Research in the UK and US into how rapid WGS can prevent deaths and improve outcomes for kids with rare genetic diseases may lead to more genetic testing based in local clinical laboratories
Genetic scientists with the National Health Service (NHS) in England have embarked on an ambitious plan to offer rapid whole genome sequencing (rWGS) for children and babies with serious illnesses, as part of a larger initiative to embrace genomic medicine in the United Kingdom (UK).
The NHS estimates that the plan will benefit more than 1,000 children and babies each year, including newborns with rare diseases such as cancer, as well as kids placed in intensive care after being admitted to hospitals. Instead of waiting weeks for results from conventional tests, clinicians will be able to administer a simple blood test and get results within days, the NHS said in a press release.
The press release notes that about 75% of rare genetic diseases appear during childhood “and are responsible for almost a third of neonatal intensive care deaths.”
Here in the United States, pathologists and clinical laboratory managers should see this development as a progressive step toward expanding access to genetic tests and whole genome sequencing services. The UK is looking at this service as a nationwide service. By contrast, given the size of the population and geography of the United States, as this line of medical laboratory testing expands in the US, it will probably be centered in select regional centers of excellence.
“This strategy sets out how more people will be empowered to take preventative action following risk-based predictions, receive life-changing diagnoses, and get the support needed to live with genomically-informed diagnoses alongside improved access to cutting-edge precision [medicine] treatments. It also outlines how the NHS will accelerate future high-quality genomic innovation that can be adopted and spread across the country, leading to positive impacts for current and future generations,” the NHS wrote.
“This global first is an incredible moment for the NHS and will be revolutionary in helping us to rapidly diagnose the illnesses of thousands of seriously ill children and babies—saving countless lives in the years to come,” said NHS chief executive Amanda Pritchard (above) in a press release announcing the program. (Photo copyright: Hospital Times.)
New Rapid Whole Genome Sequencing Service
The NHS announced the plan following a series of trials last year. In one trial, a five-day old infant was admitted to a hospital in Cheltenham, Gloucester, with potentially deadly levels of ammonia in his blood. Whole genome sequencing revealed that changes in the CPS1 gene were preventing his body from breaking down nitrogen, which led to the spike in ammonia. He was given life-saving medication in advance of a liver transplant that doctors believed would cure the condition. Without the rapid genetic test, doctors likely would have performed an invasive liver biopsy.
Using a simple blood test, the new newborn genetic screening service in England is expected to benefit more than 1,000 critically ill infants each year, potentially saving their lives. “The rapid whole genome testing service will transform how rare genetic conditions are diagnosed,” explained Emma Baple, PhD, Professor of Genomic Medicine at University of Exeter Medical School and leader of the National Rapid Whole Genome Sequencing Service in the press release. “We know that with prompt and accurate diagnosis, conditions could be cured or better managed with the right clinical care, which would be life-altering—and potentially life-saving—for so many seriously unwell babies and children,” Precision Medicine Institute reported.
According to The Guardian, test results will be available in two to seven days.
Along with the new rWGS testing service, the NHS announced a five-year plan to implement genomic medicine more broadly. The provisions include establishment of an ethics advisory board, more training for NHS personnel, and an expansion of genomic testing within the existing NHS diagnostic infrastructure. The latter could include using NHS Community Diagnostics centers to collect blood samples from family members to test for inherited diseases.
UK’s Longtime Interest in Whole Genome Sequencing
The UK government has long been interested in the potential role of WGS for delivering better outcomes for patients with genetic diseases, The Guardian reported.
In 2013, the government launched the 100,000 Genomes Project to examine the usefulness of the technology. In November 2021, investigators with the project reported the results of a large pilot study in which they analyzed the genomes of 4,660 individuals with rare diseases. The study, published in the New England Journal of Medicine (NEJM) titled, “100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care—Preliminary Report,” found “a substantial increase in yield of genomic diagnoses made in patients with the use of genome sequencing across a broad spectrum of rare disease.”
The study’s findings suggest that use of WGS “could save the NHS millions of pounds,” The Guardian reported.
Whole Genome Sequencing System for Newborns in the US
“This NBS-rWGS [newborn screening by rapid whole genome sequencing] system is designed to complement the existing newborn screening process and has the potential to eliminate the diagnostic and therapeutic odyssey that many children and parents face,” Kingsmore said in a press release. “Currently, only 35 core genetic disorders are recommended for newborn screening in the United States, but there are more than 7,200 known genetic diseases. Outcomes remain poor for newborns with a genetic disease because of the limited number of recommended screenings. With NBS-rWGS, we can more quickly expand that number and therefore potentially improve outcomes through precision medicine.”
A more recent 2023 study which examined 112 infant deaths at Rady Children’s Hospital found that 40% of the babies had genetic diseases. In seven infants, genetic diseases were identified post-mortem, and in five of them “death might have been avoided had rapid, diagnostic WGS been performed at time of symptom onset or regional intensive care unit admission,” the authors wrote.
“Prior etiologic studies of infant mortality are generally retrospective, based on electronic health record and death certificate review, and without genome information, leading to underdiagnosis of genetic diseases,” said Christina Chambers, PhD, co-author of the study, in a press release. “In fact, prior studies show at least 30% of death certificates have inaccuracies. By implementing broad use of genome sequencing in newborns we might substantially reduce infant mortality.”
Pioneering work with whole genome sequencing for newborns, such as that being conducted by the clinical laboratory and genetic teams at Rady Children’s Hospital and the UK’s NHS, could allow doctors to make timely interventions for our most vulnerable patients.
Genomic sequencing continues to benefit patients through precision medicine clinical laboratory treatments and pharmacogenomic therapies
EDITOR’S UPDATE—Jan. 26, 2022: Since publication of this news briefing, officials from Genomics England contacted us to explain the following:
The “five million genome sequences” was an aspirational goal mentioned by then Secretary of State for Health and Social Care Matt Hancock, MP, in an October 2, 2018, press release issued by Genomics England.
As of this date a spokesman for Genomics England confirmed to Dark Daily that, with the initial goal of 100,000 genomes now attained, the immediate goal is to sequence 500,000 genomes.
This goal was confirmed in a tweet posted by Chris Wigley, CEO at Genomics England.
In accordance with this updated input, we have revised the original headline and information in this news briefing that follows.
What better proof of progress in whole human genome screening than the announcement that the United Kingdom’s 100,000 Genome Project has not only achieved that milestone, but will now increase the goal to 500,000 whole human genomes? This should be welcome news to clinical laboratory managers, as it means their labs will be positioned as the first-line provider of genetic data in support of clinical care.
Many clinical pathologists here in the United States are aware of the 100,000 Genome Project, established by the National Health Service (NHS) in England (UK) in 2012. Genomics England’s new goal to sequence 500,000 whole human genomes is to pioneer a “lasting legacy for patients by introducing genomic sequencing into the wider healthcare system,” according to Technology Networks.
The importance of personalized medicine and of the power of precise, accurate diagnoses cannot be understated. This announcement by Genomics England will be of interest to diagnosticians worldwide, especially doctors who diagnose and treat patients with chronic and life-threatening diseases.
Building a Vast Genomics Infrastructure
Genetic sequencing launched the era of precision medicine in healthcare. Through genomics, drug therapies and personalized treatments were developed that improved outcomes for all patients, especially those suffering with cancer and other chronic diseases. And so far, the role of genomics in healthcare has only been expanding, as Dark Daily covered in numerous ebriefings.
Genomics England, which is wholly owned by the Department of Health and Social Care in the United Kingdom, was formed in 2012 with the goal of sequencing 100,000 whole genomes of patients enrolled in the UK National Health Service. That goal was met in 2018, and now the NHS aspires to sequence 500,000 genomes.
“The last 10 years have been really exciting, as we have seen genetic data transition from being something that is useful in a small number of contexts with highly targeted tests, towards being a central part of mainstream healthcare settings,” Richard Scott, MD, PhD (above), Chief Medical Officer at Genomics England told Technology Networks. Much of the progress has found its way into clinical laboratory testing and precision medicine diagnostics. (Photo copyright: Genomics England.)
Genomics England’s initial goals included:
To create an ethical program based on consent,
To set up a genomic medicine service within the NHS to benefit patients,
To make new discoveries and gain insights into the use of genomics, and
To begin the development of a UK genomics industry.
To gain the greatest benefit from whole genome sequencing (WGS), a substantial amount of data infrastructure must exist. “The amount of data generated by WGS is quite large and you really need a system that can process the data well to achieve that vision,” said Richard Scott, MD, PhD, Chief Medical Officer at Genomics England.
In early 2020, Weka, developer of the WekaFS, a fully parallel and distributed file system, announced that it would be working with Genomics England on managing the enormous amount of genomic data. When Genomics England reached 100,000 sequenced genomes, it had already gathered 21 petabytes of data. The organization expects to have 140 petabytes by 2023, notes a Weka case study.
Putting Genomics England’s WGS Project into Action
WGS has significantly impacted the diagnosis of rare diseases. For example, Genomics England has contributed to projects that look at tuberculosis genomes to understand why the disease is sometimes resistant to certain medications. Genomic sequencing also played an enormous role in fighting the COVID-19 pandemic.
Scott notes that COVID-19 provides an example of how sequencing can be used to deliver care. “We can see genomic influences on the risk of needing critical care in COVID-19 patients and in how their immune system is behaving. Looking at this data alongside other omics information, such as the expression of different protein levels, helps us to understand the disease process better,” he said.
What’s Next for Genomics Sequencing?
As the research continues and scientists begin to better understand the information revealed by sequencing, other areas of scientific study like proteomics and metabolomics are becoming more important.
“There is real potential for using multiple strands of data alongside each other, both for discovery—helping us to understand new things about diseases and how [they] affect the body—but also in terms of live healthcare,” Scott said.
Along with expanding the target of Genomics England to 500,000 genomes sequenced, the UK has published a National Genomic Strategy named Genome UK. This plan describes how the research into genomics will be used to benefit patients. “Our vision is to create the most advanced genomic healthcare ecosystem in the world, where government, the NHS, research and technology communities work together to embed the latest advances in patient care,” according to the Genome UK website.
Clinical laboratories professionals with an understanding of diagnostics will recognize WGS’ impact on the healthcare industry. By following genomic sequencing initiatives, such as those coming from Genomics England, pathologists can keep their labs ready to take advantage of new discoveries and insights that will improve outcomes for patients.
Only 3% of histopathology departments that responded to the Royal College of Pathologists’ workforce census reported enough staff to meet clinical demand
There is a chronic shortage of histopathologists in the United Kingdom (UK) and it is being blamed for cancer treatment waiting times that now reach the worst-ever levels, as National Health Service (NHS) training initiatives and other steps fail to keep pace with growing demand for diagnostic services.
For US anatomic pathologists and clinical laboratory managers, headlines from the UK reveal the impact a shortage of trained histopathologists (UK’s version of anatomic pathologists) and support technical staff can have on patient care when longer wait times for pathology support and diagnosis become the norm.
Royal College of Pathologists Report
The extent of the UK-wide histopathology staff shortages was highlighted in a recently released 2017 workforce census by the Royal College of Pathologists (RCPath). Of the 103 histopathology departments that responded to a survey, only 3% said they had enough staff to meet the current clinical demand! And 45% of departments had to outsource work, while half of the departments were forced to use more expensive temporary workers.
“The cost of staff shortages across histopathology departments is high for both patients and for our health services,” Jo Martin, PhD, President of the Royal College of Pathologists, noted in a statement announcing the survey results. “For patients, it means worrying delays in diagnosis and treatment. For NHS hospitals, it means spending more resources on [temporary] doctors to fill staffing gaps, or outsourcing services. We estimate this cost [to be] £27 million ($35.2 million) each year across the UK health service—money that could be better invested in staff and new diagnostic equipment.”
Royal College of Pathologists President Jo Martin, PhD, is calling on the National Health Service to take additional steps to increase the number of pathologists working in the United Kingdom, including more funded training places. That’s following the release of a Royal College of Pathologists workforce survey, which reported only 3% of histopathology departments in the UK have enough staff to meet clinical demand. (Photo copyright: Twitter.)
According to iNews, NHS England recorded its worst cancer treatment waiting times on record in July 2018, with more than 3,000 people waiting longer than two months for cancer treatment to begin. NHS’ target is for 85% of patients to begin cancer treatment within 62 days of being referred by their general practitioner.
Anatomic pathologists in the United States should consider how the UK’s average delay in starting cancer treatment affects patients in that country. It is a metric that patients in the US would not tolerate. However, in the UK’s single payer system, the government’s National Health Service sets the budgets for training new physicians, including histopathologists. For many years, the pathology profession in the UK has regularly advocated for increasing the number of histopathologists trained each year by the medical schools in that country.
In July, the number of patients waiting for treatment longer than 60 days fell to 78.2%, the 31st month in a row the target was breached, iNews reported.
“We know that histopathology consultant shortages contribute to at least part of that problem,” Martin told iNews.
The RCPath report highlights the intense pressures on histopathologists—most of whom working in understaffed laboratories—face from increased workloads, as new NHS cancer screening initiatives, an aging population, and a shift toward precision medicine result in a rising number of cases being referred to labs.
“Demand for pathology services has grown significantly in recent years and continues to grow,” Martin noted in the RCPath statement. “The pathology workforce has not increased in line with this demand. If this trend continues unchecked, clinical services could be in jeopardy. Making sure pathology services can cope with current and future demand is essential if we are to ensure early diagnosis and improve outcomes for patients.”
Lack/Loss of Trained Histopathologists an Ongoing Problem
In its most recent workforce report, The Royal College of Pathologists is reiterating its call for:
Increased funding for training;
Better information technology (IT) for day-to-day work;
Capital investment to implement digital pathology more widely; and,
Development of advanced clinical practitioner apprenticeships to help more biomedical scientists become independent practitioners who would work alongside medically-qualified histopathologists.
Long-term, the organization is calling for additional training slots for pathologists in universities as well as other changes to draw more scientists into the field.
Aging Pathology Staff Means Shortages in US a Possibility
The NHS has stopped short of declaring the pathologist shortage a crisis. Instead, a Department of Health and Social Care spokesperson in an interview with the BBC highlighted recent initiatives taken in response to the shortage. “There are hundreds more pathologists in the NHS compared to 2010 and hospitals have reduced spending on temporary agency staff by over half a billion pounds in the last year,” the spokesperson noted. “We are listening to staff, encouraging more flexible working, and have increased medical training places for home-grown doctors by 25%, to ensure the NHS has the workforce it needs for the future.”
Despite those steps, the NHS may have more work to do. According to the Royal College of Pathologists workplace survey, a quarter of all histopathologists in the UK are 55 or older, adding an approaching retirement crisis to the existing shortage.
US anatomic pathology groups and clinical laboratories should monitor these events with a keen eye. The American pathology industry is challenged by many of the same trends, such as an aging workforce and lackluster replacement initiatives. Time will tell if the US learns from the UK’s experience.
Researchers are concerned about the lesser-known genes included in the test and also point out that little published research exists to support use of these genes for clinical laboratory testing
Gene-panel tests for inherited cancers were scrutinized by a group of 17 prominent international genetic researchers in a study published by the New England Journal of Medicine (NEJM) this summer titled “Gene-Panel Sequencing and the Prediction of Breast-Cancer Risk.” These experts pointed out that, for many of the genes included in these test panels, there remains much uncertainty about their role in various cancers and other diseases.
What will be of greatest interest to pathologist, Ph.D.s, and medical laboratory professionals currently performing molecular diagnostics assays and genetics is that these experts proposed greater regulation of unvalidated gene-panel tests for inherited cancers. In the NEJM, the authors provided some examples of genetic tests, such as those offered by Myriad Genetics, Inc. (NASDAQ:MYGN), Ambry Genetics, Invitae (NYSE:NVTA), and Illumina, Inc. (NASDAQ:ILMN) and noted that risks posed by many mutations occurring on these panels are unknown.
These panel tests can include more than 100 genes, 21 of which are an indication of breast cancer, including BRCA1 and BRCA2, stated the paper. (more…)
National Health Service agency admits to releasing information on 700,000 patients who opted out of nation’s new centralized medical-information database
In the United States, the debate is ongoing about how healthcare data is used while at the same time protecting patient privacy. The outcome of this debate will be increasingly important for medical laboratories because—in order to deliver more value—labs will want to combine lab test data with other sources of clinical information.
Thus, a similar debate over patient privacy and use of health data in the United Kingdom will be of interest to pathologists and clinical laboratory managers in this country. Recently, England’s National Health Service (NHS) came under fire for releasing information on about 700,000 patients against their wishes—a breach the NHS blamed on a lack of funding and “technical issues” encountered by the body responsible for overseeing the country’s big data initiative for healthcare.
700,000 Patients Opted Out of UK’s Centralized Medical Database
The Health and Social Care Information Centre (HSCIC) has admitted to Members of Parliament that medical details from as many as 700,000 patient records have been shared with organizations and companies, despite the fact that those patients opted out of NHS England’s new centralized medical database, Care.data. (more…)
