An Alternative to Alternative: Assessing the Validity of Information or Knowledge

An Alternative to Alternative: Assessing the Validity of Information or Knowledge

News Flash! The wedding between Big Foot and The Loch Ness Monster to be the event of the century! It’s going to be huuuuge! A-list celebrities plan on attending…

Now, is that a true news item or a false one? Before you hit the buzzer and say it is false, consider for a second that it just might be true. People can and do give themselves or their children unique monikers (Big Foot Smith is not outside of belief). The point is, we do not know many things for certain, but we can deduce validity — at least in part — from the source of the info. However, it can be a difficult task even for professional seekers of truth, e.g., scientists.

Traditionally, scientists turn to scholarly journals for valid information. In the olden days, researchers would dive into the bowels of the library to find the journal issue carrying a sought-after article, or send an undergrad to fetch it. Not anymore. Today, a few internet clicks and POOF! Millions of hits in mere seconds. Though it has become easier to access information, it can sometimes be more difficult to discern the legitimacy of the information or the source.

A great example of discerning legitimacy comes in the form of so-called “predatory journals.” What is a predatory journal? It is a journal that exists solely for profit making rather than disseminating knowledge. For a fee, the predatory journal publishes pretty much anything thrown at them, without thorough review of the findings. It can be difficult to spot these predators for they go by titles that sound legit, and can (and do) fool even the most senior of scientists (Cobey, 2017).

How can scientists (and the rest of us) evade these noxious predators? Confirming that a journal is listed in the PubMed database, which has banned some predatory journals, is one strategy (Deprez and Chen, 2017). Other databases such as Journal Citation Reports or Directory of Open Access Journals might be useful (Moher et al., 2017). Looking at impact factors, questioning librarians, or seeing if the journal has any characteristics that have been attributed to a predatory journal (Moher et al., 2017) may also help get to the valid data/knowledge.

However, predatory journals are not the only sources of suspect information. Digital apps and other software can crunch away data and offer something “insightful.” Yet, these data and the resulting findings are not always useable or accurate. For instance, the software that converts experimental data into a DNA sequence has about a 50% reproducibility rate (Keshavan, 2017). Think about it. Your genetic test results might be different if the samples were re-analyzed. If these results were used to decide medical treatment, the treatment might be inappropriate 50% of the time! To rein in the variability seen in DNA sequencing, the FDA is taking action. Though still short of implementing regulations, the FDA beseeches the sequencing companies to scrutinize their software and improve it (Keshavan, 2017).

So, how are consumers using results from genetic tests?  Recently, a survey showed how much consumers actually used the knowledge acquired from commercial tests (Barton, 2017). Consumers can be told of their risk for cancer based on genetic tests that look for single point mutations. These tests did not greatly sway health-related behaviors in either a negative direction or positive direction for many of the participants (except in the case for prostate cancer tests) (Barton, 2017). On the bright side, it would appear that the news is not causing everyone (except for those with worrisome test scores for prostate cancer) to rush and get potentially unnecessary diagnostic tests done, which can carry their own set of problems.

Where do we go from here? With the sheer crush of data available it seems like it is almost impossible avoid predators and wring credible and reproducible information/knowledge from the internet or companies. Yet, it is not. We need to just take the time to carefully scrutinize the information/ knowledge, investigate the publishing practices of journals, query how a company validates their results, put the claims in the context of other knowledge, etc. This is not always easy because we do not always have the time to do this well, and still read entertaining stories on the internet, such as the Big Foot and Loch Ness Monster nuptials.

 

References

Barton, M. K. (2017). Health behaviors not significantly changed by direct-to-consumer genetic testing. CA Cancer J Clin, 67(3), 175-176. doi:10.3322/caac.21368

Cobey, K. (2017). Illegitimate journals scam even senior scientists. Nature, 549(7670), 7. doi:10.1038/549007a

Deprez E. and Chen C. (2017, August 29). Medical journals have a fake news problem. Bloomberg. Retrieved from https://www.bloomberg.com/news/features/2017-08-29/medical-journals-have-a-fake-news-problem.

Keshavan, M. (2017, August 1). FDA pushes to bring order to the chaotic world of DNA sequencing. Statnews. Retrieved from https://www.statnews.com/2017/08/01/fda-dna-sequencing/

Moher, D., Shamseer, L., Cobey, K. D., Lalu, M. M., Galipeau, J., Avey, M. T., . . . Ziai, H. (2017). Stop this waste of people, animals and money. Nature, 549(7670), 23-25. doi:10.1038/549023a

 

Who to Heed for Medical Advice?

By guest blogger: N. T. Feles

I am new to this whole blogging gig, but excited for the opportunity. You see, I come from a long line of writers. Though many members in my family choose to pen their thoughts using clay as a medium, my distant cousin — who wrote an influential physics paper (Hetherington & Willard, 1975) — and I have chosen a different media: keyboards.

What does one blog about? I guess I could just say what is on my mind. Lately, I have been fascinated by how pseudoscience dictates courses of action that can have a profound impact on health. I would really love to know why people are turning away from science and embracing the absurd.

Pawing through the internet, I see products, services and news stories that leave me speechless. For instance, people listening to Hollywood types and forgoing lifesaving vaccinations for fear of developing neurological problems, an urban myth that has been disproven by science. Promotion (and presumed purchases) of gemstone eggs that can promote health. Crystal cleanses that can remove toxins from your body. (I thought this was the job of your kidneys and liver?) Supplements made from plant extracts touted as being able to restore hormone balance, etc.

Know what these situations remind me of? The era before government regulation, when people could hawk bogus treatments and make outlandish claims about their curative effects. Thank goodness for regulations. Now, we have a set of standards to ensure that approved medications are safe and can do what the manufacturers’ say. If only we had this with vitamin and supplement markets, which are still not regulated and where untested claims are still being made and believed.

I know humans can be smart and make good decisions. So, why do they fall for these hokey claims? I am neither a psychiatrist nor a psychologist, but I can guess. As I clawed through the literature, I happened upon an article that explains the power that celebrities hold. Some of the reasons are obvious, such as celebrities being the leaders of our cultural herd and many people wanting to emulate them (Not I. I am not a herd animal.) (Hoffman & Tan, 2013). But the authors also dive into rationale that made my furry chin drop. Why? Apparently, people think if a “trustworthy” celebrity is successful (i.e., paid millions or received a tiny golden statue in the film industry awards ceremony), then it means that person will automatically be successful in other ventures such as medicine, a phenomenon known as the halo effect (Hoffman & Tan, 2013).

Somehow, I do not see someone who got a tiny golden statue for playing some famous person’s love interest getting anywhere near me with a scalpel and anesthesia! Unless, of course, that person received years of practical training from a credited medical school. Which I doubt they did. Anyway, the article is eye opening and worth reading and sending to others.

So, what can be done to get people to listen more to competent professional experts instead of celebrities who deem the next unfortunate animal to be the “it” pet or preach bad medical advice? This is a hard one. The easiest thing to do would be to tell them that they are wrong for following a celebrity’s advice on a medical thing. Surprisingly, this is likely to backfire and make the person further believe the fallible medical advice (Shermer, 2017).

In an altruistic universe, celebrities would be very mindful that with their great powers of influence, comes great responsibility. They would be sure to promote sound medical advice that helps their fans and not just someone’s pocket books. It is reassuring that some celebrities do realize this and do promote the correct medical information (Hoffman & Tan, 2013). We just need more celebrities to do it.

In that same universe, perhaps celebrities would be selected for their wisdom, education or humanitarian endeavors. I do not know if someone overheard me, but a recent commercial provided a glimpse into this alternative reality. The commercial featured Mildred Dresselhaus, a notable scientist, as an A-list celebrity. People clamored to hear her talks, named their children after her, asked for her autograph, etc. How neat would it be it were not fictional? I wonder if Dr. Dresselhaus would have promoted better medical advice?

Well, I am tired of standing on my soap box and about to miss out on my 20 hours of sleep. This blogging thing was fun, but are you going to take my word about what was said? I am not a puppy wielding celebrity, but a cat named Noodle. Then again, I do know how to persuade humans to heed what I say: the science backs me up (McComb, Taylor, Wilson, & Charlton, 2009).

 

References 

Hetherington, J.H. & Willard, F. D. C. (1975). Two-, Three-, and Four-Atom Exchange Effects in bcc 3He. Phys. Rev. Lett. 35, 1442.

Hoffman, S.J. & Tan, C. (2013). Following celebrities’ medical advice: meta-narrative analysis. BMJ. 347:f7151 doi: 10.1136/bmj.f7151

McComb, K., Taylor, A. M., Wilson, C., & Charlton, B. D. (2009). The cry embedded within the purr. Curr Biol, 19(13), R507-508. doi:10.1016/j.cub.2009.05.033

Shermer, M. (2017, January). How to Convince Someone When Facts Fail. Scientific American. Retrieved from https://www.scientificamerican.com/article/how-to-convince-someone-when-facts-fail/

 

The Right Data and Critical Thinking are Key for Precision Medicine Success

The Right Data and Critical Thinking are Key for Precision Medicine Success

“Precision medicine” carries so much promise and engenders so much enthusiasm: medical care precisely assigned based on something that is measured about you uniquely. That sounds cool and so doable with today’s technology. Yet, we need to exercise caution in these early, heady days. If we do not, we will wind up overwhelmed, stuck on data that is not entirely useful, or attempt shortcuts that don’t improve medical care. As a result, the promise of precision medicine will not be realized. When it comes to our health, we will not be empowered. Let me explain.

Many things pertaining to health can be tracked/measured/tested on an almost daily basis or by the second: body mass index, calories consumed/burned, heart-rate, oxygen-levels, blood pressure, brain waves/activity, hours slept, exercise, diet, mutations, genes, proteins, RNA, cells, weight, height, respiration, body temperature, fertility status, glucose levels, sunlight exposure, electrolyte levels, pH of sweat/urine, numerous characteristics of blood, urine and fecal matter… Think about all the data being generated by this list that together describes you. And this is only the tip of the iceberg! This Mount Everest-size pile of information could very well (and does) overwhelm people who do not know what to do with it all, including our doctors (Standen, 2015).

Gorging at the data/ information buffet alone will not empower us to manage our health. Instead, we need to think critically about what we need know to answer a health question. Here is a case in point. Already, it is becoming clearer that genetics alone cannot be used to foresee susceptibility to diseases (refer to previous blogs). The groupie following is waning for the mantra that unlocking our genetic code will improve our understanding of disease and will revolutionize the way we think and approach healthcare (Joyner, 2016). Although genomics can provide beneficial information relevant to patient care, it is not successful in all cases. As an example, let us examine warfarin (a blood thinning drug that can be broken down at different rates in patients). Two genes were identified that contributed to warfarin metabolism (Drew, 2016). When patients were given the proper dose based on their genetics, the results showed no improvement in the patients’ response (Drew, 2016). Drats!

On the bright side, we are getting closer to living the precision medicine promise. From these experiences, we are gaining wisdom (i.e., a deeper understanding about the application of information (Rowley, 2007)). However, this is taking a lot of time. What if we could use technology to speed up the process? Would that help empower us sooner? Again, nope! Recently, Watson (IBM’s artificial intelligence) was fed a monstrous amount of material and expected to recommend cancer treatments to doctors (Ross and Swetlitz, 2017). Well, the supercomputer floundered and recommended treatments that would not have necessarily helped the patients (Ross and Swetlitz, 2017). What happened? Well, it is reported that the imported material had been biased by those who fed it to Watson (Ross and Swetlitz, 2017).

So how do we realize the promise of precision medicine? Until Watson (or some other nifty artificial intelligence) advances to the point of making sense and infers something unbiased and insightful from the big-heap-of-data/knowledge for us, we must focus and be sure to collect the right data that will be meaningful for an intended purpose. We should avoid at all costs the temptation to binge at the data/information buffet or continue trying to get a failing idea to work. As Eric Topol, a famed cardiologist and advocate for precision medicine, put it best, “We need to go beyond ‘big’ and go deep” (Dusneck, 2017). By thinking critically about what data we need to answer a health question, we can be empowered. Precision medicine may then become reality.

 

References

Drew, L. (2016). Pharmacogenetics: The right drug for you. Nature, 537(7619), S60-62. doi:10.1038/537S60a

Dusneck, J. (2017, May 25) Cardiologist Eric Topol on why we need to map the human body and “go deep” with big data. Scope. Retrieved from http://scopeblog.stanford.edu/2017/05/25/cardiologist-eric-topol-on-why-we-need-to-map-the-human-body-and-go-deep-with-big-data/.

Joyner, M. J. (2016). Precision Medicine, Cardiovascular Disease and Hunting Elephants. Prog Cardiovasc Dis, 58(6), 651-660. doi:10.1016/j.pcad.2016.02.004

Ross, C. and Swetlitz, I. (2017, September 5) IBM pitched its Watson supercomputer as a revolution in cancer care. It’s nowhere close. Stat. Retrieved from https://www.statnews.com/2017/09/05/watson-ibm-cancer/.

Rowley, J. (2007). The wisdom hierarchy: representations of the DIKW hierarchy. Journal of Information Science, 33 (2), 163–180.

Standen, A. (2015, January 19) Sure You Can Track Your Health Data, But Can Your Doctor Use It? NPR. Retrieve from http://www.npr.org/sections/health-shots/2015/01/19/377486437/sure-you-can-track-your-health-data-but-can-your-doctor-use-it.

 

Holding onto the Edge: A New Look at How a SOMAmer Binds

Holding onto the Edge: A New Look at How a SOMAmer Binds

A few fingers there, a couple more fingers over there and a couple well placed feet are all that separate rock climbers from the canyon floor hundreds of feet below. With the ease and grace of spiders, the experienced climbers maneuver quickly over the nearly smooth vertical rock face. What supernatural power do they have that keeps them from succumbing to gravity’s will? None. The climbers have instead developed the muscular strength, the know-how to maximize their grip and a few other handy tools to make the daunting feat easier.

SOMAmers are the elite rock climbers of the aptamer* world. They bear a set of “tools” that give them the advantage of gripping onto proteins in ways that other aptamers cannot. These tools include specialized chemical groups that provide the extra “sticky” factor necessary for SOMAmers to find new holds on their targeted proteins and latch on for an incredibly long period of time.

In recent years, a few papers have detailed how SOMAmers put these tools to work. A new discovery from Dr. Anna Marie Pyle’s lab at Yale University (in a collaboration with SomaLogic) has expanded our insight into how these super-aptamer rock climbers hold onto the rocky outcrops of proteins. They revealed the three-dimensional structure of a SOMAmer bound to interleukin 1α (IL-1α), a very difficult protein to bind with a traditional aptamer (Ren, Gelinas, von Carlowitz, Janjic, & Pyle, 2017). This detailed look at how the SOMAmer interacts with IL-1α revealed not only unique SOMAmer attributes, but also a view of IL-1α that had never been seen.

The structure of the IL-1α binder is truly unique, bearing little resemblance to anything that one might expect when told a SOMAmer is made from mostly DNA. The tiny SOMAmer looks like a ladder thrown off the side of a mountain and trampled by a herd of elephants. This contorted shape is thanks in part to the “tools” the SOMAmer possesses. Unlike other structures of SOMAmers in the literature, this one uses a fancy chemical attachment called “2Naphthyl” (Ren et al., 2017). In the structure, these 2Naphthyl tools form a building block (seen in other SOMAmer structures that use different “tools”) reminiscent of a miniature “zipper” that helps maintain the unusual bent shape (Ren et al., 2017). Aside from the little zipper, what’s really neat about this structure is its unexpectedness in this kind of molecule. It is a new take on “G-quadruplexes (Ren et al., 2017),” which are found throughout nature.

Given this unique and tortuous configuration, how does the SOMAmer hold onto its protein partner? Well, it turns out that the bent ladder structure created a “hand,” with the 2Naphthyl groups forming a sticky pocket in the palm of the hand that provided the bulk of the interaction’s strength (Ren et al., 2017). Additional contacts were made between negatively charged and positively charged atoms in the “fingers” (Ren et al., 2017).

As mentioned above, this unusual structure reveals a lot about the protein as well. Up until now, the research community was aware of the general structure of IL-1α, but knew none of the fine details (Ren et al., 2017). The inclusion of the SOMAmer hand in visualizing the structure helped pull the protein together to form an exquisite crystal that revealed the missing fine details. The research community now sees the elusive sidechains of IL-1α, which in turn illuminate the biology of inflammation and cancer development (Ren et al., 2017). As an extra bonus, the little SOMAmer could also inhibit the protein’s normal function; thus, making it a potential therapeutic for future development (Ren et al., 2017).

With a few tools and the ability to adopt contorted shapes, this tiny hand-like SOMAmer and others can tackle the most difficult of proteins and find great places to hold on. This sticky grip makes it possible to reach new vantage points not achievable by other types of technology. What can be seen from these lofty vantage points? Akin to the beautiful vistas bestowed to rock climbers, we will be able to gaze at never-before-seen vistas of our health.

*(a string of nucleic acids designed to bind to stuff)

References

 

Ren, X., Gelinas, A. D., von Carlowitz, I., Janjic, N., & Pyle, A. M. (2017). Structural basis for IL-1alpha recognition by a modified DNA aptamer that specifically inhibits IL-1alpha signaling. Nat Commun, 8(1), 810. doi:10.1038/s41467-017-00864-2

Take my Breath Away: Diagnosing Asthma’s Severity When Every Minute Counts

Take my Breath Away: Diagnosing Asthma’s Severity When Every Minute Counts

When I first came to the Colorado, the mountains captivated me. They looked so imposing, yet enchantingly beautiful at the same time. A few months later, some of my mountaineering friends convinced me to climb one of these enchantresses (known locally as “14’ers”). They picked an “easy” one because I had spent all my life at a few hundred feet above sea level near the Mississippi River.

We started out on a beautiful crisp fall morning. The sun had yet to rise and illuminate the aspen trees that were already turning a golden yellow. As we climbed higher, the aspen grew smaller and it got colder. As the air grew colder and thinner, I found myself having a difficult time breathing. I kept soldiering on, but the fight for breath was getting harder. According to one friend’s watch, I had made it about 13,700 feet before the struggle for breath grew too much. I had to retreat back to a more oxygen-rich environment. The mountain won this round.

There are individuals who experience the fight for breath every day. The cause of this fight is a condition known as asthma, which can vary greatly in its severity. Diagnosing the severity and determining the correct course of treatment is not always straightforward, quick or cheap (Israel & Reddel, 2017). If new diagnostic tests became available, could they speed up the process of determining asthma severity and thus identifying the best treatment?

An international team of researchers united to answer that very question (Rossios et al., 2017). They queried sputum (another name for phlegm) samples from patients with different degrees of asthma to look for changes in the patients’ transcriptomic (looking at all RNA levels) and proteomic (looking at all protein levels) profiles. The researchers successfully found changes in those profiles that provide new insights about the underpinnings of asthma severity and may even help expedite the diagnosis (Rossios et al., 2017).

These researchers took not just one small step, but one giant leap towards summiting Mt. Improved Diagnostics. Instead of focusing on just one biomarker and looking for its presence in samples provided by patients with different degrees of asthma severity, the researchers utilized technologies that could cast a broad net (Rossios et al., 2017). Using the SOMAscan assay, they could scan various molecular pathways simultaneously, see the differences and achieve a better understanding (Rossios et al., 2017).

The asthma researchers certainly share a great vantage point with others who use proteomics. Proteins, which are the end product of our genes, are responsible for how our bodies respond to the environment, disease, etc. Aside from responding to cues, rogue proteins can also be the cause of disease. By looking at how proteins interact with one another and the downstream effects of those interactions, the scientific community can better discern the onset of disease (Fessenden, 2017). By thinking deeply about the data, it will feasible to scale the enchantress, Mt. Improved Diagnostics, with greater ease and surer breath.

 

References

Fessenden, M. (2017). Protein maps chart the causes of disease. Nature, 549(7671), 293-295. doi:10.1038/549293a

Israel, E. & Reddel, H. K. (2017). Severe and difficult-to-treat asthma in adults. N Engl J Med, 377(10), 965-976. doi:10.1056/NEJMra1608969

Rossios, C., Pavlidis, S., Hoda, U., Kuo, C. H., Wiegman, C., Russell, K., . . . Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes Consortia Project Team. (2017). Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma. J Allergy Clin Immunol. doi:10.1016/j.jaci.2017.02.045