Findings may help clinical laboratories identify healthcare workers who could work on the front lines of the next pandemic without fear of serious infection
University of California San Francisco researchers have discovered a gene mutation that enables some people’s immune system to recognize and respond to a COVID-19 infection despite having no prior exposure to the SARS-CoV-2 coronavirus (which would produce antibodies against future infections).
This genetic advantage will be of interest to clinical laboratory professionals and pathologists involved in immune system testing. Why some individuals with COVID-19 show few if any symptoms has confounded microbiologists and virologists since the beginning of the pandemic. Now, the UC San Francisco (UCSF) scientists believe they know why.
Dark Daily previously covered the UCSF study in “UCSF Researchers Identify Genetic Mutation That Promotes an Asymptomatic Response in Humans to COVID-19 Infection.” We covered how variations in a specific gene in a system of genes responsible for regulating the human immune system appears to be the factor in why about 10% of those who become infected with the virus are asymptomatic. And we predicted that understanding why some people display no symptoms during a COVID-19 infection could lead to new precision medicine genetic tests medical laboratories could use to identify people with the mutated gene.
“If you have an army that’s able to recognize the enemy early, that’s a huge advantage,” said immunogeneticist Jill Hollenbach, PhD, in a UCSF news release. Hollenbach led the research team that identified a mutated gene responsible for immune response to COVID-19 in individuals who have not been exposed to the SARS-CoV-2 coronavirus. Clinical laboratory professionals and pathologists involved in immune system testing will find the UCSF study useful. (Photo copyright: Elena Zhukova /University of California San Francisco.)
UCSF Study Details
UCSF researchers discovered that individuals who are COVID-19 “super dodgers” have “a mutation in the proteins that helps the immune system recognize what belongs to the body and what doesn’t,” Euronews reported.
The UCSF study showed that HLA-B*15.01—a Human Leukocyte Antigen (HLA) mutation—informs the body of the presence of SARS-CoV-2, regardless of whether it has encountered the invader before. The immune system then deploys T-cells [white blood cells called lymphocytes that help the immune system fight germs and protect the body from disease] to “eliminate” the coronavirus.
“Individuals with this B*15:01 mutation who have these cross-reactive T-cells seem to be particularly effective, very early in infection, at nuking—for lack of a better word—the virus before these folks experience any symptoms at all,” Jill Hollenbach, PhD, and immunogeneticist and Professor in the Department of Neurology and Department of Epidemiology and Biostatistics at UCSF, told STAT. Hollenbach led the team that discovered the gene mutation responsible for COVID-19 super dodgers.
“The mutation—HLA-B*15:01—is quite common, carried by about 10% of the study’s population. It doesn’t prevent the virus from infecting cells but, rather, prevents people from developing any symptoms. That includes a runny nose or even a barely noticeable sore throat,” according to a UCSF news release, which added, “UCSF researchers found that 20% of people in the study who remained asymptomatic after infection carried at least one copy of the HLA-B*15:01 variant, compared to 9% of those who reported symptoms. Those who carried two copies of the variant were far more likely—more than eight times—to avoid feeling sick.”
To find study participants, the team consulted The National Marrow Donor Program (NMDP) Be the Match Registry, which pairs donors with people needing transplants. It’s the largest registry of HLA volunteer donors in the United States. “Researchers suspected early on that HLA was involved, and fortunately a national registry existed that contained the data they were looking for,” the UCSF news release states.
To fully understand how COVID-19 affected the NMDP donors, the team utilized UCSF’s COVID-19 Citizen Science Study, a longitudinal cohort study on UCSF’s Eureka Digital Research Platform which uses a smartphone app developed by UCSF to learn how to predict SARS-CoV-2’s spread throughout the world and combat it.
About 30,000 people from the registry were followed through that first year of the COVID-19 pandemic, which featured frequent testing and no vaccine access for most, UCSF stated.
“We did not set out to study genetics, but we were thrilled to see this result come from our multidisciplinary collaboration with Dr. Hollenbach and the National Marrow Donor Program,” said internal medicine physician Mark Pletcher, MD, Professor of Epidemiology and Biostatistics at UCSF, in the news release. Pletcher’s practice focuses on prevention of cardiovascular disease.
The UCSF scientists dove deep to understand how HLA-B*15:01 tackled coronavirus, and together with researchers from La Trobe University in Australia, “They homed in on the concept of T-cell memory, which is how the immune system remembers previous infections,” UCSF reported.
“It’s just one of these natural lucky breaks,” Hollenbach told STAT.
UCSF Findings Bring Hope for Improved Vaccines and Drug Therapies
HLA was a good hunch to follow. The UCSF researchers’ Nature paper claimed HLA to be “the most polymorphic and medically important human genomic region.” It noted that variations of HLA were linked to myriad diseases, especially viral infections.
“The strongest associations were seen with viral infections, and HLA was associated with rapid progression and viral load of human immunodeficiency virus (HIV), hepatitis B, and C … Also HLA class I and II alleles have been associated with severe acute respiratory syndrome caused by SARS-CoV,” the Nature paper noted.
“Specific focus on asymptomatic infection has the potential to further our understanding of disease pathogenesis and supports ongoing efforts towards vaccine development and the identification of potential therapeutic targets,” the UCSF researchers wrote in Nature.
Should further research and studies confirm these findings, it’s reasonable to speculate that, in a future outbreak of new strains of SARS-CoV-2, clinical laboratories could test individuals to identify those with the mutation making them unlikely to experience a serious infection.
Those individuals could work on the front lines of medical care with a lower risk of infection and serious disease. It might also mean that they would not need vaccinations at all.
Genetic scientists show how rapid WGS is helping doctors determine best treatments for patients with life-threatening conditions
Clinical laboratory scientists will recall that last year, Dark Daily covered how researchers at Stanford University School of Medicine had developed a method for performing rapid whole genomic sequencing (WGS) in as little as five hours. We predicted that their new ultra-rapid genome sequencing approach could lead to significantly faster diagnostics and improved clinical laboratory treatments for cancer and other diseases. And it has.
The research scientist responsible for that breakthrough is cardiologist and Associate Dean of Stanford University School of Medicine, Euan Ashley, MD, PhD. Ashley is also a professor of genomics and precision health, cardiovascular medicine, genetics, and biomedical data science and pathology.
Ashley’s success demonstrates that the drive to reduce the diagnostic time to answer is a market dynamic encouraging research companies to continue finding ways to make WGS faster to accomplish, cheaper to perform, and the DNA sequences generated more accurate.
It is precisely these developments that will provide clinical laboratories and anatomic pathology groups with new means for improving diagnosis and the identification of the most appropriate therapies for individual patients—a core element of precision medicine.
Ashley’s team is now looking at how faster genetic sequencing results could help physicians make life-and-death treatment decisions, STAT reported.
“There’s just never been a better time to be doing genomics,” cardiologist Euan Ashley, MD, PhD, Associate Dean of the Stanford University School of Medicine, told STAT. “Now there are lots of choices. If you’re a genome center and you need to do half a million genomes, you’re going to be extremely price-sensitive. If you’re a clinical lab, where you get a few exomes and a few genomes every day, and what really matters to you is the highest possible accuracy for diagnosis, then you’re definitely going to make a different choice,” he added. (Photo copyright: euanangusashley.com.)
Getting Crucial Genetic Information Faster
Ashley believes that if doctors who work with rare and deadly diseases get crucial genetic information faster, they can more precisely determine which surgical procedures are best for their patients during life-or-death situations.
Already, his work is proving highly successful. In a letter his team published in the New England Journal of Medicine (NEJM), the researchers reported 12 cases of sequencing seriously ill patients, five of whom were diagnosed in seven hours and 18 minutes. Every single case resulted in tangible changes in treatments given to the patients.
“We continue to be interested in sequencing genomes faster and more accurately, for a broader range of clinical applications. We’re recruiting from intensive care units similar kinds of patients to the ones we did before, but with every aspect of the pipeline upgraded, which helps both from a speed but also from an accuracy perspective,” he told STAT.
Ashley and his team continue to delve into the patient care aspects, striving to continue to make a big impact. In addition, the group is being sought out by cancer doctors who need faster diagnoses.
“We also have a lot of interest from cancer doctors saying it’s really important to make a cancer diagnosis quickly. And of course, there is no person who’s ever had the specter of cancer hanging over them for a moment that didn’t want some kind of an answer faster. If you can have it in the next minute, you would take it rather than waiting several weeks,” he noted.
As a result, the group has initiated pilot studies “to look at returning results faster in the same way that we were speeding up the intensive care unit with whole genome sequencing,” Ashley told STAT.
Though the work is in the early stages, the team has a few scenarios where access to genetic data changes medical decision making. For instance, when genetic test results showing a positive BRCA variant alter a doctor’s surgical plan.
“We don’t wait for a cardiac enzyme [test] if somebody’s having a heart attack. That comes back within 10 minutes to a few hours from the lab. I don’t see why you should have to wait for a test to tell you if you’re positive for BRCA variant,” he told STAT.
“Another very obvious place is acute leukemia. And there’s a number of actionable conditions where if they can be detected rapidly, then treatment can be started faster,” he added.
Improving Genetic Sequencing Accuracy while Lowering Costs
STAT asked Ashley about a claim that his team could cut their Guinness World Record sequencing time in half.
“It’s easy to throw that number around, harder to deliver on it. But I think we’re definitely on track to knock hours, not minutes, off that record,” he said.
Additionally, the team continues to work on decreasing cost per genome. In just the time since the record was set, there has already been great strides in this area. The market is filled with new companies and the competition has lowered costs.
“It has definitely come down,” Ashely noted. “In fact, by the time we ended up publishing the [NEJM] paper—as opposed to when we first did this calculation—the cost was already lower. And that was actually before the entry of these new companies to the market, which added downward pressure on costs of sequencing,” he added.
Getting Payers to Reimburse for Genetic Sequencing
Even though costs for WGS is dropping, getting health plans to reimburse for genetic testing remains difficult.
“The challenge now is persuading payers to the very obvious fact that this technology makes patients’ lives better and saves them money,” Ashley told STAT. “And that’s the amazing part. There are so many cost-effectiveness studies now for this technology and yet we are still paying people to sit on the phone all day long and debate with insurance companies.
“And in a world where we pay a very large amount of money for therapeutics, these diagnostics can be cost-saving and lifesaving. At some level, it’s hard to understand why it hasn’t been deployed much more readily,” he concluded.
Clinical laboratory leaders, pathologists, and research scientists should continue to monitor the development of rapid genetic sequencing for diagnostic purposes.
Research could lead to new microbiome assays that clinical laboratories could use to identify genetic and other health conditions in developing baby
It would seem to be common sense, but now a study conducted by the Broad Institute of MIT and Harvard confirms that a pregnant mother’s microbiome has an effect on the development of her baby’s own gut microbiota. These findings could create opportunities for clinical laboratories to help in diagnosing a broader range of health conditions by testing the gut bacteria of pregnant mothers.
The Broad Institute’s study suggests the mother’s gut microbiome helps form the baby’s gut bacteria not only during pregnancy and birth, but into the baby’s first year of life as well.
“This study helps us better understand how the rich community of microbes in the gut initially forms and how it develops during infancy,” said Tommi Vatanen, PhD, a co-first author on the study who is now a researcher and associate professor at the University of Helsinki, in a Broad Institute news release. “The microbiome is very dynamic and develops along with other systems, so there’s a lot going on in the first years of life.”
“We’ve shown that the maternal microbiome plays an important role in seeding the infant microbiome, and that it’s not a one-time event, but a continuous process,” said gastroenterologist and senior study author Ramnik Xavier, MD, of the Broad Institute. Clinical laboratories and microbiologists may soon have new tools for testing a mother’s microbiome during pregnancy. (Photo copyright: Maria Nemchuk, Broad Institute.)
Study Highlights Physiological Connection Between Mother and Child
This study, according to the Broad Institute news release, is the “first to uncover large-scale horizontal gene transfer events between different species of maternal and infant gut bacteria.” The researchers also found that the bacteria in the mother’s microbiome “donate” genes that go into the bacteria of her unborn child. The mother’s genes help the baby in other ways as well during pregnancy and after birth.
“Benign bacteria in the maternal gut share genes with the child’s intestinal microbes during early life, potentially contributing to immune and cognitive development,” states the news release, adding, “The microbiomes of the mother and baby change during pregnancy and the first year of life … some bacteria in the mother’s gut donate hundreds of genes to bacteria in the baby’s gut. These genes are involved in the development of the immune and cognitive systems and help the baby to digest a changing diet as it grows.”
The study also sheds light on a baby’s unique metabolites (chemicals produced by bacteria) and how they connect with the mother’s microbiome.
“This is the first study to describe the transfer of mobile genetic elements between maternal and infant microbiomes,” gastroenterologist Ramnik Xavier, MD, Core Institute Member, Director of the Immunology Program, and Co-Director of the Infectious Disease and Microbiome Program at the Broad Institute, told Neuroscience News.
“Our study also, for the first time, integrated gut microbiome and metabolomics profiles from both mothers and infants and discovered links between gut metabolites, bacteria, and breastmilk substrates,” he added.
Researchers Use Multiomics
The human microbiome influences health in many ways. For several years, Broad Institute scientists have been trying to better understand the human microbiome and the role it plays in diseases like type 1 diabetes, cancer, and inflammatory bowel disease.
According to the organization’s website, the scientists recently began using multiomics techniques in their research that include:
Xavier and his colleagues were particularly interested in the development of the microbiome during the first year of the baby’s life.
“The perinatal period represents a critical window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites,” the researchers wrote in Cell. “Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to one year of age using longitudinal multiomics data.”
The researchers deployed bacterial DNA sequencing from stool samples of 70 mother and child pairs.
They found “hundreds of genes” in the infant gut bacterial genome that originated in the mother. According to the scientists, this suggests a mother does not transfer her genes all at once during childbirth. Instead, it likely occurs in an “ongoing” gene transfer from mother to baby through the baby’s first year of life, the news release explains.
Here are details on the study findings, according to Neuroscience News:
Genes associated with diet were involved in the “mother-to-infant interspecies transfer of mobile genetic elements.”
Infant gut metabolomes were less diverse than maternal metabolomes.
Infants had 2,500 unique metabolites not detected in the mothers.
Infants that received baby formula had distinct metabolites and cytokine signatures as compared to those receiving breast milk.
A link between pregnancy and an increase in steroid compounds could be due to impaired glucose tolerance in mothers.
“We also found evidence that prophages—dormant bacteriophages (viruses that reside on bacterial genomes)—contribute to the exchange of mobile genetic elements between maternal and infant microbiomes,” Xavier told Neuroscience News.
Research Could Lead to New Clinical Laboratory Assays
Microbiologists and clinical laboratory scientists are gaining a deeper understanding of the role gut bacteria play in many aspects of human life. But how a mother’s microbiome influences a baby’s development during and after birth is particularly intriguing.
“We’ve shown that the maternal microbiome plays an important role in seeding the infant microbiome, and that it’s not a one-time event, but a continuous process,” said Xavier in the Broad Institute news release. “This may be yet another benefit of prolonged bonding between mother and child, providing more chances for these beneficial gene transfer events to occur.”
Pediatricians, microbiologists, and clinical laboratories may one day have new microbiome assays to help identify a broad range of health conditions in mothers and infants and explore gut bacteria’s effects on a baby’s developing health.
There’s evidence that a cancer drug can cut deaths from lung cancer by as much as 50% when pathology testing indicates the patient has the EGFR mutation
Results from a decade-long clinical trial indicate that lung cancer patients with the epidermal growth factor receptor (EGFR) mutation have significantly better survival rates when treated with the drug osimertinib. This is a positive step forward for precision medicine and will give clinical laboratories an opportunity to deliver more value to physicians and patients.
The study known as ADAURA was led by scientists at Yale University and funded by British pharmaceutical/biotechnology company AstraZeneca. The researchers recently found that taking the cancer drug osimertinib (brand name Tagrisso) reduces by half the number of deaths among patients who had undergone surgery for EGFR–mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), according to NBC News.
Lung cancer has been one of the toughest types of cancers to diagnose early. When finally diagnosed, many patients do not have a good prognosis. Thus, the results of this multi-national study—and the connection involving patients with the EGFR gene—is a welcome development that promises better outcomes for cancer patients.
At the same time, this increases the value of EGFR as a biomarker for clinical laboratories and pathology groups that offer EGFR testing. It could become a companion diagnostic test—part of a clinical guideline for diagnosing lung cancer—that helps identify appropriate anti-cancer drugs for specific patients.
“Adjuvant osimertinib is currently the only EGFR tyrosine kinase inhibitor to translate a statistically significant and practice-changing disease-free survival benefit into a significant [overall survival] benefit in a phase 3 trial, supporting osimertinib as the standard of care for patients in this setting,” said Roy Herbst, MD, PhD, Deputy Director and Chief of Medical Oncology at Yale Cancer Center, who led the Yale study, at the 2023 ASCO Annual Meeting, according to an ASCO news release. (Photo copyright: Yale School of Medicine.)
Identifying Best Candidates for Specific Cancer Drugs
The results of the Yale-led study of the cancer drug osimertinib suggest that testing for a mutation in the EGFR gene could become part of the standard-of-care for NSCLC. Researchers found that NSCLC patients with the mutation showed improved survival rates and reduced risk of recurrence when taking the drug following surgery. EGFR tests could thus become companion diagnostics to determine whether patients are good candidates for the drug.
“We have been using one-size-fits-all adjuvant chemotherapy for every patient with lung cancer despite a decade of advances in targeted treatments for select groups of patients that result in dramatically better outcomes,” Nathan Pennell, MD, PhD, Vice Chair of Clinical Research and Director, Lung Cancer Medical Oncology Program Cleveland Clinic Taussig Cancer Institute, told the ASCO Post.
Pennell, who was not involved in the Yale research, described the finding as “a first for the lung cancer field,” and said adjuvant osimertinib “should be the new standard of care” for patients with EGFR-mutated NSCLC.
‘Practice-changing’ Cancer Drug
The study was led by Roy S. Herbst, MD, PhD, Deputy Director and Chief of Medical Oncology at Yale Cancer Center and Assistant Dean for Translational Research at Yale School of Medicine. Herbst is the principal investigator for the ADAURA global multi-site clinical trial which enrolled 682 patients with stage IB-IIIA NSCLC, in an effort to determine the efficacy of the cancer drug osimertinib, a pill taken once a day, which, according to NBC News, has fewer major side effects than chemotherapy.
The FDA approved the drug in 2015 for patients with advanced lung cancer. In 2020, the agency approved its use at earlier stages of the disease.
The ADAURA study included patients from 26 countries across Europe, North America, South America, and the Asia-Pacific region. About half of the patients took the pill each day for three years following surgery. The other half received a placebo.
According to a Yale news release, the researchers reported that 88% of patients treated with the drug were still alive five years later, compared with 78% of patients who received the placebo.
Earlier research demonstrated that the drug prevented recurrence of tumors and kept the disease from spreading to other organs, NBC News reported. “However, what we are seeing now is that patients will also live longer,” said oncologist Charu Aggarwal, MD, MPH, of the University of Pennsylvania’s Perelman School of Medicine, who was not involved in the study.
Herbst described the drug as “practice-changing” in the Yale news story.
An EGFR ‘Off Switch’
Non-small cell lung cancer is the most common form of lung cancer, The Guardian reported, adding that the EGFR mutation “is found in about a quarter of global lung cancer cases, and accounts for as many as 40% of cases in Asia. An EGFR mutation is more common in women than men and in people who have never smoked or have been light smokers.”
The mutation can cause cells to “excessively divide and multiply, which may cause cancer,” NBC News explained. Herbst described osimertinib as an “off” switch for the mutation.
“I think we’re curing some patients,” he said at the ASCO annual meeting, NBC News reported. “We’re really showing progress in lung cancer like never before,” he noted, adding that the results were “about twice as good as we expected.
“Overall survival has historically been considered the gold standard efficacy endpoint for randomized adjuvant clinical trials. The results of the ADAURA trial will broaden treatment access for patients with EGFR-mutated NSCLC,” Herbst told ASCO Post. “Together with the practice-changing disease-free survival data from our primary analysis, the overall survival benefit instills confidence that adjuvant osimertinib is the standard of care for patients with resected EGFR-mutated stage IB to IIIA NSCLC.”
Side effects of the pill include skin rashes and mild diarrhea, but in general the drug is “quite well tolerated,” Herbst said.
Impact on Labs
In Herbst’s view, the results of the Yale study demonstrate that patients diagnosed with lung cancer should be tested for the EGFR mutation, which is not always the case, The Guardian reported. “This further reinforces the need to identify these patients with available biomarkers at the time of diagnosis and before treatment begins,” he said.
Aggarwal agreed, telling NBC News that data from the study could be a “call to action” for more EGFR screening.
In light of the results, clinical laboratories and anatomic pathology groups should expect that EGFR screening may soon become a companion diagnostic test as part of a precision medicine clinical guideline for early diagnosing of lung cancer.
As scientists gain new insights into the human microbiome and how it influences our health, microbiology labs may gain new diagnostic biomarkers
In a study that took more than five years to complete, researchers from Stanford University have successfully created the first synthetic microbiome model from scratch. The goal of the study was to create a baseline microbiome model so that future studies will have a better understanding of which clinical laboratory tests and medical interventions could be useful for treating specific ailments and improving patient care.
To create their synthetic human microbiome, the Stanford researchers combined 119 species of bacteria, The New York Times reported, adding that “the new synthetic microbiome can even withstand aggressive pathogens and cause mice to develop a healthy immune system, as a full microbiome does.”
According to the National Institute of Health (NIH), the human gut contains trillions of microbes, and no two people share the exact same microbiome composition. This complex community of microbial cells influences human physiology, metabolism, nutrition and immune function, and performs a critical role in overall health.
The Stanford scientists believe researchers now have a common microbiome foundation for future microbial studies.
“We were looking for the Noah’s Ark of bacteria species in the human gut, trying to find the ones that were almost always there in any individual,” said Michael Fischbach, PhD, Associate Professor in the Departments of Bioengineering and Microbiology and Immunology at Stanford University. Future microbial studies that use Stanford’s synthetic human microbiome may develop improved clinical laboratory tests and microbiome therapies. (Photo copyright: Stanford University.)
Creating the ‘Human Community One’ Microbiome
The researchers began their study by examining the gut bacteria makeup of adults involved in the Human Microbiome Project (HMP), an NIH initiative created to sequence the full microbial genomes of more than 300 adults.
The scientists then selected bacterial strains that were present in at least 20% of the HMP individuals. They focused on 104 bacterial species that they grew in individual stocks, and then mixed them into one combined culture to create what they named “Human Community One” (hCom1).
The researchers had to ensure that the final mixture had the stability to maintain a balance where no single species overpowered the rest and could perform all the actions of a natural microbiome.
After being satisfied that the bacterial strains could coexist in a lab situation, the scientists set out to determine if their community would colonize in the gut. To do this, they introduced hCom1 to germ-free mice that are designed to have no natural microbiome.
When transplanted into the mice, the researchers discovered hCom1 was an extremely stable ecosystem, with 98% of the species taking root in the guts of the mice, and the levels of each bacterial species remaining constant over a two-month period.
“We colonized germ-free mice with hCom1 and found that it was stable over time. Its species span six orders of magnitude of relative abundance: from ~10% to less than one in 1,000,000,” Michael Fischbach, PhD, Associate Professor in the Departments of Bioengineering and Microbiology and Immunology at Stanford University and one of the authors of the study, explained on Twitter.
Based on a theory called colonization resistance, the team then introduced a human fecal sample to hCom1 to ensure that all vital microbiome functions would be performed by one or more species. Colonization resistance is the phenomenon where the normal gut microbiome protects itself against invasion by new and often harmful microorganisms. This theory hypothesizes that any bacterium introduced into an existing colony will only survive if it can fill a niche that is not already occupied.
Creating a Second New Microbiome
Some researchers involved in the project were skeptical that introducing human fecal matter to hCom1 would work. They believed it would overtake the synthetic microbiome model.
“The bacterial species in hCom1 had lived together for only a few weeks,” Fischbach explained in a Stanford press release. “Here we were introducing a community that had coexisted for a decade. Some people thought they would decimate our colony.”
However, the scientists found that hCom1 thrived with only about 10% of the cells in the final community originating from the fecal transplant. A few of the original bacterial species died off and approximately 20 new bacterial species were able to successfully colonize hCom1. They ultimately catalogued 119 bacterial strains present in the colony after the transplant and dubbed the new microbiome “Human Community Two” (hCom2).
To further prove the functionality of their synthetic microbiome, the team then introduced an Escherichia coli (E. coli) sample to mice colonized with hCom2 and found that they were able to resist infection.
“Mice colonized by hCom2 look normal immunologically, have similar microbiome-derived metabolites, and exert colonization resistance against E. coli,” said Fischbach on Twitter, “There are improvements to make, but we think hCom2 (in its current form) is a good model system of the microbiome.”
Future Microbial Studies
The Stanford team hopes its synthetic microbiome model will allow researchers around the world to have a common foundation for future studies and provide them with the ability to create engineered microbiome-based therapies.
“We built this consortium for the broader research community,” said Fischbach in the press release. “We want to get this into as many hands as possible to have an impact on the field.”
While direct links to new clinical laboratory tests and microbiome therapies have not yet been established, research like the Stanford study demonstrates the increasing value of the human microbiome as a source of diagnostic information that can guide decisions on better ways to treat patients.
Both programs seek to achieve early diagnosis by detecting a range of disorders where an existing treatment can be given as early as possible
Two separate genetic sequencing projects—one in the United Kingdom and one in New York City—aim to perform whole-genome sequencing for clinical laboratory diagnostic purposes on 100,000 newborns each to identify up to 200 rare genetic disease that are treatable with early diagnosis and intervention.
Genomics England announced its Newborn Genomes Program in 2022 and plans to start signing up expectant parents for the genetic sequencing project later this year, an article in Science reported. Parents will be invited to participate in the $129 million pilot program through the UK’s National Health Service (NHS) with the goal of enrolling 100,000 newborns over the next two years.
In the US, the Guardian Study (Genomic Uniform-screening Against Rare Diseases In All Newborns) was launched last year in New York City. The program will run for four years and sequence the DNA of 100,000 newborns looking for 160 rare genetic diseases. “Parents can opt to add 100 neurodevelopmental disorders that can’t be cured, but for which speech and physical therapy could help,” Science noted.
More than 200 babies have already been enrolled in the Guardian study, and about 70% of those invited to participate have agreed to do so, according to GenomeWeb.
“I think expanding the number of diseases we look for could make a radical improvement in the way we diagnose and treat children with rare diseases,” said molecular geneticist Wendy Chung, MD, PhD, Director of the Clinical Genetics Program at New York Presbyterian Hospital/Columbia University Medical Center, in a press release. Clinical laboratories that perform newborn screenings may soon have new genomic screening tools for a larger number of rare genetic disorders. (Photo copyright: Columbia University.)
Giving Parents the Ability to Make Informed Decisions
In many countries, newborns are screened for several dozen genetic illnesses via biochemical tests using a drop of blood collected from the baby’s heel. Whole-genome sequencing could potentially detect more disorders and allow for earlier care and treatments to avoid permanent disability or death.
Parents enrolled in the US/UK genomics sequencing programs will receive results for as many as 200 genetic diseases that are known to be caused by genetic variants and which typically display symptoms before the age of five. All the illnesses are treatable with remedies ranging from a simple vitamin supplement to a bone marrow transplant.
“For the parents who may be offered whole genome sequencing for their babies as part of our pilot, they need to know which of these many conditions will be looked for, so that they can make an informed decision about whether or not to take part in the study,” said pediatrician and geneticist David Bick, MD, Principal Clinician for the Newborn Genomes Program, in a Genomics England press release.
Parents will not receive data regarding gene variants with unknown risks or variants that only cause disease in adulthood.
Detecting a Range of Genetic Disorders in Newborns
The UK’s Newborn Genomes Program expects to identify genetic disease in at least 500 newborns. Researchers involved in the project estimate that utilizing genetic sequencing in newborns could detect those diseases in up to 3,000 babies if used across the country.
“The primary goal of the program is to detect a range of disorders where we already have an intervention that could be given at the earliest possible point in life to reduce disability or potentially to avoid harm,” said Sir Mark Caulfield, MD, Director of the William Harvey Research Institute at Queen Mary University of London and Chief Scientist for Genomics England, in a Queen Mary University press release.
“It turns out that approximately one in 190 births (circa 10 babies born every day in the UK) has one of these problems, and if the intervention is employed, this could be life changing. The majority of these interventions are dietary shifts or vitamin supplements, and only 8% are expensive treatments, for example, gene therapies or transplantation,” Caulfield noted. “The children may not be cured, but the interventions may reduce disability or even allow a normal life, so getting these life-changing opportunities to children at the earliest point is so important.”
The US initiative is using genomic sequencing to screen for 250 medical conditions that are not currently detectable in newborn screenings in New York. Like the UK program, these disorders are treatable and symptomatic before the age of five. The goal is to diagnose these illnesses earlier to allow for early treatment and better health outcomes.
“I think expanding the number of diseases we look for could make a radical improvement in the way we diagnose and treat children with rare diseases”, said Chung in a Columbia University press release. “Families and pediatricians don’t need to go through those diagnostic odysseys anymore with the genomic technology we now have. We can make the diagnosis at birth.
“I think genomic screening will also make sure we leave no baby behind. It will provide equitable access to a diagnosis,” Chung added. “We want to address health disparities, which we’ve seen happen after screening for SCID (severe combined immunodeficiency disorders) was added to state newborn screening panels. When every newborn is screened, the family’s socioeconomic status is irrelevant.”
Saving Children from Lifelong Disease
The US and UK genomics sequencing programs may have considerable influence on encouraging more newborn screening all over the world. Technological advancements in recent years have dramatically reduced genomic sequencing costs.
Additionally, sequences can be done faster and more accurately, and the technology is enabling complex analysis of data in ways that expands the information contained in the genome. This could lead to life-saving breakthroughs in treatment for many rare genetic disorders.
These developments may also encourage more clinical laboratories within the United States to consider offering a genome sequencing service for newborn screening. With hundreds of diseases now detectable through genetic technology, screening a newborn’s genome for mutations could provide more accurate and faster diagnosis of illnesses and potentially help more children avoid serious diseases.
