Official Publication of the Academy of Clinical Science and Laboratory Medicine

Volume 46 Issue 1 Spring 2020

Coronavirus Coronavirus COVID-19 COVID-19 Proud Principal Sponsor of CRa1nn BioMedica Cruinn Diagnostics Limited

Providing Solutions for Laboratory Medicine In Ireland for over 22 years We look forward to seeing you at BioMedica 2020 in the Convention Centre at the rescheduled date of Monday 30th of November and Tuesday 1st of December 2020

SIEMENS.·. � • • •• Health1neers ·.• greiner bio-one Fcepheid. A better way.

lnova Diagnostics CHRQ)j}Magar A Werfen Company An Agilent Technologies Company Proud Principal Sponsor of CRa1nn BioMedica Cruinn Diagnostics Limited contents Volume 46 Issue 1 Spring 2020

editorial...... 4 message from the president...... 6 features Coronavirus Sars CoV 2 - COVID-19 ...... 9 The Blood is the Life – A Golden Age in Irish Blood Transfusion 1865 - 1879...... 12 Green Labs - Making Sustainable Labs a Reality...... 18 academy Testing Times...... 20 Zero to Three Hundred a Day...and Rising...... 22 National Transfusion Advisory Group...... 25 Page 12 CIT/UCC Biomedical Science Society...... 26 Just Another Day in the Lab...... 27 Guideline on Communication of Critical Results for Patients in the Community..... 28 The professional doctorate - a road less travelled...... 30 Providing Solutions Preparing for CORU registration - An Academy guide...... 31 cpd Let's work together...... 32 for Laboratory Medicine updates Health and Biomedical Science Updates...... 33 meetings In Ireland Page 26 Genomics Summit 2020...... 37 Multidisciplinary Seminar - Report on the joint CPD seminar ‘The Transplant/Immunocompromised Host’...... 36 for over 22 years Clinical Chemistry/Microbiology Joint Meeting...... 37 We look forward to seeing you at BioMedica 2020 in the The 16th National Health Summit...... 38 Convention Centre Dublin at the rescheduled date of research Monday 30th of November and HPV Primary Cervical Screening...... 41 Tuesday 1st of December 2020 Awards...... 42 President’s Prize...... 43 Evaluation of a Faecal Calprotectin Assay for introduction into routine testing in Biochemistry Laboratory, UHL ...... 43 Page 36 Angiotensin-Converting Enzyme 2 (Ace2) is a novel substrate for γ-Secretase-dependent Intramembrane Proteolysis...... 44 In Vitro Expansion of Human Placental Amnion Epithelial Cells...... 45 Investigation of the ability of the bacteriocin nisin to inhibit coagulase negative Staphylococci...... 46 Validation of the Ventana Mismatch Repair Immunohistochemical Panel for Colorectal Carcinoma Screening in ...... 47 Characterisation of a large group of Listeria Monocytogenes using whole genome SIEMENS.·. � sequencing: assessing their virulence potential...... 48 • • •• Health1neers ·.• greiner bio-one Fcepheid. book review A better way. The Discovery of Insulin...... 49

Page 37 ...... 50 lnova crossword Diagnostics CHRQ)j}Magar A Werfen Company An Agilent Technologies Company Spring 2020 • converse • 3 editorial

Healthcare workers have shown on Monday 30th November and 1st amazing commitment to their patients December 2020. We are aware that and communities in these extraordinary this decision will require industry times. None more so than medical professionals, exhibitors, partners scientists. I have seen at first hand and visitors to reschedule their the hard work and commitment of attendance, which will have an impact medical scientists to provide Covid-19 on their organisations, as it will for all testing. The solidarity and mutual of us. We are grateful that given the support is inspiring. Hidden heroes, current situation everyone involved rarely credited, usually mistitled and has understood and supported that hardly ever quoted about their work. decision. We are confident that these Ní neart go cur le chéile. Dr Tedros new dates will deliver an excellent Adhanom Ghebreyesus, Director of alternative. We are pleased to note the the WHO, and himself a microbiologist, large number of delegates who have has stated that diagnostic testing for registered for the conference already. COVID-19 is “critical to tracking the Registration and programme details virus, understanding epidemiology, are at www.biomedica.ie. We will keep informing case management, and all members and delegates updated to suppressing transmission”. regularly on developments. Medical scientists are vital frontline The President’s Prize competition Helen Barry professionals. Medical scientists will was as usual scheduled to be held do what is required to meet patient as part of BioMedica2020 in May. needs. Hopefully the public will see the be assured of supply. This is due to The winner of this competition goes importance of a world class laboratory global competition for the same pool forward to the European Association service. We hope, when this is all over, of reagents and consumables. We for Professions in Biomedical Science the HSE will understand the value of know how hard Anne Mannion and Student event to be held in November laboratories and medical scientists. Mary Keogan are working to identify in Spain. The Academy will organise an Maybe we are reaping the years of suppliers and ensure laboratories are alternative forum for this competition lack of investment in laboratories. As I resourced. I was delighted to hear that as soon as we return to normality. The often said back in the day, laboratories Colette Faherty had joined the team abstracts from the six finalists show yet were usually sited at the bottom of the at HSE. Colette has recently retired again the high standard of the student back stairs and microbiology was sited as Chief Medical Scientist in Galway projects. under that stairs. It surely is time for University Hospital. She is a wonderful The Academy continues to advocate investment in our medical scientists virologist with a lot of expertise and on behalf of medical scientists. and laboratories, improve infrastructure experience. She will be a great support Ensuring that medical scientists are and ensure fit for purpose laboratory to the team and to laboratories. Our represented at every relevant decision buildings. industry partners are also working making HSE and Department of Health The NVRL developed an in hard to identify solutions and develop group. We are only as strong as our house assay at the beginning of assays. membership. We would encourage this pandemic. Since then many In the context of the Covid-19 those members who have yet to renew commercial assays have been pandemic, we were obliged to their membership to do so as soon developed or are currently under postpone Biomedica2020. Working as possible. We would particularly development. However we know how in conjunction with the Convention encourage members to set up difficult it is for laboratories to access Centre Dublin (CCD) and in close standing orders. At €12.50 per month a sustainable supply of these. Even consultation with exhibitors and this is a relatively painless means of those laboratories with platforms and partners, the Academy rescheduled paying membership. contracts for supply of reagents cannot BioMedica, which will now be held Helen Barry, CEO

Editor: Helen Barry Converse is published three times a year. It is Deputy Editor: Anne Mac Lellan utilised for information exchange, communication and continuing education, managerial and Editorial Board: scientific, of the medical laboratory scientists of Anne MacLellan, Ireland. Brigid Lucey Publication of an article does not constitute Advertising: Roger Cole endorsement by the Academy of Clinical Science Silchester Marketing Ltd. and Laboratory Medicine of the products, techniques or organisations described therein. The Academy of Clinical Science and Tel: 01-285 9111 • Mobile: 087-2611597 Email: [email protected] The Academy of Clinical Science and Laboratory Laboratory Medicine, Medicine is an educational and scientific 31 Old Kilmainham, Dublin 8. Production/Design: Artworks Graphic Design organisation designed to serve as a resource Dalkey Business Centre, to advance the quality of medical laboratory Tel: 01-905 9730 17 Castle Street, Dalkey, Co. Dublin science. Fax: 01-902 2764 Tel: 01-2751707 • Mobile: 086-2611598 Members who wish to continue receiving Email: [email protected] Email: [email protected] Academy publications should notify the Academy Web: www.acslm.ie Web: www.artworksireland.com of any change of address.

4 • converse • Spring 2020 message from the president Message from the President

group listed all of their available than we have been accustomed to reagents which they were prepared to doing, while depending more upon hand to whoever needed them with no ourselves for contingency testing thoughts to their own tight budgets or solutions. their own future research needs. The launch of the Guidelines on the I have seen how groups of scientists Communication of Critical Results for working remotely were able to pool their Patients in the Community is timely and resources to assist with the production very welcome. of a reagent, which was then validated This has brought up two important for use by medical scientists. It reminds questions that should and need to me, however, that we are best placed to be addressed; (1) medical scientists act as gatekeepers in the validation of (laboratories) reporting results directly whatever is generated on our behalves to the patient, generally results are for use in the diagnostic effort as we are sent back to the requester (GP, responsible for our diagnostic work and, consultant), this guideline introduces a of course, continue to provide a quality possible deviation on that practice. We assured service. currently report and advise our medical From a training perspective, we colleagues but rarely the patient directly will need to facilitate our trainees to except in pre-defined and agreed complete their training, whenever that circumstances (e.g. anti-coagulation becomes possible. There are many and diabetes clinics). There is a need Dear All, differing arrangements ongoing for our to move this on through advanced I hope that this finds you and your trainees at the moment, depending on practice roles for our medical scientists families well and am pausing for a their stage and location. similar to the UK to expedite care to the moment to think of those who have lost Examinations have become open patient where necessary. their lives to the current pandemic. book and tending towards the broader (2) Patients having direct access to In the midst of the current challenges, interpretation in examination questions. their results. Direct reporting of selected we have simultaneously never been We have a duty to our students and test results to patients generally in the more isolated from one another nor also to keep the supply chain of newly- primary care setting is one system for more connected at the same time. trained medical scientists ongoing; we ensuring that important results are not Congratulations on your good, logical also have a duty, however to ensure missed. planning and expert work. Thank that the necessary learning outcomes Both scenarios would require specific goodness for internet and for scientific have been met for every module that we training for medical scientists dealing camaraderie. I have never felt so proud teach. with or reporting directly to the patient of our profession as during these past It cannot be argued that we have but in the long term could offer many weeks. Thank you for your helpful all had a lot of learning opportunities advantages to the patient. Literature communications also as they helped from the current crisis. When this shows that preferences for test result the Academy to know how to act in your phase of the pandemic is over we will notification can differ substantially best interests – and do continue to keep need to study what we have gleaned depending upon the test under in touch. The Academy have been quite from this learning opportunity to better consideration and results of the test. busy these past weeks in response to prepare for any other pandemic or Medical scientists with expertise your requests and I know that I speak world disaster that may come our way. in point of care testing could play an for everyone when saying that we are One wonders whether many of the important role in role in supporting glad to be of service. common colds that are inconvenient patient care in defined clinics and I do not want to miss this opportunity and highly transmissible are actually community and primary care. Medical to express gratitude to the many pandemics with lesser outcomes than scientists who lead and manage point volunteer medical scientists continually Sars-CoV-2 or whether our acceptance of care in the acute hospital are well being added to our database. This that influenza will come round year after equipped to extend that role out into the database is shared not only with year and cause thousands of deaths community. laboratory managers and with the HSE. annually is misplaced equanimity. All the very best, We have had many other scientists It seems to me that we, as medical offering to help us. One example was scientists and as part of the broader in creating a repository of information scientific community, will need to for all the diagnostic kits that were communicate better with the world available. On another day, the same scientific community to relay information

6 • converse • Spring 2020 BRENNAN

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Summer 2018 • converse • 7 BioMedica Diagnostics appoints Invitech for Ireland

BioMedica Diagnostics, the manufacturer of specialty range for several years in the UK. Invitech is also the coagulation and products for haemostasis and distribution partner for Orasure, AlphaTec, LDN and thrombosis diagnostics, has appointed Invitech Viramed and is a leading supplier of pregnancy tests Limited as its exclusive partner for the Republic of for professional use in the NHS. Ireland. Invitech, a distributor of diagnostics for Mike Annable professional use, has been promoting the BioMedica

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8 • converse • Spring 2020 feature Coronavirus Sars CoV 2 - COVID-19

n outbreak of viral pneumonia Dr. Tedros Adhanom Ghebreyesus, “So can be described as little blobs of liquid caused by a novel human every sector and every individual must be released as someone coughs, sneezes, Acoronavirus, severe acute involved in the fights. or talks. Viruses contained in these respiratory syndrome (SARS-CoV-2) The aim of this article falls in line with droplets can infect other people via the had first been detected and reported by WHO recommendations to educate all eyes, nose, or mouth either when they the World Health Organisation (WHO) and increase knowledge of this newly land directly on somebody’s face or in Wuhan City, Hubei Province of China emerged coronavirus. when they’re transferred there by people in late December 2019,1 and has since touching their face with contaminated spread throughout China and the wider Stigmatisation of hands. th Most persons infected with COVID-19 globe. One week later, on 7 January COVID-19 2020, Chinese authorities confirmed experience mild symptoms and recover. Since the emergence of COVID-19 in that they had identified a new virus in However, some go on to experience December, it’s become stigmatised humans of unknown origin. The new more serious illness and may require among specific populations, with the virus is a coronavirus. Coronaviruses hospital care. Risk of serious illness rises rise of harmful stereotypes reported by with age, individuals over the age of 40 are members of the subfamily the WHO in February of 2020. The risk “Coronavirinae” (family; Coronaviridae, seem to be more vulnerable than those associated with getting COVID-19 is under 40. Those with weakened immune 62 order; Nidovirales) that contains currently low across the globe. However, four genera alpha-coronavirus, beta- systems and people with conditions COVID-19 has been detected in almost such as diabetes, heart and lung disease coronavirus, gamma - 63 coronavirus every country. Stigmatisation could and delta -coronavirus. Coronaviruses are also more vulnerable to serious potentially contribute to more severe 6 cause illness ranging from the common illness. As the situation continues to health problems, ongoing transmission, rapidly evolve and expand, many cases cold, to more severe diseases such as and difficulties controlling infectious Severe Acute Respiratory Syndrome are appearing without a known source of diseases during an epidemic. Stigma exposure reported by the CDC.9 (SARS-CoV) and Middle-East Respiratory and discrimination can occur when Syndrome (MERS-CoV). This new virus Many governments are taking people associate an infectious disease, precautions to encourage anyone who has been officially named SARS-CoV-2, such as COVID-19, with a population may have come in contact with the virus which is responsible for the new disease or nationality. This isn’t the case, it’s a through travel to high or low risk areas COVID-19.2 global emergency and all populations are (or showing symptoms of influenza) There is still a lot unknown about associated with possible transmissions to self-quarantine for 14 days from the novel coronavirus (SARS-CoV-2), 8 and there is no time for complacency. the date they departed an affected however, current knowledge is mostly Initially, WHO stated there was a high region or country to avoid localised based on knowledge of existing risk of the 2019 coronavirus disease spreading within the community, with a coronaviruses including MERS-CoV and spreading to other countries around lot of countries enforcing “lockdown”.11 SARS-CoV.3 The WHO declared a global the world, WHO have reported that as Similar approaches to tackling emergency at the end of January. The th 4 April there are 1,133,758 cases with infectious disease spreading have been WHO director-general, Tedros Adhanom 5 62,784 deaths in 208 countries. implemented in previous epidemics Ghebreyesus stated: “The main reason Coronaviruses are zoonotic which such as the rise of Ebola in 2014 and the for this declaration is not because of what means the virus can be transmitted H1N1 influenza pandemic of 2009.12 is happening in China but because of between animals and humans.6 what is happening in other countries. Our Zoonotic viruses are commonplace greatest concern is the potential for this with approximately 60% of current Prevention of virus to spread to countries with weaker infectious diseases and 75% of all Transmission health systems, which are ill-prepared emerging infectious diseases in humans During previous coronavirus outbreaks to deal with it”.4 On 11th March the WHO being zoonotic according to the UNEP such as Middle-East Respiratory declared COVID-19 a pandemic, pointing Frontiers 2019 Report: Emerging Syndrome (MERS) and Severe Acute to the then over 118,000 cases of the Issues of Environmental Concern, Respiratory Syndrome (SARS), human- coronavirus illness in over 110 countries with approximately one new infectious to-human transmission occurred and territories around the world and the disease emerging in humans every four through droplets, contact and fomites, sustained risk of further global spread. months.7 suggesting that the transmission mode “This is not just a public health crisis, it is Like the flu, COVID-19 is spread of the COVID-19 may be similar. Issued a crisis that will touch every sector,” said primarily via respiratory droplets which by the CDC, basic principles to reduce

Spring 2020 • converse • 9 feature

the general risk of transmission of Figure 1 - Structure of the SARS- displayed similar spike studies from acute respiratory infections include the CoV-2 spike glycoprotein reveals the other coronaviruses, including SARS- following.13 architecture of the key player of viral CoV and MERS-CoV.18 • Avoiding close contact with people entry into host cells and provides a The new strain of coronavirus (SARS- suffering from acute respiratory blueprint for vaccine design. CoV-2) has spread more quickly than infections. SARS-CoV and MERS-CoV19. The new • Frequent hand-washing, especially strain of coronavirus is more severe in after direct contact with ill people or terms of the number of infected people their environment. when compared to both SARS-CoV and • Avoiding unprotected contact with farm MERS-CoV. However, the fatality rate is or wild animals. only around 2.2%, compared to SARS- • People with symptoms of acute CoV which had a fatality rate of 10%.19 respiratory infection should practice Researchers have highlighted that the cough etiquette (maintain distance, genome sequence of SARS-CoV-2 cover coughs and sneezes with also shows some similarities to that disposable tissues or clothing, and of MERS-CoV as both SARS-CoV and wash hands). MERS-CoV, cause severe respiratory • Within health care facilities, enhance syndrome in humans.20 However, greater standard infection prevention and emphasis has been placed on SARS- control practices in hospitals, especially CoV which is essentially what SAR-CoV-2 in emergency departments. has evolved from.21 Similarities of both SARS-CoV and MERS-CoV display COVID-19 –SARS, similar pathogenesis. Both SARS-CoV MERS and Coronavirus and MERS-CoV share several important Source: Gray, L. (2020). COVID-19 coronavirus common features that contribute to Composition spike holds infectivity details. Available: https:// nosocomial transmission, preferential The complete clinical picture of COVID-19 newsroom.uw.edu/news/covid-19-coronavirus- viral replication in the lower respiratory is not fully understood. Coronaviruses are spike-holds-infectivity-details. Last accessed tract, and viral immunopathology.22 a large family of viruses that are common 27th Feb 2020. SARS-CoV and MERS-CoV are the in many different species of animals, design of vaccines, antibodies, antivirals two major causes of severe pneumonia including camels, cattle, cats, and bats. and other therapeutics. In doing so, many in humans and share some common Initially, findings from the coronavirus researchers across the globe have based coronavirus structural characteristics, study group (CSG) of the international their research and practices on several which initially is the first major symptom committee of taxonomy of viruses outbreaks from the past where agents of COVID-19. Similarly, their genomic concluded that after viral genome analysis that the virus shares 88% of its Figure 2 genetic code with two bat-derived severe acute respiratory syndrome (SARS-Like) coronaviruses, however concluded the sequence was more distant from SARS- CoV. 14 The composition of coronavirus is enveloped with single-stranded ribonucleic acid, formally named for its solar corona like appearance to 9-12 nm- long surface spikes. The spikes crowning the new coronavirus that causes COVID-19 are typical of pneumonia divulging how they attach, fuse and gain entry to cells.15 Analysis of the spike architecture www.weforum.org/agenda/2020/02/comparing-outbreaks-coronavirus-mers-sars-health-epidemic/ (Figure 1) and its mechanics is locating the virus’s vulnerabilities, and revealing other information that could prompt the discovery of counter measures against this virus.16 Researchers across the globe are currently trying to determine the infectivity mechanism and to determine the structure and function of the SARS- CoV-2 spike protein and its chemical binding affinities. This understanding may allow development of an approach to ingress blockage to cells to fight off infection and to stimulate immune responses.17 Examining the spike protein structure www.weforum.org/agenda/2020/02/comparing-outbreaks-coronavirus-mers-sars-health- and function could ultimately facilitate the epidemic/

10 • converse • Spring 2020 feature

organization is typical of coronaviruses, Figure 3 - Schematic representation of the genome organisation and functional having an enveloped, single, positive- domains of S protein for SARS-CoV and MERS-CoV. stranded RNA genome that encodes four major viral structural proteins, namely spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins 3–5, that follow the characteristic gene order [5’-replicase (rep gene), spike (S), envelope (E), membrane (M), nucleocapsid (N)-3’] with short untranslated regions at both termini, as highlighted in figure 3.23 The single-stranded RNA genomes of SARS-CoV and MERS-CoV encode two large genes, the ORF1a and ORF1b genes, which encode 16 non-structural proteins (nsp1–nsp16) that are highly conserved throughout coronaviruses. These structural genes encode the structural proteins, which are common features to all known coronaviruses.24 With similarities in protein relationships among SARS-CoV, MERS-CoV and SARS-CoV-2, more and more studies have evaluated the underlying pathogenic mechanisms of SARS-CoV-2 Source: Song, Z et al. (2019). From SARS to MERS, Thrusting Coronaviruses into the Spotlight. to ensure there are more targets for Viruses MDPI. 11 (1-5), 1-30. better therapy of COVID-19. International coordination and cooperation led to the laboratory detection systems which were Martin Conway BSc Hons rapid identification of SARS-CoV and put in place in response to SARS-CoV ([email protected]) MERS-CoV in past years, combated and MERS-CoV outbreaks were both Marketing Executive by emergency control measures and exemplary. Randox Laboratories

References at: https://www.who.int/health- about/prevention-treatment.html topics/coronavirus (Accessed: 7 1) Lu R Zhao X Li J et al. (accessed 7 February 2020). February 2020). infectivity-details. Last accessed Genomic characterisation and 14) Lu R, Zhao, X, Li, J et al. 27th Feb 2020. epidemiology of 2019 novel 7) Lesney MS. 2019-nCoV: Just a Genomic characterisation and coronavirus: implications for virus Stop on the Zoonotic Highway. epidemiology of 2019 novel 19) World Economic Forum. (2020). 3 origins and receptor binding. https://www.medscape.com/ coronavirus: implications for virus charts that compare coronavirus Lancet. 2020; (published online viewarticle/924552 (accessed 7 origins and receptor binding. to previous outbreaks. Available: Jan 30.) https://doi.org/10.1016/ February 2020). Lancet. 2020 Jan 30:S0140- https://www.weforum.org/ S0140-6736(20)30251-8. 8) UN News. (2020). COVID-19: 6736(20)30251-8. doi: 10.1016/ agenda/2020/02/comparing- outbreaks-coronavirus-mers-sars- 2) Peiris JS Chu CM Cheng VC et More new virus cases outside S0140-6736(20)30251-8. health-epidemic/. Last accessed al. Clinical progression and viral China than in, ‘no time for 15) Wang Q, Wang YH, Ma JC et al. 27th Feb 2020. load in a community outbreak of complacency’, says UN health Description of the first strain of coronavirus-associated SARS agency. Available: https://news. 2019-nCoV, C-Tan-nCoV Wuhan 20) Cui, J.; Li, F.; Shi, Z.L. Origin pneumonia: a prospective study. un.org/en/story/2020/02/1058141. Strain — National Pathogen and evolution of pathogenic Lancet. 2003; 361: 1767-1772 Last accessed 27th Feb 2020. Resource Center, China, 2020. coronaviruses. Nat. Rev. Microbiol. 2019, 17, 181–192. 3) Centers for Disease Control 9) CDC. (2020). Transcript for the 2020. at http://weekly.chinacdc. and Prevention (CDC) (2020) CDC Telebriefing Update on cn/en/article/id/e3a460f1-661b- 21) A. Wu et al., “Genome How 2019-nCoV Spreads, COVID-19. Available: https://www. 4180-b562-ecd8e 9502082. composition and divergence of Available at: https://www.cdc.gov/ cdc.gov/media/releases/2020/ 16) Xu X, Chen P, Wang J et al. the novel coronavirus (2019- coronavirus/2019-ncov/about/ t0225-cdc-telebriefing-covid-19. Evolution of the novel coronavirus nCoV) originating in China,” Cell transmission.html (Accessed: 7 html. Last accessed 27th Feb from the ongoing Wuhan outbreak Host & Microbe, doi:10.1016/j. February 2020). 2020. and modeling of its spike protein chom.2020.02.001, 2020. 4) DW News (2020) Coronavirus: 10) Public Health England Novel for risk of human transmission. 22) De Wit, E.; van Doremalen, N.; WHO declares global health coronavirus (2019-nCoV) – what Sci China Life Sci. 2020 Jan 21. Falzarano, D.; Munster, V.J. SARS emergency, Available at: https:// you need to know. doi: 10.1007/s11427-020-1637-5. and MERS: Recent insights into www.dw.com/en/coronavirus- 11) https://publichealthmatters.blog. 17) Yang Y, Lu Q, Liu M et al. emerging coronaviruses. Nat. who-declares-global-health- gov.uk/2020/01/23/wuhan-novel- Epidemiological and clinical Rev. Microbiol. 2016, 14, 523. emergency/a-52209762 coronavirus-what-you-need-to- features of the 2019 novel 23) Song, Z et al. (2019). From SARS (Accessed: 7 February 2020). know/Date: 2020 (accessed Jan coronavirus outbreak in China. to MERS, Thrusting Coronaviruses 5) ECDC. (2020). Areas with 31, 2020). medRxiv preprint first posted into the Spotlight. Viruses MDPI. presumed community 12) Barbisch D, Koenig KL,Shih FY.Is online February 11, 2020. doi: 11 (1-5), 1-30. https://doi.org/10.1101/2020.02.1 transmission of COVID-19, as there a case for quarantine? 24) Du L., Yang Y., Zhou Y., Lu 0.20021675. Accessed February of 25 February 2020. Available: Perspectives from SARS to Ebola. L., Li F., Jiang S. MERS-CoV 13, 2020. https://www.ecdc.europa.eu/en/ Disaster Med Public Health Prep. spike protein: A key target for areas-presumed-community- 2015; 9: 547-553 18) Gray, L. (2020). COVID-19 antivirals. Expert Opin. Ther. transmission-2019-ncov. Last 13) Centers for Disease Control and coronavirus spike holds infectivity Targets. 2017;21:131–143. doi: accessed 26th Feb 2020. Prevention (CDC). Prevention details. Available: https:// 10.1080/14728222.2017.1271415. 6) World Health Organization (WHO) & Treatment. https://www.cdc. newsroom.uw.edu/news/covid- (2020) Coronavirus, Available gov/coronavirus/2019-ncov/ 19-coronavirus-spike-holds-

Spring 2020 • converse • 11 feature The Blood is the Life – A Golden Age in Irish Blood Transfusion 1865 - 1879.

John O'Loughlin, Laboratory Manager –

s a member of the Rotunda Historical Society and in Fig 1: Four Main Eras of Blood Transfusion preparation for the Rotunda's 275th anniversary and Athe birth of our one millionth baby, I stumbled upon Era Description a reference to a blood transfusion carried out in 1877 at the 1 - pre-19th Century Early experiments usually using artificial Rotunda and used to treat a post-partum haemorrhage. serum or animal blood usually lambs' blood I wondered if this was actually correct as blood groups were only identified at the start of the 20th century and 2 - 19th Century Human to human blood Transfusions prior the Rotunda laboratory only opened in 1898. How did to the discovery of blood groups. they manage a blood transfusion without a laboratory 3 - 20th Century Human to human Blood transfusion after or knowledge of the basic blood groups? Fortunately I the discovery of agglutinins and iso- was able to find the records of this case which then led agglutinins. me to unearth records of other transfusions that were 4 - 21st Century Molecular diagnostics, Genome attempted in Ireland in the latter stages of the 19th century. sequencing, artificial blood products etc The records gave very vivid descriptions of the blood transfusion processes, and the contemporaneous medical thinking of the time. It is in equal measures intriguing as The very first recorded non-blood transfusion in Ireland it is heartbreaking but the most fascinating aspect was can be traced back to St John's Cholera Hospital Limerick in how close some of the doctors were to understanding the 1832 where a Limerick Surgeon, Mr Ringrose Gore, used an science of blood transfusion as we know it today. artificial serum to try and alleviate the symptoms of cholera There are records of blood transfusions being in a young soldier. The case describes how a young private undertaken as long as records exist - circa 850 BCE, in the regiment was suffering from cholera and "utterly Naaman, Chief Leader of the army of the King of Syria pulseless and in the very act of dying". They transfused was treated with transfusions to try and cure his leprosy. 20oz of the serum and the patient responded very well. Other persons known to have undergone transfusion Unfortunately after a few hours he relapsed into his previous include Pope Innocent VIII in 1492. The Pope appeared state and died. A second transfusion was attempted but he to be dying, so they transfused blood from three healthy died shortly later. young men. The transfusions had no effect on the pope The first recorded case of a blood transfusion in Ireland but unfortunately all three donors died. In his landmark was in 1858 and the recipient of the transfusion was a horse. book, Roussel opens with a paragraph on the history of During the autumn of 1856 and spring of 1857 an epidemic blood transfusion and says that England ‘may with justice occurred among horses in Ireland. It was noted that claim to be the native land of transfusion, from a scientific 'bleeding' the horses appeared to make the symptoms worse point of view. It was a publically demonstrated for the first so transfusion was proposed by the Veterinary Surgeon time at the Royal Society of London, in the May meeting, to the Lord Lieutenant, James Farrell. He successfully 1665, by Richard Lower, of Oxford, and Robert Boyle’*. transfused four horses and all made a complete recovery. Blood transfusion has always been controversial and in Interestingly at the time he stated "for whatever obstacles his introduction to the second meeting of the Proceedings and objections there may be to its performance in the human of the Dublin Obstetrical Society in 1872, a Dr Ringland subject, there are none whatever to prevent its becoming a states "The introduction of the operation of transfusion into most valuable agent in veterinary science". the practice of medicine at about the year 1667, was the In total there appears to have been fifteen attempted blood starting point of one of the most violent controversies that transfusions recorded in Ireland between 1865 and 1879. has ever agitated the world of medical science". Interestingly the vast majority were carried out in private homes with only a few taking place in hospital. Of the fifteen *(Boyle (1627 – 1691) born in Lismore Castle in County Waterford) cases nine were deemed to have been successful.

12 • converse • Spring 2020 feature

Fig 2: Blood Transfusion in Ireland 1832 Date Location Diagnosis Performed by Donor Material transfused Result 1832 St John’s Cholera Hosp Cholera W.R. Gore NA Artificial Serum Some success Limerick 1854 Military Barracks Cholera W.R.Gore NA Artificial Serum Immediate recovery Limerick after first but no response to second 1856-1857 Dublin Debilitating disease J. Farrell Horse Whole Blood Successful in horses 1865 Jervis Street, Hosp Tetanus R. M'Donnell R. M'Donnell Defibrinated blood Patient relieved but RIP next day Feb 1870 Private House Dublin Post partum haemorrhage R. M'Donnell Husband Defibrinated blood Successful – (PPH) Sept 1871 Tenters Lane, Coombe PPH R. M'Donnell Anthony Cassidy Defibrinated blood Patient died after - med student  8oz were given (Patient too far gone) Oct 1871 Private House, Dublin PPH R. M'Donnell Andrew Irwin, Defibrinated blood Successful resident pupil Rotunda 1871 Suburbs of Dublin Miscarriage R. M'Donnell Husband Defibrinated blood Patient died before transfusion started Feb 1877 Rotunda PPH R. M'Donnell Mr Gage, pupil Defibrinated blood Patient died 2hrs after the transfusion 1877 - June Rotunda Accidental haemorrhage R. M'Donnell Mr Donaldson, Defibrinated blood Successful student 1877 - Sept Several miles from PPH R. M'Donnell Husband Defibrinated blood Successful Dublin Before 1879 Dublin No Details G.H. Kidd Unknown Blood Successful Before 1879 Leinster Rd, Dublin Accidental haemorrhage G.H. Kidd Husband Warm saline RIP before and premature labour blood could be given Before 1879 Camden St, Dublin NA G.H. Kidd Unknown Warm saline Patient RIP 1879 - April Coombe District Hospital PPH G.H. Kidd Husband Defibrinated blood Successful

The first recorded human blood transfusion in Ireland was recorded in Jervis Street Hospital on April 20th, 1865, by the first Irish pioneer in Blood Transfusion Dr Robert M'Donnell. The patient was a fourteen year old girl -Mary Anne Dooly. She had unfortunately severely damaged her right hand in a paper mill accident. Some days later she started to display symptoms of tetanus. The patient’s spasms were so severe quite allayed". Unfortunately the transfusion had no effect that she 'was absolutely unable to take on the spasms and she died on Friday the 21st. Her ability nutriment by the mouth, and instantly to describe the "agreeable sensation" during the transfusion rejected enemata'. Dr M'Donnell drove Dr M'Donnell on to pioneer the use of Blood proposed a blood transfusion and the Transfusion in Ireland. patient’s doctors readily agreed to the It was after the above case that Robert M'Donnell invented procedure. an apparatus for injection of defibrinated blood or any other Dr Robert M’Donnell fluid into the veins. It was a simple device made up of a long glass pipette, rubber tubing and a cannula. This is now held Dr M'Donnell voluntarily donated 12 ounces of his own in the heritage section of the Royal College of Surgeons blood. The blood was defibrinated by stirring with a glass in Ireland. The apparatus is currently on public display in rod and passing through ’scalded’ muslin. It was kept at a Beaumont Hospital. Dr M'Donnell’s instrument was forgotten warm temperature by keeping the blood in a bowl floating over time and it was a chance finding by Dr J.D.H. Widdess on hot water. It was then transfused to the patient using a in the 1920's that prompted him to write a review of Dr rudimentary syringe. Every two to three minutes during the M'Donnell. transfusion the patient was asked how she felt and she Although Mary Anne Dooly was the first recipient of a expressed herself as feeling "an agreeable sensation, an blood transfusion in Ireland the first documented case undefined sensation of warmth pervading her". An hour after was described by Dr Thomas E Beatty in 1870. Dr Beatty the transfusion her "sensations of hunger and thirst were described a "handsome and well made lady" patient of

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his who was on her 3rd pregnancy and complained of blood transfusion? Prior to the transfusion there was not any bleeding without pain every night. On the 22nd February "pulsation whatever to be felt at the wrist, although frequently at 7 o'clock Dr Beatty was called for and found that "she and anxiously sought for; but scarcely had three or four had been seized with labour an hour before, accompanied ounces of blood been transfused than, to our great joy, a with profuse haemorrhage...... a six month old child was pulse - scarcely perceptible, 'tis true, but still undoubted - expelled, alive and lying in an ocean of blood". The patient was found". Dr Ringland goes on to state that "transfusion in was "pale, pulseless, and as cold as marble". He called on her case was an imperative necessity, and I conceive that I his colleague Dr Denham to assist as "it was plain to see have fully demonstrated that our patient was snatched from that she was in imminent peril". The pulse did not return death to life...". and they continued to try and resuscitate her. The patient The first recorded Blood Transfusion in the Rotunda was dying and they could do little else than watch her die Hospital was in 1877. The case involved a thirty year old unless her "downward course was checked and I saw no lady admitted to the Rotunda Hospital on Tuesday 6th other chance for her but transfusion". They summoned February 1877 at 1:30. It was her eighth pregnancy. The Dr Robert M'Donnell. At "6 o'clock her condition further patient was "aged looking and obviously anaemic". At deteriorated and all traces of pulse had long vanished, and 16:00 a healthy baby boy was born. After about half an death seemed very near at hand". Determined not to let hour a small but steady stream of blood was noted. Even her die he again summoned Mr Colles and Dr M'Donnell after injecting cold water into the uterus the bleeding who duly arrived at 9 o'clock and it was clear that she continued. Suddenly the patient's condition deteriorated, had only minutes to live. They proceeded to transfuse her pulse could hardly be felt and she complained of her with blood donated by her husband. The blood was feeling very weak. At 17:45 the Master was summoned and prepared in the parlour and carried up to the patient. They immediately set about injecting a solution of perchloride of located a collapsed vein that resembled a "small flat dead iron. The bleeding immediately stopped and no further loss earthworm". Robert M'Donnell using exceptional dexterity occurred. The patient's condition improved and her pulse was able to open this vein and insert the cannula. The returned. She expressed herself as feeling comfortable. blood was poured into the instrument and air bubbles Unfortunately the satisfactory state did not last long and removed. About 6 or 7 ounces of blood were poured into she had collapsed a short time later. "Seeing that her life the system. "The first change I noticed was the improvement must speedily become extinct, unless the vital powers could in respiration, the long laboured, gasping sighing effort that be invigoured, I decided on trying transfusion, and sent for had been so distressing to witness became more calm". Dr R M'Donnell". He came promptly and at about 19:45 the When she awoke some hours later she immediately asked transfusion started using blood from an intern. Dr Atthill later for food and ate a good breakfast. Within a week she was stated that at this point the situation was serious but not well enough to drive in a carriage and she left town for the without hope. The blood entered the patient’s vein freely. country. Later Robert M'Donnell remarked that it was "one of Unfortunately, the pulse did not return and the patient, those cases which repay a surgeon for years of anxiety and instead of expressing any sense of improvement, became toil, and which make up for many disappointments". very restless and complained of great distress and of pain A very similar case was presented by Dr John Ringland in her chest. The whole quantity of blood was transfused in 1872. The patient was 23 years old and had delivered in the expectation of the beneficial effects but in this they two babies abroad and on both occasions she had a were disappointed. The restlessness increased, and the significant haemorrhage. The delivery went without issue breathing became shorter and shallower. She gradually but due to her bleeding history the doctor kept her under "sank" and died at 20:00, six hours after the birth of her close observation. After some time he felt it safe to leave child, two after the transfusion commenced. This is likely to the room but on his return he found that haemorrhage have been the first recorded blood transfusion reaction in had started and blood poured from her in a "profuse Ireland. stream". He tried all the usual methods of stopping the Dr Atthill brought up this case at a meeting of the Dublin bleeding including injection of cold water into the uterus Obstetrical Society in April 1877. He wanted to know but the bleeding increased. He called on help and it came what caused this patient to haemorrhage as all due care in the form of a Dr George Johnston and together they was given. He asked if the injection of the styptic was injected a solution of perchloride of iron "after which not delayed? He was concerned as to what caused the distress one drop of blood was lost". Unfortunately it now became witnessed during the transfusion? Importantly he raised the manifest to both doctors that "matters were assuming question that not only was the transfusion a failure, but had a most alarming aspect, and that a fatal issue was all it actually caused injury? And if so, how could we guard but impending." Dr Ringland at that point suggested "in against this happening in similar cases in the future? a low voice, so as not to be audible to our patient, the In reference to the first issue he elaborated on the advisability of being prepared for transfusion". They sent for patient’s history. She had given birth previously to seven Dr Robert M'Donnell. While they were awaiting his arrival children, five of whom were still alive. Shortly before her they decided to get the blood ready but that became an admission to hospital her husband knocked down and issue as there was no one suitable to donate. Dr Ringland injured a child while driving a van. He was arrested and suggested getting a medical student from the Rotunda. committed to gaol, leaving her and her five children They were not disappointed, Dr Johnston returned in a deprived of a means of support. He blamed her distressed short time, accompanied by the volunteer, Mr Andrew mental and physical state for the cause of her bleeding. On Irwin of Sligo. Interestingly in this case "her sanction was the second question he advocated the early intervention sought for, promptly assented to its performance". Might with perchloride of iron as "had never had cause to regret this be the first time patient consent was obtained for a using it in cases of post partum haemorrhage". In relation to

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The Rotunda circa 1900

the third and fourth question, he pointed out the fact that he to the bedside of a moribund creature in that condition , could not explain the cause of the great distress observed that it is necessary for us to seek very far for the cause for during the transfusion. He was absolutely convinced that the laborious and painful sinking when she came to be in the transfusion accelerated the patient's death. He went on articulo mortis....' to say - "The inference to be drawn from the foregoing facts In relation to the infarction of the lung, he vehemently is clearly this - that transfusion is not a perfectly harmless denied that it could have come from the transfusion as he proceeding". defibrinated and strained the blood prior to transfusion. The president of the Society then opened the floor to the He felt that after stirring the blood with a glass rod and members stating that "This is one of the most important straining it that it would have been impossible for the cases that could possibly come before us...". clot to have come from the transfusion. He goes on to Dr Robert M'Donnell was in attendance and was first to say that he is absolutely in favour of using defibrinated speak and answer the concerns raised by Dr Atthill. He blood – "Fibrine has long been supposed to be an all- started by acknowledging the fact that "it does not come important nutritive element of the blood. We now know...... upon me for the first time there are doubts as to whether from an accumulation of observations , that fibrine is not the operation of transfusion may not have been the means an important element in the blood plasma, but is rather an of accelerating the patient's death". He deals with the third excrementitious substance away from the tissues, than a and forth question directly - it is said that the cause of the source of nutriment for them". distress felt by the patient was the transfusion, and that After a lengthy debate Dr M'Donnell closed the meeting distress accelerated the fatal issue. Dr M'Donnell could only by saying – "I can only say it gives me the greatest pleasure refer back to the one case where a patient was sufficiently to assist in performing it on the patients of any gentleman conscious during the procedure to describe it adequately. here. I have been asked by several of them to go to the He referred back to Mary Anne Dooley who expressed Coombe and elsewhere ; and whenever they think they have that the transfusion was not distressing but was rather suitable cases, in which the operation can be performed agreeable, warm and revivifying feeling. Based on this he with any reasonable chance of saving the patient, I shall be felt that the transfusion could not be blamed for the distress delighted to lend them my assistance among the poor, at and laboured breathing experienced by the patient. 'We any hour of the day or night". need not lay the blame on the transfusion in such a case The Society then adjourned. which we have heard. We have a wretched starving woman, The resulting discussions amongst society members with a number of children starving along with her, her show that there was some resistance to performing blood husband in gaol, and unable for several days to provide transfusions. This resistance appears to have won out food for his family. I do not think, when we are brought because there is no reference or documented transfusion

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in Ireland between 1879 and 1922 when a paper written by Mr Henry Stokes was published in the Irish Journal of Acknowledgements: Medical Science in Dec 1921. Why did transfusions stop I would like to thank Ms Ellen Lennon, Prof Fionnaula Ní for this duration? It is unlikely that it became established Ainle and Ms Anne O Byrne for all their help in writing this practice because the clinical report for the Rotunda in essay. 1922 showed only transfused 2 patients all year and it is worth noting that the first recorded transfusion in the Roussel J., of Geneva (1877) Transfusion of Human Blood Mater was in 1935. Could it have been due to increased by the method of J. Roussel, J. & A. Churchill. https:// wellcomecollection.org/works/nmp52xs9 reports of severe reactions in mainland Europe? Would this have led to the complete cessation of transfusions Boyle R (1666)., Tryals proposed by Mr. Boyle to Dr. Lower when there were such successful outcomes also? The to be made by him, for the Improvement of tranfusing retirement of Dr M'Donnell in 1888 could have caused blood out of one live animal into another; promised a decline in the transfusions but again this is difficult to Numb. 20. P. 357. https://royalsocietypublishing.org/doi/ believe. Dr M'Donnell was noted as an outstanding teacher. pdf/10.1098/rstl.1665.0147 One would have assumed that he would have taught his Renwick, W. (1854). Transfusion in a case of cholera. students the process of blood transfusion? Internationally Dublin Med. Press, vol. xxxi, p. 258. there was a reduction in the use of blood transfusion as saline become more widely available. Farrall, J. (1858). Transfusion of blood in the horse in Could the Victorian obsession with vampires be a reason diseases attended with low vital action.Dubl. Q. J. Med. that blood transfusion fell out of favour? Bram Stoker’s Sci. Vol. XXV, p. 67. ‘Dracula’ was published towards the end of 1890’s but the Beatty, T. E. (1870) Transfusion successful in a case of notion of vampires was very prevalent in Victorian society. post-partum hæmorrhage. Dubl. Q. J. Med. Sci. Vol. XLIX, We know that Stoker’s father and two brothers practiced p. 325. medicine in Dublin at this time and would have been aware of Robert M'Donnell. Also the device described in ‘Dracula’ M’Donnell, R. (1870). Remarks on the operation of for transfusing blood to Lucy more than resembles Robert transfusion and the apparatus for its performance.Dubl. M’Donnell's device. Furthermore Mr William Stoker (Bram’s Q. J. Med. Sci. Vol. L, p. 257. brother) was very close friends with Dr Kidd and was Ringland, A. H. (1872). Transfusion in post-partum present at his bedside when he died. There were other Irish hæmorrhage.Dubl. Q. J. Med. Sci. Vol. LIII, p. 75. ‘horror’ writers around at that time i.e. Joseph Sheridan Le Fanu who wrote 'Carmilla' - a story of a lesbian vampire, Ringland, J. (1872). A case of post-partum uterine which predates Dracula by 26 years. Did the public hæmorrhage successfully treated by transfusion.Dubl. Q. associate blood transfusion with evil? Another reason for J. Med. Sci. Vol. LIII, p. 82. the decline in blood transfusion could be the emergence Athill, L. (1877). On transfusion in post-partum of the anti-vaccination movement in the UK. The anti- hæmorrhage.Dubl. J. Med. Sci. Vol. LXIII, p. 578. Vaccination League and the Anti-Compulsory Vaccination League were established in 1850’s and were hugely Purefoy, R. D. (1878). Paper recorded in proceedings of successful. This group likened the vampire’s fangs to the Dublin Obstetrical Society.Dubl. J. Med. Sci. Vol. LXV, p. needle of the physician. They also played on the Victorian 250. cultural anxiety and their belief in strong blood lines. M’Clintock, A. H. (1878). Successful cases of transfusion. The Master of the Rotunda in 1877 was Dr Lombe Dubl. J. Med. Sci. Vol. LXV, p. 248. Atthill and it is interesting to note that even then he wrote that 'although post partum haemorrhage is of common Kidd, G. H. (1879). A case of transfusion.Dubl. J. Med. occurrence, deaths from this cause are now infrequent'. Sci. Vol. LXVII, p. 532. He goes on to say "Still deaths from haemorrhage do Stokes, H. (1922). Transfusion of blood.Ir. J. Med. Sci. 5th from time to time occur, and in spite of our boasted series, p. 18. knowledge, will, I fear, continue to do so". A statement that is as relevant today as it was over 140 years ago. Widdess, J.D.H.(1951). Robert M'Donnell - A Pioneer of It also shows how practise can change based on belief Blood Transfusion; A survey of Transfusion in Ireland, and flawed experiments. Dr M’Donnell firmly believed that 1832 - 1922. Ir J Med Sci 27: 11 fibrin was an "excrementitious substance", the complete Fourteenth Detailed Annual Report of the Registrar inverse of what we now know to be the case. In 1872 he General or Marriages, Births and Deaths in Ireland , 1877. suggested that patients blood could be re-infused during https://www.cso.ie/en/media/csoie/releasespublications/ an operation something we call cell-salvage today. What if documents/birthsdm/archivedreports/P-VS_1877.pdf they started to employ this then would they have noticed that the patients were not having the same life threatening https://mater.ie/about/history-of-the-mater/ reactions seen in some autologous transfusions? Those https://historyof vaccines.org/content/article/history-ant- who do not learn from history are doomed to repeat it. vaccination-movements There is no doubt that medical historians of the future will hold their heads in their hands and wonder how we were http://rcsiheritage.blogspot.com/2014/08/blood-stirred- so close understanding the mechanisms of disease yet be not-shaken.html so far away.

Spring 2020 • converse • 17 feature Green Labs Making Sustainable Labs a Reality Rachel Ralph

ately it’s been hard to miss all the news articles address issues such as plastic waste, energy reduction and about rising ocean temperatures and plastics in the water usage. She says that “people who work in labs are using Lenvironment and in our food chain. Happily, there seems 15-16 times more plastic than the average person in Ireland” to be many things we, as individuals, can do about it, from and maintains that this is done “more so out of convenience using reusable bags, to riding a bike to work, to changing our than out of necessity”. diets. Yet while many of us have made efforts to reduce waste One of the most noticeable environmental impacts in the and use less resources at home, when we come to the lab it lab is the amount of waste. From gloves to pipette tips and seems a much harder task. With so much water, single-use glass bottles to cardboard boxes, laboratories generate a lot plastics, and energy-intensive equipment that seem necessary of waste. In fact, a 2015 letter to Nature estimated that labs to do science, it can be hard to imagine what can be done to discarded 5.5 million tonnes of lab plastic waste in 2014 alone. make labs more sustainable. Nevertheless, scientists around Not all these materials end up in a landfill or incinerator, but the world have been taking a closer look at how they work in even recycling requires resources and doesn’t extend the life of the lab and they are finding meaningful ways to reduce their the product forever. The best thing to do is to avoid waste from impact at the bench – and it’s easier than you might think! the start – and there are many ways to go about this. Let’s start with the products themselves - take those pipette tips as an example. Instead of buying tips in an individually wrapped box, you can buy them in reload systems that can cut the amount of plastic waste by 25-50% depending on the tip size and system, they come in sterile and non-sterile formats, so there is little reason not to use these. Buying items like bulk conical tubes instead of racked systems is another easy way to eliminate waste. Many vendors offer products that can help you eliminate waste before it is generated. Not all vendors are marking these products on their webpages so be sure to ask your sales rep or procurement manager to help you explore options. Identifying more sustainable products is also possible through environmental product labels like ENERGY STAR® and ACT. ENERGY STAR, an energy-efficiency label created by the US Environmental Protection Agency and the US Department of Energy, highlights equipment that meets certain energy This idea of making labs more sustainable is often referred efficiency standards. ENERGY STAR ratings are now available to as Green Labs and is a movement that has exploded at for -80°C and -20°C freezers. Another environmental label academic institutions and biopharma organisations around called the ACT label, is an eco-nutrition label for laboratory the world in the past decade. From the United States to products that allows scientists to compare products based Ireland to New Zealand, thousands of scientists are now on their environmental impacts related to manufacturing, engaged in Green Lab efforts either through a programme use, and end-of-life. The ACT label is independently verified at their organisation or on their own. This number is growing and is designed to enable scientists to make more informed rapidly! My Green Lab, a non-profit organisation that offers a purchasing decisions by being able to choose the product that Green Lab Certification Programme to help direct labs in their best supports their sustainability goals. sustainability efforts, recently certified Dr Una Fitzgerald’s lab Consolidating orders is another strategy for avoiding waste. at the National University of Ireland, Galway (NUI Galway), Instead of everyone ordering what they need whenever they making it the first Green Lab Certified lab in Ireland! Scientists want, explore ways that the lab could place a single order in Ireland and elsewhere that are engaged in green lab efforts with each vendor maybe once a week or even once a month. are working to reduce the environmental impact of research Working from a common supply of reagents can help make this by reducing energy and water use and waste generation in the possible, as each person isn’t ordering in order to resupply their laboratory environment. So, what are they focusing on? own stock. And, of course, taking time to plan experiments can Dr Fitzgerald, Director of the Neuroscience Centre at NUI be helpful here too. Spending an hour at the end of the week to Galway together with her “green team” of researchers and check that you have the materials you expect to use in the next staff, is working to transform practice across the campus to week can help you avoid last minute urgent purchases. Some

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vendors also have supply centers, which are single fridge vending machine that stock commonly used materials and are refilled with fewer shipments than ordering the products individually. Another big step that labs can take is to make sure they are wasting right. What can be recycled and what can be landfilled varies greatly from place to place. Working with your organisation and waste hauler to identify which products (not just material type) can be recycled is key to making sure this material gets recycled instead of landfilled. Creating clear signage with pictures of common products in the lab that go into each bin makes it easy and fast to waste correctly. Though much less visible, energy and water are also consumed in large amounts in the lab. Lighting can account for around 15% of the energy used and making sure you turn off the lights when the lab is unoccupied or when there is enough daylight is a simple way to save energy. Equipment accounts for another 20% of the energy use in the lab. Having Dr Úna Fitzgerald (front right), founder of Galway Green Labs, a group discussion about what needs to be left on and what pictured receiving Europe’s first Green Lab Certification from can be turned off can help you identify equipment that could Allison Paradise, CEO “My Green Lab”. be shut down or put on an outlet timer to turn off automatically. NUI Galway Green Labs Certification Nov 2019: “Dr. Fitzgerald If you have duplicate equipment, evaluating how frequently and lab receive their My Green Lab Certification having you use them may help you determine you could shut one achieved “Green” status, the highest level for certification.” down or share the resource with a colleague. Water gets used in the lab in a wide variety of ways. At the green lab principles are broad, but how the lab chooses to tap, faucets can be outfitted with low-flow aerators, simple implement them can be unique. For example, to save energy devices that screw onto the end and reduce the flow of it is best practice to shut down equipment when it is not in water by up to 50%. You should also check if water-cooled use, but before doing this, it is best for a lab to discuss what equipment, including ice machines and distillation set-ups, can and cannot be turned off and agree on an appropriate could be placed on a closed-loop or replaced with an air- schedule and protocol. By having these discussions as a cooled system. Large medical-grade or steam-jacketed group, your lab can determine what solutions will work best autoclaves are also water intensive as they continually run cold for you. And when everyone in the lab takes ownership of the water to cool the hot steam discharge before it goes down the change, it becomes part of the culture of that lab and the new drain. These units can be retrofitted with water-saving devices status quo. or switched out for more efficient research-grade autoclaves. So, whether it is something you do on your own, through Working towards more sustainable laboratory operations your organisation’s green labs programme, or with an doesn’t just benefit the environment, it can have a positive organisation like My Green Lab, you can get started today impact on your lab. Finding ways to reduce waste and making your lab greener! In Dr. Fitzgerald’s words: “The time consume less materials can help the lab save money – a to green our labs is now!” benefit everyone can get behind. Your organisation will see To view the Galway Green Labs short video, called 'The time big savings from reduced water and energy usage. Even to green our labs is now' if these savings don’t go directly to the lab, they help your https://vimeo.com/375847945?ref=tw-share organisation invest more in infrastructure and resources that Follow on Twitter at #GalwayGreenLabs and benefit you in the long term. Looking at science through the @GalwayGreenLabs lens of sustainability also lets you see opportunities to change and make improvements that you might not have thought of before. For example, thinking about how you might reduce Rachael Relph waste in an experiment might prompt you to find or create a Rachael is the Chief Sustainability Officer at My Green Lab, simpler procedure with fewer steps that also saves you time. a non-profit organisation dedicated to building a culture of Many laboratories find that the process of investigating and sustainability through science. Rachael helps scientists identify implementing sustainable solutions prompts discussion in the greener laboratory practices through education, outreach and lab that helps build communication and engagement amongst a Green Lab Certification programme. Prior to joining My Green lab members. Organisations are also viewing sustainable Lab, Rachael led Design for Environment and Sustainability labs as a way to recruit and retain the next generation of initiatives for Life Technologies and Thermo Fisher Scientific. scientists that are increasingly focused on minimising their Work: 858.836.3055 | Cell: 503.314.3654 environmental impact. Web: mygreenlab.org | Email: [email protected] “We found the My Green Lab certification programme to be Join our mailing list | Become Green Lab Certified an excellent tool for encouraging our researchers to examine their own laboratory practices. Once everyone understood how small changes could have such a huge impact on, for example, energy usage, they were quick to agree to changes” said Dr. Fitzgerald of the My Green Lab programme. Involving people in the lab in green lab efforts is key to success. Many

Spring 2020 • converse • 19 academy Testing Times These are indeed extraordinary times. The speed with which outside of clinical diagnostic laboratory. IT connectivity and GDPR Ireland’s medical laboratories have prepared to deliver Covid-19 concerns are but some. Research laboratories have different testing has been impressive by any standards. Scientists in the approaches, equipment and staff. Our research, academia and National Virus Reference Laboratory (NVRL) who, having acquired industry colleagues answered a cry for help last month, when an the sequence of the virus, used this to develop and validate urgent call went out over social media that there was a shortage ‘in house’ assays in advance of the arrival of any commercial of lysis buffer. Sligo IT in collaboration with medical scientists diagnostic kits. They have played a vital role in the early detection made the first batch and sent it to Sligo University Hospital of cases. Their first positive specimen was detected on February and Letterkenny University Hospital for validation. Through 29th. In an interview with the Irish Independent, NVRL Laboratory consultation with various medical scientists support also came Manager Deirdre Burke, described the sense of shock mixed with from RCSI to Beaumont, UCD to St Vincent’s University Hospital relief that they had finally detected the virus. She also clarified that and Lilly, CIT, UCC and Teagasc (collaborating with one another) a “test” means a laboratory investigating a sample (swab) taken. to , and onwards from there to other Medical scientists where naturally exasperated when the HSE hospitals and UL for University Hospital Limerick. and the Minister began talking about “testing”. They were setting A team from Cork led by Dr Brigid Lucey and her colleague up “testing centres”. Croke Park was a major centre. We watched Dr Martina Scallan and in collaboration with medical scientists as the army set up “testing centres” around the country. We on the ground, wrote listened to radio interviews whereby the public in their hundreds a validation protocol were telling the country they had been “tested” but were still for lysis buffer for waiting for their results. In spite of numerous statements sent laboratories unfamiliar by the Academy to all media outlets, to Health Correspondents with this. This in RTÉ and other media to explain the difference between collaborative effort got “sampling” and “testing”, the misinformation still continues. picked up by the media and got widespread coverage across range of print and social media. Brigid also did a piece for RTÉ Brainstorm, on "What happens to my coronavirus sample in the testing lab?" https://www.rte.ie/ brainstorm/2020/0330/1127277-coronavirus-test-laboratory- samples-ireland/. Our industry partners have also pulled out all the stops to help with UTM, swabs and developing assays. Reagents were delivered to University Hospital Waterford. Knowing how urgently these were required and to save time, Ciara Fanning, Senior Medical Scientist, drove to Limerick so that Colm McDonnell, Chief Medical Scientist in the virology The NVRL is processing most of the workload but almost 20 laboratory could get his allocation without delay. The Laboratory laboratories around the country are now testing (analysing). Manager at Galway University Hospital, Maria Molloy, drove down Figure 1 shows that our testing rate compares favourably with our from Galway to collect their supply. Great teamwork from all European neighbours. Medical scientists would like to be doing concerned. more. Certainty of supply of reagents is a serious concern and a barrier to scaling up. Laboratories could seriously ramp up testing and supply all the testing requirements if they could rely on a supply of reagents. Manufacturers are struggling to keep up with demand. There is global competition for reagents and kits. Some reagents are in short supply and some are subject to distribution bottlenecks. Some companies have overpromised and then unable to deliver. There is world wide concern that unscrupulous companies will exploit the opportunity and sell to the highest bidders. Governments may also pressurise manufacturers to keep supplies for their own people. There are calls for research laboratories to set up diagnostic facilities in their laboratories. These centres of excellence and scientists have great expertise in molecular procedures. However, there are multiple issues with setting up diagnostic testing

20 • converse • Spring 2020 academy

Almost 100 medical scientists and the last port of call, and is based on the understanding that; have sent their details to the • All existing in house resources are exhausted - e.g. Academy offering their services if everybody working full time etc needed. These are some retired • Existing recruitment panels are exhausted medical scientists but also those • Agency staff are booked if that is normal practice in that in academia, doing post graduate laboratory (national Agency Framework degrees, full time research or Many medical scientists throughout the country along with in industry. The list is updated council of the Academy and outside microbiology have been regularly and forwarded to laboratory managers and HSE HR, involved in data searches, setting up POCT and ensuring that On call for Ireland. Laboratory managers across the country are other laboratory services are prepared to deal with the patient recruiting additional staff from the list. The grade of Intern Medical once they are diagnosed with COVID-19. It is great to see the Scientist has also been approved by the HSE. From an additional commitment and support being offered at this extraordinary time. resources perspective, On Call for Ireland is for additional staff Helen Barry

for SARS-CoV-2 vid CIDR (Computerised Infectious Diseases Reporting). This a Surveillance Scientists statutory requirement under the Infectious In tandem with the demands on hospital management continue to require Diseases (Amendment) Regulations 2020 microbiology labs to introduce testing data. Line listings of lab results are in high (S.I. No. 53 of 2020) which provides for for SARS-CoV-2, there has been an demand. This allows for a quick overview the notification of Covid-19. The number increased demand on hospital-based of what's happening rather than having to of daily notifications has increased greatly. surveillance scientists to provide data drill into each patient's results. The weekly A new body has been established, both locally and nationally. Hospitals want Infection Prevention and Control meeting which will carry out national contact daily updates on numbers of patients and is also informed by surveillance data. tracing and a dropbox so surveillance staff testing positive. For instance, in our In addition, the HPSC is requesting scientists can send on relevant data in a hospital, Connolly, we are maintaining a daily cumulative data from laboratories timely fashion. spreadsheet of all those who have tested that are carrying out their own testing - It has become a very busy time for positive, keeping tabs on their status numbers of tests, positive tests, numbers both the staff of the microbiology lab and - inpatient, ICU, discharged, RIP, not of cases etc as of the previous midnight. their colleagues working in surveillance in admitted, staff. This is discussed at the This informs the national figures which we hospitals, public health and the HPSC. daily 'hospital huddle' and emailed out. hear about on the news each evening. Anne MacLellan and Gráinne Bowens Occupational health is a new consumer of Surveillance scientists continue to Surveillance Scientists, Connolly surveillance data. Bed management and notify patients who have tested positive Hospital.

Point of Care Testing COVID-19 Profession-Specific Members of the Point of Care Advisory Body, who are Academy representatives on the National Point of Care Consultative Online Resources & Education Group, have been advising the National Clinical Pathology lead, Éadaoin O’Hanlon has set up a blog on behalf of the eHealth Dr Mary Keogan on the procurement of blood gas equipment HSCP Advisory Group. She has seen first-hand the vital role for use in acute hospitals and analytical equipment more HSCP are playing in response to the COVID-19 pandemic. suited to community testing facilities. There has been excellent collaboration between sites and Point of Care Specialists, to support those who were unable to obtain additional blood gas equipment from their existing supplier. This has included the drafting of guidelines for rapid verification of new equipment, the repurposing of existing SOPs and working instructions and the provision of ongoing support through phone contacts. Video instructions for blood gas analysis and equipment maintenance have been prepared by both Manufacturers and local Point of Care Specialists, experienced in training and have been circulated. An active group of POCT specialists are collaborating with regard to ongoing equipment problems etc. Other evaluations such as an assessment of the feasibility and performance of https://hscpshare.com/2020/04/07/covid-19-profession- other Point of Care Tests such as BNP and D-dimers have been specific-online-resources-and-education/ performed. • HSCP are carrying out diagnostics and disease monitoring There has been an increased demand for training in Point • HSCP are delivering specialist treatment and rehabilitation of Care Testing as sites are re -purposing clinical areas, • HSCP are providing psychosocial and practical supports to redeploying clinical and nursing staff and adding additional patients and their families equipment such as Blood Gas Analysis and glucometry. This aims to highlight the resources available to HSCP with Bernadette Jackson links to the resource page on the professional body websites. All POCT Manager, , Academy information to be shared should be sent to [email protected] President Elect. Leo Mulvany, CPD Officer

Spring 2020 • converse • 21 academy Zero to Three Hundred a Day... and Rising Early Days in SARS-CoV-2 Testing at the National Virus Reference Laboratory

hen conducting Induction for new staff, I always say candidate diagnostic RT-PCR assays before release of the first that the NVRL is a really interesting place to work, sequence of 2019-nCoV. Upon sequence release, the assays Wyou will have a job for life as our workload has only were selected based on their matching to 2019-nCoV as per ever increased year on year, and every few years we even have inspection of the sequence alignment and initial evaluation. new viruses, to keep us on our toes. And, as now we know, So down to the business of validating a new assay while 2020 is one of those years, with Novel Coronavirus - 2019 maintaining the routine CL3 service for Zikavirus, West Nile nCoV on the scene. virus, and hazard group 3 pathogens, by the small team of STOs. It is a challenge to validate an assay in the absence of January 2020 positive patient samples, however that was the reality of the “Have you seen what’s happening in China?” A passing situation, so the process was started using what was available. comment prompted Dr Margaret Duffy, Senior Technical Officer (STO) and co-ordinator for the NVRL CL3+ facility, to do a 22nd January 2020 quick internet search. As the person responsible for SARS and A Pancoronavirus nested RT PCR in-house assay based on MERS testing, Margaret was well aware of the potential, and Drosten’s paper from 2007 was the initial screening assay consequences of novel coronaviruses, having implemented utilised as an interim, until positive control material was testing for both SARS and MERS. The CL3+ team, led by Dr available for a Realtime PCR. This nested PCR required a gel Jeff Connell immediately began to review testing options. to be run to visualise results, and any sample found positive On December 31st 2019, China had reported a cluster of would have to be sequenced to confirm a 2019 nCoV virus. cases of pneumonia in people associated with a seafood The assay was used for 4 times, over the first week of testing, wholesale market in Wuhan, Hubei Province, China. On the 7th with no patients positive for the virus. Its final run was on January, a novel coronavirus was identified by the CDC, China the 29th, set up in parallel with the assay below. NCoV test in a throat swab collected from an infected patient. It was requests were arriving at the NVRL at an average of 2 per day. subsequently named as 2019 nCoV by the WHO. The international virology community were in hot 29th January 2020 communication with daily updates from ECDC, and WHO, By the 29th January, reagents had been acquired to allow the and we were in frequent contact with our nearer colleagues roll out the Realtime PCR assay described in the WHO 2020 at Public Health England (PHE), to liaise on developments in protocol 2. Positive control material was in short supply so the China and discuss preparation for laboratory testing. Protocols NVRL had applied to the European Virus Archive group (EVAg) for reporting positive results were discussed with the Health for both Wuhan coronavirus E gene control (transcribed RNA) Protection Surveillance Centre (HPSC) and Department of and for SARS-CoV Frankfort 1 whole virus RNA, for use as Heath. control material. A number of seasonal coronavirus positive A viral genome sequence was released on the 7th January samples were also available at the NVRL. Assay performace for public use, followed by another four sequences on the was assessed by serial dilution of controls. Both RdRp and E 12th January. This was shared via GISAID (Global Initiative gene assays were used in parallel to investigate patients for on Sharing All Influenza Data). The genome sequences were 2019 nCoV infection. RdRp assay contained probe 1 for SARS closely related to members of the SARS – related CoV. and probe 2 for 2019 nCoV. With 4 detection mixes on the Dr Christian Drosten of Charité at Universitätsmedizin plate, only 18 samples could be tested per run. Berlin, was to the fore in developing assays for SARS and had published a protocol in 2007 that was widely used in the past. The profile of the Novel Coronavirus positive sample would be In collaboration with virologists in Germany, the Netherlands, ENV Gene RdRp probe 1 RdRp probe 2 Result the UK and Hong Kong, this protocol was updated, and (SARS) (2019 nCoV) after preliminary evaluation, was incorporated into WHO POS POS POS 2019 NcoV DETECTED recommendations on the 17th January 2020. Using known SARS- and SARS-related coronaviruses The Realtime PCR assay from the 29th gave results as to generate a non-redundant alignment, they designed expected, and the assay was in use again on the 30th January.

22 • converse • Summer 2020 academy

Figure 1: Number of Samples Tested per Day to Figure 2: No of SARS-Cov-2 tests reported at the 10th March at the NVRL NVRL to 10th March 2020

Subsequent runs on the 3rd, 4th, 6th and 7th February also accommodate the demand prompted by the first confirmed tested seasonal coronaviruses to ensure no crossreactivity cases in Northern Ireland, on the 27th of February. The between the assay and current circulating strains in Ireland, to average number of requests was now at 40 per day. ensure no false positives. Some of the samples tested were referred to PHE, Colindale for parallel testing, as part of the 29th February 2020 – First positive SARS- validation process. Average nCoV test requests per day were Cov-2 case in Ireland 6 and remained at this level for the next 3 weeks. On the 11th Irelands first positive case further increased the demand for February, the International Committee on the Taxomony of testing and saw average SARS-Cov-2 requests more than Viruses (ICTV ) within WHO announced named the disease double to 98 per day. Covid 19, and renamed ther virus SARS-Cov-2. Commercial supplies of PCR test kits were becoming available and one Altona Novel Corona test kit supplied by 13th February 2020 Serosep was delivered to NVRL on 3rd March and validated Positive control material containing whole genome SARS- using the positive control material received from PHE, UK. Cov-2 was received and titrated in the Realtime PCR assay, The assay ran successfully, and further kits were ordered. giving the expected results profile for the Novel Coronavirus Following delivery acceptance, SARS-Cov-2 testing was positive control, and contributing to the on going validation of switched to Serosep Altona Kit on the 6th March. As this kit the protocol in use. contains two detectors and an internal control in the one well, up to 92 patient samples can be tested per plate. This was a 24th February 2020 timely development as requests were over 400 samples per This week saw the first rise in test requests, and a move day for week beginning 9th March 2020. to offering the diagnostic service over the weekend to Contingency measures were put in place, reducing TATs for some tests, ceasing some routine tests and deferring sentinel, surveillance and genotyping at this time. Additional molecular staff were trained in the Altona PCR test, however the slowest part is the sample preparation, and this also required additional staff training. Staff were asked to volunteer for weekend rosters to manage the workload. While we have an academic interest in the virus and in laboratory testing, we are acutely aware of the human cost of this virus and are very appreciative of the accommodation by all staff at the NVRL to optimise the diagnosic service.

References 1. De Souza Luna,L. Generic Detection of Coronaviruses and Differentiation at the Prototype Strain Level by Reverse Transcription-PCR and Nonfluorescent Low-Density Microarray JOURNAL OF CLINICAL MICROBIOLOGY, Mar. 2007, p. 1049–1052 2. Laboratory testing for 2019 novel coronavirus (2019- Doireann Waldron O'Loughlin showing An Taoiseach, nCoV) in suspected human cases, Interim guidance Leo Varadkar and Minister for Health, Simon Harris, some 17 January 2020 WHO/2019-nCoV/laboratory/2020.3 aspects of SARS-Cov-2 testing.

Summer 2020 • converse • 23 academy

Denyce Browne, Medical Scientist St James.

Joe Lambe, Regional Hospital Mullingar

Brian Keogan, Medical Scientist, NVRL

Natalie Unrath,

Niamh Fitzgerald (sitting) and Nuala Kealy (standing) Snr Medical Scientists in TUH Mark McKeown Snr Medical Scientist, Regional Hospital Mullingar

Fiona Hegarty, Mater

Edel O'Regan, Mater

Adele Habington, CHI at Crumlin

Colm McDonnell Chief Medical Scientist, Virolgy Deirdre Keating UHL, Maria Molloy, Laboratory Manager, GUH, Sp Medical Scientist SVUH Nicola Boran, Mater Ciara Fanning, Snr Medical Scientist,UHW

24 • converse • Summer 2020 academy National Transfusion Advisory Group

Fergus Guilfoyle

r Joan Power, Consultant Haematologist for the Denise Neary, St Vincents University Hospital Irish Blood Transfusion Service (IBTS) in Cork Fabian McGrath, Technical University Dublin has been appointed to the role of Clinical Lead D John Sheehy, Cork University Hospital Advisor for Transfusion Services in Ireland. Dr Power is re-establishing the National Transfusion Advisory Group Margaret Tarpey, Galway University College Hospital (NTAG). The NTAG committee has representation from Martina Williams, Our Lady’s Children’s Hospital, a broad range of professional bodies and groups either Crumlin directly or indirectly involved in the Blood Transfusion Sheila Joyce, University Hospital Limerick process. Tina Coleman, The As the professional body for medical scientists in Ireland the Academy and Transfusion and Transplantation Science Advisory Body (TTSAB) were invited to The SSIG held their inaugural meeting on 11th February. participate. The requirement to have a national body The group is in the process of developing the terms for blood transfusion has been identified by medical of reference and prioritising the main issues faced by scientists for a long time. We now have the opportunity hospital blood transfusion laboratories. Over the coming to address the many common issues at a national level. weeks the SSIG will be collecting email addresses for the The main aims of the NTAG is to develop and implement main contact person in charge of each hospital blood a national framework for the delivery of a sustainable and transfusion laboratory. The SSIG will use these emails safe clinical blood transfusion service that provides expert in order to seek advice from you on various aspects of clinical advice, leadership and practical support for blood the blood transfusion process, to update and advise transfusion services. you on developments within NTAG. We hope that this The NTAG structure has three special interest two way communication will give every scientist in blood groups (SIG) to include Consultant Haematologists transfusion the opportunity to voice their opinion at this (Haematology SIG), Haemovigilance Officers time of change. The SSIG will feed back into the NTAG (Haemovigilance SIG) and Medical Scientists (Scientific committee on a regular basis. SIG). These professional bodies are the expert groups in Transfusion Practice in Ireland. The SSIG, in common The formation of the NTAG is an opportunity for all with the other two SIG’s, will play a vital role in the overall professionals engaged in transfusion practice to work function of the overarching NTAG. together to address the many identified challenges. The Scientific SIG (SSIG) membership is as follows: Email address [email protected] Fergus Guilfoyle, Chairperson TTSAB and NTAG Fergus Guilfoyle, Chair TTSAB. member Carol Cantwell, Regional Hospital Mullingar and Deputy NTAG member Anne Marie McCann, St. James Hospital Barry Doyle, IBTS

Summer 2020 • converse • 25 academy CIT/UCC Biomedical Science Society

• Another highlight for the society is our annual collaboration with UCC Surgical Society for UCC’s Blood Drive. This year there were 242 successful donors! Being chairperson of this society has been an honour and a privilege. I am very proud of what my committee and I have achieved this year. We held one of the biggest charity events on campus in the first semester. We had the largest ever attendance at the biomed ball and we have created a greater sense of community between all four years of the programme. Pádraig McKeown

Pádraig McKeown, Chair and Katie O’Brien Vice Chair, CIT/ UCC Biomedical Science Society.

he Biomedical Science Society was founded for the CIT/ UCC Biomedical Science programme in 2015 by a group Tof biomedical science students with the help of Dr Sinéad Kerins in UCC and hasn’t looked back since! The society deals with all academic and social events and issues for the Biomedical Science students and other students. Some of our Winners! major events include: On Monday March 23rd, UCC Societies held their annual STARS • Career Seminars – In the past there have been numerous awards via Zoom. These awards are one of the highlights of biomedical science students who have given presentations the society calendar and recognise the impressive work of over on where their degree has brought them in the world of work. 100 UCC Societies. The UCC Biomedical Science Society were As a society, we feel these events are some of the most thrilled to have received many acknowledgements throughout important in helping students make informed decisions on the night after an incredible, non-stop year. all the pathways available to them. Past speakers include; Dr The society were lucky enough to have two photographs Caroline Vaughan, Former medical scientist, Former Point of shortlisted for “Best Photo”, there were over 200 entries in this care technical specialist, Audit Diagnostics, Former Project category alone! Scientist & Acting Quality Manager, Waterstone Fertility The success didn’t end there for the society, as we were later Clinic. Caroline is now a full time Lecturer in the Department announced as runners up in two categories – Best Innovation of Biological Sciences in Cork Institute of Technology. Joan and Most Improved society as well as being nominated as the Dineen worked for a period in New Zealand as a medical best society within the college of Science, Engineering and Food scientist and Averil Kiely on her PhD research. We are always Science. open to hearing from past students and their journeys post This year was the first that the society had achieved this level degree! of recognition at the STARS awards and it certainly would not • Biomedical science ball – our biggest social event, held yearly have been possible without the dedication and creativity of in November where all Biomedical Science students and the 2019/2020 committee. The current chairperson, Pádraig lecturers come together for an evening of great entertainment. McKeown and vice-chairperson, Katie O’Brien both received This event really brings all years of the programme together. special acknowledgments on the evening and were presented • Can U Help Day in aid of the Cork University Hospital Charity with STARS Best Individual awards. There were 10 individual – the biggest annual charity event to happen in Semester 1. STARS presented on the night and it was an impressive With the help of five other societies, we managed to raise achievement for two of them to be presented to individuals within €2,700 in 2019 through a variety of events on campus such the one society. as raffles, bake sales and our now famous ‘’Quiz Loco’’. This year’s committee has shown levels of dedication that • 1st Year – 2nd Year Buddy System – each year we match each went above and beyond what was expected, and the incredible 1st year student to a 2nd year Biomed student who acts as a work did not go un-noticed. The current committee would like support to the 1st Year by answering any questions they may to express our gratitude to all of our collaborators over the past have and offering any helpful points they might have on 1st year, and we look forward to working together again in the near Year in an informal environment. future. • Other social events such as day trips to places like the Irish The 2019/2020 committee have set the ball rolling for the Blood Transfusion Service, to karaoke events, documentary incoming committee, and we are looking forward to following screenings, bowling and collaborations with other UCC their journey from September 2020 onwards. Societies. Katie O’Brien

26 • converse • Spring 2020 academy Just Another Day in the Lab

A freelance health journalist, Niamh Griffin, recently interviewed Catherine Dempsey, Senior Medical Scientist in CUH.

edical scientists are the unsung heroes of the have been in contact with a patient positive for COVID-19 Coronavirus outbreak coping with long days and are asked to self-isolate for 14 days, or until they receive a Mshortages of even the reagent needed to test for the negative test result. virus. Senior Medical Scientist Catherine Dempsey works at The reagent shortage in particular has become an issue Cork University Hospital and was central to recent efforts to across the laboratory system, as indeed it is globally. develop and test a new reagent for COVID-19 testing. CEO of the Academy of Clinical Science and Laboratory CUH was affected quite early in the outbreak, caring for Medicine, Helen Barry says: “We are a small country their first case on March 5th. This had an immediate impact fighting for our share. We’re pulling together, even making on the laboratory where Dempsey works. Based in CUH some reagents from scratch.” for four years, and with 14-years experience in hospital settings Dempsey still could not have predicted what followed. She says: “We got up and running with the laboratory testing the next day pretty much. We had anticipated that the situation would get worse. We had ordered in tests, kits and reagents and all of that; we have the expertise to do it.” Their shift-patterns changed to incorporate a 7am start with testing running until 8pm. In order to maintain correct social distancing, the number of people on the floor at one time had to be reduced, so the 40 microbiologists on the team work across three shifts now. One person stays on for the night shift. She says: “There are probably over 100 samples coming in each day to be tested. In the flu season I would say we have Lt to Rt: Liz O’Shea, Clíona O’Sullivan, Aoife Howard, Louise about 60 a day.” And of course, the teams continue to Barry, Denise Cronin, Isabelle O’Callaghan and Catherine work on testing for sexually-transmitted-diseases, swabs for Dempsey. wounds, viral respiratory tests among other normal work. However, less than two weeks after that initial patient, In April Dempsey got involved with an exciting move by Dr their high output was affected by shortages of both swabs Bridget Lucey, President of the Academy and virologists at and the reagent lysis buffer needed for testing. That left University College Cork to develop and test a new reagent. Dempsey and her colleagues making tough choices. This was then made up by pharmaceutical company Eli Lilly She says: “We had to make a difficult decision where we for validation by Catherine and her team at CUH. would prioritise the hospital patients (over staff). They are Like everyone else in the medical science world Dempsey vulnerable and their status has implications for infection is just getting on with her work, not seeking out the limelight. control and bed management. She says she was very moved by the public shows of “But we have to do the people who are in hospital before appreciation especially when everyone clapped to support we do the staff members. This is not good for the hospital healthcare workers recently. because we need to get people to return to work if they But she does have one small gripe. “We do get a bit can. You are isolated until the results come back, it impacts frustrated because in the media they say the paramedics massively on the running of the actual hospital.” are doing the testing or they are doing the testing at Páirc Ui Hospitals across the system have been affected by the Chaoimh. But they are just taking the swabs, that’s not the slower access to testing. Staff showing symptoms or who testing.”

Spring 2020 • converse • 27 academy Guideline on Communication of Critical Results for Patients in the Community Irene Regan

he new guidelines on "Communication of Critical the requesting clinician is aware of the urgency of the Results for Patients in the Community" were situation and to act accordingly. We know the importance Tlaunched on January 2020 by HSE CEO Paul Reid. of fast tracking the unexpected critical result. The guidelines set out the agreed approach and timelines Critical values communication is an integral part of our for communicating results to patients in the community quality management systems audited to the ISO 15189 based on the severity of potential underlying diagnoses, standard and under CORU statutory registration we are an imminent risk to the patient and the urgency of required to ensure we have the competencies in place to intervention. ensure appropriate communication of results in a way that Irene Regan represented the Academy of Clinical can be understood by the service user and others. This Science and Laboratory Medicine at the launch. includes diagnosis, prognosis, monitoring and treatment The Working Group set up to develop these guidelines options. was headed by Dr Mary Keogan, Clinical Lead for the The colleges providing our accredited programmes are Clinical Pathology Programme and included Project required to ensure that its graduates meet these standards Managers Anne Mannion and Joan McCormack, nine of proficiency. medical scientist representatives and with consultation Timely notification of critical values has also been across all stakeholders. endorsed as one of the leading quality indicators of the The aim of the document is to provide guidance on post-analytical phase by the Working Group “Laboratory communication of critical results for patients in the Errors and Patient Safety” (WG-LEPS) of the International community, whether the laboratory tests originated Federation of Clinical Chemistry and Laboratory Medicine from community or hospital settings. The procedure is (IFCC) in 2016. applicable to all laboratory results. There are many guidelines and papers on Speaking at the launch Paul Reid said: “The guideline communication of critical results but what this guideline is a welcome patient safety initiative providing clear does is, it builds on international best practice information for both staff working in laboratories and health recommendations and also gives us clear guidance on the care staff who request tests such as GPs and nursing staff pathways and stakeholders particular to Ireland and thus for communicating critical laboratory results. It will help to standardising the pathway. ensure that patients who have a lab test result indicating As we move forward to the implementation phase, they require urgent treatment, are contacted in a timely we will formalise the communication process between manner and arrangements put on place to make sure they laboratory medicine and primary care, this could be promptly receive the treatment they require.” regarded as a paradigm shift but they are already one Irene Regan stated that “Appropriate Communication of of the biggest users of laboratory services. Sláintecare results back to the patient is essential to patient care and serves to strengthen this relationship. safety and could arguably be seen as the most important The next critical step in implementation will be to put step in the pathway when a patient has a sample taken for in place the appropriate clinical governance structures laboratory analysis or ‘tests’. between laboratories or hospitals and primary care. I The lack or delayed communication of critical values has would urge that this guideline is followed through to been clearly recognised as a source of significant harm the implementation phase, it is essential that the HSE to patients, since these test results may lead to treatment led by Mr. Paul Reid adequately resources this both modification in as many as 98% of patients admitted during normal working hours and out of hours to provide to surgical wards and up to 91% of those admitted to this essential service to the community. I am sure this medical departments (2014). guideline will have an auditible impact across many clinical As one of 2,500 medical scientists we may be the first to programmes but also Sláintecare and ultimately leading to become aware of a potential medical emergency before what we all want better patient outcomes”.

28 • converse • Spring 2020 academy

Lt to Rt: Dr Louise Burke, Dean of the Faculty of Pathology; Dr Vida Hamilton, HSE National Clinical Advisor, Acute Hospitals, HSE; Dr Terry McWade, CEO, RCPI; Dr Mary Keoghan, National Clinical Lead, Clinical Programme for Pathology; Dr Cathal O’Keeffe, Head of Clinical Risk, State Claims Agency; Paul Reid, CEO, HSE; Dr Irene Regan, Past President, Academy of Clinical Science and Laboratory Medicine.

Key recommendations for Laboratories Medical Scientist Medical testing laboratories require a register of General Practitioners (GPs) and all health care professionals and Representatives on the services who send samples to the laboratory, including Working Group details of the appropriate contact number for transmission of critical results, during working hours, and out of Academy: Dr Jacqui Clarke Chief Medical Scientist, hours.(See example in Appendix 2 of the guidelines). Letterkenny University Hospital This registration process may be a standalone process, Academy: Dr Irene Regan Chief Medical Scientist, combined with data sharing agreements required Our Lady’s Children’s Hospital, Crumlin to comply with General Data Protection Regulations Academy: Mr Richard McCafferty, Chief Medical (GDPR), or part of a Service Level Agreement (SLA). Scientist, St James’s Hospital Many laboratories have a registration process in place. Academy: Ms Elaine Phelan Senior Medical Scientist, Additionally GPs and other laboratory users should be University Hospital Waterford given the option of supplying their personal mobile phone Ireland East Hospital Group: Mr John Crumlish, number or other contact details for emergency use. Staff Laboratory Manager, Mater Misericordiae University communicating critical results should include a statement Hospital of urgency, indicating whether the result requires action Ireland East Hospital Group: Mr Ray O’Hare Chief within two hours, or on a same day basis. Results should Medical Scientist, Our Lady’s Hospital, Navan. be communicated in line with accreditation requirements, and incorporate a read back procedure to ensure correct South Southwest Hospital Group: Ms Sinéad Creagh receipt of all information provided. Laboratory Manager, Cork University Hospital A local policy should be drawn up, clearly delineating Dublin Midlands Hospital Group: Ms Anne Walshe the staff responsible for the escalation procedure outlined Laboratory Manager Midland Regional Hospital in this guidance. Tullamore University of Limerick Hospital Group: Mr Kevin To read the guidelines - https://www.hse.ie/eng/about/ O’Connell Laboratory Manager, University Hospital who/cspd/ncps/pathology/resources/communication-of- Limerick critical-results-for-patients-in-the-community.pdf

Spring 2020 • converse • 29 academy The professional doctorate – a road less travelled Brigid Lucey

professional doctorate is a doctoral-level degree for experienced professionals who want to translate their Aindustry/laboratory expertise into a higher degree. At least 70% of medical scientists in Ireland hold postgraduate degrees. However, doctoral degrees are not common. Some of the reasons for this may include the fact that medical scientists who wish to qualify for a senior position need to have a Level 9 degree (MSc.) to qualify to apply for these positions. The most commonly used and cost-effective means to achieve this is through taught Master’s degree programmes (while working fulltime), rather than through an MSc. by fulltime research in a third level college. The fulltime and the part-time research Master’s Alternatively, it must have a comparable peer-recognised programmes, however, contain the option (where the impact on the postgraduate student’s profession research subject allows enough expansion) to enter the • The professional doctorate comprises an individual doctoral register and to proceed from what was originally journey of directed study designed to achieve specific intended to terminate at a level 9, emerging with a educational outcomes and a substantial programme of doctorate (level 10 award) instead. This is a Philosophiae original research Doctor (PhD/Doctor of Philosophy) degree. In contrast, • The path of progress of each individual is unique (in a professional doctorate is where one becomes a doctor this it does not differ from a PhD) but it does include an of biomedical science or a doctor of nursing practice, for individual’s professional development example. A doctorate by either route is the highest level of • The outputs of the professional doctorate ultimately degree available. In the UK, fewer than 10% of medical include a thesis or portfolio submitted for a viva voce, scientists who hold doctorates achieved them by the which may comprise the generation of new knowledge professional doctorate route; figures are not available for or original applications of existing knowledge and a Ireland. contribution to practice A PhD focuses on original research and data analysis • The results of the research must be shown to be and, normally, novel findings and substantial expertise result applicable to the workplace and/or have an impact on from those efforts. A professional doctorate, which is more practice in the profession directly applied to the workplace, focuses on conducting research to solve practical problems in the field, in deriving The PhD based on prior publication differs from the solutions to complex challenges, and in formulating effective traditional PhD in that it is normally based upon research professional practices already undertaken before registration for the PhD. This Salient points about the professional doctorate: research has normally already led to a number of coherent • It combines professional expertise with research and, publications/outputs. usually, some formal taught elements are included along the journey of the candidate (whether PhD or For further information, it may be helpful to have a look professional doctorate are being sought) at the links below as an example of a higher education • A professional in the workplace without a level 10 institutional approach to supporting the professional doctorate qualification might wish to have their expertise aligned candidate. with this award https://www.cit.ie/contentfiles/postgrad/Policy%20Docs/ • Quality and Qualifications Ireland (QQI) is the body Framework%20for%20Professional%20Doctorate%20(AC,%20 that regulates the processes for attainment of all 2012).pdf National Framework of Qualifications awards https://[email protected] • The professional doctorate must meet the same https://www.gmit.ie/ standard as the PhD, and requires the student to (GMIT are currently in the process of acquiring delegated generate significant peer-reviewed outputs from authority to confer Level 10 qualifications in their biological their research, such as (for example) publications, sciences department in which resides the medical science standards of practice, inventions/patents. degree.)

30 • converse • Spring 2020 academy Preparing for CORU Registration – An Academy Guide Bernadette Jackson

1. Who can apply and which section to apply to: Academy Letter of Eligibility/Certificate of Competency, a) Section 91 – a medical scientist working in Ireland for Placement Certificate etc. two of the last five years Remember the MSc is not usually required, it is your primary b) Section 38 – a new graduate medical scientist or recently qualification to practice that is required. qualified with less than two years as a medical scientist NOTE: If your degree parchment is not clear regarding the c) International Applicants specific degree completed (some only have the words BSc Note: If you are a medical scientist working in allied fields e.g. Science in the title of the award) further documentation may be Surveillance, Education, Research, Quality, Management, requested by CORU to confirm the specific qualification you Haemovigilance you can also apply. completed.

2. Before you Apply Online: Gather your documents - 4. Notarisation of Documents: What you need: Notarisation is verification that the photocopied documents a) Proof of Professional Employment – POPE Form https:// and the original documents correlate. Both sets must be coru.ie/health-and-social-care-professionals/registration/ available for the Notary. registration-requirements/supporting-forms-and- Notarisation is available in the Academy office most weeks documentation/ and free of charge for Academy members. There is a small Note: This must be signed by a Laboratory Manager or Head fee for non-members. of Department and must evidence two years of continuous Keep an eye on the website acslm.ie or contact the working. ACADEMY office (01 9059730) for next availability of the b) Declaration – signed and notarised https://coru.ie/health- Notary. You can submit qualifications certified a few years and-social-care- professionals/ registration/ registration- ago – if they are the original certified copies – do not submit requirements/supporting-forms-and-documentation/ a photocopied version of the certified documents. c) Qualifications – photocopied and notarised (see 3A below) 5. Lost Documents: d) Identity Card/Passport/PSC card – Photocopied and a) Parchment – contact your College Examinations Notarised department for re-issue of a letter of qualifications e) Two Passport Photos – signed on back b) Academy Eligibility Certificate - contact ACADEMY office f) When the Garda Clearance form is being processed – 01 9056730 (Re-issued Free of charge for members; fee the applicant will need to submit a certified copy of police for non-members) clearance documents from countries outside of Ireland where the applicant lived for longer than a year, over the 6. Once Documents Gathered and Notarised: age of 18. The applicant applies for these documents Apply Online, print cover page for submitting all themselves. CORU will advise on what you require. documentation - Forms should be submitted by Registered Post 3A. Qualifications for Submission - Recent Graduates: - Academy-approved from ROI – GMIT, CIT/UCC, DIT/ 7. Garda Clearance: TUDublin – BSc Parchment Instructions will be sent to you online by CORU once your - Certificate or Diploma of Placement if available application has been completed online.

3B. Qualifications for Submission – Not a Recent 8. CPD: Graduate: CORU has an online guide to the CPD requirements for - Certificates, Diplomas, ONC, HNC, Finals registered medical scientists. - Whatever were the qualifications to practice as a staff grade Medical Scientist/ Technician (e.g. Cert + Diploma or The Academy will support your CPD development through Cert + BSc as applicable) our online system and the provision of educational meetings, conferences and workshops. 3C. Qualifications for Submission – Non-Standard The Academy CPD programme is supported by two staff Academy Pathways: Jemma Kehoe and Leo Mulvaney. - Copy of your Degree Bernadette Jackson, - Copy of further Certificates/Letters of Eligibility e.g. President Elect.

Spring 2020 • converse • 31 cpd CPD Update

It was intended to provide information at the AGM in April 2020 regarding CPD and CORU registration. However, the Covid-19 pandemic has rearranged all our lives and the AGM was no exception to rearrangements.

Contact Key Points/Questions How we deliver information and communicate during the Approx. 1 CPD credit for every hour of pandemic must change in the context of CPD and may pave new or enhanced learning achieved the way for better What were the learning outcomes? communication What have you learnt through going forward. completing this activity and how have We will engage your skills and knowledge improved with you on a more or developed? What’s the impact on frequent basis practice and how have you integrated through our this learning into your practice/ newsletter by email work? How has this learning made a and we hope you will difference to your capability and performance as a Medical engage with us. Scientist?

New Initiatives Not all “Doom & Gloom” The Academy hopes to launch a short screen recording For now, remember that everything you perform workwise video of the CPD system which will be available to you on the is CPD. Especially now in this new era of Covid-19, the ACSLM website. This will allow you to see and understand value of necessary and new learning can be converted into the full functionality of how you can record your work on the CPD credits. Reflection of the "what", "so what" and "now website and the benefits to you as a member. what" are really valuable, as much as the work event or new There is a “Covid-19 Resource” page on the website. article/new procedure are in themselves. Please browse and contact us with useful information for The documenting part of inclusion. reflective practice needn't We are also producing a series of reflective practice videos be terribly laborious or time in conjunction with our HSCP CPD Network colleagues zapping. Use the voice which will be made available to you also. The first video will memo on your phone to introduce and explain the function and benefits of reflective record the key elements or practice/learning. if you're a pen and paper We are modifying the Academy’s CPD booklet (Edition 8 person, leave a notepad – January 2019) to reflect CORU’s CPD credit requirements. handy and "head-dump" Previously 50 CPD credits per year was the target but under the details in there when CORU this requirement is now 30 per year. convenient. Short notes can be developed at a deeper level at another time when you've had the chance to reflect and CPD Record catch your breath! According to Coru, March 2020, a total of 18,299 We provide our members with CPD learning opportunities professionals were registered with CORU and of these 178 through CPD of the Month, MCQs, morphology quizzes etc were Medical Scientists. All practising Medical Scientists and a system for recording their CPD activities. The CPD must apply for registration before 31 March 2021. This record template is provided in an editable electronic format marks the end of the transitional period which began on the to assist you in documenting your achievements, CPD work, 31st March 2019. There is less than a year remaining now. PDP etc in order to achieve and maintain your professional Remember, we are a resource and more than willing to registration. help you in any way possible. In brief the CPD record includes: • Implementation of learning activities that achieved 30 CPD credits of new or enhanced learning • Evaluation and reflection of the learning achieved Leo Mulvany • Review of learning needs for the next 12-month CPD Officer period [email protected] • Planned learning activities for the next 12-month period

32 • converse • Spring 2020 updates Health and Biomedical Science Updates Compiled by Helen Lambkin

1 Standardising surveillance of College of Obstetricians and Gynaecologists (RCOG) has Hepatitis E virus infection in the EU/ found that there were missed opportunities to prevent or diagnose cancer earlier in 159 cases.The review examined EEA: A review of national practices the screening histories of 1,038 women who were screened and suggestions for the way forward. by CervicalCheck since 2008, 1,034 of whom had gone on to develop cancer. Despite this, the RCOG review concluded that In immunosuppressed patients or in those with pre-existing women can have confidence in the CervicalCheck programme. liver disease, Hepatitis E virus (HEV) infection may lead "The report finds the CervicalCheck programme is to severe courses of disease and chronic or persistent working effectively and crucially, that women can have infection. Chronic HEV infection among immunocompromised confidence in the programme”. individuals is characterised by a prolonged viraemia, Lorraine Walsh of the 221+ patient support group resigned sometimes without clinical signs of viral hepatitis as well as one of the patient representatives on the CervicalCheck as absence of IgM or IgG antibodies, and may rapidly lead steering committee after she learned that some information to cirrhosis and death. HEV is a multifaceted pathogen: its being given to the HSE by the RCOG was inaccurate, epidemic genotypes 1 and 2 are transmitted faecal-orally including information relating to her own case. Speaking on through contaminated water and circulate mainly in Asia and RTÉ's Primetime she explained that she received two reports Africa, while its genotypes 3 and 4 are zoonotic infections from RCOG just 24 hours apart - one stating her slides were with an animal reservoir. In EU/EEA countries, genotype 3 concordant, and one stating they were not. predominates and has been mainly linked to the consumption To read the report: Cervical screening in cases of of undercooked pork, processed pork products (including cervical cancer in Ireland between 2008 - 2018 RCOG ready-to-eat sausages) and shellfish products but also to Independent Expert Panel Review. December 2019. https:// occupational exposure via direct contact with pigs and their www.gov.ie/en/publication/a4e567-expert-panel-review-of- manure. Rarely, transfusion- or transplantation-transmitted cervical-screening/ infections related to contaminated blood products or infected organs have been reported HEV infection is not notifiable at EU/EEA level, therefore 3 Update on Cartwright and Chido/ surveillance relies on national policies only. Between 2005 Rodgers Blood Group Systems and 2015, more than 20,000 cases were reported in EU/EEA countries. HEV testing is established in 26 countries and 19 In the Immunohaematology Journal in December 2019 two countries (including Ireland) sequence HEV viruses. updates were published on the Cartwright and Chido/Rodgers Seventeen of 20 countries with existing surveillance blood group systems. systems collect the minimal data set required to describe the Cartwright blood group system. From 1956 until 2017, epidemiology of acute cases. Eleven countries test for chronic the Cartwright (Yt) blood group system consisted of two infections. Twelve countries collect data to identify potential antigens, Yta and Ytb. Yta is a high-prevalence antigen, and clusters/outbreaks and information on possible routes of its antithetical antigen, Ytb, shows much lower prevalence. transmission. Overall, the majority of EU/EEA countries collect In 2017, YTEG was identified, and, in 2018, the International the suggested data and meet the outlined requirements to Society of Blood Transfusion added high-prevalence antigens confirm an acute case. YTLI and YTOT. Cartwright antigens result from point mutations Adlhoch C et al. J Clinical Virology 2019; vol 120; pages in the acetylcholinesterase gene on chromosome 7q. Little is 63-67. PMCID: PMC6899520 known about antibodies against YTEG, YTLI, and YTOT. Chido/Rodgers blood group system. The International Society of Blood Transfusion (ISBT) has designated the ISBT 2 Cervicalcheck Controversy number 017 to this system and the abbreviation CH/RG for the Taoiseach Leo Varadkar apologised in October 2019 for antigen or antibody notation. There are currently nine antigens the "humiliation, the disrespect and deceit" shown by the in the CH/RG system. Irish state to more than 1,000 women in the cervical cancer Immunohaematology December 2019. scandal. Mr Varadkar said that while a state apology may not An update on the Chido/Rodgers blood group system. provide closure, "I hope it will help to heal". He offered his Mougey R1. PMID: 31935328 apologies to both the women and their families. An update on the Cartwright (Yt) blood group system. A review of CervicalCheck carried out by the UK's Royal George MR. PMID: 31935332

Spring 2020 • converse • 33 updates

4 Use and Learn phase for Falsified 6 Digital PCR in Myeloid Medicines Directive extended again Malignancies: Ready to Replace Quantitative PCR? The Irish Medicines Verification Office (IMVO) is a new organisation set up to protect Irish patients from the threat This free review article examines the potential for digital of falsified medicines being supplied through legitimate PCR for detection of small leukaemic clones using a PCR channels. It is a not-for-profit organisation whose role is to technology that provides absolute DNA quantification. It set up and manage the Irish medicines verification system. reported that “dPCR is particularly useful to detect a low This is required to comply with the EU Falsified Medicines amount of target and therefore it represents an alternative Directive requirement that all medicine packs must carry a method for detecting measurable residual disease special barcode containing unique identifiers. Under the FMD, (MRD). The main advantages are the high precision, the blood products, except red cells and platelets, need to be very reliable quantification, the absolute quantification verified as genuine before they can be issued to patients. This without the need for a standard curve, and the excellent process involves a visual check that an anti-tamper device reproducibility”. on the product is intact and scanning a 2D barcode, unique However, it also discussed the disadvantages including to each pack, to confirm the product is on the approved the costs that are higher than standard qPCR, the lack list with the IMVO. Special scanners and ezFMD software of standardised methods, and the limited number of are required to verify and dispense the products. Although laboratories that are equipped with instruments for dPCR the legislation underpinning the FMD was enacted from 9th technology. In this review they summarised the available February 2019, the process is in a use and learn period, data on the use of digital PCR in investigation of acute which has been extended a number of times, most recently myeloid leukemia and myeloproliferative disorders. to September 2020. After representations to the HSE by the International Journal of Molecular Science May 2019 Academy and the MLSA, Sheila McMorrow was appointed on Cilloni D et al. PMID:31067725 a temporary contract to draft a national SOP for the verification process for Transfusion laboratories to use as a template. Sheila also visited multiple laboratories to assist with training and implementation during her contract, which has since 7 New Genetic Variant of APOE3 concluded. may postpone Clinical Onset of Alzheimer’s Disease

In their Nature Medicine study, Yakeel T. Quiroz, a clinical neuropsychologist and neuroimaging researcher at MGH, describe a patient, who had a gene mutation associated with early onset Alzheimer’s disease, who did not develop mild cognitive impairment until her 70s, nearly three decades after the typical age of onset. Like her relatives, who showed signs of dementia in their 40s, the patient carried the E280A mutation in a gene called Presenilin 1 (PSEN1), which has been shown to cause early onset Alzheimer’s disease. But she also Example of 2D barcode on blood product, containing had two copies of a gene variation called ChristChurch, information unique to that vial named after the New Zealand city where it was first Visit www.IMVO.ie for further information found, in the APOE3 gene (APOE3ch). Imaging tests revealed only minor neurodegeneration in the patient’s brain. Surprisingly, the patient had unusually high brain 5 New Immune T-Cell Found by Welsh levels of amyloid beta deposits, a hallmark of Alzheimer’s researchers disease; however, the amount of neuronal tau tangles — another hallmark of the disease — was relatively limited. Genome-wide CRISPR-Cas9 screening reveals ubiquitous The investigators suspect that carrying two copies of T cell cancer targeting via the monomorphic MHC class the APOE3ch variant may postpone the clinical onset I-Related protein MR1. of Alzheimer’s disease by limiting tau pathology and A new type of T cell has recently been discovered by neurodegeneration. researchers in Cardiff university, which has broad cancer cell “This single case opens a new door for treatments of killing activity. This cell was discovered to express a novel T Alzheimer’s disease, based more on the resistance to cell receptor which allows it to attach to most cancer cells. Alzheimer’s pathology rather than on the cause of the The cells express a HLA-like molecule called MR1. T cells disease. In other words, not necessarily focusing on equipped with this receptor were shown experimentally to kill reduction of pathology, as it has been done traditionally in lung, skin, blood, colon, breast, prostate, ovarian, renal and the field, but instead promoting resistance even in the face cervical cancer cells. of significant brain pathology,” said Quiroz. These cells, in addition to the other activated T cell cancer Nature Medicine. 2019 Nov;25(11):1680-1683. PMID: therapies, offer potential for new effective cancer therapies. 31686034 Crowther MD et al. Nature Immunology February 2020. PMID: 31959982.

34 • converse • Spring 2020 updates

8 Biomarkers for Predicting Response to migrate and to change into more specialised brain cells. to Immunotherapy with Immune "Our analyses indicate that genes influenced by SDCCAG8 are important for different brain functions and this presents us with Checkpoint Inhibitors in Cancer a model for how other genes may contribute to the biology of Patients. schizophrenia”. "This can be exploited to help understand the biology of This publication was written by Dr MJ Duffy and Professor J schizophrenia in greater detail and open up opportunities for Crown of St. Vincent’s Hospital and the Conway Institute of new drug development, which is badly needed for this mental research, UCD. illness," explained one of the study's lead researchers, Prof They describe how immunotherapy has revolutionised the Ciaran Morrison, head of NUI Galway's School of Natural management of cancer in recent years, but that only some Sciences. patients respond to the therapy. Biomarkers are required Human Molecular Genetics. Flynn M et al December which can accurately predict who will respond and ensuring 2019. PMID: 31868218. effective use of the immunotherapies. Three predictive biomarkers for immunotherapy include PD-L1 – programmed death-ligand 1, MSI/dMMR – microsatellite instability/ 10 The investigation of the role of defective mismatch repair and TMB – tumour mutational burden. However, the authors reported that despite being IL-17 using a mouse model — widely investigated assays for these biomarkers are still experimental autoimmune evolving. They recommended an urgent focus of future encephalomyelitis (EAE) — research to be on the optimisation and standardisation of that mimics human Multiple Sclerosis. methods for determining these markers. Researchers in Trinity college looked for cells that could be Clinical Chemistry 2019 Oct;65(10):1228-1238. PMID: producing IL-1-beta in response to IL-17. They found that IL- 31315901. 17A mobilized IL-1-beta-secreting immune cells (neutrophils This is supported by a recent study published in the Journal and inflammatory monocytes) to lymph nodes. In turn, these of Pathology Clinical Research in December 2019 [Dodson A cells promoted the disease-promoting activity of T-cells in the et al, PMID – 31849189] titled - External quality assessment CNS. demonstrates that PD-L1 22C3 and SP263 assays are “Our team found that IL-17 plays a critical ‘priming’ role systematically different. in kick-starting the disease-causing immune response In this study, in which Tony O Grady, Royal College of that mediates the damage in experimental autoimmune Surgeons, Beaumont hospital was an author, they reported encephalitis and MS,” Kingston Mills, a professor at Trinity’s “For two 'critical samples', in runs A and B, 22C3 IHC had School of Biochemistry and Immunology, and the study’s lead significantly higher PD-L1 expression than SP263 IHC author, said. (p < 0.001), whilst the PD-L1 scores for the other six samples “The new research shows that, instead of playing a direct were similar for all assays. Equivalency of approved PD-L1 part in CNS pathology, a key role of IL-17 is to mobilise and 22C3 and SP263 assays cannot be assumed as the scores activate an army of disease-causing immune cells in the cross the clinically relevant thresholds of 1% and 50% PD-L1 lymph nodes that then migrate to the CNS to cause the nerve expression”. damage,” Mills said. J Pathol Clin Res 2019 Dodson A et al, PMID – “As well as shedding new light on the importance of IL-17 31849189 as a drugs target in RRMS, our research highlights the huge potential of drugs that block IL-17 in the treatment of other autoimmune diseases, such as psoriasis and rheumatoid 9 Altered gene regulation as a arthritis” primary author Aoife McGinley said. candidate mechanism by which Interleukin-17A Serves a Priming Role in Autoimmunity ciliopathy gene SDCCAG8 contributes by Recruiting IL-1b-Producing Myeloid Cells that Promote Pathogenic T Cells. Immunity. McGinley et al. January to schizophrenia and cognitive 2020. PMID:32023490. function.

Irish scientists have identified how some genes may increase 11 Lab-grown Heart Muscle transplanted the risk of schizophrenia. Schizophrenia is a serious mental illness that causes disturbances in thoughts, perceptions, into a Human for the First Time emotions and behaviour. It affects about one in every 100 people worldwide and usually occurs first in adolescence or A team in Osaka university announced their heart tissue early adulthood, although it can also occur later in life. transplant recently. They grew cells from induced pluripotent Previous large-scale studies had identified SDCCAG8 stem cells into cardiac muscle cells and placed degradable as a gene involved in schizophrenia and the NUI Galway sheets containing these muscle cells onto damaged heart team decided to investigate further its role in the illness. The tissue. The advantage of these type of stem cells is that they scientists used CRISPR-Cas9 genome editing to remove can be sourced from the patient’s own blood or skin cells. This SDCCAG8 from cultured brain cells. Genome editing of means there is less chance of rejection of the new cells. SDCCAG8 caused defects in primary ciliogenesis and cilium- Yoshiki Sawa and his team announced their dependent cell signalling. This resulted in the cells struggling breakthrough in a news conference on January 28th 2020.

Spring 2020 • converse • 35 meetings Multidisciplinary Seminar Report on the joint CPD seminar ‘The Transplant/ Immunocompromised Host’

Presenter Geraldine Donnelly, Chief Medical Scientist in the National Histocompatibility and Immunogenetics Service for Solid Organ Transplantation in Beaumont.

our Academy Advisory Bodies a transplant), donor work-ups and of recipients and their potential (Immunology, Microbiology, post-transplant monitoring. Especially complications following transplant. FTransfusion & Transplantation complicated to manage are those The morning session was completed Science and Virology) put together a patients with multiple HLA antibodies, by Robert McCutcheon, Chair of joint event based on the transplant / some of whom end up only being the Irish Heart and Lung Transplant immunocompromised host. The event potentially compatible for a donation Association and a heart transplant has held on Friday 29th November in from less than 1% of the population. recipient, who gave a talk on the St Laurence’s Church in the TU Dublin Geraldine’s presentation was transplant process from the patient’s Grangegorman campus. The line-up followed by a talk from Jean O’Reilly perspective. Robert told his personal for the event was an interesting mix of of Organ Donation Transplant Ireland story of the events leading up to his speakers from a variety of disciplines (ODTI). Facts and figures on transplants transplant and subsequent recovery. and backgrounds, who focused on the performed in recent years in Ireland This was an engrossing contribution issues affecting patients undergoing a were presented. In 2018 127 kidneys, which gave some perspective on the range of transplant types. 56 livers, 28 lungs, 18 hearts and five debilitating effects to patients who are The first speaker was Geraldine pancreases were transplanted. Jean awaiting a transplant, followed by the Donnelly, Chief Medical Scientist in also gave an absorbing account of the huge positive impact that the transplant the National Histocompatibility and donor co-ordinator’s role in consulting has on their lives. Robert also gave an Immunogenetics Service for Solid with the family of a potential donor, overview of the Irish Heart and Lung Organ Transplantation (NHISSOT) while also liaising with transplant Transplant Association, which aims to (previously the Histocompatibility centres to ensure availability of provide support, help and information & Immunogenetics Laboratory) in recipients within the short window to all heart and lung transplant Beaumont. The service is currently available. recipients and their families, pre and staffed by 21 scientists with two Dr Sinéad Stoneman, Specialist post operation. consultant immunologists. Geraldine Registrar in Nephrology from Beaumont The afternoon session resumed provided a comprehensive and spoke about renal transplantation. with an engaging presentation from comprehensive overview of the work Sinéad provided a history of renal Margaret Ann Connaughton, a Senior processes within the department in transplants from the first transplant in Medical Scientist in St Vincent’s relation to kidney transplants. This December 1954 until the present. The University Hospital. For the first section included pre-transplant work-ups, current status of the kidney transplant of her presentation, Margaret Ann maintenance of the Transplant Active programme in Ireland was provided as focussed on the support the laboratory List (currently 400 patients awaiting well as a section on the management provides to the liver transplant unit

36 • converse • Spring 2020 meetings

in St Vincent’s and the changes that have occurred in the unit since it first began operations in 1993. Of particular Clinical Chemistry/ interest was the decrease in numbers of products transfused during a liver transplant from an average of 18 red cells, 34 platelets and 29 plasma in Microbiology Joint 1994 to an average of 4.5 red cells, 0.7 platelets and 3 plasma in 2018. The second section of Margaret Ann’s talk discussed the Stem Cell Meeting Laboratory, which celebrated its 25th year of service in 2019 so this was a ith emerging infections such timely presentation. The reasons for as COVID-19 grabbing all the and processes behind the collection, Wheadlines, the focus can shift processing and infusion of autologous from familiar chronic conditions such stem cell transplants were all outlined. as diabetes, even though in the long- The next speaker Dr Catherine term, such conditions have a significant Flynn, Consultant Haematologist impact on provision of healthcare and in St James’s Hospital, gave an population health. According to Diabetes overview of the Stem Cell Transplant Ireland, the total number of people living programme there. In 2018 the unit with diabetes in Ireland is over 225,000, completed 98 autologous transplants with a Healthy Ireland survey showing (>80% for lymphoid malignancies) that around 850,000 adults over 40 in the and 77 allogeneic transplants (~66% are at an increased for myeloid malignancies). Catherine risk of developing, or already have, Type Karen Hickey, Chair of the provided an in-depth overview of 2 Diabetes, approximately 18% of the Microbiology Advisory Body, the allogeneic transplant process population. An afternoon event in Sligo University introducing the meeting. in myeloid malignancies, with some Hospital was jointly organised by the interesting case studies highlighting Microbiology and Clinical Chemistry some of the long term issues such and spoke about the research being Advisory bodies to provide information patients encounter. carried out in the APC Microbiome on the clinical treatment of diabetes and Centre, where they aim to investigate how The final talk was given by Dr Breda the role, we as medical scientists, have Lynch, Consultant Microbiologist from bacteria in the gut influence health and in the overall care of the diabetic patient. disease. She has numerous publications the Mater Hospital. Breda, who has The first speaker was Dr Siobhan Bacon, in the field of functional foods and their a particular interest in heart and lung a Consultant Endocrinologist, St Vincent's impact on microbiome and overall health transplant patients, gave a presentation University Hospital, who has been and introduced us to her current research on the management of opportunistic involved extensively in the field of diabetes on natural vs artificial sweeteners and infections in the immunocompromised research for a number of years and has their effect on the gut microbiome. Her host. The reasons for and the types of numerous publications, particularly in the talk generated a lot of fascination and infections seen in a range of transplant area of Maturity- onset Diabetes of the it was followed by many interested patients, at various stages of their Young (MODY). She discussed “different” questions! treatment, was depicted. The recent diabetes, and how the results obtained Our final lecture was given by Dr Vlasta advances in prevention and treatment in the laboratory are vital in the diagnosis Zujic Atalic, Consultant Microbiologist, of infections in transplant patients was of less common types of diabetes, such who spoke on infections in diabetic discussed as well as prophylactic as MODY and LADA (Latent Autoimmune foot ulcers and the difficulties involved strategies for some common Diabetes of Adulthood). Tests in in treating them. With some real life opportunistic infections seen in this particular mentioned were C-peptide + photographs (obtained with patient patient cohort. autoantibodies. The second speaker was consent), this was a sobering end to the This discussion closed what was Claire Maye, a Paediatric Clinical Nurse day as it highlighted, in the most visual a diverse and well received seminar, Specialist, SUH, who gave an overview of way, the extent of the damage to the body which brought together speakers and how their team, with the aid of technology, caused by diabetes. are helping patients achieve target attendees with experience in a variety We are hoping to have a link in the HbA1c. It was fascinating to learn of the of medical science disciplines. Thanks near future in the members' area of advances in diabetes care technology Academy website, to either a video or again to all the speakers, organisers, and how important this is to patients and powerpoint presentation. We would also attendees and to TU Dublin for their quality of life. like to acknowledge the amazing help we providing an excellent venue. The event moved on to the received from the Academy CPD Officers, Fergus Guilfoyle, Chief Medical Microbiology side of things with the third Leo and Jemma, and the entire laboratory Scientist, Coombe Women and Infants speaker, Dr Fabiana Hoffmann Sarda, staff who helped out on the day. University Hospital. travelling from the APC Microbiome Karen Hickey, Snr Medical Scientist, Chair, Transfusion and Transplantation Ireland Research Centre in Cork. Dr Sligo University Hospital, and Chair, Science Advisory Body. Hoffman Sarda is a post-doc researcher Microbiology Advisory Body.

Spring 2020 • converse • 37 meetings

Redesigning healthcare: What sort of health service do we want and are we prepared to pay for it? Thursday, 6th February 2020, Croke Park Stadium

he 16th National Health Summit the biggest issues to health services advisory leader at EY delivered a talk was held in the Croke Park on across the western World were labelled "How Digital is Enabling the TFebruary 6th. due to changing demographics, Transformation of Healthcare". He The summit began with an opening the management of burgeoning spoke of near-future smart hospital welcome by Audrey Carville RTÉ numbers with chronic disease and the technologies including integrated broadcaster of Morning Ireland fame fragmented nature of delivery systems hospital platforms, virtual assistants, AI and was the followed by the opening and associated skills sets. Shear enhanced interpretation of lab results address delivered by Ciarán Devine, outlined how our current capacity level and even fully automated bed cleaning Chairman of the Board of the HSE. of 95% was unsustainable and referred machines. He spoke of the ‘transformational to blueprint for change outlined in WHO “What we’re seeing is technological journey ‘of the HSE and stated that Declaration of 2018 on Transforming factors driving change,” said McBride, Ireland has made the greatest gains a Healthcare system and its 2019 describing systems now being rolled in the European Union with regard to document on Integration Care and out around Europe, some of them in improvements in life expectancy. With Chronic Disease Management. This is Ireland. regard to Health spend there are only a very comprehensive plan with five key After a break the conference split into six countries that have a higher spend areas of action identified three separate streams, addressing than us with just two of this six having regional re-organisation, healthcare a higher life expectancy rating. The 1. Integrated Care Delivery Models innovation and the challenge of most significant problems associated 2 Innovation and Digital Care removing private care from public with our Health System stem from our Transformation hospitals. Having chosen Stream ageing population and flu outbreaks 3 Workforce Developments and 1, I listened to a very interesting which place acute pressure on our Digital Literacy presentation by Goran Henriks, Chief hospitals. 4 Patient and Citizen Engagement Executive of Learning and Innovation An obesity level of 18 per cent, well 5 Value based Care, Financial at Qulturum, Jonjoking County, above the European average, is also Models Incentives and Sweden. He spoke of the huge drive a significant issue. Devane stated that Assessment for decentralising their public health the newly established Board and its inspired by the case of an elderly sub committees will improve issues It is envisaged that in future health patient namely his mother and her such as patient safety, waiting lists, systems <15% of care will be delivered drive for autonomy even at ninety improved performance and budgetary in a hospital setting. five years of age. This change has management through the delivery of a A panel discussion followed debating taken over thirty years in Sweden and much more integrated health system as the future HSE and the future health is encapsulated in the phrase ‘from envisioned in Sláintcare. system in Ireland. The main obstacles Hospitals to Homespitals’. Their aim Joanne Shear, President and to a future patient centred integrated is to keep patients away from hospital Chief Executive of Primary Care health system in this country are the and to deliver as much treatment and Transformation Experts then took the massive budgetary requirements of care to the home as possible. podium and began by posing the such a change and the huge resource The biggest challenge which may question “Is changing from a hospital requirement. Jennifer Brophy, a clinical also be Sláintecare biggest challenge system to a health system the answer specialist in speech and language also is captured by Martec's law to transforming our health service? therapy at the HSE, stressed the which states that technology changes Formerly a clinical programme manager importance of listening to staff at every exponentially, but organizations change for the US government’s Department level of the organisation. much more slowly (logarithmically). This of Veteran Affairs, she outlined that Aloha McBride, global health leaves a huge gap.

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commitment he has seen from front line staff right throughout the country as he has been engaging in a country wide tour of many and varied health sector providers. He described having seen a huge amount of duplication throughout the service and suggested that this was a poor use of resources and in the new evolving HSE there would be a requirement for devolved structures with regional accountability. Whilst it currently appears to be a consensus amongst our politicians that Sláintecare is the best way forward for our health system there remains a huge inter connected tangled mass of issues yet to be resolved. These have the potential to sideline Sláintecare and remove the resources from it thereby In Sweden they have managed to action in rural Ireland. consigning it to the sorry fate of many introduce this paradigm shift with We then had a panel discussion previous laudable healthcare initiatives. tremendous results both in terms featuring Laura Magahy, Director, Speaking during his interview on the of health outcomes and budgetary Sláintecare Programme Office, number of acute hospitals in Ireland, savings but it has taken place slowly Department of Health, Dr Sara Bourke, Reid cited Roscommon and Dundalk over many years driven by a committed Health Policy Analyst and Research as successful examples, but cautioned legislature and financial resources. Associate Professor, Trinity College the opening and closing of hospitals The results are there to see but it Dublin, Roisín O’Leary, Senior Patient was ultimately a government decision. requires an end to short term one Advocate, Sage Advocacy. The day ended with a panel government period type thinking. The debate centred on the question discussion on the challenges of turning Sweden’s success may be the first whether the new Regional Areas an innovative idea into a reality. Eileen compelling case anywhere in the world proposed in Sláintecare would merely Byrne, managing director of Clanwilliam for decentralisation and investing in herald the return of the old Health Health spoke on developing prevention. Goran described how Board systems. software which supports over 20,000 Jonkoping County Council plans, funds Dr Bourke described how in pharmacies, GP’s and clinical practices and provides health care services for its Sláintecare, six new regions have across Ireland and the UK . She saw population, working in partnership with been proposed with the idea being the possibility of a much greater role in local government. It has considerable to devolve healthcare power back to the electronic prescribing of medicines autonomy and tax raising powers by the regions thus empowering people which could end the laborious and time virtue of Sweden’s system of devolved to manage their own health. This is consuming manual process currently in government. due to happen in 2022 with legislation place. The impression given was that With his presentation Dr Padraig currently being prepared in the to introduce an innovation into the HSE Collins, Senior Clinical Psychologist, Oireachtas. It is envisaged that the require huge drive and commitment as Clinical Lead Access to Psychological command and control model currently many barriers will be raised to prevent Services Ireland Roscommon provided operated by the HSE would be broken the development. a working example of how Sláintecare up with far fewer layers of control in Overall the 16th Health Summit is working and could work if rolled future. There was a note of caution was an extremely well organised out nationally. He described a local however in that this implementation event with a large attendance. Whilst I Mental Health Service Model that’s would require real political leadership. believe that the ten year vision for our successfully responding to a local After the lunch break, Paul Reid future Healthcare system in Ireland populations needs. The programme Chief Executive Officer of the HSE as envisaged in Sláintecare is full demonstrates the delivery of a service was interviewed on stage by Audrey of promise I am concerned that the near to home, which responds to Carville. Coming to the HSE from political leadership to drive such a patients needs, at the lowest complexity outside the health sector Reid credited change over a long term is not there. working upwards and indeed stepping his time working on Sláintecare for Yet despite this our health system down from acute services. He showed the insight it provided into creating a continues to deliver and our overall how the service free at the point of entry brand new strategy for the HSE “It was health indicators continue to improve. was hugely successful in providing always about the next big change, the This is testament to the massive care at the earliest possible stage thus big change that was coming soon,” commitment shown by the staff in the preventing escalation and possible Reid said. “Wouldn’t it be great if we HSE. entry into more acute care. This is could focus on running the service, and Brian O’Malley, Laboratory Manager, an award winning programme and creating change at the same time"? Cavan General Hospital, represents Sláintecare principles in Reid acknowledged the massive Academy Council.

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that we need to bring this revolution of genomics medicine to the bedside quickly and fast, especially in relation to chronic complex diseases. They both presented moving case studies, demonstrating the value of genomics. As a result of his daughter being diagnosed with a catastrophic form of epilepsy, Charles Steward initiated an international study to investigate the structure of genes involved with developmental and epileptic encephalopathies. Latterly, he moved to Congenica where as the Clinical Domain Lead for Epilepsy he now works to increase understanding of the genetics summit focused exclusively on genomics was held in behind neurological disorders, including the most devastating Ireland for the first time on Thursday 23rd January at consequence of epilepsy, sudden unexpected death in Athe Aviva Stadium Dublin. Genomics Summit 2020. It epilepsy (SUDEP). was co-hosted by Genomics Medicine Ireland and University College Dublin Research and Innovation. It was an engaging day of talks and panel discussions related to the genomics revolution sweeping Ireland and the globe. The event brought together Irish and international thought leaders and renowned experts to speak on topics that addressed the challenges and opportunities in realising the potential of genomics in healthcare. Over 350 people attended on the day, with audience members active and engaged throughout the event, providing colour and context to the high- level, informative talks given from the stage. Keynote addresses were given by Dr Robert C. Green, a Professor of Medicine at Harvard Medical School and Director at the genomes2people Research Programme, and Dr. Howard J. Jacob, Vice President and Head of Genomic Research at AbbVie. Robert Green spoke on the value and Lt to Rt: Dr Howard Jacob, Prof. Mary King, Noreen Doyle and Dr Shane McKee. benefits of preventive genomic screening. Healthy patients can obtain advanced genetic testing, including whole genome Prof Smith outlined how clinicians can often be sent on sequencing, that can identify future disease risks and offer a “diagnostic odyssey” because of the lack of genomic life-saving preventive strategies. He spoke about the power and genetic facilities in Ireland. He detailed the exhaustive of genomic information, and how the technology is being “diagnostic odyssey” for a patient and family. This was integrated into medical practice. expensive and inconclusive and described the transformation Howard Jacob described the work of Abbvie, dedicated to for the patient and family when genetic testing gave them improving the drug pipeline using genomics tools. He outlined some answers. This “diagnostic odyssey” was also the theme his work in building genomic-level blueprints of people to for a Panel discussion facilitated by Dr. Howard Jacob, and better determine how medicine works at the individual level. including Prof. Mary King, Paediatric Neurologist Professor at He stressed the importance of the relationship between Temple Street Children’s University Hospital, Dr. Shane McKee, therapies and genetic composition to the future of medicine. Chief Clinical Information Officer and Consultant in Genetic He related some personal stories on how he decoded his own Medicine at Belfast Health and Social Care Trust and Noreen genome, and discovered that some 23 commonly-prescribed Doyle, CEO The Irish Biltong Company Ltd and parent of two medicines wouldn’t work effectively—and in some cases children diagnosed with acute leukaemia. wouldn’t work at all—in his body. Dr Shane McKee is Northern Ireland Lead for the UK Further talks by a number of respected figures in the 100,000 Genomes Project and the DDD-UK study, and is field of genomics were given on the day, in addition to two involved in using digital and genomic approaches to improve panel discussions discussing “The skills required to build a healthcare processes and outcomes. He is working with the genomics infrastructure” and “Genomics and the diagnostic Northern Ireland Department of Health to implement an open- odyssey - where do patients go next?” standards openEHR data platform for genomics to ensure Dr James O’Byrne, Consultant Clinical and Biochemical clinicians can collate detailed phenotypic and genomic data Geneticist in the Mater Misericordiae University Hospital, to turn sequencing results into meaningful diagnoses. This Dublin, told attendees that although some work had been will help patients benefit fully from the revolution in Genomic done here in Ireland in the field of Genomics, he said there Medicine. was still a lot to do. He noted that there were only eight people Speakers told how sequencing for rare disease diagnosis with formal genetics training working in Ireland and welcomed is one of the fastest growing fields in genomic medicine. The the plan by the HSE to appoint a national lead. This would cost of sequencing has dipped significantly, while the number ensure a co-ordinated approach to the provision of this of known variants that cause such diseases has steadily service. risen. As a result, more and more hospitals are moving toward Dr Charles Steward gave a parent’s and scientist’s earlier, and more thorough, sequencing for infants and children perspective on genomics. Prof Owen Smith, Our Lady's with undiagnosed diseases. Hurdles still abound and not Children’s Hospital and UCD, spoke on “Swapping acuity everyone will get answers. for Chronicty and its associated Complexities” and said Helen Barry

40 • converse • Summer 2018 research

HPV Primary Cervical Screening: Making the Switch from Cytology to HPV testing

ervical screening has employed the Papanicolaou (Pap) rather than of disease. But what about the high prevalence test for over 80 years to detect cervical pre-cancer and of HPV in our cervical screening population and are all HPV Ccancer in women. The Pap test can be considered one positive women at equal risk? The HPV primary screening of the most effective disease prevention strategies, preventing approach will require that a positive HPV result is further countless cases and mortalities associated with cervical triaged to take that test of risk into a test of disease. While cancer. However, it has its limitations, even with modern many triage options exist e.g. p16/Ki67 staining of cytology improvements such as liquid based cytology, sampling, smears and host gene methylation markers, with some of them sensitivity and screening subjectivity has reported up to a 40% being more informative than others, it has been recommended false negative rate globally. The Human Papillomavirus (HPV) that the Pap test which has served us well so far is used to has long been known to be the primary aetiological factor in further stratify HPV positive women. There is no doubt that the pathogenesis of cervical cancer and there are 14 known the addition of further risk stratification tests or the expansion high-risk HPV subtypes [16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68]. Of these HPV 16 and 18 are associated with ~70% of all cervical cancer cases. HPV testing has been used with great success in Ireland to triage low-grade cytology screening results since 2015. It has also been used as a test of cure following treatment and in the management of uncertainty at colposcopy since 2012 and 2014. More recently, using HPV rather than Cytology as the primary screening test has been shown in numerous international randomised control trials to have a significantly higher sensitivity and negative predictive value and based on this evidence, organised screening of cytology as a “test of disease” will present opportunities to programmes worldwide are making the switch to HPV primary enhance the specificity of HPV primary screening and further screening. refine the definition of risk. Following the HIQA “Heath technology assessment of In the future, we may see a more tailored approach, where HPV testing as the primary screening method for cervical the triage test for a HPV positive woman at the beginning of screening” in 2017, The Irish Cervical Screening Programme, her cervical screening journey is different to a woman near CervicalCheck, had committed to making this switch. In exiting the programme, with HPV vaccination status also a preparation for HPV primary screening, Coombe Women and factor. After nearly 80 years since the introduction of the Pap Infants University Hospital, which houses the only remaining test cervical screening is set to dramatically change for the accredited Public Hospital Cervical Cytology Screening better with innovation and good science leading the way Laboratory in the country, had begun a programme of forward to a better cervical screening programme. readiness for HPV testing and recently received ISO 15189 accreditation for HPV DNA testing on the Roche Cobas 4800 platform. Dr Stephen Reynolds, Dr Helen Keegan, The core concept of HPV primary screening is to detect all Dr Christine White, Roisin O’Brien, Stephen Dempsey, women with high-risk HPV and thus those women at risk of Dr Cara Martin, Martina Ring, Prof. John O’Leary. developing cervical pre-cancer or cancer. Essentially, HPV - on Behalf of the Cytopathology Dept. Coombe primary screening is a test of risk for cervical malignancy, Women and Infants University Hospital, Dublin

Summer 2018 • converse • 41 research

Technological Higher Education Association International Women's Day

To celebrate International Day, The Technological Higher Education Association (THEA) featured leading researchers across the Institutes of Technology. The Academy is delighted to report our President, Brigid Lucey was one of those researchers featured.

Dr Brigid Lucey, FACSLM, FIBMS, PG Dip TLHE, FRCPath Senior Lecturer, Biological Sciences, President of the Academy of Clinical Science & Laboratory Medicine, Cork Institute of Technology

Brigid joined the staff in the Dept. of Biological Sciences at CIT in 2010, having worked previously as a senior medical scientist and head of molecular diagnostics in the department of medical microbiology at Cork University Hospital. Her current roles include lecturing biomedical science students in diagnostic microbiology, quality management and scientific writing, and in supervising undergraduate and PhD students on research projects that include improving diagnosis of infection, epidemiology, investigations for novel bacteria and the use of bioremediation microbes in space-simulated environments. Brigid is also currently the president of the Academy of Clinical Science and Laboratory Medicine, the professional body for medical scientists in Ireland.

The Irish Laboratory Awards 2020

Launched in 2013, the Irish Laboratory Awards recognise and celebrate the accomplishments of those working in the laboratories across Ireland at this year's awards ceremony.

The Irish Laboratory Awards 2020 ceremony took place on Thursday, March 5th, at the Ballsbridge Hotel, Dublin.

Laboratory Scientist of the Year Dr. Jaythoon Hassan UCD National Virus Reference Laboratory

PICTURED: Matt Moran, Judging Co-ordinator, presents the Laboratory Scientist of the Year award to Dr. Jaythoon Hassan - UCD National Virus Reference Laboratory.

42 • converse • Spring 2020 research President’s Prize Although Biomedica 2020 has been postponed to November 30th, the Academy continues with it’s award scheme for graduates in the degree courses in Biomedical Science from TU Dublin, GMIT and CIT/UCC. Each year the colleges are requested to nominate their two students who have achieved the highest marks in the project component of their final exams. The nominated students are invited to our annual conference to give a 15 minute presentation. The President’s Prize is awarded to the student who presents a project judged to be the winner by a panel of selected members and other professionals. The winner goes forward to compete for the Martin Nicholson Award at the EPBS (European Association for Professions in Biomedical Sciences) annual conference. This is expected in early November 2020. The Academy will organise an event in early summer so the nominated students can present. Helen Barry Evaluation of a Faecal Calprotectin Assay for introduction into routine testing in a Biochemistry Laboratory, UHL

AUTHOR: Lalor C, McGrath M, Conmy B. bias of 88.9% and Passing-Bablok analysis revealed poor Dept. of Biochemistry, University Hospital Limerick in agreement between the two methods, further emphasised by collaboration with Dept. of Biopharmaceutical and Medical a p value of 0.007 (α=0.05). The null hypothesis was thereby Science, Galway-Mayo Institute of Technology. rejected.

Conclusion: The fCAL turbo assay performed in Clinical Chemistry accordance with the manufacturer’s specifications of precision. However, accuracy and method comparison results were unsatisfactory for the verification of the assay. Introduction: Faecal calprotectin (FC) is a routinely used, Further analysis is required before introduction of the assay into routine testing. Once the analytical performance is non-invasive biomarker for the diagnosis and monitoring evaluated successfully, the assay will be implemented on of Inflammatory Bowel Disease (IBD) [1]. The primary site, drastically reducing turnaround times, decreasing aim of this study is to evaluate the Bühlmann fCAL faecal referral costs and improving service to users. calprotectin turbo assay in order to bring FC testing into routine testing on site in University Hospital Limerick (UHL). REFERENCES: 1. Seenan JP, Thomson F, Rankin K, Smith K, Gaya DR. Are we Material and Methods: The performance characteristics exposing patients with a mildly elevated FC to unnecessary of fCAL turbo assay were verified on the Abbott Architect investigations? Frontline Gastroenterology. 6th ed. 2015; 156-160. C16000 analyser. Precision was carried out by analysing two levels (low and high) of Internal Quality Control (IQC) in Clodagh Lalor graduated in three replicates, daily for five days. Accuracy was measured 2019 with a BSc. in Medical by analysing nine EQA samples. Additionally, a comparison Science from GMIT. She study was performed which involved the measurement of 20 completed her clinical patient samples on both the Abbott Architect C16000 and laboratory placement in University Hospital Limerick Phadia 250 instrument. (UHL). Following this, She majored in Clinical Results: The precision study confirmed consistency with Chemistry and Medical the manufacturer’s claims and revealed a total coefficient Microbiology and is now of variation (CV) of 1.53% and 3.8%, respectively. A high working in the Biochemistry percentage inaccuracy of 21.83% and significant negative Laboratory, UHL. bias was observed for accuracy studies. A percentage

Summer 2018 • converse • 43 research Angiotensin-Converting Enzyme 2 (Ace2) is a novel substrate for γSecretase-dependent Intramembrane Proteolysis

AUTHORS: Harte, J.V.1,2, McCarthy J.V.3 Conclusions: These observations demonstrate that ACE2 1. Department of Biological Sciences, Cork Institute of is a novel γ-secretase substrate and the formation of a Technology, Rossa Avenue, Bishopstown. potentially biologically active intracellular domain may be 2. School of Biochemistry and Cell Biology, University partly responsible for the counter-regulation of the “classical” College Cork. RAS. Internalization-dependent cleavage may also partly 3. Signal Transduction Laboratory, School of Biochemistry explain the uptake of zoonotic coronaviruses. Thus, the and Cell Biology, University College Cork. identification of ACE2 as a γ-secretase substrate may facilitate translational approaches for manipulating RAS activity in vivo, with potential biomedical significance in terms Clinical Chemistry of health and disease.

Introduction: The renin-angiotensin system (RAS) is a REFERENCES: critical component of the response to hypovolaemia and 1. Forrester S, Booz G, Sigmund C, Coffman T, Kawai T, Rizzo V, et al. Angiotensin II Signal Transduction: An Update on Mechanisms hypotension; however, RAS dysfunction is an appreciable of Physiology and Pathophysiology. Physiological Reviews. 1 mechanism of disease . The recently discovered 2018;98(3):1627-1738. angiotensin-converting enzyme 2 (ACE2) is known to 2. Paz Ocaranza, M, Riquelme, J, García, L, et al. Counter-regulatory counterregulate the potentially destructive effects of renin–angiotensin system in cardiovascular disease. Nature Reviews uncontrolled angiotensinergic activity2. Subversion of ACE2 Cardiology. 2020;17(2):116-129. 3. McCarthy, A, Coleman-Vaughan, C, and McCarthy, J. Regulated by pathophysiological conditions, including infection by intramembrane proteolysis: emergent role in cell signalling pathways. zoonotic coronaviruses, can contribute to inappropriate Biochemical Society Transactions. 2017; 45(6); 1185– 1202. activation of the RAS and accentuate inflammatory and fibrotic disease. Although ACE2 is known to undergo ectodomain shedding, a feature shared by many substrates of γ-secretase-dependent regulated intramembrane proteolysis3, no studies have investigated the subsequent cleavage of the ACE2 carboxyl-terminal fragment (CTF).

Materials and Methods: The molecular mechanism of ACE2 cleavage following ectodomain shedding was investigated by Western blot analysis in cultured cells expressing exogenous or endogenous ACE2 using pharmacological inhibitors and genetic deficiency of presenilin. The subcellular localization of γ-secretase- dependent proteolysis was also investigated using inhibitors of clathrin-dependent endocytosis.

Results: In this study, we show that following ectodomain shedding, the membrane-bound ACE2 CTF is subsequently cleaved by γ-secretase, and that specific biochemical and genetic loss of γsecretase activity independently compromise sequential cleavage of ACE2. Pharmacological inhibition of proteasomal degradation also revealed a putative γ-secretase generated ACE2 intracellular James Harte is a graduate of the BSc (Honours) in Biomedical domain (ICD). Moreover, we show that clathrin-mediated Science from Cork Institute of Technology and University internalization of ACE2 is necessary for γ-secretase- College Cork, and is currently completing his Diploma in dependent proteolysis. Clinical Laboratory Practice in Cork University Hospital.

44 • converse • Summer 2018 research In Vitro Expansion of Human Placental Amnion Epithelial Cells.

AUTHOR: O’ Connor, AOC., Brankin, BB., to the current gold standard medium formulation. Gramignoli, RG. Our results showed AE cells proliferated robustly in PneumaCult™. Gene expression analysis by qRT-PCR Karolinska Institutet, Flemingsberg, Sweden. showed expanded AE cells maintained their native epithelial marker expression (CD326 and cytokeratin 18). Using albumin ELISA quantitation AE cells secreted albumin upon expansion, albeit at levels equal to half of Transfusion and what is observed in healthy hepatocytes. Focusing on the wider clinical application of AE cells, it could be envisaged Transplantation Science from these results that AE cells may aid in expanding the donor hepatocyte pool, generating functionally improved hepatocytes without the need to increase hepatocyte Liver failure represents a major public health concern donor source. worldwide. According to the World Health Organisation, the total deaths caused by cirrhosis and liver cancer have increased by 50 million/ year since 1990 (1). REFERENCES: Until recently orthotopic liver transplantation (OLT) 1. Murray, C. and Lopez, A. (2013). Measuring the Global Burden of has remained the only established curative therapy Disease. New England Journal of Medicine, 369(5), pp.448-457. for treating acute, chronic liver disease or metabolic 2. Iansante, V., Mitry, R., Filippi, C., Fitzpatrick, E. and Dhawan, defects in liver function. However, organ donor availability A. (2017). Human hepatocyte transplantation for liver disease: remains one of the main constraints on health services. current status and future perspectives. Pediatric Research, 83(1- Over the past 3 decades, cell-based therapies have 2), pp.232-240 been gaining importance since they can contribute to regeneration of failing organs or damaged tissues by Áine O’Connor either direct replacement of the lost cells or by facilitating graduated with a the body’s natural regenerative processes. Hepatocyte first class degree transplants (HT) have been gaining recognition as an honours in Biomedical alternative therapeutic option, although it is limited by the Science (BSc) from TU need for strict immunosuppressive therapy in support of Dublin- City Campus. long-term engraftment. Furthermore, allograft rejection She completed a remains a primary issue that prevents the long-term translational research sustained therapeutic benefits of HT (2) project in Karolinska Institutet Sweden for The placenta, or specifically the amniotic epithelial her undergraduate (AE) cells are a promising non-controversial source of thesis, analysing the potential stem cells. Their constitutive ability to mature regenerative potential into different cell types and correct life threatening liver of human placental disease in preclinical models have highlighted them as amnion epithelial cells. a potential candidate for liver-based therapy. Ex vivo She is currently working expansion of AE cells may be important to generate an in Tallaght University adequate yield for transplantation, in addition to reducing Hospital. the number of allogenic donor AE cells per recipient. We isolated AE cells from six gestational full term placentas which generated high amounts of cells (up to 240 million of AE cells per placenta) characterised by high viability (91.5 ± 3.4 %). Whilst preserving several of their native characteristic features, we successfully expanded AE cells in a xenobiotic-free culture medium (PneumaCult™) supplemented with human platelet lysate in comparison

Summer 2018 • converse • 45 research Investigation of the ability of the bacteriocin nisin to inhibit coagulase negative Staphylococci

AUTHORS: O’ Shea, C., Twomey, E., Field, D., Begley, M. densities of crystal violet stained biofilms. It was observed Department of Biological Sciences, Cork Institute of using the agar-based deferred antagonism assays, that Technology a nisin producing bacterium had the ability to inhibit the growth of all CoNS. The minimum inhibitory concentration of nisin against the tested CoNS strains was shown to be in the micromolar (μM) range. The addition of Medical Microbiology nisin during microtiter plate-based assays resulted in a significant reduction of biofilm formation. Furthermore, biofilm formation on stainless steel was also shown to be Introduction: Coagulase negative Staphylococci (CoNS) significantly reduced in the presence of nisin. are ubiquitous colonizers of human skin(1). While previously seen as harmless commensals, CoNS are now viewed as Conclusion: In summary, this study reports the ability opportunistic pathogens and are reported to be the leading of nisin to inhibit a bank of CoNS and their ability to form cause of infections related to implanted medical devices(2). biofilms. Nisin may ultimately be used to develop novel Of particular concern, is the increasing development of coatings for medical devices, or be impregnated into them, resistance to conventional antibiotics. Furthermore, CoNS with the aim of reducing the incidence of or preventing, can form biofilms that aid adherence to biotic or abiotic medical device related infections caused by CoNS. surfaces, and biofilms are inherently refractory to treatment with antibiotics(3). As the number of medical device REFERENCES: implantation surgeries is projected to increase, owing to the 1. Otto, M. 2009. Staphylococcus epidermidis – the “accidental” ageing population and improving healthcare in developing pathogen. Nat. Rev. Microbiol. 7:555-67. countries, alternative approaches to control CoNS are therefore urgently required. The present study investigates 2. Campoccia D., Montanaro L., and Arciola C.R. 2006. The the ability of the natural microbially-produced peptide significance of infection related to orthopaedic devices and issues bacteriocin nisin to inhibit CoNS. of antibiotic resistance. Biomaterials 27:2331-9. 3. McCann M., Gilmore B.F. and Gorman S.P. 2008. Staphylococcus Materials and Methods: A bank of commensal and clinical epidermidis device-related infections: pathogenesis and clinical CoNS was assembled, and strains were characterized management. J. Pharm. Pharmacol. 60:1551-71. using a variety of standard microbiological and biochemical tests. The ability of the strains to form biofilm was examined Clíona O' Shea graduated in 2019 with a first-class honours using a standard plastic microtiter plate-based assay. joint Biomedical Science Agar-based deferred antagonism assays were employed to degree from Cork assess whether CoNS were inhibited by a nisin producing Institute of Technology bacterium. Nisin peptide was purified from the nisin producer and University College by reversed-phase high performance liquid chromatography Cork (CIT/UCC). She (RP-HPLC), and minimum inhibitory concentration assays is currently completing were carried out. The microtiter plate-based assay was her 5th year clinical employed again to assess how nisin affected biofilm placement in the Mercy University formation on plastic surfaces. Subsequent experiments Hospital (MUH) in of this study focused on optimizing a method to examine Cork City. She is biofilm formation by CoNS on a medical device substrate i.e. investigating Uncertainty stainless steel. of Measurement for antibiotic susceptibility Results: All of the CoNS strains in this study were shown testing using the disc to form biofilm, however the extent of biofilm formation diffusion method. varied between strains, as determined by final optical

46 • converse • Spring 2020 research Validation of the Ventana Mismatch Repair Immunohistochemical Panel for Colorectal Carcinoma Screening in Cavan General Hospital.

AUTHORS: O’Toole R1., Irvine B2., Muldoon T.3 Conclusion: The Ventana MMR Panel was successfully 1 Galway Mayo Institute of Technology, validated for colorectal cancer screening and is now on 2 Cavan General Hospital, the scope for INAB accreditation 2020. The successful 3 University Hospital Galway validation of this assay will ensure that the correct course of clinical care is delivered to each patient and may help to determine more accurate patient prognosis. Cellular Pathology

REFERENCES: 1. Kawakami, H., Zaanan, A. and Sinicrope, F.A. (2015). Introduction/ Background: Patients with colorectal Microsatellite instability testing and its role in the management of cancer display significant variability regarding their colorectal cancer. Current treatment options in oncology, 16 (7), clinical outcome, despite being of the same disease 30. stage. This stems from the fact that it is a disease than can arise through many molecular pathways. A person’s 2. Kheirelseid, E.A.H., Miller, N., Chang, K.H., Curran, C., Hennessey, E., Sheehan, M. and Kerin, M.J. (2013). Mismatch susceptibility to cancer and responsiveness to treatment repair protein expression in colorectal cancer. Journal of is highly personal and is largely influenced by the gastrointestinal oncology, 4 (4), 397. molecular pathway through which their cancer arose. 3. O'Kane, G.M., Ryan, É., McVeigh, T.P., Creavin, B., Hyland, J.M.P., O'Donoghue, D.P., Keegan, D., Geraghty, R., Flannery, D. and A small number of cases develop from microsatellite Nolan, C. (2017). Screening for mismatch repair deficiency in instability due to mismatch repair (MMR) protein loss. colorectal cancer: data from three academic medical centers. Patients expressing MMR protein loss are resistant to Cancer medicine, 6 (6), 1465-1472. certain forms of chemotherapy. Therefore, detecting MMR protein expression in these patients is fundamental Rebecca O'Toole graduated in 2019 with a BSc (Honours) in determining the correct course of clinical care. in Medical Science The aim of this study was to optimise and validate from Galway an immunohistochemical assay designed to screen Mayo Institute of colorectal cancer patients for MMR deficiency. Technology (GMIT). She specialised Methods: A group of 20 patients with known MMR status in Histopathology, were tested using the new immunohistochemical assay Haematology and by Ventana in order determine the expression of MMR Blood Transfusion and proteins in formalin fixed tissue. The overall concordance completed her clinical laboratory placement or level of agreement between the true MMR result in Cavan General and the result achieved using the new assay was then Hospital. She returned determined for the purpose of assay validation. to Cavan to carry out her research project. Results: All four antibodies in the panel were successfully She is currently working optimised. 100% positive concordance was achieved for Eurofins Biomnis between the two sets of results, surpassing the as a medical scientist recommended benchmark concordance of 90%. in their Histopathology department.

Spring 2020 • converse • 47 research Characterisation of a large group of Listeria Monocytogenes using whole genome sequencing: assessing their virulence potential

AUTHORS: Unrath, N., McCabe, E., Hurley, D., Herra, WGS can achieve more than just discrimination between C., Fanning, S. unrelated isolates. An additional benefit of WGS is the opportunity to extract specific information, such as, the UCD-Centre for Food Safety, School of Public Health, determination of virulence, antibiotic or biocide resistance Physiotherapy and Sports Science, Science Centre South, status, as well as the assignment of serotypes. WGS is University College Dublin, Belfield, Dublin D04 N2E5 the ultimate tool for characterization of bacterial isolates as it provides the highest possible resolution in strain typing and represents a paradigm shift for outbreak investigation and contamination-source tracking. Medical Microbiology

REFERENCES: (1) EFSA and ECDC. The European Union One Health 2018 Listeria monocytogenes is the etiological agent of Zoonoses Report. EFSA Journal. 2019;17(12): 5926. listeriosis, a foodborne illness associated with high hospitalization and mortality rates.(1) L. monocytogenes (2) Maury MM, Tsai YH, Charlier C, Touchon M, Chenal-Francisque may be classified as hypovirulent, intermediate and V, Leclercq A, Criscuolo A, Gaultier C, Roussel S, Brisabois A, hypervirulent, based on the presence of Listeria Disson O, Rocha EPC, Brisse S, Lecuit M. Uncovering Listeria (2) monocytogenes hypervirulence by harnessing its biodiversity. pathogenicity islands (LIPIs). This bacterium can exist Nature Genetics. 2016;48(3): 308-313. in food associated environments for years with persistent strains being linked to outbreaks of foodborne disease(3) (3) Ferreira V, Wiedmann M, Teixeira P, Stasiewicz MJ. Listeria This study aimed to improve food-borne subtyping and monocytogenes persistence in food-associated environments: identification of virulent and persistent L. monocytogenes epidemiology, strain characteristics, and implications for public health. Journal of Food Protection. 2014;77(1): 150-170. in food associated environments through the application of whole genome sequencing (WGS). Natalia Unrath graduated from Technological University Dublin in 2019 with WGS was applied to a collection of 143 L. monocytogenes a BSc in Biomedical from a longitudinal study of a large food production Science. She facility, collected between 2014 and 2017. Sequence started her career data was analysed using bioinformatic tools. Virulence in the microbiology was assessed using the Virulence Factor Database department in Connolly (VFDB). Persistent strains were detected using multilocus Hospital. She is currently sequence typing (MLST) in silico, single nucleotide pursuing a PhD in the polymorphism (SNP) analysis and the determination of Centre for Food Safety, biocide resistance using the BacMet database. University College Dublin specialising The assessment of virulence profiles revealed that in the use of Whole only one isolate was hypovirulent and two others were Genome Sequencing to hypervirulent, with the majority (98%) being intermediate. assess the virulence and In silico MLST and SNP analysis showed that 77% of the persistence potential of isolates are potential persisters and harbor resistance Listeria monocytogenes genes to biocides commonly used in food environments. under the principal These findings suggest that virulent L. monocytogenes supervision of Professor are present and persisting within Irish food environments Séamus Fanning. which can have adverse effects on both the food producer and public health.

48 • converse • Spring 2020 book review

Breakthrough: 1923, the Nobel prize in physiology coma and death a real possibility. was awarded to Macleod and However, she quickly began to thrive. Banting but not to Best and Collip. On August 25, she ate a piece of Elizabeth Hughes, the Much argument ensued. That’s the white bread for the first time in three Discovery of Insulin, and the short version familiar to most of us. and a half years. On September 21, making of a medical miracle. Thea Cooper and Arthur Ainsberg she ate bananas. On September 22, Thea Cooper and Arthur Ainsberg. (St tell the long version in their book she ate plums. Martin’s Griffin, 2010, pp 306). entitled Breakthrough. They cleverly By the time she died, many turn their investigative lens on four decades later, Elizabeth had received Review by Anne Mac Lellan characters: the researcher Frederick some 42,000 insulin injections over Banting, the diabetic patient 58 years, probably more than anyone Elizabeth Hughes, the eccentric on earth at that time. However, doctor Frederick Allen and the Elizabeth chose to keep her diabetes industrial chemist George Clowes. a secret. Cooper and Ainsberg J. K. Lilly and sons who employed suggest that this may have been Clowes also make an appearance. partly due to an awareness that her The resulting narrative is a page- father’s influence had ensured that turner. I read it in a single sitting. she was one of the early group of In 1918, at age 11, Elizabeth patients to receive insulin. So, she Hughes, the daughter of Charles may have had a ‘dim awareness that Evan Hughes, the US Secretary at the heart of the glorious miracle of State, developed a ‘ravenous through which she was saved lay appetite’ and an ‘unslakable thirst’. the dark possibility that another child The diagnosis of juvenile diabetes died in her place’. was a death sentence. Elizabeth’s This book meticulously details life expectancy was less than one the difficulties and pettiness that year from the onset of symptoms. often mar research while using Her only hope lay in Dr Frederick the patients’ voice effectively to Allen who had invented a dietary show how this research was sorely regime that could prolong the lives needed. The problem for me is that of diabetics in hopes of a cure the authors did a heroic amount being found. For Elizabeth, he of research and then filled out the suggested a fast followed by a diet inevitable elisions with imagined of 400 calories daily with almost no detail. In keeping with their novelistic Here’s how I heard it: In 1921, Prof carbohydrates. Her parents were approach, they have invented some Macleod went on holidays loaning horrified but felt that they had no dialogue and some situations. In his research lab in the University of choice. They engaged a nurse and Toronto to researchers Frederick Elizabeth’s long fast began. one affecting scene, Banting buries Banting and Charles Best. They She was eventually admitted to the engagement ring that his fiancée wanted to try and isolate a substance Dr Allen’s ‘Physiatric Institution’ returned to him. This burial and from the pancreas of dogs. Banting in New Jersey which opened in the subsequent scrabbling in the and Best were successful: the 1921 and housed patients, mainly soil to find the ring was a device pancreatic extract became known children, who existed on frighteningly to ‘represent Banting’s struggle as insulin. When injected into a dog restricted diets losing weight and to reach a final solution about his which had had its pancreas removed occasionally, accidentally, dying engagement.’ The authors are clear the dog reportedly sat up and from starvation. His motto was ‘the that they do not know how this began to wag its tail. The first insulin less food the more life’ while he also struggle actually manifested. There injection given to a human was to an stated that ‘to starve was to survive’. are other inventions and insertions eight-year-old boy in Toronto General Some of his patients are reputed to which the authors allude to in the Hospital who was dying from type 1 have weighed as little as 30 pounds. prologue and spell out in the notes. diabetes. He also sat up although he However, he believed that a cure was For a historian, these are simply didn’t have a tail to wag. imminent and that the cruel regime frustrating. Work continued on refining would allow some patients to survive If you can set aside the difficulties insulin and a fourth researcher, long enough to be cured. of not knowing what is true and James Collip, was instrumental Elizabeth did, indeed, live long what is a device then this book is a in its purification. Insulin quickly enough to become one of Banting’s compelling read. came of age with some help from early patients. In 1922, she began Dr Anne Mac Lellan is a manufacturers Lilly & Sons, saving a regime of insulin injections and professional historian and a the lives of thousands of children urinanalysis. There were still dangers; surveillance scientist (jobsharing) who would otherwise have died. In dosage was difficult to stabilise, in Connolly Hospital

Spring 2020 • converse • 49 crossword

Name: Name: Complete the crossword puzzle below Complete the crossword puzzle below 1 2 1 2 3 4 5 3 4 5

6 6 7 8 7 8 9 9 10 10 11 11 12 13 12 13

14 14

15 16 15 16 17 17

18 18

19 20 19 20

21 21 22 22

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