What is a biomarker? A cornerstone of personalized medicine.

What is a biomarker? Biomarkers are biological measures of health or disease and are a cornerstone for personalized medicine.Historically, diagnosing a disease was based on symptoms. This reminds me of a joke.  A patient goes to see the doctor and tells him “Doctor, I hurt everywhere.” The patients touches his head “I hurt here”, he touches his arm “I hurt here”, he touches his stomach “I hurt here” and on and on.  The doctor looks at him and says “I know what’s wrong with you!  You have a broken finger!”

No one wants to be diagnosed or misdiagnosed with a broken finger. This isn’t to say understanding symptoms and using this information to contribute to a diagnosis isn’t important.  But what if…
…symptoms don’t lead to an obvious diagnosis?
…two patients have the same symptoms, but different diseases?
…two patients have the same disease, but different causes – either the root cause is different or they both have lung cancer but the genetic mutations in each cancer is different.  In this case different treatments would be are needed.
…two patients have different diseases, but similar causes – maybe they both have the same genetic mutation in two different kinds of cancer –  so the same treatment can be used?

biomarkerThis is where biomarkers come in.  Biomarkers are things in the body that can be measured to give us information about a disease or other condition.  Biomarkers can be a variety of things including

  • Imaging methods
  • Genes (presence or absence)
  • Specific gene mutations
  • Proteins or antibodies
  • Metabolites
  • Microbes?

And these things can be measured to in some way indicate if the person is healthy or has a disease.  Other biomarkers may be used to detect a disease earlier than when the patient is showing symptoms.  Detecting a disease early may allow the patient to change a behavior to decrease the likelihood of developing the disease or to start treating a patient earlier when it is easier to successfully treat a disease. Biomarkers may also be used to determine the severity of a disease or whether or not the disease is progressing.

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Some biomarkers that you may be familiar with are cholesterol, temperature, and blood pressure.  There are a number of biomarkers for pregnancy. Home pregnancy tests look for the presence of the protein beta human chorionic gonadotropin (also called beta-HCG) in the urine.  This protein biomarker is in the blood after the zygote implants 6-12 days after fertilization.  Other biomarkers such as serum creatinine and liver enzymes are markers for kidney and liver function, respectively.

So what makes a good biomarker?  First, it needs to be different if the patients has a disease.  For example, higher than normal blood glucose levels may indicate that a patient has diabetes and these levels of blood glucose would not be found in a patient who didn’t have diabetes.  Second, the biomarker would have to correlate with the outcome.  What this means is that as the patient’s condition changes, the biomarker would also change. In the case of the patient with high blood glucose and diabetes, when the patient starts regulating their diet or taking insulin, the blood glucose levels will go down.  Third, biomarkers should be easy to access, and one of the main reasons for this is so that testing for the biomarkers isn’t too expensive.  Blood is a common location for biomarkers, including in our example of blood glucose levels.  Finally, biomarkers should be consistent.  It wouldn’t be useful to have a biomarker that changes based on whether it’s noon or midnight.  It needs to be dependent on the health of the patient.

Biomarkers are a cornerstone of personalized medicine because they allow clinicians to use symptoms along with measurable and quantifiable factors in the body (the biomarkers) to diagnose, track, and treat disease. Learn more about biomarkers in this YouTube video

What is a biobank? And why do scientists collect human tissue for research?

To understand what a biobank is and why they exist, it helps first to understand what type of “currency” is stored in the “bank” and what this “currency” will be used to purchase. Biobanks are a collection of “biospecimens” (the “currency”) and knowledge through research or preservation is often what can be “purchased” with this currency.  And as a quick FYI, biobank and biorepository are words that can be used interchangeably to describe the same thing.

Biospecimens can be any type of biological sample or material.  Seed biobanks, like the Svalbard Global Seed Bank in Norway, hold tens of thousands of seeds from over 4000 essential food crops.  The purpose of this biobank is to function as a back-up for seeds being stored in various countries. If a crop is wiped out because of disease or a zombie apocalypse, these seeds can be used to grow these crops again a biobank.

butterflies

photo credit Christian Guthier

The collection of birds, insects, butterflies, spiders and other animals and plants stored at the National Museum of Natural History at the Smithsonian Institute are also considered a biorepository.  There are a few reasons that these types of collections exist.  First, they are interesting to the public to show off the diversity of animals and plants found around the world and throughout time (I mean, who doesn’t like dinosaurs?).  But more than that, they are also immensely useful to scientists interesting in studying the animals themselves – including extinct animals, diversity, and evolution.

Biobanks that contain human tissue are most applicable to the study of humans and disease.  The biospecimens stored in these biobanks may include urine, blood, tissue (for example, extra tumor tissue removed during a surgery), feces (aka poop), cells (for example, cells scraped from the inside of the cheek or skin cells), cerebral spinal fluid, DNA or RNA.   The purpose of repositories that store tissue and fluids from people is to better understand diseases and use this understanding to develop molecular diagnostics and treatments. How is this done? Generally, scientists will compare biospecimens from many patients with a particular disease (for example, tumor tissue removed during surgery from patients with breast cancer or blood from patients with diabetes) to samples from patients who do not have that disease using one of those “-omic” analyses. Through understanding what causes the disease, methods can be devised to better detect the disease early or treatments can be developed to target the cause.

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But you may be wondering how tissue biorepositories exist at all?  It is all because patients have been gracious enough to contribute some tissue, blood, skin, or nails for researchers to use in their research.  Biorepositories do not own this tissue and neither do the researchers – we are merely custodians of the tissue with the ultimate purpose to use the biospecimens for research.  The patient always comes first. Therefore, the first thing that is done before collecting tissue for research is to talk to the patient and explain why it is biobankers would like to collect and store their tissue.  The risks are explained and we ask for their permission through a process called informed consent (more on this in future posts).  If a patient does not consent to donate tissue for research, this does not affect their care in any way whatsoever.  It is the patients choice.  However, if they do agree to donate tissue, it will either be collected in the operating room (in the case of tumor tissue) or in pathology.  This tissue collection never disrupts medical care or diagnosis.  If all of the tissue is needed for diagnosing the patient, then that’s what happens and none is collected for research. Again, the patient and their medical care always come first.  If we are able to collect samples, they are stored in liquid nitrogen tanks until they are requested by a researcher.  We then make sure that the samples safely get to the researcher.biobank_workflow

Thousands (likely hundreds of thousands) of studies have relied on biospecimens to better understand the underlying disease in or to develop treatments.  For example, tissue from melanoma patients was used to identify a mutation found ~50% of patients who have melanoma.  This mutation can be specifically targeted by a drug that significantly improved progression-free survival in patients who typically have a dismal prognosis.  Even more studies on ongoing, with the goal of using knowledge gained from these priceless biospecimens to reach the promise of personalized medicine.