RNA in DNA—Mistake or Mystery?

  • Human DNA Misincorporates >1,000,000 Ribonucleotides Per Replication Cycle
  • These Mistakes are Likely Biological Mysteries
  • Four New Sequencing Methods May Demystify Why There’s “R in DNA”

When I came across a publication on the presence of RNA in DNA my initial reaction, frankly, was great surprise, if not outright disbelief. As the so-called “blueprint” of life, I reckoned that DNA is virtually sacred in terms of its chemical composition, albeit subject to base mutations as well as insertions and deletions of sequence. In other words, I had heretofore been under the impression that DNA’s repeating units are 100% deoxyribonucleotide (and conversely that RNA’s are ribonucleotides), thus giving DNA (and RNA) the eponymous name is has. So, I thought to myself, if that’s reportedly not the case for DNA, what are the facts and implications, i.e., is RNA in DNA just a rare “mistake” or is this yet another example of a “mystery” of Nature. Below is what I’ve learned about this revelation.
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Holy Toledo! What’s In Your Tap Water May Be Toxic!

  • Toxins from Harmful Algae Blooms (HABs) Shut Down Toledo’s Drinking Water Supply
  • Fertilizer Run-off is to Blame, Along with Global Warming
  • Beware of Dead Zones that Result from HABs

While the origin of the now-not-trendy exclamation “Holy Toledo!” is subject to much speculation, the origin of a deadly toxin in the water supply for Toledo, Ohio last year is quite clear: algae growing in Lake Erie near the city’s water intake system. Having grown up in Buffalo, NY located at the opposite end of Lake Erie, which is the 4th largest lake in the U.S., I can still clearly remember seeing this algae as seemingly endless greenish muck. I also remember gagging from its stench, wondering when something would be done to stop it. That was many years ago, and sadly this situation still persists and has led to a real crisis in water contamination, as well as created massive areas of water ominously called “dead zones.” After you read the following short synopsis of these troublesome problems, you may want to forego drinking tap water in favor of pure glacier water—while it lasts (but that’s a whole other scary story about global warming that we’ll save for another time).
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Three Fascinating Facts about Epigenetics

  • You Are What Your Father Eats
  • Exercise Affects Epigenetics
  • There’s an Epigenetic Clock

Before getting to some truly fascinating—in my opinion—facts about epigenetics, I thought it would be worth briefly explaining the essence of epigenetics to get us in sync. Many similar but differently worded definitions of epigenetics have been proposed over the years; however, I favor this one, which a group of experts hashed out at venerable Cold Spring Harbor Laboratory—and published, together with their detail reasoning:

“An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence.”

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Gene-Expression Biomarkers Can Detect Depression

  • First-ever Lab Test for Depression Found Using RT-PCR
  • FDA Approval as Diagnostic Possible by Early 2016
  • Huge Potential Market as 1-in-10 US Adults Suffer from Depression

While it’s normal for everyone to occasionally feel blue or sad, prolonged bouts of depression that interfere with normal life are indicative of a serious mental health issue. While there are numerous forms and differing severity of depressive disorders, as described at a National Institute of Mental Health (NIMH) website, only two factual aspects of this illness really stand out in my opinion:

Redder countries have higher depression rates. Bluer countries have lower depression rates. Taken from The Washington Post.

Redder countries have higher depression rates. Bluer countries have lower depression rates. Taken from The Washington Post.

  • Depression is a very common illness. The Centers for Disease Control and Prevention estimates that 1-in-10 US adults suffer from depression, which reportedly costs close to $50B annual in lost productivity in the work place. Globally, more than 350 million people of all ages are afflicted with depression, according to recent statistics from the World Health Organization (WHO). By the year 2020, WHO estimates that depression will be the second leading cause of “lost years of healthy life”, following heart disease. Incidentally, as seen from the map below, depression rates around the world vary significantly among countries.
  • Depression is diagnosed based on the patients’ self-report of their symptoms and the evaluation of one or more structured psychiatric interviews with the patient by a psychiatrist, psychologist or primary care physician. The absence of direct, non-subjective measures of depression can lead to relatively lengthy time-to-treatment, non-reporting, or—sorry to say—fraudulent claims and/or treatments based solely on what is said as opposed to what is objectively measured.
Bi-polar Depression © Mena Purdy oil on canvas.

Bi-polar Depression © Mena Purdy oil on canvas.

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The Most Interesting Scientist in the World: George M. Church

  • Mind Boggling Breadth and Significance of Scientific Publications
  • Serial Entrepreneur and Science Advisor to Many Companies
  • Radical Advocate of Total Openness for Personal Genomics

While seeing for the umpteenth time a Dos Equis beer commercial featuring The Most Interesting Man in the World, I was suddenly inspired to write a blog about The Most Interesting Scientist in the World. After scrolling and polling my memory to decide who that would be, it was an easy decision to pick George M. Church, professor of genetics at Harvard. As I’ll briefly highlight herein, Prof. Church’s contributions continually span a mind boggling spectrum of science that cuts across academic theory, ground breaking “how to” methods, serial entrepreneurship, and—perhaps most importantly—radical openness for personal genomics.

George M. Church and The Most Interesting Man in the World: ‘I don’t always read science, but when I do it’s by George M. Church.’ (taken from Bing Images)

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We’re Celebrating Click Chemistry In Honor of National DNA Day

  • The Verbification of Click Chemistry 
  • Old Chemistry Morphs into New Applications for DNA and RNA  
  • Amazingly, Phosphorus in DNA and RNA is not Needed for Function 

This post comes only two days after National DNA Day 2015 on April 25th so it’s apropos to feature DNA, but I’d also like to give a nod to the lesser recognized RNA, without which DNA would be akin to music notes in search of a melody.  If you’re a regular reader of this blog, you know my stance on this subject and so I digress…

So-called “Click Chemistry” is trending so “hot” that it has led to a phenomenon known as verbification, which is when a noun becomes a verb by virtue of popularity and linguistic convenience. So, just as Google has become to google for virtually everyone, Click has become to click for synthetic chemists and biotechnologists. Whether or not you’re already familiar with Clicking, I hope to provide herein some interesting snippets about Click, its growing ubiquity, and how it has enabled synthesis of a completely novel, non-phosphorous linkage in DNA that nevertheless functions flawlessly in vivo—a stunning feat never before achieved that has intriguing implications about life. More on that later, but first some snippets about Click.

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DNA’s Forgotten Discoverer: Swiss Scientist Friedrich Miescher 

  • Discovered in 1869 in Pus Cells from Bandages of Crimean War Soldiers
  • Miescher Named this New Matter Nuclein and Intuited that it Played a Fundamental Role in Heredity
  • This put the “N” in DNA—Deoxynucleic Acid
  • Children now Isolate DNA from Fruits & Vegetables in Elementary School 

Truth be told, what led me to writing this post was suddenly realizing one day that, although the vast majority of my professional career involves nucleic acids—and DNA in particular—I did not know anything about the discovery of DNA or its naming. My follow-on thoughts were that this was somewhat embarrassing for a blogger focused on nucleic acids, and should be remedied by some homework! This is also good timing since my mind is currently aflutter with all things DNA in anticipation of National DNA Day coming up on April 25. In the event that you recall my past commentary about the bias toward DNA, yes I am still supporting a National RNA Day to balance the ranks, but I digress…

Friedrich Miescher as young man (taken from cienciaytecnicasuabia.blogspot.com via Bing Images)

Friedrich Miescher as young man (via Bing Images)

In doing my so-called homework, I learned about Swiss scientist Friedrich Miescher’s life story and circumstances surrounding his discovery in the late 1860s of new matter that he named nuclein, which eventually became incorporated into the term nucleic acid. Those circumstances, including Miescher’s unusual source of nuclein, were quite interesting to me so I thought they’d be worth sharing in this post, which draws upon a lengthy article by Ralf Dahm, who has written extensively about Miescher, and has a website worth visiting.

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Liquid Biopsies Are Viewed as “Liquid Gold” for Diagnostics

  • Invasive Needles and Scalpels Seen as Passé
  • Noninvasive Sampling Advocates Focusing on Circulating Tumor Cells (CTCs) 
  • New Companies are Pursuing the Liquid Biopsy “Gold Rush”

Biopsy Basics

Ultrasound is a real-time procedure that makes it possible to follow the motion of the biopsy needle as it moves through the breast tissue to the region of concern, as discussed elsewhere (taken from oncopathology.info via Bing Images).

Ultrasound is a real-time procedure that makes it possible to follow the motion of the biopsy needle as it moves through the breast tissue to the region of concern, as discussed elsewhere (taken from oncopathology.info via Bing Images).

As defined in Wikipedia, a biopsy is ‘a medical test commonly performed by a surgeon or an interventional radiologist involving sampling of cells or tissues for examination.’ Biopsies can be excisional (removal of a lump or area), incisional (removal of only a sample of tissue), or a needle aspiration (tissue or fluid removal). Despite the value of these traditional types of biopsies, they are more or less invasive, lack applicability in certain instances, and require accurately “going to the source” of concern, as pictured to the right, for ultrasound-guided breast cancer biopsy. Better methodology is highly desirable and is the topic of this post. By the way, if you want to peruse a lengthy list of scary risks associated with various type of common invasive biopsies, click here to see what I found in Google Scholar by searching “incidence of complications from biopsies.”

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Drug Developer’s Dream-Come-True May Be Patient’s Nightmare

  • HCV ‘Miracle’ Cure’s $84,000 Price Tag Causes Significant Controversy
  • 2014 Sales of the Drug Register Over $10 Billion
  • Competition is Rising, but Prices aren’t Getting Lower
  • Hepatitis C Vaccination Seems Elusive

Having been involved in drug discovery and development for many years, I can assure you Gilead’s new drug, Sovaldi™, is truly a drug developer’s dream come true. Solvaldi™ (sofosbuvir) is a drug used to protect against hepatitis C virus (HCV). Compared to other antiviral or anticancer agents, this nucleotide-analog prodrug, pictured below, produces an extraordinarily high cure rate of well over 90% in HCV-infected patients after only a 12-week (84-day) course of treatment that involves simply taking only one pill per day. That’s amazing!

Stereochemical structure of sofosbuvir (taken from positivelyaware.com via Bing Images).

Stereochemical structure of sofosbuvir (taken from positivelyaware.com via Bing Images).

This miracle-like drug, however, comes at a seemingly very high price: a single pill costs $1,000—adding up to a total treatment cost of $84,000 per patient. The estimated cost of manufacturing this pill is only $68-$136, so there’s been quite a bit of media coverage devoted to discussing why the cost to consumers is so high, how this effects drug payment systems, and strong concerns about the viability of treatment in underdeveloped countries where HCV infection is relatively high. This seeming price-gouging is also causing a budget dilemma for whether or not to treat U.S. prisoners who have rampant rates of HCV infection. Before getting to these prickly issues, let’s start at the beginning with the discovery of this “drug developer’s dream-come-true.”

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Top Picks from Tri-Con 2015

  • “Honey I Shrunk the qPCR Machine” Tops Presentations
  • High School Student Wins Popular Vote for Best Poster
  • BioFire Defense FilmArray is More Interesting Exhibitor
  • Extra Bonus: Swimming with the Sharks

The 22nd International Molecular Medicine Tri-Conference—better known as Tri-Con—took place on Feb 15-20 in San Francisco, where I and 3,000+ other attendees from over 40 countries took part in a jam-packed agenda. In this blog I’ll briefly share my top 3 picks—and an “extra bonus”—but first some insights into the challenges involved in navigating a large conference like this.

The first challenge was scoping out four simultaneously occurring “channels”—diagnostics, clinical, informatics, and cancer—to select as many interesting items as possible from all the presentations (500), panel discussions (30), posters (150), and free “lunch-nars.” The new Tri-Con’15 app with a word and name-searchable agenda (including abstracts) made this easier than previous years. I was even able to put selected items into a calendar/to-do list with 15-min reminder alarms—very slick and convenient. Every big conference should have an app like this!

The second challenge came once I was physically onsite. It took a bit of effort to navigate from one room to another in the huge, multi-room Moscone Center without GPS guidance. I was also struggling to make it to the talks and events on time without getting hijacked by bumping into friends—which happened a lot.

The third and final challenge had to do with posters. Given all of the other exciting options during the conference, I really had to focus to stay on-task and make sure I was present at my poster at the specified times, yet alone try to get around to the other posters of interest. This was definitely not easy, since my poster entitled Pushing the Limits of PCR, qPCR and RT-PCR Using CleanAmp™ Hot Start dNTPs attracted a steady stream of interested visitors. But that’s a great challenge to have, so I can’t complain too much.

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