Since 1996, the rise of genomics and the increasing practicability of precision medicine have shifted biobanking away from the first generation of cell repositories. The same forces driving consolidation of large healthcare organizations have driven major research efforts built around combinations of clinical specimens, large numbers of electronic healthcare records, large-scale genomic and proteomic research expertise, and the computer-science tools to undertake complex analyses of extremely large datasets.
Biobanks have expanded, proliferated, and, in a sense, speciated. Biospecimen source guides now list hundreds of biobanks pursuing multiple business models to collect, hold, distribute, annotate, index, and analyze specimens (mostly human-derived) for biomedical research. (See sidebar, “A Field Guide to the Biobanks.”)
March milestones
The biggest push in current biobanking—measured in funds brought to bear and activity generated—is coming from national precision-medicine initiatives like the “All of Us” biobank in the U.S. and the UK Biobank in Britain—both of which achieved important milestones earlier this year.
On March 11, the UK Biobank released exome sequence data on 50,000 people. These volunteers represent a cross-section of Great Britain’s population, and the records are linked to National Health Service Records. The exome release followed 19 months after UK Biobank released genotyping data on 500,000 participants.1
A few days earlier, a younger initiative had passed a milestone of its own. The “All of Us” data browser went live on May 6, allowing anyone to view anonymized summaries of electronic health records and health-assessment self-surveys for 160,000 U.S. volunteers.2 From early 2020 on, says Mark Caulder, NIH program director for “All of Us,” approved researchers will be able to analyze anonymized participant data using the program’s Researcher Workbench.
Meanwhile, noted Nature Research, “[p]rojects of this type are being pursued in a number of countries including Iceland, Japan, and Canada.”2
All of us
In the message accompanying its FY 2020 budget outline, the National Institutes of Health says that the “All of Us” research program is “a key component of the Precision Medicine Initiative (PMI) and the 21st Century Cures Act [and] an ambitious effort to accelerate health research and medical breakthroughs.”3
Study participants can enroll online at joinallofus.org and supply samples at any of more than 340 participating locations—health care providers (such as hospitals and regional provider organizations), clinical labs (like Quest Diagnostics), drugstores (Walgreens clinics are participating), and similar facilities.4
In July, when the “All of Us” research team reported on the project in the New England Journal of Medicine, 175,000 people had enrolled, taking the project a long stride toward its goal of 1 million participants by 2024. Volunteers contribute blood or saliva samples in addition to granting access to their records and completing general baseline health surveys. New participants are coming in at the rate of about 3,100 per week.4
“All of Us” currently compiles information from health surveys (several modules on health, lifestyle, drug use, demographics, family history, and access to health care), physical measurements (heart rate, weight, and BMI), blood, urine, and saliva (for DNA, RNA, and blood workups), EHRs, and personal digital health devices. As time goes on, “All of Us” will add additional surveys, genotype and whole-genome analyses, health insurance claims data, environmental data, and (possibly) pipelines from social media.4
By the end of September 2019, said “All of Us” program director Caulder, more than 268,000 people had joined the program, and some 206,000 had completed the initial surveys and biospecimen donation. (Anyone can track project enrollment progress at researchallofus.org/data/data-snapshots/.)
“One strength of our program,” Caulder sums up, “is the diversity of data types we’re gathering to make accessible to researchers all in one place. That includes survey information on participants’ lifestyles and family health histories, genome sequences, electronic health records, and more. Together, this information may help researchers better understand how behavioral, biological, and environmental factors combine to influence heath.”
Image: Figure 1. "All of Us" Enrollment as of Oct. 1, 2019. “All of Us” is based in the NIH director’s office, with basic support running about $190 million a year from the director’s budget.
Challenges
Despite deep financial support and research commitment, the current generation of biobanks face some challenges—sustainability, standardization, and security rank high among them.
Sustainability: Smaller-scale research projects have “predictable experimental costs, predetermined procedures, and a finite” active life. Big biobanks require lots of staff, equipment, and facilities—but their exact costs cannot be defined at the outset. And at any rate, they typically rely on enormous amounts of governmental or other grant funding—which can be fickle. “[B]iobanks leverage the financial potential of their specimens and data, but this may lead to ethical and legal issues…. International biobanks have agreed that the human samples stored cannot be used for commercial purposes.”5
The U.S. National Cancer Institute’s Biorepositories and Biospecimen Research Branch (BBRB) surveyed biobanks worldwide to gauge their concerns about financial and operational sustainability.6 They found that older biobanks (in operation five years or more) worried most about securing sustainable funding and replacing declining funding sources, while newer operations were concerned at first about sustaining growth and acquiring new specimens; concerns about keeping up with quality standards increased through the first five years of operation to rank with acquisitions as the chief concerns. Big biobanks (holding more than 500,000 specimens) worried less about securing or replacing funding than they did about acquisitions and sustaining growth (and, judging by the responses, by the time they’ve grown to their current size, they have nailed standards compliance). Small and medium groups focus on securing funding and replacing declining funding sources.
Standardization: Because biobanking emerged from the ground up, standards for informed consent, preservation, storage, rights-management, materials transfer agreements, classifications, and a host of other factors were slow to harmonize. It wasn’t until the U.S. National Cancer Biobank introduced its standard operating procedures that an effort began to make materials compatible and comparable.5
Security: Because personal health data is so sensitive, much current writing on biobanking focuses on participant privacy and security, and a lot of energy goes into building in security… and double-checking to make sure that it works. In June, the Inspector General of the U.S. Department of Health and Human Services released a report (gently titled “The National Institutes of Health Could Improve Its Monitoring to Ensure That an Awardee of the All Of Us Research Program Had Adequate Cybersecurity Controls to Protect Participants’ Sensitive Data”) recounting the discovery, and repair, of security flaws in one of the seven principal IT components of “All of Us,” leading to a redoubling of NIH’s data oversight efforts.7
Rewards
Asked for the most interesting thing “All of Us” has revealed so far, Caulder said, “We’ve been excited to see the diversity of our participant community. So far, over 80% of our participants who’ve completed the initial steps of the program come from communities that have been historically underrepresented in medical research. About 50% are racial and ethnic minorities. It was our goal all along to enroll not only a large cohort, but a diverse one, so it’s encouraging to see this level of interest across different groups.”
“There are many challenges with any new effort, especially one as ambitious as ours,” he said, looking ahead. “To be successful, we’ll need to continue expanding our reach to more remote areas, keeping participants engaged over the long term, and harmonizing data from different systems, for instance. Work is underway on all these fronts.”
A Field Guide to the Biobanks
Why worry about classifying biobanks?
As a pair of researchers at the British Columbia Cancer Agency put it in the early days of the biobank classification effort, categorization is “important… for several reasons: to ensure that the diversity of biobanks is appreciated, to assist researchers in understanding what type of biobank they need access to, and to help institutions/funding bodies appreciate the varying level of support required for different types of biobanks.”8
A single research group, for example, might manage a small collection of tissues, model organisms, and data central to its research effort; collaborate with closely related labs to establish a common biobank focused on the disease they are studying; obtain research samples from other institutions through the American Type Culture Collection (ATCC); and, when they publish, comply with publisher’s specimen-availability requirements (and relieve themselves of the headaches of fulfilling multiple requests) by depositing samples at a disease-centered biobank in their field or at ATCC and sending model mouse mutants to the Jackson Laboratory.9 Depending on the context, anything from a seed vault for ancestral crops to a morgue processing donated cadavers might be considered part of the process.
Classification schemes
Some researchers distinguish between repositories and biobanks, or, rather, class biobanks as a subcategory of repository. By their definitions, a repository, or biorepository, collects, processes, stores, and distributes biological specimens of any type, from any kingdom, from virions to human.
To them, biobanks are specialized repositories, characterized by a focus on medical samples, mostly human-derived, by extensive annotation (up to and including donors’ electronic health records and insurance claims information), by heavy emphasis on genomic and proteomic analyses, and by developing and using informatic tools to maintain and analyze extremely large datasets.
Beyond that, biobanks differ in their approaches to collection. “There are several types of biobanks. Including those that are disease-centric, population-based, genetic or DNA/RNA, project-driven, tissue versus multiple specimen type, commercial, and virtual biobanks.”10
The character of a biobank is influenced by its setting—in a government healthcare agency, and academic research medical centers, a disease-focused non-profit, a project consortium, or a for-profit company.
This all leads up to a lot of options, and current data indicates that every niche in the biobanking ecosystem may be filled.
Biobank directories
Coppola, et al. cite six primary national cell-line repositories.5
The eldest is the American Type Culture Collection, which will see its 100th birthday in 2025. With reported 2017 revenues of some $99.6 million,10 ATCC houses and distributes more than: 3,000 human and animal viruses; 18,000 bacterial strains from 750 genera, 7,600 yeast and fungus species; and 3,400 continuous cell lines derived from humans and more than 150 animal species.
Other national and regional repositories include Germany’s Leibniz-Institute Deutsche Sammlung von Mikroorganismen und Zellkulturen with 31,000 bacterial strains, 840 human and animal cell lines, and a large collections of phages, fungi, and viruses; the European Collection of Cell Cultures; the Japanese Cancer Research Resources Bank RIKEN BioResource Center; and the Korean Cell Line Bank.
A diversity of biobanks
In 2004, The International Society for Biological and Environmental Repositories had 102 member organizations (and 70 individual members). By the end of 2018, the numbers had grown to 261 organizations (36 large, 70 medium, and 155 small) and 412 individuals.12
BBMRI-ERIC (the Biobanking and BioMolecular Resources Research Infrastructure-European Research Infra structure Consortium) biobank database includes more than 600 European Union biobanks, searchable by county (18 of them, collection types (11 kinds, including birth cohort, disease specific, longitudinal, twin-study), or types of materials (17, including cDNA/mRNA, DNA, whole blood, FFPE, and more).
The smaller directory at Biobanking.org includes 203 biobanks, many in Canada and the U.S.13
And the National Cancer Institute’s Specimen Resource Locator includes 392 collections from 42 sources in the U.S.14
For those interested in the evolving biobanking taxonomy, Srikanth Adiga—CEO of OpenSpecimen, an open-source biobank informatic software company in Pune, India—gives a very nice summary of classification options on his company’s blog.15
References
1. Kaiser J, Gibbons A. Huge trove of British biodata is unlocking secrets of depression, sexual orientation, and more. Science (80- ). January 2019.
2.Marx V. UK Biobank and NIH’s “All of Us” release large-scale datasets | Nature Research Bioengineering Community. Nature Research Bioengineering.
3. National Institutes of Health Office of the Director. OD-2: National Institutes of Health, Office of the Director (OD) FY 2020 Budget Narrative.; 2019. Accessed September 28, 2019.
4.The All of Us Research Program Investigators. The “All of Us” Research Program. N Engl J Med. 2019;381(7):668-676.
5. Coppola L, Cianflone A, Grimaldi AM, et al. Biobanking in health care: Evolution and future directions. J Transl Med. 2019;17(1).
6. Rao A, Vaught J, Tulskie B, et al. Critical Financial Challenges for Biobanking: Report of a National Cancer Institute Study. Biopreserv Biobank. 2019;17(2):129-138.
7. Jarmon GL. The National Institutes of Health Could Improve Its Monitoring to Ensure That an Awardee of the All of Us Research Program Had Adequate Cybersecurity Controls to Protect Participants’ Sensitive Data, A-18-17-09304.; 2019. Accessed September 28, 2019.
8. Watson PH, Barnes RO. A proposed schema for classifying human research biobanks. Biopreserv Biobank. 2011;9(4):327-333. 0
9. Reporting standards and availability of data, materials, code and protocols: Availability of materials. Nature Research. Accessed September 29, 2019.
10. De Souza YG, Greenspan JS. Biobanking past, present and future: Responsibilities and benefits. AIDS. 2013;27(3):303-312.
11. Nonprofit Explorer - AMERICAN TYPE CULTURE COLLECTION - Form 990 - ProPublica. Accessed September 28, 2019.
12. The International Society for Biological and Environmental Repositories. 2018 Annual Report - ISBER.; 2019. Accessed September 26, 2019.
13. University of British Columbia Office of Biobank Education. Biobank Resource Centre: Biobanks. Accessed September 29, 2019.
14. National Cancer Institute Specimen Resource Locator. Accessed September 29, 2019.
15. Srikanth Adiga. Should we classify biorepositories? Published 2019. Accessed September 27, 2019.