Bank With Us
The more we learn about disease, the more essential biobanks become – so why aren’t more people aware of their value?
Biobanking – the act of preserving and storing samples of biomaterial – is an often-overlooked aspect of biomedical research, diagnostics, and prognostics. The samples stored in biobanks can yield valuable insight into disease processes over time, assist with retrospective studies of conditions and their causes, and stand families in good stead when a seemingly isolated instance of disease turns out to have a hereditary culprit. Not only researchers, but also pathologists, laboratory medicine professionals, and patients should value these resources. And yet, many people outside the laboratory aren’t even aware of the existence of biobanks, let alone the varied purposes they serve. Fewer still know how biobanks are changing to keep pace with our increasingly computerized world and the growing value of the data that accompanies samples – after all, what is a whole slide image archive if not a digital biobank? And what is a small piece of tissue without its accompanying clinical data?
We spoke to three experts from the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) – two pathologists involved in research and clinical care, and one trained patient expert – to learn more about what biobanking can do for today’s laboratory medicine.
The Power of Planning
Biobanks can meet current and future pathology research needs – if we anticipate those needs
With Daphne de Jong
Why is biobanking valuable for medical research?
The fundamental importance of biobanking is that it lets us translate findings from basic research to the patient level. For that, we need patient data that are complete, accessible, and as unbiased as possible. Why? So that by the time we have a pertinent question, we also have the resources to pose that question to a relevant patient cohort. And that is why you must set up a biobanking system that has all the prerequisites in place – so that it’s there when you need it and you do not have to start from scratch. In other words, it’s important to have the right samples and their accompanying medical information – before a specific question even arises.
Basic research is usually on a small scale, with a limited number of samples. When you translate it into practice, you need a much greater scope, which can be extremely time-consuming to identify and collect if you haven’t already prepared for that. And the task only grows as the prerequisites to remain in compliance with privacy and safety legislation increase – so unless we take the necessary steps ahead of time, we won’t be able to move forward.
Do biobanks hold value outside a research context?
As pathologists, we have an archive of pathology material. Historically, national regulatory bodies, have not always sufficiently appreciated the importance of those archives – either for our education or for our patients’ health. Let’s not forget about families, either; the more we learn about hereditary health issues, the more important it is to have those records so that we can go back to the material and perform new tests that can impact clinical care.
In the past, some regulatory bodies made the mistake of saying that, for privacy reasons, archives must be destroyed after a certain number of years. This error of judgement has done massive damage; various pathology labs in the Netherlands, where I live, have actually destroyed part of their archives, doing irreparable harm to their records, especially now that patients’ life expectancy is so much longer and our need to go back to previous material has increased.
Is it important for you and your colleagues to have input into biobanking decisions?
I think it’s very important for people in pathology and laboratory medicine to be involved in biobank design, especially to help connect samples from disparate registries. I think it’s very powerful that, in the Netherlands, we have been able to link physical biobanks (such as pathology archives) to virtual records (such as cancer registries). Because our work requires us to know the design of both databases, we can associate them – which lets us accomplish things like assembling a population-based cohort of a rare disease, including clinical data, without going back to the patients and without falling afoul of privacy legislation. And that is fantastic. We’ve only been able to do that because we have had an influence on the design of both databases and have therefore been able to suggest useful features.
Of course, we aren’t the only people who should have a say. Biobank design should be a multidisciplinary effort. You need the input of administrators, database experts, ethics experts, and users. Above all, it’s important to future-proof biobanks. These archives are supposed to last us for decades, so we must consider not only our current needs, but also what we might ultimately need. Ask yourself, “What will we be doing with this biobank in five or 10 years’ time?”
How did your biobank come about?
My colleagues in pathology and laboratory medicine and I came up with the idea for a pathology facility to support our work for the national hematology clinical trial organization Hemato-Oncologie voor Volwassenen Nederland (HOVON). We set the project up on a research basis and received support from related institutions; they lent us their experience and support and helped us to understand both their needs and our own. It was particularly helpful that one organization had previously dealt with database building and biobanking as one package, so they were well-versed in coordinating the two. We couldn’t have done this work without our advisors.
Why did we do it? The pathologists and hematologists involved in HOVON wanted to do clinicopathological side studies on clinical trials. From the early 1990s onward, we had always collected material after the conclusion of each trial. For some trials, it took us two years of full-time work to collect the blocks, review, biobank, and then ultimately conduct a side study. It was an expensive, time-consuming undertaking – and it was often performed by a single institute; sometimes even by a single person. There was no sustainability and the material was not available to others, so other researchers had to start from scratch each time. The primary reason we built our facility was to streamline tissue quality control and the research process.
It works fantastically well! Within three months of concluding a large trial in central nervous system lymphomas, we had the entire review completed, including all the biomarkers needed for a primary publication – something that might previously have taken years. That demonstrated to us that our new approach works. We are now already working on the a clinicopathological side study, so it’s clear how much faster things are moving than with our old system.
How can others promote biobanking?
Pathologists and laboratory medical professionals must show clinicians that we can really deliver. Our HOVON pathology facility is a showcase for that, so I hope our colleagues will use our success as proof of concept.
When we started building our biobank, I said to the board at HOVON, “My aim is that, by the time we finish, you won’t remember a time when this facility didn’t exist. You won’t even be able to imagine that there was a time when you couldn’t rely on it for your work.” And indeed, four years later, the president of the board said, “You were right. We can’t imagine not having this facility – it’s an integral part of what we do.” It helps to have a wide support network; not just pathologists, but clinicians, basic and translational scientists, and administrators too.
For non-pathologist laboratory staff, I think it helps them to know why they’re doing the work of biobanking. For us, that has meant hosting meetings on biobanking – or traveling to laboratories to attend meetings – and explaining what biobanking is, how it’s used, and why it’s valuable. I’ve noticed that understanding the importance of their work really motivates people to do it well.
In the Netherlands, we have a very active patient support organization, called HEMATON, which is very involved in policy. They have a research advisory group for clinicians and researchers, so we told them about our biobanking project and asked for their thoughts. They immediately adopted the idea and began promoting it for us! They even educate patients entering clinical trials and encourage them to consent to the use of their material for research purposes. The patients get very enthusiastic – we have almost a 100 percent rate of consent – thanks to our close relationship with patient organizations; something I recommend for others moving into the world of biobanking.
What input do you have into routine biobanking?
I’m a hematopathologist; I diagnose and do research on lymphoma. The HOVON pathology facility and biobank is completely separate from our pathology lab; it’s part of HOVON, so governance is in the hands of the HOVON board and any researcher in the Netherlands can submit a proposal to use that material. The system to efficiently collect and bank biopsy samples runs smoothly because we, the users, are the people who have designed it: what we want to biobank, how we want to bank it, who owns the material, how we deal with practical, ethical, and legislative issues – all of the considerations taken into account when starting a new biobank from scratch.
In our case, it was particularly valuable to have the possibility of linking various biobanks and databases to one another. For example, we were studying a rare form of lymphoma that occurs in women with breast implants, known as breast implant-associated anaplastic large-cell lymphoma. As you can imagine, it’s difficult to locate these very rare patients for an informative study – but we were able to retrospectively identify every case since 1990 in the Netherlands and also associate with a registry of breast implants! That allowed us to retrieve data on the breast implants with which the disease is associated, as well as a high percentage of the biomaterial – so we have a unique clinicopathological series with valuable biomaterial, thanks to having anticipated our need for such studies. It pays to “future-proof!”
Daphne de Jong is Professor of Pathology at Amsterdam University Medical Center, Amsterdam, the Netherlands. She is also Coordinator of the HOVON Pathology Facility and Biobank.
Prospecting the Goldmine
Biobanking has a lot to offer, but requires careful explanation and education
With Folkert van Kemenade
What makes biobanking so valuable?
Biobanking is vital for translational research (for instance, investigating biomarkers) and epidemiological research (to better understand disease). You can bank with healthy volunteers, the approach taken by the Lifelines biobank in the Netherlands. But you can also use existing biobanks, which give you follow-up for free: once a disease manifests itself, you can go back to the archive of samples to take a closer look at previous cases and controls. Prospective longitudinal biobanking delivers insight into things like polygenic risk scores, interactions between genes (and other disease factors), whole exomes or even genomes, and so forth. Existing biobanks, with samples collected for diagnostic reasons, are ideal for observational studies – and, in my opinion, the only feasible way to study rare diseases.
For diagnostics, biobanking has a different significance to its value for prospective, cohort-based studies. In diagnostics, one needs to maintain files and samples – if possible; you can’t bank all blood samples, for instance, but you can preserve tissue. Diagnostic tissue forms a bio-archive with a dual purpose: not only the diagnostic process for which it was collected, but also research. In pathology, I call this the “tissue bonus.” Any patient’s archived tissue can double as diagnostic file that can be reconsulted (and re-tested) while, at the same time, serving as a basis for biomarker discovery. Just make sure that you adhere to due diligence for sample anonymization!
What kind of input should pathologists have into biobanking?
The pathology residual tissue bank typically tends to be one the biggest collections; in ours, we have more than 1,000,000 FFPE samples. We pathologists and laboratory medicine professionals are keen on economy of scale and well-accustomed to fair governance and responsible use. We can, in other words, provide valuable help with general decisions. Our hospital biobank has a central council, and we have a delegate on that council who represents our interests and helps develop solutions when conflicts arise.
All of the pathology residual banks in my country are linked to one database, known as PALGA (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief). That’s extremely useful for studying rare diseases (among other things). My colleagues and I conducted a nationwide study to test the hypothesis that two rare conditions were related. We ended up collecting 32 blocks assembled over many years from a range of laboratories – although our hypothesis was unfortunately incorrect. Or take the breast implant-associated anaplastic large-cell lymphoma study my colleague Daphne de Jong is conducting; thanks to biobanking, she can collect blocks from all over the country.
But even studies of this size are small compared to the possibilities for more common diseases. I was recently involved in a nationwide procurement of 18,000 blocks from residual archives in different labs. My colleagues and I helped pick the blocks, the researcher assembled tissue microarrays (a herculean task), and we helped return the blocks to the archive. Large-scale, residual, biobank-based research is possible! Incidentally, in the slipstream of that project, we were able to provide help for the HOVON project Daphne mentioned earlier. The next step to ensure accessibility is to streamline the organization and make sure to return information to stakeholders. Scientific results should be shared with all stakeholders, including patients.
I think that, in general, my colleagues in pathology and laboratory medicine have a clear grasp of the pathology biobank concept – here, in Finland where they have similarly teamed up to form a national organization, and elsewhere. If you wake a pathologist or laboratory medicine professional up in the middle of the night and ask them about biobanking, they will agree that it’s a gold mine – but one that needs careful mining…
What would you like others to know about the pathologist’s role in biobanking?
The concept of a tissue block should be better-known outside the pathology silo. We must also explain the diagnostic process – over and over again until everyone (physicians, researchers, patients, the public) understands that we store samples for patient care, and that we combine care with research. Outside pathology, it is often believed that we store everything (which we don’t) or that we can culture cells back to life from blocks (which we can’t). Blocks of archived tissues are wonderful, stable items for archiving and research. They can yield DNA sequence information; they are relatively low-cost (unlike stored digital data); they cannot crash; they cannot be hacked; and they have great battery life!
Folkert van Kemenade is Chair and Professor of Pathology at Erasmus University Medical Center, Rotterdam, the Netherlands. He is also part of the BBMRI-NL Scientific Executive Committee.
A Winning Collaboration
To tackle rare diseases, biobanking partnerships between patients and pathologists are vital
With Marleen Kaatee
Why is biobanking valuable for patients?
Biobanking is an essential part of medical research. Many diseases – especially rare diseases – do not yet have a cure, so those of us who experience them are eager to do what we can to help with research.
Personally, I find that that patients in general know very little about biobanks. We may be missing opportunities to have patients to consent to banking their samples simply because they don’t know what a biobank is or what the implications of contributing their samples might be. The simple fact is that, with enough samples, I truly believe that biobanking might hold the key to cures.
As a patient expert, I did a course on biobanking and saw the range of possibilities – especially with the rise of digital biobanking (wherein users can access computerized whole slide images, rather than obtaining the glass slides themselves). There are so many opportunities, and as research progresses, it could be that our samples point scientists in the direction of a cure. That’s especially true with the amount of high-quality international collaboration taking place right now. Organizations like BBMRI-ERIC, a European research infrastructure for biobanking, encourage researchers to share both samples and data. I think that, if we link all of that information together, we’ll have a pool of easily accessible data ready for researchers and healthcare providers to examine for answers.
As we say in the Netherlands, “unknown is unloved.” That’s why I really hope that we – patients and professionals together – can bring the public up to speed on the hows, whats, and whys of biobanking. It’s especially important for patients who, like me, have a rare disease. If there’s no cure, hope is the best you have – so if you understand that biobanking can help research move forward faster, you feel empowered to help yourself and others by signing the consent form. You finally feel like you’re contributing to a solution.
It takes an average of five years for a person with a rare disease to get the correct diagnosis (1), so anything that can help make that diagnosis earlier saves patients and families a lot of trouble. If we can get researchers and clinicians familiar and comfortable with biobanking – especially digital biobanking – then everyone will have more samples for comparison, which gives us a better chance of finding the right diagnosis fast.
Patients who aren’t offered the option of biobanking can take the initiative to encourage it, too. Ask your doctors and researchers, “Have you looked into biobanking? Do you know about the incredible collaborations that are taking place?” Right now, a lot of biobanks are static sample archives, whereas they should be active, evolving, collaborative ecosystems – and it’s up to us to drive that. The more people know about biobanking, the better and more powerful it will become.
Should patients have input into general decisions on biobanking?
I joined the BBMRI-ERIC Stakeholder Forum because I think biobanking is overlooked by the general public. It doesn’t get the attention I think it should get. When the average person thinks about research, they picture microscopes and laboratories and tubes – but biobanking is an essential part of that research.
Patients have a lot of power to drive change. For instance, I’ve learned that there isn’t any standardization for saving samples within specific rare disease areas. As a patient advocate, I can encourage research and clinical professionals to address that issue and to work together to resolve it. It’s not always easy for researchers to share data, but patient requests carry a lot of weight. We can also bring additional information to the table. Of course, biobankers know more about sample storage and preservation than we do – but we have insider information about our own conditions. What a scientist or doctor might see under a microscope, we live with 24/7. For instance, a group of patients with primary sclerosing cholangitis, a rare liver disease, discovered that many feel much better with specific, often non-obvious, diets. Perhaps we can advise researchers to take that into account when collecting samples. They get more information and we get more insight into our bodies – a win-win!
Have you personally had the opportunity to weigh in on biobanking?
I shared my interest in biobanking with one of my hepatologists. At the next annual conference on my disease, they – for the first time – invited a pathologist to speak. After all, some of us had been contributing samples for years – and a liver biopsy is no walk in the park; it’s a real commitment – so we were eager to know what happened to our tissue and how it had benefited disease research. It was a great success; the hepatologist and the pathologist gave a presentation together and patients were very appreciative.
It’s also interesting for people to actually see tissue samples from different disease stages. It really helps clarify the difference between severity levels, why it’s important to identify and adhere to the right treatment, why patients shouldn’t miss tests or checkups… Primary sclerosing cholangitis, for instance, causes inflammation, stricture, and sclerosis of the bile ducts. Seeing actual bile ducts – and the difference between a healthy and a diseased duct – helps you to understand what is happening in your body and why you might need procedures such as stent placements.
I found that such concrete representations had three positive outcomes: educating patients about their conditions, encouraging them to consent to biobanking, and prompting them to consider their lifestyle and its potential contribution to disease. A liver biopsy can reveal a lot of secrets!
How did you get involved in biobanking?
I initiated the process myself. I consented to banking a few liver biopsies – but that was when I was still what we call a “naïve patient,” one who is just starting to learn about the world of chronic illness. Just last week, I got a letter asking to use my samples for a new research project, and of course I agreed. Many people don’t know that can happen – that they can have a liver biopsy and then, five years later, someone may ask to use their samples for unrelated research. If you aren’t aware of biobanking, you might not be pleased to find that your samples are “out there” and available to strangers. But if you’ve been educated, you know that it’s all part of studying the condition – part of finding better diagnostic tests, better treatments, and maybe, one day, a cure – and you might be thrilled to help.
I think patients should be offered the opportunity to consent to research, not only on their own diseases, but also for comparative purposes. That way, you may be helping both yourself and others. There should be a warm relationship between healthcare providers, researchers, and the patient community, because each of us can contribute in ways that benefit all of us.
In June 2018, I took a summer course on Fundamentals of Biobanking and Cohort Research at University Medical Center Groningen, the Netherlands. After our introduction to biobanking, we were taught in depth about clinical biobanking and sample analysis, ICT and infrastructure, regulation, participation, and practical considerations such as standardization and essential biobanking tools.
We also received a tour of the Lifelines biobank in the north of the Netherlands. They have collected samples for quite a few years; long enough that they can work on prospective studies using samples from healthy people, as well as retrospective studies from individuals with specific conditions. To see the way they operate – all of the machines, the freezers at -80°C, the size of their building – was amazing. Even better was to hear the passion with which the people there spoke about their work, and the care and concern with which each sample was treated. Imagine how I felt when I saw how my samples could contribute to the greater good.
In all honesty, before becoming a patient, I had never heard of biobanks. I’ve now mentioned to the Ministry of Health that it should be a part of the high school curriculum, so that everyone is aware of these institutions and what they do. Eventually, you or a family member may need a biobank. It’s not common to know about biobanks but it’s certainly not uncommon to need one!
What should “the experts” know about the patient’s role in biobanking and in medical research?
It’s good to look into your patients’ diseases and try to gain an understanding of them, because that will help you form a good relationship with your patients. For rare diseases, especially those without a cure, your interest in the disease – and the patient – offers hope. The more extensive your knowledge of that condition, the more likely you are to understand the intricacies of the patient’s needs, and that will come across to the patient.
Speaking as a patient expert, it would be great if more pathologists proactively asked patient advocates to get involved with their work – especially as it pertains to research. A lot of patient advocates are well-trained, and they have information (ranging from anecdotes to scientific surveys of the community) that could help highlight unmet needs and research priorities. It’s also nice when the pathologist gets out of the laboratory, so that people know who they are. They often seem to be the people behind the scenes, but the more they interact with patients and the public, the more motivated those people will be to assist with their work.
Patient advocates can also pass on questions from pathologists and laboratory medical professionals to the community. I haven’t spoken to many pathologists, but the ones I have met were all very enthusiastic; they are proud of their biobanks and I’ve been invited to visit! I recommend having some basic information about biobanking available for patients and working with patient advocates to open up opportunities for research. Perhaps we can help you find answers faster; perhaps we can help you investigate in more depth; there are a zillion possibilities. The more proactively you approach the patient community, the more we can (hopefully) help. All you need is to ask – we are eager to answer!
Marleen Kaatee is the founding President of PSC Patients Europe and a fellow of the EUPATI Patient Expert Training Course. She is also a member of the BBMRI-NL Patient and Public Advisory Council.
- Global Commission to End the Diagnostic Odyssey for Children With a Rare Disease, “Ending the Diagnostic Odyssey for Children With a Rare Disease: Global Commission Year One Report” (2019). Available at: bit.ly/2Uf3yQR. Accessed August 30, 2019.
While obtaining degrees in biology from the University of Alberta and biochemistry from Penn State College of Medicine, I worked as a freelance science and medical writer. I was able to hone my skills in research, presentation and scientific writing by assembling grants and journal articles, speaking at international conferences, and consulting on topics ranging from medical education to comic book science. As much as I’ve enjoyed designing new bacteria and plausible superheroes, though, I’m more pleased than ever to be at Texere, using my writing and editing skills to create great content for a professional audience.