Researchers at UC Berkley developed new ways to use CRISPR as a genetic “search engine” in addition to a cut and paste tool
Clinical pathology laboratory professionals have long been aware of the potential diagnostic properties related to CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology. Now, new tests using the gene-editing tool show that potential is being realized.
One example involves using CRISPR to detect diseases in Nigeria, where a Lassa fever epidemic has already led to the death of 69 people this year alone. According the journal Nature, this diagnostic test “relies on CRISPR’s ability to hunt down genetic snippets—in this case, RNA from the Lassa virus—that it has been programmed to find. If the approach is successful, it could help to catch a wide range of viral infections early, so that treatments can be more effective and health workers can curb the spread of infection.”
Researchers in Honduras and California are working on similar projects to develop diagnostic tests for dengue fever, Zika, and the strains of human papillomavirus (HPV) that lead to cancer. There’s also a CRISPR-based Ebola test pending in the Democratic Republic of Congo.
These new genetic tests, which may be as simple as at-home
pregnancy tests to use, could save many lives throughout the world. They will
give medical laboratories new tools for diagnosing disease and guiding
therapeutic decisions.
Shift in How
Researchers View CRISPR
“We really think of CRISPR fundamentally as a kind of search engine for biology—like Google for biology—rather than [a kind of] word processing tool, although it’s really good at that too,” Trevor Martin, PhD, co-founder and CEO of Mammoth Biosciences, told CRISPR Cuts, a Synthego CRISPR podcast.
Professor of Biochemistry and Molecular Biology, and Li Ka
Shing Chancellor’s Professor in Biomedical and Health.
Martin’s statement represents a shift in how researchers are thinking about CRISPR. At first, CRISPR was seen as a tool for cutting and pasting genetic material. Scientists could tell it to find a target DNA sequence, make a cut, and paste in something different. However, by thinking of the tool as a search engine, CRISPR’s tremendous diagnostic potential becomes apparent.
“This is a very exciting direction for the CRISPR field to
go in,” Doudna told Nature.
Martin told CRISPR
Cuts that diagnostics is “fundamentally a search problem,” adding, “Now you
can program [CRISPR] to find something, and then tell you that result.”
Doudna notes in Technology Networks that, “Mammoth’s technology exemplifies some of the most urgent, impactful, and untapped potential in the CRISPR space.”
Fehintola Ajogbasile (above), a graduate student at the African Centre of Excellence for Genomics of Infectious Diseases in Nigeria, uses a CRISPR diagnostic test to look for Lassa virus in a blood sample. Similar clinical pathology laboratory tests are becoming available in the US as well. (Photo and caption copyright: Nature/Amy Maxmen.)
Investors See
Economic Benefits of CRISPR
The potential financial and economic impact of simple-to-use CRISPR-based diagnostic tools is considerable. Technology Networks notes that the diagnostics market is estimated at $45 billion, and that venture capital firms Mayfield, First Trust Mid Cap Core AlphaDEX Fund (NASDAQ:FNX), and 8VC have all invested in Mammoth Biosciences.
Although the diagnostics market is huge, a critical aspect
of the Lassa fever diagnostic test the Nigerian researchers are developing is
that it will be as accurate as conventional clinical laboratory testing
methods, but much simpler and less expensive.
Dhamari Naidoo, a technical officer at the World Health Organization (WHO) told Nature that researchers often fail to think about the fact that new technology must be affordable for use in low-income countries.
About a dozen diagnostic tests for Ebola have been
developed, according to Naidoo, but only two have been used recently in the
Democratic Republic of Congo, where the virus is resurging, due to economic
concerns. To be useful, medical laboratory tests in low-income countries must
be affordable to license and distribute, and critically, the manufacturers must
identify a market large enough to motivate them to make and distribute such
diagnostic tests.
Future Directions for
CRISPR and Clinical Pathology
Researchers first discovered what would come to be known as CRISPR in the early 1990s. However, it wasn’t until 2012 – 2013 that scientists used CRISPR and Cas9 for genome editing, a Broad Institute CRISPR timeline notes.
Now, researchers around the world are finding innovative
ways to employ the technology of CRISPR to detect disease in some of the most
remote, challenging areas where diseases such as Lassa fever, Zika, and dengue
fever among others, have devastated the populations, as Dark Daily has previously reported.
What’s next for clinical and pathology laboratories and
CRISPR? We’ll let you know.
Additional studies will be needed, but if the apparent causality proves out, it could lead to new clinical laboratory biomarkers to help determine women’s risk for developing cervical cancer.
New Cervical Cancer
Screening Biomarker for Clinical Labs, Pathology Labs?
Human gut bacteria (aka, gastrointestinal microbiota, a component of human microbiome) has been at the center of many revolutionary studies in past years, and has been the subject of many Dark Daily e-briefings. But this may be the first instance of the cervical microbiome being thought of as a potential biomarker in cancer screening.
To perform the research, the scientists obtained tissue samples taken from cervical lesions of 144 women who had undergone cervical cancer screenings in various locations throughout Tanzania between March 2015 and February 2016. The researchers then used a technique known as “deep sequencing” to sequence 16 Ribonucleic acid (RNA) genes from the samples.
One hundred and twenty-six of the women tested positive for HPV
and 41 tested positive for HIV. In addition, 50 of the women were diagnosed
with high-grade lesions that were likely to become cancerous.
And here is where the researchers made their discovery. They found that the “women with the high-grade lesions had a more abundant and diverse microbial mix in their cervical microbiomes than women who had no lesions or less serious lesions,” noted a UNL news release.
“There are certain families of bacteria that appear to be associated with the higher grades of precancerous lesions,” Lead Author Peter Angeletti, PhD, Associate Professor, Biological Sciences, University of Nebraska-Lincoln, noted in the news release. “What we know so far is that there is a relationship between the virus commonly associated with cervical cancer and the microbiome.”
Peter Angeletti, Associate Professor, School of Biological Sciences, and Cameron Klein, graduate student in virology, have discovered a link between the HPV (Human papillomavirus) virus and how various bacteria effect it’s growth. February 18, 2019. Photo by Craig Chandler / University Communication
The researchers found that a certain group of bacteria known as Mycoplasma may play a role in the growth of HPV-related cervical lesions. According to UNL, this type of bacteria is known to cause illnesses such as:
The World Cancer Research Fund (WCRF) lists cervical cancer as the fourth most common cancer occurring in women worldwide and the eighth most common cancer overall.
Cervical Cancer Rates in Sub-Saharan Africa
Nineteen of the top 20 countries for cervical cancer are located in Sub-Saharan Africa. The Centers for Disease Control and Prevention (CDC) reports that about one in four individuals in the US—nearly 80-million individuals—are currently infected with HPV.
At
one time, cervical cancer was the leading cause of cancer deaths for women in
the US. According to the CDC, there were 12,845 new cases of cervical cancer
reported in the US in 2015, and 4,175 women died of the disease that year.
Those numbers correlate to eight new cervical cancers reported per 100,000
women and two cancer deaths per 100,000 women in the US.
By contrast, in 2018, for every 100,000 women there were 75.3 new cervical cancer cases reported in Swaziland, the country with the highest rates of the disease, according to WCRF statistics.
There
were more than 500,000 new cases of cervical cancer reported worldwide in 2018.
However,
new cases of the disease and deaths from cervical cancer have decreased
significantly since regular Pap smears became a standard test for women in the
US.
The findings of this study indicate additional examination
of cervical microbiome could result in useful clinical laboratory data for
developing diagnostic tests and possible new treatments for cervical cancer.
That’s the premise behind a population health informatics program from Sonic Healthcare called iMorpheus. The program—in conjunction with Sonic Healthcare USA (SHUSA) laboratories throughout the US—provides physicians with “real-time clinical decision support and advanced healthcare informatics capabilities utilizing an agile pattern recognition software.”
This program is also a noteworthy example that demonstrates
two characteristics vital to the future success of the clinical laboratory industry.
First, the program is an early example of how clinical laboratories and
anatomic pathology groups can use lab test data to collaborate with physicians
in ways that add value in patient care. Second, this program also shows that
providers and others are ready to pay labs for that added value.
Sonic Healthcare is a global company serving the laboratory
medicine/pathology, radiology/diagnostic imaging, and primary care industries.
“If we have the laboratory data to identify people, what we
can do is help bring them in and get taken care of before a catastrophic event
happens. That is what our program is all about—how we use laboratory data to
identify people with chronic disease who are not being managed according to clinical
guidelines,” Philip
Chen, MD, PhD, a board-certified pathologist and the Chief Strategy Officer
at Sonic Healthcare USA, told Dark Daily.
Dr. Chen will be speaking on “How Labs Can Support Precision
Medicine and Shared Saving Initiatives” during a General Session at the 24th Annual Executive War College
April 30-May 1 in New Orleans.
Medicare Shared
Savings Program and Sonic’s iMorpheus Program
Data provided by Sonic Healthcare suggest its program—along
with services provided by clinical laboratories and physicians—can reduce
healthcare costs while helping providers earn rewards for their initiatives. “Laboratory
data are very strong. And a lab needs to have a basic knowledge of the
population. So, labs should look at their database, find out what they have,
and reach out to physician partners and find out what they have,” he added.
Sonic Healthcare aims to use iMorpheus to identify care gaps
and leverage clinical laboratory data to identify and help people manage their
chronic conditions, such as diabetes and other
chronic diseases.
As clinical laboratory leaders know, diabetics need to
obtain a hemoglobin
A1c (HbA1c) test every three to six months to gauge blood glucose levels
over a period of time. When Sonic Healthcare and ACO physicians roll out an
iMorpheus program, practice partners deploy Sonic’s automated technology to
share voice alerts with patients informing them that it’s time to follow-up
with their physicians. Patients also can connect to a scheduling center to set
an appointment.
The iMorpheus alerts encourage diabetics to get their lab
tests done in advance of the physician office visit, thereby saving the time
and expense of a second office visit.
“There are a lot more details to executing this. But what
the technology does is identify high-risk patients and bring them in before
they run into trouble,” Chen said.
The cost of treating diabetes in the US has risen to $327 billion in 2017, up from $245 billion in 2012, according the American Diabetes Association (ADA). The ADA study also indicated hospital inpatient care is 30% of cost, while physician office visits make up 13% of medical expenditures.
“This is not just a Sonic company program. It is a legitimate practice for legitimate value for the entire clinical laboratory and pathology profession. It’s what we can bring to the table, and we can become recognized for the value of the medical laboratory,” noted Philip Chen, MD, PhD, board-certified pathologist and Chief Strategy Officer at Sonic Healthcare USA. Chen will be speaking at the 24th Annual Executive War College in New Orleans April 30-May 1. (Photo copyright: Sonic Healthcare.)
iMorpheus Gets People
to Medical Labs, Physicians’ Offices
Sonic Healthcare studied the effectiveness of automated
patient engagements and pre-visits for lab services. They surveyed 39 primary
care practices with 207,248 patients, 14,438 of which are diabetics. According
the data, through the iMorpheus program:
The average days between visits for a diabetic
fell from 278 days to 218 days;
44% of patients returned to the clinic and had care
gaps and lab test needs fulfilled;
Half of the patients returning to outpatient
clinics had lab tests done within 24 hours;
35% to 45% of patients did not return to the physician’s
office (largely due to wrong phone numbers or new home addresses); and,
7% of patients chose to opt out of the automated
engagement service.
Clinical Laboratories
as Agents of Change
Sonic Healthcare’s program also contributed to lowering
Medicare costs, while enabling providers to share in the savings, according to case
study data shared by Chen. “With our program, the Shared Savings went from $12.8
million in the first year to $26 million in the second year of the program—with
payouts to laboratories,” Chen said.
Chen wants the clinical laboratory profession to be widely
recognized for its strategic use of big data. “This is one of those transformational
practices that labs can provide to fill a significant gap in the healthcare
ecosystem,” he said.
He describes the key takeaway: “We have been talking for
years about the medical laboratory being 3% of the healthcare spend, while it
influences 70% of healthcare decisions. We need to show that value and tie
things together.”
Lab100 is designed to be easily upgraded with the latest medical laboratory technologies for tracking patients’ health metrics and risk for chronic diseases
Mount Sinai Hospital
and Cactus, a New York City-based
design studio, are creating a hybrid clinical laboratory/research lab that uses
the latest diagnostic technologies to assess peoples’ health, provide them with
an overview of their current condition, and suggest lifestyle changes to
prevent future diseases.
Though still under development, Lab100 is an innovative approach to
modernizing annual physical/medical check-ups. It was created to empower
patients to track and understand their own health metrics and optimize their overall
health.
Lab100 looks at an individual’s medical history and measures
vital signs, blood analysis, anthropometrics, body
composition, cognition, dexterity, strength, and balance. It’s designed to be
more extensive than the traditional, annual physical, as well as to support the
implementation of preventative measures to avoid disease.
8-Station Clinical
Laboratory Built for Future Expansion
Lab100 consists of eight stations that are built on a
reconfigurable grid system that ensures the system can easily be upgraded with new
technology as it becomes available.
“By definition, no one knows what the future of healthcare
is, and neither do we. We made our best initial guess, recognizing that we’re
going to change based on the data we collect,” David Stark, MD, the
Director and founder of Lab100, told Business Insider. “It may turn out
that we jettison some of these stations and put in additional stations.”
“We’re trying to give patients more visibility, not only into their health, but into how healthcare happens with the hope that that visibility engages them as patients,” David Stark, MD, MS (above), Director and founder of Lab100, told Business Insider. Should Lab100 prove successful, it could become a model for future similar medical laboratories nationwide. [Photo copyright: Business Insider.]
Before visiting Lab100 patients complete a pre-visit
assessment consisting of standardized medical surveys including medical
history, nutritional habits, physical activity, mental health, and sleep
habits. With patients’ consent, individual data are shared with a select group
of researchers to potentially power new discoveries.
Lab100’s eight stations and their purposes are:
Station
One: A patient’s photograph is taken to put a face with the medical record.
The picture also allows researchers to perform more speculative work by
extracting facial features and correlating them with health metrics.
Station
Two: The patient’s vital signs (temperature, height, weight, blood
pressure, pulse, and oxygen levels) are taken.
Station
Three: A venous blood sample is extracted to measure electrolytes, nutrient,
and cholesterol levels. Patients do not need to fast for the blood draw. The
blood test is analyzed onsite and the results are available within 30
minutes.
Station
Four: The patient steps on a 3D full-body scanner where a depth-sensing
camera scans the body and creates a high-resolution 3D avatar of the
individual.
Station
Five: A body composition test is performed using bioelectrical
impedance analysis. A small electrical current is run through the body to
determine the distribution of water, fat, protein, and minerals in the body and
to measure how muscle and fat are distributed throughout the body.
Station
Six: Cognition is
analyzed using a traditional pegboard dexterity test. To perform this test, a
patient dons headphones and interacts with an Apple iPad to test vocabulary,
processing speed, flexibility, episodic memory, and attention.
Station
Seven: The patient’s overall strength is measured by utilizing virtual
reality to determine grip strength and push the patient to give their maximum
performance.
Station
Eight: The patient steps onto a balance pod to test their balance. An iPod
with an accelerometer
placed around the patient’s waist measures sway as the individual tries to stay
as still as possible.
The entire Lab100 process takes about 90 minutes and is one-on-one between patient and physician. Test results at each of the eight stations are held until the end of the visit where they are cumulatively displayed on a screen for the patient and physician to review. Blood analyses are included in patients’ work-ups. (Photos copyright: Lab100.)
Engaging Patients in
Their Own Healthcare
When patients complete their Lab100 experience, they should
have a better understanding of their current health and any changes they can make
in their lives to improve their health and possibly avoid future disease. The
results allow a patient to learn their risks for some diseases and whether
interventions—such as changes in diet and exercise—could alter those risks.
“The idea here is not to obsess over every number, but to
holistically look at what’s going well, what isn’t going well, and come away
with one to three domains that you as the patient want to focus on,” Stark
noted.
The initial Lab100 visit serves as a baseline for comparing
with future visits to measure improvements as a result of lifestyle changes. It
also allows patients to compare their health metrics to others in the same age
range.
Lab 100 is still in the testing stages and could be
available to the public later this year. It is not intended to be a replacement
for primary care and does not diagnose disease. It is intended to serve as a
complement to a traditional office visit and focuses on preventative measures
to avoid illness. The researchers involved in the Lab100 project hope the
environment can ultimately be used to produce new diagnostics, therapeutics, and
tools for measuring health.
Clinical laboratories could soon have new tests for determining how fast a patient’s digestive system is aging as part of a precision medicine treatment protocol
When it comes to assessing human age and longevity, much research has focused on telomeres in recent years. Now clinical laboratory managers and pathologists will be interested to learn that provocative new research demonstrates that the human microbiome may also contain useful information about aging. Microbes that can be diagnostic biomarkers may be one result of this research.
From preventing weight loss to improving cancer treatments to stopping aging, human microbiome—especially gut bacteria—are at the heart of many near miraculous discoveries that have greatly impacted clinical pathology and diagnostics development. Dark Daily has reported on so many recent studies and new diagnostic tools involving human gut bacteria it’s a wonder there’s anything left to be discovered. Apparently, however, there is!
Using artificial intelligence (AI) and deep-learning algorithms, researchers at Insilico Medicine in Rockville, Md., have developed a method involving gut bacteria that they say can predict the age of most people to within a few years. Located at Johns Hopkins University, Insilico develops “artificial intelligence for drug discovery, biomarker development, and aging research” notes the company’s website.
According to a paper published on bioRxiv, an online biomedical publications archive operated by Cold Spring Harbor Laboratory, the Insilico scientists have “developed a method of predicting [the] biological age of the host based on the microbiological profiles of gut microbiota” as well an “approach [that] has allowed us to define two lists of 95 intestinal biomarkers of human aging.”
“This microbiome aging clock could be used as a baseline to test how fast or slow a person’s gut is aging and whether things like alcohol, antibiotics, probiotics, or diet have any effect on longevity,” Alex Zhavoronkov, PhD (above), one of the study’s authors and founder of Insilico Medicine, told Science. (Photo copyright: Insilico Medicine.)
Clinical Laboratories
Might Be Able to Use AI and Gut Bacteria to Predict Age
To perform the study, the researchers collected 3,663 gut bacteria samples from 10 publicly available data sets containing age metadata and then analyzed the samples using a machine learning algorithm. The samples originated from 1,165 healthy individuals who were between the ages of 20 and 90. The individuals used for the study were from Austria, China, Denmark, France, Germany, Kazakhstan, Spain, Sweden, and the US.
The researchers divided the samples equally among three age
groups:
20 to 39 years old (young);
40 to 59 years old (middle aged); and,
60 to 90 years old (old).
The samples were then randomly separated into training and
validation sets with 90% of the samples being used for training and the
remaining 10% making up the validation set.
The scientists trained a deep neural network regressor to predict the age of the sample donors by looking at 95 different species of bacteria in the microbiome of the 90% training set. The algorithm was then asked to predict the ages of the remaining 10% of the donors by looking only at their gut bacteria.
They discovered that their computer program could accurately
predict an individual’s age within four years based on their microbiome. They also
were able to determine that 39 of the 95 species of bacteria examined were most
beneficial in predicting a person’s age.
In addition, the researchers found that certain bacteria in
the gut increase with age, while other bacteria decrease as people age. For
example, the bacterium Eubacterium
hallii, which is associated with metabolism in the intestines, was found to
increase with age. On the other hand, one of the most plentiful micro-organisms
in the gut, Bacteroides
vulgatus, which has been linked to ulcerative colitis,
decreases with age.
Understanding
Microbiome’s Link to Disease
The human microbiome consists of trillions of cells
including bacteria, viruses, and fungi, and its composition varies from
individual to individual. Scientific research, like that being conducted at
Insilico Medicine, expands our understanding of how gut bacteria affects human
health and how diseases such as inflammatory bowel disease, arthritis, autism, and obesity, are linked to the
microbiome.
This type of research could be used to determine how the
microbiomes of people living with certain illnesses deviate from the norm, and
possibly reveal unique and personalized ways to create healthier gut bacteria.
It also could help researchers and physicians determine the best interventions,
drugs, and treatments for individual patients dealing with diseases related to
aging. Such advancements would be a boon to precision medicine.
“Age is such an important parameter in all kinds of diseases.
Every second we change,” Zhavoronkov told Science. “You
don’t need to wait until people die to conduct longevity experiments.”
Further research is needed to develop these findings into
diagnostic tests acceptable for use in patient care. However, such tests could
provide microbiologists and clinical laboratories with innovative tools and
opportunities to help physicians diagnose patients and make optimal treatment
decisions.
Crash into Lake Zurich of American-made drone carrying blood specimens is first setback for pioneering Swiss Post medical drone program
Medical drones shuttling clinical laboratory specimens across open terrain is an exciting reality that Dark Daily has reported on in previous e-briefings. However, the medical drone revolution experienced a setback in January when drone-pioneer Swiss Post (Switzerland’s postal service) saw one of its American-made Matternet drones crash into Lake Zurich, Switzerland.
According to a Swiss Post news release, the drone went down carrying a “non-vital” blood sample (one that had been previously analyzed). The flight was part of a recently launched pilot program transporting blood samples between Zurich’s central laboratory and the Hirslanden Klinik Im Park, a private clinic on the opposite side of Lake Zurich.
A drone can cover the 5.8-kilometres across the water in seven minutes—five times faster than an on-the-road courier, according to Swiss Post.
Zurich city police recovered the drone from the lake on
January 28. However, until the cause of the accident is determined, Swiss Post has
grounded all drone flights, the news release noted.
This was the first accident involving Swiss Post drones,
which have successfully completed more than 3,000 flights in Lugano, Berne, and
Zurich.
A drone from California-based Matternet (shown above) flies toward the opposite side of Lake Zurich in Switzerland. Swiss Post, Switzerland’s postal service, is using drones to quickly transport clinical laboratory samples between hospitals in urban areas (Photo copyright: Swiss Post.)
Christian Hegner, Director General of Switzerland’s Federal Office of Civil Aviation, is proud of his country’s contribution to the development of performance-based regulatory models for the drone industry, which are detailed in the World Economic Forum (WEF) Advanced Drone Operations Toolkit. “The goal of this toolkit is to enable regulators to learn from the innovative policy experiments occurring around the world and empower them to adopt these governance models that accelerate the promise of drones for all,” he states in the toolkit.
“We have learned a lot in the last few years,” Hegner told SWI swissinfo.ch (SWI), the international reporting service of the Swiss Broadcasting Corporation (SBC). “Sharing our expertise and learning from other countries will help speed up and extend drone security around the world.”
Timothy Reuter, Head of Drones and Tomorrow’s Airspace at the World Economic Forum, and co-author of the Advanced Drone Operations Toolkit, believes it is only a matter of time before ecommerce and medical drones rule the skies. “We are witnessing the beginning of a logistics revolution; one that will redefine the way goods and people are moved around the world, and one that will drive social change alongside societal impact,” he states in the Advanced Drone Operation Toolkit. (Photo copyright: Quartz.]
Might Medical Drones
in the US Carry Clinical Laboratory Samples?
Now that the World Economic Forum has issued its “toolkit,” which is aimed at helping countries replicate the pioneering success of Switzerland and Rwanda in transporting blood and other medical specimens using unmanned aerial vehicles (drones), could the use of medical transport drones to deliver clinical laboratory specimens throughout the US could take off as well?
Maybe. Creation of such a medical transport network using
drones faces headwinds from aviation industry regulators.
“We haven’t seen the [FAA] be interested in a one-off approach,” Susan Roberts, PhD, told NPR. Roberts is Global Commercial Head of Innovation and Sales Excellence for Panasonic Avionics, and founder and former policy leader at AiRXOS, a General Electric subsidiary focused on drone infrastructure technology. “It doesn’t do anybody any good for a delivery company to be able to fly from two specific points if they can’t then scale that over and over again,” she noted.
Nevertheless, in its Advanced Drone Operations Toolkit, the WEF
argues a “unique opportunity exists today to harness the revolutionary power of
drones and autonomous aerial mobility,” and it provides a regulatory framework
to do so.
The crash of the Swiss Post drone carrying clinical
laboratory samples is a setback. However, it is also a learning experience. As Swiss
Post and other nations gain experience, and as regulatory models become established,
anatomic pathology groups and medical laboratories worldwide may finally have a
solution for delivering specimens over long distances while maintaining the
integrity of samples.
