The Guiding Light: How Medical Insights Can Steer Us to Better Health

I love the map feature on my smart phone. I am no longer burdened by carrying a stack of maps that feel like they could fill every library in the world thrice over. And unlike print maps, the map program can tell me if I’m about to encounter bumper-to-bumper traffic or some other horrible event. It truly is a wonderful piece of technology. If only, we could have something similar when it comes to our health. Well, maybe we do.

The market is inundated with wearable devices and other pieces of technology that can help improve our healthcare. Using personal data and other bits of data, we can have a lovely voice, vibration, etc. tell us it’s time to move, what exercises to do or what foods to eat. Technology has even advanced to the point that wearables can deliver insulin (or another medication) when a patient needs it (Amgen, 2017; Falcone, 2015). These technological advancements have provided people wonderful new ways to manage their health.

What if, though, we could see deeper, casting light all the way to the molecular level? Would we get more insightful information? Evidence already suggests yes. Consider the emerging field of proteomics (measuring the constant changes in the proteins that constitute us). Proteins are the products encoded by our genomes and responsible for what happens in the cell. Changes in protein concentrations or combinations can be an early warning of an oncoming health event (Schubert, Rost, Collins, Rosenberger, & Aebersold, 2017). To measure thousands of proteins over a very broad concentration range simultaneously and quickly, however, proves to be a daunting challenge long recognized (Chandramouli & Qian, 2009).

SomaLogic, a company nestled in Boulder, CO, has discovered a way to achieve what may have seemed impossible. Instead of relying upon mass spectrometry (a conventional means of looking at proteins), SomaLogic has developed a unique, chemically-synthesized affinity agent (known as a SOMAmer) for each protein. At the moment, over 1,300 SOMAmers are available and more are in the works. SomaLogic incorporates the SOMAmers into a SOMAscan assay to detect changes in the proteome (over a very large concentration range).

The SOMAscan platform can provide insights that are invaluable to the medical community. For example, the information gleaned from the technology provided risk scores for an oncoming health event (such as a stroke or heart attack), which was better than conventional methods (Ganz et al., 2016). In another instance, the SOMAscan platform could retroactively identify patients who would suffer an adverse reaction to a drug being tested in clinical trials. The platform even identified the organ systems that would be affected by the new drug (in progress).

The power of the SOMAscan assay is being increasingly recognized by many different researchers in many different fields. In recognition of its potential, the Chinese “Digital Life” company iCarbonX invested $161 million dollars into SomaLogic to push protein-based health insight generation further and faster (Bonislawski, 2017). In the near future, the SOMAscan platform is going to expand from the currently offered 1,310 SOMAmers to more than 5,000. It is envisioned that a version of the SOMAscan platform will one day be able to identify and monitor the 20,000 proteins that constitute our bodies (Bonislawski, 2017). By coupling the technology with biological samples provided by collaborators/partners, the company intends to deliver deep insights that carry the potential of identifying oncoming medical events, grade a response to a medical treatment or lifestyle choice, and more.

With this type of molecular vision, it is possible that individuals will be empowered to take progressive action to enjoy greater health for most their lives. This may prove beneficial in other ways, such as decreasing medical care costs by catching things early and decreasing health insurance costs because people are staying healthier longer. I can hardly wait till my phone has a feature linked to this technology. I can already hear the lovely voice say, “Alert. A (insert a medical event of choice here) is in your near future. Time to change direction.”

References

Amgen (2017, April 18). Retrieved from https://www.amgen.com/media/news-releases/2017/04/amgen-launches-neulasta-pegfilgrastim-onpro-narratives/.

Bonislawski, A. (2017, May 25). With $161M In Funding, SomaLogic Shifting Focus to Dx and Wellness Products. Retrieved from https://www.genomeweb.com/proteomics-protein-research/161m-funding-somalogic-shifting-focus-dx-and-wellness-products

Chandramouli, K., & Qian, P. Y. (2009). Proteomics: challenges, techniques and possibilities to overcome biological sample complexity. Hum Genomics Proteomics, 2009. doi:10.4061/2009/239204

Falcone, A. (2015, October 13). Doctors and Patients See Benefits of Wearable Technology. Retrieved from http://wnpr.org/post/doctors-and-patients-see-benefits-wearable-technology/.

Ganz, P., Heidecker, B., Hveem, K., Jonasson, C., Kato, S., Segal, M. R., . . . Williams, S. A. (2016). Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients With Stable Coronary Heart Disease. JAMA, 315(23), 2532-2541. doi:10.1001/jama.2016.5951

Schubert, O. T., Rost, H. L., Collins, B. C., Rosenberger, G., & Aebersold, R. (2017). Quantitative proteomics: challenges and opportunities in basic and applied research. Nat Protoc, 12(7), 1289-1294. doi:10.1038/nprot.2017.040



Before It’s Too Late: Finding and Diagnosing Cancer Correctly

Beep. Beep. Beep. Shhhh. Whoosh. Beep. These noises fill the sterile cold hospice room. Benevolent Uncle Ted lies unconscious with a steady drip of pain relieving medicines entering his once muscular arms via an IV. Uncle Ted has prostate cancer that spread throughout his body. As the curtain slowly closes on young Uncle Ted’s life, one wonders, “If the cancer had been found sooner, would Uncle Ted be playing with his kids, sailing, hiking or enjoying a fine wine with friends and family right now?”

This sentiment is a commonly held belief. But what if screening yields many false positives and could cause more harm than good? Recently, the U.S. Preventive Services Task Force has recommended that people who are not at high risk forgo screening for thyroid cancer. It was found that in places where over diagnosis occurs, patients have undergone surgeries to remove growths found on the thyroid, but the overall number of thyroid cancer-related deaths remains unchanged. Also, the patients getting the growths removed were undergoing unnecessary treatment that carried the potential of causing more harm than good (Jin, 2017).

With prostate cancer, the same holds true. Out of 1000 men, 100 to 120 men may get a false-positive result, which leads to further testing and biopsies (National Cancer Institute, 2017a). The biopsy procedures are not without risk and the description of the procedures would cause most men to cringe (National Cancer Institute, 2017b). With all this prostate screening, only about 0.1% may have benefitted from the early screening (National Cancer Institute, 2017a). Maybe a more definitive test that does not require biopsies could be developed and save more lives?

International efforts are underway to probe easily acquired samples, such as blood and urine, to identify better biomarkers that could identify individuals with deadly prostate cancer. In these samples, researchers are targeting exosomes (small packages that originated from cells, such as prostate cancer cells, that are full of proteins that may be useful biomarkers). After optimizing a protocol for harvesting exosomes, one group identified several biomarker candidates from individuals with metastatic prostate cancer using the SOMAscan assay (Welton et al., 2016). Another group also used the SOMAscan assay to examine exosomes (originated from prostate cancer cell lines) and found biomarker candidates for prostate cancer (Webber et al., 2014). The biomarkers identified by both groups could one day be used to screen men to determine if they have the deadly prostate cancer. While the work is very encouraging, further evaluation is still needed.

With the SOMAscan assay yielding valuable insights into one’s health, the number of unnecessary risky (and cringe-worthy) medical procedures could go down. Also, people may learn of detrimental diseases earlier through the non-invasive testing. If Uncle Ted had the opportunity, he may have found himself in a different scenario at the closing of his life story.

References 

Jin, J. (2017). Screening for thyroid cancer. JAMA, 317(18), 1920. doi:10.1001/jama.2017.5254

National Cancer Institute (2017a). Benefits and Harms of PSA Screening for Prostate Cancer. Retrieved from https://www.cancer.gov/types/prostate/psa-fact-sheet.

National Cancer Institute (2017b). Prostate-Specific Antigen (PSA) Test. Retrieved from https://www.cancer.gov/types/prostate/psa-fact-sheet.

U.S. Preventive Services Task Force (2017). Final Evidence Review: Thyroid Cancer: Screening. Retrieved from https://www.uspreventiveservicestaskforce.org/Page/Document/final-evidence-review159/thyroid-cancer-screening1

Webber, J., Stone, T. C., Katilius, E., Smith, B. C., Gordon, B., Mason, M. D., . . . Clayton, A. (2014). Proteomics analysis of cancer exosomes using a novel modified aptamer-based array (SOMAscan) platform. Mol Cell Proteomics, 13(4), 1050-1064. doi:10.1074/mcp.M113.032136

Welton, J. L., Brennan, P., Gurney, M., Webber, J. P., Spary, L. K., Carton, D. G., . . . Clayton, A. (2016). Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array. J Extracell Vesicles, 5, 31209. doi:10.3402/jev.v5.31209



Expensive Doesn’t Always Mean Better: Looking for Ways to Keep Medical Costs Down

A candle flickers. Steam from a loaf of freshly baked bread entwines with the candle smoke like ballroom dancers. I look at the wine list. A loud thud echoes throughout the intimate dining establishment as my jaw hits the floor. One bottle of wine commands a price tag comparable to three times my salary from my first job after college.

I pondered if this expensive wine was truly that superior. I am not the first to ask this question: Numerous others have posed it. Blind taste tests with wine experts are arranged, and a humble wine often prevails over the expensive one (Bell, 2012). In the tests, tasters had used metrics such as cost, winemaker labels or let personal expectations or biases sway their judgement.

These metrics are not only used in assessing wine quality, but also the quality of medical care. The newer, more expensive or fancier the technique, the more effective an intervention must be! Right? But, like the expensive wine, this is not always the truth. Recently, Consumer Reports found that primary-care doctor groups can provide high quality care for a lower cost compared to other groups involved in the analysis (Consumer Reports, 2012).

With healthcare costs sky rocketing and becoming too expensive for many people (even for those with insurance), the topic of cost-conscious care is an imperative one. In an article pertaining to medical waste, newly minted doctors tend to embrace the newest technology, but this technology tends to be pricey (Knowledge@Wharton, 2016). Most of these very same doctors also don’t receive formal training in cost-conscious care. Fortunately, many (but not all) residency programs are incorporating programs pertaining to cost-conscious care (Knowledge@Wharton, 2016).

Aside from learned habits driving the overboard use of unnecessary tests and treatments, fear of litigation can be another driver (Knowledge@Wharton, 2016). While improvements in training or changes to litigation policies may change how doctors approach medicine, improving diagnostic tests or diagnostic protocols may be another alternative that can reduce cost without sacrificing quality. On paper, this sounds achievable through initiatives set forth by the precision medicine movement (Personalized Medicine Coalition, 2017).

Recently, a physical exam regimen highlighted in Sciencemag and offered by Health Nucleus appears to be taking the cost saving opportunities offered by precision medicine in the opposite direction. For a mere $25,000 (This is definitely more than my salary from my first job.), the company offers a medical exam that includes full body magnetic resonance imaging, highly detailed imagery of how well the heart moves blood, other tests that look at heart function, sequencing of the bacteria in the gut, analysis of the metabolites found in the body, genomic sequencing, tests for brain function, and more (Cross, 2017; Health Nucleus, 2017).

A description of the “experience” certainly makes one feel that they are receiving state-of-the-art medical care, but at a high cost. At this price, many insurance companies are not likely to rapidly adopt this type of care. A “bargain package” exists, but costs $7,500 (Cross, 2017). It is doubtful that even Cadillac insurance policies will cover this “bargain” testing.

These expensive diagnostic packages show promise in catching problems early (Perkins et al., 2017), but can researchers produce a diagnostic test that can yield just as comprehensive medical insights at a lower cost? If so, would doctors, patients, and insurance companies readily adopt cheaper, but highly effective tests? Would these lower-cost diagnostics be judged as equivalent or superior to more expensive options? These questions are tougher than deciding which wine to pair with my evening meal. Maybe a blinded assessment is in order?

References

Bell, K. K. (2012). Is There Really A Taste Difference Between Cheap and Expensive Wines? Forbes. Retrieved from https://www.forbes.com/sites/katiebell/2012/07/09/is-there-really-a-taste-difference-between-cheap-and-expensive-wines/#2c42b7253ae2

Cross, R. (2017, May 12) This $25,000 physical has found some ‘serious’ health problems.

Others say it has serious problems. Retrieved from http://www.sciencemag.org/news/2017/05/25000-physical-has-found-some-serious-health-problems-others-say-it-has-serious

Health Nucleus (2017, May) Retrieved from https://www.healthnucleus.com/clinical-tests-and-imaging.

Medical care cost vs. quality: You don’t have to pay the highest prices to get quality care.

Consumer Reports (2012, October). Retrieved from http://www.consumerreports.org/cro/magazine/2012/10/when-costlier-medical-care-isn-t-better/index.htm

Medical Waste: Why American Health Care Is So Expensive. Knowledge@Wharton (2016,

August 18). Retrieved from http://knowledge.wharton.upenn.edu/article/medical-waste-american-health-care-expensive/

Perkins, B. A., Caskey, C. T., Brar, P., Dec, E., Karow, D., Kahn, A., . . . Venter, J. C. (2017). Precision Medicine Screening Using Whole Genome Sequencing And Advanced Imaging To Identify Disease Risk In Adults. bioRxiv. doi:10.1101/133538

The Personalized Medicine Report 2017 Opportunity, Challenges, and the Future. Personalized

Medicine Coalition (2017). Retrieved from http://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/The-Personalized-Medicine-Report1.pdf



More Than Meets The Eye: The Growing Complexity Of Genomics

I’m mystified. It sounded so easy on paper and more accurate than gazing into a crystal ball to see what my future has in store. I only had to give a sample and let the experts decipher my future encased within my genetic code. Yet, science indicates that forecasting with the genetic code may be no more accurate than gazing into a crystal ball. Let me explain…

First, our genetics are only predictive. Just because we carry a gene does not mean that it is being actively used by our bodies. It could just be going along for the ride or be negated by external factors.

Second, many of us (if not all) are walking around with a smorgasbord of genomes. Evidence exists that people can have different genomes in different parts of their body. The acquisition of multiple genomes can happen in the early days in the womb between twins (Boklage, 2006), between mother and fetus (Boddy, Fortunato, Wilson Sayres, & Aktipis, 2015; Stevens, 2016) or because an embryonic cell develops a mutation that gets perpetuated to various parts of the body (but not the entire body) (Lupski, 2013). Also, genomes can be picked up from other people, such as via a bone marrow transplantation (Hung et al., 2009). As we age, mutations can occur in localized parts of the body too, which can contribute to cancer or age-related issues (Aguilera & Garcia-Muse, 2013). Pending the location that the sample was taken from, one can obtain very different genetic test results from the same person!

Third, the procurement of the genetic knowledge could have been compromised. It is not uncommon for samples to pick up mutations during the sequencing of the DNA, which were not present in the original sample (Chen, Liu, Evans, & Ettwiller, 2017).  Hence, the resulting data set has become damaged. In a recent publication, it was found that 41% of the 1000 Genomes project and 73% of The Cancer Genome Atlas data sets showed damage (Chen et al., 2017). This can play significant havoc when inferring from the data sets or determining a course of medical treatment based on damaged data sets.

From sequencing our genetic material, we must step aside and ask ourselves what it is that we want to learn. If it is to see that we are 10% (insert favorite ethnicity here), then wonderful. If it is to glean serious medical information, we must remember that the information is only predictive, not absolute and could be an incomplete picture of our multigenome. It is also probable that an error occurred during the DNA sequencing, and does not truly reflect a change in the sequence of the gene in question. To complement genetic testing, additional parameters that may glean more insight about what is actively going on our bodies must be measured too.

References

Aguilera, A., & Garcia-Muse, T. (2013). Causes of genome instability. Annu Rev Genet, 47, 1-32. doi:10.1146/annurev-genet-111212-133232

Boddy, A. M., Fortunato, A., Wilson Sayres, M., & Aktipis, A. (2015). Fetal microchimerism and maternal health: a review and evolutionary analysis of cooperation and conflict beyond the womb. Bioessays, 37(10), 1106-1118. doi:10.1002/bies.201500059

Boklage, C. E. (2006). Embryogenesis of chimeras, twins and anterior midline asymmetries. Hum Reprod, 21(3), 579-591. doi:10.1093/humrep/dei370

Chen, L., Liu, P., Evans, T. C., Jr., & Ettwiller, L. M. (2017). DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification. Science, 355(6326), 752-756. doi:10.1126/science.aai8690

Hung, E. C., Shing, T. K., Chim, S. S., Yeung, P. C., Chan, R. W., Chik, K. W., . . . Lo, Y. M. (2009). Presence of donor-derived DNA and cells in the urine of sex-mismatched hematopoietic stem cell transplant recipients: implication for the transrenal hypothesis. Clin Chem, 55(4), 715-722. doi:10.1373/clinchem.2008.113530

Lupski, J. R. (2013). Genetics. Genome mosaicism–one human, multiple genomes. Science, 341(6144), 358-359. doi:10.1126/science.1239503

Stevens, A. M. (2016). Maternal microchimerism in health and disease. Best Pract Res Clin Obstet Gynaecol, 31, 121-130. doi:10.1016/j.bpobgyn.2015.08.005



Regeneration Powers Activated! Regrowing the Liver from Stem Cells

“Form of rhino! Form of tidal wave!” The Wonder Twins from the TV show, Super Friends, fascinated me as a small child. With a simple uttered phrase the twins could transform into a rhino surfing a tidal wave. The hitch to their power was that it took both to transform. The adult science me finds this fact very reminiscent of stem cells that rely on communications from neighboring cells to transform into a specific cell type.

What is the power phrase uttered to adjacent stem cells? Do the cells require physical contact like the Wonder Twins to transform? To answer these questions, Asai and colleagues investigated the requirements for stem cells to transform into the form of a liver (Asai et al., 2017). They tested if the cells had to contact one another to initiate transformation, the key requirement for the Wonder Twins. In a special chamber, the group placed different types of stem cells. They found that while the stem cells could differentiate into liver cells, they could not fully form a liver-like structure unless they touched. To understand the power phrases uttered by stem cells, Asai and colleagues used the SOMAscan assay to tease out the communications between stem cells and their neighbors to transform into a liver. They found that the power phrases, which consisted of protein signals, changed depending on which types of cells were present.

This work is a large step forward in understanding the mechanisms employed by the body to regenerate the liver. These insights will no doubt will be invaluable to the research and medical community who seek to understand the secrets of the Wonder Stem Cells.

References

Asai, A., Aihara, E., Watson, C., Mourya, R., Mizuochi, T., Shivakumar, P., . . . Bezerra, J. A. (2017). Paracrine signals regulate human liver organoid maturation from induced pluripotent stem cells. Development, 144(6), 1056-1064. doi:10.1242/dev.142794