Six years ago, Gail Onderak of Rochester, Minnesota, was invited to join a community advisory board for an ambitious new biobank the nearby Mayo Clinic aimed to start. The clinic had set a goal of collecting 50,000 blood samples from community members, with the aim of making the samples available to researchers. The advisory board gathered opinions about the hopes that such research could bring. The board also voiced privacy and confidentiality concerns that the community might have about collecting and storing a large number of blood samples and medical information from healthy donors.
For the past 100 years, researchers have collected and stored tissue samples to study diseases such as Alzheimer’s, heart disease, and every type of cancer. These tissue collections are called biobanks, and they can range from a small assortment of samples in a laboratory freezer to a collection of bar-coded vials or other collection containers housed in state-of-the art freezer farms.
“Virtually everywhere there’s medical research involving human specimens, there’s a biobank,” says Helen Moore, the chief of the Biorepositories and Biospecimen Research Branch at the National Cancer Institute.
The way that large institutions collect and store tissue samples for research is changing. Doctors collect samples as part of routine clinical care — anything from saliva, blood, or urine to a biopsy or surgical sample. A pathology department analyzes and then archives the samples. Usually doctors take only the amount needed for analysis and discard the rest. The extra tissue, which contains valuable genetic information, goes to waste. However, the increase in molecular genetic testing has sparked the need for higher-quality tissue samples and boosted the demand for blood samples from healthy donors. Now institutions are actively recruiting tissue from people with and without disease. Genomic research relies heavily on such data.
“A lot of the research can’t be done, or won’t be done as quickly, if these samples aren’t available,” says Onderak.
Cornerstones of Research
Researchers need super-biobanks with well-maintained specimens and high numbers of patients, so they can look for what’s unique and what’s common in a particular disease. Some studies need hundreds, perhaps thousands, of patients.
Size is relative in tissue banking, depending on the goals of the bank and the type of samples. For a rare disease, a bank with a few hundred samples may be large. And a bank with a relatively small number of samples may still be considered large if many researchers use those samples for a lot of studies, says Ty Hoover, a pathologist and the director of Biorepository Regulatory Support at the University of Texas MD Anderson Cancer Center in Houston.
The Mayo Clinic Biobank reached its goal of 50,000 blood samples from healthy donors in April 2015. That doesn’t count the smaller, disease-specific tissue collections that Mayo investigators have gathered in other efforts.
There are hundreds of biobanks in the United States. Institutions with large biobanks that conduct research include the Moffitt Cancer Center in Tampa, Florida; the Marshfield Clinic in Marshfield, Wisconsin; Vanderbilt University, in Nashville, Tennessee; and the MD Anderson Cancer Center.
“Biobanks or biorepositories are really the cornerstone of translational research,” says Stephen Thibodeau, a laboratory medicine specialist at the Mayo Clinic. One of the advantages of having such a large collection of blood samples from generally healthy donors is that the Mayo team can follow the donors over time. Some donors could develop disease, at which time they might have additional blood and tissue samples taken, allowing researchers to compare the original blood sample to later ones to look for biomarkers of, say, prostate cancer or bipolar disease. Samples from the Mayo collection are also used as controls for the study of disease by other investigators.
At the University of Michigan in Ann Arbor, Thomas Carey, a head and neck cancer specialist, collects, stores, distributes, and studies biopsy tissues with the hopes of finding out if biomarkers distinguish patients who did better or worse with a particular treatment. “We search for a weak spot that can be targeted to stop cancer cells from dividing,” says Carey. Researchers can also use tissue in biobanks to study how people react to pain and anesthesia. Finding genetic markers would allow physicians to sort out who is likely to have an adverse reaction or who will need more or less pain medication.
“Some studies, like the anesthesia study, need thousands of samples to find common genetic markers, and samples from healthy people make such comparisons possible,” says Carey. “I have great enthusiasm for what can be learned from storing annotated specimens on many people.”
Collecting and storing tens of thousands of blood samples requires tremendous effort in both the laboratory and the regulatory environment.
For starters, blood samples are drawn from the donor into a collection tube, the same way blood is drawn in a doctor’s office. In biobanking, the blood samples are further divided into tiny portions (aliquots), so potentially hundreds of researchers can use each sample. Samples are stored in mechanical or in liquid nitrogen freezers to preserve DNA and proteins.
The donor’s detailed medical history, including past illnesses, current and past medications, mental health, and family history, may be collected with the sample, and this information needs to be kept private and confidential.
To protect the donor’s privacy, coded identification numbers or bar codes are used on test tubes, rather than patient names. The codes are linked back to the donor’s medical record, but the researchers who use the samples rarely need to learn the donor’s identity.
Likewise, researchers learn only the information in the patient’s medical history that’s relevant to a specific project. “It’s not possible to have a 100 percent safeguard for privacy, but we use many types of safeguards, including physical safeguards, electronic security measures in the computer system, training and education for employees who deal with that type of information, and institutional review board oversight,” says Hoover.
Because laws and regulations regarding ownership of research data are evolving, patients’ tissue consent forms for research projects need to be detailed and informative, says Hoover. Consent forms differ by institution and project.
Some consent forms are used for one specific project, basically allowing scientists to use the tissue or information gathered in a questionnaire for just one research project. By signing the form, donors give permission for use of their tissue or their answers on a questionnaire. Other consent forms can be more inclusive. For instance, the consent form in the Mayo Clinic Community Blood Bank is open, granting permission for the blood sample to be used for any approved current and future research.
Onderak says Mayo’s community advisory board considered allowing donors to check boxes that would direct their blood samples toward specific types of research but opted instead for a consent form that allows them to be used for any type of research. Donating a blood sample was not a requirement for participation in the advisory board, but eventually Onderak decided to donate. “I didn’t hope to get a personal benefit, but I was hoping this would be helpful for researchers who are trying to use genetics and for health care in general,” she says. Two of Onderak’s children were adopted from Guatemala, and she doesn’t know much about their birth family’s medical history. She’s hoping that genomic research can help treat any medical issues her children and others might develop someday.
Potential tissue donors for genomics research need to be especially careful about signing forms. DNA frozen in test tubes can last a very long time, says Mark Frye, a psychiatrist and researcher at the Mayo Clinic who studies the genomics of mood disorders. Frye found several challenges in developing the 19-page consent form for his project on bipolar disorder. The language needed to be understandable by someone with an eighth-grade education, but the medical and technical terms were hard to translate to that educational level.
Health and science journalist Gretchen Cuda-Kroen concurs that forms can be overwhelming. A few years ago, Cuda-Kroen participated in a research study designed to assess attitudes about noninvasive fetal testing. Though she has a background in journalism, has completed coursework for a PhD in pharmacology, and has a husband who’s a physician, Cuda-Kroen says it would have been very easy to miss something. She recommends that participants read the forms carefully with the researcher. Ask questions so you don’t overlook anything or agree to something you don’t understand. “Realize what permissions you are giving, and whether you feel comfortable with what’s been explained.”
Although donors don’t find out their individual results as part of a research project, sometimes results can show, for instance, that the donor might be at increased risk of a disease. Right now, such results are handled by committees at the institution on a case-by-case basis, and patients don’t usually get the results unless they are considered actionable.
Tissue donors don’t typically directly benefit from biobanks, other than getting to feel altruistic. In the future, though, that could change. “That’s the hope and promise of tissue-based research and banking and personalized medicine and translational therapies,” says Hoover. If enough people donate tissue, there will be a critical mass of patients whose samples are in the research pipeline, and if their tissue has a specific marker that makes them eligible for future treatment, “they would still be alive and well enough to participate in another research study that may benefit them,” says Hoover.