February 1, 2017 (Vol. 37, No. 3)
Philippe Desjardins Scientific Marketing Consultant Venture Novo, LLC
Imagine the U.S. Population in Microcosm, With All of Its Diversity Represented by Tissue Samples from More Than 1 Million Participants
The Precision Medicine Initiative (PMI) was created by the NIH to answer broad questions on a scale that might be missed by more specialized cohort collections. The production of highly diverse libraries, on a population-wide scale of tens to hundreds of millions of samples, will drive medical understanding by harnessing the statistical power of such great numbers to elucidate questions that cannot otherwise be answered.
The All of UsSM biobank, currently being assembled at the Mayo Clinic, aims to fulfill this initiative by collecting samples from over 1 million participants. This massive cross-section of society will generate over 35 million biological samples. “The cohort is not disease-specific and is representative of the entire population, including cancer patients, Alzheimer’s patients, and even healthy people—it could be anyone,” explained Mine S. Çiçek, Ph.D., director of biospecimens accessioning and processing at the Mayo Clinic.
“We want to make sure that the population is represented as diversely as possible. The goal is make this cohort of samples available to researchers who have questions to be addressed that benefit the health of the population.”
Dr. Çiçek described why the All of Us biobank is so different when compared to more focused biobanks:
- The numbers: Having greater numbers of samples afford researchers the statistical power to be confident that results are actually caused by X or Y, and that what they are seeing are true findings and not false positives.
- Rare diseases: Once again it comes down to the numbers. Some questions cannot be answered for rare diseases because there simply aren’t enough samples of a rare condition to examine. A cohort of over 1 million participants provides a better chance of finding enough samples of a rare disease to answer some of those unique questions.
- Environment: Not everything is genetics. Some diseases are greatly influenced by the environment and other factors. By having participants widely represented across all states, science can be done from various perspectives. The sample collection process is disparate enough to pick up differences such as environment factors.
- Electronic health records: Ongoing access to electronic health records will help the project to proactively follow participants. If an individual is healthy now but in ten years develops a disease, then there will be enough historical information to determine if there is any science behind the finding. Researchers can then start to examine factors within the life of the individual that might have caused the disease.
- All of us: From the participants’ point of view, “Why should I participate? What’s in it for me?” There is a strong initiative regarding participant engagement. By communicating closely with participants, they truly feel like they are contributing to a project for the greater good and that they are in this for all of us.
The Growing Scale of Automation
The 35-million-plus samples that will constitute the All of Us biobank will require processing, storage, and access on an unprecedented scale. “In order to manage a biobank of this scale, automation is absolutely necessary—there is simply no way to do this in a manual environment,” stated Matt Hamilton, president of Hamilton Storage.
“The basis for our collaboration with the Mayo Clinic is to prepare technologies that bring value to such a scope in terms of how sample quality, processing speed, and applications are performed on an automation platform. The project is entirely automated from the point when samples are received all the way to when they are requested for downstream research purposes, which may be months, years, or even decades later. A project of this scale will catapult the industry forward, allowing a high level of consistency at every step of the process, while ensuring quality and integrity throughout the entire lifetime of the sample.”
Biobanking is often composed of different components akin to many puzzle pieces, some steps are manual while other steps are automated. “Now the biobanking industry has a new standard with a fully automated workflow,” Hamilton continued. “Instead of everyone doing their own best practices, we’re creating a full solution of best practices that can be applied to every level of the process. This will drive the industry forward not only today, but ten, twenty years from now.”
Once a baseline has been established and proven on such a large scale, the new standards can then be applied to other projects that may be focused on a specific population or disease. Ultimately, this new benchmark will not only provide consistency across the PMI but potentially for multiple projects throughout the world.
Specificity and Translational Solutions
While diversity is a key component for population-wide biobanking, there is also a continuing demand for the creation of specialized libraries that can address medical solutions with greater specificity.
One good example is the cancer research community’s growing need for the creation of animal models that accurately represent precise cancers in humans. Patient samples must be acquired, processed, and stored in a manner that produces the most viable material for this highly specified purpose.
The Jackson Laboratories has formed the Human Tumor Consortium of medical institutions to achieve this goal. “We have developed a relationship with several clinical centers that provide us with tissue to create patient-derived, xenograft mouse models (PDX). What is important is that the patients are currently undergoing cancer treatment in the clinic today,” explained Susan Airhart, senior director, strategic research initiatives.
“We can now acquire tumors that have become resistant to current standards of care and have been exposed to other clinical components that are potentially driving tumor behavior. This is one of the most important contributions PDX models are making to cancer drug discovery and development. Pharmaceutical companies and academic institutions can then use these highly specialized models to overcome resistance to newer agents and accelerate the development of more clinically relevant drugs for our cancer patients.”
The Eastern Maine Medical Center (EMMC) is at the epicenter of the tumor consortium. There are several important components that are essential to the success of the xenograft program.
“First you need an interface with the patients to explain in great detail what is going to happen with their tissue,” stated Jens Rueter, M.D., medical director, Maine Cancer Genomics Initiative, The Jackson Laboratory, and former medical director of the EMMC oncology research program. “The most extraordinary aspect of patient consent process is that we’ve made it very clear that this research isn’t necessarily for them but for the greater good—for future patients.”
The physical sample integrity as well as all of the pertinent information associated with each sample is critical to the engraftment success rate. “Specimens used for creating new xenograft models have to be handled appropriately. There is only so much time after surgery for tissue to be placed in the appropriate medium, shipped in the right conditions, or properly preserved for later use,” Dr. Rueter continued.
“We also want to have good information about each tumor. What is the exact histologic diagnosis? What are the characteristics of the tumor as it is removed from the patient? All of this information needs to be collected, summarized, and entered appropriately into a database.” By maintaining sample integrity and information, the PDX models produced are much more powerful for downstream translational research purposes.
Informatics and Sample Intelligence
A key discussion being made throughout the biobanking community revolves around the handling of information. “Our informatics strategy is about connecting samples with data to enable those samples to be effectively sourced and used for research,” stated Mark Fish, general manager of informatics at Brooks Life Science Systems. “The sample itself isn’t going to answer the big questions unless you can connect it with data that makes it valuable to researchers.”
Biobanks tend to go through a large collection phase of expansion that focus on acquiring lots of samples from the medical community, but the real value comes from how those samples can be used in research to help further healthcare innovation.
New informatics platforms must go beyond the operational and physical aspects of sample management to include informed consent and phenotypical data. “The BioStudies interactive software provides a research-centric lens to help biobank customers connect sample inventories to data that make samples useful and valuable,” Fish explained. This connectivity enables researchers to mine clinical and phenotypical datasets that link therapies and clinical outcomes. This allows them to understand why a treatment works well for one group and not another. By unlocking sample intelligence, researchers can drill into the information that makes samples ‘smart’, and they can then start to answer the larger questions surrounding precision medicine.”
We Are All Biobankers
From a broad perspective, the biobanking industry must standardize the physical handling and storage of every sample, while at the same time bring consistency to all data associated with each sample.
“There is no standardized practice in biobanking in terms of these two critical elements,” stated Jeffrey Goldman, director, applications marketing, laboratory products group, Thermo Fisher Scientific. “Inconsistent practices in tissue preparation, sample collection, sample storage, or even transportation methods, can have a dramatic effect on the integrity of the samples. The issue of data quality may also prevent some samples from ever being used, because there is no standardization across the information architecture.”
Biobank industry providers will not only have to provide comprehensive portfolios of equipment adhering to international standards, but will also need to educate the marketplace regarding best practices for state-of-the-art biobanking solutions.
As a final thought, “how do we broaden the scope of biobanking as a discipline?” Goldman asked. “A true, dedicated biobanker will be aware of these issues as well as the industry trends that will eventually solve them. Life science researchers who are storing samples outside of that traditional biorepository model don’t really think of themselves as doing biobanking, yet every cell and molecular biology lab has freezers that store their life’s work.”
The variability in sample integrity is orders of magnitude higher when expanded to include all laboratories across in the world. Valuable and irreplaceable research is lost every year due to poor practices in cryopreservation and sample storage. “By bringing awareness of what biobanking really is to the entire scientific community, one can easily extrapolate biobanking as a global sample structure, where all life science researchers begin to think of themselves as biobankers,” Goldman added.