May 16, 2018 | Digital Pathology, Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
Harvard School of Medicine researcher discovers only a fraction of all known human genes are ever included in research studies
It seems every day that diagnostic test developers are announcing new genetic tests for everything from researching bloodlines to predicting vulnerability to specific chronic diseases. However, as most pathologists know, there are more than 20,000 protein-coding genes in the human genome. Thus, an overwhelming majority of genes are not being researched or studied.
That’s according to Peter Kerpedjiev, PhD, a Postdoctoral Fellow at Harvard Medical School in Boston. Kerpedjiev analyzed US National Library of Medicine (NLM) data from its PubMed database. He found that roughly 25% of the articles tagged by the NLM only featured 100 of the 20,000 human genes.
Kerpedjiev studied approximately 40,000 NLM articles that were tagged as describing the structure, function, or location of a particular gene. He then created a list of the top-10 most-studied genes of all time, which contained interesting and unforeseen disclosures.
“The list was surprising,” Kerpedjiev told Nature. “Some genes were predictable; others were completely unexpected.”
Guardian of the Genome
According Kerpedjiev, the top-10 most-studied genes are:
- TP53;
- TNF;
- EGFR;
- VEGFA;
- APOE;
- IL6;
- TGFBI;
- MTHFR;
- ESR1; and,
- AKT1.
Kerpedjiev discovered that the top gene on the list—Tumor protein p53 (TP53)—was mentioned in about 8,500 articles to date, and that it is typically included in about two PubMed papers per day. When he began his research three years ago, TP53 was referenced in about 6,600 articles.
Peter Kerpedjiev, PhD (above), is a Postdoctoral Fellow in the lab of Nils Gehlenborg at Harvard Medical School. Previously, he was a PhD student working on modelling the tertiary structure of RNA molecules at the Theoretical Biochemistry Group at the University of Vienna. (Photo and caption copyright: Gehlenborg Lab.)
The National Library of Medicine describes the TP53 gene as a tumor suppressor that regulates cell division by preventing cells from growing and proliferating too quickly or uncontrolled. It is mutated in approximately half of all human cancers and is often referred to as the “guardian of the genome.”
“That explains its staying power,” Bert Vogelstein, MD, Professor of Oncology and Pathology at Johns Hopkins School of Medicine in Baltimore, Md., told Nature. “In cancer, there’s no gene more important.”
Critical Roles in Prevention/Treatment of Chronic Disease
The remaining genes on the list also have crucial roles in the functioning of the human body and disease prevention and treatment. Below is a brief summary of genes two through 10 on the list:
TNF encodes a proinflammatory cytokine that is part of the tumor necrosis factor superfamily. This family of proteins was originally distinguished by their ability to cause the necrosis of neoplasms. The TNF gene has been a drug target for cancer and inflammatory diseases, such as:
EGFR makes a protein known as the epidermal growth factor receptor, which positions the cell membrane to bind to other proteins outside the cell to help it receive signals to trigger cell growth, division, and survival. At least eight known mutations of the EGFR gene have been associated with lung cancer and often appear in drug-resistant cases of the disease.
Vascular Endothelial Growth Factor A (VEGFA) contains a heparin-binding protein that promotes the growth of blood vessels and is critical for physiological and pathological angiogenesis. Variants of the VEGFA gene have been affiliated with microvascular complications of diabetes mellitus and atherosclerosis.
ApoE produces a protein named Apolipoprotein E, which combines with lipids in the body to form lipoproteins that carry cholesterol and other fats through the bloodstream. ApoE-e3 is the most common allele (a variant of the gene) and is found in more than 50% of the general population. In addition to its role in cholesterol and lipoprotein metabolism, ApoE is also associated with:
- Alzheimer’s disease;
- Age-related hearing loss; and,
- Macular degeneration.
Interleukin 6 (IL6) is a cytokine that is mainly produced at locations of acute and chronic inflammation. Once there, it is secreted into the serum where it incites an anti-inflammatory response. The IL6 gene is connected with inflammation-associated diseases such as:
Transforming Growth Factor Beta 1 (TGFB1) initiates chemical signals that regulate various cell activities including the proliferation, maturation, differentiation, motility, and apoptosis of cells throughout the body. The protein created by TGFB1 is abundant in skeletal tissues and regulates the formation and growth of bones and cartilage. Mutations in the TGFB1 gene have been associated with breast, colorectal, lung, liver, and prostate cancers. At least 12 mutations of this gene are known to cause Camurati-Engelmann disease, which is distinguished by hyperostosis (abnormally thick bones) in the arms, legs, and skull.
MTHFR makes methylenetetrahydrofolate reductase, an enzyme that performs a crucial role in processing amino acids. Polymorphisms of this gene have been linked to risk factors for a variety of conditions including:
- Cardiovascular disease;
- Stroke;
- Hypertension;
- Pre-eclampsia;
- Glaucoma;
- Psychiatric disorders; and,
- Various cancers.
Estrogen Receptor 1 (ESR1) is a ligand-activated transcription factor that is significant for hormone and DNA binding. Estrogen and its receptors are crucial for sexual development and reproductive functions. They also can affect pathological processes including breast and endometrial cancers and osteoporosis.
AKT1 provides instructions for producing a protein known as AKT1 kinase that is located in many cell types throughout the body and is essential for the development and function of the nervous system. This gene belongs to a classification of genes known as oncogenes, which when mutated have the potential to cause normal cells to turn cancerous.
We Don’t Know What We Don’t Know
“It’s revealing how much we don’t know about because we just don’t bother to research it,” noted Dr. Helen Anne Curry, Senior Lecturer and Historian of Modern Science and Technology at the University of Cambridge, UK, in the Nature article. As far back as 2010, Dark Daily reported on university researchers predicting massive growth in anatomic pathology and clinical laboratory diagnostic testing based on the human genome.
How Kerpedjiev’s discovery might impact future genetic diagnostic test development remains to be seen. It will, however, be fascinating to see how this top-10 list of the most studied genes will change over time and how medical laboratory genetic testing may be affected.
—JP Schlingman
Related Information:
The Most Popular Gene in the Human Genome
Top 10 Genes in the Human Genome (by Number of Citations)
Explore the Normal Functions of Human Genes and the Health Implications of Genetic Changes
Stanford Study Shows How Pathologists May Eventually Use the Whole Human Genome for Diagnostic Purposes
May 11, 2018 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory Pathology, Laboratory Testing
Chronic disease monitoring at home has become a boon to patients as well as hospitals that are finding cost savings in programs designed to monitor/treat patients at external locations
Many clinical pathologists and medical laboratory scientists will be wary about the news that a California company wants to have cancer patients do their own CBCs at home, and that a device to enable such testing is being prepped to go through the FDA clearance process.
Home-based medicine care and chronic disease therapy treatments are gaining in popularity. Patients, understandably, would prefer to stay in the comfort of their homes then be exposed to stressful, germ-laden healthcare environments. And healthcare providers are finding cost savings in home-healthcare programs, which Dark Daily recently reported.
However, each new breakthrough in home medical care impacts clinical laboratories when specimen collection, near-patient medical laboratory testing, and therapy administration/monitoring shifts from traditional healthcare environments to home settings.
Nevertheless, new devices that enable chronic disease patients to monitor and report findings to care providers continue to be developed and embraced by healthcare consumers.
Complete Blood Count at Home
One such device from Athelas, a diagnostic test developer based in Mountain View, Calif., makes it easier and less expensive for patients undergoing cancer therapy to monitor their complete blood counts (CBC) at home without the need to travel to a doctor or medical laboratory to have the blood work performed, Medgadget reported. The device, which is undergoing the FDA Class 2 clearance process, enables patients to test their complete blood count (CBC) in the privacy of their own homes and report the results to their oncologists.
Athelas co-founders Tanay Tandon (left) and Deepika Bodapati (right) secured $3.7 million in funding from Sequoia Capital, Y Combinator, and NVIDIA, to produce their blood analysis device. (Photo copyright: Sina.)
To use the Athelas device, patients perform a simple finger prick and place a drop of blood on a proprietary testing strip. The strip is then inserted into the device where the blood is analyzed. Patients can view their lab-grade blood test results in about a minute.
Information gathered by the device can be sent to Android or iOS devices/apps and also to the patient’s doctor. The process allows patients and their doctors to receive frequent updates for monitoring treatments and disease progression and precisely observe changes in immune health.
According to Athelas, in about 60 seconds the blood analyzer provides accurate reading for:
“Athelas is bringing cancer patients a quick and reliable way to test their blood levels from within their home,” noted Alfred Lin, partner at Sequoia, in a statement. “Their new platform empowers patients to confidently monitor their condition and will cut down on unnecessary urgent care visits. We believe in Tanay and Deepika’s bold vision to transform at-home blood tests into an easy and accurate diagnostics tool that’s as trusted as a thermometer.”
The home-testing platform will cost consumers $20 per month, which Athelas hopes will eventually be covered by insurance companies.
Additional Benefits to At-Home Monitoring
The Athelas device also has functions beyond chronic disease monitoring. It can be used to determine if a viral or bacterial infection is present in an individual. In addition, the company is currently testing the machine with 100 patients at risk for a cardiac event to evaluate whether or not it can predict such an event days before it occurs.
“There’s a lot of research out there that shows inflammatory markers inside your own body will spike a couple days in advance,” Tandon told TechCrunch.
In the video above, Deepika Bodapati, co-founder of Athelas, describes how the diagnostic device operates. Click on the image above to view the video. (Video copyright: TechCrunch.)
The Athelas device is not yet cleared to market by the Food and Drug Administration (FDA) and more clinical research may be needed to validate the efficacy of the product. Athelas is currently loaning the device to cancer patients for the purpose of monitoring their chemotherapy progress, and is conversing with healthcare professionals, hospitals, and pharmaceutical companies regarding the benefits of the device.
Other CBC Devices
In 2017, Sysmex America announced it had received clearance from the FDA for the Sysmex XW-100 hematology analyzer, the first CBC system that allows in-house staff to perform CBC tests at Clinical Laboratory Improvement Amendments (CLIA)-waived locations. The Dark Report reported on this last year. (See TDR, “FDA Clears Waived CBC For Near-Patient Testing,” November 20, 2017.”
The XW-100 device enables physicians to perform in-office blood tests and receive results in as little as three minutes. This allows treatment plans to be initiated without interacting with clinical laboratories, which clearly impacts test ordering and lab revenue.
At-home and onsite blood testing devices serve an important role in patient care and provide healthcare professionals with expeditious and convenient test results. However, with the arrival of these new technologies, clinical laboratories will need to find new ways to bring value to physicians who employ them in their offices.
—JP Schlingman
Related Information:
Athelas Device Provides Accurate CBC Testing—From Home
Athelas Launches a New Type of Blood Testing Device for the Home
Precise Blood Testing from a Fingerprick? Tanay Tandon and Deepika Bodapati Think It’s Possible
Athelas Releases Automated Blood Testing Kit for Home Use
Athelas Announces $3.7m Funding Led by Sequoia Capital
Primary Care Doctors Can Provide Blood Test Results in Minutes, Onsite, With New Sysmex XW-100
May 7, 2018 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory Pathology, Laboratory Testing
Genomic analysis of pipes and sewers leading from the National Institutes of Health Clinical Care Center in Bethesda, Md., reveals the presence of carbapenem-resistant organisms; raises concern about the presence of multi-drug-resistant bacteria previously undetected in hospital settings
If hospitals and medical laboratories are battlegrounds, then microbiologists and clinical laboratory professionals are frontline soldiers in the ongoing fight against hospital-acquired infections (HAIs) and antibiotic resistance. These warriors, armed with advanced testing and diagnostic skills, bring expertise to antimicrobial stewardship programs that help block the spread of infectious disease. In this war, however, microbiologists and medical laboratory scientists (AKA, medical technologists) also often discover and identify new and potential strains of antibiotic resistance.
One such discovery involves a study published in mBio, a journal of the American Society for Microbiology (ASM), conducted by microbiologist Karen Frank, MD, PhD, D(AMBB), Chief of the Microbiology Service Department at the National Institutes of Health (NIH), and past-president of the Academy of Clinical Laboratory Physicians and Scientists (ACLPS). She and her colleagues identified a surprising source of carbapenem-resistant organisms—the plumbing, sewers, and wastewater beneath the National Institutes of Health Center (NIHCC) in Bethesda, Md. And they theorize similar “reservoirs” could exist beneath other healthcare centers as well.
Potential Source of Superbugs and Hospital-Acquired Infections
According to the mBio study, “Carbapenemase-producing organisms (CPOs) are a global concern because of the morbidity and mortality associated with these resistant Gram-negative bacteria. Horizontal plasmid transfer spreads the resistance mechanism to new bacteria, and understanding the plasmid ecology of the hospital environment can assist in the design of control strategies to prevent nosocomial infections.”
Karen Frank, MD, PhD (above), is Chief of the Microbiology Service Department at the National Institutes of Health and past-president of the Academy of Clinical Laboratory Physicians and Scientists. She suggests hospitals begin tracking the spread of the bacteria. “In the big picture, the concern is the spread of these resistant organisms worldwide, and some regions of the world are not tracking the spread of the hospital isolates.” (Photo copyright: National Institutes of Health.)
Frank’s team used Illumina’s MiSeq next-generation sequencer and single-molecule real-time (SMRT) sequencing paired with genome libraries, genomics viewers, and software to analyze the genomic DNA of more than 700 samples from the plumbing and sewers. They discovered a “potential environmental reservoir of mobile elements that may contribute to the spread of resistance genes, and increase the risk of antibiotic resistant ‘superbugs’ and difficult to treat hospital-acquired infections (HAIs).”
Genomic Sequencing Identifies Silent Threat Lurking in Sewers
Frank’s study was motivated by a 2011 outbreak of antibiotic-resistant Klebsiella pneumoniae bacteria that spread through the NIHCC via plumbing in ICU, ultimately resulting in the deaths of 11 patients. Although the hospital, like many others, had dedicated teams working to reduce environmental spread of infectious materials, overlooked sinks and pipes were eventually determined to be a disease vector.
In an NBC News report on Frank’s study, Amy Mathers, MD, Director of The Sink Lab at the University of Virginia, noted that sinks are often a locus of infection. In a study published in Applied and Environmental Microbiology, another journal of the ASM, Mathers noted that bacteria in drains form a difficult to clean biofilm that spreads to neighboring sinks through pipes. Mathers told NBC News that despite cleaning, “bacteria stayed adherent to the wall of the pipe” and even “splashed out” into the rooms with sink use.
During the 2011-2012 outbreak, David Henderson, MD, Deputy Director for Clinical Care at the NIHCC, told the LA Times of the increased need for surveillance, and predicted that clinical laboratory methods like genome sequencing “will become a critical tool for epidemiology in the future.”
Frank’s research fulfilled Henderson’s prediction and proved the importance of genomic sequencing and analysis in tracking new potential sources of infection. Frank’s team used the latest tools in genomic sequencing to identify and profile microbes found in locations ranging from internal plumbing and floor drains to sink traps and even external manhole covers outside the hospital proper. It is through that analysis that they identified the vast collection of CPOs thriving in hospital wastewater.
In an article, GenomeWeb quoted Frank’s study, noting that “Over two dozen carbapenemase gene-containing plasmids were identified in the samples considered” and CPOs turned up in nearly all 700 surveillance samples, including “all seven of the wastewater samples taken from the hospital’s intensive care unit pipes.” Although the hospital environment, including “high-touch surfaces,” remained free of similar CPOs, Frank’s team noted potential associations between patient and environmental isolates. GenomeWeb noted Frank’s findings that CPO levels were in “contrast to the low positivity rate in both the patient population and the patient-accessible environment” at NIHCC, but still held the potential for transmission to vulnerable patients.
Antibiotic-Resistance: A Global Concern
The Centers for Disease Control and Prevention (CDC) reports that more than two million illnesses and 23,000 deaths in the US are caused each year by antibiotic resistance, with 14,000 deaths alone linked to antibiotic resistance associated with Clostridium difficile infections (CDI). Worldwide those numbers are even higher.
Second only to CDI on the CDC’s categorized list of “18 drug-resistant threats to the United States” are carbapenem-resistant Enterobacteriaceae (CRE).
Since carbapenems are a “last resort” antibiotic for bacteria resistant to other antibiotics, the NIHCC “reservoir” of CPOs is a frightening discovery for physicians, clinical laboratory professionals, and the patients they serve.
The high CPO environment in NIHCC wastewater has the capability to spread resistance to bacteria even without the formal introduction of antibiotics. In an interview with Healthcare Finance News, Frank indicated that lateral gene transfer via plasmids was not only possible, but likely.
“The bacteria fight with each other and plasmids can carry genes that help them survive. As part of a complex bacterial community, they can transfer the plasmids carrying resistance genes to each other,” she noted. “That lateral gene transfer means bacteria can gain resistance, even without exposure to the antibiotics.”
The discovery of this new potential “reservoir” of CPOs may mean new focused genomic work for microbiologists and clinical laboratories. The knowledge gained by the discovery of CPOs in hospital waste water and sinks offers a new target for study and research that, as Frank concludes, will “benefit healthcare facilities worldwide” and “broaden our understanding of antimicrobial resistance genes in multi-drug resistant (MDR) bacteria in the environment and hospital settings.”
—Amanda Warren
Related Information:
Genomic Analysis of Hospital Plumbing Reveals Diverse Reservoir of Bacterial Plasmids Conferring Carbapenem Resistance
Snooping Around in Hospital Pipes, Scientists Find DNA That Fuels the Spread of Superbugs
CSI Bethesda: Sleuths Used Sequenced Genome to Track Down Killer
Antibiotic/Antimicrobial Resistance
Study Tracks How Superbugs Splash Out of Hospital Sink Drains
CDC: Biggest Threats
Antimicrobial Stewardship: How the Microbiology Laboratory Can Right the Ship
Superbugs Breeding in Hospital Plumbing Put Patients at Risk
Microbiologists at Weill Cornell Use Next-Generation Gene Sequencing to Map the Microbiome of New York City Subways
Apr 25, 2018 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Management & Operations
Direct-to-consumer medical laboratory testing company gets a major shot in the arm as developers find ready investors and increasing consumer demand
Clinical laboratory tests, usually performed without fanfare, were thrust into the limelight during a recent episode of Shark Tank, an American reality TV show on which aspiring entrepreneurs compete for the attention and partnership funds of various investors.
EverlyWell, a direct-to-consumer (DTC) company that offers at-home lab tests without lab visits or doctor referrals, obtained a $1-million line of credit from Lori Greiner, one of Shark Tank’s participating entrepreneurs, according to MobiHealthNews. EverlyWell has consumers collect their own specimens at home, which are then sent to a medical laboratory testing facility.
Based in Austin, Texas, EverlyWell was founded in 2015 by Julia Taylor Cheek, CEO, with an aim to “make lab tests accessible, simple, and meaningful,” according to a news release. Cheek is also a Venture Partner with NextGen Venture Partners and formerly the Director of Strategy and Operations with the George W. Bush Institute.
“It’s incredible for the industry that we were selected and aired on a show like Shark Tank. It really shows the intersection of what’s happening in consumer healthcare and the high cost in healthcare and that people are really responding to new solutions,” Cheek told MobiHealthNews.
“I think the product is brilliantly crafted,” Greiner stated during the episode’s taping, according to MobiHealthNews. “It’s really nice; it’s really easy. It’s super clear. I think the state of healthcare in our country now is so precarious. I think this gives people an empowered way … to know whether or not they have to go find a doctor,” she concluded.
Greiner offered the $1 million line of credit (with 8% interest) in exchange for a 5% equity stake in EverlyWell, explained Austin360. According to SiliconHillsNews, she did so after reviewing certain EverlyWell financial indicators, including:
- $2.5 million in revenue in 2016;
- $5 million expected revenue in 2017; and
- 20% monthly growth rate.
Julia Cheek, CEO and Founder of EverlyWell (above), in a news release following her success on reality show Shark Tank, said, “We’re leading a major shift in the consumer health marketplace by bringing the lab to consumers’ doorsteps, and we are moving quickly to expand our channels, launch innovative tests, and deliver a world-class customer experience.” (Photo copyright: Forbes/Whitney Martin.)
Physician Review Still Part of Home-testing Process
EverlyWell lists 22 home lab tests on its website and a market share that encompasses 46 states. Shoppers can search for specific tests based on symptoms or by test categories that include:
- General Wellness;
- Men’s Health;
- Women’s Health;
- Energy and Weight; and
- Genomic Test (through a partnership with Helix, a personal genomics company).
The most popular test panels include:
- Food sensitivity;
- Thyroid;
- Metabolism;
- Vitamin D; and,
- Inflammation.
Prices range from $59 for a glycated hemoglobin (HbA1c) test (found under the general wellness category) to $399 for a women’s health testing kit. EverlyWell explains that it has no insurance contracts for these diagnostic tests, which do not require office or lab visits.
The testing process, according to EverlyWell’s website, proceeds as follows:
- After ordering and paying online, kits arrive at the customer’s home;
- The consumer self-collects a sample (such as blood spots, dried urine, or saliva) and returns it by prepaid mail to a medical laboratory that partners with EverlyWell. The company notes that it works with CLIA (Clinical Laboratory Improvement Amendment)-certified laboratories;
- A board-certified doctor reviews the lab results; and,
- A report is available online in a few days.
“Our goal is not to remove the importance of physician review. It’s to make the experience easier for the consumer,” Cheek told Texas CEO Magazine. “We designed a platform that is all about access and empowering consumers to have access to and monitor their own health information,” she continued.
Texas CEO Magazine explained that Cheek was inspired to create the company following “a bad personal experience with health and wellness testing that sent her to seven different specialists, cost $2,000 out of pocket, and left her with pages of unreadable results.”
Since then, the three-year old start-up company has garnered more than $5 million in venture capital, noted the news release.
Many Choices in Direct-to-Consumer Lab Company Market
EverlyWell is not the only player in the DTC clinical laboratory test space. According to MedCityNews, there are at least 20 other DTC lab test companies in the market including:
- 23andMe;
- Laboratory Corporation of America (LabCorp);
- Mapmygenome;
- Pathway Genomics;
- Quest Diagnostics (Quest);
- Sonora Quest Labs;
- Theranos; and others.
The direct-to-consumer lab test market grew from $15 million to about $150 million in 2015 and includes both large and small clinical laboratory test developers, noted Kalorama Information.
Clearly, the DTC testing market is expanding and garnering the attention of major developers and investors alike. This growing demand for home-testing diagnostics could impact anatomic pathology groups and smaller clinical laboratories in the form of reduced order testing and decreased revenue.
—Donna Marie Pocius
Related Information:
Mail-Order Lab Test Startup EverlyWell Makes Million Dollar Deal on ABC’s Shark Tank
EverlyWell Raises Additional Capital, Bringing Total to $5 Million
This Austin Entrepreneur Scored Historic Deal on Shark Tank
Austin-based EverlyWell Lands Deal on Shark Tank
Innovative Texas Businesses: Empowering Consumers; Julia Cheek’s EverlyWell’s Health and Wellness Testing
Meet the Start-up Revolutionizing the Lab Testing Industry
20 Key Payers in the Direct-to-Consumer Lab Testing Market
Direct-to-Consumer Services Put Down Roots in US Lab Testing Market
Clinical Pathology Laboratories Should Expect More Direct-to-Consumer Testing
Sales of Direct-to-Consumer Clinical Laboratory Genetic Tests Soar, as Members of Congress Debate How Patient Data Should be Handled, Secured, and Kept Private
Apr 18, 2018 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
Three innovative technologies utilizing CRISPR-Cas13, Cas12a, and Cas9 demonstrate how CRISPR might be used for more than gene editing, while highlighting potential to develop new diagnostics for both the medical laboratory and point-of-care (POC) testing markets
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is in the news again! The remarkable genetic-editing technology is at the core of several important developments in clinical laboratory and anatomic pathology diagnostics, which Dark Daily has covered in detail for years.
Now, scientists at three universities are investigating ways to expand CRISPR’s use. They are using CRISPR to develop new diagnostic tests, or to enhance the sensitivity of existing DNA tests.
One such advancement improves the sensitivity of SHERLOCK (Specific High Sensitivity Reporter unLOCKing), a CRISPR-based diagnostic tool developed by a team at MIT. The new development harnesses the DNA slicing traits of CRISPR to adapt it as a multifunctional tool capable of acting as a biosensor. This has resulted in a paper-strip test, much like a pregnancy test, that can that can “display test results for a single genetic signature,” according to MIT News.
Such a medical laboratory test would be highly useful during pandemics and in rural environments that lack critical resources, such as electricity and clean water.
One Hundred Times More Sensitive Medical Laboratory Tests!
Co-lead authors Jonathan Gootenberg, PhD Candidate, Harvard University and Broad Institute; and Omar Abudayyeh, PhD and MD student, MIT, published their findings in Science. They used CRISPR Cas13 and Cas12a to chop up RNA in a sample and RNA-guided DNA binding to target genetic sequences. Presence of targeted sequences is then indicated using a paper-based testing strip like those used in consumer pregnancy tests.
MIT News highlighted the high specificity and ease-of-use of their system in detecting Zika and Dengue viruses simultaneously. However, researchers stated that the system can target any genetic sequence. “With the original SHERLOCK, we were detecting a single molecule in a microliter, but now we can achieve 100-fold greater sensitivity … That’s especially important for applications like detecting cell-free tumor DNA in blood samples, where the concentration of your target might be extremely low,” noted Abudayyeh.
“The [CRISPR] technology demonstrates potential for many healthcare applications, including diagnosing infections in patients and detecting mutations that confer drug resistance or cause cancer,” stated senior author Feng Zhang, PhD. Zhang, shown above in the MIT lab named after him, is a Core Institute Member of the Broad Institute, Associate Professor in the departments of Brain and Cognitive Sciences and Biological Engineering at MIT, and a pioneer in the development of CRISPR gene-editing tools. (Photo copyright: MIT.)
Another unique use of CRISPR technology involved researchers David Liu, PhD, and Weixin Tang, PhD, of Harvard University and Howard Hughes Medical Institute (HHMI). Working in the Feng Zhang laboratory at the Broad Institute, they developed a sort of “data recorder” that records events as CRISPR-Cas9 is used to remove portions of a cell’s DNA.
They published the results of their development of CRISPR-mediated analog multi-event recording apparatus (CAMERA) systems, in Science. The story was also covered by STAT.
“The order of stimuli can be recorded through an overlapping guide RNA design and memories can be erased and re-recorded over multiple cycles,” the researchers noted. “CAMERA systems serve as ‘cell data recorders’ that write a history of endogenous or exogenous signaling events into permanent DNA sequence modifications in living cells.”
This creates a system much like the “black box” recorders in aircraft. However, using Cas9, data is recorded at the cellular level. “There are a lot of questions in cell biology where you’d like to know a cell’s history,” Liu told STAT.
While researchers acknowledge that any medical applications are in the far future, the technology holds the potential to capture and replay activity on the cellular level—a potentially powerful tool for oncologists, pathologists, and other medical specialists.
Using CRISPR to Detect Viruses and Infectious Diseases
Another recently developed technology—DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR)—shows even greater promise for utility to anatomic pathology groups and clinical laboratories.
Also recently debuted in Science, the DETECTR system is a product of Jennifer Doudna, PhD, and a team of researchers at the University of California Berkeley and HHMI. It uses CRISPR-Cas12a’s indiscriminate single-stranded DNA cleaving as a biosensor to detect different human papillomaviruses (HPVs). Once detected, it signals to indicate the presence of HPV in human cells.
Despite the current focus on HPVs, the researchers told Gizmodo they believe the same methods could identify other viral or bacterial infections, detect cancer biomarkers, and uncover chromosomal abnormalities.
Future Impact on Clinical Laboratories of CRISPR-based Diagnostics
Each of these new methods highlights the abilities of CRISPR both as a data generation tool and a biosensor. While still in the research phases, they offer yet another possibility of improving efficiency, targeting specific diseases and pathogens, and creating new assays and diagnostics to expand medical laboratory testing menus and power the precision medicine treatments of the future.
As CRISPR-based diagnostics mature, medical laboratory directors might find that new capabilities and assays featuring these technologies offer new avenues for remaining competitive and maintaining margins.
However, as SHERLOCK demonstrates, it also highlights the push for tests that produce results with high-specificity, but which do not require specialized medical laboratory training and expensive hardware to read. Similar approaches could power the next generation of POC tests, which certainly would affect the volume, and therefore the revenue, of independent clinical laboratories and hospital/health system core laboratories.
—Jon Stone
Related Information:
Multiplexed and Portable Nucleic Acid Detection Platform with Cas13, Cas12a, and Csm6
Rewritable Multi-Event Analog Recording in Bacterial and Mammalian Cells
CRISPR-Cas12a Target Binding Unleashes Indiscriminate Single-Stranded DNase Activity
Researchers Advance CRISPR-Based Tool for Diagnosing Disease
CRISPR Isn’t Just for Gene Editing Anymore
CRISPR’s Pioneers Find a Way to Use It as a Glowing Virus Detector
With New CRISPR Inventions, Its Pioneers Say, You Ain’t Seen Nothin’ Yet
New CRISPR Tools Can Detect Infections Like HPV, Dengue, and Zika
Breakthrough DNA Editing Tool May Help Pathologists Develop New Diagnostic Approaches to Identify and Treat the Underlying Causes of Diseases at the Genetic Level
CRISPR-Related Tool Set to Fundamentally Change Clinical Laboratory Diagnostics, Especially in Rural and Remote Locations
Harvard Researchers Demonstrate a New Method to Deliver Gene-editing Proteins into Cells: Possibly Creating a New Diagnostic Opportunity for Pathologists
Mar 30, 2018 | Compliance, Legal, and Malpractice, Digital Pathology, Instruments & Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
Developers believe participants will be interested in controlling how their private health data is provided to medical laboratories, drug companies, research organizations, and the federal government, while also earning an income
Bitcoins for blood tests, anyone? A new venture is examining the idea of exchanging cryptocurrency, a digital asset, for the results of weekly clinical laboratory tests and photographs of body parts from healthcare consumers. If successful, in a couple of years, people might be able to earn a “basic income” from selling their private health data to pharmaceutical companies, medical laboratories, research organizations, the federal government, and more.
Insilico Medicine, a Baltimore developer of artificial intelligence (AI) solutions for research and pharmaceutical companies, and the Bitfury Group, a blockchain technology company based in Amsterdam, Holland, are working together on the project they call Longenesis, a blockchain-based platform that uses AI to collect, store, manage, and trade data, such as medical records and health data.
Marketing Human Life Data
The two participants presented their novel idea this past November in Taipei, Taiwan, at the TaiwanChain Blockchain Summit. They published their report in Oncotarget, an open-access biomedical journal that covers oncology research. The authors of the paper believe blockchain and AI technologies could support patients and physicians in working with medical data.
“There are many companies engaged in the marketplaces of human life data with billions of dollars in turnover. However, the advances in AI and blockchain allow returning the control of this data back to the individual and make this data useful in the many new ways,” Alex Zhavoronkov, PhD, founder of Insilico Medicine, told Cryptovest.
“I would love to live in a world where I’m motivated to regularly take all kinds of medical tests for free, I get the data back, and I will be able to sell this data to the marketplace, and I earn all kinds of goods and services—primarily health related,” Zhavoronkov told Motherboard.
Alexander Zhavoronkov, PhD, Founder and CEO of Insilico Medicine, told Motherboard, “Right now, it’s difficult to predict. But I think that if [users] submit blood tests, pictures, transcriptomes let’s say on a weekly basis, you probably will be able to earn a good universal basic income.” Zhavoronkov is describing a new business model involving clinical laboratory testing. (Photo copyright: Insilico Medicine.)
Combining blockchain and AI technologies is one of the many emerging technological advances emerging to enhance the medical and pharmaceutical industries.
“Recent advances in machine intelligence turned almost every data into health data. The many data types can now be combined in the new ways: one data type can be inferred from another data type and systems learning to optimize the lifestyle for the desired health trajectory can now be developed using the very basic and abundant data,” noted Polina Mamoshina, research scientist at Pharma AI, a division of Insilico Medicine, during the company’s presentation at TaiwanChain. “Pollen, weather, and other data about the environment can now be combined with the human biomarkers to uncover and minimize the allergic response among the myriad of examples. People should be able to take control over this data.”
Because pharmaceutical companies rely on data mining to obtain individual demographic information and medical records, the growth potential for this type of product is huge.
Clinical Laboratory Test Results Earn LifePound Tokens
Longenesis is still being tested, but Zhavoronkov hopes it will be ready for the public within the next two years. The plan is to utilize blockchain technology to collect and store patient medical data in exchange for their cryptocurrency, known as LifePound.
According to the Longenesis website, “Longenesis is a marketplace, which uses personal health data, transformed into a LifePound token. LifePound is used inside a marketplace as a monetary system, powered by Exonum blockchain technology to keep data secure and transparent. Tokens are distributed between Longenesis marketplace members and are used for transactions between the following elements:
- Developers;
- Users;
- Data providers;
- Customers; and the,
- Stock cryptocurrency market.
The developers believe the “Longenesis Data Marketplace will be able to provide new insights in the fields of healthcare research and development. It will provide analysis and recommendations to pharmaceutical companies to help develop new drugs.”
It’s too early to predict whether Longenesis will be successful and catch on with the public. However, the popularity of cryptocurrency, and the opportunity to earn an income from one’s clinical laboratory data, could encourage individuals to participate in this type of endeavor.
In addition, this is a highly unusual and unexpected approach to encourage consumers to undergo regular medical laboratory testing in order to earn payment by a digital currency. It is a reminder of how rapid advances in a myriad of technologies are going to make it possible for entrepreneurs to create new business models that involve clinical laboratory tests and the data produced by such tests.
—JP Schlingman
Related Information:
This Biotech Company Wants You to Give It Selfies and Blood Tests in Exchange for Cryptocurrency
A Decentralized Medical Record Marketplace Powered by Human Data
Blockchain, AI Could Spur Biomedical Research, Insilico Medicine Says
Converging Blockchain and Next-generation Artificial Intelligence Technologies to Decentralize and Accelerate Biomedical Research and Healthcare
Blockchain, Explained
