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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Cambridge University Researchers Develop and Administer Lab-developed Red Blood Cells in Clinical Study with Promising Results for the Blood Supply

Sickle cell patients and others who need long-term blood transfusions provided by clinical laboratories and others would benefit most from successfully lab-grown blood

Administering lab-developed red blood cells in humans in a clinical study conducted in the United Kingdom (UK) is being hailed as a significant step forward in efforts to supplement the supply of whole blood through the development of synthetic blood products. Of interest to those clinical laboratory managers overseeing hospital blood banking services, researchers were able to create this new blood product from normal blood pints collected from donors.  

What caused this clinical study to gain wider attention is the fact that previous attempts to create synthetic whole blood products have proved to be unsuccessful. For that reason, this new research has raised hopes that lab-grown blood may be just around the corner.

The initiative, known as RESTORE, is a joint research project conducted by scientists from the UK’s:

According to the researchers, it is the first such clinical trial performed in the world. Partial funding for this clinical study was provided by an NIHR grant, according to an NHS press release.

Most hospital laboratories also manage a blood bank. Thus, this breakthrough will be of interest to many clinical laboratory managers and blood bankers who are concerned about the shortage of blood products. Plus, blood products are quite expensive. This research could develop solutions that both ease the tight supply of blood and lower the cost of these critical products while improving patient care.

Neil O'Brien

“This research, backed by government investment, represents a breakthrough for patients and means treatment could be transformed for those with diseases including sickle cell,” said Neil O’Brien (above), Minister of State for Health, in an NHS press release. “Once again this shows the UK is leading the world when it comes to scientific innovation and collaboration while delivering high quality care to those who need it the most,” he added. If the lab-grown products prove clinically viable, medical laboratories in the UK may soon suffer less from a shortage of available blood. (Photo copyright: UK Parliament.)

Manufacturing Blood from Stem Cells

“This world-leading research lays the groundwork for the manufacture of red blood cells that can safely be used to transfuse people with disorders like sickle cell,” hematologist Farrukh Shah, MD, Medical Director Transfusion, NHS Blood and Transplant, told BBC News. “The need for normal blood donations to provide the vast majority of blood will remain. But the potential for this work to benefit hard-to-transfuse patients is very significant.”

The process of manufacturing blood cells starts with a normal donation of a pint of blood. The researchers then use magnetic beads to single out flexible stem cells that can become red blood cells. Those flexible stem cells are grown in large quantities in the lab and then guided to transform into red blood cells.

“This challenging and exciting trial is a huge stepping stone for manufacturing blood from stem cells,” said Ashley Toye, PhD, Professor of Cell Biology at the University of Bristol in the NHS press release. “This is the first-time lab grown blood from an allogeneic donor has been transfused and we are excited to see how well the cells perform at the end of the clinical trial.”

The process to create the lab-grown blood cells takes about three weeks, and a pool of approximately half a million stem cells can result in 50 billion red blood cells. These cells are then clarified further to reap about 15 billion red blood cells that are at the optimum level to transplant into a human patient.

“Some blood groups are extremely rare, to the point that only 10 people in a country can donate blood,” Toye told BBC News. “We want to make as much blood as possible in the future, so the vision in my head is a room full of machines producing it continually from a normal blood donation.”

Transforming Care for Patients Who Need Long-term Blood Transfusions

To date, only two patients have taken part in the clinical trial. Next, the researchers plan to perform two mini transfusions on 10 volunteers at least four months apart. One transfusion will contain traditional donated red blood cells and the other will consist of the lab-grown cells. This experiment will show which blood cells last longer in the body. The findings could ultimately allow a patient to receive fewer transfusions and prevent iron overload, which can be a side effect of blood transfusions.

“We hope our lab-grown red blood cells will last longer than those that come from blood donors,” said Cédric Ghevaert, MD, Senior Lecturer in Transfusion Medicine at the University of Cambridge, in the NHS press release. “If our trial—the first such in the world—is successful, it will mean that patients who currently require regular long-term blood transfusions will need fewer transfusions in the future, helping transform their care.”

More research and clinical trials will be necessary to validate the efficacy and safety of these lab-grown blood products. However, such a breakthrough could potentially revolutionize treatments for patients with blood disorders, complex transfusion needs, and rare blood types, as well as reduce healthcare costs and curb blood shortages.

At the same time, this technology would also contribute to expanding the supply of useful blood products, a development that would be welcomed by those pathologists and clinical laboratory professionals overseeing the blood banks in their respective hospitals and integrated delivery networks (IDNs).   

JP Schlingman

Related Information:

First Ever Clinical Trial of Laboratory Grown Red Blood Cells Being Transfused into Another Person

Lab-grown Blood Given to People in World-first Clinical Trial

Lab-grown Red Blood Cells Transfused into People in First Trial—NHS

Laboratory-Grown Blood Has Been Put into People in a First Clinical Trial

A Tale of Two Countries: As the US Ramps Up Medical Laboratory Tests for COVID-19, the United Kingdom Falls Short

Media reports in the United Kingdom cite bad timing and centralization of public health laboratories as reasons the UK is struggling to meet testing goals

Clinical pathologists and medical laboratories in UK and the US function within radically different healthcare systems. However, both countries faced similar problems deploying widespread diagnostic testing for SARS-CoV-2, the novel coronavirus that causes COVID-19. And the differences between America’s private healthcare system and the UK’s government-run, single-payer system are exacerbating the UK’s difficulties expanding coronavirus testing to its citizens.

The Dark Daily reported in March that a manufacturing snafu had delayed distribution of a CDC-developed diagnostic test to public health laboratories. This meant virtually all testing had to be performed at the CDC, which further slowed testing. Only later that month was the US able to significantly ramp up its testing capacity, according to data from the COVID Tracking Project.

However, the UK has fared even worse, trailing Germany, the US, and other countries, according to reports in Buzzfeed and other media outlets. On March 11, the UK government established a goal of administering 10,000 COVID-19 tests per day by late March, but fell far short of that mark, The Guardian reported. The UK government now aims to increase this to 25,000 tests per day by late April.

This compares with about 70,000 COVID-19 tests per day in Germany, the Guardian reported, and about 130,000 per day in the US (between March 26 and April 14), according to the COVID Tracking Project.

“Ministers need to explain why the NHS [National Health Service] is not testing to capacity, why we are falling behind other countries, and what measures they will put in place to address this situation as a matter of urgency,” MP Keir Starmer (above) said in Parliament in late March, The Guardian reported. (Photo copyright: The Guardian.)

What’s Behind the UK’s Lackluster COVID-19 Testing Response

In January, when the outbreak first hit, Public Health England (PHE) “began a strict program of contact tracing and testing potential cases,” Buzzfeed reported. But due to limited medical laboratory capacity and low supplies of COVID-19 test kits, the government changed course and de-emphasized testing, instead focusing on increased ICU and ventilator capacity. (Scotland, Wales, and Northern Ireland each have separate public health agencies and national health services.)

Later, when the need for more COVID-19 testing became apparent, UK pathology laboratories had to contend with global shortages of testing kits and chemicals, The Guardian reported. At present, COVID-19 testing is limited to healthcare workers and patients displaying symptoms of pneumonia, acute respiratory distress syndrome, or influenza-like illness, PHE stated in “COVID-19: Investigation and Initial Clinical Management of Possible Cases” guidance.

Another factor that has limited widespread COVID-19 testing is the country’s highly-centralized system of public health laboratories, Buzzfeed reported. “This has limited its ability to scale and process results at the same speed as other countries, despite its efforts to ramp up capacity,” Buzzfeed reported. Public Health England, which initially performed COVID-19 testing at one lab, has expanded to 12 labs. NHS laboratories also are testing for the SARS-CoV-2 coronavirus, PHE stated in “COVID-19: How to Arrange Laboratory Testing” guidance.

Sharon Peacock, PhD, PHE’s National Infection Service Interim Director, Professor of Public Health and Microbiology at the University of Cambridge, and honorary consultant microbiologist at the Cambridge clinical and public health laboratory based at Addenbrookes Hospital, defended this approach at a March hearing of the Science and Technology Committee (Commons) in Parliament.

“Laboratories in this country have largely been merged, so we have a smaller number of larger [medical] laboratories,” she said. “The alternative is to have a single large testing site. From my perspective, it is more efficient to have a bigger testing site than dissipating our efforts into a lot of laboratories around the country.”

Writing in The Guardian, Paul Hunter, MB ChB MD, a microbiologist and Professor of Medicine at University of East Anglia, cites historic factors behind the testing issue. The public health labs, he explained, were established in 1946 as part of the National Health Service. At the time, they were part of the country’s defense against bacteriological warfare. They became part of the UK’s Health Protection Agency (now PHE) in 2003. “Many of the laboratories in the old network were shut down, taken over by local hospitals or merged into a smaller number of regional laboratories,” he wrote.

US Facing Different Clinical Laboratory Testing Problems

Meanwhile, a few medical laboratories in the US are now contending with a different problem: Unused testing capacity, Nature reported. For example, the Broad Institute of MIT and Harvard in Cambridge, Mass., can run up to 2,000 tests per day, “but we aren’t doing that many,” Stacey Gabriel, PhD, a human geneticist and Senior Director of the Genomics Platform at the Broad Institute, told Nature. Factors include supply shortages and incompatibility between electronic health record (EHR) systems at hospitals and academic labs, Nature reported.

Politico cited the CDC’s narrow testing criteria, and a lack of supplies for collecting and analyzing patient samples—such as swabs and personal protective equipment—as reasons for the slowdown in testing at some clinical laboratories in the US.

Challenges Deploying Antibody Tests in UK

The UK has also had problems deploying serology tests designed to detect whether people have developed antibodies against the virus. In late March, Peacock told members of Parliament that at-home test kits for COVID-19 would be available to the public through Amazon and retail pharmacy chains, the Independent reported. And, Politico reported that the government had ordered 3.5 million at-home test kits for COVID-19.

However, researchers at the University of Oxford who had been charged with validating the accuracy of the kits, reported on April 5 that the tests had not performed well and did not meet criteria established by the UK Medicines and Healthcare products Regulatory Agency (MHRA). “We see many false negatives (tests where no antibody is detected despite the fact we know it is there), and we also see false positives,” wrote Professor Sir John Bell, GBE, FRS, Professor of Medicine at the university, in a blog post. No test [for COVID-19], he wrote, “has been acclaimed by health authorities as having the necessary characteristics for screening people accurately for protective immunity.”

He added that it would be “at least a month” before suppliers could develop an acceptable COVID-19 test.

Meanwhile, in the US, on April 1 the FDA issued an Emergency Use Authorization (EUA) for the qSARS-CoV-2 IgG/IgM Rapid Test developed by Cellex Inc. in N.C., the Washington Times reported. Cellex reported that its test had a 93.75% positive agreement with a PCR (polymerase chain reaction) test and a 96.4% negative agreement with samples collected before September 2019.

In the United States, the Cellex COVID-19 test is intended for use by medical laboratories. As well, many research sites, academic medical centers, clinical laboratories, and in vitro diagnostics (IVD) companies in the US are working to develop and validate serological tests for COVID-19.

Within weeks, it is expected that a growing number of such tests will qualify for a Food and Drug Administration (FDA) Emergency Use Authorization (EUA) and become available for use in patient care.

—Stephen Beale

Related Information:

Why the UK Failed to Get Coronavirus Testing Up to Speed

Even the US Is Doing More Coronavirus Tests than the UK. Here Are the Reasons Why

Fall in Covid-19 Tests Putting Lives at Risk, Critics Claim

UK Ministers Accused of Overstating Scale of Coronavirus Testing

Coronavirus: Government Sets Target for 100,000 Tests Per Day by End of Month

Coronavirus Test: UK To Make 15-Minute At-Home Kits Available ‘Within Days’

Coronavirus: Can I Get a Home Testing Kit and What Is an Antibody Test?

Covid-19 Testing in the UK: Unpicking the Lockdown

Current COVID-19 Antibody Tests Aren’t Accurate Enough for Mass Screening, Say Oxford Researchers

Thousands of Coronavirus Tests Are Going Unused in US Labs

Exclusive: The Strongest Evidence Yet That America Is Botching Coronavirus Testing

Coronavirus Testing Hits Dramatic Slowdown in US

Coronavirus Testing Is Starting to Get Better—But It Has a Long Way to Go

Was It Flu or the Coronavirus? FDA Authorizes First COVID-19 Antibody Test

Medical Laboratories Need to Prepare as Public Health Officials Deal with Latest Coronavirus Outbreak

Owlstone Medical and UK’s NHS Study Whether Breath Contains Useful Biomarkers That Could Be Used in Medical Laboratory Tests for Multiple Cancers

Owlstone Medical’s breath biopsy platform takes aim at breath biomarkers for an earlier diagnosis of cancer; could it supplant tissue biopsies sent to pathology labs?

For many years, medical laboratory scientists and pathologists have known that human breath contains molecules and substances that have the potential to be used as biomarkers for detecting different diseases and health conditions. The challenge was always how to create clinical laboratory test technology that could use human breath samples to produce accurate and clinically useful information.

Stated differently, breath, the essence of life, may contain medical laboratory test biomarkers that could provide early-detection advantages to pathology groups in their fight against cancer. Now diagnostics company Owlstone Medical—developer of the Breath Biopsy platform—is about to conduct a clinical study in collaboration with the United Kingdom’s (UK’s) National Health Service (NHS) and others to demonstrate the effectiveness of its breath-based diagnostic tests.

Anatomic pathology groups and clinical laboratory leaders know human breath contains volatile organic compounds (VOCs) that can be useful diagnostic biomarkers for medical laboratory testing. Many possible breath tests have been researched. One such test, the urea breath test for detecting Helicobacter pylori (H. pylori), has been in clinical use for 20 years. As part of the test, patients with suspect stomach ulcers or other gastric concerns, swallow a tablet with urea and exhale carbon dioxide that is measured for H. pylori bacteria.

According to an Owlstone Medical news release, the new study, called the “PAN Cancer Trial for Early Detection of Cancer in Breath,” will explore the ability of Owlstone Medical’s Breath Biopsy platform to detect cancers of the:

Current medical care standards call for these cancers to be diagnosed by analyzing biopsied tissue specimens. If Owlstone Medical’s breath test performs well during trial, it could provide advantages over traditional tissue-based cancer testing that include:

  1. A non-invasive approach to finding cancer earlier;
  2. A lower price point as compared to a tissue biopsy cancer test; and
  3. Faster return of test results, since tissue would not need to be collected from patients during surgical procedures and sent to medical laboratories for analysis.

“By 2030, the number of new cancer cases per year is expected to rise to around 22-million globally. Some cancers are diagnosed very late when there are few treatment options available. Non-invasive detection of cancer in breath could make a real difference to survival,” stated Richard Gilbertson, PhD, Li Ka Shing Chair of Oncology, Director of the CRUK Cambridge Center, and Oncology Department Head at University of Cambridge, in the news release.

How the Breath Biopsy Platform Works

The Breath Biopsy platform relies on Owlstone Medical’s Field Asymmetric Ion Mobility Spectrometry (FAIMS) technology, which the diagnostics company explains is a “fast means to identifying volatile organic compound biomarkers in breath.”

Billy Boyle (above), co-founder and Chief Executive Officer at Owlstone Medical, demonstrates the ReCIVA Breath Sampler. “Positive results from the PAN cancer trial could be game-changing in the fight against cancer,” he noted in the news release. “Success in this study supports our vision of saving 100,000 lives and $1.5 billion in healthcare costs.” This technology has the potential to be disruptive to anatomic pathology, which relies on the analysis of biopsied tissue to detect cancer. (Photo copyright: Owlstone Medical.)

Here is how FAIMS works in the Breast Biopsy platform, according to the Owlstone Medical website:

  • Gases are exchanged between circulating blood and inhaled fresh air in the lungs;
  • VOC biomarkers in the body’s circulation system pass into air in the lungs, along with oxygen, carbon dioxide, and other gases;
  • Exhaled breath contains those biomarkers exiting the body;
  • Because it takes one minute for blood to flow around the body, a breath sample during that time makes possible collection and analysis of VOC biomarkers of any part of the body touched by the circulatory system.

One publication compared the capture of VOCs to liquid biopsies, another possible non-invasive cancer diagnostic technique being widely researched.

“The advantage to VOCs is that they can be picked up earlier than signatures searched for in liquid biopsies, meaning cancer can be diagnosed earlier and treated more effectively,” reported Pharmaphorum in its analysis of five technology companies fighting cancer.

As part of the clinical trial, breath samples will be collected in clinic settings with the hand-held Owlstone Medical ReCIVA Breath Sampler (equipped with a dime-sized FAIMS silicon chip). The samples will come from people with a suspected cancer diagnosis who are seeking care at Cambridge University Hospital’s Addenbrooke’s Hospital. To test reliability of the biomarkers, breath samples from patients with cancer and without cancer will be analyzed.

“You’re seeing a convergence of technology now, so we can actually run large-scale clinical studies to get the data to prove odor analysis has real utility,” stated Owlstone Medical co-founder and Chief Executive Officer Billy Boyle, in a New York Times article.

Breath Tests Popular Area for Research

The company’s Breath Biopsy platform is also being tested in a clinical trial for lung cancer being funded by the UK’s NHS. The study involves 3,000 people, the New York Times article reported.

This is not the first time we have reported on Owlstone Medical. A previous e-briefing explored the company’s technology in a study focused on diagnosis of lung cancer (See Dark Daily, “In the UK, Pathologists Are Watching Phase II of a Clinical Trial for a Breathalyzer System That Uses Only a Breath Specimen to Diagnose Lung Cancer,” May 11, 2015.)

Breath tests in general—because they generally are non-invasive, fast, and cost-effective—have been the subject of several other Dark Daily e-briefings as well, including those about:

Owlstone Medical’s ability to get backing from Britain’s NHS, as well as investments to the tune of $23.5 million (the most recent coming from Aviva Ventures) is a positive sign. That Owlstone Medical’s Breath Biopsy platform is credible enough to attract such respected collaborators in the cancer trials as the Cancer Research UK Cambridge Institute (CRUK), University of Cambridge, and Cambridge University Hospitals (CUH) NHS Foundation Trust is evidence that the company’s diagnostic technology is considered to have good potential for use in clinical care.

Medical laboratory managers and pathology group stakeholders will want to monitor these developments closely. Once proven in clinical trials such as those mentioned above, breath tests have the potential to supplant other medical laboratory diagnostics and perhaps lower the number of traditional biopsies sent to labs for diagnosis of cancer.

—Donna Marie Pocius


Related Information:

Owlstone Medical and Cancer Research UK (CRUK) Initiate Pan Cancer Clinical Trial to Evaluate Breath Biopsy for Early Detection of Disease New Cancer Detecting Breath Test to Undergo Clinical Trials

Five Tech Companies Advancing Against Cancer

Aviva Invests in Owlstone Medical Breath Biopsy Platform and its Expected Drive Adoption of Breath Biopsy in Healthcare

Owlstone Medical’s ReCIVA Named Invention of the Year in Top 50 Digital Health Awards

One Day a Machine Will Smell Whether You’re Sick

Cancer Breath Biomarker: CRUK and Owlstone Start Multi-Cancer Trail

In the UK, Pathologists Are Watching Phase II of a Clinical Trial for a Breathalyzer That Uses Only a Breath Specimen to Diagnose Lung Cancer

Companies Developing Non-Invasive and Wearable Glucose-Monitoring Devices That Can Report Test Data in Real Time to Physicians and Clinical Laboratories

Wisconsin Company Developing Breath-Based Diagnostic Test Technology That Can Detect Early-Stage Infections Within Two Years of Onset

Study into Use of Breath Analysis to Monitor Lung Cancer Therapy Enhances Clinical Laboratories Ability to Support Precision Medicine

Rapid DNA Sequencing Used with Clinical Laboratory Tests to Halt MRSA Outbreak in English Hospital

Advanced DNA sequencing is poised to provide pathologists with a new tool for the management of infection control in hospitals

This may be a first for medical laboratory medicine. In England,  researchers used real-time advanced DNA sequencing to contain an infectious disease outbreak at a hospital. Rapid gene sequencing technology allowed them to bring the outbreak to a quick close. This saved other patients from harm and saved money for the hospital.

Clinical laboratory managers will be interested to learn that this ground-breaking episode occurred at Cambridge University Hospitals with the participation of the Wellcome Trust Sanger Institute and the University of Cambridge. Researchers from these institutions used insights gained from DNA sequencing to help stop a potentially deadly outbreak of Methicillin-resistant Staphylococcus Aureus (MRSA) at one of the Cambridge hospitals. The journal The Lancet Infectious Diseases  published the report. (more…)