An Assessment of the National Institute of Standards and Technology Material Measurement Laboratory: Fiscal Year 2014 (2015)

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Biosystems and Biomaterials Division

The mission of the Biosystems and Biomaterials Division (BBD) is to address the nation’s needs for measurement science, standards, data, methods and technology in the quantification of complex biological systems and materials and processes. The BBD partners with U.S. industry, government agencies, and scientific institutions to develop the infrastructure supporting quantitative biology and biomaterial measurements, with the intent of fostering innovation in health care, manufacturing, food safety, environmental health, and national security.¹ The BBD consists of 114 staff members in four organizational groups that support 15 technological application teams.

The Bioassay Methods Group addresses areas such as flow cytometry, reference gene assays, and cancer biomarker standards for cancer diagnosis and therapeutics.

The Biomaterials Group includes application teams in cell materials interactions, three-dimensional (3-D) tissue engineering scaffold material characterization, and protein stabilization. The Biomaterials Group’s imaging and spectroscopy technologies focus area includes application teams in benchmarking and calibrations, broadband coherent anti-Stokes Raman Scattering (BCARS) microscopy, live single-cell analysis, and flow cytometry.

The Cell Systems Science Group includes application teams in cell-based therapies; microscopy benchmarking; synthetic biology; cell line identification; nanotechnology environment, health, and safety (NanoEHS); and measurements for assessing nanoparticle effects on biological systems.

The Genome Scale Measurements Group includes application teams in clinical diagnostics, synthetic biology, and microbial identification.

The BBD research activities focus on providing validated methods and measurements, technologies, and data and standards to advance the understanding of complex biological systems and biomaterials through characterization and quantification. This is accomplished by working from the molecular to supramolecular scale, examining the complexity of communication between cells and cell interactions with materials, developing tools to address the challenges of measuring biological functions, and enabling biology to become more of an information science for health, predisease, and disease.

ASSESSMENT OF TECHNICAL PROGRAMS

Accomplishments

Bioassay Methods Group

There are four major programs within the Bioassay Methods Group (BMG): spectroscopy standards, biomarker quantification, flow cytometry, and engineering biology. Staff expertise is very diverse and broad. The staff have supported the development of wavelength, photometric and stray light standards for ultraviolet, visible, and near infrared (UV-Vis-NIR), Raman, and fluorescence

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¹ NIST Material Measurement Laboratory, “2014 National Research Council Assessment of the NIST Material Measurement Laboratory: Read-Ahead Materials,” Gaithersburg, Md., June 2014.

spectroscopies, developing 20 SRMs and 200 recalibrations of photometric standards every year; established traceability in flow cytometry with fluorophore solutions and calibrated beads; developed reference materials and protocols for benchmarking fluorescence microscopes; developed the first international reference standard for CD4+ cell counting for HIV/AIDS monitoring²; developed an equivalent reference fluorophore unit for microsphere calibration materials and directed a fluorescence value assignment training program to bead manufacturers with the International Society for Advancement of Cytometry; established assays for HER2 using quantitative PCR and digital PCR; established reference gene assays on chromosomes that are not commonly mutated in cancer; and started high-throughput DNA sequencing for cancer genes on the DNA standards.

The BMG has generated assay, data handling, and results interpretation schemes for assessing the characteristics of mitochondrial DNA as a potential prostate cancer biomarker using qPCR assay and first reported that a 3.4 kilobase mitochondrial DNA deletion and an increase in mitochondrial DNA copy number, as potential prostate cancer biomarkers, can be detected in urine and serum.

The group developed an internal fluorescence reference method to allow quantitative comparison of expression of markers for pluripotency and patented the method for potential development as a kit to enable widespread application; in collaboration with NIST’s Information Technology Laboratory, developed methods for automatically scoring stem cell colonies for their pluripotent character; developed a bioinformatics approach to identify potential short tandem repeat (STR) markers and analytical measurements to measure multiplex STR markers; developed an African green monkey cell line multiplex STR assay; developed a mouse multiplex STR assay and applied for a U.S. patent (the assay was licensed and is being commercialized by DNA Diagnostics Inc.); began development of an STR multiplex assay for Chinese hamster ovary (CHO) and rat cell lines; used cause-and-effect diagrams to identify sources of variability in an MTS nano-cytotoxicity assay protocol, leading to redesign of the protocol to include seven additional control experiments; designed and executed an interlaboratory (including measurement institutes in the European Union, Korea, Switzerland, Thailand, and the United States) comparison study of the MTS cell viability assay as a nano-cytotoxicity assay; and used advanced statistical analysis techniques to quantify nano-cytotoxicity assay variability and to identify steps in the protocol that are likely contributing to variability in the assay result.

The Bioassay Methods Group has produced 18 unique SRMs for ultraviolet-visible, near infrared, and Raman spectroscopy, fluorescence, and flow cytometry techniques—SRM sales have been approximately 170 units per year; developed methods and standards to support cell line authentication; developed the equivalent reference fluorophore calibration approach that has been accepted by the flow cytometry community; and with two other national metrology institutes developed the first international reference cell standard for CD4+ cell counting for HIV/AIDS monitoring (WHO/BS/10.2153).

Biomaterials Group

In 2001 the work of the Biomaterials Group was expanded beyond dental research to include standards and advanced technologies for emerging diagnostics and therapies. The group is working in the areas of dental materials, 3-D scaffolds for tissue engineering, broadband coherent anti-Stokes Raman scattering (BCARS), and protein preservation.

Its accomplishments include new materials, theories, and models; measurement technologies and standards aimed at assuring safety and performance of devices; a large research portfolio that includes tissue engineering, cell–material interactions, stabilities of protein therapeutics (drug delivery), biomineralization, smart materials, antimicrobial materials, and measurement of complex structure–property relationships of dental and biomaterials development of international documentary standards; a validated, patented instrument for simultaneous measurement of polymerization kinetics, reaction

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² World Health Organization, “Requests to Initiate New WHO Reference Material Projects,” WHO BS/10.2153, Geneva, Switzerland, June 22, 2010.

exotherm, and polymerization stress for photopolymerized composites; a long-term collaboration (since the 1930s) with the American Dental Association (ADA), which now represents over 150,000 dentists, to provide assurance for the program’s strategic directions; a tabletop steady-state fluorescence instrument that could easily be used in a biopharmaceutical laboratory to provide relevant nanosecond dynamics; four NIST reference materials for measuring porosity of and cell proliferation on scaffolds; combinatorial cassettes as high-throughput, systematic in vivo testing platforms to increase measurement confidence and reduce the number of animals needed for testing; 3-D image analysis methods for quantitative descriptors of cell and scaffold shape metrics; and the largest study of 3-D stem cell morphology, involving 1,500 z-stacks of stem cells and 1 TB of data, to determine the role of cell shape in biological response.

Major research findings from the Biomaterials Group have been published in 17 peer-reviewed papers. Since October 2012, 11 invited presentations have been delivered and one patent application has been filed. The group has developed new methods using coherent Raman effects (BCARS) to acquire vibrational spectroscopic image data at ever-shorter acquisition times—the group demonstrated acquisition of spectral images from live cells at 50 ms/pixel, at least 100 times faster than spontaneous Raman, and in 2013 was the first laboratory to demonstrate spectral image acquisition from tissues at 3.5 ms/pixel.

Cell Systems Science Group

The Cell Systems Science Group has demonstrated SPR imaging through a high numerical aperture (NA) microscope objective and the novel use of a digital light projector to achieve near diffraction limited in spatial resolution (representing a 10-fold improvement), allowing for unprecedented visualization and quantitation of subcellular features, including measurement of protein density in focal adhesions. It also developed a prototype standard reference image database (SRD 159) to discover and disseminate the image data—the discoverability of the data is made possible through annotation with an advanced rule- and root-based terminology technology designed to enable federated database storage.

The group addresses applications in emerging stem cell technologies, organismal scale metrology, and nanotoxicity. It focuses on the cell as a system and tools that measure and characterize system properties in basic biomedical research, biomanufacturing, and regenerative medicine, and on other applications that depend on understanding and predicting complex cellular activities. It assesses sources of variability in a protocol using experimental design and control experiments. The group also participates in standards committees to facilitate dissemination and knowledge transfer of good measurement practice and development tools that facilitate validating cellular populations as reagents.

Team scientists develop measurement assurance strategies for cell biology that include cell-based assays for nano-cytotoxicity measurements and measurement needs in the cell therapy community. The Cell Systems Science Group conducts four programs: assurance and comparability in cellular measurements, tools for terminology development for annotating biological data, assurance in organism scale measurements, and live cell imaging and modeling.

The group developed a bioinformatics approach to identifying potential STR markers and analytical measurements of multiplex STR markers; developed African green monkey and mouse cell line multiplex STR assays; formed a cooperative research and development agreement (CRADA) with DNA Diagnostics, Inc., to jointly work on the mouse assay (DNA Diagnostics is planning to develop a database of profiles of mouse cell lines to facilitate identification, and other companies have expressed interest); supported development of an ANSI/ATCC consensus standard to identify cell lines at the species level using DNA bar-coding; completed design and construction of a Caenorhabditis elegans laboratory; initiated adaptation of the ISO C. elegans toxicity assay to a C. elegans nano-cytotoxicity assay for a document for the Organization for Economic Cooperation and Development; collaborated with the Alliance for Regenerative Medicine on white papers on measurements for cell therapy products; through the ASTM F04 and ISO 276 committees, worked with the community to identify reference materials and

standards needed for cell therapies; and collaborated with Lonza Group Ltd. on statistically evaluating the accuracy of cell enumeration by automated NucleoCounter and manual hemocytometer methods.

Genome Scale Measurements Group

The Genome Scale Measurements Group has facilities in Gaithersburg, Maryland, and at Stanford University in Palo Alto, California. It is organized to develop and disseminate new measurement science, reference materials, data, and methods for genomics. The group works closely with many stakeholders, such as public–private–academic consortia, the External RNA Controls Consortium, the Genome in a Bottle Consortium, and the Synthetic Biology Standards Consortium. It also works with many of the federal agencies, including the FDA, NIH and its National Cancer Institute (NCI), the Defense Advanced Research Projects Agency (DARPA), and the Department of Homeland Security (DHS).

The Genome Scale Measurement Group’s accomplishments include methods for genome scale measurement assurance and sequence certification; DNA library reference materials, data, and methods; reference materials, data, and methods for the External RNA Controls Consortium (ERCC) dashboard. The software package analyzes results from measurements of RNA spike-in experiments to understand technical performance of single-cell transcriptome sequencing.

In 2012, NIST convened the Genome in a Bottle Consortium, a NIST-hosted public–private–academic partnership to develop the metrology infrastructure for widespread adoption of human genome sequencing in research and regulated clinical applications. The Genome Scale Measurements Group worked with Ambion^® to develop an accurate set of controls, consulting on the design of the mixes and their quality assurance protocols; it also developed reference materials and methods for the Genome in a Bottle project. The group is planning to develop a refined set of controls as a follow-on product to address new RNA measurement science needs, including small nontranslated RNAs, transcript isoforms, and microRNAs (miRNAs)—this refined set of controls will be established as a rebooting of the ERCC (ERCC 2.0 was initiated at an open public workshop in July 2014). The group is also working with more than 75 organizations to develop methods to use these validated reference materials to understand the measurement performance of sequencing instruments and bioinformatics work flows.

The group is also developing standards for cancer diagnosis and therapeutics, such as candidate NIST SRM 2373, which consists of genomic DNA samples that have been extracted from five human breast cancer cell lines with HER2 gene copies ranging from no amplification to low, medium, and high levels. It is evaluating additional copy number standards for the cancer genes MET and EGFR and working on mixture designs for genome scale measurement assurance by establishing reference materials and methods for RNA-sequencing experiments using samples made from well-established mixtures of (usually three) human tissue total RNA isolates.

The group is also working on microbial detection and quantitation with qPCR. In partnership with their colleagues at the Institute for Bioscience and Biological Research (IBBR), they have developed yeast strains with nonnative sequence inserted into the yeast genome (sequence inserts are derived from SRM 2374) to use as controls for microbial detection methods that rely on detection of genomic DNA sequences. In principle, qPCR or other sequence-based assays can be validated by using the inserted sequence as the putative target. This work was initiated to support DHS validation needs. The group is developing four microbial strain whole-genome reference materials intended for use as reference samples to understand sequencing performance.

Opportunities and Challenges

Based on the publications, patents, and discussions, the BBD evinces scientific expertise on a par with that of leading researchers in the areas being researched and developed. However, the talent pool is stretched to capacity. It will be challenging for the BBD to set priorities and cut programs if necessary,

because every research area for which the BBD is developing standards, measurement science, and validation of methodology is of great value to the biological and life science arenas.

The Bioassay Methods Group has developed potential intellectual property and could be a very valuable partner for NIH by providing controls and reference materials that NIH lacks for research studies. The group is demonstrating that biology is indeed greater than the sum of its parts. The newly formed engineering biology team has the potential to accelerate innovation and broadly impact the ability of U.S. companies to compete in the global marketplace for biomanufacturing and synthetic biology. The team is working on ways to enable quantitative measurements of complex biosystem behaviors and enhance the ability to extract predictive and actionable knowledge from data about complex biosystems. There is great potential in the stem cell area, which would benefit from predictive modeling. The group’s challenge is to find ways to formally partner with NIH and the FDA as well as with industry to ensure continual resources, because the area of bioassays continually changes with the integration of improved technology and new information produced by the research community.

The Biomaterials Group is well positioned for expansion and taking a leadership position to coordinate all NIST biomaterial reference materials and standards. Its achievements are many, and it is in high demand from several health industries that are developing novel scaffolds for tissue engineering and protein-to-protein interactions. The research being done using BCARS microspectroscopy for digital pathology is impressive. The need for its capabilities is going to grow, and the challenge will be to keep up with all the stakeholders’ demands. This group is also a very strong research partner for NIH, from which funds could be supporting some of the programs within this group.

The Cell Systems Science Group is involved in and performing many cutting-edge experiments and building integrated research programs that are leading to some very advanced technologies. The opportunities are almost endless in medical research and will multiply in the agricultural arena, in which the group is not currently much involved. Some businesses could be spun out of this group. One of their challenges is managing the amount of data they are collecting. The very broad scientific community that they work with is going to demand more from this highly trained and competent team of scientists.

The Genome Scale Measurement Group, partnered with Stanford University, has many opportunities for collaboration with small and large biotechnology companies in the San Francisco Bay area, which are diverse and numerous. This group has set up a beachhead for the MML on the West Coast and can serve as a conduit for many of NIST’s programs. The research science is exciting and addressing large gaps and needs in the “-omics” sciences. The opportunity to hire postdoctoral researchers from Stanford and the other eminent research universities to work for NIST without their having to relocate to the East Coast provides an advantage with respect to bringing in new talent from the West Coast. Geographical distance between the two sites is a potential challenge. However, they communicate well through use of social media and other conferencing technologies. Another challenge is the cost of living in the Bay area. It would be worthwhile to consider salary adjustments for employees who are assigned to the Stanford campus.

Overall Assessment of Technical Programs

Research at the BBD is cutting edge and on target in addressing needs in biology and life sciences measurement technologies. The output of the BBD is measured by the output of publications and reports as well as by the reference materials and standards for measurements it has provided. The BBD is doing very well in the publication arena given that many of their papers are published in tier 1 scientific journals.

The quality of the research reviewed is very good, and each group is on target to reach the stated technical objectives. The Stanford model appears to be working and may be worth repeating in different parts of the country.

The BBD has demonstrated an impressive ability to leverage talent from other divisions and from other parts of NIST to grow its programs. However, the BBD is understaffed, considering its mission

statement. One example is in the microbiology application arena: The research focus is very much on target with both the human biome and food safety and security research, and although the group is very small compared to some university departments, the quality of its work is outstanding and would be of interest to the U.S. Department of Agriculture (USDA) and the Department of Defense (DoD).

The BBD’s scientific expertise supports NIST’s technical programs at a very high level of quality and, in some cases, quantity. Working in the diverse areas of health care, manufacturing, food safety, environmental health, and national security, the BBD has a commendable grasp and knowledge of the gaps and needs as well as the ability to foster innovation and strategic partnerships. One concern is what can be done today to ensure not only stability of the groups but also strategic partnerships with other federal laboratories and research universities. The BBD stays very focused on its mission and has put into place people and programs to implement the goals of its mission.

PORTFOLIO OF SCIENTIFIC EXPERTISE

The Bioassay Methods Group is highly trained and motivated to bring quality assurance and quality control methodology to the novel tools being developed that will both qualify and quantify biological activity, wellness, predisease, and disease. This group has impressive researchers doing cutting-edge research; they effectively collaborate within and outside of the group to leverage needed talent.

The Biomaterials Group is focusing on areas that are very current in biotechnology. It possesses a highly qualified staff and a strong external network of collaborators at the federal agencies and in industry and academia. Demand for the services of this group is likely to grow in the next 2 years.

The Cell Systems Science Group has a major focus in medical research and is at the center of many of the major research programs being undertaken by NIH and pharmaceutical and biotechnology companies.

The expansion of the Genome Scale Measurement Group to the West Coast is good for the BBD. It establishes a footprint on the West Coast and will attract new talent to work on genomic science, which is in great need of reference materials, controls, measurement science, and validation. The highly creative and trained NIST group at Stanford is doing well and continues to try to include the Gaithersburg staff in many platforms and in developing and/or expanding their capabilities. This expanded center of excellence model is a good one; the MML might consider developing more of these types of partnerships.

ADEQUACY OF FACILITIES, EQUIPMENT, AND HUMAN RESOURCES

The BBD laboratories visited are well equipped with the latest and best equipment for doing research in biotechnology. In addition, the scientists are very good at tweaking the instruments to do more and at integrating systems and creating new instruments. Given that biotechnology is a rapidly evolving technology and that the BBD is trying to anticipate emerging measurement needs as well as hiring and training experts to provide results that have an impact in biotechnology standards and measurements, overall the division has done an excellent job of acquiring the best tools in the toolbox to advance the understanding of complex biological systems on many fronts and at many levels.

The facilities visited were designed for maximum output and very well kept with respect to clean laboratory benches, well-stocked supplies, and a good flow of laboratory capabilities. The equipment of the BBD is state-of-the-art. There are several instruments that will support advances in the understanding of cancer therapies. As an example, within the Genome Scale Measurements Group’s laboratory, near-state-of-the-art sequencing technology is deployed, with four different platforms (Illumina HiSeq 2500, Illumina MiSeq, Life Technologies SOLiD 5500W, and Ion Torrent PGM). There is also access to other sequencing platforms at the FDA, NIH, Mt. Sinai School of Medicine, and Stanford University. Another example is the protein preservation project, whose facilities include a novel, red-edge tabletop

fluorescence instrument—a real advantage in understanding protein–protein interactions. The dental materials program has unique capabilities to simultaneously measure curing kinetics, stress evolution, and reaction exotherms of photopolymerized materials—another advantage in having companies work with the BBD.

Given that the tools in the biotechnology toolbox are continually being redesigned for more quantitative analysis, to remain competitive, purchasing new or retrofitting existing equipment will be high on the investigators’ list. Partnering with instrumentation companies is something that the BBD already does extremely well; it is important that it continue to seek companies that have developed the next generation of biotechnology tools for alpha and beta testing and obtain the instruments at a reduced cost.

With respect to human resources, the BBD is a lean but highly productive division. It is effective and efficient regarding output, considering such a lean staff. The BBD manages to achieve its stated objectives even with its small staff, diverse thrust focus areas, and four major programs. The ratio of Ph.D.s to technicians is high, and in some applications more technicians could be employed to carry out some of the required maintenance of reference standards. The BBD management needs to consider adding more staff to the four divisions if it is going to continue to lead and form strategic partnerships for measurement standards, reference materials, and validation within the many and varied areas of biotechnology.

Working mainly in the biotechnology arena, the BBD has both challenges and opportunities. This unique group of scientists, whose expertise includes biology, chemistry, mathematics, computation, engineering, and physics, is addressing well the complex biological sciences that are continually in flux and driven both by policy and regulatory issues that seem to change frequently. Recognizing that there is a need for better measurements and standards for data sharing, reproducibility, scale-up, and commercialization, the BBD is working on the right things at the right time. For example, it is working in microbial measurements, cell manufacturing and therapies, synthetic biology, and predictive biology. However, there is not a critical mass in any of these areas sufficient to make the BBD a focal point for more outside collaborations.

The new programs in microbial measurements, cell manufacturing and therapies, and predictive biology hold great promise for huge successes. All three areas are being invested in today within the field of biotechnology. Without the required personnel and the right infrastructure, these three programs may not reach their full potential. These programs are also reaching out across the MML and to other laboratories at NIST to leverage resources and talent. The vision that stimulated the creation of these programs is commendable.

The BBD appears to have deep technical expertise in measurement of biological systems and is developing the same capacity for bioengineering. The caliber of the science being performed at the BBD is excellent. The staff are very motivated, highly trained in their respective fields, and enjoy working at NIST. The groups are working well together, and morale appeared to be high. They believe in BBD’s mission and want to do as much as they can. They choose programs and projects in a strategic manner by integrating strong stakeholder input and aligning outside capabilities to their internal strengths. A good example is the collaborative program at Stanford University on advances in biological/medical measurement science, where they are in the heart of biotechnology entrepreneurialism and commercialization at Palo Alto, California. Access to faculty and students at Stanford is a win-win for both the BBD and Stanford. This model seems to be working with the other partners they have at the University of Maryland’s IBBR, located in Rockville, Maryland.

The group leaders appear to communicate and work well together. They are respected and admired by the scientists and technicians at the BBD. Their knowledge of what is going on in many fields and their network of scientists outside of NIST is impressive. They know that they have to attend external meetings, deliver presentations, and publish as well as patent their findings. There is a can-do atmosphere, especially on the innovation and entrepreneurial—bench-to-bank—side of the equation to meet societal needs. A concern is the lack of effective communication with a broad customer base and stakeholders. The BBD needs to do a better job of marketing itself, including making its website easier to navigate.

With respect to human resources, there appears to be a need for the BBD to help the human resources professionals to develop improved ways to recruit the talent that the BBD needs. The challenge is to retain the early-career scientists by devising ways to recognize their many contributions and providing incentives to stay. New policies for promotion that include various tracks for promotion would be welcomed. Excellent hires of research staff at all levels have been made, with one recently hired scientist targeted to enhance the microbial program. The motivation to succeed appears to be infectious across the groups within the BBD.

DISSEMINATION OF PROGRAM OUTPUTS

The BBD is well driven by the stakeholder needs, and its continual outreach to federal agencies, academia, and industry is commendable. The publications were very impressive, especially those published in Science, Nature, and Proceedings of the National Academy of Sciences. The BBD needs help in filing more patents and licensing/codeveloping more of the creative innovations and technologies developed in its laboratories.

However, the BBD staff are not as effective or efficient as they want to be. They mentioned several lost or missed opportunities for commercialization. It appears that in order to better develop translational research outcomes, the BBD may have to perform a complete review and overhaul of their technology transfer operations. The BBD does not seem to be deriving optimal benefit from the NIST technology transfer mechanisms and the NIST Innovation and Industry Services (IIS) office. A good start to remedying the situation would be to review the BBD’s accountability and outcomes for both the technology transfer office and IIS and see if other units are getting better input and support from these two offices, which are responsible for interfacing with industry and moving technology out the doors of NIST. Better integration and coordination between the BBD and the NIST public relations, communication, and IIS offices would enable the BBD to do more monitoring and more external customer interactions. The BBD is doing a relatively good job of monitoring stakeholder use and the impact of the program outputs. They have a very diverse group of stakeholders, as evidenced in Table 4-1.

The MML created the position of safety program coordinator, and it holds an annual safety day. It also developed an online system for hazard review and approval that is now used by other operating units, and it designed an iPad tool for safety inspections that was piloted in the MML but built for all of NIST to use. This could be an application that research laboratories would purchase. In addition, the newly created Office of Data and Informatics will enable much more data to be shared and examined throughout the MML and especially within the BBD.

There is a need for biological measurements and reference materials if the United States is to remain in a leadership position in both biotechnology and the life sciences. NIST’s creation of the BBD by integrating some divisions has proven to be a very successful decision. The BBD’s stakeholders and areas of applications are many, as illustrated in Table 4-1.

The number of the BBD’s industry partnerships and its knowledge of which companies to contact and collaborate with are impressive. The number of partnerships with other federal laboratories and nonprofit institutions is equally impressive. The BBD is planning to do more external communications. The challenge, given the current budget and human resources, is how to keep all these major stakeholders involved and at the same time grow the programs to include more stakeholders. The opportunities are many and significant, considering the capabilities and instrumentation within the BBD. Additional staff and equipment will be needed to stay at the forefront of biotechnology, which is a moving target with many anticipated emerging measurement needs. The BBD needs to continue developing the expertise to make an impact in the field and at the same time create and increase more effective and efficient communication with their very broad base of customers and stakeholders.

TABLE 4-1 Major Stakeholders for the Measurement Technologies and Application Areas Within the BBD

NOTE: ABMS, American Board of Medical Specialties; ADA, American Dental Association; ARM, Alliance for Regenerative Medicine; CRM, Center for Regenerative Medicine; EDRN, Early Detection Research Network; ISAC, International Society for the Advancement of Cytometry; JCVI, J. Craig Venter Institute; NEI, National Eye Institute; NIBSC, National Institute for Biological Standards and Control; NIDCR, Institute of Dental and Craniofacial Research; and NNI, National Nanotechnology Initiative.

Metrology is based on three elements: traceability, measurement uncertainty, and method validation. The BBD is developing a very strong metrology base for biotechnology and the life sciences arena. The BBD is meeting many of biotechnology’s current and future needs to enable U.S. competitiveness and global leadership. It needs to work more on informing others about its programs, and it needs to work on obtaining external resources from industry. The division is to be congratulated for achieving so much in such a short time. The leadership and staff work closely as a team; they are well-polished, well trained, and very focused.

FINDINGS AND RECOMMENDATIONS

The BBD has many cross-cutting activities within and outside of NIST. BBD staff work closely with the MML divisions engaged in the fields of manufacturing, biomanufacturing, biosciences, health and safety, security, and forensics. Overall, the division possesses a high level of technical skills and works on cutting-edge science that requires both reference materials and standards. They perform work in many areas with only 54 full-time equivalent staff. The division is lean in administration and technicians but has a good selection of Ph.D. scientists at all levels, from junior to very senior fellows. They have learned to leverage resources very well and chose strategic partners that can enhance or complement their in-house skill sets and capabilities. Unfunded mandates from Congress detract from programs from which funding is taken to address the unfunded mandates.

BBD staff reported that the procurement procedure is a barrier to getting much-needed supplies on time; procurement dollar limits and procedures imposed by the Department of Commerce delay the ordering of supplies and the conduct of business with external entities; limitations on and administrative procedures for securing approval for attending meetings and for associate travel are counterproductive; and the human subject review, which is critical for success of many BBD projects, often gets bogged down.

BBD staff reported that there is a disconnect between various central administrative functions and the BBD laboratories with respect to appreciating the needs of the scientists and how to make BBD capabilities known to potential stakeholders, clients, and the public. For example, BBD staff reported that there is little communication between the technology transfer group and laboratory staff. The BBD staff do not believe that they have had good interaction with and support from the technology transfer group at NIST and believe that the group responsible for innovation and industry services (IIS) has not adequately supported the scientists. They noted that the IIS met with them only once in the past few years. To make their work better known, the BBD might consider updating their NIST webpage to include videos, stories, and more pictures.

There is no program in place to train junior scientists to take over the maintenance of the standards that are developed. Currently the Ph.D.s maintain the standards. Some Ph.D.s do not object to that, but others prefer to do more research. There is also a need for a succession or protégé plan; currently, succession planning is performed as needs arise. This has engendered concern that in the absence of a clear plan the younger researchers are restless and would probably leave if the economy improves.

There are few bachelor and master’s degree level technicians that could take on some of the more repetitive work currently being done by the senior staff. The BBD also needs to expand its working relationships with academic and industry partners.

BBD staff noted that laboratory equipment purchases are overtaxed and that there has been a reduction in the amount of money for equipment purchases and maintenance contracts. Equipment has an

institutional overhead cost of 30 percent to pay for human resources, safety, and other infrastructure support. BBD staff indicated that equipment taxes significantly reduce the amount of equipment they can purchase.

The BBD depends on the materials with which they work, but they do not have the capability to make the materials.