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Official Publication of the Academy of Clinical Science and Laboratory Medicine Volume 46 Issue 1 Spring 2020 Coronavirus Coronavirus COVID-19 COVID-19
CRa1nn Cruinn Diagnostics Limited Proud Principal Sponsor of BioMedica Providing Solutions for Laboratory Medicine In Ireland for over 22 years We look forward to seeing you at BioMedica 2020 in the Convention Centre Dublin 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
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 Preparing for CORU registration - An Academy guide............................................ 31 cpd Let's work together................................................................................................... 32 updates Health and Biomedical Science Updates................................................................ 33 Page 26 meetings Genomics Summit 2020.......................................................................................... 37 Multidisciplinary Seminar - Report on the joint CPD seminar ‘The Transplant/Immunocompromised Host’.......................................................... 36 Clinical Chemistry/Microbiology Joint Meeting........................................................ 37 The 16th National Health Summit............................................................................. 38 research HPV Primary Cervical Screening.............................................................................. 41 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 Cavan General Hospital............................ 47 Characterisation of a large group of Listeria Monocytogenes using whole genome sequencing: assessing their virulence potential...................................................... 48 book review The Discovery of Insulin........................................................................................... 49 Page 37 crossword..................................................................................................... 50 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, Tel: 01-285 9111 • Mobile: 087-2611597 techniques or organisations described therein. The Academy of Clinical Science and The Academy of Clinical Science and Laboratory Laboratory Medicine, Email: roger@silchestermarketing.com 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: mail@acslm.ie Email: design@artworks.ie 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 Brennan & Company authorised representatives of Qiagen Clinical Diagnostics in Ireland. enquiries@brennanco.ie QIAstat-Dx The next generation of syndromic insights Expanding diagnostic capabilities Detection of more than 20 respiratory pathogens by RT-PCR is available in about one hour, including valuable insights on coinfection and sample quality. • Ct values and amplification curves • Real-time PCR technology • Comprehensive and accurate results • Detects the 2019 novel coronavirus (2019-nCoV) in 1 hour Learn more at QIAstat-Dx.com Trademarks: QIAGEN®, Sample to Insight®, QIAstat-Dx® (QIAGEN Group). PROM-14358-001 05/19 © QIAGEN 2019, all rights reserved. Sample to Insight 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 Registration and Programme: www.biomedica.ie 8 • converse • Spring 2020
feature Coronavirus Sars CoV 2 - COVID-19 A 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, coronavirus, 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. globe. One week later, on 7th January Most persons infected with COVID-19 2020, Chinese authorities confirmed COVID-19 experience mild symptoms and recover. Since the emergence of COVID-19 in However, some go on to experience that they had identified a new virus in December, it’s become stigmatised more serious illness and may require humans of unknown origin. The new among specific populations, with the hospital care. Risk of serious illness rises virus is a coronavirus. Coronaviruses rise of harmful stereotypes reported by are members of the subfamily with age, individuals over the age of 40 the WHO in February of 2020. The risk seem to be more vulnerable than those “Coronavirinae” (family; Coronaviridae, associated with getting COVID-19 is 62 order; Nidovirales) that contains under 40. Those with weakened immune currently low across the globe. However, systems and people with conditions four genera alpha-coronavirus, beta- COVID-19 has been detected in almost coronavirus, gamma - 63 coronavirus such as diabetes, heart and lung disease every country. Stigmatisation could are also more vulnerable to serious and delta -coronavirus. Coronaviruses potentially contribute to more severe cause illness ranging from the common illness.6 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), and there is no time for complacency.8 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 4th April there are 1,133,758 cases with infectious disease spreading have been WHO director-general, Tedros Adhanom 62,784 deaths in 208 countries.5 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 (martin.conway@randox.com) 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- topics/coronavirus (Accessed: 7 about/prevention-treatment.html 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. 7) Lesney MS. 2019-nCoV: Just a 27th Feb 2020. epidemiology of 2019 novel 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- More new virus cases outside S0140-6736(20)30251-8. outbreaks-coronavirus-mers-sars- 2) Peiris JS Chu CM Cheng VC et China than in, ‘no time for health-epidemic/. Last accessed al. Clinical progression and viral 15) Wang Q, Wang YH, Ma JC et al. complacency’, says UN health 27th Feb 2020. load in a community outbreak of 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. 9) CDC. (2020). Transcript for the 2020. at http://weekly.chinacdc. Microbiol. 2019, 17, 181–192. 3) Centers for Disease Control 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. transmission of COVID-19, as there a case for quarantine? https://doi.org/10.1101/2020.02.1 24) Du L., Yang Y., Zhou Y., Lu of 25 February 2020. Available: Perspectives from SARS to Ebola. 0.20021675. Accessed February L., Li F., Jiang S. MERS-CoV https://www.ecdc.europa.eu/en/ Disaster Med Public Health Prep. 13, 2020. 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 – Rotunda Hospital A 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 the 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 Spring 2020 • converse • 13
feature 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 14 • converse • Spring 2020
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feature 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 16 • converse • Spring 2020
feature 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
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