Aug 1, 2018 | Digital Pathology, Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
Identifying patients who will likely develop prolonged concussion symptoms could lead to new clinical laboratory tests and personalized medicine treatments
Researchers are homing in on a new diagnostic assay for concussion that could potentially generate significant numbers of test referrals to the nation’s clinical laboratories. This innovative work is targeting how concussions are diagnosed and treated.
Each year, thousands of children receive sports-related injuries, including concussions. There are ways for anatomic pathologists and hospital medical laboratories to diagnose concussions; however, testing can be invasive and doesn’t always reveal a complete picture of the injury state.
Additionally, about one third of children with concussions develop prolonged symptoms. However, when prescribing treatment plans, physicians have been unable to predict which patients are likely to recover quickly versus those who will have a longer recovery.
Now, researchers at Penn State College of Medicine (Penn State) believe they have discovered five microRNAs in saliva that could be used to identify patients who will likely experience prolonged concussion symptoms even one month after the initial injury.
The study also found that certain materials in saliva can help diagnose the severity of concussions and could hold the key to more effective clinical laboratory tests and personalized medicine treatments.
The Penn State researchers published their study results in JAMA Pediatrics, a publication of the Journal of the American Medical Association (JAMA).
Concussion Leading Sports-related Brain Injury
There are approximately 3.8 million sports and recreation-related traumatic brain injuries in the United States each year and the majority of those cases are concussions, according to The Concussion Place. Most concussions treated in emergency rooms are due to falls, motor-vehicle related injuries, being struck by an object, assaults, or playing sports.
Also known as mild traumatic brain injuries (mTBI), concussions are caused by blows or jolts to the head or body that cause the brain to move with excessive force inside the skull. The sudden impact damages brain cells and causes chemical changes within the brain that alter normal functioning. Though usually not life threatening, the damage can be serious and linger for months.
Symptoms of concussion include: headaches, fatigue, nausea, vomiting, dizziness, balance problems, confusion, memory problems, sleep disturbances, and double or blurry vision. Symptoms usually occur immediately, but could take days or even weeks to appear.
Identifying Severity/Predicting Prolonged Symptoms of Traumatic Brain Injuries
After a concussion occurs, brain cells release small fragments of genetic material known as microRNAs while they attempt to repair themselves. A portion of these microRNAs appear in the injured person’s blood and saliva.
In order to determine whether these microRNAs could be used to determine the severity of a traumatic brain injury and predict whether prolonged symptoms would occur, the prospective cohort study researchers gathered saliva samples from 52 concussion patients between the ages of seven and 21:
- The average age of the subjects was 14;
- Twenty-two of the participants were female;
- They were all athletes; and,
- The majority of the samples were collected one to two weeks after the initial injury.
The researchers examined distinct microRNAs in the samples and identified some that enabled them to predict how long a patient’s concussion symptoms might last. In addition, they found one microRNA in children and young adults that accurately predicted which subjects would experience memory and problem-solving difficulties as part of their symptomatology.
The researchers also evaluated the concussion patients using the Sport Concussion Assessment Tool (SCAT-3), Third Edition. Physicians use this questionnaire to assess the symptoms and severity of concussions. The researchers also asked the parents of the concussed patients for observations about their children’s symptoms.
During follow up visits, which occurred at four- and eight-week increments following the original assessment, the Penn State researchers collected additional saliva samples and re-evaluated the patients using SCAT-3.
New Biomarkers Based on MicroRNAs Instead of Protein
“There’s been a big push recently to find more objective markers that a concussion has occurred, instead of relying simply on patient surveys,” Steven Hicks, MD, PhD, Assistant Professor of Pediatrics, Penn State College of Medicine, Hershey, Pa., one of the study researchers, told Penn State News.
“Previous research has focused on proteins, but this approach is limited because proteins have a hard time crossing the blood-brain barrier. What’s novel about this study is we looked at microRNAs instead of proteins, and we decided to look in saliva rather than blood,” he noted.
According to Steven Hicks, MD, PhD (above), who worked on the Penn State College of Medicine study, microRNAs could be more accurate than the traditional questionnaire when diagnosing and forecasting the effects of concussions. “The microRNAs were able to predict whether symptoms would last beyond four weeks with about 85% accuracy,” he told Penn State News. “In comparison, using the SCAT-3 report of symptoms alone is about 64% accurate. If you just go off the parent’s report of symptoms, it goes down to the mid-50s. In this pilot study, these molecular signatures are outperforming survey tools.” (Photo copyright: MD Magazine.)
The goal of this research was to develop a way to definitively ascertain that a concussion had occurred, predict the length and type of symptoms, and then use that data to improve and personalize care for children and young adults who have had a concussion.
“With that knowledge physicians could make more informed decisions about how long to hold a child out of sports, whether starting more aggressive medication regimens might be warranted, or whether involving a concussion specialist might be appropriate,” Hicks told MD Magazine. “Anytime we can use accurate, objective measures to guide medical care, I think that represents an opportunity to improve concussion treatment.”
Further research and clinical trials will be needed to solidify the effectiveness and accuracy of these new biomarkers. However, a rapid, non-invasive saliva test that can determine the severity of a concussion, and predicted whether prolonged symptoms will likely occur, would be widely used and could be an important assay for clinical laboratories. Particularly those associated with hospital medical laboratories and emergency rooms.
—JP Schlingman
Related Information:
Association of Salivary MicroRNA Changes with Prolonged Concussion Symptoms
Saliva Test May Detect Biomarker for Prolonged Concussion
Molecules in Spit May be Able to Diagnose and Predict Length of Concussions
Prolonged Concussion Symptoms Identifiable by Salivary MicroRNA
Spit Test May Help Reveal Concussion Severity
Saliva Test May Lead to Improved Concussion Care for Youths
Jul 30, 2018 | Laboratory Management and Operations, Laboratory News, Laboratory Pathology, Laboratory Testing, Management & Operations
DOJ says now-defunct clinical laboratory in New Jersey generated test orders by bribing physicians with cash, concert tickets, vacations, high-end automobiles, and prostitutes
It finally happened! Two medical laboratory executives were given jail sentences for their role in the rampant fraud and abuse committed during the operation of Biodiagnostic Laboratory Services (BLS) of Parsippany, N.J. The court accepted their guilty pleas in 2015, but delayed sentencing until this year, because the two defendants cooperated with prosecutors.
Anatomic pathologists and clinical laboratory managers pushing for stronger enforcement of anti-kickback laws may have gotten their wish with the sentences announced by the federal judge. The two BLS executives admitted to bribing doctors in a $100-million kickback scheme. Thirty-eight doctors also have been convicted of criminal felony charges during the more than five-year investigation.
On June 13, the judge sentenced David Nicoll, 44, President of now-defunct BLS, to six years in federal prison. His brother Scott Nicoll, 37, a concert ticket broker who became a senior BLS employee, received a 43-month sentence. Each defendant previously had pled guilty to one count of conspiracy to violate the Anti-Kickback Statute and the Federal Travel Act and one count of money laundering.
“Today, the president of a diagnostic lab company and his brother were sentenced for their leading roles in a scam that led to one of the largest ever prosecutions of medical professionals in a bribery case,” U.S. Attorney Craig Carpenito, JD, stated in a U.S. Attorney’s Office news release. “Medical referrals from a doctor should be based on what’s in the patient’s best interest, not on how much money the doctor is offered in kickbacks. The number of doctors and medical professionals sent to prison in this case should make that message abundantly clear.”
Hundreds of Doctors Bribed!
Prosecutors believe BLS may be one of the largest medical frauds ever prosecuted, with the federal investigation into the scheme leading to convictions of 53 defendants including:
- BLS President David Nicoll;
- BLS employee Scott Nicoll;
- 38 physicians and physician assistants;
- Three Nicoll extended-family members; and,
- 10 others, including numerous other BLS employees.
While the brothers’ sentences were far below the 25-year combined maximum jail time they faced after pleading guilty to conspiracy to bribe doctors and money laundering, their cooperation with prosecutors led to reduced sentences.
A one-time nurse and former pharmaceutical sales representative, David Nicoll purchased BLS in 2005, which was then a failing clinical testing laboratory. In his testimony for the government prosecution, the 44-year-old Nicoll described how his company took business away from competing labs by bribing doctors to steer blood samples to BLS for testing.
Now-defunct Biodiagnostic Laboratory Services President David Nicoll (second from left) and his brother Scott Nicoll (far right) leave a Newark courthouse in 2013 accompanied by their representatives. The two New Jersey brothers, who admitted to bribing hundreds of doctors and laundering money for fraudulent blood testing services, recently were sentenced to prison for their roles in the $100-million scheme. (Photo copyright: Associated Press.)
According to the Associated Press, Nicoll changed the lab’s fortunes by signing phony leases for space in doctors’ offices. After New Jersey outlawed the practice, BLS “switched to bribing doctors with bogus consultant agreements paid for by shell corporations formed specifically for that purpose.” Nicoll testified he bribed “the large majority” of the “probably hundreds” of doctors with whom he did business.
NJ Advance Media detailed the wide-reaching bribery scheme. It included not only monthly payments to physicians to keep the blood work orders flowing, but also big ticket payoffs, according to a U.S States Attorney’s Office District of New Jersey news release. The briberies included:
- $50,000 Audi S5 turbocharged coupe;
- Private jet to Key West for deep-see fishing;
- Charter flight to the Super Bowl;
- Tickets to a Katy Perry concert; and,
- Prostitutes provided to at least five physicians.
Nicoll is alleged to have reaped huge personal gain from the fraud, including more than $33 million in distributions from the $200 million BLS received from the testing of blood specimens and related services between 2006 and 2013. In another article NJ Advance Media outlined some of the millions Nicoll spent to enhance his lifestyle, including an $800,000 Mickey Mouse-shaped backyard pool, trips on charter jets to four Super Bowls, and a collection of classic American muscle cars.
“The president and other employees of BLS bribed physicians to refer patients to their lab and order unnecessary lab tests, reaping millions of dollars, all in the name of greed,” Shantelle P. Kitchen, Acting Special Agent in Charge, IRS Criminal Investigation/Criminal Enforcement, Newark field office, stated in the U.S. Attorney’s Office statement, released in 2013 when the Nicolls’ brothers and a third BLS employee were arrested.
“Medical tests should only be run when medically necessary, not so someone can buy exotic cars and charter private jets. This type of healthcare fraud will not be tolerated and IRS-Criminal Investigations, along with our law enforcement partners, will vigorously investigate these crimes to bring the perpetrators to justice.”
More Physicians Plead Guilty to Fraud, Money Laundering, Tax Evasion
While dozens of physicians ultimately admitted to accepting bribes to refer business to BLS, New Jersey internist Frank Santangelo, MD, may have reaped the biggest payoff. Santangelo pleaded guilty in July 2013 of accepting more than $1.8 million in bribe payments from BLS for referrals, for which the lab was paid more than $6 million by Medicare and various insurance agencies between 2006 and 2012.
According to a July 8, 2015, U.S. Department of Justice (DOJ) news release, Santangelo was sentenced to 63 months in prison, fined $6,250 and forfeited $1.8 million as part of his plea agreement for violations of the Federal Travel Act, money laundering, and failing to file tax returns.
“Santangelo admitted he violated the trust of his patients, who should be able to count on their doctors’ prescribing only tests that are necessary, and recommending providers based solely on their qualifications,” stated then-U.S. Attorney Paul J. Fishman for the District of New Jersey, in the DOJ statement.
In another highly publicized case, George Roussis, a pediatrician, and his brother Nicholas Roussis, an obstetrician-gynecologist, both with practices in Staten Island, N.Y., were convicted of accepting cash payments totaling $175,000 from BLS employees and associates between 2010 and 2013. In addition, the U.S. Attorney’s Office said in a 2017 statement that BLS paid for strip club trips for the brothers, who in return funneled $1,450,000 and $250,000 of lab business to BLS, respectively. George Roussis, 45, was sentenced to 37 months in prison, while Nicholas Roussis, 49, received a 24-month sentence.
According to the U.S. Attorney’s Office statement, the government has recovered more than $15 million through forfeiture in what is believed to be a record-setting healthcare fraud case.
Criminal prosecution by federal prosecutors of both the clinical laboratory owners and the physicians who accepted bribes and illegal inducements in return for referring medical laboratory tests is not common. That fact makes this case noteworthy. It serves as a warning to all clinical laboratory professionals and the physicians who may accept kickbacks or illegal inducements that there is a risk that they can be prosecuted for these crimes.
—Andrea Downing Peck
Related Information:
He Bribed Doctors with Cash and Prostitutes. Here’s How much Time He’ll Spend in Prison
President of New Jersey Clinical Laboratory and his Brother, a Senior Employee, Sentenced to Prison in $100m+ Test Referral/Bribery Scheme
Doctor Sentenced to 63 Months in Prison for Accepting $1.8 Million in Bribes for Test Referrals
Brothers Who Ran $100M Health Fraud Scam Sentenced to Prison
Strip Clubs Bribes and Blood Money: The Inside Story of a $150M Medical Fraud
New Jersey Clinical Lab at Center of Largest Physician Bribery Case Ever Prosecuted Pleads Guilty
Five Doctors Plead Guilty in Connection with Test-Referral Scheme with New Jersey Clinical Lab
Jul 27, 2018 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Pathology, Management & Operations, News From Dark Daily
Tuft’s proof-of-concept demonstration study shows how changes in saliva can be employed as biomarkers for development of future diagnostic monitoring devices and applications
For years, pathologists and dentists have recognized that the mouth contains many useful biomarkers for a wide range of health conditions and diseases. Now a study by a research team at Tufts University School of Engineering (Tufts) has demonstrated that a tooth-mounted sensor can reliably measure certain target markers.
In this proof-of-concept study, Tufts researchers developed a tooth-mounted sensor that monitors food consumption as it enters the body. This potentially adds behavioral data to the growing list of exploitable biomarkers available to developers of in vitro diagnostics (IVDs) and wearable medical monitoring devices. For that reason, many clinical laboratory managers and anatomic pathologists will want to track further development of this technology, which uses the mouth as the source of the markers to be measured.
A report detailing the device was first published in the scientific journal Advanced Materials in March of this year.
Sensor Reacts to Biomarkers in Saliva
The 2×2-millimeter flexible sensor consists of three layers and adheres to the tooth like a sticker. It has two gold outer rings surrounding an inner layer of bio-responsive material that is highly sensitive to glucose, salt, and alcohol. The presence of any of these substances alters the electrical properties of the sensor and incites it to transmit radio frequency waves that can be received by mobile devices.
Researchers conducting a proof-of-concept study at Tufts University School of Engineering have developed “a materials‐based strategy to add utility to traditional dielectric sensors by developing a conformal radiofrequency (RF) construct composed of an active layer encapsulated between two reverse‐facing split ring resonators,” their paper published in Advanced Materials notes. The sensor is shown above mounted to a tooth, where it reacts to the presence of certain biomarkers in the saliva, triggering the transmission of an RFID signal. This device has the potential to also measure the same biomarkers used in clinical laboratory tests. (Photo copyright: Smithsonian Magazine/Tufts University School of Engineering.)
There are many possible uses for this tooth-mounted sensor. Individuals with medical conditions such as diabetes, celiac disease, or hypertension, which require them to avoid certain substances in their diet, could benefit from utilizing a device that employs the technology under development at Tufts.
Such a gadget might also help those trying to lose weight. The creators hope to enhance the material, so it has the ability to discern additional nutrients and chemicals.
“If you can evolve the sensor and engineer it to have a database of food consumption, then you could think about nutrition management,” Fiorenzo Omenetto, PhD, Professor, Department of Biomedical Engineering at Tufts and one of the authors of the research told Smithsonian Magazine. “That could be reminding us that we’re indulging too much in sugar or something like that.”
It also could potentially detect physiological or chemical changes taking place in the body by detecting certain bio-markers in the saliva.
“In theory we can modify the bio-responsive layer in these sensors to target other chemicals. We’re really limited only by our creativity,” Omenetto noted in a news release. “We have extended common RFID [radio frequency identification] technology to a sensor package that can dynamically read and transmit information on its environment, whether it is affixed to a tooth, to skin, or any other surface.”
Other Food Intake Devices
There have been previous attempts to develop wearable devices that monitors food intake. However, those gadgets usually required the use of mouth guards and head gear, which are too cumbersome for continuous everyday use. The minute size of the Tufts tooth-mounted device renders it more practical for consumers. And, since it can be mounted anywhere on a tooth—front or back—it can be made undetectable while being worn.
“This study is an interesting proof-of-concept demonstration that small, wireless biosensors can detect changes in saliva due to the presence of compounds such as salt, sugar, and alcohol,” Ben Almquist, PhD, a lecturer in the Department of Bioengineering at Imperial College London, told Smithsonian Magazine.
“For instance, for continuous monitoring of food intake, the sensors will need to be robust enough to withstand abrasion during chewing,” Almquist noted. “In addition, foods are complex mixtures of compounds including salts, sugars and proteins, and the relative amounts of each that enter into saliva will depend on factors such as the nature of the food [i.e., cooked versus fresh], the amount of chewing, and the time in the mouth before swallowing.”
The device currently remains in the prototype stage and more testing will be needed to determine its efficacy and durability. However, the emergence of such wearable devices for medical use suggests valuable opportunities for clinical laboratories.
Because data captured from the tooth-mounted device is transmitted wirelessly, clinical laboratories could potentially store and monitor the data, compare the collected data to other medical laboratory test results for the same patient, then communicate that information to clinicians, other caregivers, and even the patients. This would be a new way for clinical laboratories to provide innovative, value-added services to healthcare professionals and consumers.
—JP Schlingman
Related Information:
This Tiny Tooth Sensor Could Keep Track of the Food You Eat
Scientists Develop Tiny Tooth-mounted Sensors That Can Track What You Eat
A New Tooth-mounted Sensor Will Soon Help You Lose Weight
Functional, RF‐Trilayer Sensors for Tooth‐Mounted, Wireless Monitoring of the Oral Cavity and Food Consumption
Jul 25, 2018 | Digital Pathology, Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
While Apple recently debuted features to bring personal health records and protected health information to its mobile devices, Microsoft shuttered HealthVault in favor of focusing on AI-powered healthcare advances
As clinical laboratories and anatomic pathology groups know, lab testing data comprise more than 70% of the average patient’s health record. Thus, creating a universal platform on which consumers can share or review health information and medical histories with caregivers is a critical, yet elusive goal for most major tech companies, including tech giants Apple (Nasdaq:AAPL) and Microsoft (Nasdaq:MSFT).
Apple has big plans for patient health records and is working to bring protected health information (PHI) and healthcare advice to iPhones, iPads, and Apple Watch. Meanwhile, Microsoft is reducing its footprint in the mobile device healthcare market. Instead, it appears to be banking on its Artificial Intelligence (AI) platform. How these two diverging paths play out could have ramifications for the pathology and clinical laboratory industries.
HealthVault Insights versus AI versus Apple Health Mobile Apps
Launched in February 2017, Microsoft’s HealthVault Insights combined machine learning and AI with patients’ PHI and mobile activity tracking. The intent was to create an accessible, interactive platform for patients to monitor important health trends.
However, as of January 2018, Microsoft pulled the mobile app from Android, iOS, and Windows App stores. While summary information that draws on previously collected data is still available from the HealthVault website, new data and detailed insights are no longer available.
“We launched HealthVault Insights as a research project … with the goal of helping patients generate new insights about their health,” states Microsoft’s HealthVault Insights website. “Since then, we’ve learned a lot about how machine learning can be used to increase patient engagement and are now applying that knowledge to other projects.”
According to ZDNet, the closing of HealthVault Insights does not impact the Microsoft Health platform or the HealthVault patient-records system.
However, Microsoft’s shuttering of HealthVault Insights, and Google’s shuttering its Google Health platform in 2012, does seem to make Apple the last major tech company developing apps target at healthcare consumers designed to help them exchange private health information with caregivers through mobile devices. Dark Daily reported on Apple’s update earlier this year. (See, “Apple’s Update of Its Mobile Health App Consolidates Data from Multiple EHRs and Makes It Easier to Push Clinical Laboratory Data to Patients,” March 21, 2018.)
AI Will ‘Dramatically Transform Healthcare’
Shuttering HealthVault highlighted Microsoft’s shift away from consumer-facing health efforts and toward assisting medical laboratories, physicians, and research groups discover and implement treatments driving modern personalized medicine.
In a Microsoft blog post, Peter Lee, Corporate VP of Microsoft Healthcare, stated that Microsoft hopes its Healthcare NeXT platform will “dramatically transform healthcare, will deeply integrate Greenfield research and health technology product development, as well as establish a new model at Microsoft for strategic health industry partnerships.”
HealthVault Insights was one of several projects in Microsoft’s Healthcare NeXT initiative. Run by Microsoft’s AI and Research Group and partnering with major healthcare and research facilities across the country, other projects in the Healthcare NeXT initiative include:
Speaking with Business Insider, Lee noted that healthcare is becoming a “very large business” for Microsoft. “We don’t talk publicly about the dollars, but it’s large,” he concluded.
Microsoft’s EmpowerMD website states the eventual goal is to use the system to connect conversations with the growing trove of healthcare data available. “Our long-term vision is a learning system that incorporates data from longitudinal medical records, medical devices, genomics, population health, research papers, and more.”
AI a ‘Sleeping Giant for Healthcare’
“AI can be viewed as a sleeping giant for healthcare,” Eric Horvitz, PhD, Director of Microsoft Research Labs, told Nasdaq, when discussing Microsoft’s view of technology and healthcare. “AI methods show promise for multiple roles in healthcare. [This includes] inferring and alerting about hidden risks of potential adverse outcomes, selectively guiding attention, care, and interventional programs where [they are] most needed and reducing errors in hospitals.”
One such project involves a strategic partnership with the University of Pittsburg Medical Center (UPMC), which is a “$13-billion Pittsburgh-based system, comprising more than 25 hospitals, a three-million-member health plan, and 3,600 physicians, [that] will be a core partner in our efforts to improve healthcare delivery through a series of projects, beginning with a focus on transforming clinician empowerment and productivity,” according to Microsoft.
“Despite UPMC’s efforts to stay on the leading edge of technology, too often our clinicians and patients feel as though they’re serving the technology rather than the other way around. With Microsoft, we have a shared vision of empowering clinicians by reducing the burden of electronic paperwork and allowing the doctor to focus on the sacred doctor-patient relationship,” Steven D. Shapiro, MD (above), Chief Medical and Scientific Officer of UPMC and President of UPMC’s Health Services division, stated in the Microsoft blog. [Photo copyright: University of Pittsburg Medical Center.]
Medical laboratories and anatomic pathology groups may soon contribute health information to databases that one day will power AI systems. These trends highlight opportunities to both educate physicians on the tools available to utilize patient health data in an effective manner, and on new platforms that clinical laboratories could use to further streamline operations, reduce costs, and boost efficiency.
—Jon Stone
Related Information:
How Microsoft Is Using Advanced Technology in Healthcare
Microsoft Scrapping Personal Health Data App-Based Research Project
An Update on HealthVault Insights
How Microsoft’s Top Scientists Have Built a Big Business in Hacking Healthcare and Helped a Lot of People Along the Way
Microsoft Abandons Its Own HealthVault App: Is This Part of Something Larger?
Here’s How Microsoft Is Investing in AI
Microsoft Rolls Out More AI-Infused Healthcare Services, Software
Microsoft and Partners Combine the Cloud, AI, Research and Industry Expertise to Focus on Transforming Health Care
In Healthcare Push, Microsoft Launches Genomics Service on Azure Cloud
Apple’s Update of Its Mobile Health App Consolidates Data from Multiple EHRs and Makes It Easier to Push Clinical Laboratory Data to Patients
Jul 20, 2018 | Digital Pathology, Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing
Should greater attention be given to protein damage in chronic diseases such as Alzheimer’s and diabetes? One life scientist says “yes” and suggests changing how test developers view the cause of age-related and degenerative diseases
DNA and the human genome get plenty of media attention and are considered by many to be unlocking the secrets to health and long life. However, as clinical laboratory professionals know, DNA is just one component of the very complex organism that is a human being.
In fact, DNA, RNA, and proteins are all valid biomarkers for medical laboratory tests and, according to one life scientist, all three should get equal attention as to their role in curing disease and keeping people healthy.
Along with proteins and RNA, DNA is actually an “equal partner in the circle of life,” wrote David Grainger, PhD, CEO of Methuselah Health, in a Forbes opinion piece about what he calls the “cult of DNA-centricity” and its relative limitations.
Effects of Protein Damage
“Aging and age-related degenerative diseases are caused by protein damage rather than by DNA damage,” explained Grainger, a Life Scientist who studies the role proteins play in aging and disease. “DNA, like data, cannot by itself do anything. The data on your computer is powerless without apps to interpret it, screens and speakers to communicate it, keyboards and touchscreens to interact with it.”
“Similarly,” he continued, “the DNA sequence information (although it resides in a physical object—the DNA molecule—just as computer data resides on a hard disk) is powerless and ethereal until it is translated into proteins that can perform functions,” he points out.
According to Grainger, diseases such as cystic fibrosis and Duchenne Muscular Dystrophy may be associated with genetic mutation. However, other diseases take a different course and are more likely to develop due to protein damage, which he contends may strengthen in time, causing changes in cells or tissues and, eventually, age-related diseases.
“Alzheimer’s disease, diabetes, or autoimmunity often take decades to develop (even though your genome sequence has been the same since the day you were conceived); the insidious accumulation of the damaged protein may be very slow indeed,” he penned.
“But so strong is the cult of DNA-centricity that most scientists seem unwilling to challenge the fundamental assumption that the cause of late-onset diseases must lie somewhere in the genome,” Grainger concludes.
Shifting Focus from Genetics to Proteins
Besides being CEO of Methuselah Health, Grainger also is Co-Founder and Chief Scientific Advisor at Medicxi, a life sciences investment firm that backed Methuselah Health with $5 million in venture capital funding for research into disease treatments that focus on proteins in aging, reported Fierce CEO.
Methuselah Health, founded in 2015 in Cambridge, UK, with offices in the US, is reportedly using post-translational modifications for analysis of many different proteins.
“At Methuselah Health, we have shifted focus from the genetics—which tells you in an ideal world how your body would function—to the now: this is how your body functions now and this is what is going wrong with it. And that answer lies in the proteins,” stated Dr. David Grainger (above), CEO of Methuselah Health, in an interview with the UK’s New NHS Alliance. Click on this link to watch the full interview. [Photo and caption copyright: New NHS Alliance.]
This is how Methuselah Health analyzes damaged proteins using mass spectrometry, according to David Mosedale, PhD, Methuselah Health’s Chief Technology Officer, in the New NHS Alliance story:
- Protein samples from healthy individuals and people with diseases are used;
- Proteins from the samples are sliced into protein blocks and fed slowly into a mass spectrometer, which accurately weighs them;
- Scientists observe damage to individual blocks of proteins;
- Taking those blocks, proteins are reconstructed to ascertain which proteins have been damaged;
- Information is leveraged for discovery of drugs to target diseases.
Mass spectrometry is a powerful approach to protein sample identification, according to News-Medical.Net. It enables analysis of protein specificity and background contaminants. Interactions among proteins—with RNA or DNA—also are possible with mass spectrometry.
Methuselah Health’s scientists are particularly interested in the damaged proteins that have been around a while, which they call hyper-stable danger variants (HSDVs) and consider to be the foundation for development of age-related diseases, Grainger told WuXi AppTec.
“By applying the Methuselah platform, we can see the HSDVs and so understand which pathways we need to target to prevent disease,” he explained.
For clinical laboratories, pathologists, and their patients, work by Methuselah Health could accelerate the development of personalized medicine treatments for debilitating chronic diseases. Furthermore, it may compel more people to think of DNA as one of several components interacting that make up human bodies and not as the only game in diagnostics.
—Donna Marie Pocius
Related Information:
The Cult of DNA-Centricity
Methuselah Health CEO David Grainger Out to Aid Longevity
VIDEO: Methuselah Health, Addressing Diseases Associated with Aging
Understanding and Slowing the Human Aging Clock Via Protein Stability
Using Mass Spectrometry for Protein Complex Analysis
Jul 13, 2018 | Digital Pathology, Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Management & Operations, News From Dark Daily
Popularity of the pocket-sized gene-sequencing device continues to prove that DNA testing away from clinical laboratories in remote clinics and outlying field laboratories is not just possible, but in some cases preferable
Once again, Oxford Nanopore Technologies (ONT) is demonstrating how next-generation gene sequencing technology can make it cheaper, simpler, and faster to sequence without the need for big clinical laboratories. And its successful raising of $180 million to expand development worldwide shows the support it has with capital funding investors.
Dark Daily has repeatedly reported on the development of the UK-based company’s point-of-care DNA sequencer going back to 2011. Called MinION, we predicted in 2015, that once brought to market, the pocket-sized gene sequencing machine “could help achieve the NIH’s goal of $1,000 human genome sequencing and, in remote clinics and outbreak zones, shift testing away from medical laboratories.” (See Dark Daily, “Point-of-Care DNA Sequencer Inching Closer to Widespread Use as Beta-Testers Praise Oxford Technologies’ Pocketsize, Portable Nanopore Device,” November 4, 2015.)
Since then, MinION’s use worldwide “for a number of biological analysis techniques including de novo sequencing, targeted sequencing, metagenomics, epigenetics, and more” has only expanded, according to multiple sources and ONT’s website.
How Does MinION Work as a Gene Sequencer?
The MinION nanopore sequencing device weighs about 100 grams (less than four ounces), is about the size of a standard deck of cards, operates off a laptop USB plug, and can sequence genetic material in a matter of minutes.
To perform the nanopore sequencing, a strand of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) is pushed through small pores in a membrane. An ionic current is then applied to the material and voltage is implemented to measure any disruptions in the current. The resulting measurement represents an electrical signal that is converted to human-readable sequence.
“It’s like the ultimate barcode,” Gordon Sanghera, PhD, Chief Executive Officer at Oxford Nanopore, told BBC News.
Oxford Nanopore Technologies’ diminutive MinION gene-sequencing device has the capacity to directly recognize epigenetic markers that control gene activity and cellular processes involved in the onset and development of disease. Early detection of cancers, testing for birth defects and infectious diseases, and blood screening are possible future clinical laboratory applications for the MinION. Click on this link to watch video on MinION. (Photo copyright: Oxford Nanopore Technologies.)
Why is MinION Important?
One advantage to this technology is that it has the ability to sequence much longer strands of DNA when compared to existing technologies. The MinION can sequence over a million letters or bases, around 2% of a DNA strand or chromosome with 96% or above accuracy. The device can read remarkably long stretches of consecutive DNA letters. Readouts of several thousand letters are common and the record for the MinION is 882,000 consecutive DNA letters, Technology Review noted.
“One of the most important findings of this research was that, even though the human genome reference was completed or thought to have been completed a while ago, it still contains many missing pieces and we were able to close some of those gaps in the sequence by developing a new method for developing these extremely long reads using nanopore sequencing,” Nick Loman, PhD, Professor of Microbial Genomics and Bioinformatics at the School of Biosciences at the University of Birmingham, UK, told Pharmaphorum. Loman worked on research with Oxford Nanopore on nanopore sequencing.
“We’ve gone from a situation where you can only do genome sequencing for a huge amount of money in well-equipped labs to one where we can have genome sequencing literally in your pocket just like a mobile phone,” Loman told BBC News. “That gives us a really exciting opportunity to start having genome sequencing as a routine tool, perhaps something people can do in their own home.”
Using MinION in the Field
According to the Oxford Nanopore website, the MinION:
- Is pocket-sized and portable;
- Has up to 512 nanopore channels;
- Has a simple 10-minute sample preparation time;
- Allows real-time analysis for rapid and efficient results; and,
- Is adaptable to direct DNA or RNA sequencing.
The MinION Starter Pack is available for purchase on the company’s website with prices starting at $1,000. The kit includes:
- The MinION device;
- Flow cells;
- Sequencing kits;
- Wash kits; and,
- MinION community support.
Researchers at The Kinghorn Center for Clinical Genomics at the Garvan Institute of Medical Research in Darlinghurst, Australia, are currently using the MinION for research purposes.
Members of the Zebra Project (above), an international group of scientists, used Oxford Nanopore Technologies’ MinION to sequence genomes during epidemics in Latin America. With just a laptop computer for power, MinION can run complex gene-sequencing and achieve superior results than other similar technologies. It is in use worldwide bringing clinical laboratory testing to patients in remote, outlying locations. (Photo copyright: Ricardo Funari.)
“I think it’s really expanding the arsenal of tools we have to peer into cell biology and the root causes of cancer and various diseases,” Dr. Martin Smith, Head of Genomic Technologies at the center, told Australian Financial Review. “It’s really just starting to open the lid off the jar and peer more deeply into the genomics of the cell.”
Dr. Sanghera hopes the gadget could be utilized in the future to identify common infections at home and help consumers avoid unnecessary trips to doctors, clinics, and hospitals, and avert the misuse and overuse of prescription medications. He also feels MinION has applications outside the healthcare industry, such as detecting the presence of harmful microbes in food and water supplies.
As gadgets like MinION become more popular, the potential to move DNA sequencing closer to the patient (and out of the core lab) has implications for clinical laboratories and anatomic pathology groups. However, core labs would still be a preferred source to collect the raw data, store that data, then do the annotation of the DNA sequences and report the findings to the referring physician.
—JP Schlingman
Related Information:
How Knowing Your Genetic Code Could Lengthen Your Life
Genome in the Palm of Your Hand
Molecular Machines and the Place of Physics in the Biology Curriculum
Oxford Nanopore’s Hand-Held DNA Analyzer Has Traveled the World
Hostplus Sinks $27m Into Hand-held DNA Sequencing Firm Oxford Nanopore
GIC, Others Invest £100m In Hand-held DNA Sequencing firm Oxford Nanopore
Handheld Device Sequences Human Genome
Breakthrough Leads to Sequencing of a Human Genome Using a Pocket-sized Device
Oxford Nanopore’s Tech Reaches Genome Sequencing Landmark
Point-of-Care DNA Sequencer Inching Closer to Widespread Use as Beta-Testers Praise Oxford Technologies’ Pocketsize, Portable Nanopore Device
$900 Point-of-Care DNA Nanopore Sequencer May Hit Market in Next 12 Months
Is Whole-genome Sequencing Reaching a Tipping Point for Clinical Pathology Laboratories?
