The term “diagnostics,” for some, probably conjures images of the character Dr. Gregory House from the popular Fox television show, House. But diagnostics is actually a multibillion-dollar-a-year business that has until recently lagged other medical innovations, costing billions of dollars and countless lives in the process. That is all changing rapidly now. If you’ve never seen the show, House invariably saves his patients’ lives by diagnosing some obscure ailment based on a controversial insight that only a genius of his caliber (and lovable, curmudgeonly demeanor) could have spotted, and gets the patient on the correct treatment regimen just in time. It makes for good TV. But the real world of medical diagnostics is not so reliant on the whims of madmen. House’s portrayal of diagnostics was true to life in one regard: doctors need better tools to diagnose disease, lest they be left with what amounts to a guessing game. Think about it. How much can a stethoscope really tell you about the health of a heart, never mind the miles of arteries and veins that meander throughout the body? That’s not to say that advancements like MRI machines and CT scans are not big diagnostic improvements. They are. Nevertheless, as Alex Daley wrote in a recent issue of Casey Extraordinary Technology: “[T]he vast majority of what happens inside our bodies happens at a subcellular level, even an atomic one. The complex interactions between proteins, amino acids, lipids, and all the other things that make us biological have been, until now, a virtually impossible puzzle to understand. Simply put, doctors don’t really know what’s going on inside of you. We are macroscopic beings trying to conjure up cures for what happens in a molecular world.” Thankfully, this is changing for the better. And today, we stand at the threshold of an exciting leap forward in medical care, one that is poised to change the way doctors work in fundamental and compelling ways. It’s called molecular diagnostics, or MDx for short. Molecular diagnostics is the term used for a new class of tests that identify nucleic acids or proteins that belong to the patients themselves or foreign organisms, in order properly to diagnose disease and get the right treatment to the patient at the right time. It’s basically augmenting the physician’s decision-making process through the analysis of genetic content for disease information. And it’s only possible thanks to technologies like polymerase chain reaction (a process of selectively amplifying and replicating DNA to look for disease-causing organisms) and advancements in DNA sequencing. Molecular diagnostics has applications in infectious disease, cancer, genetic ailments, and pharmacogenomics (which analyzes how one’s genetic makeup affects one’s response to certain drugs), to name just a few areas. Because of all these applications and the advantages of the tests discussed below, MDx is the fastest-growing segment in the $50 billion/year in-vitro diagnostic space. Estimates of the size of the global MDx market vary, but a 2012 report from Frost & Sullivan pegged it at $4.1 billion in 2010. That same report forecast global sales to exceed $6.2 billion in 2014, with double-digit growth rates baked into the cake for the foreseeable future. Other sources are projecting even higher growth rates, with one industry source predicting the market will reach $15 billion by 2015. Regardless of the source or the accuracy of a given figure, it’s safe to say that growth in this market will be robust for many years to come. There are hundreds of companies with many different tests operating in the molecular diagnostic space. In the interest of time, let’s use one company and one test to highlight some of the advantages of MDx over traditional methods. First, some background on a condition known as sepsis, which may be the deadliest medical condition you’ve barely heard of. Septicemia is the technical term for an infection in the bloodstream, usually bacterial. Left unchecked, such an infection (which usually begins with a common, local infection that goes untreated and which the immune system struggles to control) often leads to sepsis, a deadly condition that sends the whole body into a dangerous inflammatory state. Think of sepsis as your immune system gone mad. It occurs in response to a bloodstream infection and destroys your body from within. In the words of Dr. Kevin J. Tracy, a neurosurgeon and immunologist who wrote a book on sepsis titled Fatal Sequence: The Killer Within, once it starts, every white blood cell in the body is activated, “turning them into uncontrolled roving gangs of street fighters.” This frightening infectious attack is also one of the most expensive reasons for hospitalization in the US. According to the Agency for Healthcare and Research Quality (AHRQ), septicemia cost hospitals an aggregate $15.4 billion in 2009 and was responsible for a total of 1.7 million inpatient hospital stays. That’s nearly one out of every 23 patients in the hospital. Septicemia isn’t just prevalent, it also advances quickly and carries an extremely high in-hospital mortality rate, at about 16% overall in 2009 – more than eight times higher than the average for other reasons, according to the AHRQ. Because septicemia is such a pervasive problem, carries a high mortality rate, and kills quickly, doctors must act quickly and decisively – first to determine what bacteria caused the underlying infection in the first place, and then to identify and eliminate any drugs to which that bacterial strain may be resistant. But all too often, they can’t. The traditional test for septicemia is called a “gram-positive blood culture,” and has barely changed over the past half-century. And, although the test works, it takes a long time to deliver useful results. To perform the test, they start by drawing large volumes of blood from the patient. Then the blood is shipped to a lab, where it’s put in an incubator and allowed to slowly grow into a culture, which can take anywhere from six hours to five days. Explains Dr. Nathan Ledeboer, who oversees the clinical microbiology and molecular diagnostics laboratories at the Medical College of Wisconsin: “When the blood culture signals positive, and in most cases those blood cultures will signal positive within 6 to 24 hours of initial incubation, the laboratory technologist is going to perform a gram stain which is basically taking a sample of that positive blood culture, smearing it out onto a slide and looking for the presence of bacteria.” If the lab tech sees bacteria and they are stained dark blue or violet from the gram stain, he or she will alert the doctor to the presence of gram-positive bacteria, which account for 50% to 65% of bloodstream infections. If the test is negative, they begin again and start looking for the other side of the spectrum, gram-negative bacteria, which cannot retain the crystal violet dye used in the gram-staining protocol, by administering a counterstain coloring all gram-negative bacteria with a red or pink color. Once the gram-positive or gram-negative bacteria have been detected, the doctor will start “empiric therapy,” which is medical lingo for a shotgun approach: administering the antibiotic he or she thinks, based mostly on intuition, is mostly likely to work, or just dosing the patient with several different antibiotics at once. Scientific, huh? It’s not the doctor’s preferred treatment method, of course. The doctor would rather know for sure, but sepsis moves so fast and the test so slowly that a physician has no other choice today. While the doctor is busy shooting at rough shadows, the laboratory continues to work up the results by subculturing the organism they found in the blood, trying to grow enough to get colonies that can be identified. This adds anywhere from 12 to 24 hours to the overall identification process, according to Dr. Ledeboer – meaning it’s now been up to 48 hours since the blood was drawn. For every hour that the patient is not on appropriate therapy, mortality increases. But the lab work is still not over. Even once you know what organism you are dealing with, you have to start resistance testing to see what therapies it might be immune to. The sad reality is that bacteria are adapting to our cures, in part because of our overuse, partly as cited in the previous “shotgun” treatment approach. In the end, a full 48 to 72 hours will have passed from the original blood draw to the moment the lab is finally able to tell the physician, “This is what you’re dealing with, and this is how to treat it.” What if we could cut off those last two steps of subculturing and resistance testing, and alert doctors to both what bacteria they are dealing with and what it’s resistant to in as few as 10 hours? The benefits would be huge. Hospitals could potentially save billions by considerably cutting the duration of stay for patients with septicemia; it would promote responsible antibiotic use in an era of increasing drug resistance; and most important, diagnoses would be more prompt, and lives would be saved. That’s where MDx come in. Specifically, in this case, a company called Nanosphere (NSPH). Nanosphere has developed a test for sepsis called the Gram-Positive Blood Culture assay (BC-GP) to run on its Verigene molecular diagnostic platform. The test is capable of providing results just 2.5 hours after a positive blood culture and requires only five minutes of simple, hands-on technician time. This is not some test that’s still in the early stages of development, either. The BC-GP assay was cleared for sale and marketing by the FDA in June of 2012 and is the first and only one of its kind. It detects 13 of the most common bacterial targets – which account for 90% of the gram-positive bloodstream infections – along with three common antibiotic resistance determinants, all with greater than 95% accuracy. The value of a test like this is profound. Studies have demonstrated a drop in mortality in the ICU from 50% to 10%, as well as a 6.2-day reduction in length of stay, saving over $21,000 per patient. And Nanosphere’s customers have already documented numerous cases where the test has provided critical information that doctors couldn’t have known or acted on without the speedy new test. In one such instance, the test identified a deadly Enterococcus faecium infection that was resistant to vancomycin, the usual first-line therapy given to sepsis patients. The doctor immediately escalated therapy to restricted, last-line linezolid, which worked. The hospital estimates that the rapid diagnosis saved up to eight days of hospital stay, if not the life of the patient. For us as investors, the prospects of MDx are exciting – it’s a technology that patients, hospitals, insurance companies, and everyone else involved can get behind because it saves money as well as lives. Early-stage companies with new tests and technologies are popping up all over the place. Sure, there is risk in these early-stage companies. But there is also immense opportunity to buy in to future game-changers early on, amplifying your potential return. In Casey Extraordinary Technology, we are following this emerging sector closely, and have already made a few key investments that we believe hold enormous potential for our subscribers. One returned over 96% for subscribers in a few short months, and we’ve just added another to our portfolio that we think holds as much or more promise. Of course, we invite you to judge for yourself – take CET for one of our risk-free, 90-day test drives and we’re confident you’ll see for yourself the great opportunity in this sector and how a subscription to CET will easily pay for itself many times over. For us as human beings, the prospects of MDx are even more exciting – with the promise to provide doctors with the right information at the right time to improve patient outcomes and save lives. Bits & Bytes 3D-Printed Gun Fires First Shot (Discovery) Late last week, the “Liberator” became the first known 3D-printed gun to fire a shot. That’s right; someone has printed a plastic firearm that actually works. You can watch the Liberator unload a .38 caliber bullet in this video. Coming Soon: Your Personal Flying Car (Mashable) Has the age-old promise of flying cars finally come to fruition? Massachusetts-based Terrafugia has announced its Transition design, which is part sedan, part private jet with two seats, four wheels and wings that fold up so it can be driven like a car. Tesla CEO Talking with Google About “Autopilot” Systems (Bloomberg) Two of the world’s most innovative companies may soon join hands. According to Bloomberg, Tesla Motors is interested in self-driving cars and is in talks with Google on how to bring that technology to Tesla’s electric vehicles. Tesla CEO Elon Musk says that self-driving cars are the next step in car technology.