Does a photograph provides the most realistic picture of you? It does not. A painting of you represented by thousands of small dots (an art style known as pointillism) would be the most realistic – especially from a health perspective. Why?
Just like pointillism works of art, we can see the outlines of a complete individual from a distance. When we start getting closer and closer and look at a person from a molecular standpoint, we see that a person is made up proteins, DNA, RNA, fat molecules, etc. Getting even closer, it seems that each dot or molecule can tell us a little bit about the subject, but not provide a fuller picture.
An example may illustrate the point (!). Medical tests, such as the one for prostate-specific antigen (PSA), often look at a single protein in the screening for a disease. However, PSA screening can be problematic for some, leading to unnecessary procedures and unnecessary patient/family anxiety. Looking at just a single protein can warp the perception of the current health status of the patient. As in the case of PSA, a step back to look at all the dots (proteins) that make up you could help provide a clearer picture of your health and indicate what directions need to be taken (Webber et al., 2014; Welton et al., 2016).
Why on earth would looking at thousands of proteins simultaneously provide a better picture of your health? Well, it turns out that proteins are involved in pretty much every single function that your body does to keep you alive and grooving to your tunes. Significant numbers of these proteins are dynamic, meaning that their concentration changes in relation to your lifestyle choices and current health status. Looking at how your proteins change with time can indicate your health journey: whether it will be a healthy one or one plagued with horrendous pitfalls.
Sadly, before now the research/medical community could only get small glimpses into your protein portrait. But now we have the ability to see a more complete picture of how the wide range of protein changes are related to the fuller picture of your health and disease. With the ability to look at thousands of proteins at once, our SomaScan® Platform allows us to paint your protein portrait — your current health status and trajectory — across multiple diseases and conditions.
This new technology is just now becoming available in select places, and it will take some time to become more widely accessible. When it does, we believe that each person will benefit from having their portrait done in a way that captures what is most “real” about their health at that moment in a very precise and personal way.
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
I would like to introduce you to you, but not the person you see in the mirror. No, I want to introduce you to “proteo-you,” the version of you made up of proteins. Meeting proteo-you could lead to a healthier you.
It is easy to overlook the fact that we are biologically a lot more than the caloric remnants of lemon curd donuts, bone and sinew, and a couple pounds of bacteria. But proteo-you consists of the building blocks, marvelous communicators and battle-ready warriors for your body – all lumped together under the name “proteins.”
Making their way through the Manhattan-like circulatory subway system of you, thousands of your proteins carry on with their business of making you, “you,” such as relaying messages to other proteins or carrying out specific critical chemical tasks (Lin et al., 2008). In the hustle and bustle of your busy infrastructure, it is also likely that other proteins that originated from microbes, or even from your own dying or damaged cells can be found doing their thing for good or bad. Imagine what we could learn about your body if we could tap into and translate the chatter in your subways.
There is so much information to be had from careful listening. Recently we published the largest protein-focused study of its kind, analyzing blood samples from 17,000 participants — almost 85 million different protein measurements (Williams et al., 2019). From these massive data, we have learned how to extract a range of info from a sample that can reveal a person’s current health status such as having a fatty liver, kidney function, percent body fat, lean body mass, amount of abdominal fat and aerobic fitness. We can even determine how the body responds to alcohol consumption, smoking and physical activity – all from the chatter of proteins. Our findings can also sound alarms about the development of type 2 diabetes or having a heart attack in the next few years.
We are not only listening and translating the protein chatter, but also helping people embrace their proteo-selves to become healthier. For example, we recently started a new study with the Leeds Centre for Personalised Medicine and Health. The aim of the project is to determine if being provided with their protein-based real-time health status will help people at risk of type 2 diabetes make adjustments to their lifestyles to prevent the disease onset and enjoy healthier lives.
And far more than just an academic exercise, we have just begun to offer “proteo-you” tests through select healthcare providers, and expect to continue expanding both the number of tests and number of providers in the foreseeable future.
Why not bypass the doctor and make proteo-you guidance directly available to customers? As Roy Smythe, M.D., our CEO says, we absolutely believe in the democratization of medical information, but want first to vet our technology with doctors and then directly provide people with meaningful relevant information. We don’t want to repeat other companies’ mistakes and bypass the medical community from the outset. We also need to make sure we have all the competencies necessary to deliver directly into a consumer market – things like customer service, and mobile interfaces – that will take us some time to build. And last but not least, we want to get the price of our tests into a range that consumers will find reasonable – that’s achievable in the near term, and we’re working out the science needed to do that now.
As more people become comfortable with their proteo-selves, the realization that proteins are the harbingers of our future health status will become more evident. The final question remaining is, what would the chatter arising from your internal hustle and bustle say about you? Curious? Stay in touch.
Lin, H., Lee, E., Hestir, K., Leo, C., Huang, M., Bosch, E., . . . Williams, L. T. (2008). Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science, 320(5877), 807-811. doi:10.1126/science.1154370
Williams, S. A., Kivimaki, M., Langenberg, C., Hingorani, A. D., Casas, J. P., Bouchard, C., . . . Wareham, N. J. (2019). Plasma protein patterns as comprehensive indicators of health. Nature Medicine. doi:10.1038/s41591-019-0665-2
 SomaLogic, Inc. has developed these tests and determined their performance characteristics. The tests have neither been cleared nor approved by the US Food and Drug Administration.
Do I want to know how I will look in 50 years? A recent viral smartphone app can show me. Though extremely popular, how accurate is it? The test images do look convincing. Yet, when it is used to “age” young pictures of old celebrities, the results are a bit off. Some actors look way older or younger to the app’s edited photo. What is the app missing?
Answers may roll off the tongue quicker than a cat responding to the sound of a can opener. “Oh, they had great/terrible plastic surgery.” “They have good genes.” “Wow! That’s what they get for partying, etc. too much.” “They had the money to take care of themselves.”
A few of these answers are not too far off from the correct one: You will not look exactly like the app’s generated “old” photo because it cannot capture your exposure to your surroundings/environment and the choices you make as you age. These factors are ultimately the single greatest determinants as to how “well” we age.
However, your proteins can reveal how these interactions and choices impact you on the molecular level. Preliminary research has already shown how proteins can reveal our true age. Hey, I might actually be biologically 10 years younger than what it says on some document! Then again, I could also be 50 years older (Cringe!). Proteins can also show us that, in some cases, the aging process can be reversed (Hurray!).
How well we age and what we will ultimately look like in our later years (if we get there) is, to a degree, within in our control. I would surely like to be able to bust out a few dance moves when I am 80 in calendar years. Working with my proteins may just help me have the best chance of achieving that goal.
A 2014 study estimated that about 5% of those who went to a doctor were misdiagnosed (Rettner, 2014). If the underlying condition was serious, misdiagnosis jumped to 20% (Bernstein, 2017). Yikes!
However, given the state of medical knowledge in the past centuries, today’s diagnostic accuracy looks pretty good. In medieval times and even back to Hippocrates, the doctors considered the balance of the four “humors” to diagnose patients. The humors included melancholic (black bile), phlegmatic (phlegm), choleric (yellow bile) and sanguine (blood). It was believed that an imbalance of these four humors in the body was the root cause of the patients’ woes. To us, this ideology is, well, humorous, but it was cutting-edge for centuries. It is no wonder few people lived past the age of 40.
Since the days of the humors, the ability to collect all sorts of other data – and derive knowledge from those data — has increased impressively. Yet, people are still getting misdiagnosed. Would even more data be helpful? It turns out that simply binging at the data buffet or tapping into the omics geyser does not help. It just overwhelms. Or worse – it contributes to the misdiagnosis.
Tim Caulfield, Canada Research Chair in Health Law and Policy at the University of Alberta, writes about how the “datapocalypse” is not making us healthier, just more overwhelmed (Caulfield, 2019); people become less motivated and unhealthier. In the piece, he advocates for people to not buy into the hype that more data will empower healthier lives. Instead, he says, just do more living.
More data alone is unlikely to be beneficial to people’s health. However, it is important to recognize that having the right data is critical to help improve health and reduce misdiagnosis. Proteins could be those data. Your proteins can help diagnose the status and direction of your health, and show the consequences of decisions made in response to that information. Hundreds of publications using our protein-measurement technology demonstrate this to be true.
So, Caulfield’s suggestion of a medical declutter seems a reasonable approach to us. We believe that protein data in its own right will spark joy and be more informative than the four humors (or even genomics) in assisting doctors to more accurately diagnose and help people live healthier lives.
Bernstein, L. (2017, April 4) 20 Percent of Patients with Serious Conditions are First Misdiagnosed, Study Says. The Washington Post. Retrieved on July 18, 2019 from https://www.washingtonpost.com/national/health-science/20-percent-of-patients-with-serious-conditions-are-first-misdiagnosed-study-says/2017/04/03/e386982a-189f-11e7-9887-1a5314b56a08_story.html?noredirect=on&utm_term=.17afac99b0e3.
Caulfield, T. (2019, July 21) Wellness Culture’s Obsession with Fitbits, 23andMe and Data Isn’t Necessarily Making Us Healthier. NBC News. Retrieved on July 21, 2019 from https://www.nbcnews.com/think/opinion/wellness-culture-s-obsession-fitbits-23andme-data-isn-t-necessarily-ncna1029946
Rettner, R. (2014, April 16) 12 Million Misdiagnoses Occur Yearly in US, Study Finds. Livescience. Retrieved on July 18, 2019 from https://www.livescience.com/44888-misdiagnosis-doctors-visits.html.
Finding DNA mutations that drive cancer development and growth can be akin to finding Waldo, the plucky 80’s cartoon lad wearing red and white stripe clothing and glasses hidden amongst a plethora of quirky characters.
One strategy to find the cancer-driving mutations involves analyzing DNA directly from tumors. If a particular mutation keeps popping up, then it is concluded that the mutation may be giving a competitive edge in allowing a cancer cell to proliferate and grow. Hence, the term “driver” mutation. As it turns out, this strategy only rarely identifies true cancer driving mutations.
One example of such a false driver mutation arose in a recent study of esophageal tissue. Two research groups probed for mutations that drive esophageal cancer (Martincorena et al., 2018; Yokoyama et al., 2019). They learned that the genes most often mutated in the healthy tissue were from the NOTCH family, set of proteins that are vital in embryo development, determining the fate of stem cells, suppression of cancer, promotion of cancer, etc. (Hori, Sen, & Artavanis-Tsakonas, 2013). The two groups also reported that the mutations were known cancer-driving mutations. Yet, no cancer cells or tumors were present.
Just how can mutations potentially mislead? Well, as in the previous example, the mutations may just be acquired with age. In another case, the misleading mutations may be attributed to the actions of a protein. Yep. A protein can create Waldo look-alike mutations and make scientists think they are looking at a legit mutation that drives cancer. How? During DNA replication, DNA takes on a shape that is just too irresistible to the APOBEC3A protein (Buisson et al., 2019). This protein binds to the DNA shape and introduces a mutation. Upon searching the genome, these tantalizing sites occur in numerous places and not just sites labelled as the Waldo driver mutations. If they are occurring in sites previously labelled as driver mutations, are they now really Waldo-esque seahorses?
If anything, these examples show that identifying true mutations that will lead to cancer is not trivial. They also raise a worrisome question: If false driver mutations popup and misdirect cancer researchers, what are the chances it is also happening in other diseases or conditions where researchers are trying to determine health risks from peoples’ DNA?
Buisson, R., Langenbucher, A., Bowen, D., Kwan, E. E., Benes, C. H., Zou, L., & Lawrence, M. S. (2019). Passenger hotspot mutations in cancer driven by APOBEC3A and mesoscale genomic features. Science, 364(6447). doi:10.1126/science.aaw2872
Hori, K., Sen, A., & Artavanis-Tsakonas, S. (2013). Notch signaling at a glance. J Cell Sci, 126(Pt 10), 2135-2140. doi:10.1242/jcs.127308
Martincorena, I., Fowler, J. C., Wabik, A., Lawson, A. R. J., Abascal, F., Hall, M. W. J., . . . Jones, P. H. (2018). Somatic mutant clones colonize the human esophagus with age. Science, 362(6417), 911-917. doi:10.1126/science.aau3879
Yokoyama, A., Kakiuchi, N., Yoshizato, T., Nannya, Y., Suzuki, H., Takeuchi, Y., . . . Ogawa, S. (2019). Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature, 565(7739), 312-317. doi:10.1038/s41586-018-0811-x
2016 brought to public consciousness a new threat to humanity, arriving on the wings of mosquitoes: Zika virus (WHO, 2018a). Symptoms are mild for most of those infected, but the truly insidious and headline-making aspect to the disease is what happens to pregnant women. The World Health Organization (WHO) estimates that 5-15% of children born to Zika-infected women suffer serious complications, including dramatically small heads and incomplete brain development.
The fear surrounding Zika virus was understandably palpable. Doctors alerted their patients and paid extra close attention to those who may have been exposed. Pregnant women chose to remain indoors to avoid being bitten by the mosquitos that transmit the virus (Cohen, 2016).
In February of 2016, the WHO declared Zika a global health emergency. WHO Director-General, Dr. Margaret Chan, called for an increase in research to develop the means to treat or prevent the disease (WHO, 2018b). Among the teams who heard the call, a group in Canada used SomaLogic® technology to get a better understanding of how Zika wreaks havoc on its host.
To get an initial baseline on the biological havoc, the researchers used vero cell (a type of monkey cell used to test antiviral treatments) to determine what happens during the first 48-hours of infection (Glover, Gao, Zahedi-Amiri, & Coombs, 2019). From the data, the team saw the Zika virus alter the levels of immune-response proteins, proteins involved in initiating protein production, and proteins involved with cellular communications. The group even saw Zika sharing protein profile similarities with Dengue-2 and West Nile Virus. At the end of the study, the group uncovered a series of protein changes that could show how Zika infects is different and that could potentially serve as prognostic markers.
Because the monkey cells cannot truly mimic the human immune response, the team looked at how Zika infects astrocytes, one of the most abundant cells in the human central nervous system (Sher, Glover, & Coombs, 2019). Using the same SomaLogic® technology, the team saw just how profoundly Zika could alter the normal biology of the astrocytes, which could explain all the neurodevelopmental problems. The team also gained insight into how the immune system may react to the infection.
Where did all this proteomic work get us? It is hoped that the biological insight gleaned from analyzing the proteins may aid in directing the scientific and medical communities to new ways to treat, monitor and hopefully prevent the spread of this frightening new threat.
Cohen, E. (2016, August 22) Pregnant Obstetrician Faces Zika Firsthand. CNN. Retrieved on June 26, 2019 from https://www.cnn.com/2016/08/22/health/zika-pregnant-florida-obstetrician-karla-maguire/index.html.
Glover, K. K. M., Gao, A., Zahedi-Amiri, A., & Coombs, K. M. (2019). Vero Cell Proteomic Changes Induced by Zika Virus Infection. Proteomics, 19(4), e1800309. doi:10.1002/pmic.201800309
Sher, A. A., Glover, K. K. M., & Coombs, K. M. (2019). Zika Virus Infection Disrupts Astrocytic Proteins Involved in Synapse Control and Axon Guidance. Front Microbiol, 10, 596. doi:10.3389/fmicb.2019.00596
World Health Organization (WHO) (2018a, July 20). Zika Virus. Retrieved on June 26, 2019 from https://www.who.int/en/news-room/fact-sheets/detail/zika-virus.
World Health Organization (WHO) (2018b, July 23). Progress Toward Discovery of Zika Virus Vaccines and Therapeutics. Retrieved on June 26, 2019 from https://www.who.int/emergencies/diseases/zika/discovery-of-vaccines/en/.