In banks for human biomaterials we systematically store samples such as tissue, cells and blood, or DNA or proteins isolated from human blood, on a long-term basis. In addition, we collect medical data from the patient/donor of the materials. So, in essence, a biobank is the combination of a collection of biomaterial samples together with the relevant medical data such as age, medical history and life circumstances. Only by means of connecting such information is it possible to, systematically, research causes and mechanisms of certain diseases. This research, in turn, creates the basis for the development of new and improved therapies.
The idea to store human tissue and organs is not novel. Especially universities have anatomic and pathologic collections and many of them have been in existence for centuries. For the longest time it was not possible to store these materials in a fashion that would not compromise their biological characteristics. Thanks to cryo-conservation, rapid freezing of the material at extreme temperatures, and the development of stabilizing agents, this has changed. Furthermore, various techniques have been developed that allow for rapid analysis of many liquid- and/or tissue samples. Paired with the rapid development in computer technology, storage and processing of biomaterials and their corresponding data has become considerably easier. All this has contributed to the fact that, today, biobanks are considered one of the great beacons of hope for medical research in the 21st century.
By the late 1980s a large epidemiological study called KORA (Kooperativen Gesundheitsforschung in der Region Augsburg) had started to establish a biobank hosted by the Helmholtz Centre Munich (http://www.helmholtz-muenchen.de/kora/ueber-kora/index.html). KORA is a population based biobank, primarily collecting materials from healthy probands, respectively from people at a very early stage of disease onset. Researchers use the data to decipher genetic background information on cardio-vascular diseases, diabetes, allergies, chronic lung diseases and skin diseases. Since 2003, the Kiel and Lübeck based project PopGen (short for „Populationsgenetik“) collects genetic and epidemiological data and materials on cardio-vascular, neuro-psychiatric and environmentally triggered diseases. The complete retrospective recording of data from patients within a certain geographic area is intended to give insights to relative genetic risk factors for complex diseases. The involved biobanks are incorporated in a network (PopGen 2.0 Netzwerk). Similar aims, with a national rather than a local focus, are pursued by the project „national cohort” („Nationale Kohorte“); a network consisting of partners from the Helmholtz-Community, Universities, the Leibniz-Community and the national portfolio research (“Ressortforschung”). In this longitudinal population-based study blood samples from 200.000 probands will be collected and centrally stored in a biobank. A follow-up data collection will be performed after 10-20 years . The great hope is that the initial data combined with the longitudinal data collection will generate crucial insights and strategies for better prevention and treatment options for the most widespread diseases, such as cardio-vascular diseases, cancer, diabetes, dementia and infectious diseases. Disease specific biobanks collect biomaterials and data from patients that suffer from certain medical conditions. Just as in population-based biobanks, the main goal is to decipher causes for the disease as well as disease mechanisms. In addition, a big hope is to improve means of diagnosis and generate new and improved therapies.
The media likes to call biobanks “treasure chests of the 21st century”. And even if this expression is not to be taken literal, medical and scientific expert circles mostly agree: biobanks can contribute considerably to deciphering causes, mechanisms and relevant influences on diseases and disease progression. They can contribute to determine these factors with more precision and improve time to diagnosis and efficiency of treatment. A crucial role in this is played by so called biomarkers. Biomarkers are biological characteristics that can be traced in tissue and bodily fluids and that point towards an abnormal process in the body, in this way giving information on type and progress of a disease. Biomarkers can vary greatly: it can be increased growth factors, disease specific cells or genetic changes, so called mutations, or many other types of marker.
Despite intensive research efforts, many severe diseases such as cancer or chronic lung diseases can still often only be diagnosed (too) late. Research on biomarkers has increased considerably over the last years, has already yielded first results, and is constantly extended further. The material necessary to conduct such research is collected in biobanks. It is not unrealistic to imagine that in the near future a biomarker will have been discovered that will allow for identification of lung fibrosis at a very early stage. Such insights are often reached in small studies with few patients, or even in the test-tube, and therefore they only have limited significance. Biobanks, storing tissue and blood samples from many patients, allow for these results to be checked in order to find out if the correlation is verified in a larger sample. To verify such research results, that are of utmost importance for early detection of a disease, is one of the fields of application of biobanks. But they also serve to answer many other research questions, by allowing for rapid access of large sample populations, thereby, for example, allowing to assess if a biomarker increases with disease progression.
For the patient, the most important factor is the potential that biobanks have in helping develop new and more effective therapies for their disease, for example lung cancer. This requires that causes and disease mechanisms are deciphered as completely as possible. To achieve this goal, research has to be performed on tissue und blood samples of the largest possible patient population. Biobanks, as repositories of hundreds and thousands of such samples, create the basis to come to representative results and conclusions. Here researchers can systematically search for genetic and biochemical markers connected to a certain disease, in order to develop individualized therapies for each patient. This approach is imaginable for lung diseases with a genetic cause or with a disease progression that is influenced by genetic factors, such as cystic fibrosis, BMPR2 mutations in pulmonary hypertension or surfactant protein C mutations in familiar forms of lung fibrosis. Non-small-cell lung cancer (NSCLC) is one of the best examples for how tissue samples from biobanks were used to develop such an individualized therapy and implement it clinically. A few years back research showed that a partial population of the NSCLC patients possessed a mutation that altered the so called EGF-receptor. Via this receptor the growth of cancer cells was triggered. Tyrosinkinase-inhibitors block the over-active EGF-receptor and thus can stop tumor growth. This medication has now been in use on NSCLC patients with the described EGF-receptor mutation since 2009. To develop such individualized therapies – not just for cancer, but also for other lung diseases – counts as one of the major goals of medical research. Biobanks are a crucial tool in reaching this goal.
Indispensable prerequisite in order to obtain biomaterials and data for the storage in biobanks is the voluntary, written consent of the patient. This informed consent is usually collected from the patient by the treating physician or biobank personnel. The informing person explains the purpose of the biobank and the procedure of participation, thereby duly fulfilling the duty to inform the patient, which is the basis for any informed consent. In this context it is important to know that the majority of samples to be stored are bodily fluids or tissue that was primarily collected for diagnostic purposes, for example as part of a bronchoscopy or routine blood draw or an operation. In other words: usually, no additional biomaterial is taken from the patient for the biobank, but residual amounts of biomaterial – so, biological material that is left over from acute, medically required procedures that would otherwise be discarded. The same rule applies for tissue, respectively complete organs that are taken in the frame of an organ transplant. In some cases, additional material can be taken from the patient, if he has explicitly consented to this. But this is an exception to the rule and usually limited to liquid biomaterials such as urine or blood. The samples are then professionally processed and placed in freezers or tanks, specifically designed for long term storage, to hold the samples at temperatures as low as -180 °C. Under these conditions, biomaterials can be stored for many years without compromising their quality. Critical is mostly the time until the sample is frozen. It is a known fact that gene activity changes rapidly after tissue has been removed from the body. Cells also diminish fast if they are not supplied with oxygen-rich blood. So, it has to be a priority to keep the timespan between sample extraction and storage as short as possible and the handling and processing of samples has to be performed under optimally standardized conditions. Each sample entered into the biobank receives a specific, unique number (the sample is “encoded”). All information necessary to perform research with this sample is also stored under this number (age, gender, medical history, diagnostic results, disease progression and information on the treatment). For the person who will in the end perform research with this sample, the identification of the patient who donated the material is not possible based on these data.
As biobanks predominantly make use of leftover tissue and/or blood no additional risk is associated with the participation in a biobank. Even if additional blood is extracted for research purposes, the patient does not carry any considerable health risk. The same goes for potential disadvantages in his medical treatment. As the insights gained from the biomaterial does not influence the current treatment plan. So, the patient is not a study proband as he would be, for example, in a clinical trial assessing the efficacy of a new drug. But the donation of a biomaterial sample can, in the future, help people who suffer from the same disease.
With his signature the participant consents to his biomaterials and data being included in the biobank and made available for the purpose of medical research. This means, researchers can use the samples and data for research projects on diseases such as lung cancer or lung fibrosis. Usually it is not possible to already tell the patient what exact project his biomaterials will be used for as many projects will only be performed in the future, building on information not yet available. Important to know is that the participant can, at any point, withdraw his consent again. No reasons have to be given for this action. If the consent is withdrawn, all samples will be destroyed and all data and research results will be irrevocably anonymized, so that nobody can trace them back to the person anymore.
Information such as medical history, examination results or information on life circumstances cannot fall in the hands of unauthorized third parties or the general public. To protect the data correspondingly, the national ethics council has issued a concept in 2010 that recommends a biobank confidentiality concept. Even if the concept is currently still in the feedback loop, one core item is already set in stone: samples and data are only permitted for use in medical research projects. Furthermore, the work of a biobank requires approval of the responsible data safety officer of the state and the local ethics committee of the hospital/university.
The researchers do not know the identity of the donating person, as they receive the material and corresponding data encrypted – in technical language this is called pseudonymized -, meaning labeled with a number. Conclusions on the identity of the donating person are not possible based on this number. This ensures maximum security of personal information. The TMF (Technologie- und Methodenplattform für die vernetzte medizinische Forschung e.V.), serving as a platform for communication and networking among biobanks in Germany, has developed generic data safety concepts for biobanks, that have been approved by state and federal data safety officers and have already been implemented by the majority of biobanks. This concept entails a two-tierd encryption (generation of a PD = simple encryption of the patient identifier und additional encryption of the PID into PSN = pseudonym, 2 step encrypted patient identifier), as well as the separate storage of patient-identifying data (IDAT) and medical data (MDAT); in this way guaranteeing the highest possible data safety for long term use of the research database. When research results are published, this always happens in anonymized form. This means that, for example, a medical journal presents an exemplary medical case no one can draw conclusions as to the identity of the patient described. Not even members of the biobank. Biobanks uphold highest standards of confidentiality and protection of data. On the one hand, because the legal framework prescribes it, on the other hand, to protect a crucial part of a biobank’s success: the trust of the donating patients.
