Viruses are between 27,000 to 48,500 years old and not dangerous, but researchers say thawing permafrost may one day release pathogens capable of infecting humans
Last fall, European researchers working with virologists and genetic scientists at the Aix-Marseille University in France reported having revived and characterized 13 previously unknown “zombie” viruses isolated from Siberian permafrost samples, including one that was almost 50,000 years old. This will be of particular interest to microbiologists and clinical laboratory managers since these organisms are new to science and may be precursors to infectious agents active in the world today.
The work of the European scientists demonstrates how advancements in genome sequencing and analysis of DNA data are becoming, faster, less expensive, and more precise. That’s good because the researchers warned that, should the permafrost continue to thaw, other previously dormant viruses could be released, posing potential risks for public health.
The pathogens isolated by the researchers are so-called “giant viruses” that infect Acanthamoeba, a commonly found genus of amoeba, and thus are not likely to pose an immediate health threat, the researchers wrote.
However, the scientists expressed concern. “We believe our results with Acanthamoeba-infecting viruses can be extrapolated to many other DNA viruses capable of infecting humans or animals. It is thus likely that ancient permafrost … will release these unknown viruses upon thawing,” they stated in their Viruses paper.
It’s unknown how long the viruses “could be infectious once exposed to outdoor conditions (UV light, oxygen, heat), and how likely they will be to encounter and infect a suitable host in the interval,” they added. However, “the risk is bound to increase in the context of global warming, in which permafrost thawing will keep accelerating, and more people will populate the Arctic in the wake of industrial ventures.”
“In nature we have a big natural freezer, which is the Siberian permafrost,” virologist Paulo Verardi, PhD (above), head of the Department of Pathobiology and Veterinary Science at the University of Connecticut, told The Washington Post. “And that can be a little bit concerning.” However, “if you do the risk assessment, this is very low. We have many more things to worry about right now.” Nevertheless, clinical laboratories may want to remain vigilant. (Photo copyright: University of Connecticut.)
Extremely Old, Very Large Viruses
The newly discovered viruses were found in seven different permafrost samples. Radiocarbon dating determined that they had been dormant for 27,000 to 48,500 years. But viruses contained in permafrost could be even older, the researchers wrote, as the time limit is “solely dictated by the validity range of radiocarbon dating.”
In their Viruses paper, the researchers noted that most of the 13 viruses are “at a preliminary stage of characterization,” and others have been isolated in the research laboratory “but not yet published, pending their complete genome assembly, annotation, or detailed analysis.”
“Every time we look, we will find a virus,” study co-author Jean-Michel Claverie, PhD, told The Washington Post. “It’s a done deal. We know that every time we’re going to look for viruses—infectious viruses in permafrost—we are going to find some.”
Claverie is a professor emeritus of genomics and bioinformatics in the School of Medicine at Aix-Marseille Université in Marseille, France. He leads a university laboratory known for its work in “paleovirology,” and in 2003, discovered the first known giant virus, dubbed Mimivirus. The research team included scientists from Germany and Russia.
According to CNN, unlike regular viruses that generally require an electron microscope to be viewed, giant viruses can be seen under a standard light (optical) microscope. Claverie’s laboratory previously isolated giant viruses from permafrost in 2014 and 2015.
Protecting Against Accidental Infection
To demonstrate the infectious potential of the viruses, the researchers inserted the microbes into cultured amoeba cells, which the researchers describes as “virus bait,” The Washington Post reported. One advantage of using Acanthamoeba cultures is to maintain “biological security,” the researchers wrote in their paper.
“We are using [the amoeba’s] billion years of evolutionary distance with human and other mammals as the best possible protection against an accidental infection of laboratory workers or the spread of a dreadful virus once infecting Pleistocene mammals to their contemporary relatives,” the paper noted. “The biohazard associated with reviving prehistorical amoeba-infecting viruses is thus totally negligible compared to the search for ‘paleoviruses’ directly from permafrost-preserved remains of mammoths, woolly rhinoceros, or prehistoric horses.”
The paper cites earlier research noting the presence of bacteria in ancient permafrost samples, “a significant proportion of which are thought to be alive.” These include relatives of contemporary pathogens such as:
“We can reasonably hope that an epidemic caused by a revived prehistoric pathogenic bacterium could be quickly controlled by the modern antibiotics at our disposal,” the researchers wrote, but “the situation would be much more disastrous in the case of plant, animal, or human diseases caused by the revival of an ancient unknown virus.”
However, according to The Washington Post, “Virologists who were not involved in the research said the specter of future pandemics being unleashed from the Siberian steppe ranks low on the list of current public health threats. Most new—or ancient—viruses are not dangerous, and the ones that survive the deep freeze for thousands of years tend not to be in the category of coronaviruses and other highly infectious viruses that lead to pandemics.”
Cornell University virologist Colin Parrish, PhD, President of the American Society for Virology, told The Washington Post that an ancient virus “seems like a low risk compared to the large numbers of viruses that are circulating among vertebrates around the world, and that have proven to be real threats in the past, and where similar events could happen in the future, as we still lack a framework for recognizing those ahead of time.”
Anthony Fauci, MD, former Director of the National Institute of Allergy and Infectious Diseases (NIAID), responded to an earlier study from Claverie’s lab by outlining all the unlikely events that would have to transpire for one of these viruses to cause a pandemic. “The permafrost virus must be able to infect humans, it must then [cause disease], and it must be able to spread efficiently from human to human,” he told The Washington Post in 2015. “This can happen, but it is very unlikely.”
Thus, clinical laboratories probably won’t see new diagnostic testing to identify ancient viruses anytime soon. But it’s always best to remain vigilant.
Project aims to create a new pangenome for genetic testing that will ensure better clinical laboratory testing and healthcare outcomes
Recent advances in genetics are motivating some scientists to proclaim the need to update the existing “master human genome”—currently based on a single individual’s genetic sequence—to make it more inclusive. This international research effort will have implications for personalized clinical laboratory testing and precision medicine.
Genetic scientists at the Human Pangenome Reference Consortium (HPRC), a project funded by the National Human Genome Research Institute (NHGRI), are working “to sequence and assemble genomes from individuals from diverse populations in order to better represent [the] genomic landscape of diverse human populations,” according to the organization’s website.
The project plans to evaluate a wide variety of reference genomes and develop a more diverse human pangenome (a multi-genome reference sequence) that will contain a larger cross-section of the human population. The HPRC scientists will be looking at genomes from specific countries, including Denmark, Japan, South Korea, Sweden, and the United Arab Emirates, The Guardian reported.
The increased diversity of reference genetic data will enable genomic researchers to increase the accuracy of precision medicine diagnostics and clinical laboratory testing.
“One person is not representative of the world,” Pui-Yan Kwok, MD, PhD (above), Henry Bachrach Distinguished Professor, Cardiovascular Research Institute at the University of California, San Francisco, told The Guardian. “As a result, most genome sequencing is fundamentally biased.” And that bias, the researchers claim, affects the accuracy of clinical laboratory treatments and diagnostics. (Photo copyright: UCSF.)
Reference Genome for Genetic Sequencing is Based on One Person
Launched in 1990, The Human Genome Project studied all DNA in a select set of organisms. The project completed its first sequence of the human genome in 2003, which became the reference genome for thousands of genomic discoveries since then.
But there’s a problem.
Although a revolutionary breakthrough in genetic sequencing, that reference genome came from just one person. This means a significant portion of the human population is not represented in genetic research, and that bias, according to some scientists, “limits the kind of genetic variation that can be detected, leaving some patients without diagnoses and potentially without proper treatment,” according to The Guardian.
“Getting the right medicine to the right patient at the right time is the tagline,” Neil Hanchard, MD, DPhil, physician scientist and senior investigator for precision health research at the NHGRI in Bethesda, Maryland, told The Guardian.
The HPRC’s goal is to help mitigate reference biases that could hamper disease diagnoses and ensure all populations receive the best treatments for illness.
According to its website, the organization’s main purpose includes:
Gene sequencing from a diverse set of samples with the newest technologies.
Fostering an ecosystem of assembly and pangenome tools.
Creating and releasing high-quality assemblies and pangenomes.
Embedding a team of scholars to address ethical, legal, and social implications of their work.
Forming international partnerships for the research.
HPRC Scientists Find Never-Sequenced Genetic Variants in Africa
Standard gene sequencing works by dividing DNA into tiny portions known as short reads, then sequencing and organizing the reads into a genome using an existing reference as a guide. However, this process renders larger blocks of variants, called structural variants (SVs), more difficult to read or even remain undetected, which can translate to a sequence that does not completely represent personal variations.
In 2019, the HPRC team of scientists analyzed genetic samples from 154 people from various parts of the world and discovered SV content that was missing from their reference sequence. A further study of genetic samples from 338 individuals that examined only extra inserted DNA detected the presence of almost 130,000 new sequences.
More recently, the HPRC researchers sampled 426 individuals from 50 ethnolinguistic groups from Africa and discovered a few million new single nucleotide variants (SNVs). Most of these distinct SNVs derived from populations that had not been previously sampled.
“We haven’t even touched SVs,” Hanchard told The Guardian. “But our preliminary data suggests it’s going to be more of the same.”
“We may miss risk variants in those regions not represented in the reference,” he added.
HPRC Receives Clearance from NHGRI to Continue Research
Hanchard recognizes the benefits of regional references in genomic sequencing and is optimistic about the future of genomics and the ability to sequence more diverse populations.
“I would love to get to a point where everyone feels represented and that this is for them, as much as it is for any particular group,” he told The Guardian. “We are from one humanity, that’s the important part.”
On February 13, the HPRC received concept clearance for renewal of the program from the NHGRI, which plans to commit up to $10 million in total costs per year for the program over the next five years.
Genetic sequencing continues to emerge as a vital tool in the diagnoses and treatment of diseases. Ensuring that as many diverse populations as possible are included in genomic research is an important element for precision medicine and optimal healthcare.
Clinical laboratory managers and pathologists will want to stay updated on these developments, because much of this new knowledge about the pangenome will need to be incorporated when interpreting genetic sequences and developing diagnoses in support of personalized medicine.
NIH program could lead to new diagnostic biomarkers for clinical laboratory tests across a more diverse segment of US population
In another milestone in the US National Institutes of Health’s (NIH) plan to gather diverse genetic information from one million US citizens and then use that data to inform clinical care in ways consistent with Precision Medicine, the NIH’s All-of-Us Research Program announced in a news release it has “begun returning personalized health-related DNA results” to more than 155,000 study participants.
In addition, those participants who request them will receive genetic reports that detail whether they “have an increased risk for specific health conditions and how their body might process certain medications.”
The All-of-Us program, which began enrolling people in 2018, is one of the world’s largest—if not the largest—project of its kind. It could result in more than a million human whole genome sequences to drive medical research and speed discoveries. Study findings, for example, may produce new biomarkers for clinical laboratory tests and diagnostics.
In 2020, the All-of-Us program “had begun releasing genetic results for ancestry and a small number of nonclinical genetic traits,” according to GenomeWeb. Now, the program is taking on the greater challenge of sharing health-related genetic test results directly with its participants.
“We really wanted to make sure that we are providing a responsible return to our participants,” Anastasia Wise, PhD, All-of-Us Program Director for the Genetic Counseling Resource, told GenomeWeb. “They might get information that’s unexpected,” she explained.
So far, about 10,000 people received the NIH’s invitation and 56% have shown interest in receiving their genetic test results, GenomeWeb noted.
“Knowledge is powerful,” said Josh Denny, MD (above), Chief Executive Officer, NIH All-of-Us Research Program, in an NIH news release. “By returning health-related DNA information to participants, we are changing the research paradigm, turning it into a two-way street—fueling both scientific and personal discovery that could help individuals navigate their own health,” he added. The NIH’s research could lead to new clinical laboratory precision medicine diagnostics for chronic diseases across a more diverse segment of the US population. (Photo copyright: National Institutes of Health.)
Two Types of Genetic Health Reports
Study participants who provided a blood sample and gave their consent to receiving genomic information may also receive a Hereditary Disease Risk report that includes 59 genes and genetic variants linked to serious and “medically actionable” health conditions.
About 3% to 5% of participants will have findings suggesting a high risk for a genetic disease such as breast and ovarian cancers as indicated by BRCA1 and BRCA2 genes, Medical Xpress reported.
“I kind of shudder to think about what could happen if I hadn’t known this [finding that she has the BRCA2 gene],” said Rachele Peterson, All-of-Us Chief of Staff, who spoke to the Associated Press about her receiving own Hereditary Disease Risk report.
Participants can also choose to receive an All-of-Us Medicine and Your DNA report with insights on seven genes that affect how specific medications are metabolized. This pharmacogenetics report is important for those who could learn, for example, that they have a 50% to 60% greater risk of a second heart attack when they continue to take the standard medication, as opposed to a different medication, Medical Xpress noted.
“The information on metabolizing medication can be particularly important for people who need treatment after a heart attack,” Josh Denny, MD, Chief Executive Officer, NIH All-of-Us Research Program, told Medical Xpress.
“Such transparency of genetic information about a massive group—as well as the genetic information on individuals—can be used to improve patient care and clinical outcomes,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.
“The program provides a roadmap for other healthcare organizations to follow. And this is useful strategic knowledge for clinical laboratory leaders to understand and incorporate into their plans to support precision medicine with genetic testing and whole human genome sequencing,” Michel added.
Rich Genetic Data Across a More Diverse Population
As to its goal to reflect national diversity, NIH reported about 80% of All-of-Us participants reside in communities that have been unrepresented in medical research, and that 50% are part of a racial or ethnic minority group.
By combining this information into a single database, the MVP promises to advance knowledge about the complex links between genes and health, according to an MVP news release.
Researchers tapping All-of-Us and MVP data may ultimately produce enlightening and impactful study findings, which could enable clinical laboratories to perform new diagnostic precision medicine tests that identify diseases early and save lives.
Proof-of-concept study ‘highlights that using AI to integrate different types of clinically informed data to predict disease outcomes is feasible’ researchers say
Artificial intelligence (AI) and machine learning are—in stepwise fashion—making progress in demonstrating value in the world of pathology diagnostics. But human anatomic pathologists are generally required for a prognosis. Now, in a proof-of-concept study, researchers at Brigham and Women’s Hospital in Boston have developed a method that uses AI models to integrate multiple types of data from disparate sources to accurately predict patient outcomes for 14 different types of cancer.
The process also uncovered “the predictive bases of features used to predict patient risk—a property that could be used to uncover new biomarkers,” according to Genetic Engineering and Biotechnology News (GEN).
Should these research findings become clinically viable, anatomic pathologists may gain powerful new AI tools specifically designed to help them predict what type of outcome a cancer patient can expect.
“Experts analyze many pieces of evidence to predict how well a patient may do. These early examinations become the basis of making decisions about enrolling in a clinical trial or specific treatment regimens,” said Faisal Mahmood, PhD (above) in a Brigham press release. “But that means that this multimodal prediction happens at the level of the expert. We’re trying to address the problem computationally,” he added. Should they be proven clinically-viable through additional studies, these findings could lead to useful tools that help anatomic pathologists and clinical laboratory scientists more accurately predict what type of outcomes cancer patient may experience. (Photo copyright: Harvard.)
AI-based Prognostics in Pathology and Clinical Laboratory Medicine
The team at Brigham constructed their AI model using The Cancer Genome Atlas (TCGA), a publicly available resource which contains data on many types of cancer. They then created a deep learning-based algorithm that examines information from different data sources.
Pathologists traditionally depend on several distinct sources of data, such as pathology images, genomic sequencing, and patient history to diagnose various cancers and help develop prognoses.
For their research, Mahmood and his colleagues trained and validated their AI algorithm on 6,592 H/E (hematoxylin and eosin) whole slide images (WSIs) from 5,720 cancer patients. Molecular profile features, which included mutation status, copy-number variation, and RNA sequencing expression, were also inputted into the model to measure and explain relative risk of cancer death.
The scientists “evaluated the model’s efficacy by feeding it data sets from 14 cancer types as well as patient histology and genomic data. Results demonstrated that the models yielded more accurate patient outcome predictions than those incorporating only single sources of information,” states a Brigham press release.
“This work sets the stage for larger healthcare AI studies that combine data from multiple sources,” said Faisal Mahmood, PhD, Associate Professor, Division of Computational Pathology, Brigham and Women’s Hospital; and Associate Member, Cancer Program, Broad Institute of MIT and Harvard, in the press release. “In a broader sense, our findings emphasize a need for building computational pathology prognostic models with much larger datasets and downstream clinical trials to establish utility.”
Future Prognostics Based on Multiple Data Sources
The Brigham researchers also generated a research tool they dubbed the Pathology-omics Research Platform for Integrative Survival Estimation (PORPOISE). This tool serves as an interactive platform that can yield prognostic markers detected by the algorithm for thousands of patients across various cancer types.
The researchers believe their algorithm reveals another role for AI technology in medical care, but that more research is needed before their model can be implemented clinically. Larger data sets will have to be examined and the researchers plan to use more types of patient information, such as radiology scans, family histories, and electronic medical records in future tests of their AI technology.
“Future work will focus on developing more focused prognostic models by curating larger multimodal datasets for individual disease models, adapting models to large independent multimodal test cohorts, and using multimodal deep learning for predicting response and resistance to treatment,” the Cancer Cell paper states.
“As research advances in sequencing technologies, such as single-cell RNA-seq, mass cytometry, and spatial transcriptomics, these technologies continue to mature and gain clinical penetrance, in combination with whole-slide imaging, and our approach to understanding molecular biology will become increasingly spatially resolved and multimodal,” the researchers concluded.
Anatomic pathologists may find the Brigham and Women’s Hospital research team’s findings intriguing. An AI tool that integrates data from disparate sources, analyzes that information, and provides useful insights, could one day help them provide more accurate cancer prognoses and improve the care of their patients.
Genetic testing for the health and wellbeing of beloved pets is not unlike clinical laboratory testing to develop personalized treatments for humans
Clinical laboratory professionals know that the same patients who complain about a $10 copay for their own laboratory testing will happily pay veterinarians tons of cash to test and treat their beloved pets. And as genetic testing for humans becomes commonplace, more people are seemingly willing to pay for genetic analyses of their pets as well.
In June, animal health company Zoetis, Inc. announced it had completed the acquisition of pet care genetics company Basepaws. The financial terms of the deal were not disclosed.
California-based Basepaws is a privately-held company that provides pet owners with analytics, genetic tests, and early health risk assessments for their pets through oral microbiome analysis. Founded in 2017, Basepaws was responsible for the creation of the first at-home genetic testing platform for cats.
Basepaws sells easy-to-use genetic testing kits for cats that allow pet owners and veterinarians to better understand an individual pet’s predisposition to certain illnesses and increase the likelihood of early detection and treatment of those diseases.
It’s not unlike the drive toward personalized medicine and genetic testing that is at the core of human precision medicine.
Different Breeds, Different Needs
Basepaws has a slogan: “Different breeds, different needs.” This means, according to their website, each individual cat has a unique composition of genetic traits that can relate to its needs for optimal health and wellbeing. Obviously, this would apply to all pets.
“As a pioneer in pet care genetics, the California-based Basepaws offers easy-to-use genetic screening tools for the early detection of disease risk in pets, as well as individualized breed and health reports that can identify traits, biomarkers, and potential hereditary conditions for pets. Basepaws helps pet owners and veterinarians understand an individual pet’s risk for disease and can lead to more meaningful engagements and increased likelihood of early detection and treatment of disease,” states a Zoetis press release announcing the acquisition.
“The addition of Basepaws will enhance our portfolio in the precision animal health space and inform our future pipeline of pet care innovations,” said Kristin Peck, CEO of Zoetis, in the press release. “Working together, we can continue to provide veterinarians and pet owners with more comprehensive ways to proactively manage the health, wellness, and quality of care for their animals.”
“Basepaws and Zoetis both consist of pet lovers with a passion for science, and our mission is to create better and longer lives for our pets through knowledge and data,” Anna Skaya (above), CEO of Basepaws, told ROI-N.J. “We look forward to expanding our business and the impact of our genetic products with the global scale and [research and development] experience of Zoetis, the world leader in animal health. We believe that, together, we can bring the benefits of a more proactive healthcare approach to pet parents around the world.” Genetic testing for optimum pet health is not unlike the drive for personalized clinical laboratory genetic testing for humans. (Photo copyright: Los Angeles Times.)
Test Results for Hundreds of Genetic Disorders and Health Markers
Basepaws currently sells three DNA test kits for felines on their webpage. The current price for an oral health test kit that identifies active signs of dental diseases is $69. Their breed and cat health DNA test kit, which provides results for over 115 known feline genetic markers, is $129. Their most comprehensive testing kit is a whole genome sequencing (WGS) kit which is currently on sale for $399.
After receiving a test kit by mail, the purchaser registers the kit online, takes a single buccal swab from their kitty’s inner cheek, and then mails the sample to Basepaws. Lab personnel then extract the cat’s DNA from the sample and perform quality checks to ensure the sample is acceptable for genetic testing. It takes four to six weeks for consumers to receive test results.
According to the company’s website, Basepaws’ WGS test provides results related to 43 genetic disorders that are represented by 65 health markers. The listing of genetic disorders contained in the Health Marker section of the Basepaws report includes data on:
Metabolic disorders,
Musculoskeletal and connective tissue disorders,
Renal disorders,
Cardiovascular disorders,
Blood disorders,
Eye disorders,
Endocrine disorders,
Skin disorders, and
Autoimmune disorders.
“The Basepaws team has done an amazing job demonstrating how genetic testing and data can improve how we care for the pets in our lives,” Abhay Nayak, Executive Vice President at Zoetis, told ROI-NJ. “With the addition of Basepaws, Zoetis will continue to strengthen our portfolio of products for precision animal health, across genetics, diagnostics, and data analytics for pets and livestock. We are also excited by how Basepaws’ feline genomic and microbiome database will help enhance our [research and development] capabilities and inform the future of our pet care pipeline.”
Zoetis, based in Parsippany, N.J., manufactures vaccines, medicines, clinical laboratory diagnostics, and other technologies for the benefit of companion pets and livestock. The Fortune 500 company generated $7.8 billion in revenue in 2021, according to its website.
The article also stated that the global animal genetic testing market was valued at $990 million in 2020 and is only expected to rise.
Thus, spending money keeping our pets healthy is not only a typical element of Americans’ lives, but also a mega-billion-dollar industry. With at-home genetic testing for humans increasing in popularity, it’s likely testing for animals will follow that trend as well.
In the future, some clinical laboratory organizations may want to consider assessing the animal DNA testing market for its potential to be a useful source of new revenue, especially because potential customers will pay cash when they order genetic tests for their dogs and cats.
