A geneticist is a medical professional that works in the field of genetics. A geneticist can specialize in agriculture, biomedicine, forensics, archaeology and bioinformatics among others. A geneticist will perform tasks such as planning and conducting research. They also keep notes that record their methodology, procedures and results while results are analyzed via mathematical and statistical methods.
A biopsy is a test that is used to help determine the composition and structure of the cells and tissues of the body. The test can be used to evaluate human tissue samples from part of the body to allow the examination of the tissue sample under a microscope. Since most biopsies are minor procedures, patients do not usually require sedation. Patients may only require local or no anesthesia. The term biopsy is of Greek origin “bios” and “opsis” where the word “biopsy” can be loosely translated to “appearance of life” or “view of the living”. Biopsy is a good way to evaluate for the presence of malignancy or for confirmation if the abnormality is benign. If there is cancer, a pathologist studies the tissue sample to determine the type and grade of malignancy.
Why is a Biopsy Performed?
A biopsy is usually performed when there are lesions that can be felt or seen on imaging such as ultrasound, X-ray, computed tomography (CT) scan, or magnetic resonance imaging (MRI) scan. The biopsy is used to help determine the nature of the suspected abnormality. In cases of suspected cancer, the biopsy helps determine if the area involved is malignant or benign. One good example is the biopsy of a breast lump for histologic examination to determine if it is cancerous. The laboratory analysis of the specimen is performed by a clinical pathologist. A definitive and correct diagnosis is usually arrived through histological and cytological examination.
When a tumor is malignant, biopsies of the lymph nodes and surrounding tissues are performed to determine if the cancer has metastasized. Biopsy also helps to determine the grade of cancer. Surgical biopsy is a procedure that removes the entire tumor and can be done with the guidance of endoscopy or imaging. The pathologist can usually tell if the cancer is a slow or aggressive form.
Types of Biopsies
There are many types of biopsies. The type of biopsy used for the patient will be determined based on several factors such as:
• Location, body part, or organ to be sampled
• Number of lesions
• How suspicious the lesion appears to be
• Characteristics such as shape and size of the lesion
• Existing comorbid and patient preference
• Facilities and systems available at the current healthcare facility
Some examples of biopsy procedures include
a) Aspiration or fine needle aspiration (FNA) biopsy
b) Cone biopsy
c) Core needle biopsy
d) Endoscopic Biopsy
e) Surface biopsy
f) Vacuum assisted biopsy
g) Punch biopsy
h) Surgical biopsy or excisional biopsy
Image Guided Biopsy
There are many biopsy procedures that are done with the help of image guidance such as CT and ultrasound. There are many breast biopsies that have been done with the guidance of stereotactic mammography. CT is increasingly used to guide the biopsy of liver and lung lesions. Interventional CT now helps to allow real time CT imaging during biopsy increasing diagnostic accuracy and shortening procedure times. Ultrasound is also useful as it offers great flexibility to follow the path of the needle to the lesion, provide real time display, and allows professionals unlimited imaging. In stereotactic mammography, it helps to show images of two angled directions to guide the needle. MRI helps provide real time images that guides the trajectory of the needle approaching the lesion. It also provides a high contrast resolution helping radiologists to differentiate between abnormalities and organ structures.
Risks of Biopsy
Although biopsy is a minimally invasive and relatively safe procedure, there are still certain risks that are involved. Some examples of risks for needle biopsy include:
• Infection of the area being biopsied
• Puncture of structures near the biopsy target
• Vasovagal response
For surgical biopsy, risks include
• Scarring due to stitches after excision
• Mortality due to risks of anesthesia
• Possibility of infection, bleeding, and delayed wound healing
• Longer recuperation necessary compared to needle biopsy
Biopsy results can be negative or positive. A negative result usually means that there are no abnormal cells seen in the examined tissue sample while a positive result means that abnormal cells are seen in the cell sample. Abnormal results help to identify:
- A possible infectious agent, changes to the cells caused by infection or disease.
- The presence of a benign growth or process.
- The presence of abnormal cells where cancer cells are seen. With these findings, the pathologist may be able to determine the origin of cancer cells to see if it is from a primary tumor or from metastasis.
Who Performs Biopsies?
Biopsies can be performed as an outpatient or inpatient bases by medical doctors or doctors of osteopathy. Surgeons are individuals who perform excisional and open biopsy. More invasive percutaneous biopsy such as the liver or lungs will be performed under guidance of medical imaging usually by a radiologist .The biopsy specimen is then analyzed by a pathologist who then renders a medical diagnosis based on the tissue sample.
1) Biopsy procedure – what is a biopsy. Imaginis. Accessed 12/11/2018. http://www.imaginis.com/biopsy/biopsy
2) What is biopsy: overview, benefits, and expected results. Docdoc. Accessed 12/11/2018. https://www.docdoc.com.sg/info/procedure/biopsy/
There have been several high-profile legal cases which have ended in the removal of human biospecimens from research teams. One case resulted in the destruction of more than 5 x 106 dried blood spots that were obtained from infants after a suit challenged the state of Texas’ right to store these blood spots for future research. All these cases have one thing in common: the argument whether participants were properly informed regarding how their samples will be used for research. Informed consent is being increasingly discussed not only by professionals but also by the public. These cases have also prompted discussions regarding the timing and type of consent required, use of samples, and more.
This article highlights the opinions of the following experts who all represent different viewpoints on informed consent:
David S. Wendler (D): Advocate for rights of research donors
Arthur L. Caplan (A): Bioethicist
Michael Christman (M): President and Chief Executive Officer (CEO) for an independent non-profit biomedical research institution with a large biorepository
Jack Moye Jr. (J): Researcher
Is consent necessary or do you prefer a presumed consent with an opt-out option with the idea that human biospecimens should be a common heritage that is used for the collective good?
David: The tissues are not just “a collective good”. Tissues are obtained from specific individuals with their use involving the interests of donors and participants. Some of the things to keep in mind include the risks involved when obtaining samples, privacy, contribution, and use of the sample in future research. The necessity of obtaining consent allows donors to decide if they are willing to face the risks involved, increase awareness of the possibility of new information, and the advantages of contributions.
Arthur: The efforts taken to obtain informed consent are doomed to failure as there are many programs that use open-ended informed consent forms that are incomplete and vague. There are also those that ask donors or participants to waive their commercial interest such as the use of blanket waivers. A more appropriate way would be through altruistic gifting. This means that the specimens are made a gift making it clear that commercial interest is forgone, the use of specimen is open-ended, and possession has been transferred to a third party. A presumed consent to gifting would make more sense as long as patients retain the ability to opt out of gifting.
Michael: Current specimens that are anonymous should be allowed for use by research without the need of consent as there identification of donors will not be required. While studies that use anonymous specimens are usually exempted from the institutional review board (IRB) review, proper regulations should be implemented to ensure that this is upheld. However, an exception should be made for the use of anonymous specimens in genomic research as there is a possibility of identification.
Jack: The concept of human biospecimens as a shared resource for the collective good is a fascinating idea that should be given more attention. A framework where human tissue is a common heritage of humanity that is to be used for the collective good can help prevent disputes about both specimens that are left over from clinical purposes and those obtained for research.
What type of informed consent is best: general permission, tiered consent, specific consent, or other?
David: Many studies have been conducted regarding individuals’ attitudes about consent. They have consistently observed that the majority of donors want to control if their samples are used for research. Most participants are also willing to contribute when asked. These studies have also found that most donors support one-time general consent with the understanding that future use will require a review and approval from the ethics review committee such as the IRB. A widespread support shows that the one-time general consent offers the choice most donors would make. It also offers an opportunity to decline from contributing for those unwilling to contribute or for those who want more specific control over their specimens.
Arthur: A tiered consent would outline the likely uses of the specimen, disposition of materials, policy regarding the sale of material to third parties, transfer of control, and availability of clinical findings that would be relevant to donors.
Michael: A consent menu that has multiple choices would be best. A study found that although 10 percent support the consenting menu, most prefer 48 percent of blanket consent while the rest (42 percent) prefer re-consenting when a new research project begins.
Jack: Specific consent would help provide assurances that both the participants and researchers are equal in the enterprise. It is also easily accomplished when samples are obtained for a specific project. However, it can become impractical if the samples are stored for long-term with undefined uses. Most participants that are based in the United States are willing to contribute their samples.
What about property rights to specimens? Should research participants share potential financial gain?
David: Generally, individuals should share the benefits to the project they contributed to. Failing to provide a fair level of benefit can be regarded as a case of exploitation. Since the samples are part of an important contribution, it would suggest that the participants should share the benefits such as financial gain from the research projects. However, this can become complicated in practice as it is unclear what is a fair level of benefit or how benefits can be provided.
Michael: As part of the consent process, participants should be informed about property rights, the potential for financial gain (for the investigator), and if they themselves will share any financial gain. Once the participant is aware before enrolled in the study, the allowing or disallowing of financial gain and property rights should be acceptable. Consent should not be waived in cases if there is expected financial gain for the investigator.
Jack: Unless the research is conducted with the objective of developing a commercial product, proprietary interest in research by the donors can be difficult. It can be hard to put a value on something that has yet to exist especially in cases where there is an assertion of property rights where there is litigation corresponding with perceived value.
Gronowski AM, Moye J, Wendler DS, Caplan AL, Christman M. The use of human tissues in research: what do we owe the research subjects? Clinical Chemistry. 2011; 57 (4): 540-544.
What is a Biorepository?
A biorepository is an organization that collects, processes, stores, and distributes tissue samples for clinical research or other scientific investigations. They assist in maintaining and managing specimens such as tissue samples from humans, animals and other living organisms. A biorepository functions to maintain biospecimens, collect relevant information and assure the quality of the samples in their collection. They follow standard operating procedures (SOPs) that reduce anomalies in samples and which also provide guidelines for storage and maintenance. SOPs also ensure that biospecimens collected closely resemble that of their natural state. It helps biorepositories maintain a standardized framework for conducting operations and allows for the seamless implementation of processes.
What is Custom Procurement?
Some biorepositories, like Geneticist Inc., provide custom tissue procurement. This means that they are able to provide custom collection of biofluids, tissue samples, and blood samples in various specialties such as gastroenterology, oncology, rheumatology, neurology, and dermatology. Biorepositories that offer custom collection services have the ability to collect from a vast range of medical procedures such as elective skin biopsies, resections, autopsies, endoscopies, blood draws, and more. Due to the nature of the collection processes and procedures, biorepositories need to have a skilled logistics team and an expert medical courier network. The custom procurement of biospecimens is important especially if:
Fresh collections are required
There is a necessity for matched tissue pairs
Rare indications or specific specimens
The need for specific procedures during the collection and processing of samples
Active cases and autopsies are needed
The study or research is complicated
Examples of Biospecimens
Biofluids – Examples of biofluids include stool, urine, whole blood, serum, plasma, cerebrospinal fluid, saliva, sputum, and swabbed material. Biofluids can be available frozen or fresh. Depending on client preference, it can be with or without additives.
Tissue – Some examples of human tissue include fresh tissue, fixed tissue, frozen tissue, formalin-fixed paraffin-embedded (FFPE) blocks, whole tissue samples, stained slides, unstained slides, tissue microarrays, and more. These samples can be annotated with the proper genetic and molecular characterizations, outcomes data, pathology reports, and patient characteristics.
Cells – Some research may require frozen or fresh cells that are still viable. These cells can be isolated from peripheral blood, cord blood, and bone marrow of normal donors and those with disease. Some examples include myeloid cells, pluripotent stem cells, mononuclear cells, and lymphoid cells.
What to Look For?
There are several factors that help decide which biorepository to go with when custom collection services are needed. Some of the factors that can help decide are:
a) Procurement format options
Since prospective collection enable clients to decide which elements fit their needs, a custom procurement format can be designed with the help of our experienced team of scientists. Depending on the need of clients, custom procurement of biofluids, fresh tissue, frozen tissue, and more are available. Clients can also set the exclusion and inclusion criteria for specimens and donors.
It is important to look for a biorepository that has a vast network of clinical partners to help ensure the highest quality of required biospecimen collection. It would also increase the access to more human tissue samples in various formats.
c) Team members
A biorepository with experienced and certified team members would be the best choice as they would be well-trained with the ability to better understand the needs of researchers and to help find better solutions if necessary. With a great team on hand, specimens are more likely to be of the highest quality and fulfill the requirements of clients.
d) Quality assurance
It is important for the biorepository to perform quality control checks to ensure that specimens are of the highest quality. This means that the staff should understand the appropriate storage or procurement procedures and ensure that the SOPs are adhered to strictly.
e) Consent and privacy
Biorepositories should follow the procedures and guidelines during the procurement of human tissue samples. Informed consent and privacy of the donors should be of the highest priority to protect their interests.
For custom collection services, the staff at Geneticist can design custom collections of a wide variety of biospecimens. Our staff are certified, experienced, and highly trained. Geneticist is a biorepository that is compliant with the Institutional Review Board (IRB) standards and provides the highest quality of collections. All our biospecimens and material adheres to the official protocols and is approved by the IRB and Independent Ethical Committee (IEC). Geneticist operates in accordance with current Federal Regulations, Health Insurance Privacy and Portability Act (HIPAA) and International Conference on Harmonisation – Good Clinical Practice (ICH-GCP) guidelines. With the proper inventory management process and extensive procurement formats, Geneticist strives to fulfill client requirements and satisfaction.
What actually happens to newborn DNA samples once its been tested for genetic disorders?
In the last five decades, most babies born in the United States have unknowingly participated in a test called the Newborn Genetic Screening program. The test has been established to identify treatable genetic disorders in newborn infants. Early identification of these disorders is crucial in addressing symptoms and preventing a lifetime of disability. The test is a simple one: one small prick to the heel to collect a blood sample. With this sample doctors and nurses test for a variety of hereditary and congenital disorders. The controversy surrounding this program doesn't start until after the completion of the testing, whereby the samples are often stored in state-run biobanks.
Your or your child's DNA may have been stored and shared without your consent. Given that this has been going on since the 1960’s it is more likely than not that your samples are out there without your knowledge. Most people don't even know what the Newborn Genetic Screening test is or that they were a part of it. It’s importance and significance in identifying preventable disorders is not under question, but what happens to residual samples should be brought to light. State-run biobanks (or data repositories as the Association of Public Health Laboratories calls them) are established to store these samples and are shared with departments such as law enforcement for analysis and research.
What is the Newborn Genetic Screening Test?
The Newborn Genetic Screening test began in the 1960’s. Back then it served to simply detect one genetic disorder, phenylketonuria. A condition that causes brain damage but, if caught early enough can be treated. Since then our knowledge of genetic disorders has improved immensely, largely due to the NGS Program. Collection of the blood sample must be completed within 12 to 48 hours after birth and can now detect between 30 and 50 genetic disorders. It is without a doubt an important and lifesaving program, and an estimated 12,500 newborns are diagnosed and saved annually. Participation in the NGS Program is a legal requirement. and therefore, parental consent is not required. However most states allow parents to “opt out” if there are religious or philosophical reasons. However hospitals do not usually inform the parents that the test will be conducted, making it challenging to opt out.
Duration and Location of DNA Storage
Your blood sample storage is different depending on state of birth. The most common practice is for it to be stored in state-run biobanks. Parental consent laws also differ for storage, in some states parental consent is necessary before storage of samples. In California for example, once tested the state retains the rights to store the samples. other states destroy the samples after six to twelve months whilst other store it much longer, ranging from 21 years to indefinitely.
How are These Samples Used?
Even though states might not use the samples, other researchers and government agencies still have access to them. It might be necessary for parents to find out what their or their children residual blood spots are used for. Residual blood spots storage can be used in the following.
a. Research purposes such as:
Retesting the samples to confirm the screening results
Developing new screening tests
Developing new techniques for forensic studies
Identification of new diseases
Quality control purposes
Access for those who are not biorepository lab technicians (such as those people in law enforcement)
b. Law enforcement purposes such as:
According to a Columbia Broadcasting System (CBS) report, they discovered that a minimum of four court orders and fie search warrants were obtained for identified blood spots. One of these cases involved a request to test the residual blood spot for drugs at birth. There are also cases where coroners use these samples to help in the identification of bodies or parents who request it to prove paternity.
Most famously the issue of storing these samples was brought to light during the trial of the Golden State Killer. The DNA from the crime scene was matched by law enforcement officials with DNA from a California state-run biobank. They used an open-source genetic database, called GEDmatch to identify the killer.
As you can imagine the NGS Program presents several opportunities for abuse. These residual blood spots are easily accessed and many issues can be raised, including:
Parents of the children are not usually informed or asked for consent to the screening. Given the nature of the information collected during this test many people are concerned with the number of loopholes that exist. In the Genetic Information Nondiscrimination Act of 2008 that exists to prevent genetic discrimination from health insurance companies. Since the screening is paid for through health insurance companies. Many fear that a positive test could very well taint a child's record and that insurance companies could use it against people in the future.
There are ethical concerns surrounding residual bloodspots. Some are concerned that residual blood spot research is a way for the government to further control its citizens and have access to not only their records but also their genetic material.
While some believe that de-identification of DNA is possible by not storing the identifying information together with the blood samples, many argue that the DNA itself is an individual’s unique code and can always be used to identify individuals.
The laws for residual blood spots vary depending on the state one is born in. Those concerned should read up on the state’s procedures and policies. It is also important to note that policies and laws can change with time. This means individuals concerned with what happens to DNA samples should stay up-to-date with the new policies.
Many current literatures have demonstrated TMAs using paraffin medium and FFPE blocks for most studies due to the ease of specimen availability, long term storage, and cost-effectiveness for specimens. The TMA platform is an unparalleled tool to optimize assay and adapt novel molecular assays to archival paraffin tissues which are still a large and relatively untapped molecular repository. The remarkable value of TMA applications has been the efficiency and accuracy in the detection of clinicopathologic associations in a wide variety of diseases. The portability of this technique has also played a vital role in the widespread use of it and will continue to drive TMA applications.