Biobanking Can Boost Scientific Productivity

Achieving greater degrees of specialization, biobanking is improving reproducibility and helping researchers focus on their core competencies

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biobanking
The word “biobank” will probably always conjure images of frost-covered samples tucked inside laboratory-grade freezers. But any biobank that is worthy of the name is quite a bit more. In addition to being a collection of biosamples, a biobank is a collection of logistical protocols, consulting services, and data structures. Moreover, today’s biobanks are anything but rigid. They often evidence flexibility, for example, by working with multiple institutions and accommodating a range of research needs. [iStock/©annedde]
In the Wealth of Nations, Adam Smith celebrated specialization, the driver, he insisted, of productivity growth. Although he illustrated his argument by describing the operations of a pin factory, he probably expected that posterity would see his ideas borne out less prosaically. Well, for the record, Smith was right. By now, the connection between specialization and productivity has been affirmed in all sorts of activity, not the least of which is scientific research.

In scientific research, as in pin factories, automobile assembly plants, and chip foundries, much is to be gained through the division of labor. Not so long ago, biological and medical researchers collected tissue samples, stored them in freezers in their laboratories, and returned to them as necessary to conduct their investigations. However, in the last decade or so, these activities have become a specialty, one that is increasingly the business of dedicated third parties—institutions known as biobanks.

To operate on a large scale and serve multiple clients, biobanks must do more than keep freezers running. Biobanks, or biorepositories, must become adept at logistics.

“Biobanking is its own dimension of science,” says bioethicist Kyle Brothers, MD, PhD, an associate professor of pediatrics at Louisville University. Biobanking, he elaborates, requires an ongoing cultivation of expert knowledge. This process, which has accelerated since 2000, is trying to keep pace with the new genomics technologies. “Geneticists really picked up on this and ran with it,” Brothers points out. “You started to see the larger biorepositories [reflect genomics advances] in the first 10 or 15 years of the century.”

But in scientific research, as in any field adjusting to new divisions of labor, fresh challenges arise constantly. For example, the biobanking domain of scientific research is still exploring its boundaries. While some biobanks take “banking” quite literally, focusing on the exacting details of storing biological samples at precise temperatures at a central location, other biobanks are more decentralized affairs, harnessing networks of biobanks to achieve cooperative research ends.

Cold storage plus hot tips

Founded in 1953 in New Jersey, the nonprofit Coriell Institute has been storing tissues for decades longer than the term “biobanking” has existed. Today, the organization hosts an extensive collection of induced pluripotent stem cells and neurological disorder samples, according to chief scientific officer Alissa M. Resch, PhD. As technology and research have evolved, however, so have biobanks, and the Coriell Institute has started offering more than just storage and access to tissue samples.

“When most people think about a biobank, they envision a room full of liquid nitrogen tanks and freezers,” Resch notes. A biobank, however, is more than a collection of frozen samples. “Our experience,” Resch points out, “has shown that the more data associated with a sample, the more valuable the sample.”

Coriell provides custom storage and preparation of samples and has developed consulting expertise in drafting study protocols and obtaining informed consent, Resch says, and the institute has its own internal review board dedicated to ensuring patient privacy. Operating as more than just a supplier of tissues, Coriell has contributed its expert advice to several large NIH-funded consortia projects, such as the 1000 Genomes Project and the Congenital Heart Disease Genetic Network Study. “[Consulting] is an activity that more biobanks will be involved with in the future,” says Resch, “as more and more studies with thousands and millions of participants are rolled out.”

The line between order and disorder

Founded in 2010 and based in Lund, Sweden, Birka BioStorage focuses on the logistical side of biobanking—the storage, documentation, and disposal of samples for a global clientele of startup and midsized companies. The company’s founder and director of commercial operations, Ali Ismail, maintains that logistics is all about collaboration. When Birka assumes logistical burdens, he emphasizes, clients are free to focus on their research.

Trained as a chemical engineer and a longtime member of the biotech industry, Ismail is familiar with the problem of supporting complex operations that rely on orderly resource flows. “I faced that kind of problem in managing logistics of samples,” he recalls. “[When I had to worry about] receiving, sending, and transporting samples, [I would start] waking up in the middle of the night.”

Logistics issues remain even for those companies that implement virtual business models. “They don’t even have their own laboratories,” Ismail points out. For these companies, he adds, assistance with “a lot of the practical work and the logistical work is very appreciated.”

Logistical assistance also facilitates the increasingly distributed nature of research. “Biotech and pharma projects are very distributed all over the world,” Ismail says. It’s possible to do development in one country, scale-up in a second country, and manufacturing in a third country, he elaborates, adding that when clinical trials start, a project can become global.

Ismail keeps a focus on risk mitigation at Birka, and for him, that means good infrastructure. And to support a good infrastructure, he emphasizes, “the main pillar you need to have in place is a solid team.”

For example, biobank personnel may accept the thermometer reading on a freezer as the final word on whether biological samples are being safely, consistently stored. But it’s possible for said personnel to be more conscientious. Ismail’s team, for example, worked to map the temperature variations within their freezers. In some cases, they found differences of 10 °C. “You can buy very nice equipment,” Ismail advises, “but it’s how you handle the equipment that determines the quality of storage you get at the end.”

Such fine attention to detail is important to researchers, but as the industry grows, Ismail says, one of the most basic and universal challenges every successful biobank will have to meet is the raw need for space to store growing collections and create adequate workspace. Birka is in currently moving to a new facility in Lund that is six times larger than its first. “In two years, it will be full,” Ismail predicts. “It’s another kind of headache.”

Ensuring reproducibility of scientific work

Biobanking doesn’t just serve industry and industrial-scale science, it is an industry. And like any industry, it must, as it grows, attend to increasingly challenging quality issues. These issues are familiar to Jan-Eric Litton, PhD, professor of medical epidemiology and biostatistics, Karolinska Institutet. In 2010, he helped launch a national network for biobanking. And in 2014, he was named the first director general of the BioBanking and BioMolecular Resources Research Infrastructure—European Research Infrastructure Consortium (BBMRI-ERIC), a pan-European research project with a catalog of more than 20 million human biological samples.

Litton has come to see biobanking as having a role in upholding a fundamental principle of science—reproducibility. Prompted, in part, by a 2013 cover story in The Economist, “How Science Goes Wrong,”1 Litton began considering how health research infrastructure could improve the reproducibility and reliability of biological samples and data. In 2018, he summarized his thoughts in a paper that appeared in Biopreservation and Biobanking.2

“There is an increasing concern about the reliability of medical research,” he wrote, “with recent articles suggesting that up to 85% of research is wasted.” One possible cause? Variations in reagents and biological substrates that are unaccounted for by researchers because provenance information goes unrecorded.

“People were collecting samples, but they were also sloppy,” Litton says. “They didn’t think about the importance of documenting everything.” For any given sample, Litton continues, relevant factors include the time of collection; the person who took the sample; the collection method; and transport, handling, and storage details, such as temperature. “Extracting DNA—that’s an easy one because it doesn’t really matter,” Litton notes. “But for some of the proteins we are studying now with biobank samples, little things about how the sample was collected can totally change the history.”

In 2015, 2016, and 2017, BBMRI-ERIC took on a massive quality assurance program with five working groups composed of researchers from 18 different member states, working toward developing international standards for data recording along with biobank samples. “Doing that has helped enormously,” Litton declares. He also believes, however, that the work is far from done, particularly because it’s hard to know just what types of information about a sample may become available as more advanced analytic technologies are deployed.

At the same time, he says, there are opportunities for collecting even more samples in areas that are not yet well represented in biobanking, such as microbiome samples and data. Good biobank catalogs and databases of microbiome data, along with the genomic data collected by companies such as 23andMe, will be essential for preventative and precision medicine. “I think the sample is important,” Litton explains, “because we are so different—not only between humans, but also between cultures, between countries.”

FinnGen

Although cultural and genetic differences often pose biobanking challenges, they occasionally present opportunities. For example, in Finland, cultural and even genetic difference are proving to be an advantage for FinnGen. Although FinnGen is more of a biobanking research project than an actual biobank, it does make use of a network of 10 biobanks in the country, including those at university hospitals, according to FinnGen’s scientific director, Aarno Palotie, MD, PhD.

FinnGen has been collecting personal genomic and other data on Finns in a manner similar to that used by the U.S. National Institutes of Health’s All of Us Research Program, and with an eye to making progress in personalized medicine, basic research, and economic development. FinnGen has been helped along, Palotie adds, by Finland’s centralized healthcare system. In Finland, the utilization of health services by every citizen, from birth to death, is recorded in healthcare registers. Thorough records have long supported epidemiological studies in the country.

“This is a research project funded by the Finnish Innovation Fund and, currently, nine international pharmaceutical companies. The aim is to collect samples from 500,000 individuals in Finland, which is roughly 10% of the entire population,” he details. “We have already collected samples from 324,000 individuals. So, we are well on the way.”

Besides collecting blood samples, FinnGen is extracting DNA and conducting genome-wide association studies (GWASs), Palotie continues. The ability to rely on GWASs rather than full sequencing is a cost efficiency made possible by the unique genetic profile of the Finnish population. “We don’t sequence everyone because we are the largest population isolate/genetic isolate in Europe,” he notes. “Our accuracy and specificity on genotyping is much higher than in New York or London or Paris.

Biobank-based projects need to harmonize genomic information with phenotype information. In a country like the United States, for example, where personal medical data is often siloed in disparate electronic health record systems that use different data structures to store patient data, it is difficult to even collect all the necessary information. In Nordic countries, accessing data is less of a challenge.

“We have the luxury of consulting national healthcare registers, which have structured data,” Palotie declares. “We know how the registers are constructed, so it’s a much easier setting than a mixed bag of questionable electronic health record data.”

But one challenge Finnish biobanks share with biobanks around the world is the delay between investment and returns. “One of the misconceptions of some of the hospitals when they started biobanks is that they think it’s a money-making machine,” Palotie remarks. “It won’t be.” Instead, biobanks are about investing in future returns that may not be imagined yet. “You build for the future,” Palotie insists, “and the revenue horizon is longer than a few years.”

 

 

References
1. Leaders. How science goes wrong: Scientific research has changed the world. Now it needs to change itself. Economist 2013; Oct. 19: 13. https://www.economist.com/leaders/2013/10/21/how-science-goes-wrong
2. Litton, J-E. Launch of an Infrastructure for Health Research: BBMRI-ERIC. Biopreserv. Biobank. 2018; 16(3): 233–241.

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