not security but was parking, and open parking for visitors and staff was even permitted underneath the Ambulatory Clinical Research Center.

Today, operational security measures in place at the NIH campus have been addressed holistically, at multiple scales and utilizing an all-hazards resilience planning and recovery approach. After 9/11, NIH completely transformed the campus from an open one to one today that has limited, controlled access and a sophisticated physical security perimeter. Individual facilities with limited access are part of a larger comprehensive system of security.

The 2013 Comprehensive Master Plan—NIH Bethesda Campus (NIH ORF, 2013) refers to security consideration as follows:

The security management measures for the NIH-BC includes use of campus perimeter fencing that has incorporated surveillance systems of cameras and other sensors. Access control is limited to eight entry gates and access portals. The public, including all NIH staff and NIH visitors, must enter only at the Gateway Center (see Chapter 4, Figure 4.2) near the Metro Center portal on Wisconsin Avenue, where they are screened and issued temporary access. All service vehicles and trucks are inspected and screened for site access only at the gate on the northeast corner of the site. Employees are permitted access at six designated portals, where they are processed and screened utilizing individual ID passes. Patients access the campus at a dedicated portal off West Cedar Lane on the north perimeter, where the Clinical Research Center provides a listing of expected patient arrivals on a daily basis.

The Mark O. Hatfield Clinical Research Center is always open to the general public. Although the main lobby functions as a point of central control and inspection, there are numerous points of entry widely scattered in and around the center, all of which remain open 24 hours a day. Ongoing security considerations include assessment of the operational impacts of reducing the number of access portals to the center. In addition, over the years there has been discussion regarding potential enhanced security measures associated with maintaining or eliminating the vehicular parking located below the Ambulatory Clinical Research Facility portion of the Clinical Research Center. Vehicles are currently permitted access to this

below-grade parking structure following extensive screening prior to entry. The clinical laboratory zone of the Clinical Research Center is open during the working day but is secured from 6 PM to 7 AM, with access limited to use of an access control system (currently keypad operated). Consistent with all clinical facilities, specific functional areas are secure at all times, including the mental health unit, medications and pharmacy, medical records, and mechanical and other building system support areas. Campus-wide, animal care facilities and a majority of NIH Bethesda Campus facilities utilize access control and allow access only if the individual holds NIH-approved identification.

VALUE AND ACCOMPLISHMENTS OF NIH INTRAMURAL PROGRAM

NIH IRP Level of Investment in an International Context

Scientific discoveries are costly, especially in today’s technology-driven, rapidly changing, multidisciplinary global research environment. They require extensive training and a long-term commitment by scientists devoted to their fields, as well as a significant investment by the public, who ultimately benefit in improved health outcome, reduced illness and disability, and increased life expectancy. While the United States has been able to maintain its leadership in past times of funding uncertainties, the lack of significant increases in IRP funding has raised concerns among some observers that NIH, and the United States in general, may lose its global edge in such metrics as scientific research articles, patents, and technology workforce development (Moses et al., 2015).

This concern is supported by the increase in research infrastructure funding in Europe, in particular in the European Union (EU) as part of the EU 2020 effort, and a relative decline in public and private sector R&D expenditures in the United States (compound annual growth rate of 1.9 percent for 2007-2012, adjusted for inflation), as compared to an increase of 32.8 percent in China and 10-11 percent in South Korea and Singapore (Chakma et al., 2014; Moses et al., 2015). When compared to China, the U.S. readout of research output during 2000-2015 based on original articles from U.S.-based authors published in high-ranking clinical and basic science journals declined, whereas China-based investigators’ output in mid- and high-ranking journals steadily increased over the same time period (Conte, 2017).

While the United States is reducing federal funding for R&D, the EU has made major investments under the EU 2020 strategy in building the European Research and Innovation Area to provide open access to scientific resources and services for all scientists across Europe (ESFRI, 2016; EMRC, 2011; Smith et al., 2011). The EU has over 500 research infrastructures (RIs), with over 300 RIs having strong international visibility that attracts world-class researchers. Supported by an investment of over 100 billion euros, the RIs are conceived, funded, and managed as open research institutes to attract scientists from around the world, and drive excellence in innovation to ensure that the EU economy remains competitive (ESFRI, 2016). Located across the EU, the RIs are seen as high-performance platforms for cooperation among universities, enterprises, and research institutions. While there is a wide gap between research productivity among EU countries, there is strong commitment to develop a diverse research workforce, engage the public, and build a shared research infrastructure across the member countries.¹² The new EU Coordinated Research Infrastructures Building Enduring Life-Science Services (CORBEL) consortium brings together 13 new state-of-the-art Biological and Medical Sciences RIs, including biological data, physical biobank samples, imaging facilities, and molecular screening centers to boost the efficiency, productivity and impact of European biomedical research. Both China and Europe have placed a great emphasis on international collaborations. While in the past the evaluations of collaborations based on existing literature have primarily focused on China and U.S. collaboration, more recently China and EU collaborations have increased owing to the EU’s integration strategy, which has a special emphasis on the strategic linkage of EU member states with middle or low scientific capacity and China (Wang et al., 2017). The number of papers co-authored

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¹² See the CORBEL Shared Services for Life-Science website at http://www.corbel-project.eu/aboutcorbel/corbel-partner.html.

by Chinese and European authors increased from 2,500 in the year 2000 to more than 19,000 in 2014. This makes China the second most prolific external EU partner after the United States (Wang et al., 2017). In addition to focusing on international collaboration, China is making significant investments in research infrastructure with a focus on translational research. The National Centre for Translational Medicine in Shanghai is the first of five translational research centers under development (Williams, 2016).

Given China’s investment in biomedical infrastructure and international collaboration, Senator Bill Nelson of Florida warned at a January 2018 congressional hearing on the state of American science: “At this rate, China may soon eclipse the U.S. and we will lose the competitive advantage that has made us the most powerful economy in the world” (Guarino, 2018).

Intramural Assets

Cores

Scientific Core Facilities

In response to the Advisory Committee to the Director’s (ACD’s) report, Long-Term Intramural Research Program (LT-IRP) Planning Working Group Report (NIH ACD, 2014), the 2015 NIH Response and Implementation Plan (NIH ACD, 2015) outlined that the use of the IRP’s research infrastructure was historically not strategically integrated or optimized to build efficiencies, ensure awareness, or expand access to investigators across the ICs of the IRP. Funding, administration, and access to instrumentation and core facilities¹³ varied widely across the IRP—ranging from those shared by multiple ICs to those funded by individual ICs or lab-/branch-specific funding. Until recently, no central catalogue was available that listed the complete inventory of the IRP core facilities.

In 2017, the NIH IRP adopted the NCI’s system as the NIH-wide Collaborative Research Exchange (CREx)—a marketplace connecting IRP investigators with 110+ IRP cores, including many trans-NIH cores and 10,000+ external vendors.¹⁴ The majority of the 110 core facilities are sponsored by NCI and 10 ICs, with most of the trans-NIH-wide operated facilities being supported by either the Clinical Center (CC) or ORS (Gottesman and Baxevanix, 2017).

The services provided by the cores are wide ranging, from the NCI’s nanotechnology core; the National Institute of Diabetes and Digestive and Kidney Diseases mouse knockout core tasked with producing transgenic mice; the National Heart, Lung, and Blood Institute biochemistry facility; as well as an extensive list of multiple imaging, microscopy, genomics, and proteomics cores across the ICs.¹⁵ In 2017, the Office of Intramural Research (OIR) Director’s Challenge Fund provided the initial funding to implement CREx, with commitments by the ICs and OIR to support this effort in the long term. The Shared Resources Subcommittee of the Board of Scientific Directors oversees multiple trans-NIH initiatives and facilities supported by voluntary contributions from the IC IRPs. Contributions are based partially on the size of the IC IRP’s budget and on the IC’s use of the facility.

CREx access is limited to NIH investigators, who have the ability to compare cost and services of NIH-based and outside-based vendors, in addition to giving feedback on service quality. The system’s reporting tools can guide decision making in regard to prioritization of which internal cores to support and when to redirect resources to fund emerging technologies (Gottesman and Baxevanix, 2017). The recent implementation of CREx is a significant step toward providing access to core services across the IRP.

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¹³ Core facilities are centralized shared research resources that provide access to instruments, technologies, and services, as well as expert consultation and other services to scientific and clinical investigators. See NIH, “Frequently Asked Questions,” revised April 18, 2018, https://grants.nih.gov/grants/policy/core_facilities_faqs.htm.

¹⁴ The site can be accessed by those with log-in credentials at https://nih.scientist.com/users/sign_in.

¹⁵ See NIH Intramural Research Program, “Research Resources,” https://irp.nih.gov/our-research/research-resources, accessed April 1, 2019. Cores also include such capabilities as single-cell genomics, cryo-electron microscopy, RNA interference, PET and MR imaging, drug candidate screening, natural products, mass spectrometry, transgenic facilities, combinatorial chemistry, bioinformatics and computational biology.

However, it is likely that redundant core resources were developed by ICs, given the lack of a comprehensive central system to track the core facilities, available utilization, and incentives to integrate core resources.

In responses to the Advisory Committee Report, critical new technology needs were identified. Requests include technology incubators, optical microscopy, instrument development, clinical imaging, and enhanced computational resources to support big data analysis.

To support the strategic core integration plan, new payment models are being implemented for easy transfer of funds from one IC to another to cover service costs. In addition, the SRC model for more expensive shared cores will be extended to include shared large capital equipment purchases of emerging novel technologies (NIH ACD, 2015).

Compared to the IRP, NIH has long invested in the integration of NIH-supported core facilities and services in the extramural program. Given the NIH investment in extramural research infrastructure, totaling approximately $900 million in 2015, the consolidation of core facilities has been a strategic priority. For large grant programs such as the NCI Cancer Centers and Clinical and Translational Science Awards program supported by National Center for Advancing Translational Sciences, NIH has emphasized that research organizations receiving support must implement programs to enhance core resource efficiencies (Chang and Grieder, 2016; Farber and Weiss, 2011; Reeves et al., 2013). Recently published results of an NIH pilot program, conducted under the American Recovery and Reinvestment Act, indicated that financial incentives that support centralization of core services can successfully optimize core administration, increase efficiencies, and eliminate redundancy (Chang et al., 2015; NIH ACD, 2015). This justifies the large investment in the advanced, high-throughput instrumentation and expertise. A similar approach should be considered to bring efficiencies to the IRP research cores.

Animal Facilities

The NIH provides an extensive animal research infrastructure at the Bethesda Campus as well as at the NIH animal center in Poolesville, Maryland, for IRP investigators.

The role of the Division of Veterinary Resources (DVR) of the IRP may be described as follows:¹⁶

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¹⁶ NIH Office of Management, Division of Veterinary Resources, https://www.ors.od.nih.gov/sr/dvr/Pages/default.aspx, accessed March 8, 2019.

¹⁷ NIH Office of Management, “Animal Facility Management,” https://www.ors.od.nih.gov/sr/dvr/facility/Pages/AnimalFacilityManagement.aspx, accessed March 8, 2019.

¹⁸ NIH Office of Management, “DVR,” https://www.ors.od.nih.gov/sr/dvr/Pages/default.aspx?, accessed March 8, 2019.

The DVR program is AAALAC¹⁹ accredited. In addition, several of the ICs run smaller vivarium facilities, as well as specialized animal resource cores. Of the 23 buildings housing vivarium functions, greater than 50 percent are more than 45 years old. The Building 14/28 complex is the largest holding facility on the Bethesda Campus and the only one not connected to a laboratory building. The complex is lacking essential mechanical infrastructure upgrades to reliably maintain the facility. The long-term plans (NIH ORF, 2013) set forth in the campus Master Plan call for replacing the facility as part of the Center for Disease Research (CDR) North development on the existing Building 7 and 9 sites, although the NIH Office of Research Facilities advises that the location of the CDR is being reevaluated. There will be a continuing need to optimize animal research holding and core facilities across the IRP.

Data Science Infrastructure and High-Performance Computing

The recently published the NIH Strategic Plan for Data Science (NIH OD, 2018b) outlines the need to build a state-of-the-art data ecosystem able to support “big data” and high-performance computing (HPC) infrastructure. A new NIH chief data science officer position was developed to lead this critical strategic effort. Understanding basic biological mechanisms and clinical research focused on precision medicine depend on vast amounts of data. The storage and analysis of big data from interdisciplinary research efforts requires a sophisticated data infrastructure, a modernized data ecosystem, data management and analytics tools, a data-science workforce, as well as stewardship and sustainability (NIH, 2018b).

The NIH HPC group “plans, manages, and supports high-performance computing systems specifically for the intramural NIH community.”²⁰ Examples include the following: “Biowulf, a 90,000+ processor Linux cluster; Helix, an interactive system for file transfer and management; Sciware, a set of applications for desktops; and Helixweb, which provides a number of web-based scientific tools.”²¹ The NIH HPC group supports computational applications in such fields as genomics, molecular and structural biology, mathematical and graphical analysis, and image analysis. There are several options for disk storage on the NIH HPC. There are no quotas, time limits, or other restrictions placed on the use of space on the NIH HPC.²² The Biowulf HPC Environment is the only large-scale central computational resource dedicated to biomedical computing in the IRP. It is designed for general-purpose scientific computing—not dedicated to any single application type—and has dedicated staff with expertise in high-performance computing and computational biology to support research teams.

In response to the increasing data infrastructure needs of IRP investigators, Biowulf capabilities were expanded in FY 2014-FY 2018. This included modern architecture to provide both power and flexibility to IRP investigators, support data sharing and scientific collaborations through central data storage, and provide the ability to create an “NIH private cloud,” as well as common application support and sufficient high availability to secure storage. These efforts have resulted in the NIH improved global ranking of HPC infrastructures from not being included in the top 500 in 2014 to being ranked 66 in 2017.

The immediate needs of smaller lab programs to support bioinformatics and computational biology have been met through limited renovation. This has provided high-end performance computing to “dry lab” teams who work in close proximity to “wet lab”-based teams where genomic sequencing and related biotechnology instrumentation is located. The programs were linked to the IC-specific HPC cluster or the campus Biowulf HPC.

Given the increased need for big data and HPC across the ICs, significant investments in the infrastructure outlined in the Strategic Plan will be required to support the IRP research enterprise. The current Biowulf “Buy-In” Model, in which nodes and storage are purchased by ICs but operated and maintained by the Center for Information Technology HPC staff, can be reviewed to ensure economies of scale across the IRP through consolidation while ensuring equal access for IRP investigators and trainees.

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¹⁹ Further information is available at the AAALAC International website at https://aaalac.org/.

²⁰ NIH, “BIOWULF: High Performance Computing at the NIH,” https://hpc.nih.gov, accessed March 8, 2019.

²¹ Ibid.

²² Ibid.

One promising area is the current activity with respect to cloud computing for the entire NIH enterprise. Work with Google Cloud and Amazon Web Services through the Data Sciences strategy is moving along at a good rate, and plans are to use the cloud not simply for data storage but also for data calculations. The same amount of intensity is needed with respect to augmented and artificial intelligence across all of the NIH intramural programs.

Multi-Institute Facilities

The NIH CC links patient care with basic research discoveries and programs for the study of undiagnosed diseases and rare diseases and conditions. The vision of the Clinical Center is to lead the global effort in training today’s investigators and discovering tomorrow’s cures.²³ Since 1953, over 500,000 adult and pediatric research participants have come to the CC to enroll in clinical research studies not otherwise available. All patients are enrolled in research studies, and treatment at the CC is free of charge to the patients. In addition, housing facilities are available for research participants and their families on or in close proximity to the NIH campus. The CC sees about 10,000 new research participants a year. The CC is a mission-critical trans-NIH clinical research core facility. The Mark O. Hatfield Clinical Research Center (CRC) was opened in 2005 and houses adult and pediatric inpatient units, day hospitals, and research labs, and connects to the original Clinical Center building. The 870,000-square-foot CRC currently has 200 inpatient beds and 93 day-hospital stations. The development of first-in-human novel therapies requires state-of-the-art investigational pharmacy, dietary, laboratory, surgery, imaging, cellular therapy, immunotherapy, transfusion medicine, and pathology support services.

Approximately 1,200 credentialed physicians, dentists, and Ph.D. researchers; 620 nurses; and 450 allied health-care personnel work in patient care units and laboratories to support clinical study.²⁴ The collaborative environment of the NIH Clinical Center makes it possible for investigators to provide immediate testing and consult with a multidisciplinary team of scientists to come up with the best approach for diagnosing and treating patients. The freedoms of the NIH Clinical Center enable clinician-scientists to think out of the box and consider new approaches to treat diseases. The unique CC ecosystem allows for clinician scientists’ research labs to be located in close proximity to the dedicated hospital wings and floors.

The NIH Clinical Center offers an extensive range of clinical research training including courses in pharmacology, principles and practice of clinical research, and bioethics.²⁵

The John Edward Porter Neuroscience Research Center—delivered in two phases in 2004 and 2014—is a state-of-the-art 500,000-square-foot energy-efficient life science facility that brought together 800 scientists and 85 research labs from 10 ICs under one roof (Figure 3.5). Shared facilities include a peptide sequencing facility, a magnetic resonance imaging (MRI) suite, and a light imaging facility. The research programs span from basic to clinical neuroscience and focus on increasing understanding of typical and atypical brain development and function. This new facility provides an ecosystem that supports close proximity or interdisciplinary research teams and access to experts across disciplines for trainees. There is growing evidence that co-locating interdisciplinary research groups of investigators from different departments, institutes, and research disciplines can result in increased interactions between individual investigators, as well as discoveries/publications, grants/awards, and higher educational levels (Ravid et al., 2013).

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²³ NIH, Clinical Center, “Office of Clinical Research Training and Medical Education,” updated June 14, 2019, https://clinicalcenter.nih.gov/training/index.html.

²⁴ HHS, “HHS FY 2017 Budget in Brief–NIH,” reviewed February 16, 2016, https://www.hhs.gov/about/budget/fy2017/budget-in-brief/nih/index.html; NIH Intramural Research Program, “What Is the IRP?” http://irp.nih.gov/about-us/what-is-the-irp.

²⁵ Further information is available at NIH Clinical Center, “Office of Clinical Research Training and Medical Education,” updated June 14, 2019, https://clinicalcenter.nih.gov/training/training.html.

NIH Library Reserve Workspace

The NIH Library Collaboration Pods are an example of how modern workspace environment pilot projects can be implemented to facilitate collaboration and provide access to critical shared resources. The pods can be used for small meetings to explore and use a variety of software programs and library resources. The library also provides access to HPC bioinformatics workspaces for high-throughput data analysis. Expanding these shared research environments strategically across the campus will provide the modern work environment required to support collaboration.

NIH Collaborative Forum

The NIH Human Resource Department’s NIH Training Collaborative Forum brings together key stakeholders from the ICs training communities to foster inter-IC partnerships and information sharing. These efforts support the development of shared understanding and training standards in support of IC infrastructure integration.²⁶

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²⁶ NIH Office of Human Resources, “NIH Training Collaborative Forum,” https://hr.nih.gov/trainingcenter/resources/nih-training-collaborative-forum, accessed October 18, 2018.

Legacy of Scientific Accomplishments

The NIH IRP has made major contributions to the state of knowledge and practice, for the United States and the world. Nobel Prize-winning discoveries that were made at NIH include deciphering the genetic code, demonstrating that protein folding can be predicted from primary amino acid sequences, and discovering that “slow viruses” can cause degenerative neurological diseases. Five Nobel Prizes were awarded for research conducted at the NIH IRP, and an additional 22 NIH-trained investigators have been awarded the Nobel Prize. In addition, NIH IRP research has won 34 Lasker Awards (often termed the U.S. equivalent of the Nobel Prize), including 2 Lasker Awards in the past 7 years. Three IRP scientists have been awarded the National Medal of Science, which is bestowed by the President of the United States, and two NIH Directors have been awarded the Presidential Medal of Freedom.²⁷ As noted above, the NIH Biowulf HPC developed and used by IRP researchers was ranked 66 out of 500 most powerful such centers in the world.

The NIH IRP has also developed significant innovations in medical research and practice. Its core activities post-World War II resulted in the first formal review of clinical protocols, which became the model for the Institutional Research Board protocols throughout the United States and the world. NIH IRP also developed the first volunteer program to recruit “normal” (i.e., healthy) volunteers for control studies, and developed the processes, protocols, and means to deliver chemotherapy for cancer treatments. (Additional innovations are listed in Table 3.3.)

Many vaccines currently in use throughout the world are based on NIH IRP work, including vaccines for hepatitis A, Human Papilloma Virus, Rotavirus, and H. zoster (i.e., shingles). In addition, groundbreaking technologies developed at NIH IRP include the Coulter Counter (which is used to determine cellular constituents in the blood) and the spectrofluorometer (which is used to quantitatively determine fluorescence in chemical and biological samples). The software used to analyze MRI images was developed at NIH, as was the fPALM, a super-high-resolution cellular imaging microscope, which led to the award of the Nobel Prize to Dr. Eric Betzig (Gottesman and Baxevanix, 2017). Indeed, in 2017, Reuters ranked NIH/HHS first among the “Top 25 Global Innovators Government,” ahead of France’s Alternative Energies and Atomic Energy Commission²⁸ (CEA), and Germany’s Fraunhofer Society²⁹ (see Ewalt, 2017).

TABLE 3.3 Examples of Significant NIH Intramural Research Program Innovations

^a P.K. Mistry, G. Lopez, R. Schiffmann, N.W. Barton, N.J. Weinreb, and E. Sidransky, 2017, Gaucher disease: Progress and ongoing challenges, Molecular Genetics and Metabolism 120(1-2): 8-21.

SOURCE: Michael Gottesman, Deputy Director for Intramural Research, “The NIH Intramural Research Program is Recognized as a Premier Biomedical Research Facility,” presentation to the committee on May 15, 2018.

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²⁷ NIH Intramural Research Program, “Honors,” https://irp.nih.gov/about-us/honors.

²⁸ Commissariat à l’énergie atomique et aux énergies alternatives.

²⁹ Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V.

Partnerships

Selected Extramural and Intramural Research Program Collaborations

The NIH has a long history of establishing partnerships and networks to catalyze collaboration across HHS, other governmental organizations, and the extramural research community (NIH, 2018b). However, integration of the ICs’ intramural resources and programs to foster collaborations has been a more recent strategic priority and is less well developed.

Table 3.4 gives examples of collaborations that have been initiated by NIH in order to advance its mission of improving human health and leveraging a valued national resource.

Training Programs

Training of the national and global biomedical research workforce is a primary focus of NIH and is stated in the organization’s mission “to improve the health of the public through the support of biomedical research and the training of biomedical scientists” (Pool et al., 2016). To fulfill this mission, the Bethesda Campus’s teaching, clinical practice, and research facilities must achieve an unprecedented level of success in fostering collaborative, multidisciplinary work in a highly efficient and adaptable environment while attracting the best clinicians, researchers, and students.

Training programs in biomedical sciences available to those working in the IRP span the continuum of education from undergraduate to postdoctoral training (see Figure 3.6). Over 5,000 basic scientists and clinicians from the United States and around the globe train at IRP. There is no other place in the world with a concentration of laboratories and individuals focused on improving the health of humankind.³⁰

In fiscal year 2017, OIR educated 5,413 trainees (see Table 3.5). In addition to providing access to some of the world’s leading research programs, the IRP along with the entire NIH community has developed unique training programs to address challenges such as diversity, global workforce capacity, and the shortage of physician researchers that threaten the biomedical workforce.

Office of Intramural Training and Education

The office coordinates training programs in biomedical science for all degree levels from high school summer internships to postdoctoral programs. The Graduate Partnership Program has formal institutional training partnership with academic institutions but also allows for individual agreements. Over 4,000 postdoctoral trainees come from across the United States and around the world to train at NIH. This unique and vibrant ecosystem serves as a foundation fostering future scientific collaboration as individuals progress in their careers. The Clinical Center provides yearlong research enrichment programs as well as short-term clinical electives for medical and dental students with the goal to attract the most creative research-oriented students to the Bethesda Campus. Many of the Office of Intramural Training and Education workshops and science skills tutorials are now available online to trainees outside of NIH.³¹

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³⁰ NIH Office of Intramural Research, “Research Training,” https://irp.nih.gov/research-training.

³¹ NIH Office of Intramural Training and Education, “Training Programs in the Biomedical Sciences,” https://www.training.nih.gov/programs, accessed November 9, 2018.

TABLE 3.4 Selected Extramural and Intramural Research Collaborations and Partnerships

a Frederick National Laboratory for Cancer Research, “About the Frederick National Laboratory for Cancer Research,” https://frederick.cancer.gov/about/overview, accessed March 8, 2019.

^b NIH and NASA, “History of NIH and NASA Collaborations,” https://ncats.nih.gov/alliances/nasa/collaboration-history, accessed October 18, 2018.

^c NIH, 2017, “NIH Partners with 11 Leading Biopharmaceutical Companies to Accelerate the Development of New Cancer Immunotherapy Strategies for More Patients,” News release, October 12, https://www.nih.gov/news-events.

SOURCE: NIH Clinical Center, “Planning a Collaboration—Frequently Asked Questions,” updated January 26, 2017, https://clinicalcenter.nih.gov/translational-research-resources/faq-1-planning.html-collaborations_3; AACR (2014); NIH NCI (2018a); EurekAlert! (2018); NIH National Institute on Aging, “About IRP,” https://www.nia.nih.gov/research/labs/about-irp, accessed November 5, 2018; NIH (2017); Ravid et al. (2013).

TABLE 3.5 Number of Intramural Research Trainees in Fiscal Year 2017

SOURCE: National Institutes of Health, Office of Intramural Research, “IRP Demographics,” https://oir.nih.gov/sourcebook/personnel/irp-demographics, accessed January 30, 2019.

Diversity

Increasing the diversity of researchers and physician researchers is critical to the future of biomedical research in the United States, particularly as the share of the U.S. population comprised of underrepresented groups increases. In 2015, the Long-Term IRP Planning Working Group Report to the NIH ACD found that the IRP should lead in the development of new approaches to train and recruit a diverse biomedical workforce. The following training recommendations were recommended and adopted by the IRP (NIH ACD, 2015):

• Creation of a centralized program for recruitment, mentoring, and career development of postdoctoral fellows; and the
• Addition of a high-school summer enrichment program, and enhanced graduate and medical training programs.

The IRP implemented the Hi-STEP graduate summer program and developed a program to strengthen both extramural and intramural mentoring of young investigators. The number of full-time graduate students receiving funding from research assistantships from NIH in 2011 increased 60 percent to 65 percent in 10 years, emphasizing the importance of both formal and informal mentorship (Rockey, 2014).

To ensure the quality of the IRP training programs the IRP in collaboration with the National Academy of Sciences developed and implemented a training and mentoring guide to assist both trainees and mentors in outlining principles for training programs, criteria for good mentoring, and guidelines for the conduct of research. This guide assists individual laboratories, institutes, and centers in evaluating the success of their training programs and ensuring that programs are effective and current (NIH OD, 2008; Valantine, 2016).

Global Workforce Capacity

Chronic and infectious diseases continue to have an enormous toll on the world’s population, and especially the poorest populations. To combat these health issues, substantial investments are being made in the development of new health technologies. While many of the interventions are safe and effective, they cannot be implemented broadly due to logistical, cultural, financial, and other barriers. Addressing these barriers will require that trained researchers can most effectively translate research findings into practice. NIH supports international research training of over 5,000 researchers from low- to middle-income countries. Every year, NIH trains more than 2,500 foreign scientists in its intramural laboratories.³²

Physician Scientists

Survey data from the American Medical Association show a decline of 5.5 percent in the number of physicians conducting research between 2003 and 2012. Over the same time span, the demographics of NIH-funded principal investigators have changed; when viewed by decade of life, it is apparent that the proportion of individuals in their 60s and 70s has increased and those under 60 declined (see Figure 3.7).

Although NIH has been concerned about the aging of the biomedical workforce, the need for younger physician-scientists is even more pressing (Kaiser, 2014).

The NIH’s Clinical Center offers a unique environment for training physician-scientists with hospital facilities that house both basic and clinical research in one location. Clinical research training courses offered at NIH and at remote sites have trained over 18,000 students since 1995. The annual Clinical Investigator Student Trainee Forum hosted by the CC provides an intensive educational experience for medical and dental students. The Clinical Center also holds a clinical management course on campus to expose experienced investors to the skills needed to run a clinical research program.³³

In order to be able to develop and implement unique training programs, IRP must maintain and enhance both the culture and facilities needed for outstanding contemporary basic laboratory and clinical research and training. The campus’s teaching, clinical practice, and research facilities must address existing needs and the emerging biomedical trends as identified in Chapter 2. Facilities must accommodate advances in technology, simulation, interdisciplinary research, and clinical care and maintain the flexibility to accommodate ongoing changes in the delivery of education and training of healthcare professionals. Amenities such as hoteling workspaces, fitness/wellness centers, and green spaces that enhance the campus’s work environment are also needed if the IRP is to continue to attract excellent researchers, clinicians, and trainees.

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³² NIH, “Building Global Health Research Capacity,” Fact Sheet, updated June 30, 2018, https://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=74.

³³ NIH, “Clinical Research Training at the NIH Clinical Center,” Fact Sheet, updated June 30, 2018, https://report.nih.gov/nihfactsheets/ViewFactSheet.aspx?csid=82.